An efficient and scalable approach to the synthesis of 3,5-dichlorobenzoic acid

Abstract

3,5-Dichlorobenzoic acid is a crucial intermediate with extensive applications in pharmaceuticals, agrochemicals and the chemical industries. Conventional synthetic methods typically involve harsh reaction conditions, exhibit poor regioselectivity, and raise environmental concerns. Here, a three-step synthetic approach starting from p-chlorobenzoic acid has been developed for the synthesis of 3,5-dichlorobenzoic acid, without chromatographic purification. The synthetic route includes efficient amination to form p-aminobenzoic acid, selective dichlorination guided by the amino group, and a mild diazo deamination reaction. The entire synthetic process utilizes commercially available and cheap starting materials, features simple operation and high purity, and affords a total yield of over 60%, showing great potential for industrial production. This offers an optimal green synthetic route for this type of key intermediate.