Exploration of Mesyl Chloride in a One Pot Conversion of Carboxylic Acids to Ketones

Abstract

Background: Due to the ubiquitous nature of the ketone functionality, it is considered an important functional group in organic chemistry. Hence, the synthesis of ketones from readily available starting materials is an important chemical transformation in organic synthesis. Consequently, several research efforts have been reported in the literature for the transformation of carboxylic acids to ketones in a one-pot synthesis. However, some of the procedures have limitations, such as long reaction times, harsh reaction conditions, and usage of expensive metal catalysts. Thus, a simple and convenient one-pot conversion of carboxylic acids to ketones remains desirable. Objective: We intended to develop a simple and convenient one-pot methodology for the synthesis of ketones from carboxylic acids. Our objective was to build up a carboxylic acid-based chemical template where various types of organometallic reagents can interact to produce the desired ketone. Methods: In this procedure, a carboxylic acid was converted to a mixed anhydride using mesyl chloride in the presence of a base. This mixed anhydride was then reacted with a suitable organometallic reagent at -20°C to obtain the desired ketone. The reaction was performed in a one-pot fashion. Results: Under the optimized reaction conditions, various aromatic and heteroaromatic carboxylic acids were converted to the corresponding ketones using organolithium and organomagnesium reagents with short reaction times. Moderate to good yields of the desired ketones were observed in many of these transformations. Conclusion: A simple and convenient one-pot method for the conversion of carboxylic acids to ketones has been reported. Specifically, various aromatic and `heteroaromatic carboxylic acids have been converted to the corresponding ketones in moderate to good yields. Organomagnesium and organolithium reagents were used as nucleophiles for this reaction.