Direct synthesis of 2-(benzylamino)benzoic acids by using benzaldehydes and 2-aminobenzoic acids with catalysis of p-toluenesulfonic acid

Direct reductive amination of carbonyl compounds is a promising method for the synthesis of amine derivatives. Usually, stoichiometric reducing agents generate significant waste products, some of which are hazardous and difficult to handle. Therefore, it is highly desirable to synthesize amines using reducing agents that cause low environmental pollution and minimize hazardous by-products. In this work, It was discovered that substituted benzaldehydes and substituted 2-aminobenzoic acids can be directly converted into substituted 2-(benzylamino)benzoic acids using p-toluenesulfonic acid (TsOH) as a catalyst in a one-pot method, where the only by-product is substituted benzoic acid. The reaction mechanism was investigated, and the results showed that the Schiff base's carbon-nitrogen double bond is reduced by benzaldehyde under TsOH catalysis, resulting in 2-(benzylamino)benzoic acid. This phenomenon was not observed previously. The advantage of this method lies in its mild reaction conditions, as it requires neither metal catalysis nor additional reducing agents.