Diethyl Carbonate

(R = Et)

[105-58-8]  · C5H10O3  · Diethyl Carbonate  · (MW 118.13) (R = Me)

[616-38-6]  · C3H6O3  · Dimethyl Carbonate  · (MW 90.08)

(C-alkoxycarbonylations of carbanions2-12 and other nucleophiles;13 synthesis of ketones14 and tertiary alcohols;15 allylations with allyl alkyl carbonates;16 alkylations of nucleophilic substrates;17-20 heterocyclic synthesis21)

Physical Data: R = Et: bp 127 °C; d 0.975 g cm-3. R = Me: bp 90.3 °C; d 1.070 g cm-3.

Solubility: miscible organic alcohols, esters, ethers. R = Et: insol H2O. R = Me: sol 13.9 g per 100 g H2O at 20 °C.

Form Supplied in: readily available; inexpensive.

Handling, Storage, and Precautions: inhalation of the vapors of dimethyl carbonate may cause irritation.

Alkoxycarbonylations of Carbanions.

Diethyl and dimethyl carbonate are valuable reagents for the C-alkoxycarbonylation of enolate anions derived from active methylene compounds.1,2 The yields, in general, are comparable to those found using other electrophilic alkoxycarbonylating agents. Various bases such as Sodium Hydride, NaH-KH mixtures, metal alkoxides, and nonnucleophilic species such as Lithium Diisopropylamide at low temperature have been utilized to generate enolate anions. The latter method is particularly useful, since enolate formation is complete, and competitive condensations of the enolate anions with the substrate are avoided. Ketones3 can readily be converted into b-keto esters and esters into malonate esters.4 Selected examples for the conversion of a cyclic (eq 1)3f and an alicyclic ketone (eq 2)3b to the respective b-keto esters are illustrated. In the acyclic example, the kinetically formed enolate is C-ethoxycarbonylated.

The conversion of t-butyl acetate to the t-butyl methyl malonate ester (eq 3)4 and a C-methoxycarbonylation of g-butyrolactone (eq 4) have been described.5

Aryl and alkyl cyanides are readily alkoxycarbonylated.6 The a-ethoxycarbonylations of phenylacetonitrile (eq 5)6c and cyanopentanecarbonitrile (eq 6)6a are typical examples.

The transformations of primary nitro compounds (eq 7)7 and isocyanides (eq 8)8 into the a-ethoxycarbonylation products have been reported.

The conversion of 2,6-dimethylpyridine to ethyl 6-methylpyridine-2-acetate has been accomplished using Potassium Amide and diethyl carbonate (eq 9).9

The dianions formed from cyclic or acyclic carboxylic acids on treatment with dimethyl or diethyl carbonate lead to monoesters of malonic acid (eq 10).10

Carboxylic acid esters can be synthesized from aryl11 or alkyl halides11b by treatment of the corresponding Grignard reagents with dimethyl or diethyl carbonate. For example, addition of Phenylmagnesium Bromide in THF to a THF solution of dimethyl carbonate (2.0 equiv) at 0-5 °C leads to methyl benzoate (87%).11

Carbanions formed via directed metalations undergo facile a-alkoxycarbonylations.12 Lithiation of 1-(t-butoxycarbonyl)-1,2-dihydropyridine followed by addition of dimethyl carbonate leads to the a-methoxycarbonylated product (eq 11).12a The retention of configuration found in the alkoxycarbonylation of a benzyllithium analog is of interest (eq 12).12b

Other nucleophiles such as amines and hydrazines react with dimethyl or diethyl carbonate to yield the corresponding carbamates or carbazates. Treatment of hydrazine with diethyl carbonate leads to ethyl hydrazinecarboxylate (77-85%).13

Ketone Synthesis.

The synthesis of ketones can be effected by treatment of organometallics with diethyl carbonate.14 The addition of 2 equiv of 4-chloro-3-lithiopyridine to diethyl carbonate affords bis(4-chloro-3-pyridyl) ketone (eq 13).14c

Tertiary Alcohol Synthesis.

Dimethyl or diethyl carbonate on treatment with organometallics lead to tertiary alcohols.15

Allylations and Alkylations.

The allylations of b-keto esters, b-diketones, malonate esters, nitriles, and nitro analogs can be accomplished under neutral conditions by use of a variety of allylic carbonates in the presence of a palladium-phosphine catalyst.16 A typical procedure is shown (eq 14).16a

The selective mono-N-methylation of aromatic amines such as aniline17 and mono-C-methylations of arylacetonitriles18 by dimethyl carbonate can be performed by gas-liquid phase transfer catalysis. Dimethyl carbonate in the presence of potassium carbonate and 18-Crown-6 (or Aliquat 336) is useful for the S-methylation of alkyl or aryl thiols (eq 15), the O-methylation of phenols, and the N-methylation of imidazole.19

The a-methylation and a-methoxycarbonylation of primary esters has been accomplished by addition of the ester in dimethyl carbonate to a mixture of NaH in dimethyl carbonate (eq 16).20

Synthesis of Heterocycles.

Many substrates react with dimethyl or diethyl carbonate to form heterocyclic compounds. Treatment of 1,2-amino alcohols with dimethyl carbonate affords 2-oxazolidinones.21 The preparation of (S)-4-(phenylmethyl)-2-oxazolidinone (eq 17) is illustrative.21c

Related Reagents.

