Kinetic study of the neutral and base hydrolysis of diketene

摘要

Diketene (4-methylene-2-oxetanone) is inactive as a carcinogen, although it is more reactive toward nucleophiles than the analogs beta-propiolactone and beta-butyrolactone, both of which are alkylating agents of known carcinogenicity. In the literature the lack of carcinogenic effects has been ascribed to the rapid hydrolysis of diketene, which could preclude its in vivo alkylating capacity. In this work, the kinetics of the neutral and alkaline hydrolysis of diketene in aqueous and different water-dioxane media have been studied. The following conclusions can be drawn: (i) The neutral hydrolysis of diketene is slightly faster than that of beta-propiolactone and beta-butyrolactone. (ii) The hydrolysis reaction of diketene is very slow when compared to its alkylation reaction of a DNA-model nucleophile, suggesting that, contrary to earlier results, competitive hydrolysis is not the cause of its lack of carcinogenicity. (iii) The diketene neutral hydrolysis rate constant increases with the water/dioxane ratio, the opposite occurring in base hydrolysis.