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

The hydrolysis of azetidin-2-ylideneammonium salts gives a mixture of -lactams, by exocyclic C–N bond fission, and -amino amides, by endocyclic C–N bond breakage and opening of the four-membered ring. The reaction is general-base catalysed and more -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 -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 1g for endocyclic C–N bond fission and -amino amide formation is –0.52 whereas that for exocyclic C–N bond fission and -lactam formation is –0.83. Substituent effects on the nitrogen amine which is not expelled but forms the product amide or -lactam generate 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