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ABSTRACT CLARK IV, JOE BOAZ. The Synthesis and

1. WONCIUSIONS enaa AA Sota NG Cita hala hn Sata ai a eat ar 119 3 9 Experimental Section e carcg es ccete wate vetezcuetvtate tet paataseestetetes saat weetes tend 121 3 9 1 General Procedures and Equipment ccccceeeeeeeeeeteereeeeees 121 3 9 2 Experimental Procedures and Characterizations 0008 123 3 10 REfreNCeS eeeeceeceeeeeeeeeeeeeeeeeeeeeeeeeeaaaaeeeeeeeeeeeeesaaaaaaaeeeeeeeeeeeeeenaaaees 148 APPENDICES komes ioiii e deena iat nan S E E 149 Appendix 1 Filter Paper Covered Vacuum Needle Assembly Instructions 150 Appendix 2 Guide to Vacuum Manifold Maintenance eeeeeeeeeeeeeeeeerereeeenn 159 Appendix 3 Creating an Improvised Holding Devise for Molecular Sieves 181 Appendix 4 Varian NMR Users Manual cccceceesesneeeeeeeenneeeeeeenneeeeeeeeaaes 185 vii Section 1 Essential Operations for Basic 1D Spectra eeeeeeeeeeee 186 Section 2 Optional Operations for Basic 1D Spectra Enhancement 190 Section 3 Glide Program Operations for Advanced 1D amp 2D Spectra 192 Section 4 Manual Setup Operations for Advanced 1D Experiments 196 Section 5 Operations for Collecting Spectra at Variable Temperatures 200 Table 1 Freezing amp Boiling Point of Deuterated Solvents 0 08 203 Table 2 Commands for Access to Standard Solvent Parameters 204 Table 3 Comprehensive Reference Chart of Solvent Chemic
2. Begins experiment and saves data to any pre Set Directory 207
3. acetate potassium cyanide and 4 dimethylaminopyridine have each been reported to catalyze transesterifications though none of these successfully facilitated transesterification of pendant esters on a heavy fraction of poly lll When initially tested with a lower molecular weight fraction of the prototype Hg OAc 2 did show some promise as evidenced by changes in the H NMR spectra Figure 3 4 98 Before Exposure to Acidic Conditions Acidic Conditions for 1 Week at 25 C Acidic Conditions for 1 Week at 60 C 10 0 9 0 8 0 7 0 6 0 5 0 4 0 3 0 2 0 1 0 ppm Figure 3 3 H NMR spectra of poly lll before and after 1 week of reaction with 2 methoxyethanol in the presence of p toluenesulfonic acid 2 1 equivalents repeat in chloroform solvent The most prominent change in the spectra is the replacement of broad proton signals with sharp signals consistent with decomposition of the polymer into smaller molecules Increasing the reaction temperature greatly accelerates the decomposition process 99 Original Polymer s ha J Methyl Ester J Proton Set Transesterified Polymer 2 Methoxy Ester Proton Sets Original Alcohol 4 0 3 8 3 6 3 4 3 2 3 0 2 8 2 6 2 4 ppm Figure 3 4 Expanded view of the region of interest on the H NMR spectra of a relatively light fraction of poly lll before and after transesterification with 2 methoxyethanol catalyzed by mercury Il acetate The notab
4. been polymerized Figure 2 1 a Sa o Figure 2 1 The two polycarbodiimides bearing an ester pendant group synthesized by Jeonghan Kim Each of these structures was synthesized via living polymerization with a titanium catalyst A noteworthy feature later proven essential for the utilization of titanium catalysts is the lack of enolizable protons 44 2 2 Syntheses of Novel Ester Bearing Carbodiimides Following the establishment of living polymerization methodologies for carbodiimides and prior to initiation of this work the predominant focus of research has been the exploration of properties inherent in the polycarbodiimide structures themselves The revelation that these polymers adopt a helical conformation in the solid state that persists in solution led to voluminous chiro optic experiments on the induction of biases in the helical conformation via chiral catalysts or pendant entities Other works have explored the liquid crystalline properties of polycarbodiimides or the mechanics of a chiroptical switching phenomenon associated with pendant 1 napthyl or 1 anthryl substituents 2 Only perfunctory efforts have been made to modify polycarbodiimide structures following polymerization predominantly in the interest of altering the solubility This being the case there has been little effort to synthesize and polymerize carbodiimide structures bearing functionally modifiable pendant groups which is the moti
5. Department of Chemistry Varian NMR User s Manual st f OF WA by J B Clark IV Dissertation Edition 05 21 2010 185 Section 1 Essential Operations for Basic 1D Spectra Preparing a Sample To prepare a sample for H NMR analysis dissolve 5 to 10 mg of sample in approximately 0 6 mL of deuterated solvent The ideal concentration for C NMR analysis is higher such as 50 mg in 0 6 mL deuterated solvent Log In Consult your Research Group for the username and password with which to log in Upon logging in left click on the Varian NMR Icon 6 icon from the bottom left of the screen showing blue peaks on a black background to bring up the NMR program Loading a Sample To eject the standard type e into the keyboard window and hit enter Remove the sample by grabbing the sample tube holder rather than the sample tube itself to avoid allowing the holder to slip off and fall down the loading tube f the outside of the sample tube is not clean wipe it with a Chem Wipe Place the sample tube holder in the sample tube gauge Insert the sample tube into the holder and line the middle of the sample volume up with the prominent black line on the measuring scale or at the lowest flush with the bottom of the gauge Set the loaded sample tube holder back in the NMR loading tube Type i and hit enter to insert the sample into the NMR Locking onto the Solvent Deuterium Signal Type getshim and hit
6. Synthesis of an L alanine methyl ester bearing carbodiimide via desulfurization of a 1 3 disubstituted thiourea generated in situ Mercuric oxide the classical metal oxide utilized for this method is coupled with the dehydrating reagent magnesium sulfate used to remove the H2O byproduct HgS is also generated and can be easily removed by filtering through diatomaceous earth ccccceeeeeees 47 xiv Figure 2 4 Figure 2 5 Figure 2 6 Figure 2 7 Figure 2 8 The reaction of N N di t butylthiourea with DCC leads to N N di t butyl carbodiimide and N N dicyclohexylthiourea Curiously the reaction of DCC with N N dimethylthiourea under the same conditions is reported to produce dimethyl cyanamide MezNCEN instead 49 Phosphorus pentachloride is a highly reactive reagent In this experiment not only did it generate the chloroformamidine hydrochloride intermediate which reacted with base to form the carbodiimide it also chlorinated the benzylic position of the 4 methylphenyl substituent eee eee cece ee eeeeeeee eee eeeeeeeeeeeeaaeeeeeeeeeeeeeees 50 1H NMR spectrum of the product resulting from carbodiimide III reacted with CpTiClLOCH2CF3 The profile indicates high molecular weight materials characterized by broad signals mixed with a comparable quantity of low molecular weight materials characterized by sharp SIONS resa e A c ttre Metal atc ratc ticle atta eMac rele tats 54
7. a 100 excess was added and the reaction mixture was heated for 5 days at 60 C The chloroform solvent was removed by rotovap Chloroform 15 mL was added to re dissolve the product The product was then precipitated in magnetically stirred pentanes 80 mL Collection and drying of the precipitate revealed 7 60 g of white powder 79 yield IR KBr Pellet 3346 s 3016 vw 2951 m 2929 m 2866 m 1716 s 1668 s cm H NMR 300 MHz Acetone de 5 ppm 8 22 s br 1H 7 87 d J 9 0 Hz 2H 7 60 d J 9 0 Hz 2H 5 91 t br 1H 3 82 s 3H 3 21 m 2H 1 52 m 2H 1 31 m br 6H 0 88 t J 6 8 3H N hexyl N p 2 2 2 trifluoroethoxy carbonylphenyl urea Chloroform 50 mL and t 2 2 2 trifluoroethyl p aminobenzoate 4 60 g 30 4 mmol were added to a 100 mL round bottom flask Hexyl isocyanate 97 3 99 g 30 4 mmol was 130 added The flask was placed in an oil bath heated to 60 C to facilitate the reaction 10 days later the flask was removed from heat The insoluble crude product was collected by filtration The crude product was dissolved in acetone 40 mL and then precipitated from the solution in ice cold hexanes 200 mL The solid white product was collected on filter paper Drying of the product under high vacuum revealed 1 05 g of white flakes 10 yield Concentrating the supernatant collected 3 48 g of white crystals an additional 33 yield bringing the total yield to 43 IR KBr
8. assignment is the one having the higher signal to noise ratio To re access a saved DEPT file highlight the file select LOAD and then AutoProcess The four spectra can be printed on the same page by selecting Autoplot Each of the four spectra may also be displayed and printed individually Utilize the command ds 1 to display the all protonated carbons spectrum ds 2 ds 3 and ds 4 can be utilized to display the CH carbons CH2 carbons and CH3 carbons spectra respectively The command sequence pl pscale page can be used to print any spectrum on display 195 Section 4 Manual Setup Operations for Advanced 1D Experiments Inverse Gated Decoupled Carbon 13 Spectroscopy Quantitative C Analysis Go through the normal C NMR analysis setup routine Utilize the command pw 90 to determine the length of a 90 pulse width Change the pulse width to 90 with the command format pw Type dm nny and hit enter Type d1 10 and hit enter to change the delay time to 10 seconds A delay of up to 20 seconds may be required for the carbons in some samples Set nt 1 collect a rough spectrum and adjust the sweep width Be sure that the width includes every anticipated peak of the sample solvent and standard To maximize the number of transients with the chosen parameters in a given run time first set the number of transients to some high value such as nt 10000 then type time and hit enter to
9. having NCN anions paired with 10 11 13 14 cations ranging from alkali alkali earth and transition metals to a variety of rare earth elements The reactivity of carbodiimides bearing inorganic substituents differs fundamentally from that of organically substituted carbodiimides The latter have proven exceedingly useful in organic synthesis while the former are of increasing interest as ceramic material precursors For instance bis trimethylsilylcarbodiimide is used to obtain silicon carbonitride films by RF plasma enhanced chemical vapor deposition Perhaps the most prominent application of a carbodiimide in organic chemistry is the Merrifield Method the standard for automated peptide synthesis which utilizes dicyclohexylcarbodiimide to promote amide bond formation by activating the carbonyl group for condensation with an amine Having such an ability to facilitate the formation of amide bonds between molecules without becoming a part of the bonds themselves carbodiimides are referred to as zero link crosslinking agents The utility of carbodiimides as dehydrating agents in the Merrifield Method and others such as the Reverse Merrifield led to the development of polymers containing carbodiimide units as solid phase dehydrating agents Figure 1 1 One such polymer is polyhexamethylenecarbodi imide which incorporates the carbodiimide unit as a part of the polymer backbone
10. 105 Aliphatic region of poly N hexyl N phenylcarbodiimide made with copper versus chiral titanium catalyst The sharper carbon signals of the latter are a consequence of both its higher regioselectivity and its more singular GHONY ae kant te ehh eo he a tec ee heel hte ah 107 Expanded view of the signals for the alpha methylene carbons Notice that the minor regiochemistry having the hexyl substituent in the imine position is significantly more prevalent from the copper catalyzed polymerization gc2ct tac ica etee hate t tts ete iee teh ats elt ett es ae 108 Four new derivatives of the old ester bearing carbodiimide design by Jeonghan Kim Monomer VIII and IX were made by dehydrating the corresponding urea precursor while VII and X were made from the corresponding TMOUlEA ns ee eee ee ee aacaten teeth ecenatenarcneteneceuneie 110 XX Figure 3 12 Figure 3 13 Figure 3 14 Figure 3 15 Hybrid design crossing Kim s ester bearing polycarbodiimide which is unstable under conditions that are strongly acidic or basic and even decomposes upon mere sonication with a structure proven to be robust even when sonicated under strongly acidic or basic conditions TOR AWE TE ek ce faethe ehh eared EEE EE eared eared E 112 Infrared spectrum of poly X The only observable imine absorption is at 1635 cm suggesting the aromatic pendant group occupies the imine position The infrared spectrum does not provide any indication of the altern
11. All septa were dried overnight in a vacuum chamber and stored under nitrogen in the dry box until used All filter paper covered vacuum needle assemblies utilized for air and moisture sensitive procedures were dried overnight in an oven at 140 C 122 3 9 2 Experimental Procedures and Characterizations t Butyl p Aminobenzoate p Aminobenzoic acid 13 7 g 99 9 mmol was weighed and transferred to a 1000 mL round bottom flask Toluene 200 mL dried by standing over calcium hydride and a magnetic stir bar were added Thionyl chloride 55 mL 89 7 g 753 mmol a 650 excess was added to the reaction flask The reaction mixture was refluxed overnight under an atmosphere of nitrogen Removal of the volatiles by rotovap the next day revealed an amber oil Note Oil free water cooled vacuum aspirators such as the Brinkman Model B 169 Vacuum Aspirator that are designed to be corrosive resistance are the correct type to use for rotovaping samples containing thionyl chloride Not even a liquid nitrogen cooled cold trap can prevent thionyl chloride from damaging an oil lubricated vacuum pump attached to a rotovap t Butyl alcohol 250 mL 194 g 2 61 mol a 2 500 excess and a magnetic stir bar were placed in a 500 mL round bottom flask The amber oil p aminobenozyl chloride was transferred by pipet to the flask The exotherm did not increase the temperature of the reaction above 40 C Following complete addition of the p aminobenozyl
12. Counts vs Acquisition Time min Figure 2 12 Extracted lon Chromatograph of the 409 m z ratio corresponding to twice the mass of N phenyl N L alanine methyl ester carbodiimide The Total lon Chromatograph indicates the dimer eluted at 15 2 min as the predominant small molecule Plot Window Report EIC 613 0000 Scan 080295 d x10 2 EIC 613 0000 Scan 080295 d 1 613 m z Extracted lon 09 Chromatograph EIC 0 8 0 7 0 6 0 5 0 4 0 3 0 2 0 1 128 13 132 134 136 138 14 142 144 146 148 15 152 154 156 158 16 162 164 166 168 7 17 Counts vs Acquisition Time min Figure 2 13 Extracted lon Chromatograph of the 613 m z ratio corresponding to three times the mass of N phenyl N L alanine methyl ester carbodiimide The profile of the plot indicates at least seven trimeric stereoisomers two predominant four trace 68 2 4 2 Fractional Precipitation and Extraction The Disposal of Disorderly Dimers To review the optimum polymerization conditions for our prototype ester bearing carbodiimide Ill unavoidably produce small stable molecules as well Aside from facilitating polymerization heating with copper I butanethiolate also catalyzes dimerization The dimerization process becomes increasingly competitive at higher temperatures where entropy disfavors polymerization leading almost exclusively to dimers with a trace of trimers above the ceiling temperature Since the broad overl
13. Figure 1 9 Hypothetically either the hexyl or the phenyl substituent might occupy the amine or the imine position The extent to which a polymerization dictates which substituent is placed in which position is referred to as the regiospecificity of the reaction Bi CH 2 5CH 5 T Ay hy N CH 5 sCH g Te Ss zO Z Figure 1 9 Two regiochemistries of an asymmetrically substituted repeat unit Early efforts to quantify the regioselectivity of carbodiimide polymerizations relied on thermal degradation studies If thermally induced scissions were random scissions across the original monomer units would be as likely as scissions between them Scissions between the original monomers yield the original monomers regardless But for cases in which adjacent repeat units have opposite regiochemistries scissions across the original monomers lead to metathesis monomers Figure 1 10 However such scissions are not random When a polycarbodiimide microstructure entails structural irregularities all bonds are not created equal Some are cleaved more easily than others biasing the degradation pathways and thus precluding quantitative interpretations 13 Regiospecific Polymer Non Regiospecific Polymer A A A A A A B A Y t 1 t 1 1 Y 1 ta B i bo Ma ey B B B B Heat Heat Original Ba Monomer ae N C N lt __ N C N ba Y ae N C N Metathesis N Monomers a N C N e Figure 1 10 Illustration of depolymeriz
14. Pellet 3440 s 3062 vw 2960 m 2933 m 2860 w 1732 s 1647 s 1171 s cm H NMR 300 MHz CDCls amp ppm 8 35 2 br 1H 7 93 d J 8 9 Hz 2H 7 65 d J 8 9 Hz 2H 5 98 t br 1H 4 87 q J 8 7 2H 3 21 m 2H 1 51 m 2H 1 30 m br 6H 0 88 t J 6 6 Hz 3H N methyl N p t butoxy carbonylphenyl carbodiimide Acetone 150 mL dried over sodium sulfate was added to a 250 mL round bottom flask N methyl N p t butoxy carbonylphenyl thiourea 9 68 g 36 3 mmol and a magnetic stir bar were added A reflux condenser was attached and the flask was positioned in a hot oil bath heated to 75 C Mercury Il oxide 99 11 9 g 54 4 mmol was added at a rate of approximately 2 g every 10 minutes After the last addition the reaction was refluxed for 3 hours The product was removed from heat allowed to cool for 1 hour and then filtered under pressure through a column pre soaked with acetone consisting from top to bottom of 2 mm sand 5 mm diatomaceous earth Celite 545 Filter Aid 2 mm sand and 6 5 mm silica gel 60 200 Mesh Grade 62 Acetone 300 mL was used to rinse the product from the column The total 131 volume of solution collected from the column was 473 mL The solution was dried over magnesium sulfate Upon transferring to another flask the magnesium sulfate was rinsed with enough acetone to bring the total solution volume to 500 mL Removal of the acetone
15. Step through the stopcock channel The drag of the untwisted end the Kimwipe should leave the channel relatively grease free Use a clean Kimwipe for each channel 164 Step 12 The stopcock socket on the manifold is most easily cleaned with a solvent soaked paper towel Tear a paper towel in half widthwise roll it fold the roll in half and position the folded roll on a long pair of needle nose tweezers as illustrated Kimwipes can be used for this application but keep in mind that Kimwipes are thin and easily torn Scratching a stopcock socket with metal tweezers will assuredly ruin it SO proceed with caution if using Kimwipes Step 13 Soak the paper towel with halogenated solvent Chloroform works well for removing high vacuum silicon grease 165 Step 14 Repeatedly insert and withdraw the chloroform soaked paper towel into the socket with a twisting motion to remove old silicon grease deposits Step 15 Apply a fresh coat of silicon grease to each stopcock before returning it to its respectively numbered joint Dow Corning high vacuum grease is recommended for mobile joints such as stopcocks 166 Step 16 Return each stopcock to its properly numbered joint Double check that the joint number matches the stopcock number as each custom fit maximizes the vacuum capability of the system Step 17 socket ends of each ball and socket joint with a solvent soaked Kimwipe Hexanes work
16. The polymerization of N N bis 4 n butylphenyl carbodiimide fails at room temperature due to the heightened activation energy resulting from the steric hindrance of the bulky pendant groups and ligand respectively on the carbodiimide and catalyst Gentle heating provides sufficient energy to facilitate polymerization 0 55 1H NMR spectrum of the product resulting from carbodiimide III reacted with CuCl for 1 month at 60 C The profile indicates primarily high XV Figure 2 9 Figure 2 10 Figure 2 11 molecular weight material as evidenced by the predominance of broad versus sharp SIQMal Scxcicacccucs cocsnciecctmeciencercegetiemciecaneneciened ee 57 1H NMR spectrum of the thermal polymerization product resulting from heating carbodiimide III at 60 C for 4 weeks in the absence of catalyst When compared with the spectrum of the polycarbodiimide formed under the same conditions in the presence of CuCls Figure 2 8 this spectrum has fewer and less intense sharp signals suggesting that thermal polymerization in the absence of CuCl proceeds more cleanly and that rather than facilitating polymerization CuClz actually catalyzes the formation of small molecules such as dimers and trimers 59 1H NMR spectrum of the product resulting from heating carbodiimide III with copper l butanethiolate Though the spectrum consists predominately of broad polymer signals the intensity of sharp signals indicates gre
17. alanine methyl ester bearing carbodiimide via desulfurization of a 1 3 disubstituted thiourea generated in situ Mercuric oxide the classical metal oxide utilized for this method is coupled with the dehydrating reagent magnesium sulfate used to remove the H2O byproduct HgS is also generated and can be easily removed by filtering through diatomaceous earth 47 The 4 chlorophenyl analogue of this carbodiimide was synthesized via the alternate urea precursor route But the yield 3 was too low for subsequent polymerization studies which leads to an important point Beyond consideration of the commercial availability of isocyanate versus isothiocyanate starting materials the choice of which route to utilize for a given synthesis is often dictated by the influence of the resulting carbodiimide s physical properties on purification efforts Desulfurization of the thiourea proves to be the route of choice in cases such as these where the resulting carbodiimides are very polar Strong dipole dipole interactions make the volatility of the carbodiimide comparable to that of the triphenylphosphine oxide byproduct of the urea precursor route which precludes purification via vacuum distillation Having a high polarity also complicated separation of the carbodiimide from triphenylphosphine oxide via column chromatography where too little time on the column would have led to co elution while too much led to a greatly reduced recovery as a result of p
18. amidinate complexes were difficult to make or more specifically challenging to purify Finally polycarbodiimides made with copper catalysts were often colored suggesting contamination of the sample with residual copper following the workup In contrast titanium catalysts exhibit good solubility in a variety of solvents including benzene toluene methylene chloride chloroform diethyl ether and tetrahydrofuran The titanium metal is also easily removed by precipitating a hydrocarbon solution of the crude polymer in alcohol And though titanium catalysts are moisture and air sensitive they are not difficult to make or challenging to purify for researchers who are skilled in the art of Schlenk techniques Furthermore recent research detailed in Section 3 5 indicates that polymerizations of asymmetric carbodiimides facilitated by titanium IV are more regioselective than those carried out in the presence of copper II 52 Nevertheless it is the ability of copper catalysts to tolerate a larger array of functional groups that ultimately proved decisive in the quest to polymerize novel ester bearing carbodiimides Preliminary studies revealed titanium catalysts to have little or no compatibility with carbodiimides Il and Ill Our most active titanium catalyst TiClsOCH2CFs3 failed to polymerize any of the three A less active titanium catalyst CpTiClheOCH2CF3 also failed to polymerize carbodiimides and Il but did polymerize
19. an ice water bath After cooling to 0 C a filter paper covered vacuum needle assembly was utilized to remove the supernatant See Appendix 1 for filter paper covered vacuum needle assembly instructions The remaining volatiles were removed by rotovap followed by high vacuum to reveal 14 1 g of white powder 90 yield IR KBr Pellet 3342 s 3093 w 3054 w 3027 w 2983 m 2959 m 2934 m 1735 vs 1638 vs 1227 s 640 m cm HNMR 300 MHz Acetone de 5 ppm 8 09 s br 1H 7 46 d J 8 4 Hz 2H 7 22 m 74 2H 6 92 t J 7 5 Hz 1H 6 13 d br J 5 4 Hz 1H 4 41 m 1H 3 69 s 3H 1 36 d J 7 2 Hz 3H C NMR 300 MHz CDCls 8 ppm 175 156 139 129 123 120 52 4 48 9 18 4 N 4 methylphenyl N L alanine methyl ester urea A procedure analogous to the one for the preparation of N phenyl N L alanine methyl ester urea was employed The quantities of reagents used were 10 0 g 71 0 mmol L alanine methyl ester hydrochloride 99 50 mL pyridine and 9 54 g 71 0 mmol p tolyl isocyanate 99 Yield 17 4 g White Powder 90 IR KBr Pellet 3323 s 3098 w 3032 w 2992 m 2953 m 1740 s 1637 vs 1222 s cm H NMR 300 MHz Acetone de 5 ppm 8 0 s br 1H 7 35 d J 8 6 Hz 2H 7 04 d J 8 6 Hz 2H 6 10 d br J 6 0 Hz 1H 4 39 m 1H 3 68 s 3H 2 23 s 3H 1 35 d J 7 2 Hz 3H C NMR 300 MHz CDCls 8 ppm 175 156 136 133 1
20. and diethyl ether and pyridine The only appreciable difference among polymerization rates in these solvents was observed with the strongly coordinating pyridine for which the rate of polymerization is reported to be substantially slower The salient drawback of these titanium complexes is their high degree of sensitivity to atmospheric impurities namely oxygen and water The search for a more robust alternative led to the discovery that simple copper salts CuCl and CuCl also initiate living polymerizations of carbodiimides culminating in the design of the air and moisture tolerate copper Il and copper Il amidinate complexes shown in Figure 1 5 Furthermore these copper complexes proved capable of polymerizing carbodiimides in enolyzable solvents such as acetone and ethyl acetate that were problematic for the more reactive titanium initiators i N Cl ae A n Cu N Cu N Ph lt ye N aah N R x ve Cu N a Cu N T re t a N A T Si CH3 3 Ar p t Bu Ph Figure 1 5 Copper lI and Copper Il catalysts incorporating amidinate initiating groups as coordinating ligands As with the aforementioned titanium IV complexes these copper I and copper Il catalysts initiate polymerization through insertion of the carbodiimide into the bond between the metal and the initiating group forming an intermediate amidinate complex through which subsequent carbodiimide insertions propagate chain growth T
21. and properly secured oil waste container Step 33 Refill with clean vacuum pump oil to the top oil level mark shown above Monitor the oil level between changes If the oil level falls below the bottom mark the vacuum capability of the pump will drop precipitously Step 34 Apply a fresh coat of Apiezon grease to the vacuum pump tube connecter and to the inside of the rubber tubing Step 35 Attach the tubing to the vacuum pump and secure the connection with the hose clamp as illustrated 176 Step 36 Inspect the Teflon plugs Replace the O rings if they appear cracked or worn Applying a very thin coating of Apiezon M grease to each O ring is recommended as doing so will allow the O ring to slide on the glass with less friction Step 37 Inspect the rubber tubing to be attached to each stopcock line Cut off the ends if they appear cracked from previous wear Step 38 Clean the manifold stems to which each rubber tube will be attached 177 Step 39 Apply a thin coat of high vacuum silicon grease to each stem before attaching each tube 178 Step 40 Turn the vacuum pump on Twist and press each stopcock to uniformly distribute the silicon grease and tighten the seal Each stopcock should rotate smoothly If not remove the stopcock and apply more grease Step 41 traps back and vacuum to ensure a proper seal Gently twist the cold forth under As with the stopcocks apply m
22. and shim at room temperature A lock level setting of 70 to 80 is optimum Select Setup Make the appropriate Nucleus Solvent selections Type temp 40 su and hit enter to turn VT on and set the temperature to 40 C Re optimize the lock level and re shim the magnet at 40 C Increase the temperature re optimize the lock and re shim the magnet in increments of 20 C 100 C is the high temperature limit DO NOT set for greater than 100 C Also take care not to exceed the boiling point of the solvent listed in Table 1 Wait at least 10 minutes after reaching the desired temperature and then proceed with the analysis Type temp n su and hit enter to turn VT off The sample will need to cool to approximately room temperature before the software will allow sample ejection 202 Table 1 Freezing amp Boiling Point of Deuterated Solvents Warning Do not attempt analyses below 80 C or above 100 C as such extreme temperatures will damage the probe Freezing Solvent Point Boiling Point Acetic Acid d 15 C gt 100 C Acetone d lt 80 C 55 C Acetonitrile ds 45 C 80 C Benzene dg 7 C 79 C Chloroform d 63 5 C 60 C Cyclohexane d12 T C 80 C Deuterium Oxide 3 8 C gt 100 C 1 2 Dichlorobenzene d 17 C gt 100 C 1 2 Dichloroethane d 35 C 83 C Diethyl d1o Ether lt 80 C 34 C N N Dimethy
23. bearing carbodiimide structures derived by reacting L alanine methyl ester hydrochloride with various aliphatic or aromatic isocyanates in pyridine solvent and dehydrating the resulting 1 3 disubstituted ureas with triphenylphosphine dibromide in methylene chloride and triethylamine 46 2 2 2 Standard Desulfurization of 1 3 Disubstituted Thioureas The second most commonly utilized class of carbodiimide precursors in the Novak Group is 1 3 disubstituted thioureas These precursors are synthesized typically in situ via reaction of amines with isothiocyanates and are the fallback when the isocyanate needed to synthesize the analogous urea precursor is not commercially available Desulfurization of a 1 3 disubstituted thiourea produces the carbodiimide Though a variety of metal oxides such as those of zinc arsenic lead and silver are reported to effect thiourea desulfurizations and have been sporadically tested by our group members the one that remains our standard is the classical method utilizing mercuric oxide in the presence of a dehydrating agent In an effort to expand the library of novel ester bearing carbodiimides for polymerization testing L alanine methyl ester hydrochloride was reacted with 4 fluorophenylisothiocyanate which was then desulfurized in situ to afford an 83 yield of the corresponding carbodiimide Figure 2 3 0 tte aN o Sh HgO MgSO ee th nia E Sadana 4 F Figure 2 3 Synthesis of an L
24. by rotovap revealed 8 16 g of crude yellow oil The oil was dissolved in 10 mL of chloroform for column chromatography 163 g of silica 60 200 Mesh Grade 62 which is approximately 20 g per 1 g of oil were used in this column Subsequent consultation with other members of the Novak Group who utilize column chromatography routinely for carbodiimide purification suggests that using 20 g of silica per gram of carbodiimide may be far too much Best estimates are that the optimum range is from 6 to 12 g of silica per gram of carbodiimide 2 5 L of chloroform were used to develop the column The first fraction 400 mL was discarded The pure carbodiimide was isolated from the next fraction 800 mL Removal of the chloroform by rotovap followed by high vacuum revealed 1 5 g of clear slightly viscous nearly colorless oil 18 yield The much greater weight of crude oil loaded onto the column 8 16 g which would be 97 of the anticipated yield suggests that this reaction resulted in a very high yield but that the majority of the product was lost on the column IR Neat 3037 w 2978 m 2935 m 2144 s 1709 s 1599 s 1292 s cm H NMR 300 MHz CDCls 8 ppm 7 90 d J 8 4 Hz 2H 7 07 d J 8 4 Hz 2H 3 20 s 3H 1 58 s 9H N benzyl N p t butoxy carbonylphenyl carbodiimide Acetone 100 mL dried over sodium sulfate was added to a 250 mL round bottom flask N benzyl N p t butoxy carbonylphenyl thioure
25. carbodiimide Ill to a limited extent The H NMR spectrum indicates the presence of both high and low molecular weight products in comparable quantities as evidenced respectively by the mixture of broad and sharp signals having relatively equal intensities Figure 2 6 Following reflection on these preliminary results one salient feature of carbodiimides l Il and Ill conceivably responsible for their incompatibility with titanium catalysts is the presence of an enolizable proton a feature conspicuously absent on the structure of the pair of ester bearing carbodiimides successfully polymerized by Jeonghan Kim with a titanium catalyst in earlier studies Anticipating that copper catalysts capable of polymerizing carbodiimides in ethyl acetate would prove more compatible with these structures polymerization feasibility studies on carbodiimides I Il and Ill were initiated with copper ll chloride In contrast to their mixture with titanium catalysts which resulted in decomposition characterized by darkening discoloration and a loss of intensity for the N C N infrared absorption the mixture of these carbodiimides with copper Il chloride resulted in no discernible reaction 53 CDCI 3 Weeks O i oR i well cam 150 1 oi OCH CF N y 10 9 8 7 6 5 4 3 2 1 ppm Figure 2 6 H NMR spectrum of the product resulting from carbodiimide IIl reacted with CpTiCleOCH2CF3 The profile indicates high molecular weight ma
26. chloride the reaction mixture was refluxed for 1 hour 20 minutes 143 mL of t butyl alcohol were removed by rotovap at 65 C Note the freezing point of t butyl alcohol is 23 to 26 C Hence a large quantity of it will freeze to the cold finger in the rotovap Of the 143 mL of t butyl alcohol recovered 88 mL were initially recovered in liquid from the receiving flask and 55 mL were recovered from the receiving flask the next day after all of the alcohol that had frozen to the cold finger had melted Upon rotovaping to this concentration the 123 alcohol solution was saturated Saturated sodium carbonate 120 mL was added to crushed ice 2000 mL and room temperature water 500 mL The reaction mixture was transferred to a separatory funnel which was used to deliver the mixture in a steady stream to the cold sodium carbonate slurry A very large spatula was used to thoroughly mix the slurry while adding the reaction mixture The product formed yellow clumps when added to the aqueous sodium carbonate mix The resulting slurry was divided into two 1000 mL separatory funnels The product was extracted with five successive portions of chloroform 100 mL each Each chloroform portion was poured first through one funnel then the other where they were shaken vigorously in each case These extractions were performed while the water was still ice cold The chloroform collected from these extractions formed two layers the top layer of which is
