The alkyl halide catalysed pseudomolecular rearrangement of imidates to amides: an explanation for the ambident nucleophilic properties of neutral amides

Abstract

Kinetic studies are reported for the pseudomolecular rearrangement of N-methylbenzimidates to tertiary amides in nitrobenzene at 138°. The reaction is readily catalysed by alkyl halides (rate =k₂[N-methylbenzimidate][alkyl halide]) and is shown to proceed by a two-step mechanism involving a benzimidonium ion intermediate. Formation of this intermediate by an S_N2 reaction between substrate and alkyl halide is rate limiting. Quantitative yields of tertiary amide are usually obtained but, for the isopropyl halide catalysed conversion of isopropyl N-methylbenzimidates, a competitive E2 elimination gives ca. 40% propene and N-methylbenzamide. These results are discussed in relation to the ambident nucleophilic properties of neutral amides. They suggest that alkylation occurs more rapidly at the amide oxygen atom to give an imidate (kinetic product) which then rearranges in the presence of alkyl halide to the N-substituted amide (thermodynamic product). It is shown that silver salts inhibit the imidate–amide rearrangement by precipitating nucleophilic anions. This partly explains the preferential O-alkylation of amides in the presence of silver salts.