[116-16-5]  · C3Cl6O  · Hexachloroacetone  · (MW 264.73)

(chlorination of enamines;1 preparation of trichloroacetamides2,3 and trichloroacetates4,5 under neutral conditions; conversion of allyl6 and cyclopropylcarbinyl7 alcohols to the corresponding chlorides)

Alternate Name: hexachloro-2-propanone.

Physical Data: bp 66-70 °C/4 mmHg; mp -30 °C.

Solubility: sol CH2Cl2, CHCl3, benzene.

Form Supplied in: commercially available as a liquid in 98-99% purity.

Analysis of Reagent Purity: GC, HPLC.

Purification: distillation.

Handling, Storage, and Precautions: is highly toxic and is suspected to be mutagenic. This reagent should be handled in a fume hood.

Chlorination of Enamines.

Hexachloroacetone rapidly reacts with enamines in THF at -78 to 0 °C to give, after acid hydrolysis, good yields of the corresponding a-chloroketones.1 The reagent does not affect enol ethers, alkenes, or thioethers at rt.

This reagent is reported to provide cleaner products than Cl2 or NCS in the chlorination of cyclohexanone enamines. For example, treatment of cyclohexanone enamines with hexachloroacetone followed by acid hydrolysis cleanly gives a-chlorocyclohexanone, whereas use of N-Chlorosuccinimide results in formation of substantial amounts of dichlorinated ketone byproduct. Direct chlorination of the ketone can also be problematic. Treatment of 2-methylcyclohexanone with Chlorine gives 2-chloro-2-methylcyclohexanone as the major product, plus cis- and trans-6-chloro-2-methylcyclohexanone along with 2,6-dichloro-2-methylcyclohexanone.

This reagent can exhibit different regioselectivity from other chlorinating agents. For example, the pyrrolidine enamine of 2-methylcyclohexanone reacts with hexachloroacetone to produce a 9:1 mixture of 6-chloro-2-methylcyclohexanone and 2-chloro-2-methylcyclohexanone (eq 1),1 whereas Sulfuryl Chloride gives 2-chloro-2-methylcyclohexanone as the predominant product.

Trichloroacetylation of Alcohols and Amines.

Hexachloroacetone reacts under neutral conditions with dipeptides at rt in DMSO to produce the corresponding trichloroacetamides in high yield.2 No reaction with the carboxylic acid functional group is observed (eq 2).

With modification of the reaction conditions, a number of alkyl, aryl, and heteroaryl amines can be efficiently trichoroacetylated using this reagent.3

Hexachloroacetone in the presence of a strong hydrogen bond acceptor such as DMF will convert alcohols into the corresponding trichloroacetates in high yield (eq 3).4 This reaction is sterically sensitive, and thus can be used to selectively acylate less hindered hydroxy groups.5

Chlorination of Allyl and Cyclopropylcarbinyl Alcohols.

Hexachloroacetone reacts with allyl and cyclopropylcarbinyl alcohols in the presence of Triphenylphosphine to produce the corresponding chlorides. With primary and secondary allyl alcohols, the reaction proceeds to give mostly unrearranged allyl chloride with retention of double bond stereochemistry and inversion of configuration at the hydroxy-bearing carbon (eq 4).6 Tertiary allylic alcohols predominantly give rearranged products. This reagent system is a useful substitute for Triphenylphosphine-Carbon Tetrachloride in preparing volatile allyl chlorides that are not easily separable from CCl4.

Cyclopropylcarbinyl alcohols react with hexachloroacetone in the presence of triphenylphosphine to give high yields of cyclopropylcarbinyl chlorides that are free of homoallylic rearrangement products (eq 5).7

Related Reagents.


1. (a) Laskovics, F. M.; Schulman, E. M. TL 1977, 759. (b) Laskovics, F. M.; Schulman, E. M. JACS 1977, 99, 6672.
2. Panetta, C. A.; Casanova, T. G. JOC 1970, 35, 2423.
3. (a) Bew, C.; de Joshi, V. O.; Gray, J.; Kaye, P. T.; Meakins, G. D. JCS(P1) 1982, 945. (b) Rudavskii, V. P.; Khaskin, I. G. UKZ 1967, 33, 391 (CA 1967, 67, 63 963).
4. Freedlander, R. S.; Bryson, T. A.; Dunlap, R. B.; Schulman, E. M.; Lewis, C. A., Jr. JOC 1981, 46, 3519.
5. Haines, A. H.; Sutcliffe, E. J. Carbohydr. Res. 1985, 138, 143.
6. (a) Magid, R. M.; Fruchey, O. S.; Johnson, W. L. TL 1977, 2999. (b) Magid, R. M.; Fruchey, O. S.; Johnson, W. L.; Allen, T. G. JOC 1979, 44, 359. (c) Magid, R. M.; Talley, B. G.; Souther, S. K. JOC 1981, 46, 824.
7. Hrubiec, R. T.; Smith, M. B. JOC 1984, 49, 431.

George D. Maynard

Marion Merrell Dow, Cincinnati, OH, USA

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