Determination of isotope effects on acid–base equilibria by ¹³C NMR spectroscopy

Abstract

New results from isotope effect measurements on acid–base equilibria by ¹³C NMR spectroscopy show that in fatty acids deuterium isotope effects extend at least up to seven bonds and have unexpectedly small attenuation. In deuterium-substituted benzoic acids the isotope effect on pK_a is practically independent of the site of deuterium substitution. ²H isotope effects on carboxy ionization in glycine and alanine are smaller than in the corresponding carboxylic acids. Different protonation shifts in unlabelled and labelled compounds are recorded. ¹⁸O and ¹³C isotope effects in acetic acid and ¹⁵N effects in glycine isotopomers were measured. The application of auxiliary isotope substitution is demonstrated for the measurement of very small differences in pK_a values.

References

1. T. Pehk, E. Kiirend, E. Lippmaa and U. Ragnarsson, J. Chem. Soc., Perkin Trans. 2, 1996, 2351.
2. S. L. R. Ellison and M. J. T. Robinson, J. Chem. Soc., Chem. Commun., 1983, 745.
3. C. L. Perrin and J. D. Thoburn, J. Am. Chem. Soc., 1989, 111, 8010.
4. W. B. Knight, P. M. Weiss and W. W. Cleland, J. Am. Chem. Soc., 1986, 108, 2759.
5. J. P. Jones, P. M. Weiss and W. W. Cleland, Biochemistry, 1991, 30, 3634.
6. D. L. Rabenstein and S. V. S. Mariappan, J. Org. Chem., 1993, 58, 4487.
7. E. A. Halevi, M. Nussim and A. Ron, J. Chem. Soc., 1963, 866.
8. A. Streitwieser Jr. and H. S. Klein, J. Am. Chem. Soc., 1963, 85, 2759.
9. M. Tashiro, K. Nakayama and G. Fukata, J. Chem. Soc., Perkin Trans. 1, 1983, 2315.
10. L. Grehn, T. Pehk and U. Ragnarsson, Acta Chem. Scand., 1993, 47, 1107.
11. B. Halpern and D. E. Nitecki, Tetrahedron Lett., 1967, 3031.
12. L. Lankiewicz, B. Nyasse, B. Fransson, L. Grehn and U. Ragnarsson, J. Chem. Soc., Perkin Trans. 1, 1994, 2503.
13. T. Yonemitsu, H. Tuzuki, S. Mataga and M. Tashiro, Kyushu Sangyo Daigaku Kogakubu Kenkyu Hokoku, 1993, 30, 145; Chem. Abstr., 1995, 122, 9376x.
14. E. Breitmaier, G. Jung, W. Voelter and L. Pohl, Tetrahedron, 1973, 29, 2485.
15. C. K. Ingold, Structure and Mechanism in Organic Chemistry, Cornell University Press, 1969, Table 57-8.
16. L. S. Bartell, J. Am. Chem. Soc., 1961, 83, 3567.
17. F. A. L. Anet, V. J. Basus, A. P. W. Hewett and M. Saunders, J. Am. Chem. Soc., 1980, 102, 3945; T. Pehk, A. Laht and E. Lippmaa, Org. Magn. Reson., 1982, 19, 21.
18. B. Nyasse, L. Grehn and U. Ragnarsson, J. Chem. Soc., Chem. Commun., 1994, 2005.
19. R. P. Bell and W. B. T. Miller, Trans. Faraday Soc., 1963, 59, 1147.