Zwitterionic Ring-Opening Polymerization of N-Substituted Eight

Letter pubs.acs.org/macroletters

Zwitterionic Ring-Opening Polymerization of N‑Substituted EightMembered Cyclic Carbonates to Generate Cyclic Poly(carbonate)s Young A. Chang, Andrey E. Rudenko, and Robert M. Waymouth* Department of Chemistry, Stanford University, Stanford, California 94305-5080, United States S Supporting Information *

ABSTRACT: The zwitterionic ring-opening polymerization of N-functionalized eight-membered cyclic carbonates with Nheterocyclic carbenes (NHC) in the absence of alcohol initiators generates cyclic polycarbonates of Mn ∼ 30−100 kDa. The polymerization behavior of these eight-membered cyclic azacarbonates depends sensitively on the nature of the nitrogen substituent. The N-benzyl-substituted eight-membered cyclic carbonate (8CCBn) polymerizes readily with 1,3-diisopropyl-4,5dimethylimidazol-2-ylidene to generate cyclic polycarbonates with molecular weights of Mn = 14 000 to 96 000 Da. In contrast, the N-phenyl-substituted cyclic carbonate (8CCPh) catalytically dimerizes in the presence of the NHC to afford the crystalline cyclic dimer. The zwitterionic ring-opening copolymerization of δ-valerolactone (VL) and the cyclic carbonates afford gradient cyclic copolymers. The cyclic topology of both the homopolymers and copolymers was supported by MALDI-TOF MS and intrinsic viscosity measurements. 13C NMR and differential scanning calorimetry of the cyclic copolymers are indicative of a gradient sequence distribution as a consequence of the more rapid enchainment of the cyclic carbonates relative to valerolactone.

C

was recently reported.35 Aliphatic poly(carbonate)s are attractive targets due to their biocompatibility and biodegradability,36,37 as well as the relative ease in which functional groups can be incorporated into the monomers and resultant polymers.37−39 Herein we report that the zwitterionic ringopening polymerization strategy25 provides an expedient synthesis of amine-containing cyclic poly(carbonate)s from N-substituted eight-membered cyclic carbonates. The polymerization of N-substituted eight-membered cyclic carbonates (8CC)s was carried out in the absence of alcohol initiator using 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene (NHC-1) as the catalyst in THF at room temperature (Scheme 1). The N-benzyl-substituted cyclic carbonate 8CCBn readily homopolymerizes under these conditions to yield N-benzyl poly(carbonate) with molecular weights up to Mn = 96 000 Da and polydispersities of ∼1.5−1.9 (Table 1). The polymerization was found to be slightly faster in toluene while yielding lower molecular weights and polydispersities. Initial attempts to purify the polymer via dialysis in methanol resulted in degradation of the polymer, as well as evidence of methanol adducts by MALDI-TOF MS. The presence of a basic tertiary nitrogen in the backbone of the polymer likely facilitates methanolysis of the polymer. Precipitation of the

yclic polymers are an intriguing class of macromolecules as both the topology and the lack of chain ends lead to different behavior from conventional linear polymers.1−4 Experimental and theoretical studies have shown that the conformations,5,6 entanglement and reptation behavior,3,7 rheology,4,8 and crystallization behavior9−12 of cyclic polymers differ from those of chemically identical linear polymers. The entropic penalties associated with coupling the chain ends of high molecular weight chains3,13−17 have led to creative chainexpansion strategies for the synthesis of cyclic polymers.14−16,18−21 Zwitterionic ring-opening polymerization (ZROP) with N-heterocyclic carbenes (NHCs) and related nucleophiles22,23 is an effective method of producing cyclic polymers from lactones,24−28 carbosiloxanes,29 and cyclic phosphates.30 Herein we report an extension of this method for the synthesis of functionalized cyclic poly(carbonate)s of eight-membered cyclic carbonates derived from diethanolamines. Although cyclic oligomers31 and polymers32,33 of carbonates have been made by step-growth methods, the chain-growth zwitterionic ring-opening polymerizations of diethanolamine carbonates provide an expedient route to a novel class of functionalized34 cyclic polymers derived from carbonates. The ring-opening polymerization of N-substituted eightmembered cyclic carbonates in the presence of alcohol initiators with organic catalysts derived from triazabicyclodecene (TBD) or 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU) © XXXX American Chemical Society

