The hydrolysis of azetidinyl amidinium salts. Part 2. Substituent effects, buffer catalysis, and the reaction mechanism

Abstract

The hydrolysis of azetidin-2-ylideneammonium salts gives a mixture of β-lactams, by exocyclic C–N bond fission, and β-amino amides, by endocyclic C–N bond breakage and opening of the four-membered ring. The reaction is general-base catalysed and more β-lactam is formed using a less basic buffer. The mechanism of the buffer-catalysed reaction is the general-acid-catalysed breakdown of a reversibly formed neutral tetrahedral intermediate. The Brønsted α-values vary with substituents in the amidinium salt so that they decrease with increasing electron withdrawal in the nitrogen amine which is expelled. Electron-withdrawing substituents attached to either nitrogen of the amidinium salt favour expulsion of that leaving-group amine. The Brønsted β_1g for endocyclic C–N bond fission and β-amino amide formation is –0.52 whereas that for exocyclic C–N bond fission and β-lactam formation is –0.83. Substituent effects on the nitrogen amine which is not expelled but forms the product amide or β-lactam generate β_p values of –0.71 and –0.07, respectively. Changes in structure–reactivity relationships with substituents are examined by an analysis of the reaction mechanism.