J. Saavedra
Dec 1, 1990
Citations
0
Influential Citations
3
Citations
Journal
Journal of Organic Chemistry
Abstract
Nitrosoureas are compounds of increasing interest due to their carcinogenic and mutagenic activities and for their therapeutic properties in the treatment of cancer. During the course of these studies, it was necessary to synthesize 1-nitroso-1-methyl-3-(2-hydroxyethyl)urea (1) and nitroso-1-(2-hydroxyethyl)-3-methylurea (2). Nitrosation of 1-methyl-3-(2-hydroxyethyl)urea with nitrous acid gave a mixture of 1 and 2 in a 9:1 ratio. Although the mixture decomposed slowly as a neat oil, the pure major isomer 1 was stable in acetone, or ethyl acetate, solution. However, this compound decomposed explosively when in it was handled in its crystalline form, with evolution of nitrogen. Further studies of 1 were abandoned due to its explosive nature; however, the compound's unusual decomposition prompted the authors to look at one of its stable analogues, 1-nitroso-1-ethyl-3-(2-hydroxyethyl)urea. In summary, 1-(nitrosoalkyl)-3-(2-hydroxyalkyl)ureas break under neutral conditions to the corresponding 2-ozazolidone and the alkldiazonium ion. These reactions take place via a nucleophilic attack by the hydroxyl group of the electrophilic urea carbonyl to give a hemiacetal intermediate.