Synthesis of 6-membered cyclic carbonates from 1,3-diols and low CO₂ pressure: a novel mild strategy to replace phosgene reagents

Abstract

Low pressure carbon dioxide is used as the carbonation agent in a simple, safe and efficient procedure for the synthesis of 6-membered cyclic carbonates from 1,3-diols. Using readily available reagents and proceeding at room temperature, this route offers a novel mild alternative to phosgene derivatives.

---

Unlike aromatic polycarbonates, aliphatic polycarbonates (APCs) have been little explored commercially. However, their low toxicity and biodegradability make them excellent candidates for biomedical applications.¹ Recently, they have also been investigated as thermoplastics,² binders for photovoltaics,³ polymer electrolytes⁴ and adhesives.⁵

Part of this renewed attention stems from the possibility to obtain APCs via the copolymerisation of CO₂ and epoxides,⁶ an attractive reaction which uses an abundant and virtually free source of carbon, but is limited by the scope of usable epoxides. APCs can also be synthesised by polycondensation of diols with phosgene derivatives or dialkyl carbonates,⁷ but the control of the polymer molecular weight is highly sensitive to the reaction conditions. Hence, Ring-Opening Polymerisation (ROP) of cyclic carbonates has become the method of choice for APC synthesis,^1b,8 as the development of ROP catalysts⁹ has enabled controlled polymerisation of highly functionalised monomers¹⁰ under mild conditions (usually 6-, 7-,¹¹ or strained 5-membered rings¹²).

A common preparation of cyclic carbonate monomers involves the transesterification of diols with phosgene,^8,13 a toxic reagent synthesised from CO and Cl₂ in an energy intensive process. Nevertheless, phosgene is still widely employed due to its efficiency and the lack of a more versatile and sustainable alternative. Safer phosgene derivatives¹⁴ include di-tert-butyl dicarbonate,¹⁵ 1,1′-carbonyldiimidazole,¹⁶ and aromatic carbonates,¹⁷ but these reagents all derive from phosgene, and can lead to unwanted side reactions, low reactivity and difficult workups.

Alternative methods, such as the Pd-catalysed oxidative carbonylation of diols using CO pressure,¹⁸ or the catalytic coupling of CO₂ with oxetanes,¹⁹ have also been reported. The latter however, is limited by the availability of oxetanes.²⁰ Transesterification of diols with urea, industrially produced from CO₂, is also described but with moderate success.²¹

Using CO₂ as a C1-carbonation agent is an attractive goal for phosgene related emissions mitigation and direct CO₂ utilisation. The direct coupling of CO₂ with diols, where water is the sole by-product, would be an attractive process. However, the reaction is generally not kinetically and thermodynamically favoured. Therefore, a catalyst and an efficient stoichiometric dehydrating strategy (e.g. nitriles, zeolites, orthoesters, or Mitsunobu reagents) are necessary for the reaction to proceed.²² Despite recent advances, such as the use of CeO₂ catalyst in tandem with a large excess of 2-cyanopyridine as a dehydrating agent,²³ or the in situ introduction of a leaving group based on dibromomethane,²⁴ high CO₂ pressures (10–50 bar) and high temperatures (70–140 °C) are still required, particularly for the synthesis of 6-membered rings.

Herein, we report a safe and efficient one-pot procedure for the synthesis of 6-membered cyclic carbonates directly from 1,3-diols, which uses CO₂ as the carbonation agent instead of phosgene derivatives. This methodology proceeds at room temperature, needs only 1 atm. of CO₂ and common lab reagents (Scheme 1), and does not require the preliminary preparation of oxetanes or chloroalcohols.²⁵

Scheme 1 Strategy for the synthesis of cyclic carbonate from 1,3-diols and CO₂ (R¹–R⁴ are the various substituents of 1,3-diols used, see Table 2).