Received: August 1, 2016 Accepted: September 22, 2016

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DOI: 10.1021/acsmacrolett.6b00591 ACS Macro Lett. 2016, 5, 1162−1166

Letter

ACS Macro Letters Scheme 1. Zwitterionic Ring-Opening Polymerization of Eight-Membered Cyclic Carbonate Monomers with NHC-1

Table 1. NHC-1-Catalyzed Zwitterionic Ring-Opening Polymerization of 8CCBn entry

solvent

time (min)

% conv.

Mnb

Mwb

Đb

1 2 3 4 5 6 7 8 9

THF THF THF THF THF THF toluene toluene toluene

3 6 10 20 40 60 10 20 45

16.9 46.7 61.3 73.5 79.5 94.0 76.5 89.1 97.0

14100 25500 38300 55200 83200 96100 42100 48200 69700

23100 39600 61800 106000 150000 176000 72300 82800 117000

1.64 1.56 1.61 1.92 1.80 1.83 1.72 1.72 1.68

Mwc

169600

147600

a

Conditions: [M] = 0.5 M, [NHC-1] = 0.01 M in solvent at room temperature and quenched by addition of solid 4-nitrophenol. bDetermined by SEC with polystyrene calibration. cDetermined by SEC-MALS.

Figure 1. MALDI-TOF MS spectrum of low-molecular-weight 8CCBn cyclic poly(carbonate). Masses correspond to (DP8CCBn*221.25 Da) + 23 Da (Na+)/1 Da (H+).

of low mass samples confirming the absence of any end groups (Figure 1). The zwitterionic ring-opening polymerization behavior of the eight-membered carbonates is sensitive to both the nature of the NHC and the substituent on the nitrogen. Attempts to polymerize 8CCBn with the more sterically hindered NHC 1,3-

polymer in aprotic solvents such as diethyl ether or pentane yielded the intact polymer without any evidence of alcoholysis. The polymer topology was shown to be cyclic by two methods: (1) intrinsic viscosity comparison of the sample against a linear poly(8CCBn) prepared independently using BnOH as the initiator (see Supporting Information), and (2) MALDI-TOF 1163

