Chemistry of nitrosoureas. Intermediacy of 4,5-dihydro-1,2,3-oxadiazole in 1,3-bis(2-chloroethyl)-1-nitrosourea decomposition

Abstract

A new product, ethylene glycol, was identified from BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] decomposition. The variation of ethylene glycol yield with pH indicates that there are two competing mechanisms of decomposition. At pH 7.4 the decomposition is predominantly through 2-chloroethyldiazohydroxide, an chloroethanol and acetaldehyde are the major products. At pH 5, the decomposition is predominantly through 4,5-dihydro-1,2,3-oxadiazole and 2-hydroxyethyldiazohydroxide, and ethylene glycol and acetaldehyde are the major products. Deuterium labeling shows that at both pH's the acetaldehyde arises through a mechanism involving a hydride shift. At pH 5 in the presence of bromide, 2-bromoethanol is a major product and deuterium labeling shows that the hydroxyl is predominantly on the carbon which bore the chlorine in BCNU.