General base catalysis in acidic solutions. Acceleration of intramolecular phosphonate-assisted amide hydrolysis

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Abstract
The hydrolysis of the amide linkage of 2′-phosphonobenzanilide, 1, occurs with nucleophilic assistance from the adjacent phosphonic acid moiety. The basic component of buffers in acidic solutions provides additional rate acceleration. A Brønsted plot yields a straight line for buffers of phosphoric acid, cyanoacetic acid, chloroacetic acid, and dichloroacetic acid with [Formula: see text]. It is suggested that the second acidic group of the phosphonic acid of 1 dissociates upon formation of an addition intermediate, leading to a zwitterion (T±). This zwitterionic intermediate decomposes in the rate-determining step, with added base or water removing a proton from a hydroxyl group of the intermediate. The product is a mixed phosphonic–carboxylic anhydride which hydrolyzes rapidly. It is concluded that a phosphoric acid derivative is a particularly good catalyst for this type of reaction since a stabilized intermediate can be internally generated along the reaction coordinate.

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