View PDF Version
 
DOI: 10.1039/A803858I (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 2, 1998, 1869-1876

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

(Note: The full text of this document is currently only available in the PDF Version )

Severino Amado, Andrew P. Dicks and D. Lyn H. Williams

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 (KN) 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 KN 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.

References

  1. P. R. Myers, R. L. Minor, R. Guerra, J. N. Bates and D. G. Harrison, Nature, 1990, 345, 161 CAS; J. S. Stamler, O. A. Jaraki, J. A. Osborne, D. I. Simon, J. F. Keaney, D. J. Singel, C. R. Valeri and J. Loscalzo, Proc. Natl. Acad. Sci. USA, 1992, 89, 7674 CAS.
  2. A. P. Dicks, H. R. Swift, D. L. H. Williams, A. R. Butler, H. H. Al-Sadoni and B. G. Cox, J. Chem. Soc., Perkin Trans. 2, 1996, 481 RSC.
  3. P. Herves and D. L. H. Williams, Chem. Commun., 1997, 89 RSC.
  4. D. J. Barnett, A. Rios and D. L. H. Williams, J. Chem. Soc., Perkin Trans. 2, 1995, 1279 RSC.
  5. A. P. Munro and D. L. H. Williams, unpublished results.
  6. S. P. Singh, J. Wishnock, M. Keshive, W. M. Deen and S. R. Tannenbaum, Proc. Natl. Acad. Sci. USA, 1996, 93, 14 428 CrossRef CAS.
  7. T. Komiyama and K. Fujimori, Bio. Med. Chem. Lett., 1997, 7, 175 Search PubMed.
  8. A. P. Dicks, E. Li, A. P. Munro, H. R. Swift and D. L. H. Williams, Can. J. Chem., 1998, 76 CrossRef CAS , in the press.
  9. D. L. H. Williams, Nitrosation, Cambridge University Press, Cambridge, 1988, ch. 7, pp. 173–180 Search PubMed.
  10. J. Barrett, D. F. Debenham and J. Glauser, J. Chem. Soc., Chem. Commun., 1965, 248 RSC.
  11. R. A. Jones and A. R. Katritzky, J. Chem. Soc., 1958, 3610 RSC.
  12. A. Albert and G. B. Barlin, J. Chem. Soc., 1959, 2384 RSC.
  13. M. S. Garley and G. Stedman, J. Inorg. Nucl. Chem., 1981, 43, 2863 CAS.
  14. J. R. Leis, M. E. Pena, D. L. H. Williams and S. D. Mawson, J. Chem. Soc., Perkin Trans. 2, 1988, 157 RSC.
  15. D. L. H. Williams, Nitrosation, Cambridge University Press, Cambridge, ch. 1, pp. 10–16 Search PubMed.
  16. D. A. Wink, J. F. Darbyshire, R. W. Nims, J. E. Saavedra and P. C. Ford, Chem. Res. Toxicol., 1993, 6, 23 CrossRef CAS.
  17. B. R. Penfold, Acta Crystallogr., 1953, 6, 707 CrossRef CAS.
  18. S. Stoyanov, I. Petkov, L. Antonov, T. Stoyanova, P. Karagiannidis and P. Aslanidis, Can. J. Chem., 1990, 68, 1482 CAS.
  19. A. E. Werner, J. Chem. Soc., 1912, 101, 2180 Search PubMed.
  20. K. Al-Mallah, P. Collings and G. Stedman, J. Chem. Soc., Dalton Trans., 1974, 2469 RSC.
  21. P. Collings, K. Al-Mallah and G. Stedman, J. Chem. Soc., Perkin Trans. 2, 1975, 1734 RSC.
  22. D. H. L. Williams, Nitrosation, Cambridge University Press, Cambridge, ch. 1, pp. 8–10 Search PubMed.
  23. J. H. Ridd, Adv. Phys. Org. Chem., 1978, 16, 1 CAS.
  24. I. D. Biggs and D. L. H. Williams, J. Chem. Soc., Perkin Trans. 2, 1975, 107 RSC.
  25. P. Collings, M. Garley and G. Stedman, J. Chem. Soc., Dalton Trans., 1981, 331 RSC.
  26. M. S. Garley, G. Stedman and H. Miller, J. Chem. Soc., Dalton Trans., 1984, 1959 RSC.
  27. T. A. Meyer and D. L. H. Williams, J. Chem. Soc., Perkin Trans. 2, 1981, 361 RSC.
  28. T. Bryant, D. L. H. Williams, M. H. H. Ali and G. Stedman, J. Chem. Soc., Perkin Trans. 2, 1986, 193 RSC.
  29. L. R. Dix and D. L. H. Williams, J. Chem. Res. (S), 1984, 96 Search PubMed.