In 2005, Jessop and coworkers reported the reversible carbonation of alcohols with CO₂ promoted by 1,8-diazabicyclo-[5.4.0]-undec-7-ene (DBU).²⁶ The conversion was later found to depend on the choice of solvent with almost full conversion of 1-hexanol being achieved in CDCl₃.²⁷ Inspired by these reports, we investigated the selective mono-insertion of CO₂ into one alcohol moiety of 1,3-diols in various solvents. The slow addition of DBU under 1 atm of CO₂ to solutions of (±)-1,3-butanediol (1a) was monitored and the conversion to alkyl carbonate species assessed by ¹H NMR (Table 1). Regardless of the solvent used, the carbonation of 1a by CO₂ proceeded quickly at low pressure and room temperature, with good selectivity towards the mono-insertion products (ca. 90% of products). A slight preference for the primary alcohol moiety was also observed, in agreement with DFT calculations (see ESI Fig. S4†). In neat diol, the conversion was limited by the increased viscosity upon CO₂ insertion (Table 1, Entry 1), but even in solution and with the addition of ionic liquid bmimPF₆, as used by Lim et al. (Table 1, Entry 5),²⁴ full conversion of 1a was not observed with only one DBU equivalent. Apolar toluene-d₈ gave less conversion than more polar solvents, whereas more dicarbonated product was obtained in acetonitrile-d₃ (Table 1, Entry 2 and 4). Overall, optimal results were obtained in CDCl₃, and despite it not being a desirable solvent which should be replaced in the future, chloroform was used in the rest of our study. Addition of DBU at low temperature resulted in no further improvement in mono-insertion selectivity (Table 1, Entry 7), while increasing the temperature promoted decarboxylation. A lower concentration of diol slightly decreased the amount of disubstituted product (Table 1, Entry 6) but did not affect the global conversion. The use of stronger base 1,5,7-diazabicyclo[4.3.0]-undec-7ene (TBD) in place of DBU resulted in less conversion, which is attributed to an increased sensitivity to moisture (Table 1, Entry 8). The use of triethylamine resulted in no carbonation of 1a.

Table 1 Reaction of 1,3-butanediol 1a with DBU under 1 atm of CO₂^a

Entry	Solvent	T (°C)	[1a] (M)	Conv. into carbonated products^b (%)
				Total	1′aI+II	1′aI	1′aII	1′abis
a Reactions conditions: diol (5.6 mmol, 1.7 M), DBU (5.6 mmol), room temperature, CO2 (1 atm), 2 h (saturation).b Based on diol conversion and determined by relative integration of methine signals in ^1H NMR (e.g. 4.64 ppm for 1′aII/see ESI Fig. S1–S3).c Addition of 1-butyl-3-methylimidazolium hexafluorophosphate (bmimPF6, 5.6 mmol); [diol] = 0.4 M.d Addition of DBU at T = −78 °C then rt.e 1 equiv. of TBD was used instead of DBU.f 3 equiv. of DBU were used.
1	Neat	25	n/a	47	44	30	14	3
2	C7D8	25	1.7	60	56	37	19	4
3	CDCl3	25	1.7	78	69	46	23	9
4	CD3CN	25	1.7	73	58	40	18	15
5^c	CDCl3	25	1.7	69	52	35	17	17
6	CDCl3	25	0.1	78	73	49	24	5
7^d	CDCl3	−78	1.7	77	68	45	23	9
8^e	CDCl3	25	1.7	62	56	37	19	6
9^f	CDCl3	25	1.7	>99	57	40	17	43

---

Further DFT calculations showed that the direct coupling of 1a and CO₂ to form cyclic carbonate 2a is slightly thermodynamically disfavoured (ΔΔG = +3.0 kcal mol⁻¹). Following the DBU-aided insertion of CO₂, the activation barriers are then too high for the cyclisation of 1′a_I (or 1′a_II) to proceed under mild conditions (61.1 and 42.2 kcal mol⁻¹ via an S_N2 or addition/elimination mechanism, respectively) (see Fig. S4†). An in situ leaving group strategy was thus applied experimentally to overcome the kinetic as well as the thermodynamic limitation of the reaction. After the selective mono-insertion of CO₂ into 1a in CDCl₃ at low concentration, 1 equivalent of tosyl chloride and triethylamine were added to the reaction mixture and stirred at room temperature overnight. Rapidly, the cyclic carbonate 2a was detected by ¹H NMR (addition of triethylamine alone did not result in any product). The pure product was later isolated by column chromatography in a 44% yield, i.e. 60% conversion based on the mono-CO₂ inserted products (Table 2‡, Entry 1). A higher concentration of diol (1.7 M), despite being slightly detrimental to the first step of the procedure, proved to lead to a higher isolated yield of cyclic carbonate (68%, i.e. 99% conversion based on CO₂ mono-insertion, Table 2, Entry 2). This compares well with the traditional phosgene-based method (50%)²⁸ as well as oxidative carbonylation methods (45%).^18a The procedure was found to be robust: CO₂ from sublimed dry ice could be used and yielded cyclic carbonate 2a, albeit in lower yield (48%, Table 2, Entry 3). The reaction also proceeded without solvent (30% yield). Investigation into the scope of the procedure was carried out with various 1,3-diols. The cyclisation step proceeded efficiently from the CO₂-mono insertion products and all cyclic carbonates were isolated in moderate yields (Table 2), comparative with phosgene-based and alternative methods. For example, the isolation of 2d from 2,2-dimethyl-1,3-propanediol (53%, Table 2, Entry 8) was previously reported using phosgene derivatives (60%),²⁹ oxidative carbonylation (50%),^18b and metal free cyclisation (50%).²⁴ O-isopropylidene-xylose was also successfully transformed, though isolation proved challenging (11%, Table 2, Entry 12).

