NUCLEOPHILIC-ATTACK VS GENERAL BASE ASSISTED HYDROLYSIS IN THE REACTIONS OF ACETIC-ANHYDRIDE WITH PRIMARY AND SECONDARY-AMINES - PH-YIELD STUDIES IN THE RECOGNITION AND ASSESSMENT OF THE NUCLEOPHILIC AND GENERAL BASE REACTIONS

The reaction of a set of primary and secondary amines with acetic anhy dride in water at 25 degrees C gave variable yields of the N-substitut ed acetamide in seven of the eight amines studied. The yield of the am ide as a function of pH revealed the incursion in most cases of a gene ral base assisted hydrolysis of the acetic anhydride by the amine. Fro m the pK(a)'s of the amines and k(W) and k(OH) for acetic anhydride (t he specific rates for the reaction of the anhydride with water and hyd roxide, respectively), both k(DN) (for the formation of the acetamides ) and k(GB) (for the general base assisted hydrolysis) may be readily evaluated by fitting the pH-yield data to pH-yield or pH-product ratio profiles. The reactions of ethyl chloroformate with aniline and benzy lamine in water also showed the presence of the general base assisted reaction. It is concluded that (a) pH-yield data provide a new way of showing the existence of a general base assisted hydrolysis in the pre sence of a direct nucleophilic displacement reaction, (b) the general base promoted reaction is sufficiently prevalent that it would be prud ent to check specifically for its presence in any investigation of mec hanisms of acyl transfer in water, and (c) until the extent of general base promoted hydrolysis can be predicted adequately, the possibility of such a reaction makes it difficult to predict yields of the produc ts of the direct attack, and hence just how suitable a medium water ma y be for a particular preparative acyl transfer reaction.