27. chloroform of poly N N di n hexylcarbodiimide as a function of champhorsulfonic acid concentration R hollow boxes S Solid dots eeee 30 Titanium IV catalysts with chiral amide initiators shown in color utilized to polymerize N N di n hexylcarbodiimide for chiral end group StU E Sins bcp d tte A DA Ae a heeled 32 The R BINOL Ti O Pr 2 catalyst When polymerizing the achiral N hexyl N phenylcarbodiimide this catalyst preferentially induces a right handed P helix as assigned by comparing the spectrum observed via xii Figure 1 18 Figure 1 19 Figure 1 20 vibrational circular dichroism VCD with the one simulated by theoretical modeling calculations Curiously replacing the isopropoxides with tert butoxides reverses the helical selectivity dictating preferential induction of the left handed M helix instead Anisotropic changes in the aromatic region among variable temperature H NMR spectra of _ poly N 1 napthyl N octadecylcarbodiimide in THF dg The most noteworthy trend with increasing temperature is the disappearance of the signals for two protons from the region of broad overlap centered at 7 0 ppm corresponding with their re emergence upfield at approximately 6 5 Schematic representations of four prominent liquid crystalline phases A common feature shared by all liquid crystal phases is an orderly orientation of the molecules The distinguishing feature of phases that
28. enter to load pre programmed shim parameters that are a good starting point for further adjustment Select Acqi to enter the acquisition menu Select LOCK to enter the lock submenu Select on for the spin The spin is customarily set to 20 Hz Select off for the lock Begin by setting the lockpower and lockgain to their maximum value Adjust ZO until the resonance line rises sharply from the left and levels off as a plateau Left or right click on 4 to decrease or increase by 4 increments respectively Fine tune with 1 increment adjustments If the line fails to fully plateau change the lockphase and re adjust ZO Select on for the lock Set the lock level to 70 by reducing the lockpower and or lockgain Adjust the lockphase to maximize the lock level The optimum range for the lockpower will depend on the number of deuterium atoms on the solvent For solvents that have a weak deuterium signal such as CDCl reduce the lockpower to between 20 and 25 before reducing the lockgain For stronger solvents such as DMSO d or benzene de reduce the lockpower to between 10 and 20 before reducing the lockgain 186 Shimming the Magnet Select SHIM to enter the shim submenu Alternate 1 increment adjustments of Zc and Zc to maximize the lock level If the lock level reaches 100 return to the lock submenu and reduce the lockpower and or lockgain to lower the lock level for further shimming After maximizing the lock
29. ester bearing carbodiimide design by Jeonghan Kim Monomer VIII and IX were made by dehydrating the corresponding urea precursor while VII and X were made from the corresponding thiourea 110 Unfortunately neither poly VIll nor poly IX proved capable of transesterification Both were tested with 250 equivalents per repeat of 2 methoxyethanol in the presence of appropriate catalytic amounts of either mercury Il acetate or potassium cyanide with 18 crown 6 in chloroform at both room temperature for 3 days in one set of experiments and at 60 C overnight in another The most remarkable observation from these experiments was the thermal instability exhibited by poly VIll and poly IX Both polymers decomposed appreciably in all reactions in which they were heated as evidenced on the H NMR spectra by the replacement of broad polymer signals with the sharp signals characteristic of small molecules This thermally induced decomposition was observed even in control reactions lacking catalyst indicating that both poly VIII and poly IX are inherently unstable with respect to elevated temperatures In either case the instability appears to be a consequence of the electron withdrawing effect of the ester unit on the phenyl pendant group as the 2 2 2 trifluoroethyl ester of poly IX exacerbated this instability leading to decomposition at an accelerated rate The fourth derivative of Kim s ester bearing carbodiimide X differs from the origin
30. from the glass While taking care not to scratch the glass cut along the length of the tubing with a razor blade until the glass stem can be pulled free 169 Step 22 After trimming off the damaged portion of the tubing clean the end section of old grease deposits by use a long pair of needle nose tweezers to insert and withdraw a hexane soaked paper towel with a twisting motion Step 23 Smear Apiezon grease Step 24 Use the pipet to apply a on the thick end of a glass pipet fresh coat of grease several inches deep on inside of the rubber tubing 170 Step 25 Use a hexane soaked Step 26 Apply Apiezon grease paper towel to clean the glass to the half of the glass stem to be stem of the manifold tube inserted in the rubber tubing connecter 171 i 2 ti Step 27 Soften the grease Step 28 Insert half the length of applied to the inside of the rubber the glass stem into the rubber tubing by heating briefly with a tubing heat gun This will make it much easier to insert the glass stem 172 Step 29 Secure the connection with a hose clamp 173 Step 30 Disconnect the rubber tubing from the vacuum pump and use a hexane soaked paper towel to clean the vacuum pump tube connecter Step 31 Use a hexane soaked paper towel on a long pair of needle nose tweezers to remove old grease deposits from the tubing 174 Step 32 Drain the old vacuum pump oil into an appropriately labeled
31. level with the course shims continue shimming by alternating 4 increment adjustments of the fine shims z1 and z2 Readjust the lock level to between 70 and 80 and then select CLOSE to exit the acquisition menu Collecting a Spectrum Select Main Menu Select Setup For a sample in chloroform d select H1 CDCI3 for proton analysis or C13 CDCI3 for carbon 13 analysis For other solvents select Nucleus Solvent Select the nucleus and then the solvent from the subsequent option displays See Table 2 for the commands with which to access Other solvents Type zg and hit enter to begin the analysis The spectrum should appear on the screen once data collection is complete If the spectrum does not appear type wft and hit enter To remove extraneous traces that appear on the display type ds and hit enter Adjusting the Vertical Scale The command vsadj will optimize the vertical scale so that the fit of the most intense peak is maximized on the screen Autophasing Type aph and hit enter to autophase the spectrum This command automatically adjusts the zero and first order phasing If there is only one peak on the spectrum utilize aphO instead to adjust the zero order phasing only Manual Phasing If autophasing proves insufficient select Phase and then Left click on a peak on the far right side of the spectrum Click and hold inside the blue region and drag up or down to adjust the zero order phasing Left
32. methyl t butylcarbodiimie dicyclohexylcarbodiimide and diisopropylcarbodiimide were not Robinson also investigated the autopolymerization of diethylcarbodiimide in the absence of catalyst identifying an optimal temperature range Autopolymerization was reportedly slow at 25 C 100 C proved sub optimal converting approximately 1 of diethylcarbodiimide to polymer in 8 hours Heating at 115 to 125 C converted 50 of the carbodiimide to polymer in 30 hours while heating at 150 C resulted in less complete polymerization likely a consequence of convergence on the ceiling temperature of poly N N diethylcarbodiimide 1 3 Living Polymerization of Carbodiimides Living polymerization is most simply defined as a polymerization reaction lacking chain terminating or chain transferring side reactions Practically speaking side reactions that terminate chains prematurely and those that transfer reactivity to other species such as monomers solvent molecules or previously terminated chains lead to polymers of lower molecular weight and higher chain length variability Polymerizations of a living nature promote the synthesis of higher molecular weight materials through an exclusive reaction in which all of the monomer is consumed through growth of the originally initiated polymer chains The absence of chain terminating or chain transferring reactions significantly reduces chain length variability while also facilitating the synt
33. nitrogen in the dry box All septa were dried overnight in a vacuum chamber and stored under nitrogen in the dry box until used All filter paper covered vacuum needle assemblies utilized for air and moisture sensitive procedures were dried overnight in an oven at 140 C 73 2 6 2 Experimental Procedures and Characterizations N phenyl N L alanine methyl ester urea L alanine methyl ester hydrochloride 99 10 0 g 70 9 mmol a magnetic stir bar and reagent grade pyridine 50 mL were added to a 100 mL round bottom flask Once the L alanine methyl ester hydrochloride had dissolved hexyl isocyanate 98 8 62 g 70 9 mmol was transferred into the flask by pipet A pyridine rinse 1 mL of the weighing vial was utilized to facilitate quantitative transfer The reaction mixture was magnetically stirred overnight The next day pyridine was removed by rotovap at 50 C followed by high vacuum for two days with the flask submerged in an oil bath heated to 50 C Chloroform 50 mL and deionized water 50 mL were added to the resulting goop The flask was shook vigorously to achieve complete dissolution Following separation the chloroform extract was dried with a saturated sodium chloride wash 25 mL followed by standing for 30 minutes over sodium sulfate The solution was then added dropwise to refluxing hexanes 250 mL to precipitate the urea After cooling to room temperature the flask containing the precipitated urea was placed in
34. optimum for molecular weights of up to 2 000 while an initial selection of 100 ms is recommended for studying molecular weights in excess of 2 000 Select 2 sec for NOESY relaxation time Select OK Select DO Processing operations are analogous to those described under COSY 193 Heteronuclear Correlation Spectroscopic Techniques HMQC Heteronuclear Multiple Quantum Coherence Correlation Spectroscopy Select 16 to 32 for HMQC Scans per inc Select 128 to 256 for HMQC number of inc The aforementioned settings are fine for gHMQC as well Select the minimum spectral width that will include all carbon peaks Select OK and then select DO Processing operations are analogous to those described under COSY The scale of the carbon and proton spectra found respectively on the vertical and horizontal axes can be adjusted by selecting Proj followed respectively by V proj max or H proj max Use the middle mouse button to adjust the scale and select Plot after each respective adjustment Use the command pcon to also plot the 2D contour and page to send all of the preceding commands to the printer The command dconi will return the original display ll HSQC Heteronuclear Single Quantum Coherence Correlation Spectroscopy Appropriate settings for HSQC and gHSQC are the same as the aforementioned ones for HMQC and gHMQC Select No for the additional setting of C H multiplicity edit Process
35. point If the instrument loses the lock signal with the temperature change it may turn the lock signal off In this case turn the lock on before proceeding with the analysis Use the go command to initiate acquisition Special Notes np is the number of points in the t dimension n is the number of points in the t dimension Manual Setup for DEPT Distortionless Enhancement Polarization Transfer First setup for a routine carbon 13 experiment type nt 1 and zg to collect a single scan spectrum This will set the receiver gain Next type DEPT and hit enter Subsequent adjustments of d1 and nt can be applied to the DEPT analysis at this point Use the go command to initiate acquisition Fluorine 19 and Phosphorus 31 NMR Spectroscopy To prepare a sample for F or P NMR analysis dissolve 10 to 20 mg of sample in approximately 0 6 mL of deuterated solvent Perfluorobenzene C F referenced to Freon 11 CFCl3 as 163 0 ppm is an often used standard for fluorine 19 analyses H3PQu referenced as zero ppm is the customary standard for phosphorus 31 analyses The simplest means of referencing a compound is to add a trace of the appropriate standard directly to the sample However if the standard is not miscible in the analysis solvent or if in the case of phosphorus 31 analysis the compound to be analyzed is acid sensitive the standard may be isolated in a specially designed coaxial insert tube After locking and shimming s
36. poly N benzyl N 4 n butylphenyl carbodiimide does not decompose under analogous conditions 103 Original Polymer After 1 Week of Stirring with NaOH J i aldh After 1 Week of Sonicating with NaOH Me S bons adl 3 2 1 10 9 8 7 6 5 4 ppm Figure 3 7 H NMR spectra of poly VI before and after stirring or sonicating in a 4 1 mixture of acetone and 2 5 wt aqueous sodium hydroxide for 1 week Both stirring and sonicating in the presence of aqueous base lead to hydrolysis of the polymer backbone as evidenced by the replacement of broad polymer signals with sharp small molecule signals When compared with the ratio of broad to sharp signals in Spectrum B of Figure 3 6 the relatively lower intensity of broad signals in the bottom spectrum here indicates that sonicating in the presence of sodium hydroxide significantly accelerates the breakdown of the polymer 104 pe Original Polymer fe 0 After 1 Week of Stirring with PTSA After 12 Hours of Sonicating with PTSA PEN 10 9 8 7 6 5 4 3 2 1 ppm Figure 3 8 H NMR spectra of poly VI before and after stirring or sonicating in a 4 1 mixture of acetone and 2 0 wt aqueous p toluenesulfonic acid When compared with the ratio of broad to sharp signals in the Figure 3 7 spectra it is clear from the relatively lower intensity of broad signals here that the polymer backbone hydrolyzes more rapidly under acidic conditions than under basic cond
37. respectively Type time and hit enter to get a run time estimate with the new setting A second parameter that may be adjusted is the pulse width which may be increased to 90 degrees Type pw90 and hit enter to prompt the display to return the value of a 90 degree pulse Type pw 77 5 and hit enter if the returned value is 17 5 for instance Increase the delay time as well as outlined under Improving the Accuracy of Integration Ratios to 190 compensate for the increased pulse width Again utilize the time command to get a run time estimate with the new settings A third parameter adjustment that may be applied after collecting the data is line broadening Line broadening sacrifices resolution to improve the signal to noise ratio Type Ib 7 0 wft and hit enter to apply line broadening of 1 0 Hz To calculate the magnitude of line broadening in ppm divide the value in Hz by the field strength of the spectrometer For example on a 400 MHz spectrometer 1 Hz 400 MHz 0 0025 ppm for H or 1 Hz 100 MHz 0 01 ppm for 8C To display the signal to noise ratio for a given peak left click on top of the peak to mark it type dsn and hit enter Be aware that the exact value of this ratio is relative to the noise within the region of expansion in which the command is executed Improving the Accuracy of Integration Ratios Several factors may negatively affect the accuracy of integration ratios the most common being an insufficie
38. sets coupled with the absence of a corresponding signal for the hydroxyl proton set of 2 methoxyethanol as shown in Figure 3 4 is consistent with a high degree of transesterification for this low molecular weight batch of polymer 147 3 10 References 10 11 12 13 14 Padovani M Hilker Duxbury C Heise A Macromolecules 2008 41 2439 2444 Otera J Chemical Reviews 1993 93 1449 1470 Yamaguchi H Fujiwara Y Minoura Y Die Makromolekulare Chemie 1974 175 7 16 Yuki H Hatada K Nagata K Kajiyama K Bulletin of the Chemical Society of Japan 1969 42 3546 3550 Birch A Corrie E Macdonald P Rao G Perkin Transactions 1 1972 1186 1193 Taber D Amedio J Patel Y Journal of Organic Chemistry 1985 50 3618 3619 Kim J PhD Dissertation North Carolina State University 2002 Olah G Ho T Synthesis 1977 1977 417 418 Olah G Ho T Angewandte Chemie International Edition in English 1976 15 774 775 Taylor E Fletcher S Sabb A Synthetic Communications 1984 14 921 924 Goodwin A PhD Dissertation University of California at Berkley 1996 Schlitzer D PhD Dissertation University of Massachusetts Amherst 1998 Tang H Boyle P Novak B Journal of the American Chemical Society 2005 127 2136 2142 Purification of Laboratory Chemicals Perrin D Armarego W Eds Pergamon Press Oxford 1988 148 APPENDICES 14
39. the American Chemical Society 1995 117 4181 4182 Aly A Nour El Din A ARKIVOC 2008 2008 153 194 Noyori R Asymmetric Catalysis in Organic Synthesis Wiley New York 1994 Mikami K Terada M Nakai T Journal of the American Chemical Society 1989 117 1940 1941 Matsukawa S Mikami K Tetranedron Asymmetry 1995 6 2571 2574 Keck G Geraci L Tetrahedron Letters 1993 34 7827 7828 Casolari S D Addario D Tagliavini E Organic Letters 1999 1 1061 1063 Tang H Garland E Novak B Macromolecules 2007 40 3575 3580 http obarrett group mcgill ca teaching liquid_crystal LC01 htm Aharoni S Macromolecules 1979 12 94 103 Aharoni S Walsh E Macromolecules 1979 12 271 276 Bianchi E Ciferri A Krigobaum W Macromolecules 1984 17 856 861 43 Chapter 2 Polymerization of Novel Ester Bearing Carbodiimides 2 1 Introduction Since the first living polymerization of a carbodiimide reported in 1994 several dozen polycarbodiimide structures have been synthesized and characterized by the Novak Group The vast majority of these structures have simple aliphatic or aromatic pendant groups as substituents Only a handful of them have pendant groups containing a heteroatom and most of these are either halogens attached to an aromatic ring or oxygen in the form of relatively inert ether groups Prior to the work in this chapter only two carbodiimides containing ester functionalities have
40. to develop photoswitchable chiral pendant groups preparation of polycarbodiimide coated nanoparticles development of cross linked cholesteric polycarbodiimide gels and the synthesis and characterization of water soluble polycarbodiimides The focus of this dissertation is the synthesis and characterization of polycarbodiimides presenting ester bearing pendant groups 1 2 Early Studies on Carbodiimide Polymerization The first publication on the polymerization of carbodiimides was authored by G C Robinson in 1964 Upon testing several anionic and cationic initiators under a variety of conditions the only combination that proved even a qualified success was n butyllithium in hydrocarbon solvents reported to yield low molecular weight polymer regardless of the solvent temperature or monomer to initiator ratio Conditions that failed to facilitate polymerization include sodium dispersion in dimethylformamide at 20 or 40 C anhydrous aluminum bromide in toluene at 25 C methyl iodide in xylene at 25 C and p bromobenzenesulfony chloride in toluene at 25 C Monomers successfully polymerized by n butyllithium in hydrocarbon solvent include diethylcarbodiimide di n butylcarbodiimide di n hexylcarbodiimide diphenylcarbodiimide and diallylcarbodiimide While methylisopropylcarbodiimide having one secondary alkyl substituent also proved capable of anionic polymerization monomers of greater steric hindrance such as
41. vis a vis acids and bases When stirred or sonicated in a mixture of acetone and either aqueous 2 5 wt sodium hydroxide or 2 0 wt para toluenesulfonic acid this polycarbodiimide proves completely inert Comparisons by gel permeation chromatography before and after such treatments revealed no appreciable change in molecular weight estimates relative to polystyrene standards Another common feature of dead polycarbodiimides bearing simple alkyl and aryl substituents is their relative stability in solution at the elevated temperatures with which annealing studies are conducted where racemization of single handed helices are observed without appreciable polymer decomposition The extensive investigations that follow suggest these properties robustness vis a vis acids and bases as well as stability in solution at elevated temperatures to be artifacts of the electron donating ability of the alkyl or aryl substituents rather than inherent properties of the polycarbodiimide backbone The placement of an electron withdrawing ester group in close proximity to the backbone easily undermines such felicitous properties leading to thermally unstable structures that hydrolyze at least as well with acids or bases as the ester groups themselves 94 3 2 Base Catalyzed Hydrolysis of a New Ester Bearing Polycarbodiimide The prototype of the novel ester bearing polycarbodiimides discussed in Chapter 2 is poly lll Attached to the polymer backbone t
42. which the helical conformation may be biased The first is via the effect that the pendant chiral entity has on the conformation adopted by the subsequent repeat unit during the polymerization process When chiral monomers approach the site of 20 chain propagation steric interactions with the chiral entity on the previously inserted monomer dictate the rate at which a given monomer orientation and angle of approach are utilized Insertions from some orientations and angles are more facile than those from others resulting in chain conformations that are controlled by the kinetics of these chiral interactions In this manner a polycarbodiimide adopts what is referred to as a kinetically controlled conformation However such conformations are not necessarily the most stable Indeed the most stable conformation is occasionally the exact opposite of the one dictated by kinetics Poly N R 2 6 dimethylheptyl N phenylcarbodiimide for instance adopts a kinetically controlled conformation exhibiting an optical rotation a 435 of 209 However when annealed at temperatures between 50 and 85 C the optical rotation changes to 255 Given that the original monomer had a rotation of merely 0 32 the magnitudes of these measurements are due almost exclusively to the chirality of the helix The sign change in this case is consistent with a reversal of the handedness of the helix Thus through an annealing process a polycarbodiimide may
43. 296 s cm H NMR 300 MHz Acetone dg 5 ppm 7 87 d J 8 7 Hz 2H 7 5 to 7 2 m 5H 7 08 d J 8 7 Hz 2H 4 71 s 2H 1 56 s 9H 133 N methyl N p methoxycarbonylphenyl carbodiimide Acetone 100 mL dried over sodium sulfate was added to a 250 mL round bottom flask N methyl N p methoxycarbonylphenyl thiourea 4 20 g 18 7 mmol and a magnetic stir bar were added A reflux condenser was attached and the flask was positioned in a hot oil bath heated to 75 C Mercury Il oxide 99 6 14 g 28 1 mmol a 50 excess was added at a rate of approximately 1 to 1 5 g every 12 minutes After the last addition the reaction was refluxed for 3 hours Immediately upon removing the flask from heat the supernatant was recovered with a filter paper covered vacuum needle assembly See Appendix 1 for filter paper covered vacuum needle assembly instructions This worked well only a trace of the mercury sulfide byproduct transferred with the supernatant The mercury sulfide precipitate was rinsed with two portions of acetone 5 mL each to facilitate transfer of the carbodiimide The acetone solution was concentrated to approximately 20 mL and loaded onto a column consisting of 2 cm sand and 35 0 g silica gel 60 200 Mesh Grade 62 The column was developed with chloroform 300 mL The first fraction 50 mL was discarded The second fraction 50 mL characterized by a strong yellow discoloration was isolated for fur
44. 30 121 52 4 48 9 20 8 18 5 N n propyl N L alanine methyl ester urea A procedure analogous to the one for the preparation of N phenyl N L alanine methyl ester urea was employed The quantities of reagents used were 6 04 g 43 7 mmol L alanine methyl ester hydrochloride 99 25 mL pyridine and a 10 excess 4 04 g 48 0 mmol of propyl isocyanate 99 Yield 6 54 g Off White Powder 80 IR KBr Pellet 3334 s 2964 w 2876 w 1748 s 1634 s 1219 s cm H NMR 300 MHz Acetone de 5 ppm 4 32 q 1H 3 65 s 3H 3 06 t 2H 2 84 s br 1H 2 72 2 br 1H 1 40 m 2H 1 29 d 3H 0 87 t 3H 75 N n hexyl N L alanine methyl ester urea A procedure analogous to the one for the preparation of N phenyl N L alanine methyl ester urea was employed The quantities of reagents used were 5 01 g 35 5 mmol L alanine methyl ester hydrochloride 99 25 mL pyridine and an 8 excess 5 02g 38 3 mmol of hexyl isocyanate 97 Yield 6 07 g Tan Powder 74 IR KBr Pellet 3336 s 2962 w 2875 w 1734 s 1633 s 1217 s cm H NMR 300 MHz CDCls amp ppm 5 29 s br 1H 4 84 s br 1H 3 99 q 1H 3 78 s 3H 3 25 t 2H 1 45 m 2H 1 42 d 3H 1 22 m 6H 0 87 t 3H N 4 chlorophenyl N L alanine methyl ester urea A procedure analogous to the one for the preparation of N phenyl N L alanine methyl ester urea was employed The quantities of reagents used w
45. 4 m cm H NMR 300 MHz Acetone de 8 ppm 9 24 s br 1H 7 91 d J 9 0 Hz 2H 7 84 s br 1H 7 67 d J 8 7 Hz 2H 7 4 to 7 2 m 5H 4 89 d J 5 1 2H 1 57 s 9H N methyl N p methoxycarbonylphenyl thiourea Methyl p aminobenzoate 6 00 g 39 7 mmol was weighed and transferred to a 250 mL round bottom flask Chloroform 100 mL and a magnetic stir bar were added Methyl isothiocyanate 97 2 99 g 199 mmol a 400 excess was added and the reaction mixture was heated for 6 days at 60 C The product a light brown solid was suspended in the chloroform at the time the reaction was removed from heat 129 After cooling to room temperature the flask was stoppered and placed in the refrigerator for 2 hours The cold supernatant was removed by use of a filter paper covered vacuum needle assembly See Appendix 1 for filter paper covered vacuum needle assembly instructions Removal of the remaining volatiles by high vacuum revealed 8 84 g light brown powder 99 yield IR KBr Pellet 3448 s 3386 s 3026 w 2945 w 1707 s 1533 s 1173 m 1111 m cm H NMR 300 MHz CDCI 8 ppm 8 06 d J 8 7 Hz 2H 7 95 s br 1H 7 25 d J 8 7 Hz 2H 6 26 s br 1H 3 90 s 3H 3 16 s J 4 5 3H N hexyl N p methoxycarbonylphenyl urea Methyl p aminobenzoate 5 25 g 34 7 mmol was added to chloroform 50 mL in a 100 mL round bottom flask Hexyl isocyanate 97 9 11 g 70 9 mmol
46. 50 mL to precipitate the polymer Removal 143 of the methanol by filtration followed by high vacuum revealed 2 28 g of fine yellow powder 81 yield IR KBr Pellet 3068 vw 2952 m 2931 m 2858 w 1722 s 1631 s 1591 s 1275 s 1113 s cm H NMR 300 MHz CDCI 5 ppm 7 80 6 74 6 47 5 61 4 21 3 82 3 64 3 44 3 16 3 06 2 88 2 52 1 58 1 03 0 72 0 4 all broad 169 6 C Decomposition Temperature 5 Loss of Mass Specific Optical Rotation measured 31 2 0 4 Poly N hexyl N p 2 2 2 trifluoroethoxy carbonylphenyl carbodiimide S 1 1 Binapth 2 2 ol titanium IV diisopropoxide 682 mg was dissolved in anhydrous chloroform 2 0 mL in a nitrogen filled dry box N hexyl N p 2 2 2 trifluoroethoxy carbonylphenyl carbodiimide 89 1 91 g 5 18 mmol was dissolved in anhydrous chloroform 1 mL in a separate 10 mL glass vial A magnetic stir bar was added 0 50 mL of the catalyst solution 25 5 mg 52 0 umol was transferred to the vial containing the carbodiimide IR analysis after 3 days revealed only a trace of remaining carbodiimide Following failure of microscale workup experiments the reaction mixture was transferred to a 100 mL round bottom flask Several methylene chloride rinses were utilized to facilitate quantitative transfer Removal of the volatiles by rotovap followed by high vacuum revealed a crunchy orange powder The characterization data that follow are for the cr
47. 6 3 3 Transesterification Studies on a New Ester Bearing Polycarbodiimide As mentioned in Chapter 2 the incentive for developing a novel class of ester bearing polycarbodiimides is to provide these architectures with a modifiable pendant group One route to modifying compounds having an ester group is to hydrolyze the ester and then react the resulting carboxylic acid or carboxylate with an alcohol or an amine to respectively create a new ester or amide linkage But the susceptibility of the prototype to base catalyzed hydrolysis of the backbone precludes modifications in this manner An alternative strategy is transesterification with an alcohol Transesterification enzymes are often employed to facilitate such reactions When compared with chemical catalysts enzymes offer several advantages such as milder reaction conditions Enzymes are also capable of regio and stereoselective transesterifications But for the purposes of modifying pendant esters enzymes can exhibit one salient drawback which is a complete lack of reactivity for ester groups located in close proximity to the backbone as reported in the case of poly styrene co methyl 2 4 styryl acetate This in spite of the fact that the monomer methyl 2 4 styryl acetate is transesterified with alcohols by resin bound Candida Antarctica Lipase B in high yields When a diester derivative of the aforementioned polymer incorporating five methylene spacers between the proximal and dista
48. 8 vw 2952 m 2929 m 2858 w 2141 vs 1720 s 1275 s cm H NMR 300 MHz Acetone de 5 ppm 7 95 d J 8 7 Hz 2H 7 17 d J 8 7 Hz 2H 3 86 s 3H 3 55 t J 6 8 Hz 2H 1 73 m 2H 1 46 m 2H 1 33 m 4H 0 88 t J 7 0 Hz 3H N hexyl N p 2 2 2 trifluoroethoxy carbonylphenyl carbodiimide Dibromotriphenylphosphorane salt 98 7 04 g 16 3 mmol a 25 excess was dissolved in methylene chloride 40 mL in a 100 mL round bottom flask A magnetic stir bar was added and the flask was placed in an ice water bath Triethylamine 99 4 8 mL 3 45 g 34 1 mmol a 33 excess was added to the reaction at a rate of approximately 1 mL every 5 minutes N hexyl N p 2 2 2 trifluoroethoxy carbonylphenyl urea 4 53 g 13 1 mmol was suspended in methylene chloride 50 mL The suspension of urea was added at a rate of approximately 6 mL every 5 minutes The next day the product solution was washed with deionized water 100 136 mL followed by two successive washes of saturated sodium chloride 100 mL each Then the solution was dried by standing over sodium sulfate for 30 minutes The solution was filtered into a 100 mL graduated cylinder and the sodium sulfate was rinsed with sufficient methylene chloride to bring the total volume of the solution to 100 mL The solution was divided into two equal portions 30 g of silica gel Davisil Grade 644 100 200 mesh was loaded onto a 4 cm diameter column Dav
49. 9 Appendix 1 Filter Paper Covered Vacuum Needle Assembly Instructions Fisherbrand Fil Paper Step 1 Begin by cutting out a Step 2 Position the hilt of a 12 quarter section of 11 cm diameter inch 18 gauge needle at the Qualitative P8 creped center of the quarter cut as Fisherbrand Filter Paper shown Folds to be made in Steps 3 and 4 are outlined by the dashed lines 150 Step 3 Fold the left side of the Step 4 Fold the right side of the quarter cut across the top of the quarter cut as well as the overlap needle hilt as illustrated from the left side fold back across the top of the needle hilt 151 Step 5 At this point the folds should amount to a cone over the needle hilt The next fold to be made is outlined by the dashed line p mep Pg Step 6 Fold the top of the cone down and over the needle hilt until it is flush with the opposite side Step 7 Turn the hilt over and pinch the edges of the overfold flush with the sides of the needle as shown 153 Step 8 Begin securing the filter paper to the needle hilt by wrapping Teflon tape around the top edge of the needle hilt first Do not wrap the Teflon tape over the end of the hilt the end should only by covered by the filter paper Step 9 Tightly continue the Step 10 Cut the tape from the Teflon tape wrap down the roll sparing several inches with needle until the entire length of which to tie the tape to the fol
50. 930 s 2858 m 2130 vs 1467 w 1342 w 725 vw cm H NMR 300 MHz CDCl 6 ppm 3 17 t J 6 8 Hz 2H 1 54 m 2H 1 28 m 6H 0 88 t J 6 7 Hz 3H C NMR 300 MHz CDCls 8 ppm 141 47 9 31 6 31 5 26 7 22 8 14 3 CpTiCls In a dry box Cp TiCl 10 0 g 40 38 mmol and a large magnetic stir bar were placed in a 250 mL 3 neck flask A reflux condenser topped with a joint to hose adapter having a stopcock was attached to the center neck Each side neck of the flask was sealed with a rubber septum The assembly was removed from the dry box attached to a Schlenk line and opened to a positive pressure of nitrogen Dry toluene 100 mL was added to the flask via syringe The flask was submerged in an ice water bath on top of a magnetic stir plate Titanium IV chloride 13 5 mL 123 mmol was added to the stirring contents of the flask via syringe The flask was removed from the ice water bath wiped dry and placed in an oil bath heated to 135 C The reaction mixture was refluxed for 6 hours and then 83 left to stir at room temperature overnight The following day the flask was submerged in an ice water bath for 30 minutes The solvent was removed with a filter paper covered vacuum needle assembly See Appendix 1 for filter paper covered vacuum needle assembly instructions Following removal of the solvent the septa were replaced with glass stoppers lubricated with high vacuum silicon grease Vacuum d
51. ABSTRACT CLARK IV JOE BOAZ The Synthesis and Characterization of Ester Bearing Polycarbodiimides Under the direction of Bruce M Novak Over the last decade and a half research in the Novak Group has focused predominantly on a class of helical macromolecules known as polycarbodiimides As a group our earliest works focused on the living polymerization of carbodiimides with both early and late transition metal catalysts The extensive studies that followed probed the cooperativity of the helix with various pendant catalytic or ionically associated chiral entities Investigations into the optical properties of these materials identified liquid crystalline behavior as well as an optical switching phenomenon in association with certain architectural features The vast majority of the polycarbodiimides that have been synthesized and studied to date bore simple aliphatic or aromatic pendant groups Though they have proven highly stable under both acidic and basic conditions and relatively stable at elevated temperatures few efforts have been made to develop structures capable of utilizing these properties for subsequent pendant group modifications The efforts described herein recount the ordeal of synthesizing a new subclass of polycarbodiimides bearing ester pendant groups and chronicle what the reactivity of these novel structures has taught us about the fundamental properties of the polycarbodiimide structure The ester bearing carbodiimi