Table 2 Synthesis of various cyclic carbonates from 1,3-diols and CO₂

Entry	Substrate		% Yield^a [conv.1′→2]^b	Product
a Isolated yield based on starting diol.b Spectroscopic conversion of CO2 mono-insertion products 1′ into cyclic carbonate 2.c [Diol] = 0.1 M.d CO2 from the sublimation of dry ice was used.
1^c		1a	44 [60]		2a
2		1a	68 [99]		2a
3^d		1a	48		2a
4		(R)-1a	68		(R)-2a
5		(S)-1a	70		(S)-2a
6		1b	53 [71]		2b
7		1c	55 [96]		2c
8		1d	53 [82]		2d
9		1e	49 [78]		2e
10		1f	46 [71]		2f
11		1g	41 [70]		2g
12		1h	11		2h

---

As cyclisation happens readily, reaction intermediates could not be isolated, but DFT calculations on model compound (R)-1a and additional experiments with optically active diols were carried out to investigate the reaction mechanism. After insertion of CO₂, tosylation can occur at the carbonate or at the remaining alcohol group, so that cyclisation proceeds via either an addition/elimination or a S_N2 pathway, leading to retention or inversion of stereochemistry (see Scheme 2). However, the exclusive formation and isolation of (R,R)-cyclic carbonate 2b from (R,R)-2,4-pentanediol, as well as the optical activities of the cyclic carbonates obtained from enantiopure (R) and (S)-1,3-butanediol (Table 2, Entries 4–6),³⁰ both indicated an addition/elimination pathway, with no racemisation or inversion of stereochemistry being observed.

Scheme 2 DFT computed pathways (6-31+G(d)/rωb97xD/cpcm = chloroform/298 K protocol) and mechanism for the cyclisation of 1′a_I to 2a, as supported by experiments and calculations (see ESI Fig. S4† for full details of calculations).

DFT calculations supported these conclusions and gave supplementary insight into the selectivity. Scheme 2 illustrates the computed pathways for the cyclisation of 1′a_I to 2a. As expected with a tosyl leaving group, the formation of the cyclic carbonate is strongly favoured (ΔΔG = −36.7 kcal mol⁻¹). Additionally, the activation energy barriers for both the nucleophilic addition/elimination and S_N2 ring-closing mechanisms are similar and low enough to happen at room temperature (ΔΔG^TS = +18.9 and +22.3 kcal mol⁻¹ respectively). The tosylation of the second alcohol moiety is however more favoured thermodynamically than that of the carbonate (ΔΔG = −25.4 vs. = −2.3 kcal mol⁻¹). Yet, the activation barrier for the tosylation of the carbonate is lower than that of the alcohol moiety (ΔΔG^TS = +23.8 and +29.7 kcal mol⁻¹ respectively). Hence, we believe that the addition/elimination pathway, resulting in stereochemical retention, is kinetically favoured over the S_N2 (ΔΔG^TS = +5.9 kcal mol⁻¹).

In conclusion, in the wider context of an ever-growing need for innovative materials and CO₂ emissions mitigation and utilisation, a novel one-pot procedure that uses safe and readily available reagents yielded 6-membered cyclic carbonates directly from abundant 1,3-diols and carbon dioxide under mild conditions (room temperature and low pressure), and compared well with toxic or expensive alternative methods. Computational and experimental evidence shows that the reaction proceeds through an addition/elimination pathway. On-going work is now aiming at replacing chloroform for a more environmental benign solvent and making the procedure catalytic in order to reduce the amount of salts produced.

