The mechanism of hydrolysis and ethylaminolysis of N-benzoylglycine and N-benzoylsarcosine esters

Abstract

The hydrolysis and ethylaminolysis of N-benzoylglycine and N-benzoylsarcosine esters have been studied for a range of leaving hydroxy-functions with pK_a from 5.45 to 15.5. Ethylaminolysis of N-benzoylglycinate esters involves kinetic terms in [EtNH₂] and [EtNH₂][OH^–]. The mechanism of ethylaminolysis of the glycinates does not involve the oxazolinone intermediate as a major contributor to the reaction flux; more than 99% of oxazolinone formed is partitioned to amide. The reactions studied encompass Class I, II, and III mechanisms as demonstrated by characteristic ‘S-shaped’ Brønsted profiles. The absence of kinetic terms in [EtNH₂]² is taken as evidence for a concerted formation of anionic tetrahedral intermediate (T^–) from hydroxide-assisted attack of ethylamine on N-benzoylglycinate ester. The hydrolysis of 2-chloro-4-nitrophenyl N-benzoylsarcosinate in neutral solution involves an intermediate; this is shown not to be the N-methylphenyloxazolinone cation but results from intra-molecular attack of the neutral amide on the activated aromatic nucleus.