Practical and Chemoselective Reduction of Acyl Chloride to Alcohol by Borohydride in Aqueous Dichloromethane

Abstract

A simple methodology for the reduction of acid chlorides to their corresponding alcohols has been developed. Various carboxylic acids were converted to alcohols in excellent yields using NaBH₄-K₂CO₃ in a mixed solvent system of dichloromethane and water (1:1) in the presence of a phase-transfer catalyst at low temperature. The importance of the work is its simplicity, selectivity, excellent yield, and very short reaction time. This new reduction condition has proved to be an excellent chemoselective method for a range of acid chlorides in the presence of various functional groups.

Keywords:

• Acyl chloride
• alcohol
• aqueous dichloromethane
• base
• borohydride
• phase-transfer catalyst

ACKNOWLEDGMENTS

We gratefully acknowledge the management of Syngenta for their support and encouragement for this work. We thank Dr. C. S. Prasanna for some technical suggestions and also Saikat Banerjee and Naresh Koneru for recording the spectral and analytical data.

Notes

^a Yield 98% (PTC-PEG-400).

^b Yield 95% (PTC-TBAF).

^c Yield 97% (PTC-TBAB).

^d Yield 95% (PTC-18-Crown-6).

^e Dry THF was used as solvent.

^f KBH4 was used as reducing agent.

^g Reaction was carried out without using any base, and along with the mixture of products the ester (d) derived from the starting acyl chloride and alcohol (a) was isolated in 35%.

^h The desired alcohol was isolated along with the lactone in a ratio of 1:2. The lactone was derived from the intramolecular reaction of the reduced alcohol with the adjacent ester, thus proving that the ester functionality does not get reduced under this reaction condition.

ⁱ Reaction was carried out in toluene/water (1:1) as the solvent, keeping the rest of the conditions unchanged (11% starting acid chloride also was recovered along with the corresponding alcohol and acid).