Acknowledgements

We thank Sue and Roger Whorrod, the University of Bath, and the UK Engineering and Physical Sciences Research Council (EPSRC) (NSCCS/CHEM752 and CDT in Sustainable Chemical Technologies) for financial support.

Notes and references

1. (a) J. Xu, E. Feng and J. Song, J. Appl. Polym. Sci., 2014, 131, 39822–39838; (b) J. Feng, R.-X. Zhuo and X.-Z. Zhang, Prog. Polym. Sci., 2012, 37, 211–236.
2. (a) K. Kobayashi, S. Kanmuri, Y. Kimura and K. Masutani, Polym. Int., 2015, 64, 641–646; (b) G. A. Luinstra and E. Borchardt, in Synthetic Biodegradable Polymers, ed. B. Rieger, A. Künkel, G. W. Coates, R. Reichardt, E. Dinjus and T. A. Zevaco, Springer Berlin Heidelberg, 2012, vol. 245, pp. 29–48; (c) C. Koning, J. Wildeson, R. Parton, B. Plum, P. Steeman and D. J. Darensbourg, Polymer, 2001, 42, 3995–4004.
3. S.-Y. Ku, C. D. Liman, J. E. Cochran, M. F. Toney, M. L. Chabinyc and C. J. Hawker, Adv. Mater., 2011, 23, 2289–2293.
4. Y. Tominaga, T. Shimomura and M. Nakamura, Polymer, 2010, 51, 4295–4298.
5. N. Fritz, H. Dao, S. A. B. Allen and P. A. Kohl, Int. J. Adhes. Adhes., 2012, 38, 45–49.
6. M. R. Kember, A. Buchard and C. K. Williams, Chem. Commun., 2011, 47, 141–163.
7. (a) J. H. Park, J. Y. Jeon, J. J. Lee, Y. Jang, J. K. Varghese and B. Y. Lee, Macromolecules, 2013, 46, 3301–3308; (b) W. Zhu, X. Huang, C. Li, Y. Xiao, D. Zhang and G. Guan, Polym. Int., 2011, 60, 1060–1067; (c) G. Rokicki, J. Pawlicki and W. Kuran, Polym. J., 1982, 14, 839–845; (d) Y. Ono, Catal. Today, 1997, 35, 15–25; (e) D. J. Brunelle, in Advances in Polycarbonates, ed. D. J. Brunelle and M. R. Korn, American Chemical Society, 2005, vol. 898, pp. 1–5.
8. G. Rokicki, Prog. Polym. Sci., 2000, 25, 259–342.
9. S. M. Guillaume and J.-F. Carpentier, Catal. Sci. Technol., 2012, 2, 898–906.
10. (a) S. Tempelaar, L. Mespouille, O. Coulembier, P. Dubois and A. P. Dove, Chem. Soc. Rev., 2013, 42, 1312–1336; (b) D. P. Sanders, D. J. Coady, M. Yasumoto, M. Fujiwara, H. Sardon and J. L. Hedrick, Polym. Chem., 2014, 327–329.
11. G. Rokicki and P. G. Parzuchowski, in Polymer Science: A Comprehensive Reference, ed. K. Matyjaszewski and M. Möller, Elsevier, Amsterdam, 2012, pp. 247–308.
12. (a) M. Azechi, K. Matsumoto and T. Endo, J. Polym. Sci., Part A: Polym. Chem., 2013, 51, 1651–1655; (b) W. Guerin, A. K. Diallo, E. Kirilov, M. Helou, M. Slawinski, J.-M. Brusson, J.-F. Carpentier and S. M. Guillaume, Macromolecules, 2014, 47, 4230–4235; (c) W. Guerin, M. Helou, M. Slawinski, J.-M. Brusson, J.-F. Carpentier and S. M. Guillaume, Polym. Chem., 2015, 6, 1972–1985; (d) A. K. Diallo, E. Kirillov, M. Slawinski, J.-M. Brusson, S. M. Guillaume and J.-F. Carpentier, Polym. Chem., 2015, 6, 1961–1971.
13. A.-A. G. Shaikh and S. Sivaram, Chem. Rev., 1996, 96, 951–976.
14. H. A. Staab, Angew. Chem., Int. Ed. Engl., 1962, 1, 351–367.
15. Y. Basel and A. Hassner, J. Org. Chem., 2000, 65, 6368–6380.
16. J. Mindemark and T. Bowden, Polymer, 2011, 52, 5716–5722.