52. Another polymer developed for these applications places the carbodiimide unit as a pendant group rather than as part of the polymer backbone Though these materials consist of repeat units that are not derived from the polymerization of a carbodiimide monomer and are thus not polycarbodiimides in this customary sense the fact that they contain many carbodiimides has led to their description as polycarbodiimides QIO Re aS Sn Ne r Figure 1 1 Examples of polymers containing carbodiimide units Polyhexamethylenecarbodi imide was obtained by the stepwise decarboxylation of 1 6 di isocyanate hexane with 3 methyl 1 phenyl 3 phospholene 1 oxide catalyst in N methyl 2 pyrrolidone solvent Crosslinked polystyrene presenting 2 4 mmol pendant carbodiimide per gram was obtained from chloromethylated crosslinked polystyrene via Gabriel Synthesis followed by reaction with isopropylisocyanate and subsequent dehydration with p toluenesulfonyl chloride and triethylamine in refluxing methylene chloride On the other hand authentic polycarbodiimides i e those obtained via polymerization of carbodiimides are often referred to as polyguanidines Glancing at a 1 dimensional representation Figure 1 2 the structure might appear to showcase repeating guanidine units but the dihedral angle between one amidine unit and the next is approximately 60 breaking the planarity that is a defining feature of the guanidine unit R R R R R R R
53. Collectively occupying either of two positions having dipole moments aligned with or against the helical director these flap like appendages often rearrange synchronously in response to changes in solvent polarity or temperature as illustrated in Figure 1 18 an 9l u lt Figure 1 18 Two states resulting from shutter like motions of 1 napthyl substituents The specific optical rotation changes dramatically in response to these reversible rearrangements ranging from 1300 at 0 C to 400 at 50 C for poly N 1 naphthyl N octadecylcarbodiimide in THF as an example The rotation of the 1 naphthyl units changes their 1 electron interactions with the nitrogen lone pairs on the backbone leading to a switch observable via ECD and anisotropic changes among variable temperature H NMR spectra Figure 1 19 while leaving the chirality of the backbone sensed by the VCD absorption of the C N bond unchanged 35 BRSRARSS BABAR BOARS BARES BARES OR SAS EAS BOOS BOOS BREA S BORA BBR BEES BS 9 5 9 0 8 5 8 0 7 5 7 0 6 5 6 0 5 5 5 0 Chemical Shift ppm San faa OA fn le Enea ae te een an Sate eh eee Oa Figure 1 19 Anisotropic changes in the aromatic region among variable temperature H NMR spectra of poly N 1 napthyl N octadecylcarbodiimide in THF dg The most noteworthy trend with increasing temperature is the disappearance of the signals for two protons from the region of broad overlap centered at 7 0 ppm corre
54. Levy M Milkovich R Journal of the American Chemical Society 1956 78 2656 2657 Goodwin A Novak B Macromolecules 1994 27 5520 5522 Patten T Novak B Journal of the American Chemical Society 1991 113 5056 5066 Goodwin A PhD Dissertation University of California at Berkley 1996 Shibayama K Seidel S Novak B Macromolecules 1997 30 3159 3163 Butler G Cyclopolymerization and Cyclocopolymerization Marcel Dekker Inc New York 1992 Patten T PhD Dissertation University of California Berkeley 1994 Madorsky S Thermal Degradation of Organic Polymers John Wiles amp Sons New York 1964 Gao Y Kogler F Schubert U Journal of Polymer Science Part A 2005 43 6586 6591 Schlitzer D PhD Dissertation University of Massachusetts Amherst 1998 Debye P Journal of Physical and Colloid Chemistry 1947 51 18 32 Flory P Principles of Polymer Chemistry Cornell University Press Ithaca 1953 Green M Reidy M Journal of the American Chemical Society 1989 111 6452 6454 42 49 50 51 52 53 54 55 56 57 58 59 60 61 62 Langeveld Voss B Waterval R Meijer E Macromolecules 1999 32 227 230 Jin W Fukushima T Niki M Kosaka A Ishii N Aida T Proceedings of the National Academy of Sciences of the United States of America 2005 102 10801 10806 Green M Garetz B Munoz B Chang H Journal of
55. NERIAN EiS 7 Copper I and Copper Il catalysts incorporating amidinate initiating groups as Coordinating ligands ccccccececeeeeeeeeeeeeeeeeeeseeeteeeeeeees 8 Illustration of initiation propagation and termination steps of carbodiimide polymerization with a titanium alkoxide complex These Figure 1 7 Figure 1 8 Figure 1 9 Figure 1 10 Figure 1 11 living polymerizations are typically terminated by precipitating a hydrocarbon solution of the polymer in methanol though exchangeable protons from any source terminate propagation in an analogous VDERINEV SE sees save et ca a aoe le ih a ti ria est he pr 9 Thermally induced free radical depolymerization mechanism 11 Structure of the dicarbodiimides 1 4 di N methylcarbodiimidio butane and 1 4 di N methylcarbodiimido hexane utilized for the crosslinking of poly N N di n hexylcarbodiimide cccceeeeeeeeeeeeeeeeeeeeeeeeeeeeeees 12 Two regiochemistries of an asymmetrically substituted repeat unit 13 Illustration of depolymerization product s resulting from scissions across original monomer units for regiospecific versus non regiospecific microstructures irregularly inserted monomer shown in red The alternative scissions between the original monomer units would return the original monomer exclusively in either case 14 Pyramid of Cooperativity The hierarchy of the pyramid illustrates the lengths to which a given polym
56. R 7 7 7 7 4 N N N N N N N N AIII AA Ban N N N N N N N N R R R R R R R R Figure 1 2 1 Dimensional representation of atom connectivity within the polymer obtained via polymerization of a carbodiimide The result is a polymer that adopts a 6 1 helix Figure 1 3 in the solid state as suggested by molecular modeling and confirmed by X ray scattering studies e amp e e 9E e e VP LO s oP So ae Y oe a gt tggl shee Figure 1 3 Ball and stick model of the 3 dimensional helical arrangement of carbon and nitrogen atoms within the polycarbodiimide backbone colored black and blue respectively and substituents colored gray The persistence of the helical conformation in solution suggested by viscosity and light scattering data led to chiro optic experiments probing the cooperativity of polycarbodiimides with various chiral entities towards induction of right or left handed biases between helical conformations These studies culminated in the helix sense selective polymerization of achiral carbodiimides with chiral catalysts while also leading to publications on polycarbodiimides displaying liquid crystalline 25 26 27 29 properties and a chiroptical switching phenomenon Unpublished works that have been the subject of dissertation research within the Novak Group include the exploration of polycarbodiimide absorption properties 0 at solution solid interfaces efforts
57. V is thought to be initiated via insertion of the carbodiimide into the bond between the metal and the initiating ligand it is logical to ask whether limitations in this regard for a given combination of carbodiimide and catalyst relate to the nucleophilicity of the initiating ligand The failure of copper Il chloride to initiate the polymerization of carbodiimide Ill is a case in point Given that chloride is generally considered a fair nucleophile the question is whether a ligand that is a good nucleophile such as cyanide or an alkoxide or an excellent nucleophile such as a thiolate might succeed in initiating carbodiimide polymerizations with copper I or Il where chloride fails Earlier research on the polymerization of carbodiimides with copper 1 and Il explored the utility of two catalysts using alkoxide initiating ligands One Cu O t Bu polymerized N N di n hexylcarbodiimide within 1 week at room temperature but the yield of the reaction 54 was relatively low compared with that of the analogous reaction using CuCl 96 The other Cu OMe Cl polymerized N N di n hexylcarbodiimide in much higher yield 99 a result that is more likely attributable to the enhanced oxidative state of the copper rather than to the reduced steric hindrance of the smaller methyl substituent When compared with the 100 yield of the analogous reaction using CuCl2 again there appears to be no inherent advantage from the use of an
58. a 5 00 g 12 6 mmol and a magnetic 132 stir bar were added A reflux condenser was attached and the flask was positioned in a hot oil bath heated to 70 C Mercury Il oxide 99 4 79 g 21 9 mmol was added at a rate of approximately 1 g every 12 minutes After the last addition the reaction was refluxed for 4 hours Immediately upon removing the flask from heat the supernatant was recovered with a filter paper covered vacuum needle assembly See Appendix 1 for filter paper covered vacuum needle assembly instructions The mercury sulfide precipitate was rinsed with two portions of acetone 5 mL each to facilitate transfer of the carbodiimide The acetone was removed by rotovap revealing 4 63 g of yellow oil The oil was dissolved in chloroform 10 mL for column chromatography 46 2 g of silica 60 200 particle size 62 Grade which is approximately 10 g per 1 g of oil topped with 2 cm of sand were used in the column The sample was loaded onto the chloroform soaked column and developed with chloroform The structure of the column was compromised somewhat from the force of pouring in the developing solvent with less than appropriate care The first 100 mL fraction was discarded The carbodiimide was isolated from the next 350 mL Removal of the chloroform by rotovap followed by high vacuum revealed 2 30 g of clear oil 49 yield IR Neat 3087 vw 3064 w 3030 w 3005 w 2978 m 2931 m 2870 w 2135 vs 1709 s 1
59. age the probe Select OK and then select DO Processing operations are analogous to those described under COSY IV NOESY1D 1D Nuclear Overhauser Effect SpectroscopY 1D NOESY reveals through space H H correlations with the proton signal of a selected frequency For observations of NOE it is important to deoxygenate the sample prior to analysis One simple but crude deoxygenating method is to begin with a sufficient excess of solvent and bubble nitrogen through the sample for five minutes The more thorough recommended method is to utilize several freeze pump thaw cycles under Nb After selecting desired parameters and running the 1D analysis box and Expand the proton signal to be analyzed for through space correlations Place the cursor on the center of the signal peak and select Select You may select multiple peaks to set up a series of analyses After selecting all peaks of interest select Proceed Each of the resulting spectra will reveal the through space correlations with one of the selected proton signals for the given mixing time V NOESY 2D Nuclear Overhauser Effect SpectroscopY Select 64 for NOESY scans per inc to maximize the signal to noise ratio Select 128 for NOESY number of inc The optimum selection for NOESY mixing time will depend on the distance of the spatial interaction one wishes to observe and on the molecular weight of the molecule being analyzed 500 ms to 1000 ms is typically
60. al Shifts 205 List of Useful Varian NMR Software Commands 2 c0cceecceeceeeeeeeeeees 206 viii LIST OF TABLES Table 1 1 Optical rotation data of poly N N di n hexylcarbodiimides prepared with chiral initiators measured in chloroform at the sodium D line 598 Figure 1 1 Figure 1 2 Figure 1 3 Figure 1 4 Figure 1 5 Figure 1 6 LIST OF FIGURES Examples of polymers containing carbodiimide units Polyhexamethylenecarbodi imide was obtained by the stepwise decarboxylation of 1 6 di isocyanate hexane with 3 methyl 1 phenyl 3 phospholene 1 oxide catalyst in N methyl 2 pyrrolidone solvent Crosslinked polystyrene presenting 2 4 mmol pendant carbodiimide per gram was obtained from chloromethylated crosslinked polystyrene via Gabriel Synthesis followed by reaction with isopropylisocyanate and subsequent dehydration with p toluenesulfonyl chloride and triethylamine in refluxing methylene Chloride cccceeeeeeeeeeeeeeees 2 1 Dimensional representation of atom connectivity within the polymer obtained via polymerization of a carbodiimide cccccccceeeeeeeees 3 Ball and stick model of the 3 dimensional helical arrangement of carbon and nitrogen atoms within the polycarbodiimide backbone colored black and blue respectively and substituents colored gray Titanium catalysts first found to initiate the living polymerization of CARD OCIIMOS S39 ccs inca isinisisi rA E As inte E A
61. al in that the pendant methyl is replaced with a benzyl group The aim was to develop a more robust structure on which the t butyl ester substituent could be hydrolyzed without compromising the polycarbodiimide backbone By replacing the pendant methyl with a benzyl group the resulting polycarbodiimide would hybridize Kim s design with one proven to be stable in strong acid or base Figure 3 12 111 Hybridization of Unstable amp Stable Polycarbodiimide Designs x O iy cm1 N 1635 cm1 1044 cm1 Ox j n wan Stable Figure 3 12 Hybrid design crossing Kim s ester bearing polycarbodiimide which is unstable under conditions that are strongly acidic or basic and even decomposes upon mere sonication with a structure proven to be robust even when sonicated under strongly acidic or basic conditions for 1 week 112 Curiously poly X exhibited the instability of Kim s design with respect to sonication and aqueous base but it inherited the robustness of poly N benzyl N 4 n butylphenyl carbodiimide with respect to aqueous acid Unfortunately the t butyl ester substituent proved to be just as stable under acidic conditions when presented from this structure thus precluding subsequent polycarbodiimide modifications via coupling of alcohols or amides with a pendant free acid 3 7 Polycarbodiimide Regiochemistry Microstructural Determination via C NMR As mentioned in Section 1 5 for any asymmetrically substitute
62. al nematic or cholesteric phase Smectic phases are characterized by the restricted layering of molecules In the smectic A phase the orientation of the molecules is perpendicular to the layering In the smectic C phase the molecules are tilted relative to the layering 37 Combining side chains capable of imparting both fluidity and chirality with a helical backbone that acts as a mesogen polycarbodiimides can be modified to induce a variety of lyotropic liquid crystalline phases The versatility afforded by two side chains per repeat proves felicitous in this regard When comparing poly N N di n hexylcarbodiimide with its isocyanate analogue poly n hexyl isocyanate the former forms more highly ordered smectic textures while the latter adopts nematic phases Here the polycarbodiimide s higher side chain density enhances the corona barrier leading to more uniform separation of the helices Figure 1 19 By varying the length of the two side chains per repeat polycarbodiimides can also be induced to form nematic liquid crystal phases Poly rac N methyl N a methylbenzyl carbodiimide for instance adopts a nematic texture Its optically pure analogue poly A N methyl N a methylbenzyl carbodiimide exhibits a cholesteric phase The latter also forms mesophases at lower concentrations an observation that correlates with data from light scattering and thermal analyses suggesting that the optically pure chains a
63. alkoxide initiating ligand 60 The earlier studies also investigated three copper amidinate complexes Figure 1 5 2 The good nucleophilicity of the amidinate ligand coupled with the enhanced solubility of their copper complexes did make the copper amidinates highly active polymerization catalysts for carbodiimides However as mentioned earlier the challenges of synthesizing and purifying these copper amidinate complexes discouraged their utilization in subsequent research Given this consideration efforts to find a superior copper catalyst for the polymerization of novel ester bearing carbodiimides began with a search of commercially available copper salts A quick survey of the Aldrich catalogue revealed several candidates pairing copper with ligands having a nucleophilicity predictably greater than that of chloride including CuBr CuBrz CuCN and Cul Considering that thiolates are excellent nucleophiles the two commercially available salts that seemed most tantalizing were copper I butanethiolate and copper l thiophenolate Since carbodiimides and the solvents in which they are often polymerized tend to be relatively non polar the alkyl and aryl chains respectively attached to these thiolates would enhance their carbodiimide solubility relative to that of the aforementioned commercially available copper salts Preliminary experiments with these copper I thiolates utilizing a 100 1 ratio of monomer to initiator revealed butaneth
64. and doti will prompt the entry of three parameters ENTER MINIMUM T1 EXPECTED ENTER MAXIMUM T1 EXPECTED and ENTER EXPERIMENT TIME hours For protons 0 1 seconds would be a good starting point for the minimum T1 estimate while 2 seconds is a good first guess for the maximum Following entry of these parameters utilize the command go to initiate the sequence of analyses Save the data following acquisition To analyze the data select Load Analyze Exponential T1 Proc and then T1 Analysis The program will display the plots horizontally by default To view and print a stacked plot of the spectra begin by selecting Main Menu Display Size and then Left Type vs and hit enter to find out the default vertical scale setting Use the command format vs 200 to reduce the vertical scale as needed to create an appropriate fit Determining the optimum vertical scale for a given number of spectra will be a matter of trial and error Type vp 10 pscale and hit enter to set the scale to plot at the bottom of the page Type vp 0 dssa to display the stacked plots and set the first one to print 10 mm above the scale Use the commands pl all to plot the stacked spectra and page to send the preceding commands to the printer 197 APT Attached Proton Test The appropriate sample concentration for an Attached Proton Test is the same as for a basic C spectrum Before running an Attached Proton Test collect and sa
65. ant group to induce its thermodynamically preferred helical sense a study with enantiomerically pure camphorsulfonic acids finds that a tightly bound chiral counteranion favoring the opposite helical sense can exert an even greater conformational influence When virgin _ poly N R 2 6 dimethylhexyl N hexylcarbodiimide a ses 7 5 is protonated with R CSA in chloroform the net optical rotation of the polymer measures 300 However when protonated with S CSA the net rotation measures 24 When dissolved in tetrahydrofuran rather than chloroform this chiral counteranion effect is essentially negated by the more distanced ion pairing resulting in net rotations of 123 and 102 following protonation with R and S CSA respectively This chiral counteranion has also proven capable of chaperoning the induction of a single handed helix from a racemic mixture of helices on a 28 polycarbodiimide bearing achiral substituents When _ poly N N di n hexylcarbodiimide is protonated with increasing amounts of S CSA an exponential increase in the net specific rotation is observed Figure 1 15 Here too an essential element in the efficacy of helical induction is a tight pairing of the chiral counteranion with the protonated polycarbodiimide backbone When protonated with 4 25 equivalents of S CSA in chloroform the net rotation of the polymer is 250 but when equivalently protonated in tetrahydrofuran the more
66. ap of conditions catalyzing both polymerization and dimerization precludes exclusive polymer synthesis the challenge becomes removing the dimers afterward The standard approach to isolating high molecular weights utilizes the general principle that with rare exception a polymer s solubility decreases with increasing molecular weight The two general methods of doing this are fractional precipitation which progressively precipitates lighter fractions and fractional extraction which progressively extracts heavier fractions Through a process of trial and error following the synthesis of each batch of poly lIll a crude method was developed to successfully remove the vast majority of small molecule contaminants The general procedure involves precipitating a single heavy fraction followed by extracting a single light fraction from the heavy fraction As a rule the relative quantity of small molecules that remain is directly proportional to the total recovery In other words the higher the recovery the higher the relative amount of contaminants The H NMR spectrum of a typical clean polymer reveals negligible amounts of dimer following a 33 recovery Figure 2 14 69 CDCI Clean Polymer 12 Days 60 C 10 9 8 7 6 5 4 3 2 1 ppm Figure 2 14 H NMR spectrum of a clean polymer isolated by precipitation of a single heavy fraction followed by washing away a single light fraction The relative absenc
67. are nematic is a lack of positional order When the mesogens in a nematic phase are chiral they adopt a twisted orientation with respect to one another creating what is referred to as a chiral nematic or cholesteric phase Smectic phases are characterized by the restricted layering of molecules In the smectic A phase the orientation of the xiii Figure 1 21 Figure 2 1 Figure 2 2 Figure 2 3 molecules is perpendicular to the layering In the smectic C phase the molecules are tilted relative to the layering eeceeeeeeeeeeeeeeeeeeees 35 Schematic representation of A the smectic phase of poly N N di n hexylcarbodiimide versus B the nematic phase of poly n hexyl ISOC Atl She E ah ee eae ot nee aah en eee aes 39 The two polycarbodiimides bearing an ester pendant group synthesized by Jeonghan Kim Each of these structures was synthesized via living polymerization with a titanium catalyst A noteworthy feature later proven essential for the utilization of titanium catalysts is the lack of enolizable Protons eeeeeeeeeeeeeeeeeeeeeeeees 44 Illustration of four methyl ester bearing carbodiimide structures derived by reacting L alanine methyl ester hydrochloride with various aliphatic or aromatic isocyanates in pyridine solvent and dehydrating the resulting 1 3 disubstituted ureas with triphenylphosphine dibromide in methylene chloride and triethylamine cccceeeeeeeeeeeneeeeeeeeeeeeee 46
68. are not present in comparable quantities the close proximity of these imine absorptions precludes observing both since the higher intensity signal of the predominant imine absorption overlaps the lower intensity signal from the imine of the lesser regiochemistry In situations such as these it is easy to assume the polymer to be regioregular when such assumptions seem unlikely to be valid in light of the aforementioned thermal degradation studies The infrared spectrum of poly X Figure 3 13 is a case in point As the only observable imine signal the absorption at 1635 cm indicating the aromatic group to occupy the imine position would appear to suggest a single regiochemistry a regioregular polycarbodiimide in other words However a thorough investigation via SC NMR indicates a structure that is more regiochemically complex As an analytical technique for polycarbodiimide analysis the use of SC NMR has fallen into disfavor over the years The quality of a spectrum collected overnight is typically insufficient to provide useful information in standard form as illustrated by the SC NMR spectrum of poly X The only signal that can be distinguished from the noise is the one for the three methyl carbons of the t butyl group Figure 3 14 A 114 66 Infrared Spectrum of Poly X ve 65 O T 60 N ia 1635 cm A Nitgg KBr Pellet 4000 3000 2000 1000 400 Wavenumber cm 1 Figure 3 13 Infrared spectrum of p
69. asic NMR Experiments 1998 196 Inversion Recovery Experiments for Determining Spin Lattice Relaxation Times T4 Having an approximate idea of the T values within a molecule can be useful when optimizing the delay time for a variety of NMR analyses Since the speed of relaxation correlates directly with the strength of coupling to other nuclei T values can also be used for structural assignments For small organic molecules T values of 1 to 5 seconds are typical for protons while those of carbons generally range from 1 second to greater than 10 seconds To begin lock on the solvent and shim the magnet To measure the T of the protons in the sample begin by selecting the submenu options that are appropriate for a basic H analysis Utilize the commands nt 1 and zg to collect a single scan spectrum Type gain and hit enter A message should appear stating gain Not Used 32 Type gain y and hit enter The command gain should now prompt the return message of gain 32 Use the command pw90 to prompt the display to provide the value of a 90 degree pulse width If the returned value is 17 5 for instance use the command pw 17 5 to set the pulse width to 90 degrees Set p1 to 180 degrees by setting the value to double that of pw p1 39 in this case d1 should be set to at least five times the longest anticipated T Set the number of transients nt to 16 or 32 for proton or to a minimum of 1024 or 2048 for carbon The comm
70. ater contamination from small molecules than when the polymer is formed upon heating in the absence of catalyst Figure 2 9 It seems that greater diversion of carbodiimide down byproduct pathways leading to dimers and trimers is an unavoidable cost of utilizing copper l butanethiolate to accelerate these heated polymerization reACtiONS cccceeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeees 63 Four of the many conceivable stereoisomers that may be formed from the dimerization of N phenyl N L alanine methyl ester carbodiimide Others could have one phenyl substituent in an imine position while the xvi Figure 2 12 Figure 2 13 Figure 2 14 Figure 3 1 other occupies an amine position The pair at the top are referred to as E E isomers while the pair beneath are referred to as Z Z isomers Theoretical considerations are said to favor the formation of Z Z SOT ES sc csces ccs occas ence ences eee dave ene ake aig ca ak a 67 Extracted lon Chromatograph of the 409 m z ratio corresponding to twice the mass of N phenyl N L alanine methyl ester carbodiimide The Total lon Chromatograph indicates the dimer eluted at 15 2 min as the predominant small molecule cee eee eeeeeeeeeeeeeeeeeteeeeetteeeeeeeees 68 Extracted lon Chromatograph of the 613 m z ratio corresponding to three times the mass of N phenyl N L alanine methyl ester carbodiimide The profile of the plot indicates at least seven trimeric stereo
71. ation product s resulting from scissions across original monomer units for regiospecific versus non regiospecific microstructures irregularly inserted monomer shown in red The alternative scissions between the original monomer units would return the original monomer exclusively in either case 14 Given that adjacent repeat units paired in a less stable regiochemical orientation may favor cleavage between the original monomers the absence of metathesis monomers alone does not prove regioregularity Nevertheless the presence of metathesis monomers is a certain indicator of regioirregularity Hence these studies found that regiospecific polymerizations of carbodiimides are the exception rather than the rule as metathesis monomers are commonly observed The two exceptions that degrade exclusively to yield the original monomers suggest that extreme differences between the asymmetric substituents may be required to achieve highly regioselective polymerization The first poly N methyl N a methylbenzyl carbodiimide exhibits the largest steric difference that is achievable as carbodiimides pairing a methyl substituent with one that is tertiary rather than secondary are not polymerizable The second poly N hexyl N pentafluorophenylcarbodiimide is facilitated by extreme electronic effects The strongly electron withdrawing pentafluoropheny substituent heavily biases the regioselectivity of the propagation pathway
72. ation through P8 filter paper failed the polymer was centrifuged at 3500 rpms for 20 minutes at room temperature The supernatant was decanted and the polymer was dissolved with toluene and transferred into a 100 mL round bottom flask Removal of the toluene by rotovap followed by high vacuum revealed 636 mg of brown polymer 64 yield H NMR 300 MHz CDCls 5 ppm 7 00 6 76 3 46 2 59 1 54 1 23 1 06 0 73 all broad 145 Hydrolysis of Poly N Phenyl N L Alanine Methyl Ester Carbodiimide A heavy fraction of poly N methyl N L alanine methyl ester carbodiimide 504 mg synthesized with copper I butanethiolate 500 1 at 60 C was weighed and transferred to a 100 mL round bottom flask Sodium hydroxide 250 mg was dissolved in deionized water 10 mL The sodium hydroxide solution and acetone 20 mL were added to the reaction flask The flask was submerged in a FS30H Ultrasonic Bath for 5 days On the fifth day the solution was neutralized with concentrated HCI to a pH of approximately 7 The product formed a sticky black mass at this pH The pH was adjusted to approximately 1 in an effort to fully protonate any carboxylate units on the polymer The product was extracted from the aqueous mixture with five successive portions of ethyl acetate 150 mL X 2 then 50 mL X 3 Removal of the volatiles by rotovap followed by high vacuum revealed 154 6 mg of brown paste 30 yield Analysis by H NMR indicated that both the es
73. ative regiochemistry thus allowing observers to speculate that the structure is regioreQular ceeeeeeeeeseeeeeeeeeeeeeeeeeeeeeeeeeeees 115 13C NMR spectra of poly X before and after applying 30 Hz 0 40 ppm of line broadening to the data Notice the latter provides much greater detail such as the signal of the carbonyl carbon at 166 ppm and that of the quaternary t butyl carbon just downfield of the solvent signal at 80 Q PON ariin tAchtco phen haha nine ch DA cath Se She ANNA 117 Highlighted and expanded views of the benzylic methylene carbon signals Even with merely 5 Hz of line broadening a signal clearly stands out from the noise Further application of line broadening reveals two slightly overlapping signals corresponding to each anticipated regiochemisStry ccccceeeeeesseeeeeeeeeeeeeeeeeessneeeeeeeeees 118 xxi Chapter 1 The History of Polycarbodiimides 1 1 Introduction Carbodiimides are an important class of compounds having the structure R N C N R The substitutes R and R are commonly carbon attached structures typically aliphatic or aromatic hydrocarbon substituents But there are a variety of other atoms through which the carbodiimide functional group may be substituted 8 substituted carbodiimides Silicon nitrogen phosphorus and sulfur constitute diverse architectural subclasses There are also a variety of salts loosely referred to as metal substituted carbodiimides
74. aying A Journal of Organic Chemistry 1964 29 2410 2404 Ulrich H Saying A Journal of Organic Chemistry 1965 30 2779 2781 Wyman D Wang J Freeman J Journal of Organic Chemistry 1963 28 3173 3177 Brubaker C Wicholas M Journal of Inorganic and Nuclear Chemistry 1965 27 59 62 Novak B Electronic Correspondence Hartke K Rossbach F Angewandte Chemie 1968 80 83 Zetzche F Friedrich A Chemische Berichte 1940 73 1114 Ishii l Ito K Yasuda K Jap Pat 7 115 501 1971 Rapi G Sbrana G Gelsomini N Journal of the Chemical Society C 1971 3827 Draun D Cherdron H Rehahn M Ritter H Voit B Polymer Synthesis Theory and Practice Fundamentals Methods Experiments 2005 Purification of Laboratory Chemicals Perrin D Armarego W Eds Pergamon Press Oxford 1988 Paul R Sharma P Gupta P Chadha S Inorganica Chimica Acta 1976 20 7 9 92 36 Patten T Novak B Journal of the American Chemical Society 1996 118 1906 1916 93 Chapter 3 The Stability and Reactivity of Ester Bearing Polycarbodiimides 3 1 Introduction A common feature among the dozens of polycarbodiimide structures that have been synthesized and characterized by the Novak Group is their stability under both strongly acidic and strongly basic conditions The stability of poly N benzyl N 4 n butylphenyl carbodiimide for instance typifies the robustness of these structures
75. benzylic methylene carbon signals Even with merely 5 Hz of line broadening a signal clearly stands out from the noise Further application of line broadening reveals two slightly overlapping signals corresponding to each anticipated regiochemistry 118 3 8 Conclusions The stability of our latest model ester bearing polycarbodiimide synthesized from the chiral amino acid L alanine has been investigated under both strongly acidic and basic conditions Efforts to transesterify the methyl ester substituent in the presence of para toluenesulfonic acid reveal the polymer to decompose under strongly acidic conditions doing so at an accelerated rate if heated Base catalyzed hydrolysis of the pendant ester substituent with sodium hydroxide hydrolyzes the polycarbodiimide backbone as well leading to a well characterized urea structure Efforts to utilize mercury Il acetate potassium cyanide or 4 dimethylaminopyridine to catalyze transesterification of the methyl ester pendant group with an alcohol were generally unsuccessful though mercury II acetate did show promise with a sample of low molecular weight Re opening our study of an earlier ester bearing polycarbodiimide design previously synthesized by Jeonghan Kim a thorough investigation indicates the polymer to be unstable under conditions that are strongly basic or strongly acidic revealing the polymer to decompose most rapidly when sonicated in the presence of a strong acid The ab
76. bit a maximum optical rotation in chloroform that is approximately 640 in magnitude which is roughly 140 greater than that of a homochiral composition The chiral pendant group on the terpene precursor from which those isocyanates are derived rotates the sodium D line merely 7 0 in the opposite direction in chloroform But the scale of that influence is doubled in the Majority Rules experiment in that every incremental increase in chiral purity not only adds chiral pendant groups having an opposing rotational influence but also removes groups that were reinforcing the dominant rotational influence of the helix Given this report it was not surprising when an analogous optical trend was observed in the first Majority Rules experiment on a polycarbodiimide When 24 varying enantiomeric ratios of R and S N methyl N a methylbenzyl carbodiimide are co polymerized an enantiomeric excess of 65 proves optimum yielding an optical rotation a sss in chloroform of 135 for excess R As the enantiomeric excess approaches purity the rotation declines modestly settling at roughly 85 In terms of the percentage change in optical rotations this trend is significantly greater in magnitude than the one observed among the aforementioned polyisocyanates However in absolute terms the magnitude of this trend is not as dramatic as the numbers alone might intimate considering that the measurements were taken at 365 nm which
