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

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