DOI: 10.1021/acsmacrolett.6b00591 ACS Macro Lett. 2016, 5, 1162−1166

Letter

ACS Macro Letters di-tert-butylimidazol-2-ylidene or less reactive aryl-substituted NHCs 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) or 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (DIPP) were unsuccessful. These observations are consistent with prior studies which demonstrate that zwitterionic ring-opening polymerization requires the appropriate matching between the reactivity of the NHC and the nature of the monomer.25 The zwitterionic ring-opening polymerization of the N-butyland N-tBu-substituted diethanolamine carbonates was unsuccessful; these monomers did not polymerize either in solution or in neat monomer in the presence of NHC-1. Similarly, the zwitterionic ring-opening polymerization of the N-butyl- or N-tBu-substituted 8CC’s with the more reactive 1,3,4,5-tetramethylimidazol-2-ylidene (NHC-2) failed to yield polymer. Attempts to copolymerize these monomers with δvalerolactone (VL) in the presence of NHC-1 only yielded homopoly(δ-valerolactone), suggesting that the N-butyl- and N-tBu-substituted diethanolamine carbonates are unreactive under conditions where lactones are readily polymerized. To assess this in more detail, we investigated the polymerization of the N-butyl-substituted diethanolamine carbonate with a benzyl alcohol initiator in the presence of the highly active guanidine catalyst triazabicyclodecene (TBD),40,41 but only starting material was recovered (see SI). The reticence of the Nbutyl- and N-tBu-substituted monomers to polymerize is not yet well understood but may be related to the pyramidalization at the nitrogen center,35 as was observed for related lactones.41 While a previous report had indicated that the eight-membered N-benzyl carbonates polymerize much more slowly than the Naryl or N-acyl carbonates,35 our results would suggest that the N-alkyl-substituted carbonates are considerably less reactive than even the N-benzyl-substituted eight-membered cyclic azacarbonates. Further studies are underway to investigate this behavior more fully. The polymerization behavior of the N-phenyl-substituted carbonate 8CCPh provides further insights on the features of these zwitterionic polymerization reactions. Treatment of 8CCPh with NHC-1 in THF or toluene led to the immediate precipitation of an insoluble product. 1H NMR analysis of this product was consistent with the formation of low molecular weight oligomers, although characterization was difficult due to the limited solubility of this product in solvents such as acetone, THF, DCM, DMSO, MeOH, and water. Crystallization of this insoluble product was carried out by mixing a stoichiometric ratio of NHC to 8CCPh and allowing it to crystallize over several days in toluene. X-ray crystallography of the needle-like crystals revealed the cyclic dimer of 8CCPh (Figure 2), which crystallizes as a slightly puckered 16-membered ring. The distance between the two carbonyl centers and the two nitrogens on the opposite sides of the ring is 3.72 and 6.78 Å, respectively. The nitrogen center is nearly planar, with a C1−N1−C5 bond angle of 115.97° and C1−N5−C6 bond angle of 121.01°. The phenyl ring is slightly twisted from the C1−N1−C6 nitrogen plane at an angle of 21.21°. DFT calculations (Gaussian 09, M06-2X DFT hybrid functional, 6-311+G(d,p) basis set with the CPCM solvent model in THF) indicated that the catalytic dimerization of these eight-membered cyclic carbonates is thermodynamically favorable with a calculated ΔH°dimerization of −23.5 kcal/mol for 8CCPh, −20.3 kcal/mol for 8CCBn, and −17.2 kcal/mol for 8CCBu. These calculations indicate that catalytic dimerization is thermodynamically favorable for all three eight-membered

Figure 2. X-ray crystal structure of the 8CCPh dimer. Thermal ellipsoids are set to 50% probability. Selected bond lengths (Å) and angles (deg): N1−C6 1.394, N1−C1 1.459, N1−C5 1.461, C3−O1 1.338, C3−O2 1.200, C3−O3 1.345, C1−N1−C5 115.97, C1−N1− C6 121.01, O1−C3−O3 107.79, and O1−C3−O2 126.49.

carbonates; thus the selective dimerization of 8CCPh is likely kinetically controlled. We propose that the selective cyclization of the phenyl-substituted carbonate 8CCPh is kinetically favored for conformational reasons. As revealed in the crystal structure of the 8CCPh dimer (Figure 2) the conformational restrictions imposed by the planar N-aryl nitrogen lead to favorable conformation for cyclodimerization. Our hypothesis is that once two monomers of 8CCPh are enchained in the zwitterion, cyclization for the N-phenyl-substituted, it is facile (Scheme 1, kc2 fast), leading to selective dimerization (and subsequent precipitation). In contrast, for the N-benzyl monomer 8CCBn, the more pyramidal N−R nitrogen35 would not likely have the same favorable conformation for cyclodimerization. As an indirect test of this hypothesis, we investigated the copolymerization of 8CCPh with δ-valerolactone (VL), reasoning that zwitterions containing one 8CCPh monomer unit and a valorolactone monomer should not exhibit a favorable conformation for dimerization and thus be likely to add additional monomers, leading to higher molecular weight polymers. This prediction was born out as the copolymerization of 8CCPh and VL proceeds rapidly in THF at room temperature using NHC-1 catalyst to yield copolymers with a range of compositions and molecular weights ranging from Mn = 30−50 kDa and Đ = 1.7−1.9 (Table 2). Unlike the 8CCBn homopolymer, the basicity of the N-phenyl nitrogen did not cause issues during workup, and these copolymers could be precipitated into MeOH without any signs of molecular weight degradation. Intrinsic viscosity measurements against an independently prepared linear copolymer of the same composition and MALDI-TOF MS (see Supporting Information) of low molecular weight samples show that the topology of the copolymer is cyclic. Attempts to follow the monomer consumption by 1H NMR for 1:1 mixtures of VL:8CCPh were compromised by the competitive formation of precipitates when the reaction aliquots were diluted for NMR. This is presumably due to the competitive formation of dimers at low conversion, where [8CCPh] is still relatively high. When the monomer ratio was adjusted to 2:1 VL:8CCPh, the aliquots were found to be fully soluble in CDCl3. Analyses of these samples showed that 8CCPh is consumed more rapidly than VL, where 90% of 8CCPh was consumed in the initial 60s of polymerization (Figure 3a). 13C NMR analysis of the methylene carbon next to the ester/carbonate center showed a greater relative fraction of homodyad sequences (VL−VL and 8CCPh−8CCPh) over the 1164