77. bubbly texture than the chloroform layer Even still the boundary between layers was not clear After draining a large portion of the chloroform 120 mL additional chloroform 60 mL was added to the separatory funnel The newly transparent chloroform layer revealed black sediment After draining all portions through filter paper to remove the sediment the boundary between the chloroform and aqueous layers became clear Following separation the chloroform layer was dried over sodium sulfate and 81 rotovaped to reveal a dark solid Short path distillation utilizing a Buchi Glass Oven B 580 w a Buchi Drive Unit at temperatures ranging from 195 to 210 C and pressures down to 85 mtorr isolated 170 mg of clear oil 5 yield IR Neat 3025 w 2987 w 2954 w 2870 w 2132 vs 1739 s 1212 s cm H NMR 300 MHz CDCl 8 ppm 7 14 d J 8 7 2H 7 07 d J 8 7 2H 4 19 q J 5 7 1H 3 75 s 3H 3 47 s 1H 1 41 d J 5 7 3H N N di n hexylcarbodiimide Triphenylphosphine 99 14 5 g 54 8 mmol was dissolved in reagent grade methylene chloride 50 mL in a 250 mL round bottom flask The flask was submerged in an ice water bath Bromine 8 76 g 54 8 mmol weighed in a 20 mL vial and diluted in methylene chloride 9 mL was added to the flask at an approximate rate of 1 mL every 5 minutes A rinse of methylene chloride 1 mL was utilized to facilitate quantitative transfer of the bromine solution Trie
78. by a synergy of inductive and resonance influences on the metal amidinate complex Aside from the aforementioned limitations thermal degradation is also incapable of indicating which of the two possible regiochemistries may be preferred Peak broadening precludes use of H NMR to address such questions and the utility of infrared analysis alone is limited With respect to the microstructural determination of polycarbodiimides C NMR provides the greatest insights which are addressed in detail in Section 3 7 15 1 6 Polycarbodiimide Macrostructure From Worms to Rigid Rods The relationship between the size of a polymer and its macromolecular conformation in solution is often characterized by its radius of gyration Re Simply put the radius of gyration is the mean square distance of the repeating units from the polymer s center of gravity This value is experimentally determined from measurements of the angular dissymmetry of light scattered by the polymer molecules in solution The radius of gyration is proportional to the weight average molecular weight raised to a scaling factor that is highly sensitive to the macromolecular conformation of the polymer chain Re a Mx The exponent v ranges from 1 3 for a solid sphere and 1 2 for a Gaussian coil in a theta solvent to 1 0 for a rigid rod Studies on polycarbodiimides indicate macromolecular conformations that range from worm like chains to rigid rods depending on the chirality
79. by rotovap followed by high vacuum overnight to reveal the ester bearing polycarbodiimide Poly N N di n hexylcarbodiimide on the other hand was worked up instead by dissolving in a minimum amount of chloroform and precipitating in methanol Then the precipitated polymer was collected by filtering through Qualitative P8 Creped Fisherbrand Filter Paper and dried under high vacuum lt 100 mtorr Typical Procedure for the Isolation of a Clean Fraction The dark brown product 2 15 g obtained following workup of the heated reaction between N phenyl N L alanine methyl ester carbodiimide with copper I butanethiolate 500 1 was dissolved in chloroform 20 mL The solution was evenly divided among 4 centrifuge tubes Each tube was purged with nitrogen until the solution became 88 saturated At this point 10 mL of methanol were added to each tube precipitating a heavy fraction and the four samples were centrifuged at 3200 rpm and 19 C for 20 minutes The yellow supernatant was discarded Methanol 20 mL and chloroform 5 mL were added to each tube to wash away a light fraction The white suspension was centrifuged for 20 minutes at 3200 rpms and 4 C Again the supernatant was discarded Removal of the remaining volatiles by nitrogen purge followed by high vacuum revealed 716 mg of polymer having a discoloration that was merely light brown 33 recovery Poly N phenyl N L alanine methyl ester carbodiimide Clean Fractio
80. ce of instability with respect to acids bases and elevated temperatures was identified to be the electron withdrawing effect of the ester pendant group thus revealing for the first time that polycarbodiimides are not inherently stable structures that their stability is directly correlated to predictable electronic influences The Synthesis and Characterization of Ester Bearing Polycarbodiimides by Joe B Clark IV A dissertation submitted to the Graduate Faculty of North Carolina State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy Chemistry Raleigh North Carolina 2010 APPROVED BY Lin He Marian G McCord Tatyana I Smirnova Bruce M Novak Chair of Advisory Committee DEDICATION This book is dedicated to my parents Joe B Clark III and Joan W Clark who have provided unwavering support in my academic studies to my two mentors Dr Robert Morrison and Dr Robert Bereman each of whom inspired me to strive for higher academic achievement and provided sage advice to this end to my academic advisor Dr Novak who afforded me with this incredible learning experience to my brother Thomas Clark who has enriched my soul with his music and to my fianc e Erin who made the last three years of graduate school the best in life Thank you all for your support am humbled by your selfless contributions to my life and honored to know each of you BIOGRAPHY The author firs
81. click for course adjustments right click for fine adjustments Repeat the process with a peak on the far left side of the spectrum to adjust the first order phasing Select Box or Cursor to exit the manual phase correction mode Displaying the Scale Select Dscale to display the ppm chemical shift scale below the spectrum Zooming Into and Out of a Region Left click to the left of the left most point of the region Right click to the right of the right most point of the region Select Expand to zoom in or Full to zoom back out 187 Referencing the Scale Zoom in on the reference peak and left click on the highest point of the peak to mark the position with a vertical red line The command nl can be used to center the cursor on the top of the nearest signal line Select Ref Using the numbers at the top of the keyboard rather than the number keypad type the frequency of the reference peak to two decimal places and hit enter pausing the Slope and Bias Select LvI TIt to enter the slope bias adjustment mode Select No Integral then Part Integral Click and hold on the right side of the spectrum and move up or down to adjust the slope of the integration line to zero at the left edge of the integral trace Left click for course adjustments right click for fine adjustments Repeat on the left side of the spectrum to adjust the bias of the integration line so that the slope is as close to zero as po
82. collected by vacuum distillation of the carbodiimide at an oil bath temperature of up to 155 C and a pressure of down to 80 mtorr 50 yield IR Neat 3064 w 2988 w 2953 w 2905 w 2137 vs 1744 s 1213 s 604 w cm H NMR 300 MHz CDCI 8 ppm 7 34 m 2H 7 17 m 3H 4 35 q J 7 2 1H 3 77 s 3H 1 51 d J 7 2 Hz 3H N 4 methylphenyl N L alanine methyl ester carbodiimide A procedure analogous to the one for the preparation of N phenyl N L alanine methyl ester carbodiimide was employed except that calcium hydride was not used The quantities of reagents used were 7 50 g 28 3 mmol triphenylphosphine 99 in 50 mL CH2Cle 4 52 g 28 3 mmol bromine in 10 mL CH2Cle 8 0 mL 57 mmol triethylamine 99 and 5 35 g 22 6 mmol N 4 methylphenyl N L alanine methyl ester urea in 30 mL CH2Cle Vacuum distillation at an oil bath temperature of up to 173 C and pressures down to 180 mtorr collected 2 23 g of clear colorless oil 45 yield IR Neat 3056 w 2990 w 2950 w 2131 vs 1743 m 1194 s cm H NMR 300 MHz CDCl3 5 ppm 7 14 d J 8 4 Hz 2H 7 07 d J 8 4 Hz 2H 4 31 q J 7 0 Hz 1H 3 75 s 3H 1 50 d J 7 0 Hz 3H 78 N propyl N L alanine methyl ester carbodiimide A procedure analogous to the one for the preparation of N phenyl N L alanine methyl ester carbodiimide was employed The quantities of reagents used were 7 93 g 29 9 mmol tr
83. cond line of staggered puncher holes Repeat step 6 again to create a total of 15 puncher holes in the plastic syringe Step 7 Trim the edges at the top of the syringe This will become important later when fitting the syringe through the neck of a round bottom flask 182 Step 8 Insert the plunger to the 4 mL mark Measure and cut the end of the plunger as needed to fit the depth of the flask to be used Step 9 Fill the syringe to the 4 mL mark with molecular sieves that have been oven dried overnight at 220 C and cooled to room temperature in a desiccator Step 11 Re insert the plunger into syringe The three puncher holes at the 5 mL mark will function as tabs to secure the plunger in the syringe Step 10 Insert the cut end of the plunger into the underside of a Suba Seal 45 Rubber Septum Step 12 Insert the molecular sieve holding device into the reaction flask and secure the septum 183 Step 13 The headspace above the reaction may be purged via inserting two needles through the septum and applying a positive pressure of nitrogen through one needle while venting out the other 184 4A molecular sieves are useful for removing equilibrated H2O CHOH or CH3CH2OH reaction byproducts The improvised molecular sieve holding devise is useful for keeping the sieves from contacting the magnetic stir bar APPENDIX 4 VARIAN NMR USER S MANUAL North Carolina State University
84. ction flask via syringe The precipitate and rinse were stirred for 10 minutes to facilitate washing while waiting on the hexanes to cool to the ice bath temperature The hexanes were then removed as before and this rinse procedure was repeated twice Following removal of the last hexane rinse the product was dried under vacuum 86 with a slight flow of nitrogen to reveal 1 22 g white powder having a faint brown tint 20 yield H NMR 300 MHz CDCls 8 4 8 br major peak 3 7 br minor peak Catalytic activity was verified by mixing N N di n hexylcarbodiimide in a 100 1 ratio with a small portion of the product This test polymerization proceeded rapidly and exothermically increasing viscosity immediately and forming solid polymer within seconds Dimerization of N phenyl N L alanine methyl ester carbodiimide N phenyl N L alanine methyl ester carbodiimide 7 84 mmol 1 60 g was transferred to a 25 mL Schlenk flask in a No filled dry box Copper I butanethiolate 160 umol 24 mg and a small magnetic stir bar were added The flask was sealed with a glass stopper removed from the dry box attached to a N line opened to a positive pressure of No and lowered into an oil bath heated to 155 C The reaction mixture became viscous and dark purple in color After 2 hours and 30 minutes the product was removed from heat The next day the product was dissolved in acetone 5 mL and precipitated in deionized water 100 mL A
85. d and hit enter prior to selecting Data Accessing a Saved Spectrum Select Main Menu Select Data Left click on the folder containing the data file and select Set Directory Left click on the data file to highlight it and select Load Type wft and hit enter Log Out Eject the sample and return the standard Type exit and hit enter Right click on the desktop background to access the log out option Right click on Log Out Select OK 189 Section 2 Optional Operations for Basic 1D Spectra Enhancement Improving the Resolution Increasing the acquisition time will sharpen the resolution The acquisition time is directly proportional to the number of data points and inversely proportional to the sweep width Hence the resolution can be improved by increasing the number of points decreasing the sweep width or a combination of both adjustments Increasing the number of data points will improve the resolution for a given sweep width For proton spectra increasing the number of points to no more than 32 000 is recommended Use the command format np 32000 to set the number of points Reducing the sweep width will improve the resolution for a given number of points Type nt 1 zg and hit enter to collect a rough spectrum Right click 1 ppm to the right of the right most peak then left click 1 ppm to the left of the left most peak The selected region must contain all peaks including those of the solvent and standa
86. d carbodiimide there are potentially two regiochemistries for the pendant groups on a given polycarbodiimide repeat The earliest efforts to understand the regioselectivity of carbodiimide polymerizations relied on thermal degradation studies Based on the nearly ubiquitous observation of metathesis monomers following thermal degradation these studies concluded that quantitatively regioselective polymerizations of asymmetric carbodiimides are exceptionally rare requiring either an extreme difference in the size of the two pendant groups as in the case of poly N methyl N a methylbenzyl carbodiimide or an extraordinary electronic influence such as the one in poly N hexyl N pentafluorophenylcarbodiimide In recent years the Novak Group has increasingly relied on the relative intensity of aliphatic versus aromatic imine absorptions on the infrared spectrum as a qualitative measure of which regiochemistry is preferred for a given polycarbodiimide pairing aliphatic and aromatic pendant groups These estimates 113 are based on assignments of approximately 1620 and 1640 cm respectively for aliphatic and aromatic imine absorptions on such polycarbodiimides following respective observations of 1640 and 1660 cm for imine absorptions on polycarbodiimides having only aliphatic or only aromatic pendant groups Assuming these assignments to be valid the limitation of this practice is that in cases where the two regiochemistries
87. d into an oil bath heated to 85 C Saturated sodium carbonate 120 mL was added to crushed ice 2000 mL and room temperature water 500 mL The reaction mixture was transferred to a separatory funnel used to deliver the mixture in a steady stream to the cold sodium carbonate slurry A very large spatula was used to mix the slurry while adding the reaction mixture The product formed a fine white precipitate in the sodium carbonate slurry The slurry was divided into two 1000 mL separatory funnels The product was extracted with five successive chloroform portions 100 mL each Each chloroform portion was poured first through one funnel shaken vigorously and then through the other These extractions were performed while the water was still ice cold The chloroform extracts were combined dried over sodium sulfate and filtered through P8 filter paper The chloroform was removed by rotovap leaving a brown liquid that solidified on standing Attempts to recrystallize the product from chloroform proved unsuccessful The product was dissolved in hot chloroform 50 mL and transferred to a separatory funnel which was used to transfer the solution dropwise into a flask of magnetically stirred pentanes 300 mL The supernatant was removed with a filter paper covered vacuum needle assembly See Appendix 1 for filter paper covered vacuum needle assembly instructions The remaining volatiles were removed under vacuum revealing 13 7 g of slightly ye
88. d thiourea in high purity as evidenced by the absence of the signal for the amine proton set of the starting material 70 yield IR KBr Pellet 3383 s 3165 m 3049 vw 3003 w 2978 w 2933 w 1693 s 1529 s 1161 m 1124 m cm H NMR 300 MHz CDCI amp ppm 8 01 d J 8 7 Hz 2H 7 88 s br 1H 7 21 d J 8 7 Hz 2H 6 21 s br 1H 3 14 d J 4 5 3H 1 57 s 9H 128 N benzylI N p t butoxy carbonylphenyl thiourea t Butyl p aminobenzoate 6 20 g 32 1 mmol was weighed and transferred to a 100 mL round bottom flask Chloroform 50 mL and a magnetic stir bar were added Benzyl isothiocyanate 97 14 8 g 96 2 mmol a 200 excess was added to the flask The reaction mixture was refluxed for 7 days The flask was removed from heat and rotovaped until the product had a paste like consistency Since hexanes and benzyl isothiocyanate are miscible hexanes 25 mL were added producing a fine white precipitate The supernatant was removed After two subsequent hexane rinses 25 mL each the product was dried under high vacuum revealing 10 6 g of white powder H NMR analysis revealed contamination The product was washed with three portions of hexanes 25 mL and dried again under high vacuum to reveal 10 3 g of white powder 93 yield which is approximately a 1 loss per hexane rinse IR KBr Pellet 3302 m 3032 vw 3001 w 2974 w 2925 w 1695 vs 1525 vs 1304 vs 1157 m 112
89. de does not decompose under analogous CONAITIONS cceeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeereteee 103 1H NMR spectra of poly VI before and after stirring or sonicating in a 4 1 mixture of acetone and 2 5 wt aqueous sodium hydroxide for 1 week Both stirring and sonicating in the presence of aqueous base lead to hydrolysis of the polymer backbone as evidenced by the replacement of broad polymer signals with sharp small molecule signals When compared with the ratio of broad to sharp signals in Spectrum B of Figure 3 6 the relatively lower intensity of broad signals in the bottom spectrum here indicates that sonicating in the presence of sodium hydroxide significantly accelerates the breakdown of the pOlyMEr Vceceenetacaeh an ah encom R 104 xix Figure 3 8 Figure 3 9 Figure 3 10 Figure 3 11 H NMR spectra of poly VI before and after stirring or sonicating in a 4 1 mixture of acetone and 2 0 wt aqueous p toluenesulfonic acid When compared with the ratio of broad to sharp signals in the Figure 3 7 spectra it is clear from the relatively lower intensity of broad signals here that the polymer backbone hydrolyzes more rapidly under acidic conditions than under basic conditions Hydrolysis occurs most rapidly with sonication under acidic conditions leading to more complete dissolution of the insoluble polymer in 12 hours than within 1 week of simply stirring ccceeeeeeeeeeceeeeeeeeeeeeeeeaeeeeeeeeeeeeeeeeeneaaees
90. de with 11 triphenylphosphine oxide contaminate indicating a mass of 1 70 g carbodiimide a 79 yield for the second portion Upon discovering that extraction with pentanes isolates the carbodiimide in higher purity the carbodiimide isolated from the second 50 mL fraction developed from the first portion was combined with subsequent 200 mL from the column which had higher concentrations of triphenylphosphine oxide contaminant and rotovaped to remove the chloroform Extraction with two successive portions of pentanes 50 mL each followed by removal of the pentanes by rotovap and high vacuum revealed 1 10 g of viscous opaque yellow oil The relative integration ratios of the H NMR spectrum revealed a 62 purity of the carbodiimide with 38 triphenylphosphine oxide contaminate indicating a mass of 682 mg carbodiimide a 32 yield ultimately for the first portion IR Neat 3057 vw 2958 m 2931 m 2860 w 2145 vs 1736 s 1275 s 1157 s cm H NMR 300 MHz Acetone de 5 ppm 8 00 d J 8 6 Hz 2H 7 23 d J 8 6 Hz 2H 4 91 q 2H 3 57 t J 6 6 Hz 2H 1 73 m 2H 1 46 m 2H 1 34 m 4H 0 89 t J 6 9 Hz 3H S 1 1 Binapth 2 2 ol Titanium IV Diisopropoxide In a nitrogen filled dry box S 1 1 Binapthol 2 2 ol 524 mg 1 83 mmol was weighed in a 20 mL vial A magnetic stir bar and anhydrous toluene 2 mL were added A 3 excess of titanium tetraisopropoxide 536 mg 1 89
91. de DeuteriumOxide Nitromethane d CD3NO2 1 2 Dichlorobenzene ODCB Pyridine d Pyridine d 1 2 Dichloroethane d C2D4Cl2 or Tetrahydrofuran dg THF CD2CICD2CI or Dichloroethane Diethyl d Ether Ethyl_Ether Toluene ds C6D5CD3 or Toluene N N Dimethyl DMF Trifluoracetic Acid d TFA formamide d7 The command cat vnmr solvents will list the solvents recognized by the software 204 Table 3 Comprehensive Reference Chart of Solvent Chemical Shifts Solvent 5H ppm JHD 6 Carbon 13 ppm JCD Hz 6 of HOD multiplicity Hz multiplicity ppm Acetic Acid d 11 65 1 178 99 1 11 5 2 04 5 2 2 20 0 7 20 Acetone dg 2 05 5 2 2 206 68 1 0 9 2 8 29 92 7 19 4 Acetonitrile d3 1 94 5 2 5 118 69 1 2 1 1 39 7 21 Benzene de 7 16 1 128 39 3 24 3 0 4 Chloroform d 7 24 1 77 23 3 32 0 1 5 Cyclohexane di2 1 38 1 26 43 5 19 0 8 Deuterium Oxide 4 80 DSS 4 8 4 81 TSP NA NA 1 2 Dichloroethane d 3 72 br 43 6 5 23 5 Diethyl d1o Ether 3 34 m 65 3 5 21 1 07 m 14 5 7 19 N N Dimethyl 8 03 1 163 15 3 29 4 3 5 formamide d7 2 92 5 1 9 34 89 7 21 0 2 75 5 1 9 29 76 7 21 1 Dimethyl Sulfoxide dg 2 50 5 1 9 39 51 7 21 0 3 3 1 4 Dioxane ds 3 53 m 66 66 5 21 9 2 4 Ethanol de 5 29 1 5 3 3 56 1 56 96 5 22 1 11 m 17 31 7 19 Methanol d 4 87 1 4 9 3 31 5 1 7 49 15 7 21 4 Methylene C
92. de reservoir 100 mL 85 in route to the reaction flask The flask was removed from the ice water bath after 20 minutes The reaction mixture was stirred at room temperature for the next 40 minutes and then refluxed in a hot oil bath 43 C for 30 minutes 30 minutes was judged to be the optimum reflux time based on the earliest perceptible observation of white titanium deposits on the reflux condenser assumed to be a byproduct of catalyst decomposition The flask was removed from the hot oil bath and a dry nitrogen purge was used to concentrate the reaction solution to a volume of approximately 5 mL Anhydrous hexanes 10 mL were added to the flask via syringe and the solution was again concentrated to approximately 5 mL via dry nitrogen purge The flask was placed in an ice water bath to more fully precipitate the product An oven dried filter paper covered vacuum needle assembly was inserted through the bottom of an appropriately sized vacuum dried rubber septum See Appendix 1 for filter paper covered vacuum needle assembly instructions While maintaining a positive pressure of nitrogen in the reaction flask the glass stopper was removed and the rubber septum containing the oven dried filter paper covered vacuum needle assembly was inserted The filter paper covered hilt of the needle was then used to suction the solvent from the reaction flask into a 3 neck flask placed under vacuum Anhydrous hexanes 5 mL were added to the rea
93. ded filter paper is secured needle 154 Step 11 Hang the loose end of Step 12 Pull the overhand knot the tape over the needle making tight and cut off the extraneous a loop and feed it through from tape at the loose end underneath to create an overhand knot 155 Step 13 Place the filter paper covered end of the needle into the flask containing supernatant to be removed the 156 Vacuum Step 14 Assemble a 3 neck flask such that one neck is plugged with a septum the second is sealed with a glass stopper and the third is attached to a vacuum source Step 15 Puncher the rubber Step 16 The supernatant is septum with the sharp end of the sucked from the flask containing needle the precipitate to the 3 neck flask 157 Step 17 paper covered needle as needed Reposition the filter to suck the last standing remnants of supernatant from the bottom of the flask 158 Step 18 Utilize one or more rinses with a non solvent if an ultra clean sample is desired Otherwise simply remove the needle and attach the flask directly to the vacuum source to evaporate residual supernatant Appendix 2 Guide to Vacuum Manifold Maintenance Caution Take care to avoid contacting the glass surface of stopcocks and vacuum manifold joints with metal or any other abrasive The slightest scratch may significantly reduce the vacuum capacity of the system Step 1 Begin by fastening each stopcoc
94. des polymerized in the following studies fall into two divisions those that bear an enolizable proton and those that do not The ones bearing an enolizable proton are derived from L alanine while the others were made from p aminobenzoic acid While carbodiimides of the latter division can be polymerized with titanium IV catalysts those of the former are polymerized most cleanly by heating alone Though copper I butanethiolate rapidly accelerates such thermally driven polymerizations it also catalyzes the formation of small molecules predominantly dimers thus creating a trade off of small molecule contaminants in exchange for a workable polymerization rate and a measure of molecular weight control afforded by the monomer to initiator ratio Through trial and error a procedure for removing such small molecule contaminants was developed to isolate these ester bearing polycarbodiimides in high molecular weight Stability studies find ester bearing polycarbodiimides are categorically unstable under strongly basic conditions While polycarbodiimides derived from L alanine prove unstable with respect to strong acids too those derived from p aminobenzoic acid can be tailored for robustness under acidic conditions though such structures also prove resistant to pendant group modification Ester bearing polycarbodiimides prove to be relatively unstable with respect to elevated temperatures Through studies of various structural derivatives the sour
95. diimides unzip cleanly to monomer But not all carbodiimides prove stable at elevated temperatures For instance N N diphenylcarbodiimide forms dimer in 43 yield when heated at 165 to 170 C for 16 hours Examples of carbodiimide dimerization abound in the literature When catalyzed by tetrafluoroboric acid aliphatic carbodiimides are reported to undergo rapid dimerization at room temperature forming protonated dimeric salts that cleanly 65 afford the dimer upon neutralization with base Dimers of dibenzylcarbodiimide have been isolated in low yield from the distillation residue of the monomer Analogous dimerization reactions are suspected to account for much of our own loss of product while isolating carbodiimides via vacuum distillation Though less common carbodiimide trimerizations have also been reported For instance heating N N diphenylcarbodiimide with N methylhexamethyldisilazane is reported to produce the diphenylcarbodiimide trimer Unheated uncatalyzed reactions of this sort have also been observed as in the case of N N dimethylcarbodiimide reported to undergo trimerization on standing at room temperature When reacted with copper I butanethiolate above its ceiling temperature carbodiimide III undergoes relatively clean dimerization H NMR reveals only sharp signals and suggests a single low molecular weight product Analysis by LC MS reveals predominately dimer Though there are many potential stereoi
96. distanced ion pairing mitigates the helix inducing potency of the chaperone resulting in a rotation of merely 55 29 100 ae o S CSA E mol Repeat Units Z mol CSA Z 150 Poly 2 200 O SO3H R CSA 250 Figure 1 15 Normalized specific rotation in chloroform of poly N N di n hexylcarbodiimide as a function of champhorsulfonic acid concentration R hollow boxes S solid dots 30 1 7 5 Gods of Helicity The Search for an Omnipotent Chiral Center Speaking philosophically as an intensive property of a system chiral purity represents order A random distribution of right and left handed forms possesses greater entropy Regarding helical polymers a racemic mixture of right and left handed helices is favored by the second law of thermodynamics To take such a system in which opposite helices are mirror images of one another and seek to impose such order that only one form exists is a godly endeavor A theologian would argue that such an act requires the intelligent design of a supreme being A chemist on the other hand would simply formulate an intelligent design aiming to employ a supreme being an omnipotent chiral center so to speak and run reactions to explore the truth of it One such design employs a chiral end group exerting a conformational influence from the terminus of the chain Due to the cascade of steric interactions the right and left handed helices are m
97. e magnet stir bar was frozen in place The vial was noticeably warm when removed from the dry box indicating that the reaction was significantly exothermic 24 hours later anhydrous chloroform 3 mL was added and the vial was placed on an orbital shaker The following day the viscous chloroform solution was further diluted with additional chloroform 4 mL This solution was then added dropwise to magnetically stirred methanol 100 mL resulting in the appearance of a fine white precipitate in yellow supernatant The clear yellow supernatant was removed with a filter paper covered vacuum needle assembly See Appendix 1 for filter paper 140 covered vacuum needle assembly instructions This was a very slow process requiring approximately 30 min or so as the fine precipitate hindered the flow of supernatant through the filter paper The precipitate was washed with four successive portions of methanol 25 mL Removal of the methanol from the first wash revealed only a few milligrams of material indicating that the polymer was not significantly soluble in methanol Removal of the remaining volatiles from the precipitate by high vacuum revealed 1 17 g of white powder having a slightly yellow tint 80 yield IR KBr Pellet 3041 vw 2978 m 2933 w 1712 s 1641 s 1594 s 1292 s 1157 s cm H NMR 300 MHz CDCls 5 ppm 7 79 s br 2H 6 63 s br 2H 2 39 s br 3H 1 50 s br 9H C NMR 300 MHz CDCls amp p
98. e of sharp signals in this spectrum compared with the spectrum of the unclean polymer Figure 2 10 showcases the success of precipitating and extracting fractions in sequence to remove small molecule contaminants 70 2 5 Conclusions A series of novel ester bearing carbodiimides have been synthesized from the simple chiral amino acid L alanine Research on the polymerization of these carbodiimides reveals all of them to be incompatible with the commonly used titanium IV catalysts Investigations with copper catalysts led to the discovery that carbodiimides pairing an aryl substituent with the ester bearing pendant group prove capable of polymerization while those pairing an alkyl substituent with it do not The presence of an electron withdrawing group on the aryl substituent accelerates polymerization Control reactions reveal the rate of heated polymerization to be unaffected by the presence of copper Il chloride that heat alone facilitates polymerization and that CuCl merely catalyzes the formation of small molecules such as dimers and trimers Studies with copper lI thiolates suggest that the nucleophilicity of the anion plays a vital role in determining its ability to initiate carbodiimide polymerizations exhibiting high activation energies Copper l butanethiolate greatly accelerates the thermal polymerization of our prototype ester bearing carbodiimide The exploration of this carbodiimide s reactivity above the ceiling tem
99. e typical cooperative optical response plateauing at an enantiomeric excess of 60 With respect to the apparent trend the magnitude of the a ss5 7 6 influence of the chiral pendant group measured on the monomer in hexane contributes negligibly to the 170 rotation of the annealed R homochiral polymer in chloroform 1 7 4 Protons amp Polycarbodiimides The Chaperoning of Orderly Affairs Upon polymerization of a carbodiimide the 60 dihedral angle between one repeat unit and the next partitions the chain into amidine units Amidines are organic bases Protonation occurs at the imino nitrogen leading to the resonance stabilized amidinium ion Figure 1 13 that depending on the substituents has a pKa value ranging from 5 to 13 Upon protonation the solubility of a polycarbodiimide often changes remarkably For instance poly N N diethylcarbodiimide becomes water soluble when protonated by hydrochloric acid and precipitates when deprotonated with sodium hydroxide 26 a HN R N n R Figure 1 13 The respective exo and endo resonance forms of the amidinium ion resulting from protonation of the polycarbodiimide backbone Aside from altering the solubility protonating a polycarbodiimide also facilitates transformation into the most thermodynamically stable conformation For instance poly N R 2 6 dimethylhexyl N hexylcarbodiimide is reported to adopt a kinetically controlled co
100. elect Nucleus Solvent select F19 for fluorine 19 or P31 for phosphorus 31 and then select the solvent from the subsequent option display See Table 2 for the commands with which to access Other solvents Alter the number of transients nt as needed to achieve the desired quality of spectra The Time command can be used to prompt the display to provide a time estimate for a given number of transients For F19 analysis the command zg will initially prompt an error message stating P S G Aborted At the bottom of the screen the error will read oversamp sw gt 100000 000000 Hz In this case the default sweep width which is set at 50000 is problematic Use the command format sw 50200 to alter the sweep width by plus or minus 200 A subsequent command of zg should successfully initiate acquisition 199 Section 5 Operations for Collecting Spectra at Variable Temperatures This guide is a supplement to training not a substitute DO NOT attempt to run Variable Temperature NMR Experiments without training authorized by Dr Sankar Carefully follow instructions and keep a vigilant eye on the instrument status window at all times when operating below or above room temperature The 40 000 to 45 000 NMR probes are fragile and easily damaged You are responsible for ensuring not only that you do not make a mistake but also that all components of the system are operating properly Notice Under no circumstance are NMR users allo
101. enyl N L alanine methyl ester carbodiimide A procedure similar to the one for the preparation of N phenyl N L alanine methyl ester carbodiimide was employed Quantities of reagents used were 4 53 g 17 1 mmol triphenylphosphine 99 in 50 mL CHe2Cle 2 76 g 17 3 mmol bromine in 10 mL CH2Cl2 4 8 mL 34 mmol triethylamine 99 and 4 30 g 16 8 mmol of the urea in 30 mL CH2Clo After allowing the reaction to proceed overnight the sample was washed with deionized water 210 mL followed by saturated sodium chloride 30 mL Purification by column chromatography utilizing CH2Cl2 developing solvent and silica stationary phase isolated merely 113 mg of clear brown oil 3 yield IR Neat 2990 w 2954 w 2135 vs 1744 m 1215 s cm H NMR 300 MHz CDCl 8 ppm 7 34 d J 8 7 Hz 2H 7 22 d J 8 7 Hz 2H 4 39 q J 6 9 Hz 1H 3 77 s 3H 1 51 d J 6 9 Hz 3H N 4 fluorophenyl N L alanine methyl ester carbodiimide L alanine methyl ester hydrochloride 99 3 0 g 21 3 mmol was dissolved in reagent grade pyridine 40 mL in a 100 mL round bottom flask Mercury Il oxide 99 6 58 g 43 0 mmol was added to the flask followed by 4 fluorophenyl isothiocyanate 98 3 33 g 21 3 mmol Following addition of the isothiocyanate the reaction was allowed to proceed overnight The next morning a clear light orange solution was obtained from the gray product mixture by filtering through diatomaceous ear
