Carboxylic acid activation - Acyl chloride
Abstract
Carboxylic acids are poor electrophiles in their native form due to the resonance delocalization of the carboxylate that reduces the electrophilicity of the carbonyl carbon. Activation consists of converting the -OH into a better leaving group, generating a more reactive acyl electrophile toward nucleophiles (amines, alcohols, organometallics, etc…). Beyond the existing methods to activate a carboxylic acid, one consists in converting it into the corresponding acyl chloride using thionyl chloride (SOCl2).
Keywords
Carboxylic acid, Activation, Acyl chloride
Category
Carboxylic acid
Mechanism
Mechanistically, the carbonyl oxygen of the carboxylic acid attacks the electrophilic sulfur atom of SOCl2, displacing a chloride ion and forming a chlorosulfite intermediate. The chloride ion then attacks the carbonyl carbon, generating a tetrahedral intermediate. This intermediate subsequently collapses, yielding the acyl chloride and expelling the chlorosulfite leaving group. The expelled chlorosulfite fragment then decomposes into SO2 and HCl gases, thermodynamically driving the reaction to completion.