DOI: 10.1021/acsmacrolett.6b00591 ACS Macro Lett. 2016, 5, 1162−1166

Letter

ACS Macro Letters Table 2. Copolymerization of 8CCPh and δ-Valerolactone with NHC-1 Catalyst

a b

entry

ratio VL:8CCPh

% conv. (VL/8CCPh)

1 2 3 4 5

10:1 5:1 2:1 1:1 1:2

95/99 93/99 82/99 66/99 56/99

composition (VL:8CCPh) 90:10 82:18 65:35 40:60 29:71

(9.00) (4.56) (1.86) (0.67) (0.40)

Mnb

Mwb

Đb

Mwc

38000 49600 41700 36900 32900

83900 91400 83000 65300 79100

2.21 1.84 1.99 1.77 2.00

51000 77400 88900 59900 63100

Conditions: [M]total = 0.75 M and [NHC-1] = 0.015 M in THF at room temperature and quenched by addition of solid 4-nitrophenol after 15 min. Determined by SEC with polystyrene calibration. cDetermined by SEC-MALS.

Figure 3. Conversion vs time and molecular weight evolution plots for the copolymerization of VL and (a) 8CCPh and (b) 8CCBn. [8CCPh] = [8CCBn] = 0.25 M, [VL] = 0.50 M, [NHC-1] = 0.015 M.

heterodyad sequences (VL−8CCPh and 8CCPh−VL), which suggests either a block or a gradient copolymer.26 The formation of extended 8CCPh homopolymer sequences in the copolymers indicates that the enchainment of two 8CCPh occurs readily during propagation and implies that the dimerization of 8CCPh is primarily associated with the formation of a zwitterion comprised of two 8CCPh monomers in the initiation step. The copolymerization of the benzyl-substituted monomer 8CCBn with VL exhibited slighly different copolymerization behavior than those with 8CCPh. When these two monomers were copolymerized with NHC-1 in a 2:1 ratio, the incorporation of 8CCBn was much slower than that of VL (Figure 3b). 13C NMR analysis of the resulting copolymer revealed a higher fraction of homodyad sequences relative to the heterodyad sequences, indicative of a gradient or block copolymer.26 Analysis of the 8CCBn/VL copolymers by intrinsic viscosity measurements (relative to linear samples) and MALDI-TOF MS (see Supporting Information) is consistent with a cyclic topology for the 8CC Bn /VL copolymers. Differential scanning calorimetry of the 10:1 and 5:1 VL:8CCPh copolymers exhibited melting points that are lower (Tm = 48.9 and 40.7 °C, respectively) than that of the VL homopolymer (Tm = 57 °C) (see Supporting Information). The 1:1 and 1:2 VL:8CCPh copolymer, on the other hand, did not show distinct melting point transitions, indicating that at

higher compositions of 8CCPh, relative to VL, VL homopolymer sequences do not crystallize readily from the melt. Glass transition temperatures of −2.0 and 14.0 °C were observed for the 1:1 and 1:2 VL:8CCPh copolymers, respectively, which is significantly lower than the value of Tg ∼ 31 °C for the linear 8CCPh homopolymer reported by Hedrick et al.35 In summary, we have demonstrated the synthesis of cyclic poly(carbonate)s utilizing ZROP. Using NHC catalysts, Nbenzyl-substituted cyclic poly(carbonate)s of Mn ∼ 100 kDa can be obtained. In addition, copolymers of p(VL)p(carbonate)s can also be synthesized using both the Nphenyl- and N-benzyl-substituted cyclic carbonate as the comonomer. The polymerization rate was found to be much faster for the N-phenyl cyclic carbonate and slower for the Nbenzyl cyclic carbonate relative to VL, suggesting the possibility of making gradient copolymers. To the best of our knowledge, this is the first instance of cyclic poly(carbonate)s synthesized in one pot without the use of postpolymerization chain-end coupling.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsmacrolett.6b00591. Experimental details, NMR spectra, GPC traces, and MALDI-MS of polymers (PDF) 1165