102. er D PhD Dissertation University of Massachusetts Amherst 1998 Kim J Novak B Macromolecules 2004 37 8286 8292 Kim J Novak B Macromolecules 2004 37 1660 1662 Tang H Boyle P Novak B Journal of the American Chemical Society 2005 127 2136 2142 Tang H Novak B He J Polavarapu P Communications 2005 44 7298 7301 Kennemur J Clark IV J B Tian G Novak B Macromolecules 2010 43 1896 1873 Li H PhD Dissertation North Carolina State University 2006 Vishnyakova T Golubeva l Glebova E Usp Khim 1985 54 429 449 Bestmann H Lienert J Mott L Justus Liebigs Ann Chem 1968 778 24 32 Palomo C Mestres R Synthesis 1981 373 374 Coles R Levine H U S Pat 2942025 1960 Herzog Angewandte Chemie 1920 33 140 Chemistry and Technology of Carbodiimides Ulrich H Ed John Wiley amp Sons Ltd West Sussex 2007 91 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 Weith W Berichte der Deutschen Chemischen Gesellschaft 1873 6 1395 Appel R Kleinstueck R Ziehe K Chemische Berichte 1971 104 1335 Eilingsfeld H Seefelder M Weidinger H Angewandte Chemie 1960 72 836 Wragg R Tetrahedron Letters 1970 45 3931 3932 Ager D Froen D The Nutrasweet Company World Intellectual Property Organization WO 1991 004962 1991 Ulrich H Tilley J S
103. er system cooperates with the predominant chiral entity by adopting a preferred helical sense The pinnacle of cooperativity is the induction of a single handed helix by a single chiral entity either by a chiral catalyst exercising its influence on the active site during polymerization or through perturbation from a chiral endgroup at the chain s terminus ccceeeeeeeeeeeeeeeeeeeees 18 xi Figure 1 12 Figure 1 13 Figure 1 14 Figure 1 15 Figure 1 16 Figure 1 17 The schematic on top depicts the stereoisomeric relationships among right and left handed helices of polymers bearing chiral pendant groups The schematic beneath illustrates the energy difference between the diastereomeric interactions of the right and left handed helical conformations with a given Chiral entity ceceeeeeeeeee 19 The respective exo and endo resonance forms of the amidinium ion resulting from protonation of the polycarbodiimide backbone 27 Pendant groups on adjacent imine nitrogens may orient in either a trans cis or trans trans arrangement In theory protonation of the backbone would facilitate transformations into trans trans orientations through the free rotation of pendant entities in the endo resonance form of the amidinium ion inadvertently lowering the activation energy of the helical inversion PrOCeSS eeeeeeeecceeeeeeeeeeeeeeeaeeeeeeeeeeeeeeees 28 Normalized specific rotation in
104. ere 10 0 g 70 9 mmol L alanine methyl ester hydrochloride 99 50 mL pyridine and 11 1 g 70 9 mmol 4 chlorophenyl isocyanate 98 Yield 16 7 g White Powder 91 IR KBr Pellet 3342 s 3093 w 2992 m 2954 m 1739 vs 1640 vs 1223 s 635 m cm H NMR 300 MHz Acetone de 5 ppm 8 22 s br 1H 7 49 d J 8 1 Hz 2H 7 25 d J 8 1 Hz 2H 6 20 d br J 6 0 Hz 1H 4 40 m 1H 3 69 s 3H 1 36 d J 7 2 Hz 3H C NMR 300 MHz CDCI 8 ppm 175 156 137 129 128 121 52 6 48 9 18 3 N N di n hexylurea Hexyl isocyanate 97 6 11 g 48 0 mmol a magnetic stir bar and reagent grade chloroform 30 mL were added to a 100 mL round bottom flask The flask was positioned in an ice water bath to cool the solution to 0 C Over the next 30 minutes a solution of hexylamine 99 4 86 g 76 48 0 mmol in chloroform 10 mL was added to the reaction flask The ice water bath was removed and the reaction mixture was stirred overnight at room temperature The solvent was then removed by rotovap followed by high vacuum to reveal 10 7 g of white powder 99 yield IR KBr Pellet 3335 m 2961 m 2931 m 2857 m 1618 vs 1577 vs cm H NMR 300 MHz CDCls 8 ppm 4 41 t br 2H 3 12 m 2H 1 46 m 2H 1 27 m 6H 0 85 t J 6 6 Hz 3H C NMR 300 MHz CDCI 8 ppm 160 40 5 31 8 30 6 26 9 22 8 14 2 N phenyl N L alanine methyl ester carbodiimide Triphenylp
105. erely pseudoequivalent differing ever so slightly in energy The diastereomeric interactions manifest most sharply at reduced temperatures where thermodynamically the lower energy helix is favored Toa limited extent the magnitude of the effect is proportional to the scale of the steric interactions the bulker the chiral end group the greater its conformational influence Limitations also arise from the fact that statistically speaking the further from the chiral terminus a repeat unit is the more entropic free will it exercises in the way it rolls literally 31 Chiroptic studies on polycarbodiimides bearing chiral end groups Figure 1 16 find that they precisely embody these anticipated attributions Judging from changes in the sign and magnitude of optical rotation Table 1 1 it appears that at room temperature entropy favors a relatively equal distribution of the two helices Comparing two chains of different length bearing the same chiral end group the longer one presents a rotation of lesser magnitude at the lowest temperature thus exhibiting the limitations of conformational influence with increasing distance from the chiral terminus Also comparing analogous polymers of relatively equal length the one bearing the bulkier chiral end group displays greater rotations at reduced temperatures revealing magnitudes of influence directly proportional to the scale of the steric interactions Table 1 1 Optical rotation da
106. ergy needed to achieve it preclude utilization of chiral end groups to effect the formation of exclusive right or left handed helices on a polycarbodiimide Thus placement of the chiral center on the initiating ligand from which it becomes the end group proves suboptimal Instead the more intelligent design utilizes chirality on the persistent ligand sphere of the metallic coordination insertion catalyst From the transient vantage of the active site this single chiral entity dictates the helical conformation of the incipient polymer from beginning to end as if it were the proverbial hand of god The prototype design that has proven most successful in this endeavor is the BINOLate Ti O Pr 2 catalyst Figure 1 17 2 2 binapththol and its derivatives are among the most widely used chiral ligands in asymmetric catalysis 33 BINOLate TiX2 catalysts alone have been utilized to effect high enantioselectivity in many systems including carbonyl ene_reactions Mukaiyama aldol condensations and the allylation of aldehydes and ketones to name a few When carbodiimides pairing a hexyl substituent with either an isopropyl hexyl or phenyl substituent are polymerized with the S BINOL Ti O Pr 2 catalyst the optical rotations c 435 of the resulting polymers measured in toluene are 15 44 and 753 respectively Quantitatively the enantiomeric excess of the preferred helix in each case remain uncertain Qualitat
107. es 56 CDCI 4 Weeks 60 C 10 9 8 7 6 5 4 3 2 1 ppm Figure 2 8 H NMR spectrum of the product resulting from carbodiimide Ill reacted with CuCls for 1 month at 60 C The profile indicates primarily high molecular weight material as evidenced by the predominance of broad versus sharp signals 57 2 3 2 Thermally Induced Carbodiimide Polymerization Given that the combination of copper Il chloride with heat polymerizes carbodiimide Ill where copper Il chloride alone fails we know that heat is an essential element in the polymerization process The question that remains is whether the copper Il chloride is also an essential element whether heat alone is capable of facilitating polymerization An experiment heating carbodiimide Ill at 60 C in the absence of any catalyst revealed that heat alone does indeed facilitate polymerization and it does so at a rate that is not distinguishable from that at which heat does so in the presence of various catalytic amounts of copper II chloride The discovery that copper II chloride does not accelerate the polymerization of carbodiimide IIl opens the question of what effect if any the presence of copper Il chloride does have on the reaction process A comparison of the H NMR spectra of poly lIll synthesized by heating in the presence of CuCls Figure 2 8 with poly lll made in the absence of CuCls Figure 2 9 reveals the latter to have fewer and less inten
108. esesssssseseesseeeeeeeeees 64 2 4 2 Fractional Precipitation and Extraction The Disposal of Disorderly Dimers ccceeeeeeeeeeeeeeteeeeeeeees 69 25 CONCIISIONS 24 246 03 A asain daa as a oie lea tone enlace 71 2 6 Experimental Section lt exc20 53 rescrezevereseiceg tines tgte vel kbs vate te boats kghee hs te detenets 72 2 6 1 General Procedures and Equipment ccccceeeeeeeeeeeeteeeeeeeees 72 2 6 2 Experimental Procedures and Characterizations ccccee 74 2 7 PCISIOW COS cis s5225 o tea bercedpnie 8 hoctet heated a hath dady hse tuaetreadyentadades 91 vi CHAPTER 3 THE STABILITY AND REACTIVITY OF ESTER BEARING POLYCARBODIIMIDES 3 1 Introduction iis ctct shh eben teeitet ah othhhbebeiadeh A detected ated chocteedieta tenes 94 3 2 Base Catalyzed Hydrolysis of a New Ester Bearing Polycarbodiimide 95 3 3 Transesterification Studies on a New Ester Bearing Polycarbodiimide 97 3 3 1 News Flash Novel Polycarbodiimide Sour on PTSA 088 98 3 3 2 Transesterification Studies Under Mild Conditions 98 3 4 Follow Up Studies on an Old Ester Bearing Polycarbodiimide 101 3 5 Regioselectivity Study on Carbodiimide Polymerization Catalysts 106 3 6 Descendants of an Old Ester Bearing Polycarbodiimide 0 109 3 7 _ Polycarbodiimide Regiochemistry Microstructural Determination via C NMR c ccccccceseeesesseseseseseeteeeeees 113 3 8
109. fterwards Centers the cursor on top of the nearest peak Sets the number of points to 24 000 for instance record np from the parameter list before adjusting the sweep width and use approximately that figure as the reset value for the number of points Sets the number of transients to 32 Sends all preceding plot commands to the printer Plots all parameters Plots integral regions must be preceded by vp 12 Plots spectrum Plots line list in ppm and Hertz use pll page to plot a peak frequency list Plots text the commands pap or ppa plot the text automatically Plots a partial list of parameters Plots frequency of peaks that are above the Threshold setting Plots the axis scale Displays the value of a 90 degree pulse width Sets the pulse width to 17 5 microseconds as an example Saves data in a file named XYZ for instance Sets sweep width to 1200 for instance Creates lines of customized text use the format text Novak Group Project 7 to add two lines of text Displays an estimate of run time given the current parameter settings Moves the vertical position of the plot up by 72 mm must precede pir or dpir commands to create space below the plot for integral values Sets the vertical scale to 160 as an example the default setting is 200 Optimizes the vertical scale to the maximum value that will fit the most intense peak on the display Fourier transforms the data with weighing Zero and go begins the experiment
110. funnel then the other The volumes of the five extracts were 250 mL 100 mL 100 mL and then 50 mL A goop like substance present at the bottom of the separatory funnel was removed and discarded by filtering the extracts through 18 5 cm diameter Q8 filter paper Approximately half a dozen filters of this size were needed to collect all of this goop as the filter papers became clogged and needed replacing The combined chloroform extracts 500 mL total were pre dried with a wash of saturated sodium chloride 500 mL and then dried over sodium sulfate Removal of the chloroform by rotovap revealed 9 89 g of off white powder 65 yield IR KBr Pellet 3370 s 3248 m 3066 vw 3032 vw 2996 vw 2947 w 1682 s 1656 m 1602 vs cm H NMR 300 MHz CDCls 5 ppm 7 83 d J 8 6 Hz 2H 6 62 d J 8 6 Hz 2H 4 03 s br 2H 3 83 s 3H 2 2 2 Trifluoroethyl p Aminobenzoate The first step conversion of p aminobenzoic acid to p aminobenzoyl chloride was performed exactly as described for t Butyl p Aminobenzoate The second step reaction of the acid chloride with an alcohol differed as follows 2 2 2 trifluoroethanol 100 mL 139 g 1 39 mol a 1300 excess and a stir bar were placed in a 500 mL round bottom flask The amber oil p aminobenzoyl chloride was transferred by pipet to the flask The mixture formed a solid within a minute Additional alcohol 100 mL 139 g 1 39 mol 126 was added and the flask was lowere
111. ges the delay time between scans to 5 seconds for instance dc Corrects drift which occasionally effects the accurate of integrations dg Displays the original text screen of group parameters dli Displays a list of integrals dil Displays a list of peak lines dpf Displays the frequency of peaks that are above the Threshold setting dpir Displays integrals on the spectrum must be preceded by vp 12 ds Displays spectrum use to remove traces of previous spectra or to clear the display of peak frequencies integrals etc dsn Displays the signal to noise ratio left click on the peak to mark it with a cursor and use the command nl to center the cursor at the top first e Ejects the sample from loading tube exit Exits the Varian NMR software program ft Fourier transforms the data no weighing function fn 48000 Sets the fourier number to 48 000 in this case must be followed by wit getshim Loads pre programmed shim parameters that are a good starting point for further adjustment i Inserts the sample into the loading tube Ib 7 Applies line broadening of 7 Hertz for instance must be followed by wft 206 movesw nl np 24000 nt 32 page pap pir pl pll pltext ppa ppf pscale pw 90 pw 17 5 svf XYZ sw 71200 text time vp 712 vs 160 vsadj wit zg zg wexp svf XYZ Y Adjusts the sweep width to the region enclosed by cursor lines for improved resolution re adjust the number of points np a
112. hanges in the H NMR spectra Figure 3 6 A amp B Stirring or sonicating in aqueous base hydrolyzes the polymer backbone more rapidly than it cleaves the t butyl group from the pendant ester Figure 3 7 The polymer proves even less stable when stirred for the same amount of time in aqueous acid and it decomposes most rapidly when sonicated under strongly acidic conditions Figure 3 8 101 an ae ve A D a er 50 Yield d HgO oz 65 Yield O Acetone A zZ S BINOL a i Pr 2 18 Yield 80 Yield O O pe Poly VI Ly VI n Figure 3 5 Outline of the multi step synthetic route to the ester bearing polycarbodiimide first developed by Jeonghan Kim The initial step synthesis of t butyl p aminobenzoate was first reported by Taylor Fletcher and Sabb The original polymer synthesized by Kim was made with an achiral titanium catalyst CpTiCl2N CHs 2 rather than the chiral S BINOL titanium catalyst utilized for the follow up studied of this work 102 CDCI Spectrum A Original Polymer CDCI Spectrum B After 1 Week of Sonication bias a ell 10 he ae COE 6 5 4 3 2 1 ppm Figure 3 6 H NMR spectra of poly VI before and after sonicating in a simple 4 1 mixture of acetone and deionized water for 1 week The replacement of broad proton signals with sharp signals indicates decomposition of the polymer into smaller molecules In contrast to poly V s instability
113. hapter 1 there are two categories of catalysts developed by the Novak Group for the living polymerization of carbodiimides those based on a titanium IV species and those based on a copper species in either a 1 or 2 oxidative state To those uninitiated in polycarbodiimide research a cursory review of our literature might lead one to speculate that the copper catalyst systems are the superior choice 2 Compared to those made with titanium they are more tolerant of moisture and air They tolerate a much larger array of functional groups which allows them to polymerize carbodiimides in solvents such as acetone and ethyl acetate that are not compatible with titanium IV catalysts The polydispersity of 51 polycarbodiimides prepared with copper catalyst is comparable to that of those prepared with titanium catalysts and the yields of these copper catalyzed polymerizations are excellent ranging from 70 to 100 In spite of the aforementioned advantages copper catalysts have three salient drawbacks First copper catalysts often exhibit poor solubility The simple CuCl and CuCl salts are only sparingly soluble in low polarity solvents Cu OMe Cl is even less soluble and has been suggested by others to exist as aggregated structures in which each methoxide bridges two copper cations Even with the copper amidinate complexes solubility limitations are sometimes an issue The second problem with copper catalysts is that the copper
114. he Helix Directing Authority of the Chiral Majority 23 1 7 4 Protons and Polycarbodiimides The Chaperoning of Orderly Affairs cccccceeceeeeeeeeeeeeeeeeeeeeeeeeeeaeees 26 1 7 5 Gods of Helicity The Search for an Omnipotent Chiral Center 31 1 8 Optical Switching with a Helical Polycarbodiimide Nanoshutter 35 1 9 Liquid Crystalline Properties of Polycarbodiimides ccccceeeeeeeeeeees 37 ges 6 Patel fs 21 2 96 2 cere geen een nana N eaa TEE E En ENE EEEE 40 CHAPTER 2 POLYMERIZATION OF NOVEL ESTER BEARING CARBODIIMIDES 2s VUNMMOQUCHOW aienea AEAEE AAEE EEE ene teeetie EEA BE EEE 44 2 2 Syntheses of Novel Ester Bearing Carbodiimides ceeeeeeeeeeeees 45 2 2 1 Standard Dehydration of 1 3 Disubstituted Ureas ee 45 2 2 2 Standard Desulfurization of 1 3 Disubstituted Thioureas 47 2 2 3 Alternative Strategies for Carbodiimide Synthesis 48 2 3 Polymerization of Novel Ester Bearing Carbodiimides 000 51 2 3 1 Studies with Traditional Polymerization Catalysts 00 ee 51 2 3 2 Thermally Induced Carbodiimide Polymerization cceeee 58 2 3 3 Thiolate Initiated Thermal Polymerizations cceeeeeeeeeee 60 2 4 The Dilemma of Dimers and Troublesome Trimers ceeeeeeeeeeeeees 64 2 4 1 Raising the Roof What s Going Down Above Te sssssssssesesee
115. he analogous process for a titanium IV alkoxide complex is illustrated in Figure 1 6 In each case the first carbodiimide insertion transfers the initiating group from the metal to the electrophilic carbodiimide carbon where it terminates the inactive end of the subsequently propagated chain Initiation i L TI OCHCF NU LOOO CF3CH 20 A TiL nh z T 4 i SD R R Propagation R j i N C N i a N PON het CF CH lt lt Pai CFCH 0K En N N N R R R ae G R N i ae N C N N N ae NS N R N N R N R ay Rae Ze Z a R N R N Termination j a I N H CF MS En n ue n N n 1 R R R H pe L TIOCH Figure 1 6 Illustration of initiation propagation and termination steps of carbodiimide polymerization with a titanium alkoxide complex These living polymerizations are typically terminated by precipitating a hydrocarbon solution of the polymer in methanol though exchangeable protons from any source terminate propagation in an analogous manner 1 4 Thermal Decomposition of Polycarbodiimides The thermally induced decomposition of polycarbodiimides was first studied by Robinson who noted that it appeared to be an unzipping process given that no fragments other than monomer were detected in the pyrolyzate Subsequent research by Goodwin found that mixing a polycarbodiimide with a radical initiator 2 2 azobisisobutyronitrile AIBN facilitated the onset of decomposition at a lo
116. he first VII simply replaced the t butyl substituent on the ester with a methyl group with the aim of synthesizing a methyl ester substituted polymer capable of modification via transesterification Unlike most carbodiimides of comparable molecular weight which are typically a clear viscous oil at room temperature VII is a white solid The only suitable solvent with which it can be dissolved is pyridine and the subsequent polymerization attempt unfortunately led to a low molecular weight product The second derivative VIII differed from the first in that the non ester pendant group was an n hexyl group rather than a methyl group The aim of this modification was to alter the solubility of the monomer to facilitate polymerization in chloroform solvent This strategy proved successful leading to a chloroform soluble carbodiimide which was polymerization in high molecular weight with S BINOL Ti O Pr gt The third derivative IX differed from the second in that the methyl substituent of the ester was replaced with a 2 2 2 trifluoroethyl group which would in theory provide a better leaving group for transesterification This carbodiimide too proved chloroform soluble and was successfully polymerized in high molecular weight with the same chiral titanium catalyst 109 ns _7 CH2 5CH3 _7 CH2 5CH3 N N N N I l C C C C l N N N N O O o O O O CH CH F F F vil vill Ix x Figure 3 11 Four new derivatives of the old
117. hesis of polymers having a targeted molecular weight pre determined by the ratio of monomer to initiator The first publication on the living polymerization of carbodiimides was authored by Andrew Goodwin and Bruce Novak in 1994 Building on earlier success with the living polymerization of isocyanates which are isoelectronic with carbodiimides they found that covalent titanium amide and alkoxide complexes Figure 1 4 promoted living polymerization of carbodiimides having a variety of aliphatic and aromatic substituents i C H3 cy cy cI N Oe a cnn a enny SK N Cl cl N CH 3 2 cl OCH CF3 Si C H3 3 Figure 1 4 Titanium catalysts first found to initiate the living polymerization of carbodiimides Among carbodiimides bearing aliphatic substituents the degree of substitution at the site of attachment proved essential in determining whether and at what rate polymerization occurs Carbodiimides bearing two primary substituents polymerize rapidly while those bearing one each of a primary and a secondary substituent do so at a relatively sluggish rate A carbodiimide having one each of a methyl and tertiary substituent as well as those bearing two secondary substituents proved incapable of polymerization with titanium catalysts Solvents that proved suitable for these polymerizations included aromatic hydrocarbons benzene and toluene halogenated hydrocarbons chloroform aliphatic hydrocarbons hexanes ethers THF
118. hite powder 50 yield IR KBr Pellet 3350 s 3238 m 3071 vw 3043 vw 3009 w 2974 m 2932 w 1686 vs 1638 m 1602 s cm H NMR 300 MHz CDCls 8 ppm 7 78 d J 8 9 Hz 2H 6 60 d J 8 9 Hz 2H 3 98 s br 2H 1 55 s 9H Methyl p Aminobenzoate The first step conversion of p aminobenzoic acid to p aminobenzoy chloride was performed exactly as described for t Butyl p Aminobenzoate The second step reaction of the acid chloride with an alcohol differed as follows anhydrous methanol 250 mL 198 g 6 17 mol a 6000 excess and a magnetic stir bar were placed in a 500 mL round bottom flask The amber oil p aminobenzoyl chloride was transferred by pipet to the flask Following complete addition of the p aminobenozyl chloride the reaction mixture was refluxed for 2 hours 55 mL of methanol were removed by rotovap Saturated sodium carbonate 140 mL was added to crushed ice 2000 mL and room temperature water 500 mL The reaction mixture was transferred to a separatory funnel which was used to deliver the mixture in a steady stream to the cold sodium carbonate 125 slurry A very large spatula was used to thoroughly mix the slurry while adding the reaction mixture The product formed a fine precipitate when added to the aqueous sodium carbonate mix The aqueous suspension was divided into two 1000 mL separatory funnels Four chloroform extractions were performed by sending the extract through one
119. hloride dz 5 32 3 1 1 54 00 5 27 2 1 5 Nitrobenzene d 8 11 br 148 6 1 7 67 br 134 8 3 24 5 7 50 br 129 5 3 25 123 5 3 26 Nitromethane d3 4 33 5 2 62 8 7 22 Pyridine ds 8 74 1 150 35 3 27 5 5 7 58 1 135 91 3 24 5 7 22 1 123 87 5 25 Tetrahydrofuran dg 3 58 1 67 57 5 22 2 2 4 2 5 1 73 1 25 37 5 20 2 Toluene dg 7 09 m 137 86 1 0 4 7 00 1 129 24 3 23 6 98 5 128 33 3 24 2 09 5 2 3 125 49 3 24 20 4 7 19 Trifluoracetic Acid d 11 50 1 164 2 4 11 5 116 6 4 DSS denotes chemical shift relative to 2 2 dimethyl 2 silapentane 5 sulfonic acid sodium salt TSP denotes chemical shift relative to 3 trimethylsilyl propionic acid d4 sodium salt All other chemical shift values are relative to tetramethylsilane TMS These values were compiled from the NMR Solvent Tables of Cambridge Isotope Laboratories and Numare Spectralab Inc with deference to the former 205 List of Useful Varian NMR Software Commands aph Automatically corrects zero and first order phasing apho Corrects zero order phasing only use on single peak spectra axis h Changes axis to Hertz axis p Changes axis to ppm bs 64 Changes block size to 64 transients data can be transformed every time a block size increment of transients is reached cd Changes the directory back to the default home directory ctext Clears previous text entry CZ Clears all integral reset points d1 5 Chan
120. hosphine 99 7 45 g 28 1 mmol was dissolved in reagent grade methylene chloride 50 mL in a 250 mL round bottom flask The flask was submerged in an ice water bath Bromine 4 60 g 28 8 mmol weighed in a 20 mL vial and diluted in methylene chloride 9 mL was added to the flask at an approximate rate of 1 mL every 5 minutes A rinse of methylene chloride 1 mL was utilized to facilitate quantitative transfer of the bromine solution 30 minutes after the final addition of bromine triethylamine 99 8 0 mL 57 mmol was added to the reaction mixture at an approximate rate of 1 mL every 5 minutes N phenyl N L alanine methyl ester urea 5 00 g 22 5 mmol was dissolved in methylene chloride 30 mL 30 minutes after the final addition of triethylamine the urea solution was added to the reaction mixture at an approximate rate of 5 mL every 5 minutes Following addition of the urea the reaction was allowed to proceed overnight The following morning the product mixture was washed with deionized water 20 mL The methylene chloride solution was dried with a saturated sodium chloride wash 20 mL followed by 77 standing for 5 minutes over sodium sulfate The product solution was decanted to a vacuum dried 100 mL round bottom flask The methylene chloride was subsequently removed by rotovap A vacuum dried stir bar and approximately one spatula transfer of calcium hydride were added to the carbodiimide 2 31 g of clear yellow oil were
121. hrough the alpha carbon the inductive electron withdrawing effect of the ester unit has a surprisingly powerful influence on the polycarbodiimide s stability When sonicated in a 2 1 mixture of acetone and aqueous 2 5 wt sodium hydroxide for five days the initially insoluble polymer is hydrolyzed completely leading to the urea structure illustrated in Figure 3 1 The contrast between the respective broad and sharp H NMR signals before and after Figure 3 2 A amp B are consistent with the transition from polymer to small molecule LC MS analysis confirms the anticipated product structure exhibiting m z values of 209 and 231 corresponding respectively to the protonated urea and its sodium adduct as the two most abundant peaks Sho O Na o N NaOH H O Acetone Y Sonication O aS HN CHOH p Figure 3 1 The quantitative conversion of poly lll to a urea structure is the first case in which a polycarbodiimide has been observed to hydrolyze under basic conditions yw Poly lll CDCI SpectrumA Before Hydrolysis Reaction 10 9 ES 7 ERA 8 ahaa ea ao a ee CDCI Spectrum B 00 After Hydrolysis Reaction O HN HN ar 7 6 om 4 3 2 1 ppm wf 10 9 ane Figure 3 2 H NMR spectra before and after base catalyzed hydrolysis of poly N phenyl N L alanine methyl ester carbodiimide Both the pendant methyl ester and the polymer backbone are hydrolyzed under strongly basic conditions 9
122. iles were removed by vacuum revealing 1 06 g of yellow flakes 46 yield IR KBr Pellet 3064 vw 3035 vw 2976 m 2929 w 1713 s 1635 s 1592 s 1288 s 1163 s 1115 s cm H NMR 300 MHz CDCls 5 ppm 7 86 7 49 7 14 7 02 6 89 6 61 6 44 6 24 6 09 5 79 5 79 4 86 3 46 2 50 1 56 1 30 0 95 all broad C NMR 300 MHz CDCls 5 ppm 166 150 148 136 128 120 80 8 50 0 48 3 28 6 182 2 C Decomposition Temperature 5 Loss of Mass Tg absent from Differential Scanning Calorimetry Analysis Specific Optical Rotation measured 879 0 8 Poly N methyI N p methylcarbonylphenyl carbodiimide S 1 1 Binapth 2 2 ol titanium IV diisopropoxide 45 0 mg 99 9 umol and a magnetic stir bar were added to a 10 mL glass vial in a nitrogen filled dry box N methyl N p methylcarbonylphenyl carbodiimide 1 90 g 9 99 mmol was dissolved in anhydrous pyridine 2 mL After the carbodiimide fully dissolved the pyridine solution was transferred by pipet to the vial containing the catalyst The progress of the reaction was monitored by IR Measurements at 12 hrs 40 hrs and 64 hrs revealed a progressive reduction in the intensity of the N C N absorption at 2143 cm 142 Absence of the carbodiimide absorption after 64 hours of reaction indicated reaction completion Workup experiments indicated that the polymer does not precipitate from methanol or hexanes with trace methanol but does precipi
123. in free energy enthalpy and entropy between one mole of monomer and one mole of polymer repeat units A typical chain polymerization involves converting a monomer s higher energy II bonds into the lower energy o bonds that bind the polymers repeat units Consequently most chain polymerizations are highly exothermic exhibiting a large 64 negative AH Meanwhile the act of binding monomers into repeat units typically reduces their degrees of freedom leading to a mildly negative AS Consequently at low temperatures the large negative value of AHp dominates the free energy expression resulting in spontaneous polymerization However at higher temperatures the magnitude of the TAS term increases leading to a point at which its positive contribution to the free energy expression completely offsets the negative contribution of the AH term This point when the free energy of polymerization equals zero and equilibrium favors neither monomer nor polymer is referred to as the ceiling temperature Te Here where AG 0 Eq 3 1 simplifies to Te AHp ASp 3 2 Simply put the ceiling temperature is the temperature above which spontaneous chain growth polymerization does not occur for a given monomer For carbodiimides the ceiling temperatures that have been characterized range from 80 C for N N di n hexylcarbodiimide to 156 C for R S N methyl N a phenylethyl carbodiimide At temperatures exceeding Ty living polycarbo
124. ing operations are analogous to those listed for COSY 194 Miscellaneous Techniques HOMODEC HOMOnuclear DECoupling HOMODEC allows decoupling of a selected frequency After selecting desired parameters and running the 1D analysis box and Expand the peak of interest Place the cursor on the center of the peak to be selectively decoupled Select Select and then Proceed to run a H NMR analysis in which coupling s to the signal of the selected proton will be removed ll DEPT Distortionless Enhancement Polarization Transfer Enter the Glide Program Setup as described earlier again selecting No for both autolock and autoshim After selecting the solvent select C13 and DEPT only from the experiment submenu Select Acquire Select 1 for Relaxation delay Select Default for Pulse Angle Select Decoupled NOE for H1 dec mode Select DO NOT TEST for Carbon S N Test The appropriate selection for DEPT Scans per inc will depend on the sample concentration 512 is the minimum for highly concentrated samples while 1000 is more appropriate for a low concentration such as 20 mg 0 6 mL Select Full Edit and then Do The full edit printout will display four spectra one for all protonated carbons a second for CH carbons a third for CH2 carbons and a fourth for CH3 carbons In cases where a given signal shows up on the spectrum of two different types of carbons the correct
125. iolate to be superior polymerizing N N di n hexylcarbodiimide in 65 yield in 5 weeks at room temperature Copper I thiophenolate on the other hand took 12 weeks to polymerized N N di n hexylcarbodiimide resulting in a yield of merely 29 61 Follow up experiments revealed that heating carbodiimide III with copper I butanethiolate greatly accelerated polymerization at 60 C Whereas heating Ill in the absence of any catalyst produces a solid polymer in approximately 1 month heating in the presence of copper I butanethiolate results in solid polymer within roughly a week The rate of polymerization proves inversely proportional to the ratio of carbodiimide to catalyst For instance a ratio of 50 1 results in a highly viscous reaction mixture within 2 days while ratios of 250 1 and 500 1 require 5 and 8 days respectively to produce mixtures of comparable viscosity Sadly these reactions prove not to be well defined living polymerizations as sharp signals suggesting the presence of dimers and trimers are clearly apparent in the H NMR spectra of these thiolate initiated thermally polymerized polycarbodiimides Figure 2 10 62 CDCI 12 Days 60 C Figure 2 10 H NMR spectrum of the product resulting from heating carbodiimide III with copper I butanethiolate Though the spectrum consists predominately of broad polymer signals the intensity of sharp signals indicates greater contamina
126. iphenylphosphine 99 in 50 mL CHe2Cle 4 62 g 30 3 mmol bromine in 9 mL CH2Cle 8 4 mL 61 mmol triethylamine and 6 07 g 29 4 mmol N n propyl N L alanine methyl ester urea in 30 mL CH2Cle Two water washes 15 mL each were utilized before drying over sodium sulfate Vacuum distillation was performed at oil bath temperatures ranging from 64 to 95 C and pressures between 180 and 120 mtorr Yield 2 62 g Clear Colorless Oil 57 IR Neat 2964 w 2132 s 1744 s 1215 s cm H NMR 300 MHz CDClz 8 ppm 4 01 q 1H 3 80 s 3H 3 26 t 2H 1 59 m 2H 1 44 d 3H 0 88 t 3H N hexyl N L alanine methyl ester carbodiimide A procedure analogous to the one for the preparation of N phenyl N L alanine methyl ester carbodiimide was employed Quantities of reagents used were 7 60 g 28 7 mmol triphenylphosphine 99 in 100 mL CH2Clo 4 62 g 28 9 mmol bromine in 12 mL CH2Cle 9 0 mL 64 mmol triethylamine 99 and 6 07 g 26 4 mmol of the urea in 50 mL CH2Cle Two water washes 50 mL each were utilized before drying over sodium sulfate Vacuum distillation was performed at oil bath temperatures ranging from 175 to 230 C and a pressure of down to 500 mtorr Yield 2 65 g Clear Colorless Oil 35 IR Neat 2957 w 2876 w 2133 s 1744 s 1210 s cm 1H NMR 300 MHz CDCI 5 ppm 4 02 q 1H 3 80 s 3H 3 32 t 2H 1 59 m 2H 1 48 d 3H 1 38 m 6H 0 88 t 3H 79 N 4 chloroph