17. (a) H. Matsukizono and T. Endo, J. Appl. Polym. Sci., 2015, 41956–41966; (b) D. P. Sanders, K. Fukushima, D. J. Coady, A. Nelson, M. Fujiwara, M. Yasumoto and J. L. Hedrick, J. Am. Chem. Soc., 2010, 132, 14724–14726; (c) D. P. Sanders, D. J. Coady, M. Yasumoto, M. Fujiwara, H. Sardon and J. L. Hedrick, Polym. Chem., 2014, 5, 327–329; (d) K. Mikami, A. T. Lonnecker, T. P. Gustafson, N. F. Zinnel, P. J. Pai, D. H. Russell and K. L. Wooley, J. Am. Chem. Soc., 2013, 135, 6826–6829; (e) J. L. Hedrick, A. Nelson, D. P. Sanders, US Pat., US20100280242, 2010.
18. (a) B. Gabriele, R. Mancuso, G. Salerno, L. Veltri, M. Costa and A. Dibenedetto, ChemSusChem, 2011, 4, 1778–1786; (b) D. M. Pearson, N. R. Conley and R. M. Waymouth, Adv. Synth. Catal., 2011, 353, 3007–3013.
19. C. Martín, G. Fiorani and A. W. Kleij, ACS Catal., 2015, 5, 1353–1370.
20. J. A. Burkhard, G. Wuitschik, M. Rogers-Evans, K. Müller and E. M. Carreira, Angew. Chem., Int. Ed., 2010, 49, 9052–9067.
21. (a) Q. Li, W. Zhang, N. Zhao, W. Wei and Y. Sun, Catal. Today, 2006, 115, 111–116; (b) Q. Li, N. Zhao, W. Wei and Y. Sun, J. Mol. Catal. A: Chem., 2007, 270, 44–49.
22. (a) D. Chaturvedi, N. Mishra and V. Mishra, Tetrahedron Lett., 2007, 48, 5043–5045; (b) T. Sakakura and K. Kohno, Chem. Commun., 2009, 1312–1330; (c) M. Tamura, M. Honda, Y. Nakagawa and K. Tomishige, J. Chem. Technol. Biotechnol., 2014, 89, 19–33.
23. M. Honda, M. Tamura, K. Nakao, K. Suzuki, Y. Nakagawa and K. Tomishige, ACS Catal., 2014, 4, 1893–1896.
24. Y. N. Lim, C. Lee and H.-Y. Jang, Eur. J. Org. Chem., 2014, 9, 1823–1826.
25. M. R. Reithofer, Y. N. Sum and Y. Zhang, Green Chem., 2013, 15, 2086–2090.
26. P. G. Jessop, D. J. Heldebrant, X. Li, C. A. Eckert and C. L. Liotta, Nature, 2005, 436, 1102.
27. (a) P. M. Mathias, K. Afshar, F. Zheng, M. D. Bearden, C. J. Freeman, T. Andrea, P. K. Koech, I. Kutnyakov, A. Zwoster, A. R. Smith, P. G. Jessop, O. G. Nik and D. J. Heldebrant, Energy Environ. Sci., 2013, 6, 2233–2242; (b) L. Phan, J. R. Andreatta, L. K. Horvey, C. F. Edie, A.-L. Luco, A. Mirchandani, D. J. Darensbourg and P. G. Jessop, J. Org. Chem., 2008, 73, 127–132.
28. H. Yasuda, M.-S. Aludin, N. Kitamura, M. Tanabe and H. Sirahama, Macromolecules, 1999, 32, 6047–6057.
29. B. J. Ludwig and E. C. Piech, J. Am. Chem. Soc., 1951, 73, 5779–5781.
30. Low volatility and UV sensitivity prevented chiral GC/HPLC study.

---

Footnotes

† Electronic supplementary information (ESI) available: Full experimental and computational data. See DOI: 10.1039/c5ra07290e

‡ Typical procedure for the synthesis of cyclic carbonate monomers: under a CO₂ atmosphere, DBU (1 equiv.) was added dropwise to a stirring solution/suspension of diol (0.5 g, 1 equiv.) in dry chloroform (1.7 M). After stirring at room temperature for 2 hours, triethylamine (1 equiv.) was added dropwise to the resulting viscous solution. A solution of TsCl in chloroform (1 equiv., 0.5 M) was then added slowly and the mixture stirred overnight. Removal of volatiles in vacuo afforded an oily residue, which was purified by column chromatography.

---