The reactivity of thiourea, alkylthioureas, cysteine, glutathione, S-methylcysteine, and methionine towards N-methyl-N-nitrosoaniline in acid solution

Abstract

Thiourea and several alkylthioureas have very nearly the same rate constants for their reactions with N-methyl-N-nitrosoaniline in sulphuric acid containing hydrazine sulphate. The results are consistent with an initial S-nitrosation in which there is no significant delocalisation of the positive change to the amino-nitrogen atom in the transition state. For thiourea the detailed form of the acid catalysis is established, both H₀ and H₀‴ acidity functions represent the initial protonation reasonably well. In the same reaction cysteine and glutathione have a small but measurable reactivity, which is comparable with that of chloride ion, whilst the effect of S-methylation (for S-methylcysteine and methionine) is to increase the rate constant for S-nitrosation by a factor of ca. 20, to about the same value as found for bromide ion. Alanine is totally unreactive under these conditions, a result which supports S-rather than N-nitrosation.