127. irreversibly adopt what is referred to as a thermodynamically controlled conformation 21 1 7 2 Too Many Chiefs Not Enough Indians An Optimum Sergeant Soldier Ratio The relationships among chiral entities the helices they induce and the resulting optical properties of cooperative systems are occasionally quite complicated as the first sergeants and soldiers experiment utilizing a polycarbodiimide curiously illustrates In experiments of this type the optical activity of a co polymer system is studied as a function of varying compositions of chiral and achiral repeats i e sergeants and soldiers respectively The typical cooperative effect is an increase in optical activity corresponding with increasing relative amounts of chiral units converging into a plateau of optical activity upon exceeding the concentration of sergeants needed to fully compel the achiral soldiers to adopt the preferred helix However in the first study of this kind involving carbodiimide co polymers what was observed instead is optical activity reaching a maximum at a certain optimum composition after which subsequent increases in the ratio of sergeants to soldiers sharply decrease the optical rotation Though a subile trend of this sort has been observed before where rotational influences of the chiral pendant group and the helix are also in opposition the scale of the effect seen here is unparalleled The origins of this anomalous behavi
128. isil Grade 644 is an expensive neutral grade of silica gel Neutrality is a desirable feature in that acidic or basic gels are anticipated to react with carbodiimides reducing column recovery The column was topped with approximately 2 cm of Ottawa Sand Standard 20 30 Mesh The methylene chloride was removed from one of the two aforementioned portions by rotovap The crude product was then dissolved in chloroform 10 mL and loaded onto the chloroform soaked column The column was developed with chloroform 843 mL The first fraction 93 mL was discarded 1 90 g of opaque yellow oil was isolated from the next fraction 50 mL The four subsequent fractions 50 mL each were included in the workup as described later while the rest were ultimately discarded The opaque yellow oil was analyzed by H NMR The relative integration ratios on the spectrum revealed a 68 purity of the carbodiimide with 32 triphenylphosphine oxide contaminate indicating a mass of 1 29 g carbodiimide a 60 yield for the first column purified portion Upon removing the methylene chloride from the aforementioned second portion by rotovap the carbodiimide was extracted from the triphenylphosphine oxide byproduct with two successive portions 137 of pentanes 50 mL each Removal of the pentanes by rotovap followed by high vacuum revealed 1 91 g of clear yellow oil The relative integration ratios of the H NMR spectrum revealed an 89 purity of the carbodiimi
129. isomers two predominant four trace see 68 H NMR spectrum of a clean polymer isolated by precipitation of a single heavy fraction followed by washing away a single light fraction The relative absence of sharp signals in this spectrum compared with the spectrum of the unclean polymer Figure 2 10 showcases the success of precipitating and extracting fractions in sequence to remove small molecule contaminants ditecaiccsincsincsintsncsincenninnciintsnes oaanns 70 The quantitative conversion of poly lll to a urea structure is the first case in which a polycarbodiimide has been observed to hydrolyze under basic conditions cccceeccecceccecceeeceececceeeceeceeeaeeceeeeeseeeaees 95 xvii Figure 3 2 Figure 3 3 Figure 3 4 Figure 3 5 H NMR specta before and after base catalyzed hydrolysis of poly N phenyl N L alanine methyl ester carbodiimide Both the pendant methyl ester and the polymer backbone are hydrolyzed under strongly DASIC COMINGS assesi i iiia anaidia aaia ea iieii a a iaaa 96 1H NMR spectra of poly Ill before and after 1 week of reaction with 2 methoxyethanol in the presence of p toluenesulfonic acid 2 1 equivalents repeat in chloroform solvent The most prominent change in the spectra is the replacement of broad proton signals with sharp signals consistent with decomposition of the polymer into smaller molecules Increasing the reaction temperature greatly accelerates the decomposi
130. itions Hydrolysis occurs most rapidly with sonication under acidic conditions leading to more complete dissolution of the insoluble polymer in 12 hours than within 1 week of simply stirring 105 3 5 Regioselectivity Study on Carbodiimide Polymerization Catalysts A key distinction between the structures of the older t butyl ester bearing carbodiimide designed by Kim and the newer ones derived from methyl ester protected L alanine is that due to the position of its ester unit on an aromatic ring the former does not have any protons on the carbon that is alpha to the carbonyl It is the enolizable proton on the alpha carbon of latter structures that precludes their polymerization with titanium catalysts Thus titanium catalysts can be used to polymerize ester bearing carbodiimides having structures analogous to the one designed by Kim which is advantageous in that the chiral titanium catalyst proves to be more regioselective than copper catalysts The polymerization of N hexyl N phenylcarbodiimide with copper l butanethiolate versus the S BINOL Ti O Pr 2 catalyst serves as a case in point An expanded view of the aliphatic carbon region of the NMR spectra of this polycarbodiimide made with each catalyst Figure 3 9 A amp B respectively finds the latter to have significantly sharper carbon signals which is consistent with both a higher regioregularity and a predominance of one helical sense A close inspection of the signals for the methy
131. ive comparisons of poly N N di n hexylcarbodiimides made with the chiral catalyst versus chiral initiators are problematic in that the optical rotation measurements were made at different wavelengths in different solvents Nevertheless given that the optical rotations of poly N N di n hexylcarbodiimides bearing a chiral end group are approximately zero at room temperature it is clear from the data that helix sense selective polymerization via chiral catalyst is superior by at least an order of magnitude Figure 1 17 The R BINOL Ti O Pr 2 catalyst When polymerizing the achiral N hexyl N phenylcarbodiimide this catalyst preferentially induces a right handed P helix as assigned by comparing the spectrum observed via vibrational circular dichroism VCD with the one simulated by theoretical modeling calculations Curiously replacing the isopropoxides with tert butoxides reverses the helical selectivity dictating preferential induction of the left handed M helix instead 34 1 8 Optical Switching with a Helical Polycarbodiimide Nanoshutter Having reached the pinnacle of cooperativity with the helix sense selective polymerization of carbodiimides subsequent optical studies uncovered an intriguing switching phenomenon It turns out that many pendant polyaromatics such as 1 naphthyl 1 anthryl and 1 pyrenyl substituents behave as cylindrical nanoshutters with respect to their orientation on the polymer backbone
132. justing the lockpower and or lockgain and then re shim the magnet Lower the temperature re optimize the lock and re shim the magnet in increments of 20 C 80 C is the low temperature limit DO NOT set for less than 80 C Also be mindful not to set the temperature below the freezing point of the solvent listed in Table 1 The sample may not spin at very low temperature If it does not spin do not re shim Wait at least 10 minutes after reaching the desired temperature and then proceed with the analysis To bring the sample back to room temperature type temp 25 su and hit enter Leave the sample loaded until the outside of the line leading from the coil to the probe has completely de iced DO NOT attempt to manually remove the ice doing so could easily damage fragile probe components Instead patiently wait for the ice to melt Once the line has de iced type e and hit enter to eject the sample While retaining the sample tube holder type i and hit enter as if to load a sample but without doing so in order to turn off the ejection air flow Very slowly remove the dewar As the nitrogen inside the coil warms and expands it will vent through the ejection tube which is why it is imperative that you not insert the sample tube holder with the standard yet Wait 10 to 20 minutes until the coil has completely de iced and then type temp n su and hit enter to turn VT off Type e and hit enter to turn
133. k in place with a rubber band wrapped in a figure eight around the stopcock joint Orient each stopcock so that the valve leading to the air space within the stopcock is open to the vacuum line Step 2 clamp on the manifold at the first set of joints from the open end of the vacuum line such that the two pronged side of the clamp sandwiches the joints leading to the stopcock as illustrated Tighten a three prong Step 3 Secure the clamp holding the manifold to a ring stand at an angle of approximately 45 degrees with the stopcocks facing up and the open end of the vacuum line at the top Angling the manifold with the stopcocks up will utilize gravity to hold them in place 160 Step 4 stopcock leading to the vacuum Tighten the Teflon gauge joint until closed Don t forget to reopen this valve for a vacuum gauge reading upon reassembling the manifold and turning on the vacuum pump Step 5 Fill the vacuum line with solvent utilize a long stem funnel to minimize spillage Halogenated solvents such as chloroform and methylene chloride are the most effective at removing old silicon grease deposits Cleaning a vacuum manifold with rotovap recovered halogenated solvents is a more economical practice than doing so with reagent grade solvents 161 Step 6 Utilizing a heat gun to reflux the solvent in the vacuum line is a particularly effective way to dissolve large grease deposits It is especia
134. l pendant esters was reacted under these conditions the distal ester is reported to transesterify extensively and exclusively proving the limitation of this enzymatic transesterification to be an issue of pendant ester proximity to the backbone 97 3 3 1 News Flash Novel Polycarbodiimide Sour on PTSA Given the close proximity of the ester unit derived from L alanine to the backbone of the prototype polycarbodiimide the possibility of facilitating pendant ester transesterification with a chemical catalyst rather than an enzyme holds more promise The traditional most frequently used transesterification catalysts are acids such as H2SO4 RSO2OH H3PO3 and HCl p Toluenesulfonic acid for instance has been utilized to transesterify the pendant esters on poly methyl acrylate with optically active alcohols Unfortunately the prototype ester bearing polycarbodiimide poly IIl decomposes on exposure to strong acid In a pair of transesterification experiments on poly lll with p toluenesulfonic acid the most noticeable change over the course of the reaction was decomposition as evidenced by changes in the H NMR spectra Figure 3 3 3 3 2 Transesterification Studies Under Mild Conditions The instability of the prototype ester bearing polycarbodiimide in the presence of strong acids or bases precludes modification under harsh conditions Fortunately there are milder alternatives for the purpose of transesterification Mercury Il
135. le absence of a signal for the hydroxyl proton of the free alcohol highlighted in red from the spectrum of the transesterified polymer indicates that the additional proton signals are from newly placed 2 methoxyethyl substituents on the pendant group The relative broadness of these signals is also consistent with polymer attachment 100 3 4 Follow Up Studies on an Old Ester Bearing Polycarbodiimide Having thoroughly explored the synthesis stability and reactivity of a polycarbodiimide derived from a simple methyl ester protected chiral amino acid and finding its potential for subsequent modification to be quite limited our focus shifted to re investigating an earlier ester bearing design previously developed by Jeonghan Kim The multi step synthesis is outlined in Figure 3 5 His pilot effort to free the acid with iodotrimethylsilane renowned for mildly cleaving esters reportedly led to polymer decomposition which in hindsight is likely to have been a consequence of the elevated temperature at which such deprotections are facilitated A more thorough investigation of this earlier design revealed that unlike polycarbodiimides bearing simple alkyl and aryl substituent such as poly N benzyl N 4 n butylphenyl carbodiimide which proves stable when sonicated under strongly acidic or basic conditions for one week the ester bearing polycarbodiimide designed by Kim decomposes with mere sonication as evidenced by c
136. lene carbons directly attached to the backbone Figure 3 10 reveals not only sharper signals for the polymer made with chiral titanium catalyst but also a greater relative intensity for the carbon signal of the dominant regiochemistry which has the hexyl group on the amine position in either case 106 Spectrum A Polymerized w CuSCH CH CH CH Toluene d lt tyr Spectrum B Polymerized w S BINOL Ti O i Pr Toluene d ie a Nw as A OMe maken of swe we ey 0 sAm Figure 3 9 Aliphatic region of poly N hexyl N phenylcarbodiimide made with copper versus chiral titanium catalyst The sharper carbon signals of the latter are a consequence of both its higher regioselectivity and its more singular helicity 107 SpectrumA Polymerized w CuSCH CH CH CH Aa gt Toluene d aa w r v r 1 x r i 7 z rs Spectrum B Polymerized w S BINOL Ti O i Pr N n Toluene d ad Be a He T T oor ocs sr e st l 50 49 48 47 46 45 ppm Figure 3 10 Expanded view of the signals for the alpha methylene carbons Notice that the minor regiochemistry having the hexyl substituent in the imine position is significantly more prevalent from the copper catalyzed polymerization 108 3 6 Descendants of an Old Ester Bearing Polycarbodiimide In the interest of exploring the full potential of Kim s ester bearing carbodiimide design four derivatives were made Figure 3 11 T
137. lformamide d7 61 C gt 100 C Dimethyl Sulfoxide dg 19 C gt 100 C 1 4 Dioxane dg 12 C 99 C Ethanol d lt 80 C 78 C Methanol d lt 80 C 64 C Methylene Chloride ds lt 80 C 39 C Nitrobenzene ds 6 C gt 100 C Nitromethane ds 29 C 100 C Pyridine ds 42 C gt 100 C Tetrahydrofuran dg lt 80 C 65 C Toluene dg lt 80 C gt 100 C Trifluoroacetic Acid d 15 C 75 C 203 Table 2 Commands for Access to Standard Solvent Parameters The Nucleus Solvent submenu displays selection options from which to access standard parameters for the five most commonly used solvents CDCI3 D20 Benzene DMSO and Acetone Standard parameters for all other solvents have to be accessed by selecting Other and typing in the appropriate solvent command following the Enter Solvent prompt Some solvents have more than one command with which these parameters can be accessed as listed below Solvent Command s Solvent Command s Acetic Acid d CD3COOD or Dimethyl Sulfoxide dg DMSO Acetic_Acid Acetone d CD3COCD3 or 1 4 Dioxane dg Dioxane Acetone Acetonitrile ds CD3CN or Ethanol d CD3CD20D or CH3CN Ethanol Benzene d C6D6 or Methanol d CD30D or Benzene CH30H or Methyl_Alcohol d4 Chloroform d CDCI3 or Methylene Chloride d CD2ClI2 or Chloroform MethyleneChlorid e Cyclohexane d 2 C6D12 or Nitrobenzene d Nitrobenzene Cyclohexane Deuterium Oxi
138. llow powder 91 yield IR KBr Pellet 3350 s 3242 s 3062 vw 3043 vw 3022 vw 2983 w 1707 vs 1647 s 1599 vs cm H NMR 300 MHz CDCI 5 ppm 7 86 d J 8 7 Hz 2H 6 63 d J 8 7 Hz 2H 4 62 q J 8 4 Hz 2H 4 13 s 2H 127 N methylI N p t butoxy carbonylphenyl thiourea t Butyl p aminobenzoate 9 68 g 50 0 mmol was weighed and transferred to a 250 mL round bottom flask Chloroform 100 mL and a magnetic stir bar were added Methyl isothiocyanate 97 18 9 g 251 mmol a 400 excess was added and the reaction mixture was heated for 1 week at 60 C The reaction mixture was rotovaped at 60 C until saturated as judged by the appearance of precipitation The amount of chloroform that had been removed measured by recovery from the collection flask of the rotovap was approximately 45 mL Upon cooling to room temperature the relatively large quantity of precipitate resulted in a slurry Removal of the remaining chloroform from the slurry by vacuum filtration with a filter paper covered vacuum needle assembly was a slow tedious process See Appendix 1 for filter paper covered vacuum needle assembly instructions Upon removing the majority of the remaining chloroform a wash of hexanes 5 mL was used to facilitate purification A total of 53 8 mL of supernatant were removed Removal of the remaining volatiles by vacuum revealed 9 36 g of white powder verified by H NMR to be the desire
139. lly important that the valve leading to the air space within the stopcock is open to the vacuum line while heating as vaporization of solvent and expansion of heated air within the stopcock might otherwise lead to a violently blowout Step 7 Pour the solvent into an appropriately labeled waste flask for transfer to a halogenated waste container Repeat steps 5 through 7 with halogenated solvents for heavy grease deposits Metal deposits are best removed by soaking the line with aqua regia A base bath of potassium hydroxide in isopropyl alcohol is another useful cleaning alternative when halogenated solvents fail Note that extended soaking in a base bath will damage manifold glassware 162 Step 8 Submerge each stopcock handle down in a beaker of halogenated solvent For particularly difficult grease deposits boil the solvent to facilitate the cleaning process As with the vacuum line soaking the stopcocks in aqua regia or a base bath for a few minutes may be advisable alternatives depending on the contaminates to be removed 9 Step stopcock cleaned with a Kimwipe Tear a Kimwipe in half widthwise roll it and twist one end of the roll into a tight point Grease clogged channels can be 163 Step 10 Insert the twisted end of the Kimwipe through the stopcock channel If the channel is too clogged with grease to do so unclog it by inserting the narrow end of a glass pipet 11 Pull
140. ls thus indicating two regiochemistries Figure 3 15 B The relative intensities of the two benzylic methylene carbon signals agree with the predominant regiochemistry assignment via infrared imine absorption namely that the benzyl group predominantly occupies the amine position However unlike the infrared spectrum where only one regiochemistry is observable here through the application of line broadening to C NMR data both are apparent confirming as anticipated that the polycarbodiimide is indeed regioirregular 116 CDCI Spectrum A 13C NMR Spectrum w o Line Broadening fe fa he 220 200 180 160 140 120 100 80 6o 4 2 0 ppm CDCI Spectrum B 13C NMR Spectrum w 30 Hz Line Broadening HA fe N A hoo 200 1380 160 140 0 60 40 220 120 100 8 20 0 ppm Figure 3 14 C NMR spectra of poly X before and after applying 30 Hz 0 40 ppm of line broadening to the data Notice the latter provides much greater detail such as the signal of the carbonyl carbon at 166 ppm and that of the quaternary t butyl carbon just downfield of the solvent signal at 80 9 ppm 117 A Highlight of Region Having Most Discernable Regiochemical Difference Line Broadening 5 Hz 0 067 ppm 220 200 180 160 140 120 100 80 60 40 20 0 ppm y B Expanded View of Regiochemical Difference Line Broadening 1 7 ppm Toroa 57 56 55 54 53 52 51 50 49 48 47 46 45 ppm Figure 3 15 Highlighted and expanded views of the
141. magnifies the scale of the rotations compared with those at the more customarily utilized sodium D line For instance consider the optical rotations of R N methyl N a methylbenzyl carbodiimide for which a s98 is 10 8 while sss measures 72 0 Nevertheless it is clear from the data that co polymerizations of enantiomeric mixtures of R and S N methyl N a methylbenzyl carbodiimide do cooperate in establishing the helical sense preferred by the majority The moderate intensity of this effect affords confident deduction that the co polymerization of these enantiomers is not stereoselective In other words these chiral monomers do not polymerize into separate homochiral chains or segregated stereoblocks Were they to do so each block or chain would adopt its own preferred helical sense resulting in a decidedly linear optical response to variations in the enantiomeric ratio the very definition of non cooperative behavior 25 The atypical optical response to enantiomeric excess observed in the first study of a polycarbodiimide proves the exception rather than the rule and is a consequence of the relatively low optical rotation compared with that of the pendant chiral entity of a polycarbodiimide helix presenting as the other pendant group a miniscule methyl substituent A subsequent study revealed that annealed co polymers composed of enantiomeric mixtures of N 2 6 dimethylheptyl N hexylcarbodiimide manifest a mor
142. mic committee members Dr He Dr Smirnova and Dr McCord am honored by their service Finally ld like to thank my advisor Dr Novak who has funded my research and has patiently mentored with me for many years not only to make me a better teacher and researcher but also to guide the development of my character and perseverance TABLE OF CONTENTS HSTOF TABLES oy ree iee aee E REE Ee REO EEA EEE rA EAE EEEE E EEEE ix LIST OF FIGURES vices stveireiatsauhatanentdvieteaehedetetuaeiedvesbendvocheiatainceebysreeebsiatenetyentened x CHAPTER 1 THE HISTORY OF POLYCARBODIIMIDES Mes AiR o1S LUTO 1o A AE E A E E A AE E ae ere O 1 1 2 Early Studies on Carbodiimide Polymerization ccceeeeeeeeeeeeeeeeees 4 1 3 Living Polymerization of Carbodiimides cccceecceeeeeeeeeeeeeeeeeeeeeeeees 6 1 4 Thermal Decomposition of Polycarbodiimides eccceeseeeeeeeeeeeeeeees 10 1 5 Polycarbodiimide Microstructure The Role of Regiochemistry 13 1 6 Polycarbodiimide Macrostructure From Worms to Rigid Rods 16 1 7 Concepts of Cooperativity ccceccceeeeeeeeeeeeeeeneeeeeeeeeeeeeeeeeeneeeeeeeeeeeeeeeee 17 1 7 1 The Kinetics and Thermodynamics of Homochiral Polycarbodiimide Helicity cceeeeeeeeeeeeeeeeeeeeeeees 20 1 7 2 Too Many Chiefs Not Enough Indians An Optimum Sergeant Soldier Ratio cccccceeessceccceeeeeeeeeeeseenenees 22 1 7 3 T
143. mmol was weighed in a 138 separate 20 mL vial The titanium tetraisopropoxide was transferred by pipet to the vial containing the alcohol A toluene rinse 1 mL was utilized to facilitate quantitative transfer After 4 hours of stirring in the vial the reaction mixture and stir bar were transferred to a Schlenk flask The flask was sealed removed from the dry box and attached to a Schlenk line Using Schlenk technique the flask was placed under a positive pressure of nitrogen Removing the toluene solvent from the product while not contaminating the sample with moisture and oxygen is an art that is difficult to put into words and takes considerable practice Basically the first step was to ensure that the glass stopper used to seal the flask is properly greased in order to make an effective seal While maintaining a positive outflow of nitrogen the stopper was temporarily removed Vacuum grease was applied to the stopper which was then returned to the flask and twisted back and forth to ensure a uniform distribution The flask was placed in an ice water bath positioned on top of a magnetic stir plate Magnetic stirring was applied both to facilitate cooling and to avoid violent bumping of the solvent upon application of vacuum Two of the five ports on the inert gas vacuum manifold system were connected with a rubber hose One port was opened to a positive pressure of nitrogen the other was cracked slightly open to vacuum as needed to adju
144. n IR KBr Pellet 3060 w 2989 w 2950 w 2871 w 2848 w 1739 s 1639 s cm H NMR 300 MHz CDCls 8 ppm 6 85 6 60 6 29 5 94 3 93 3 36 1 57 1 27 0 86 all broad Figure 2 14 C NMR 300 MHz CDCI 8 ppm 172 9 146 8 138 5 130 3 129 5 128 2 126 9 126 3 124 3 55 7 51 2 20 6 18 0 Poly N 4 methylphenyl N L alanine methyl ester carbodiimide Un Fractioned H NMR 300 MHz CDCls 5 ppm 7 24 7 09 6 78 5 94 3 71 3 36 2 36 2 29 1 60 broad signals Poly N 4 fluorophenyl N L alanine methyl ester carbodiimide Universally Insoluble IR KBr Pellet 3058 w 2987 w 2954 w 2850 w 1735 m 1636 s cm 89 Poly N N di n hexylcarbodiimide IR KBr Pellet 2956 m 2927 m 2858 m 1647 m 1467 w 1354 w 725 w cm H NMR 300 MHz CDCls amp ppm 4 2 3 4 3 1 1 5 1 3 0 9 all broad C NMR 300 MHz CDCls amp ppm 148 49 0 46 5 32 6 32 2 29 9 29 4 28 0 27 7 23 2 23 0 14 4 14 3 90 2 7 References 10 11 12 13 14 15 16 17 18 Goodwin A Novak B Macromolecules 1994 27 5520 5522 Kim J PhD Dissertation North Carolina State University 2002 Shibayama K Seidel S Novak B Macromolecules 1997 30 3159 3163 Goodwin A PhD Dissertation University of California at Berkley 1996 Schlitzer D Novak B Journal of the American Chemical Society 1998 120 2196 2197 Schlitz
145. n acetone rinse 1 mL was utilized to facilitate quantitative transfer The dimer was extracted with two portions of chloroform 25 mL each The chloroform was dried with sodium sulfate and removed by rotovap followed by high vacuum revealing a crunchy black solid 1 49 g 93 yield IR KBr Pellet 3064 w 2987 w 2952 w 1749 s 1657 s 1620 s cm H NMR 300 MHz CDCls 8 ppm 7 5 to 7 3 m 10H 4 24 q 2H 4 00 s 6H 1 51 d 6H C NMR 300 MHz CDCls 8 ppm 180 158 132 129 128 126 62 4 55 8 17 5 87 Overview of Carbodiimide Polymerization Procedures All polymerization were conducted under nitrogen as detailed under the heading Inert Atmospheres in Section 2 6 1 All polymerizations discussed in this chapter were performed neat With the exceptions of the polymer obtained via exclusively thermal polymerization of Ill which was characterized in crude form and the polymer of V catalyzed by CuCls and heat which proved insoluble in every solvent tested all polymers made from these ester bearing carbodiimides were worked up by suspending the polymer with the aid of gentle heating and a Thermolyne Type 16700 Mixer in a minimum amount of acetone precipitating in deionized water and extracting the precipitated polymer with chloroform The polymer solutions in chloroform were dried with a wash of saturated sodium chloride followed by standing over sodium sulfate The anhydrous chloroform was removed
146. n be tailored to improve stability under acidic conditions While the single imine absorption on the infrared spectrum of this hybrid polymer suggests a predominance of one regiochemistry enhancement of the C NMR signal to noise ratio via line broadening reveals both regiochemistries to be present facilitating new insights into the microstructure of such polycarbodiimide architectures 120 3 9 Experimental Section 3 9 1 General Procedures and Equipment Instruments All infrared spectra were recorded on a JASCO FT IR 410 spectrometer Characteristic absorptions are reported in wavenumbers cm All nuclear magnetic resonance spectra were recorded on Varian Mercury 300 or 400 MHz spectrometers Chemical shifts are reported in ppm relative to the assignment of solvent chemical shifts referenced to tetramethylsilane as listed in Table 3 of Appendix 4 Optical rotation measurements were recorded on a Jasco P 1010 Polarimeter at 589 nm Solutions measured for optical rotation were prepared by dissolving 20 mg of sample overnight in 10 mL of solvent at room temperature Thermogravimetric analyses were recorded on a TA Instruments Hi Res TGA 2950 Thermogravimetric Analyzer Differential Scanning Calorimetry analyses were performed with a TA Instruments DSC 2920 Modulated DSC Reagents All reagents were obtained from a commercial supplier and used without further purification with the exception of solvents utilized for air and moisture sen
147. nd left limit of the region to expand Right click and drag to set the upper and right limit of the region to expand Select Expand to zoom in on the region Select vs 20 or vs 20 to magnify or reduce the vertical scale respectively Select Autoplot to plot the screen Select Full to zoom out The file is automatically saved to the group directory in a format displaying the group name followed by the day month and year such as novak_10Apr2008 To re access the COSY spectrum right click on the file to highlight and select Set Directory Right click on COSY fid to highlight select Load and then select AutoProcess 192 ll TOCSY1D 1D TOtal Correlation SpectroscopY 1D TOCSY reveals long range correlations with a proton signal of a selected frequency After selecting desired parameters and running the 1D analysis box and Expand the proton signal of interest Place the cursor on the center of the signal peak and then select Select You may select multiple peaks to set up a series of analyses After selecting all peaks of interest select Proceed Each of the resulting spectra will reveal the long range couplings with one of the selected proton signals for the given mixing time ll t90 2D TOtal Correlation SpectroscopY Select 16 to 32 for TOCSY Scans per inc Select 128 for TOCSY number of inc Select from 30 ms to 80 ms for TOCSY mixing time Warning Selecting a mixing time in excess of 80 ms will dam
148. nformation having an alse 7 5 in hexanes The monomer itself has an a sss 7 6 which suggests that the optical rotation exhibited by the polymer is essentially contributed by the chiral pendant group In this case the kinetically controlled conformation features a random distribution of right and left handed helices separated by helical reversals within the chain Reaching the thermodynamically stable conformation having an a se5 157 5 in hexanes requires slow annealing at elevated temperatures However protonation with five equivalents of benzoic acid effectively catalyzes this transformation at room temperature immediately resulting in aJses 144 in chloroform Current speculation is that protonating the imine positions catalyzes the re orientation of pendant group arrangements that typically hinder inversion of the backbone into the energetically favored helix Figure 1 14 27 woe we Pi N N N A Acid An tael n A i we N N R R trans cis trans trans Figure 1 14 Pendant groups on adjacent imine nitrogens may orient in either a trans cis or trans trans arrangement In theory protonation of the backbone would facilitate transformations into trans trans orientations through the free rotation of pendant entities in the endo resonance form of the amidinium ion inadvertently lowering the activation energy of the helical inversion process While protonating the polycarbodiimide backbone does enable a chiral ped
149. ng about random co polymers in which dissimilar monomers are incorporated randomly within a polymer chain More specifically when a chiral mixture of repeat units is interspersed in a random fashion they may interact cooperatively to determine the helical conformation that is adopted Studies of this type which involve the polymerization of chiral monomers in varying enantiomeric ratios are referred to as Majority Rules experiments The typical cooperative effect observed in these studies is an increase in optical rotation 23 corresponding with increasing enantiomeric excess converging on a plateau of optical activity following the excess needed to fully compel the minority to adopt the helical sense favored by the majority The optical effects observed in the first Majority Rules experiment on a polycarbodiimide are more elaborate Rather than exhibiting an optical rotation that plateaus as the enantiomeric excess approaches purity this system displays optical activity reaching a maximum at a certain optimum enantiomeric excess after which subsequent increases in chiral purity modestly decrease the optical rotation A decrease in optical rotation upon approaching enantiomeric purity has also been reported elsewhere in a similar case where the optical influence of the pendant 51 At an enantiomeric excess of 80 chiral entity opposes that of the helix it favors co polymers of R and S 2 6 dimethylheptyl isocyanate exhi
150. nt delay time The default delay time is 1 second Use the command d1 5 before re running the analysis to change the delay time to 5 seconds If the integration improves but is still not adequate try d1 70 or d1 20 Other factors that may negatively affect integration accuracy include poor phasing and baseline drift Carefully examine the phasing of the spectrum and re phase manually if autophasing was suboptimal Type dc and hit enter to correct drift Type cz hit enter and re integrate the spectrum to determine whether these adjustments have improved integration accuracy Adding Text to the Spectrum Use the command format text UB Clark 06 16 08 and hit enter to add lines of customized text for printing The marks open a new line of text Adding the command pltext to the print command line discussed in the previous section will add the text to the printout The command ctext will clear the previous text entry Additional Print and Display Commands Using the command axis h prior to pscale changes the scale units to Hertz while axis p changes the units back to ppm The command pli can be used to print a peak frequency list having both ppm and Hz Do not use ppa or pap when using pll To display a list of the integrals on the text screen use the command dli A list of peak frequencies can be displayed on the text screen with the command dll The command dg will return the original display of parameters to the text
151. nt was of synthetic interest the cost of the starting materials coupled with the meager reaction yield 5 precluded subsequent investigations 7 o o o o NH N l 1 PC I Pyridine Reflux Y o c 2 NaHCO Wash NH N HC cl Figure 2 5 Phosphorus pentachloride is a highly reactive reagent In this experiment not only did it generate the chloroformamidine hydrochloride intermediate which reacted with base to form the carbodiimide it also chlorinated the benzylic position of the 4 methylpheny substituent 50 2 3 Polymerization of Novel Ester Bearing Carbodiimides In the interest of developing functionally modifiable polycarbodiimides a variety of novel ester bearing monomers were synthesized Of primary interest were ester protected amino acids which if incorporated as pendant groups might open doors to the field of peptide chemistry for the polycarbodiimide architecture Using the methods discussed in the previous section approximately half a dozen designs pairing methyl ester protected L alanine with various aliphatic and aromatic substituents were synthesized for polymerization testing The discussion that follows recounts the ordeal of developing an innovative methodology for polymerizing these novel carbodiimides and for removing the low molecular weight contaminates that are inevitable byproducts of this thermally driven process 2 3 1 Studies with Traditional Polymerization Catalysts As described in C
