The nitrosation of N ‐alkylureas: Evidence for a proton transfer mechanism

The kinetics of the nitrosation of methyl, ethyl, propyl, butyl, and allyl urea were studied by conventional and stopped‐flow spectrophotometry in the presence or absence of acetate or mono‐, di‐, or trichloroacetate anions. In the presence of a large excess of urea, the observed rate equation was $$v={{\rm [urea][nitrite][H^{+}]^2}\over{\rm K_a + [H^{+}]}} \left(\vartheta+\xi{{\rm K_R[carboxylic\ acid]}\over{\rm K_R+[H^{+}]}}\right)$$ where K a is the acidity constant of nitrous acid and K R that of the carboxylic acid. The ureas exhibited the reactivity order methylurea ≫ (ethylurea ≅ propylurea ≅ butylurea) ≫ allylurea. Experiments in D 2 O afforded values of k   H   2 O/ k   D   2 Oin general agreement with the values 4.1–5.5 predicted by a semiclassical transition state theory of kinetic isotope effects [i.e., k H   2 O / k   D   2 O= exp(0.130 h v⌅/ kT )], where v⌅ is the frequency of R 3 NH stretching (2700–2250 cm −1 ) in the protonated urea. This result, the observed catalysis by carboxylate ions and the value of the Bronsted parameter β(0.45) show the rate‐controlling step of these reactions to be the transfer of a proton from the protonated N ‐alkyl‐ N ‐nitrosourea to the solvent or to the organic anion, if present. The observed order of substrate reactivities is explicable in terms of the capacity of the protonated N ‐alkyl‐ N ‐nitrosourea for forming a hydrogen bond with the water molecule to which the proton will be transferred, and the degree to which the formation of such bonds is hindered by the hydrophobic alkyl chain of the nitrosourea. © 1996 John Wiley & Sons, Inc.