Benzyl Chloroformate; Carbon Dioxide; Carbon Oxysulfide; Di-t-butyl Dicarbonate; Diethyl Oxalate; Ethyl Chloroformate; Methyl Magnesium Carbonate; Methyl Cyanoformate.

1. (a) Mathieu, J.; Weill-Raynal, J. Formation of C-C Bonds; Thieme: Stuttgart, 1973; vol. 1, pp 325-345. (b) Enichem Synthesis Technical Bulletin; Enichem America: New York, 1992; a review of dimethyl carbonate with 577 references.
2. (a) House, H. O. Modern Synthetic Reactions, 2nd ed.; Benjamin: Menlo Park, CA, 1972; Chapter 11. (b) Stowell, J. C. Carbanions in Organic Synthesis; Wiley: New York, 1979; Chapters 5 and 6. (c) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, 3rd ed.; Plenum: New York, 1990; Part B, pp 55-94. (d) Davis, B. R.; Garratt, P. J. COS 1991, 2, 795.
3. (a) Krapcho, A. P.; Diamanti, J.; Cayen C.; Bingham, R. OSC 1973, 5, 198. (b) Crombie, L.; Jones, R. C. F.; Palmer, C. J. JCS(P1) 1987, 317. (c) Kallury, K. R.; Krull, U. J.; Thompson, M. JOC 1988, 53, 1320. (d) Mori, K.; Kamada, A.; Mori, H.; LA 1989, 303. (e) Alderdice, M.; Sum, F. W.; Weiler, L. OSC 1990, 7, 351. (f) DeGraw, J. I.; Christie, P. H.; Colwell, W. T.; Sirotnak, F. M. JMC 1992, 35, 320; (g) Ruest, L.; Blouin, G.; Deslongchamps, P. SC 1976, 6, 169.
4. Hill, J. E.; Harris, T. M. SC 1982, 12, 621.
5. (a) Fieser, L. F.; Fieser, M. FF 1975, 5, 214. (b) Quesada, M. L.; Schlessinger, R. H. JOC 1978, 43, 346.
6. (a) Albarella, J. P. JOC 1977, 42, 2009. (b) van den Berg, E. M. M.; Richardson, E. E.; Lugtenburg, J.; Jenneskens, L. W. SC 1987, 17, 1189. (c) Horning, E. C.; Finelli, A. F. OSC 1963, 4, 461. (d) Pakusch, J.; Beckhaus, H.-D.; Rüchardt, C. CB 1991, 124, 1191.
7. (a) Lehr, F.; Gonnermann, J.; Seebach, D. HCA 1979, 62, 2258. (b) Seebach, D.; Colvin, E. W.; Lehr, F.; Weller, T. C 1979, 33, 1.
8. Matsumoto, K.; Suzuki, M.; Miyoshi, M. JOC 1973, 38, 2094.
9. Kofron, W. G.; Baclawski, L. M. OSC, 1988, 6, 611.
10. Krapcho, A. P.; Jahngen, E. G. E., Jr.; Kashdan, D. S. TL 1974, 2721.
11. (a) Whitmore, F. C.; Loder, D. J.; OSC 1943, 2, 282. (b) Bank, S.; Ehrlich, C. L.; Mazur, M.; Zubieta, J. A. JOC 1981, 46, 1243. (c) Satyanarayana, G.; Sivaram, S. SC 1990, 20, 3273.
12. (a) Comins, D. L.; Weglarz, M. A.; O'Connor, S. TL 1988, 29, 1751. (b) Hoppe, D.; Carstens, A.; Krämer, T. AG(E) 1990, 29, 1424. (c) Kawasaki, T.; Kodama, A.; Nishida, T.; Shimizu, K.; Somei, M. H 1991, 32, 221.
13. Cookson, R. C.; Gupte, S. S.; Stevens, I. D. R.; Watts, C. T. OSC 1988, 6, 936.
14. (a) Marsais, F.; Breant, P.; Ginguene, A.; Queguiner, G. JOM 1981, 216, 139. (b) Chen, L. S.; Chen, G. J.; Ryan, M. T.; Tamborski, C. JFC 1987, 34, 299. (c) Radinov, R.; Haimova, M.; Simova, E. S 1986, 886. (d) Chen, G. J.; Chen, L. S. JFC 1991, 55, 119.
15. (a) Colle, T. H.; Lewis, E. S. JACS 1979, 101, 1810. (b) Syper, L. Rocz. Chem. 1973, 47, 433 (CA 1973, 79, 17 981z).
16. (a) Tsuji, J.; Shimizu, I.; Minami, I.; Ohashi, Y.; Sugiura, T.; Takahashi, K. JOC 1985, 50, 1523. (b) Tsuji, J.; Minami, I. ACR 1987, 20, 140.
17. Trotta, F.; Tundo, P.; Moraglio, G. JOC 1987, 52, 1300.
18. Tundo, P.; Trotta, F.; Moraglio, G. JCS(P1) 1989, 1070.
19. Lissel, M.; Schmidt, S.; Neumann, B. S 1986, 382.
20. Sengupta, D.; Venkateswaran, R. V. JCR(S) 1984, 372.
21. (a) Schulz, K.-H.; Heine, H.-G.; Hartmann, W. OSC 1990, 7, 4. (b) Ito, Y.; Sasaki, A.; Tamoto, K.; Sunagawa, M.; Terashima, S. T 1991, 47, 2801. (c) Gage, J. R.; Evans, D. A. OSC 1993, 8, 528.

A. Paul Krapcho

The University of Vermont, Burlington, VT, USA

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