Bis(trichloromethyl) Carbonate1

[32315-10-9]  · C3Cl6O3  · Bis(trichloromethyl) Carbonate  · (MW 296.73)

(a phosgene surrogate)

Alternate Name: triphosgene.

Physical Data: mp 81-83 °C; bp 203-206 °C.

Solubility: sol methanol, ethanol, benzene, diethyl ether, hexane, THF, ethyl acetate; dec slowly in cold water.

Form Supplied in: white crystalline solid

Handling, Storage, and Precautions: the reagent is somewhat moisture sensitive, but scrupulously anhydrous conditions are not necessary. Rapid handling of the reagent in open air, in the absence of a glove bag or dry box, is usually satisfactory. This reagent should only be handled in a fume hood.

Introduction.

Phosgene gas is a versatile reagent for organic synthesis, which has been used in carbonylation, chloroformylation, chlorination, and dehydration reactions, to name a few.1 However, because of the high toxicity of Phosgene, it has not been used widely. Surrogates for phosgene have long been sought. Trichloromethyl Chloroformate (diphosgene) was introduced as one such phosgene substitute.2 To the extent that diphosgene is a highly toxic, hygroscopic, and noxious liquid, it is not a fully satisfactory phosgene substitute. On the other hand, bis(trichloromethyl) carbonate (triphosgene; 1) is a crystalline solid compound, is not very hygroscopic, and can substitute for phosgene in a plethora of chemical reactions. Triphosgene has been known since 1880,3 but its synthetic utility had not been exploited until recently.

Carbonylation.

The formation of oxazoles,4 quinazolinediones (eq 1),5 carbonates (eq 2),6 urea analogs,7 and isocyanates (eq 3)1 have been reported with triphosgene. The reactions give good to excellent yields and often require only 1/3 equiv of triphosgene.

Chloroformylation.

The use of triphosgene in the formation of chloroformates with both hydroxy compounds (eq 4) and substituted amines (eq 5) has been reported.1

Dehydration.

Synthesis of isocyanides from formamides (eq 6) is the only example of a dehydration reaction reported for triphosgene to date.1

N-Carboxyamino Acid Anhydrides.

Synthesis of N-carboxyamino acid anhydrides (NCAs) is accomplished by the reaction of the zwitterionic unprotected amino acid with triphosgene at elevated temperatures (eq 7).8 Wilder and Mobashery reported a milder version of this reaction, utilizing N-t-butoxycarbonyl-a-amino acids; in the presence of a stoichiometric quantity of Triethylamine and 1/3 equiv of triphosgene (eq 8) the reaction is believed to proceed via a chloroformic N-t-butoxycarbonyl-a-amino acid anhydride intermediate to give the corresponding NCA.9 There are many synthetic routes to NCAs;10 however, the use of triphosgene in the preparation of NCAs provides a facile, safe, mild, and practical entry to these important molecules.

Chlorination.

Triphosgene has been used in the synthesis of acyl chlorides (eq 9).1 Also, it has been shown to react with a variety of aldehydes to give a-chloro chloroformates (eq 10).11 Goren et al. have shown that triphosgene mediates chloride substitution reactions on activated alcohols (eq 11);12 this reaction involves the formation of an intermediary chloroformate species en route to the chlorinated product. The generality of the reaction was shown for benzylic (eq 12), allylic, and propargylic systems. This reaction proceeds primarily via SN2, with some contribution by SN1 and/or SNi mechanisms.12 Chlorination with triphosgene is considerably milder than the typical chlorination reactions with Thionyl Chloride, Phosphorus(III) Chloride, Phosphorus(V) Chloride, Oxalyl Chloride, and the like; for example, acid-labile functionalities, such as t-butyl carbamate (BOC), benzhydryl, and p-methoxybenzyl groups, can be tolerated in the triphosgene-mediated reactions, whereas they do not normally survive reactions with other chlorination reagents.

Oxidation.

Palomo et al. have demonstrated that primary and secondary alcohols are readily oxidized by triphosgene in the presence of Dimethyl Sulfoxide (DMSO) in good to excellent yields;13a the reaction is applicable to both activated (eq 13) and unactivated alcohols (eq 14). This reaction is a variation of the one reported by Barton with phosgene gas,14 and it is an excellent alternative to Swern-type oxidations. Indeed, in some respects, oxidation of alcohols by triphosgene is superior to the widely used Swern oxidation. The triphosgene reaction tolerates acid-labile functionalities and is not as sensitive to residual moisture as oxalyl chloride used in the Swern oxidation. An additional advantage of the method of Palomo et al. is the ease of handling of triphosgene, and the fact that the reaction is amenable to large-scale synthesis. The breadth and scope of this reaction have been investigated with a large variety of alcohol substrates.13b See also Dimethyl Sulfoxide-Triphosgene.


1. Eckert, H.; Foster, B. AG(E) 1987, 26, 894.
2. Kurita, K.; Iwakura, Y. OSC 1988, 6, 715.
3. Councler, C. CB 1880, 13, 1697.
4. Sicker, D. SC 1989, 875. Flouzat, C.; Blanchet, M.; Guillaumet, G. TL 1992, 33, 4571.
5. Cortez, R.; Rivero, J. A.; Samanathan, R.; Aguire, G.; Ramirez, F. SC 1991, 21, 285.
6. Laufer, D. A.; Doyle, K.; Zhang, X. OPP 1989, 21, 771.
7. Zhao, X.; Chang, Y.-L.; Fowler, F. W. JACS 1990, 112, 6627. Cotarca, L.; Bacaloglu, R.; Csunderlik, C.; Marcu, N.; Tarnaveanu, A. JPR 1987, 329, 1052.
8. Daly, W. H.; Poché, D. TL 1988, 29, 5859.
9. Wilder, R.; Mobashery, S. JOC 1992, 57, 2755.
10. Kricheldorf, H. R. a-Aminoacid-N-Carboxy-Anhydride and Related Heterocycles; Springer: Berlin, 1987; pp 3-58. Blacklock, T. J.; Hirschmann, R.; Veber, D. F. The Peptides; Academic: New York, 1987; Vol. 9, pp 39-102.
11. Coghlan, M. J.; Caley, B. A. TL 1989, 30, 2033.
12. Goren, Z.; Heeg, M. J.; Mobashery, S. JOC 1991, 56, 7188.
13. (a) Palomo, C.; Cossio, F. P.; Ontoria, J. M.; Odrizola, J. M. JOC 1991, 56, 5948. (b) Rivero, I. A.; Samanathan, R.; Hellberg, L. H. OPPI Briefs 1992, 24, 363.
14. Barton, D. H. R.; Garner, B. J.; Wightman, R. H. JCS 1964, 1855.

Juliatiek Roestamadji & Shahriar Mobashery

Wayne State University, Detroit, MI, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.