Kinetics and mechanism of the nitrosation of alcohols, carbohydrates, and a thiol

Abstract

Rate constants have been determined by stopped-flow spectrophotometry for the nitrosation in water of the following alcohols and carbohydrates : methanol, ethanol, propan-1-ol, propan-2-ol, ethane -1,2-diol, propane1,2,3-triol, mannitol, sucrose, and glucose, in some cases at 25° and others at O°. In all cases the reactions were reversible, forming equilibrium concentrations of the corresponding alkyl nitrites. With a large excess of the alcohol present over the total nitrous acid concentration, the observed first-order rate constants increased linearly with the alcohol concentration, and from the slope and the intercept the rate constants for the forward and reverse reactions were obtained. Both reactions were acid-catalysed and also catalysed by chloride and bromide ion. The forward reaction is interpreted as one involving O-nitrosation by H₂NO₂⁺(or NO⁺), NOCl, or NOBr. For methanol, rate constants for attack by nitrosyl chloride and by nitrosyl bromide were 2.1 × 10⁵ and 2.0 × 10⁴ l mol^–1 s^–1, respectively. There was little difference between the rate constants for chloride ion and bromide ion attack for the reverse reaction, suggesting that the reactions for attack on the protonated alkyl nitrite are very rapid, possibly approaching the diffusion-controlled limit. There was a decrease in the overall equilibrium constant for the non-halide ion-catalysed pathway, along the series MeOH, EtOH, PrⁱOH, and Bu^tOH; the value for the latter was so small as to make the quantitative determination of the rate constants impossible by this method. This decrease was due almost entirely to a decreasing value for the forward rate constant along the series, which implies that a steric effect is operational. All the carbohydrates studied had very similar equilibrium constants of ca. 1.5. In contrast the nitrosation of N-acetylpenicillamine gave the thionitrite quantitatively at low acidities. Again the reaction was acid- and halide (and thiocyanate) ion-catalysed and the reactivity sequence NOCl > NOBr > NOSCN was established. For both the alcohols and the thiol, the forward rate constants are well below the diffusion controlled values and are several powers of ten less than the corresponding values for the reactions of aniline. The results are discussed in terms of the nucleophilicities of the oxygen and sulphur sites for the forward reaction and in terms of the protonation equilibria of the nitrites and thionitrite for the reverse reaction.