Inhibition of nitrosation by the reaction medium

The nitrosation of N-methyl-, N-ethyl-, N-propyl-, and N-butylurea in water-acetonitrile mixtures in acid medium was studied. Kinetic monitoring of the reactions was accomplished by spectrophotometric analysis at 249 nm of the N-alkyl-N-nitrosoureas formed. When the percentage of acetonitrile was increased up to approximate to 50% (i) the nitrosation rate constant decreased and (ii) the reactivity of different nitrosatable substrates converged. The first of these effects can be rationalized in terms of a mechanism whose slow kinetic step is proton transfer from protonated N-alkyl-N-nitrosourea to the water of the reaction medium. The second effect can be explained by assuming that the folding of the hydrophobic alkyl group of the substrates decreases when the permittivity of the reaction medium diminishes. The finding of two isokinetic relationships supports the idea of a common reaction mechanism over the whole range of compositions of the solvent mixture. As a conclusion it is shown that, under these circumstances, the nitrosation of N-alkylureas can be strongly inhibited by lowering the dielectric constant of the reaction medium.