152. of the substituents and the steric congestion they create around the backbone The scaling factors of 0 78 for poly N N di n hexylcarbodiimide 0 89 for poly rac N methyl N a methylbenzyl carbodiimide and 1 0 for poly R N methyl N a methylbenzyl carbodiimide roughly quantify the magnitude of these influences on the macromolecular conformation adopted by a given polycarbodiimide 16 1 7 Concepts of Cooperativity The helical nature of polycarbodiimides affords preferential induction of right or left handed helical conformations via cooperation with chiral entities The extent of this cooperation in a given system can be visualized on a continuum of hierarchical levels illustrated by the Pyramid of Cooperativity Figure 1 11 In each case the cooperative effect is a result of the energy difference in the diastereomeric interaction of the chiral entity with the right and left handed conformation of the helix Figure 1 12 Through nearest neighbor interactions of identical chiral pendant groups on each repeat unit homochiral polymers achieve their cooperative influence over the shortest length scale i e those of the nearest neighbor These represent the lowest level of cooperativity at the base of the pyramid At the level of sergeants and soldiers the interaction of a chiral pendant group on one repeat unit with the achiral pendant groups on repeat units to either side can be thought of as cascading down the chain
153. oly X The only observable imine absorption is at 1635 cm suggesting the aromatic pendant group occupies the imine position The infrared spectrum does not provide any indication of the alternative regiochemistry thus allowing observers to speculate that the structure is regioregular 115 There are however a variety of ways to improve the NMR signal to noise ratio The most obvious is to simply increase the number of scans But a greater number of scans requires a lengthier analysis A better compromise given the time constraints on instrument availability is to sacrifice some of the resolution to improve the signal to noise ratio through the application of line broadening The greater separation of signals on the C NMR scale versus those on the H NMR scale provides a lot of room to sacrifice resolution without a loss of pertinent information When line broadening of 30 Hz which is merely 0 40 ppm on the chemical shift scale is applied to the C NMR spectrum of poly X what initially appeared to be relatively useless data having only one distinguishable signal Figure 3 14 A reveals information on even the faintest signals of the structure Figure 3 14 B Even with a mere 5 Hz 0 067 ppm of line broadening a faint benzylic methylene carbon signal is apparent Figure 3 15 A A closer inspection of this region with the application of 125 Hz 1 9 ppm of line broadening reveals two slightly overlapping methylene carbon signa
154. or air and moisture sensitive procedures which were purified under a nitrogen atmosphere via reflux over an appropriate drying agent followed by fractional distillation 4A molecular sieves were oven dried overnight at 215 C then cooled and stored in a desiccator The purity of commercially supplied reagents was factored into all calculations in the sections that follow 72 Inert Atmospheres All air and moisture sensitive procedures were either conducted in a nitrogen filled MBRAUN UNILab Dry Box or while utilizing Schlenk techniques facilitated by a Chemglass CG 4441 03 5 Port Glass Stopcock Inert Gas Vacuum Manifold coupled with a dual liquid nitrogen trap attached to a Welch Model Number 1402 01 Vacuum Pump Vacuum pressures were observed with a Kurt J Lesker Company Millitorr Vacuum Gauge Unopened volatile free vacuum line pressures exceeding 50 mtorr were corrected by routine typically weekly vacuum line maintenance which entailed Steps 12 through 16 of the more thorough Guide to Vacuum Manifold Maintenance procedure listed in Appendix 2 Glassware used for air and moisture sensitive procedures was dried overnight in an oven at 140 C Alternatively glassware was flame dried under vacuum lt 100 mtorr Stir bars utilized for air and moisture sensitive reactions were dried overnight either in an over at 140 C or under vacuum lt 100 mtorr Alternatively stir bars were retrieved from storage under
155. or lie in the intricate manner in which the two substituents paired on the chiral monomer effect the optical rotation of the polymers into which they are incorporated R N methyl N a methylbenzyl carbodiimide polymerizes into a preferred helical conformation exhibiting an optical rotation a s9s of merely 10 8 Such an attenuated rotation is 22 typical of a homochiral polycarbodiimide also bearing a miniscule methyl substituent The monomer itself rotates the sodium D line by 25 8 In this system the contributions to the optical rotation by the chiral pendant group and that of the helix it preferentially induces are comparable in magnitude and opposite in sign When co polymerized with the decreasing amounts of the achiral N N di n hexylcarbodiimide the optical rotation of the kinetically controlled conformation increases rapidly as the composition approaches a chiral monomer content of 20 The trend is less pronounced but continues to a content of approximately 40 where the optical rotation reaches a maximum value of 52 2 beyond which it gradually declines due to the opposing optical influence of the pendant chiral entity until it matches that of the homochiral polymer 1 7 3 The Helix Directing Authority of the Chiral Majority In the land of polymers it is occasionally the case that a particular democratic process rules in societies that are well integrated so to speak Here we are talki
156. ore grease if the traps fail to rotate smoothly and easily 179 Step 42 Align each ball and socket joint Twist the connection back and forth under vacuum to ensure a uniform coating of grease and a proper seal 180 The manifold pressure should quickly fall to less than 100 mtorr Without the use of liquid nitrogen in the cold traps it may take several hours to reach maximum vacuum as the volatile components of the Apiezon grease off gas creating a virtual leak in the system The pressure should drop steadily during this time Once the pressure stabilizes twist and press each stopcock each cold trap and each ball and socket joint again to ensure a maximum seal Appendix 3 Creating an Improvised Holding Devise for Molecular Sieves 5 P PLASTIC SYRINGE OZ 5 mL 100 PK 1000 CS A wwe Lot Number 00054832 107 CEP reay amt Mocoerent 1 31A Step 1 Begin with a 5 mL Luer Step 2 Cut off the tip Slip Plastic Syringe Step 3 Insert a small circular Step 4 Using an ice pick or a cut of filter paper to plug the end similarly shaped tool puncher the of the syringe Using the plunger Syringe at the 1 mL mark to trace a circle on a piece of filter paper will assist in making a cut that will fit appropriately 181 Step 5 Make a series of staggered puncher holes at the 2 3 4 amp 5 mL marks as illustrated Step 6 Rotate the syringe 120 and repeat steps 4 amp 5 to make a se
157. perature reveals dimerization to be a thermally favorable process Since the broad overlap of conditions catalyzing both polymerization and dimerization precludes exclusive polymer synthesis a general procedure coupling a fractional precipitation with a fractional extraction was developed to remove small molecule contaminants and isolate high molecular weights of these novel ester bearing polycarbodiimides 71 2 6 Experimental Section 2 6 1 General Procedures and Equipment Instruments All infrared spectra were recorded on a JASCO FT IR 410 spectrometer Characteristic absorptions are reported in wavenumbers cm All nuclear magnetic resonance spectra were recorded on Varian Mercury 300 or 400 MHz spectrometers Chemical shifts are reported in ppm relative to the assignment of solvent chemical shifts referenced to tetramethylsilane as listed in Table 3 of Appendix 4 Optical rotation measurements were recorded on a Jasco P 1010 Polarimeter at 589 nm Solutions measured for optical rotation were prepared by dissolving 20 mg of sample overnight in 10 mL of solvent at room temperature Thermogravimetric analyses were recorded on a TA Instruments Hi Res TGA 2950 Thermogravimetric Analyzer Differential Scanning Calorimetry analyses were performed with a TA Instruments DSC 2920 Modulated DSC Reagents All reagents were obtained from a commercial supplier and used without further purification with the exception of solvents utilized f
158. pm 166 152 148 131 127 121 80 9 34 1 28 4 185 8 C Decomposition Temperature 5 Loss of Mass Tg absent from Differential Scanning Calorimetry Analysis Specific Optical Rotation measured 22 7 0 5 Poly N benzylI N p t butoxy carbonylphenyl carbodiimide S 1 1 Binapth 2 2 ol titanium IV diisopropoxide 31 7 mg 70 4 umol and a magnetic stir bar were added to a 10 ml glass vial containing N benzyl N t butyl p aminocarbonylphenyl carbodiimide 2 29 g 7 06 mmol in a nitrogen filled dry box A chloroform rinse 0 25 mL was utilized to facilitate transfer of the catalyst Additional chloroform solvent 1 mL was added at this point The viscosity of the reaction solution increased gradually The polymer reaction formed a solid within 4 to 5 days On day 5 chloroform 3 mL was added Re dissolving was facilitated via agitation with a vortexer On day 7 the polymer was diluted with additional 141 chloroform 37 mL and precipitated in magnetically stirred methanol 200 mL The precipitate was left stirring overnight The next day the supernatant was removed with a filter paper covered vacuum needle assembly See Appendix 1 for filter paper covered vacuum needle assembly instructions This was a very very slow process requiring approximately 3 hours as the fine precipitate hindered the flow of supernatant through the filter paper The precipitate was rinsed with methanol 10 mL The remaining volat
159. prompt the display to provide a time estimate Iteratively adjust the number of transients and check the time until finding the maximum number of transients that will fit in the desired run time frame Special Note If when checking the run time the software returns an error message saying code file already exists PSG Aborted increase the sweep width by increments of from 10 to 100 until the error message is no longer returned upon utilizing the time command Since obtaining a quantitatively accurate carbon spectrum may take longer than a typical overnight analysis it becomes vitally important to save the data in case data re processing becomes necessary Therefore saving the data is the highest priority and should be done even before the first processing attempt in order to avoid accidentally forgetting to do so The Relaxation Reagent Cr acac 3 may be utilized for samples having long spin lattice relaxation times T Increasing the amount of the reagent results in shortened relaxation times and an increase in line width usually without affecting chemical shifts A concentration of 0 1 M is ideal for quantitative work The highest concentration reported to give reasonable results is 0 4 M as severe line broadening and difficulty with locking on the solvent signal become problems at higher concentrations Other relaxation reagents include Mn acac s Cu acac 2 and Gd acac 3 Braun S H O Kalinowski and S Berger 150 and More B
160. r instance poly cyclo 1 2 diisocyanateodecane exhibits an onset of decomposition at 276 C nearly one hundred degrees higher than that of poly n hexyl isocyanate at 180 C Unfortunately various cyclopolymers made from 1 2 dicarbodiimides proved no more thermally robust than linear polymers derived from monocarbodiimides Crosslinking is another strategy often utilized to improve the thermal stability of polymer structures Two examples include the crosslinking of polystyrene and poly methyl methacrylate with 0 5 of ZrgQ4 OH 4 methacrylate 12 clusters which is reported to elevate the onset of thermal decomposition by 49 C and 113 C respectively Sadly improvements in the thermal stability of polycarbodiimides via crosslinking prove negligible When poly N N di n hexylcarbodiimide is crosslinked to varying degrees with either of two dicarbodiimides Figure 1 8 elevations of the thermal decomposition onset range from merely 1 to 10 C Figure 1 8 Structure of the dicarbodiimides 1 4 di N methylcarbodiimidio butane and 1 4 di N methylcarbodiimido hexane utilized for the crosslinking of poly N N di n hexylcarbodiimide 12 1 5 Polycarbodiimide Microstructure The Role of Regioselectivity For any asymmetrically substituted carbodiimide there are potentially two regiochemistries for the pendant groups on a given polycarbodiimide repeat Consider the case of the N hexyl N phenylcarbodiimide illustrated in
161. rahedron 2003 59 2617 2623 Rankin D W H Journal of the Chemical Society Dalton Transcriptions 1972 7 869 873 Gupta R K Stammer C H Journal of Organic Chemistry 1968 33 4368 4371 Thrasher J S Howell J L Clifford A F Inorganic Chemistry 2008 21 1616 1622 Ulrich H Chemistry and Technology of Carbodiimides Wiley 2007 Down M G Haley M J Hubberstey P Pulham R J Thunder A E Journal of the American Chemical Society Dalton Transcriptions 1978 1407 1411 Becker M Jansen M Solid State Sciences 2000 2 711 715 Berger U Schnick W Journal of Alloys and Compounds 1994 206 179 184 Liu X Krott M Mller P Hu C Lueken H Dronskowski R norganic Chemistry 2005 44 3001 3003 14 Becker M Jansen M Acta Crystallographica 2001 C57 347 348 40 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Hashimoto Y Takahashi M Kikkawa S Kanamaru F Journal of Solid State Chemistry 1996 125 37 42 Zhou Y Probst D Thissen A Kroke E Riedel R Hauser R Hoche H Broszeit E Kroll P Stafast H Journal of the European Ceramic Society 2006 26 1325 1335 Rebek J Feitler D Journal of the American Chemical Society 1973 95 4052 4053 Kunkel G R Mehrabian M Martinson H G Molecular and Cellular Biochemistry 1981 34 3 13 Fridkin M Patcho
162. rd Record the default setting for the number of points np which is the fourth parameter listed under ACQUISITION on the display The software will automatically reduce the number of points in response to a decrease of the sweep width Type movesw and hit enter to reduce the sweep width to the selected region Reset the number of points to improve the resolution Type np 24000 and hit enter to approximate a previous value of 23936 for instance If a subsequent command prompts an error message saying P S G Aborted increase the sweep width from the value listed under the ACQUISITION display by increments of from 10 to 100 until executing a subsequent command no longer prompts the error message For instance type sw 4020 and hit enter for a sw value listed as 4006 After collecting the data resolution can be further enhanced by setting the Fourier number to double the number of points a process referred to as zero filling As an example use the command fn 48000 wft to adjust the Fourier number for a spectra collected with an np setting of 24000 Improving the Signal to Noise Ratio Several parameters may be adjusted to improve the signal to noise ratio One commonly applied adjustment is to increase the number of transients The signal to noise ratio is proportional to the square root of the number of transients The default setting for proton spectra is 16 transients Use the command nt 32 or nt 64 to set 32 or 64 transients
163. re more rigid Since most polycarbodiimides decompose at relatively low temperatures ca 150 200 C thermotropic mesophases are uncommon Two exceptions poly N N di n dodecylcarbodiimide and poly N 12 4 methoxybiphenyl 4 oxy dodecyl N n dodecylcarbodiimide display thermotropic mesophases just below their decomposition temperature The mesophase behavior of the former can be described as helical rods aligning in molten paraffin while latter forms a smectic layered texture due to the added influence of the mesogenic side chain entity 38 A Poly N N di n hexyicarbodiimide d d 13A B Poly n hexyl isocyanate Figure 1 21 Schematic representation of A the smectic phase of poly N N di n hexylcarbodiimide versus B the nematic phase of poly n hexy isocyanate 39 1 10 References 1 11 12 13 Gordetsov A S Kozyukov V P Vostokov I A Sheludyakova S V Dergunov Y Mironov V F Russian Chemical Reviews 1982 57 485 469 Razuvaev G A Gordetsov A S Kozina A P Brevnova T N Semenov V V Skoveleva S E Boxer N A Dergunov Y Journal of Organometallic Chemistry 1987 327 303 309 Cooley J H Evain E J Journal of Organic Chemistry 1989 54 1048 1051 Wadsworth W S Emmons W D Journal of Organic Chemistry 1964 29 2816 2820 Palacios F Ochoa De Retana A M Martinez de Margorta E Rodriguez M Pagalday J Tet
164. rnik A Katchalski E Journal of the American Chemical Society 1966 88 3164 3165 Wolman Y Kivity S Frankel M Chemical Communications 1967 629 630 Weinshenker N M Shen C M Tetrahedron Letters 1972 13 3281 3284 Nieh M P Goodwin A Stewart J Novak B Hoagland D Macromolecules 1998 31 3151 3154 Schlitzer D Novak B Journal of the American Chemical Society 1998 120 2196 2197 Tian G Lu Y Novak B Journal of the American Chemical Society 2004 126 4082 4083 Kim J Novak B Macromolecules 2004 37 1660 1662 Kim J Novak B Macromolecules 2004 37 8286 8292 Tang H Boyle P Novak B Journal of the American Chemical Society 2005 127 2136 2142 Tang H Novak B He J Polavarapu P Communications 2005 44 7298 7301 Kennemur J Clark IV J B Tian G Novak B Macromolecules 2010 43 1896 1873 Larson R J PhD Dissertation University of Massachusetts Amherst 2000 41 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 Blackburn J L PhD Dissertation North Carolina State University 2004 Lu Y PhD Dissertation North Carolina State University 2005 Zhang Y PhD Dissertation North Carolina State University 2008 Li H PhD Dissertation North Carolina State University 2006 Robinson C Journal of Polymer Science Part A 1964 2 3901 3908 Szwarc M
165. roduct degradation 2 2 3 Alternative Strategies for Carbodiimide Synthesis Aside from the aforementioned strategies there are many others reported to effect the respective dehydration and desulfurization of 1 3 disubstituted ureas and thioureas For instance in addition to its use with bromine in the dehydration of ureas triphenylphosphine is reported to effect the desulfurization of thioureas in the presence of triethylamine and carbon tetrachloride Reactive chlorine compounds such as SOCl2 SO2Cl SCle or SeCle are also reported to convert thioureas into 48 carbodiimides Another curious desulfurization strategy invokes one carbodiimide to form another where dicyclohexylcarbodiimide DCC reacts with thiourea to equilibrate a new carbodiimide and N N dicyclohexylthiourea Figure 2 4 Cy t Bu S SN ue S A 80 85 C A t Bu A tBu Cc lt C Cys Uw yO yO N JAN Sey t Bu Figure 2 4 The reaction of N N di t butylthiourea with DCC leads to N N di t butyl carbodiimide and N N dicyclohexylthiourea Curiously the reaction of DCC with N N dimethylthiourea under the same conditions is reported to produce dimethyl cyanamide MezNCEN instead Of the alternative procedures for the dehydration of ureas perhaps the one most self touted is described in a Nutrasweet Patent claiming to produce in high yield no less a carbodiimide of such immaculateness that it may be used without fu
166. rther purification This patented Nutrasweet Method of carbodiimide synthesis calls for dehydrating the urea with p toluenesulfonyl chloride and pyridine in refluxing methylene chloride followed by two aqueous washes one with sodium bicarbonate the other with aqueous acid Subsequent removal of the methylene chloride is purported to afford the pure carbodiimide Multiple attempts by several investigators within the Novak Group to replicate the stellar success of this report have failed for a variety of 1 3 disubstituted ureas including a pair derived from L alanine methyl ester hydrochloride Another procedure for the dehydration of 1 3 disubstituted ureas utilizes reactive chlorine compounds Both phosgene COCls and phosphorus pentachloride PCls reportedly react with ureas having secondary or tertiary alkyl substituents to produce chloroformamidine hydrochlorides which upon treatment with triethylamine are said to generate carbodiimides One effort to employ the latter in our research led to a curious result While dehydrating a urea derived from L alanine methyl ester hydrochloride reacted with p tolylisocyanate not only did the phosphorus pentachloride facilitate dehydration it also chlorinated the benzylic position of the 4 methylphenyl substituent Figure 2 5 A search of literature on phosphorus pentachloride reactivity revealed a previous report of analogous chlorinations Though the product of this experime
167. rying overnight at pressures down to 50 mtorr revealed 11 6 g of grayish orange powder 69 yield The product was transferred to a large scale sublimation apparatus The apparatus was submerged in an oil bath heated 90 C while the cold finger was cooled with dry ice in isopropanol After 3 days at a pressure of 25 mtorr the sublimation apparatus was filled with nitrogen and transferred into a dry box The product was rinsed from the cold finger with anhydrous chloroform into a 25 mL Schlenk flask The Schlenk flask was sealed with a rubber septum and removed from the dry box A syringe attached to a Schlenk line hose opened to a positive pressure of nitrogen was inserted into the septum An oil flow indicator was attached via a rubber hose to the side arm of the Schlenk line which was then opened to monitor the flow of nitrogen while isolating the system from the atmosphere The product was dried to a paste via nitrogen purge The side arm of the Schlenk flask was attached to a Schlenk line having a positive pressure of nitrogen The rubber septum was replaced by a glass stopper lubricated with high vacuum silicon grease The product was dried under high vacuum to reveal 435 mg of richly dark orange powder 4 recovery 84 CpTiCl OCH2CFs In a No filled dry box CpTiCls 3 16 mmol 692 mg was weighed and transferred to a 50 mL Schlenk flask A magnetic stir bar was added The flask was sealed with a rubber septum removed from the dry bo
168. screen 191 Section 3 Glide Program Operations for Advanced 1D amp 2D Spectra Glide Program Setup Lock on the solvent and shim the magnet before entering the Glide Program Select Glide Select Setup e Select No for both Autolock and Autoshim e Right click on the W button beside Solvent and select the solvent from the pull down menu e Right click on the W button beside Experiment and select H1 and H1 detected Expt from the pull down menu for 2D experiments or H1 and selective 1D Expt for advanced 1D proton experiments Select Setup Select Acquire e For PROTON Spectral Width ppm select the minimum spectral width that will include all proton signals of the sample solvent and standard e Select No for Minimize SW e Select a setting for PROTON scans e Select a setting for PROTON Relaxation Delay sec e Select Default for PROTON Pulse Angle Select the desired experiment under Select Experiments in addition to PROTON to access the corresponding popup menu settings described in the following instructions Homonuclear Correlation Spectroscopic Techniques l COSY COrrelation SpectroscopY Select 4 to 8 for COSY scans per inc Select 128 for COSY number of inc The aforementioned settings are fine for gCOSY as well Select OK Select DO Upon completion of the run select AutoProcess To expand a given region select Box and then Left click and drag to set the lower a
169. se sharp signals indicating that rather than facilitating polymerization the copper Il chloride actually catalyzes the formation of small molecules such as dimers and trimers Heating Ill in the absence of copper II chloride actually leads to a cleaner polymerization This result correlates with the observation that heating in the absence of catalyst leads to a brittle translucent light brown solid while heating in the presence of CuCl instead produces a sticky black tar In the latter case the dimer and trimer contaminants heavily discolor the product and function as plasticizers 58 CDCI 4 Weeks 60 C Thermally Polymerized epee 10 9 8 7 6 5 4 3 2 1 ppm Figure 2 9 H NMR spectrum of the thermal polymerization product resulting from heating carbodiimide Ill at 60 C for 4 weeks in the absence of catalyst When compared with the spectrum of the polycarbodiimide formed under the same conditions in the presence of CuCls Figure 2 8 this spectrum has fewer and less intense sharp signals suggesting that thermal polymerization in the absence of CuCl proceeds more cleanly and that rather than facilitating polymerization CuCls actually catalyzes the formation of small molecules such as dimers and trimers 59 2 3 3 Thiolate Initiated Thermal Polymerizations Since the polymerization of carbodiimides with catalysts based on copper I and Il as well as those based on titanium I
170. sence of enolizable protons allows ester bearing carbodiimides of this earlier design to be polymerized with chiral BINOL titanium catalysts which polymerize achiral carbodiimides with higher regioselectivity than does copper I butanethiolate Four derivatives of this earlier ester bearing carbodiimide were made three of which were successfully polymerized in high molecular weight One of these 119 three presented a methyl ester substituent another a 2 2 2 trifluoroethyl ester substituent Neither of these prove capable of transesterification catalyzed by mercury Il acetate or potassium cyanide Experiments in which these polymers are heated under refluxing conditions exhibit significant decomposition overnight even in the absence of catalyst an unprecedented level of instability wnen compared with well studied polycarbodiimides bearing simple alkyl and aryl substituents The electron withdrawing effect of the 2 2 2 trifluoroethyl substituent exacerbates this instability Blending Kim s unstable ester bearing polycarbodiimide design with that of poly N benzyl N 4 n butylphenyl carbodiimide found to be highly stable under both acidic and basic conditions the instability of the resulting hybrid featuring a benzyl pendant group coupled with the ester bearing aromatic one indicates the original ester bearing design to be inherently unstable with respect to sonication or basic conditions though the auxiliary pendant group ca
171. sitive procedures which were purified under a nitrogen atmosphere via reflux over an appropriate drying agent followed by fractional distillation 4A molecular sieves were oven dried overnight at 215 C then cooled and stored in a desiccator The purity of commercially supplied reagents was factored into all calculations in the sections that follow 121 Inert Atmospheres All air and moisture sensitive procedures were either conducted in a nitrogen filled MBRAUN UNILab Dry Box or while utilizing Schlenk techniques facilitated by a Chemglass CG 4441 03 5 Port Glass Stopcock Inert Gas Vacuum Manifold coupled with a dual liquid nitrogen trap attached to a Welch Model Number 1402 01 Vacuum Pump Vacuum pressures were observed with a Kurt J Lesker Company Millitorr Vacuum Gauge Unopened volatile free vacuum line pressures exceeding 50 mtorr were corrected by routine typically weekly vacuum line maintenance which entailed Steps 12 through 16 of the more thorough Guide to Vacuum Manifold Maintenance procedure listed in Appendix 2 Glassware used for air and moisture sensitive procedures was dried overnight in an oven at 140 C Alternatively glassware was flame dried under vacuum lt 100 mtorr Stir bars utilized for air and moisture sensitive reactions were dried overnight either in an over at 140 C or under vacuum lt 100 mtorr Alternatively stir bars were retrieved from storage under nitrogen in the dry box
172. somers of such dimers Figure 2 11 the extracted ion chromatograph of the 409 m z ratio indicates a single dominant stereoisomer along with three stereoisomers present in trace Figure 2 12 An extracted ion chromatograph of the 613 m z ratio picks up seven trimeric stereoisomers two dominant four trace Figure 2 13 Though precise quantitative comparisons among the relative amounts of dimers and trimers cannot be made it is clear from the near invisibility of peaks corresponding to the 613 m z ratio on the total ion chromatograph relative to that corresponding to the dominant 409 m z peak that one dimeric stereoisomer is the vastly predominant product 66 y N hes N Ne 0 X Figure 2 11 Four of the many conceivable stereoisomers that may be formed from the dimerization of N phenyl N L alanine methyl ester carbodiimide Others could have one phenyl substituent in an imine position while the other occupies an amine position The pair at the top are referred to as E E isomers while the pair beneath are referred to as Z Z isomers Theoretical considerations are said to favor the formation of Z Z isomers 67 Plot Window Report EIC 409 0000 Scan 080296 d x10 2 ElC 409 0000 Scan 080296 d 1 09 409 m z Extracted lon Chromatograph EIC 0 8 0 7 0 6 0 5 0 4 0 3 0 2 0 1 as m nS 6 10 8 11 11 2114 11 6 118 12 12 2 12 4 126128 13 13 2 134 136 138 14 14 2 144 14 6 148 15 15 2 154 156
173. sponding with their re emergence upfield at approximately 6 5 ppm 36 1 9 Liquid Crystalline Properties of Polycarbodiimides The term liquid crystal is used to describe phases of matter in which the molecules exhibit oriented fluid motions which in many cases are confined within layers Liquid crystals are broadly divided into two categories those exhibiting liquid crystalline behavior due to solvent effects referred to as lyotropic and those acting as liquid crystals over a certain temperature range referred to as thermotropic Perhaps the most common liquid crystals are those created by amphiphilic molecules that self assemble into micelles hexagonal arrays and lamellar structures Other molecules that display liquid crystalline behavior typically have two elements in common flexible components imparting fluidity and rigid components referred to as mesogens bestowing orientation and layering effects Chirality may endow an additional level of molecular orientation N Nematic Cholestric Smetic A Smetic C Figure 1 20 Schematic representations of four prominent liquid crystalline phases A common feature shared by all liquid crystal phases is an orderly orientation of the molecules The distinguishing feature of phases that are nematic is a lack of positional order When the mesogens in a nematic phase are chiral they adopt a twisted orientation with respect to one another creating what is referred to as a chir
174. ssible between peaks Select Box or Cursor to exit the slope bias adjustment mode Integrating the Spectrum Not viable for routine C NMR spectra Left and right click respectively on each side of the first region of interest Select Expand to zoom in Select Resets to enter the integral reset mode Left click on the left and right side of each peak to cut the integration line Select Box or Cursor to exit the integral reset mode Select Full to zoom out Repeat this process for every region of peaks If you wish to re integrate a specific cut select Reset then right click on the previous cut mark to restore the uncut line and then left click to cut the integral anew To start over completely type cz and hit enter to restore the entire uncut integration line Referencing Integration Ratios Left click at the top of the integral you want to set as the reference Select Set Int Using the numbers at the top of the keyboard rather than the numeric keypad type in the reference value to two decimal places and hit enter Setting the Peak Threshold for Print or Display Select Th to enter the threshold adjustment mode Left click and hold on the horizontal threshold line and adjust upward or downward until only the peaks of interest break the threshold Select Th again to exit the threshold adjustment mode The command dpf will display the peak frequencies while ds will remove them 188 Printing the Spectr
175. st the pressure in the vacuum manifold to approximately 500 mtorr At this point the reaction flask was opened to vacuum The flask was shook vigorously to prevent the contents from bumping violently The toluene evaporated rapidly as the nitrogen leak was gradually closed in stages over a period of 20 minutes Following the point at which only a solid remained the flask 139 was removed from the ice water bath Once the pressure had dropped to 80 mtorr the flask was filled with nitrogen the glass stopper was temporarily removed under a positive outflow of nitrogen and a flame dried spatula was used to crush the dark orange product into a powder Vacuum was re applied Once the pressure reached 45 mtorr the flask was filled with nitrogen and returned to the dry box A test of the catalyst product with N N di n hexylcarbodiimide 100 1 formed polymer within minutes proving the batch to be active Poly N methyI N p t butoxy carbonylphenyl carbodiimide S 1 1 Binapth 2 2 ol titanium IV diisopropoxide 26 8 mg 59 5 umol and a magnetic stir bar were added to a 10 ml glass vial containing N methyl N t butyl p aminocarbonylphenyl carbodiimide 1 46 g 6 24 mmol in a nitrogen filled dry box The catalyst appeared to by sparingly soluble in the carbodiimide so after approximately 5 minutes anhydrous chloroform 0 75 mL was added Following solvation in chloroform the viscosity quickly increased Within 5 minutes th
176. suspected to be predominately tert butyl alcohol Both layers were poured into a clean 1000 mL separatory funnel Saturated sodium chloride 500 mL was added and the contents of the flask were shaken vigorously Allowed to stand for 30 minutes two layers appeared The bottom chloroform layer was slowly drained and then dried over sodium sulfate Note Upon standing overnight more chloroform separated from the salt water wash This chloroform layer was collected as well The chloroform solution was initially cloudy in appearance Upon standing overnight the substance responsible for the cloudy appearance had clumped together separating from the clear yellow solution to create a white cloud like suspension The solution was filtered through 18 5 cm diameter Q8 filter paper Because the white suspension clogs the filter paper three filters were needed to 124 complete the filtration process as each filter was discarded upon clogging to the point of restricting the flow to a slow drip Subsequent removal of the chloroform by rotovap revealed 12 9 g of yellow solid The solid powder was loaded onto a chloroform soaked column 95 g silica 60 200 particle size with chloroform 50 mL Chloroform was used as the developing solvent and the column was developed under a positive air pressure The first 185 mL preceding the discolored band were discarded The next 1000 mL were collected Removal of the chloroform by rotovap revealed 9 68 g of off w