DOI: 10.1021/acsmacrolett.6b00591 ACS Macro Lett. 2016, 5, 1162−1166

Letter

ACS Macro Letters

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(26) Shin, E. J.; Brown, H. A.; Gonzalez, S.; Jeong, W.; Hedrick, J. L.; Waymouth, R. M. Angew. Chem., Int. Ed. 2011, 50, 6388−6391. (27) Brown, H. A.; Xiong, S. L.; Medvedev, G. A.; Chang, Y. A.; AbuOmar, M. M.; Caruthers, J. M.; Waymouth, R. M. Macromolecules 2014, 47, 2955−2963. (28) Chang, Y. A.; Waymouth, R. M. Polym. Chem. 2015, 6, 5212. (29) Brown, H. A.; Chang, Y. A.; Waymouth, R. M. J. Am. Chem. Soc. 2013, 135, 18738−18741. (30) Stukenbroeker, T. S.; Solis-Ibarra, D.; Waymouth, R. M. Macromolecules 2014, 47, 8224−8230. (31) Brunelle, D. J. J. Polym. Sci., Part A: Polym. Chem. 2008, 46, 1151−1164. (32) Kricheldorf, H. R.; Bohme, S.; Schwarz, G.; Schultz, C. L. Macromol. Rapid Commun. 2002, 23, 803−808. (33) Kricheldorf, H. R.; Schwarz, G.; Bohme, S.; Schultz, C. L.; Wehrmann, R. Macromol. Chem. Phys. 2003, 204, 1398−1405. (34) Cortez, M. A.; Godbey, W. T.; Fang, Y.; Payne, M. E.; Cafferty, B. J.; Kosakowska, K. A.; Grayson, S. M. J. Am. Chem. Soc. 2015, 137, 6541−6549. (35) Venkataraman, S.; Ng, V. W. L.; Coady, D. J.; Horn, H. W.; Jones, G. O.; Fung, T. S.; Sardon, H.; Waymouth, R. M.; Hedrick, J. L.; Yang, Y. Y. J. Am. Chem. Soc. 2015, 137, 13851. (36) Rokicki, G. Prog. Polym. Sci. 2000, 25, 259. (37) Feng, J.; Zhuo, R.-X.; Zhang, X.-Z. Prog. Polym. Sci. 2012, 37, 211. (38) Venkataraman, S.; Veronica, N.; Voo, Z. X.; Hedrick, J. L.; Yang, Y. Y. Polym. Chem. 2013, 4, 2945. (39) Mespouille, L.; Coulembier, O.; Kawalec, M.; Dove, A. P.; Dubois, P. Prog. Polym. Sci. 2014, 39, 1144−1164. (40) Lohmeijer, B. G. G.; Pratt, R. C.; Leibfarth, F.; Logan, J. W.; Long, D. A.; Dove, A. P.; Nederberg, F.; Choi, J.; Wade, C.; Waymouth, R. M.; Hedrick, J. L. Macromolecules 2006, 39, 8574. (41) Blake, T. R.; Waymouth, R. M. J. Am. Chem. Soc. 2014, 136, 9252−9255.

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This material is based on work supported by the NSF (NSFDMR 1407658). AER acknowledges Franklin Research Grant from American Philosophical society. Authors thank Jana K. Maclaren for help with the crystal structure refinement. Part of this work was performed at Stanford Nano Shared Facilities (SNSF) and Vincent Coates Foundation Mass Spectrometry Laboratory, Stanford University Mass Spectrometry.

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REFERENCES

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DOI: 10.1021/acsmacrolett.6b00591 ACS Macro Lett. 2016, 5, 1162−1166