Chapter 3 The Hydrolysis of Carboxylic Acid Derivatives

This chapter discusses the kinetics and mechanisms of the hydrolysis of carboxylic acid derivatives of general formula RCOX. These include carboxylic acid halides, amides, and anhydrides with small sections on carboxylic acid cyanides. The chapter presents some of the principles involved in the hydrolysis of carboxylic acid derivatives and deals with the more recent mechanistic studies. The addition of a nucleophile to a carbonyl group is aided by the polarization of the carbonyl group. The bond broken is a carbon–oxygen pi bond, weaker than a carbon–carbon pi bond. The steric hindrance is considerably reduced in comparison with both alkenes and alkyl halides by the ability of the nucleophile to interact with the carbon atom at right angles to the axis of the pi bond. However, the detection of the tetrahedral intermediate in the addition of a nucleophile to an ester, acid halide, amide, or anhydride must be adduced from kinetic evidence, in particular the evidence of oxygen exchange in such an intermediate. Such tracer work has established the presence of symmetrical addition compounds in the hydrolysis of esters, amides, and acid chlorides.