177. t 60 C At this elevated temperature carbodiimides and Il became discolored in the presence of CuCl but again failed to polymerize However the reaction of carbodiimide III with CuCl gradually increased in viscosity over the course of one month after which cooling to room temperature produced a solid black tar The H NMR spectrum following workup indicates a polymeric structure as the major product evidenced by the predominance of broad versus sharp signals Figure 2 8 Following this discovery with carbodiimide Ill a pair of derivatives having either an electron donating methyl group IV or an electron withdrawing fluorine V on the para position were synthesized for polymerization testing When heated with CuCl carbodiimide IV polymerized at a rate that was not appreciably different from the rate at which Ill did This was not surprising given that the magnitude of electron donation and hence the electronic distinction between Ill and IV is mild However when carbodiimide V was heated to 60 C with CuCls the reaction proceeded much faster indicating that the strong electron withdrawing fluorine accelerates polymerization This result correlates with general observations from the field of carbodiimide chemistry that electron withdrawing groups on aromatic substituents reduce the stability of carbodiimides increasing their polymerization tendency as noted in Henri Ulrich s book on the Chemistry and Technology of Carbodiimid
178. t matriculated at North Carolina State University in 1994 completing a B S Degree in Chemistry in 1999 Over the next four years he worked as a chemist in a variety of industrial settings first as a GC MS Chemist for CompuChem in Cary NC then as a Quality Assurance Chemist at B O C Gases in RTP and finally as an Associate Scientist at Vector Research in Durham NC While working in industry he began taking graduate level chemistry classes part time In 2004 he matriculated as a full time graduate student at N C State University with the intention of merely earning a Master s Degree After developing an affinity for teaching and then research he decided to pursue a PhD instead The document that follows is the culmination of those efforts In his time in graduate school at N C State he made an effort to develop beyond the mere academic requirements for the doctorate by participating in a variety of leadership development opportunities Within the Chemistry Department he served as the Vice President of the Phi Lambda Upsilon He also served as the Departmental Representative in the University Graduate Student Association for two years Within the University Graduate Student Association he serves as the Chairman of the Social Committee for one year and as the Vice President of Internal Affairs for a year and a half Finally in his last two and a half years at N C State he served on the Student Conduct Board Upon graduation he will contin
179. ta of poly N N di n hexylcarbodiimides prepared with chiral initiators measured in chloroform at the sodium D line 598 nm Initiator Monomer Initiator al a la a I 84 1 1 2 1 9 2 4 3 0 II 98 1 0 0 1 2 3 6 5 2 II 41 1 0 3 0 8 3 6 6 8 H3 wTi i Ti ww TSS Ww we oid o l H wO vE H3C Ph I Il Figure 1 16 Titanium IV catalysts with chiral amide initiators shown in color utilized to polymerize N N di n hexylcarbodiimide for chiral end group studies 32 So as a means of utilizing a single chiral entity to impose a transcendent helical order to selectively synthesize one of two perfectly equivalent helices the chiral end group strategy falls short here in two respects First placing a chiral terminus on the chain means that the right and left handed helices are no longer perfectly equivalent Indeed it is the subtle energy difference between the two that is the source of preferential helical induction which leads to the second shortcoming the magnitude of the ordering even when manifest most sharply at reduced temperature is meager Limitations arise from the activation energy of the helical inversion process whose increasing inaccessibility at reduced temperatures inhibits expression of the inherent thermodynamic preference In essence the incompatible thermal energy requirements of preferential helical induction and the activation en
180. tate from water The pyridine solution was transferred by pipet into a flask containing deionized water 120 mL and methanol 30 mL The product initially precipitated as globular collections but developed into a fine powder upon stirring for several hours The product was collected on P8 filter paper and rinsed from the paper with four successive portions of acetone 50 mL each Removal of the acetone by rotovap followed by high vacuum revealed 1 60 g of yellow powder 84 yield Though the H NMR spectrum does exhibit some signal broadening splitting in the aromatic region indicates a predominance of relatively low molecular weights IR KBr Pellet 3063 vw 3035 vw 2993 vw 2951 w 2845 vw 1720 s 1635 s 1589 s 1275 s cm H NMR 300 MHz CDCls 8 ppm 7 93 d J 8 4 2H 6 86 d J 8 4 2H 3 88 s 2 94 s Poly N hexyl N p methoxycarbonylphenyl carbodiimide S 1 1 Binapth 2 2 ol titanium IV diisopropoxide 46 5 mg 103 umol and a magnetic stir bar were added to a 10 mL glass vial in a nitrogen filled dry box N hexyl N p methylcarbonylphenyl carbodiimide 94 3 01 g 10 9 mmol was dissolved in anhydrous chloroform 2 mL The chloroform solution was transferred by pipet to the vial containing the catalyst and stir bar Three chloroform rinses 1 mL were utilized to facilitate quantitative transfer 4 days later the chloroform solution was added to magnetically stirred methanol
181. ter substituents and the polymer backbone were fully hydrolyzed leading to a urea structure LC MS analysis confirmed the anticipated urea structure as the two most abundant m z values matched the structure of the protonated urea 209 and its sodium adduct 231 H NMR 300 MHz Acetone de amp ppm 8 10 s br 1H 7 48 d J 7 2 Hz 2H 7 22 m 2H 6 93 t J 8 0 Hz 1H 6 10 d br J 6 9 Hz 1H 4 42 m 1H 1 41 d J 7 2 3H 146 Transesterification of a Low Molecular Weight Polycarbodiimide Poly N methyl N L alanine methyl ester carbodiimide 50 mg synthesized with copper I butanethiolate 250 1 at 60 C was weighed in a 100 mL round bottom flask Chloroform 50 mL 2 methoxyethanol 20 mL and a magnetic stir bar were added to the flask A catalytic amount of mercury Il acetate 1 mg was added to the flask Approximately three grams of molecular sieves were suspended in the flask in an improvised holding devise designed to expose the reaction solution to the sieves while keeping them from contacting the magnetic stir bar See Appendix 3 for instructions on creating an improvised holding devise for molecular sieves The headspace of the sealed flask was purged with nitrogen for approximately two minutes Both the chloroform solvent and the residual alcohol were removed four days later by rotovap followed by high vacuum The replacement of the methyl ester proton set with the 2 methoxyethyl ester proton
182. terials characterized by broad signals mixed with a comparable quantity of low molecular weight materials characterized by sharp signals 54 Considering the lack of reactivity between these carbodiimides and copper Il chloride a reasonable question to ask is whether the activation energies of these polymerizations were simply inaccessible at room temperature Predicaments of this nature observed by previous investigators in the Novak Group have been successfully resolved on occasion by running polymerizations at an elevated temperature Andrew Goodwin synthesized a pair of 1 2 dicarbodiimides that polymerized in high yield with TiCl3 0 iPr when heated to 85 C but failed to react appreciably at room temperature Jeoghan Kim successfully polymerized N N bis 4 n butylphenyl carbodiimide at 45 C with a chiral titanium catalyst a reaction that also failed at room temperature Figure 2 7 ae OP ae i pr O Ti a Oo oO DNS i pr N CHCI 45 C Figure 2 7 The polymerization of N N bis 4 n butylphenyl carbodiimide fails at room temperature due to the heightened activation energy resulting from the steric hindrance of the bulky pendant groups and ligand respectively on the carbodiimide and catalyst Gentle heating provides sufficient energy to facilitate polymerization 55 Giving consideration to those precedents follow up experiments were conducted on carbodiimides I Il and III with copper Il chloride a
183. th The product solution was dried over magnesium sulfate Rotovaping the pyridine away revealed viscous oil mixed with gray mercury ll sulfide precipitate The oil was diluted in methylene chloride 5 mL and filtered into a 25 mL Schlenk flask 80 revealing a dark reddish brown solution The methylene chloride was removed by purging to relative dryness with nitrogen followed by application of high vacuum overnight to reveal 3 92 g of viscous orange oil 83 yield IR Neat 3071 w 2989 w 2955 m 2876 w 2133 vs 1745 s 1224 s cm H NMR 300 MHz CDCls 5 ppm 7 13 m 2H 6 96 m 2H 4 16 q J 6 9 1H 3 77 s 3H 1 54 d J 6 9 3H N 4 chloromethylphenyl N L alanine methyl ester carbodiimide Phosphorus pentachloride 95 2 78 g 12 7 mmol was dissolved in reagent grade pyridine 10 mL in a 50 mL round bottom flask N 4 methylphenyl N L alanine methyl ester urea 3 00 g 12 7 mmol dissolved in pyridine 15 mL was added to the flask After refluxing for 1 hour the pyridine was removed by rotovap followed by high vacuum overnight revealing a sticky black goop Chloroform 140 mL saturated sodium bicarbonate 100 mL and deionized water 100 mL were added to the goop The mixture was so black that a distinction between layers could only be discerned by turning off the lights and shining a flashlight through the separatory funnel from behind The aqueous layer appeared to have a more
184. the ejection air flow on again Place the sample tube holder with the standard back in the loading tube Type i and hit enter to return the standard to the NMR Check the display to make sure VT is off Switch back from nitrogen to air by performing the three steps illustrated on the previous page in reverse Special Note The recommended temperature sequence for a series of analyses spanning a range from below to above room temperature is from low to high Unless the nitrogen tank is nearly empty it is not necessary to switch back from nitrogen to air until you have completed the high temperature analyses as well 201 High Temperature Analysis Warning Carefully watch the temperature status reading while operating at high temperature Going 1 or 2 C above the target temperature is typical However if there is a malfunction such as the tank running out of nitrogen the temperature may continue increasing If the temperature goes 5 C above the target setting there is a problem and you must quickly take corrective action to protect the probe If the command temp n su fails to stop the temperature from increasing turn the heater off at the Temperature Control Unit pictured below Leave the switch in the off position and notify Dr Sankar of the malfunction MERCURY Open the cabinet Flip the switch to the off position and leave it there to turn the heater off manually Model L900 Temperature Controller Lock
185. ther purification and dried with magnesium sulfate IR and H NMR analyses of the fractions that followed revealed comparable quantities of the carbodiimide product and thiourea reactant so those were discarded Removal of the acetone from the second fraction revealed a yellow oily paste This fraction was dissolved in ethyl acetate 20 mL and loaded onto a column consisting of 2 cm sand and 35 0 g silica gel 60 200 Mesh Grade 62 134 The column was developed with ethyl acetate The first 75 mL fraction was discarded The next 50 mL fraction exhibited a strong yellow discoloration Removal of the ethyl acetate revealed a viscous yellow oil IR analysis revealed the asymmetric N C N stretch to be the dominant absorption on the spectrum H NMR revealed the sample to be predominantly carbodiimide The dominant contaminant signals where identified as H2O and HOD most likely from the un dried acetone d NMR solvent No exchangeable protons characteristic of the thiourea precursor were present The sample was placed under high vacuum down to 25 mtorr for 2 hours As the volatile ethyl acetate boiled away the carbodiimide began to solidify forming white specks within the viscous yellow oil The flask containing 1 90 g 53 yield IR Neat 3068 vw 3033 vw 2993 w 2951 m 2143 vs 1718 s 1277 s cm H NMR 300 MHz Acetone de 5 ppm 7 94 d J 8 6 Hz 2H 7 17 d J 8 6 Hz 2H 3 83 s 3H 3 25 s 3H N hex
186. thylamine 99 15 6 mL 111 mmol was added at a rate of approximately 1 mL every 5 minutes N N di n hexylurea 10 0 g 43 8 mmol was dissolved in methylene chloride 20 mL 30 minutes after the final addition of triethylamine the urea solution was added to the reaction mixture at an approximate rate of 5 mL every 5 minutes Following addition of the urea the reaction was allowed to proceed overnight The following morning the product mixture was washed with deionized water 50 mL The methylene chloride solution of the product was dried with a saturated sodium chloride wash 30 mL followed by standing over sodium sulfate for 5 minutes The product solution was decanted to a 250 mL round bottom flask and rotovaped to a volume of approximately 40 mL Pentanes 240 mL were added 82 to precipitate the triphenylphosphine oxide byproduct as a loose slurry The solution was filtered into a 500 mL round bottom flask with several rinses of pentanes totaling 80 mL to facilitate transfer The slurry was transferred to a Soxhlet Extractor thimble to which 100 mg calcium hydride was also added A reflux condenser was attached The setup was attached to a nitrogen line and the slurry was extracted via overnight reflux The following day the solvents were removed by rotovap Short path distillation utilizing a Buchi Glass Oven B 580 w a Buchi Drive Unit 30 mtorr 154 C isolated a clear colorless oil 6 64 g 72 yield IR Neat 2956 m 2
187. tine Change the decoupler off set by entering the tof number recorded earlier including the sign by utilizing the command format dof to enter the specific tof number you copied Omit the minus sign from this example format if the tof number was positive rather than negative Type dmm c and hit enter Type dpwr 20 and hit enter A decoupler power of up to 25 may be used Type zg and hit enter NOE Enhanced Proton Coupled Carbon 13 Spectroscopy Go through the normal C analysis setup routine and then use the command dm yyn to turn the decoupler off during the acquisition period Since proton coupled carbon signals will appear as multiplets achieving a signal to noise ratio equivalent to that of a qualitative decoupled C spectrum may take an analysis of up to 10 times longer 198 Manual Setup for gCOSY gradient COrrelation Spectroscopy Lock on the solvent and shim the magnet as usual Type nt 1 zg and hit enter to collect a single scan spectrum Adjust the sweep width and collect a single scan spectrum again Type gain y and hit enter Change the pulse width to 90 degrees Record the displayed value of sw tof and the other acquisition parameters Type gcosy and hit enter Check that np is approximately 1000 Set the desired values of d1 nt and ni Type dg and hit enter to update the parameter display with the new settings Utilize VT NMR commands to adjust the temperature if need be at this
188. tion from small molecules than when the polymer is formed upon heating in the absence of catalyst Figure 2 9 It seems that greater diversion of carbodiimide down byproduct pathways leading to dimers and trimers is an unavoidable cost of utilizing copper I butanethiolate to accelerate these heated polymerization reactions 63 2 4 The Dilemma of Dimers and Troublesome Trimers In our efforts to develop novel ester bearing polycarbodiimides we are faced with a dilemma On one hand heat alone facilitates relatively clean thermal polymerization But these uncatalyzed reactions take many weeks and afford no control of molecular weight On the other heating with copper I butanethiolate catalyzes polymerization within days and affords molecular weight control via carbodiimide to catalyst ratio However copper I lowers the activation energy of dimer and trimer formation more than it does for the rate limiting step of polymerization Lastly the prototype carbodiimide Ill proves unreactive with copper I butanethiolate at 25 C leading to our dilemma dimers and trimers are inevitable byproducts of the optimum conditions for the polymerization of such carbodiimides 2 4 1 Raising the Roof What s Going Down Above Tc For any reaction involving an equilibrium between monomer and polymer the free energy of the polymerization can be expresses by the equation AGp AHp TAS 3 1 where AGp AHp and AS are the respective differences
189. tion PFOCESS ccceeeeeeeeeeeeeetteeeeeeeeeeeeees 99 Expanded view of the region of interest on the H NMR spectra of a relatively light fraction of poly lll before and after transesterification with 2 methoxyethanol catalyzed by mercury Il acetate The notable absence of a signal for the hydroxyl proton of the free alcohol highlighted in red from the spectrum of the transesterified polymer indicates that the additional proton signals are from newly placed 2 methoxyethyl substituents on the pendant group The relative broadness of the aforementioned signals is also consistent with polymer attachment a i ccc A scees fare dees ated da oi eed Nea adele Mate enes 100 Outline of the multi step synthetic route to the ester bearing polycarbodiimide first developed by Jeonghan Kim The initial step xviii Figure 3 6 Figure 3 7 synthesis of t butyl p aminobenzoate was first reported by Taylor Fletcher and Sabb The original polymer synthesized by Kim was made with an achiral titanium catalyst CpTiClo2N CHs 2 rather than the chiral S Binol titanium catalyst utilized for the follow up studied of this H NMR spectra of poly VI before and after sonicating in a simple 4 1 mixture of acetone and deionized water for 1 week The replacement of broad proton signals with sharp signals indicates decomposition of the polymer into smaller molecules In contrast to poly VI s instability poly N benzyl N 4 n butylphenyl carbodiimi
190. tions with a given chiral entity 19 While all three of the aforementioned levels of cooperativity rely on chiral entities that are covalently attached to the polymer structure molecular chaperoning involves non covalent interactions between small chiral molecules and the polymer These may range from subtle van der Waals forces to strong hydrogen bonding or ionic pairing interactions By generating a preferred diastereomeric complex molecular chaperons induce a preferred helical conformation on the host polymer Finally the pinnacle of cooperativity is the induction of a single handed helix by a single chiral entity There are two common manifestations of this phenomenon In one a chiral end group exerts a conformational influence from the terminus of the chain In the other a chiral catalyst exercises its influence on the propagating chain end during polymerization leaving a single handed helix in its wake Unlike the covalently attached chiral end group which has a persistent effect on the polymer following work up single handed helical polymers made with a chiral catalyst can be thought of as inheriting their conformation as the original chiral perturbant is removed when the chain is terminated 1 7 1 The Kinetics and Thermodynamics of Homochiral Polycarbodiimide Helicity Any effort to fathom the means by which a polycarbodiimide cooperates with a pendant chiral entity must begin with an appreciation of the two distinct manners in
191. to influence helicity in a cooperative fashion Majority Rules probes a slightly higher level of cooperativity due to the fact that in spite of its competing helical preference repeat units having the less prevalent pendant enantiomer defer with respect to conformation to repeat units influenced by the excess pendant enantiomer to adopt a predominant handedness 17 Chiral Catalyst or Endgroup Molecular Chaperones Cooperativity Sergeant Soldiers Homochiral Polymer RRRRRRRR WU ee Ait R Right R Left Figure 1 11 Pyramid of Cooperativity The hierarchy of the pyramid illustrates the lengths to which a given polymer system cooperates with the predominant chiral entity by adopting a preferred helical sense The pinnacle of cooperativity is the induction of a single handed helix by a single chiral entity either by a chiral catalyst exercising its influence on the active site during polymerization or through perturbation from a chiral endgroup at the chain s terminus 18 S R au aH y ttet S Right R Left z 5 5 2 D 2 2 S t A a R S URR Enantiomers p drr R Right S Left gt Figure 1 12 The schematic on top depicts the stereoisomeric relationships among right and left handed helices of polymers bearing chiral pendant groups The schematic beneath illustrates the energy difference between the diastereomeric interactions of the right and left handed helical conforma
192. ude polymer IR KBr Pellet 3055 vw 2958 m 2931 m 2860 w 1736 s 1633 s 1589 s 1252 s 1169 s 1113 s cm H NMR 300 MHz CDCls 5 ppm 7 93 6 85 4 66 3 88 3 73 3 51 3 45 3 17 2 62 1 59 1 04 0 74 all broad 164 8 C Decomposition Temperature 5 Loss of Mass Specific Optical Rotation measured 12 5 0 8 144 Poly N benzyI N 4 n butylphenyl carbodiimide Courteously supplied by Joe Desousa Poly N hexyl N phenylcarbodiimide made with Chiral Titanium Catalyst Courteously supplied by Januka Budhathoki Uprety Poly N hexyl N phenylcarbodiimide made with Copper Catalyst Copper I butanethiolate 15 2 mg 98 9 umol was transferred to a Schlenk flask N hexyl N phenylcarbodiimide 1 00 g 4 94 mmol courteously supplied by Januka Budhathoki Uprety and a stir bar were added to the flask The flask was sealed removed from the dry box and attached to a nitrogen line The reaction was run under a positive pressure of nitrogen while submerged in an oil bath heated to 60 C The reaction mixture became viscous within two days solid within five On day six the reaction was removed from heat Three days later a vortex mixer and a heat gun were employed to facilitate dissolving the polymer in three successive portions of toluene 5 mL each The polymer was then precipitated from toluene solution in magnetically stirred methanol 90 mL When an attempt to collect the polymer by filtr
193. ue his love of learning through the pursuit of a Pharm D at the University of Wisconsin School of Pharmacy ACKNOWLEDGEMENTS First I d like to thank Jan Singhass who employed her glassblowing skills to turn the vacuum manifold had initially abused into the high vacuum system on which relied so heavily in my research would like to thank her for her kindness and for teaching me the essentials of vacuum manifold maintenance Pld like to thank Dr S Sankar who trained me extensively on the NMR and mentored me in the writing of our department s first Varian NMR User s Manual I d like to thank former Novak Group members Keitaro Seto and Hyun Su Lee for taking the time to mentor me on laboratory techniques I d like to thank Justin Kennemur for collaborating with me on our his first publication I d like to thank Januka Budhathoki Uprety for the positive attitude she has brought to the group ld also like to thank other members of the Novak Group past and present who each in their own unique way have taught me invaluable lessons about the importance of courtesy when sharing a work environment of professionalism in attitude and behavior and of considering how what we say of others effects their reputation as well as our own I d like to thank my teaching mentors Dr Sandberg Dr Brown Dr Gallardo Williams and Dr Warren who have each taught me valuable lessons on the instruction of chemistry students ld like to thank my acade
194. um There are a variety of print commands that can be utilized to customize the information printed with a spectrum The two essential commands are pl the command to plot the spectrum and integrals if shown and page which sends preceding plot commands to the printer Other commands that can be used in conjunction with these are pscale which plots the frequency scale ppf which plots the frequency of peaks that break the threshold setting pir which plots the integration data and ppa which plots a partial list of the experiment parameters or pap which plots a complete list of experiment parameters There is one other command that must be entered prior to the pir command In order to make room below the spectrum for integration data the vertical position of the plot must be adjusted 12 mm higher with the command vp 12 A typical print command might read vp 12 pl pscale pir ppf ppa page to print the frequency scale integration data peak frequency data and key experimental parameters with the spectrum Creating a Personal Data Storage Directory Select Main Menu Select Data Use the command format mkdir JBClark to create a personal directory Saving a Spectrum Select Main Menu Select Data Left click on the desired directory to highlight it and select Set Directory Type svf xyz and hit enter to save the file as xyz in the current directory To return to the default home directory type c
195. ve behind the following efforts to develop novel ester bearing polycarbodiimides 2 2 1 Standard Dehydration of 1 3 Disubstituted Ureas The class of precursors most commonly utilized in the Novak Group for the synthesis of carbodiimides is 1 3 disubstituted ureas These precursors are synthesized typically in quantitative yields via reaction of amines with isocyanates Dehydration of a 1 3 disubstituted urea produces the carbodiimide 45 While several alternative routes have been reported the one that has become our standard utilizes triphenylphosphine dibromide in the presence of triethylamine In an effort to access the rich world of peptide chemistry with the polycarbodiimide architecture efforts to develop novel ester bearing carbodiimides began with the methyl ester substituted derivative of the simplest chiral amino acid alanine By reacting L alanine methyl ester hydrochloride with various isocyanates and dehydrating the resulting 1 3 disubstituted ureas several methyl ester bearing carbodiimides were synthesized for polymerization testing Figure 2 2 The noteworthy feature shared by these carbodiimides is the presence of an enolizable proton The synthesis of high molecular weight polymers from carbodiimides having enolizable protons proved to be a challenging synthetic endeavor a Be OSs i m IE y 4 rt Il l ge PS o o Pa oe a TS ae o SSN Oo N Il IV CH Figure 2 2 Illustration of four methyl ester
196. ve a good quality basic C spectrum of the sample If one is already on file begin by locking and shimming as always Next set up for a basic C analysis and then type the command apt and hit enter Now type dg and hit enter to display the group parameters Check that the parameter d2 is set to 0 007 If not type d2 0 007 and hit enter Set nt to half the number needed to collect a basic C spectrum of desirable quality Type zg and hit enter Save the APT spectrum following acquisition To phase the APT spectrum begin by loading and phasing the basic C spectrum Upon subsequent re loading the APT spectrum should be properly phased If not manually adjust the phasing of the APT spectrum until all portions of the solvent peak are up In the resulting spectrum the signal of carbons attached to one or three protons will be down while the signal of carbons attached to no protons or two protons will be up single Frequency Decoupled Carbon 13 Spectroscopy Run a quick H NMR analysis of the sample Expand the region of interest and place the cursor on the center of the peak to be selectively decoupled The command nl can be used to center the cursor on the nearest signal line Type movetof and hit enter tof stands for transmitter off set Write down the tof number from the parameter list The sign of the number positive or negative is a critical detail Now go through the normal C NMR analysis setup rou
197. wed to reboot the computer Low Temperature Analysis Do not assume nitrogen will be available at all times Plan ahead Consult with Dr Sankar several days in advance if you intend to run low temperature analyses Lock and shim at room temperature A lock level setting of 70 to 80 is optimum Select Setup Make the appropriate Nucleus Solvent selections Switch from air to nitrogen by following the three steps illustrated below Step 2 Close the air line leading to the coil a E Step 3 Open the N line Step 1 Open the No tank leading to the coil valve leading to the regulator 200 Type temp 20 su and hit enter to flush the coil with nitrogen This simply opens the valve Because the coil is not yet submerged in liquid nitrogen the temperature will not change Flush for a minimum of 20 minutes longer on a humid day The system must be purged with nitrogen to flush moisture from the line before beginning a low temperature experiment Otherwise ice may plug the coil inhibiting the flow of nitrogen leading to temperature fluctuations Add liquid nitrogen to the dewar For lengthy analyses at 30 to 40 C add enough liquid to immerse half the coil For lengthy analyses at 50 to 80 C add enough liquid to fully immerse the coil Failure to properly immerse the coil may result in uncontrollable temperature variability Once the temperature settles at 20 C re optimize the lock level by ad
198. well for Clean the ball and removing Apiezon brand hydrocarbon greases 167 Step 18 Apply a fresh coat of hydrocarbon grease to each joint after removing the old grease Apiezon grease is recommended for stationary connections such as ball and socket joints Step 19 Remove the cold traps and clean off the old grease from the contact surfaces DO NOT use force when attempting to remove the trap from the manifold If the trap is frozen or otherwise stuck twisting with excessive force will break the trap or worse still the manifold If this joint was previously sealed with hydrocarbon grease warming with the heat gun will soften the grease allowing the trap to be removed with minimum shearing force If previously sealed with silicon grease good luck 168 Step 20 Apiezon grease is especially recommended for the manifold trap connection Both silicon and hydrocarbon greases harden over time as the volatile components off gas under vacuum The difference is that the remaining heavy fraction of hydrocarbon grease can be softened with heat while the nonvolatile components of silicon based grease cannot Having an especially large contact surface trap joints are particularly susceptible to becoming stuck when sealed with silicon grease Apply hydrocarbon grease instead Step 21 Cleaning and applying a fresh coat of grease to the manifold tube connection require removing the tubing
199. wer temperature while mixing with a radical scavenger 2 6 di t butyl 4 methylphenol BHT extended the range of thermal stability These results suggest a radical chain scission mechanism Figure 1 7 through which homolytic bond cleavages on the backbone yield imidoyl and amidinate radicals that propagate along the chain unzipping the carbodiimide units Such chain scissions are not necessarily random which is why the thermal stability of polycarbodiimides made from a racemic mixture of monomer is significantly less than that of their homochiral analogues The heightened steric repulsions between adjacent pendant groups of opposite handedness create weak points between such repeats along the backbone This explains why the onset of thermal decomposition for poly rac N methyl N a methylbenzyl carbodiimide is 30 C lower than that of poly R N methyl N a methylbenzyl carbodiimide 10 R R R R R R X N N N N N N AALALA eo N N N N N N R R R R R R Heat ge ye ye Pi ZR Pi Lio hA A ad co aa R R R R R R Rn Figure 1 7 Thermally induced free radical depolymerization mechanism Efforts to improve the thermal stability of polycarbodiimides via structural modification have thus far proven impotent Semiladder architectures incorporating cyclic ring systems along the backbone often enhance the thermal stability of polymer structures relative to linear analogues Fo
200. x attached to a nitrogen line and placed under a positive pressure of nitrogen Dry triethylamine 3 16 mmol 0 440 mL was added via syringe 2 2 2 trifluoroethanol 3 16 mmol 230 uL was added via syringe 2 hours later the product solution was transferred to another 50 mL Schlenk flask with the use of a filter paper covered vacuum needle assembly to separate the soluble product from the insoluble triethylammonium chloride precipitate See Appendix 1 for filter paper covered vacuum needle assembly instructions The solvent was removed via a purge of nitrogen followed by high vacuum lt 50 mtorr revealing 510 mg of a yellow solid 57 yield 124 mg of pure yellow crystals were isolated via sublimation at 80 C and 10 mtorr 24 recovery TiClsOCH2CF3 This catalyst was synthesized via significant modification of two literature procedures Titanium tetrachloride 29 1 mmol 3 20 mL and methylene chloride 10 mL were added via syringe to a nitrogen filled 25 mL Schlenk flask containing a stir bar and fitted with a reflux condenser The flask was placed in an ice water bath set to mix with magnetic stirring and 2 2 2 trifluoroethoxide 24 7 mmol 1 80 mL was added via syringe Nitrogen gas was bubbled through the reaction mixture to facilitate removal of the hydrogen chloride byproduct To avoid concentrating the reaction solution the purge nitrogen was pre saturated by bubbling it through an anhydrous methylene chlori
201. yl N p methoxycarbonylphenyl carbodiimide Dibromotriphenylphosphorane salt 98 6 89 g 16 0 mmol a 25 excess was dissolved in methylene chloride 20 mL in a 100 mL round bottom flask A magnetic stir bar was added and the flask was placed in an ice water bath Triethylamine 99 4 8 mL 3 45 g 34 1 mmol a 30 excess was added to the reaction at a rate of approximately 1 mL every 5 minutes N hexyl N p methoxycarbonylphenyl urea 3 56 g 12 8 mmol was dissolved in methylene chloride 30 mL 1 hour after the last addition of triethylamine the urea solution was added to the reaction at a rate of approximately 5 mL every 5 minutes The next day the product was washed with 135 deionized water 50 mL followed by saturated sodium chloride 50 mL The methylene chloride extract was dried by standing over sodium sulfate for 15 minutes The methylene chloride was removed by rotovap The carbodiimide was extracted from the remaining solids with pentanes 50 mL The solid triphenylphosphine oxide precipitate was rinsed with several portions of pentanes 5 mL each to facilitate quantitative carbodiimide extraction The pentane extract was dried over magnesium sulfate Removal of the pentanes by rotovap followed by high vacuum revealed 3 01 g of yellow oil Relative integration ratios of the H NMR spectrum indicates a 94 purity of the carbodiimide 85 yield with 6 triphenylphosphine oxide contaminate IR Neat 3053 vw 301

ABSTRACT CLARK IV, JOE BOAZ. The Synthesis and

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