Reactions of Alkylnitrosoureas in Aqueous Solution

Article abstract of DOI:10.1021/jo01298a048

The acid- and base-catalyzed decompositions of N-methyl-, N,N'-dimethyl-, and N,N',N'-trimethyl-N-nitrosourea in aqueous solution have been studied.Below pH 2, the N-methyl compound undergoes both denitrosation and hydrolysis.The denitrosation yields methylurea and nitrous acid.The hydrolysis yields largely methylamine, nitrogen, and carbon dioxide.The acid-catalyzed denitrosation and hydrolysis of the trimethylnitrosourea are somewhat more rapid than the corresponding reactions of N-methyl-N-nitrosourea.The denitrosation of this compound yields trimethylurea and nitrous acid.The hydrolysis yields methanol, dimethylamine, nitrogen, and carbon dioxide.The solvent isotope effect, k_H2O / k_D2O = 1.3, and the absence of chloride ion catalysis suggest that the denitrosation reaction proceeds by a rate-determining proton transfer which is followed by the rapid loss of the nitroso group.The results for the hydrolysis reaction are compatible with a formulation in which a hydrate of the nitrosourea is protonated in a rate-determining step to form a tetrahedral intermediate which subsequently decomposes to yield methyldiazonium hydroxide and a carbamic acid derivative.The base-catalyzed reactions of the mono-, di-, and trimethylnitrosoureas are first order in hydroxide ion over a broad pH range.The hydrolysis of N-methyl-N-nitrosourea yields methanol and derivatives of carbamic acid.Salt effects on the reaction rate are negligible except for the influence of lithium ion.The rate constants for the hydrolysis of the mono- and dimethyl compounds depend upon the buffer concentration at pH 9.5.These constants reach limiting values.The rate constants for the hydrolysis of the trimethyl compound alsodepend upon the buffer concentration, but a limiting value is not achieved.The solvent isotope effect for the base-catalyzed reaction, the exchange reaction of water-18O with the carbonyl group of the urea, and the fact that N-methyl-N-nitrosourea is hydrolyzed about 2.210⁴ times more rapidly than N,N',N'-trimethyl-N-nitrosourea suggest that the hydrolysis occurs by a mechanism in which a tetrahedral intermediate is formed.Often, the formation of this intermediate is rate limiting.However, under certain conditions, its decomposition to methyldiazonium hydroxide and a carbamate anion which decompose to form methanol and the other products may be rate determining.