Kinetics and mechanism of the nitrosation of 2-mercaptopyridine [pyridine-2(1H)-thione]

Abstract

2-Mercaptopyridine (MP) reacts rapidly with nitrous acid in mildly acid aqueous solution (via the thione tautomer) to give an unstable S-nitroso ion (SNO⁺) in a reversible process with an equilibrium constant (K_N) of ca. 1 × 10⁵ dm⁶ mol^–2. SNO⁺ is readily detected by two peaks in the UV spectrum at 295 and 240 nm with extinction coefficients 9600 and 9300 dm³ mol^–1 cm^–1 respectively. MP is regenerated when the solution is made alkaline. Kinetic measurements made on the nitrosation reaction give a value of 8200 dm⁶ mol^–2 s^–1 for the third order rate constant k₃ (defined by rate = k₃ [MP] [HNO₂] [H⁺]), which is close to that believed to be the diffusion-controlled limit for attack by NO⁺ (or H₂NO₂⁺). As expected there is marked catalysis by Cl^– and Br^–, and analysis of the kinetic results obtained from variation of measured rate constants with [halide ion] gave values of 3.5 × 10⁹ and 3.7 × 10⁹ dm³ mol^–1 s^–1 respectively for the bimolecular rate constants for NOCl and NOBr reactions with MP, again values close to the diffusion limit. The same experimental results also yielded values of 30 and 2400 dm³ mol^–1 s^–1 for the second order rate constants, for the reverse process of Cl^– and Br^– reaction with SNO⁺. Values for K_N of 1.3 × 10⁵ and 7.9 × 10⁴ dm⁶ mol^–2 were obtained from the halide catalysed reactions. In acid solution SNO⁺ decomposed to the disulfide (2,2′-dipyridyl disulfide) and NO (measured with a NO-electrode). Quenching of SNO⁺ at pH 7.4 gave UV spectroscopic evidence for the neutral deprotonated form (SNO) of SNO⁺ and there was a transformation to give mainly MP together with some disulfide. There was clear evidence that SNO⁺ (and maybe SNO) can act as an efficient nitrosating species: addition of the thiol N-acetylcysteine (at pH 6.15) resulted in the almost instantaneous decomposition of SNO. Addition of N-methylaniline (NMA) to an acidified solution of SNO⁺ resulted in quantitative N-methyl-N-nitrosoaniline formation and kinetic measurements of the nitrosation of NMA in the presence of MP showed marked catalysis at low [MP], which disappeared at higher [MP]. These results are quantitatively consistent with nitrosation via SNO⁺: catalysis disappears at higher [MP] when the nitrous acid is virtually completely converted to SNO⁺. A value of 1.7 × 10⁵ dm³ mol^–1 s^–1 was obtained for the bimolecular rate constant for reaction of SNO⁺ with the free base form of NMA. MP is thus an excellent catalyst for electrophilic nitrosation. Under somewhat different conditions SNO⁺ can then act as a source of HNO₂/NO₂^–, NO or NO⁺. The chemistry reported in this paper bears many similarities to that involved in the nitrosation of thioureas, and subsequent reactions of the S-nitrosothiouronium ions.