Abstract
Ester compounds, widely found in pharmaceutical and natural products, play a crucial role in organic synthesis, prompting the development of numerous methods for their synthesis. An important chemical approach in synthesizing esters from carboxylic acids involves the activation of the carboxyl function, requiring the conversion of the hydroxyl group into a suitable leaving group. This paper presents the findings of our investigations into an efficient method for producing esters from carboxylic acids and alcohols, using the Lewis acid titanium tetrachloride. Titanium tetrachloride has proven highly effective as a coupling reagent for the one-pot formation of esters from carboxylic acids and alcohols operating under mild and neutral conditions. Notably, the reaction eliminates the need for bases, yielding carboxylic esters in high purity and yields. The method is efficient, even with long-chain carboxylic acids, and operates well with primary alcohols in dichloromethane. Steric hindrance, potentially present in carboxylic acids, has a moderate effect on the reaction. Alcohol substrates that easily form stable carbocations require, instead, the use of non-polar solvents like hexane for the reaction.