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 Assessement of the Nucleophilic and General Base Reactions

Article abstract of DOI:10.1021/jo00084a029

The reaction of a set of primary and secondary amines with acetic anhydride in water at 25 deg C gave variable yields of the N-substituted acetamide in seven of the eight amines studied.The yield of the amide as a function of pH revealed the incursion in the most cases of a general base assisted hydrolysis of the acetic anhydride by the amine.From the pK_a's of the amines and k_w and k_OH for acetic anhydride (the specific rates for the reaction of the anhydride with water and hydroxide, respectively), both k_DN (for the formation of 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 benzylamine 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 general base assisted hydrolysis in the presence of a direct nucleophilic displacement reaction, (b) the general base promoted reaction is sufficiently prevalent that it would be prudent to check specifically for its presence in any investigation of mechanisms 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 products of the direct attack, and hence just how suitable a medium water may be for a particular preparative acyl transfer reaction.