Substituent, Temperature and Solvent Effects on the Keto-Enol EQUILIBRIUM in β-Ketoamides: A Nuclear Magnetic Resonance Study


Substituent, temperature and solvent effects on tautomeric equilibria in several β-ketoamides have been investigated by means of nuclear magnetic resonance spectroscopy (NMR). Keto-enol equilibrium predominates over the amide-imidol one. The relative stability of the individual tautomers and the corresponding equilibrium shifts are explained considering electronic and steric effects and tautomer stabilization via internal hydrogen bonds. In solution, these compounds exist mainly as ketoamide and Z-enolamide tautomers, both presenting intramolecular hydrogen bonds.

Share and Cite:

S. Laurella, M. Sierra, J. Furlong and P. Allegretti, "Substituent, Temperature and Solvent Effects on the Keto-Enol EQUILIBRIUM in β-Ketoamides: A Nuclear Magnetic Resonance Study," Open Journal of Physical Chemistry, Vol. 3 No. 4, 2013, pp. 138-149. doi: 10.4236/ojpc.2013.34017.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] J. W. Bunting and J. P. Kanter, “Acidity and Tautomerism of β-Keto-Esters and Amides in Aqueous-Solution,” Journal of the American Chemical Society, Vol. 115, No. 25, 1993, pp. 11705-11715.
[2] K. Yamasaki and O. Kajimoto, “Solvent Effect in Supercritical Fluids: Keto-Enol Equilibria of Acetylacetone and Ethyl Acetoacetate,” Chemical Physics Letters, Vol. 172, No. 3-4, 1990, pp. 271-274.
[3] D. L. Ruiz, A. G. Albesa, A. Ponzinibbio, P. E. Allegretti and M. M. Schiavoni, “Solvent Effects on Tautomerics Equilibria in β-Ketonitriles: NMR and Theoretical Studies,” Journal of Physical Organic Chemistry, Vol. 23, No. 10, 2010, pp. 985-994.
[4] M. J. Hynes and E. M. Clarke, “Kinetics of Enolisation of β-Ketoamides,” Journal of the Chemical Society, Perkin Transactions 2, No. 4, 1994, pp. 901-904.
[5] H. Wengenroth and H. Meier, “(E)-und (Z)-Enole von β-Ketocarbons?ureamiden,” Chemische Berichte, Vol. 123, No. 6, 1990, pp. 1403-1409.
[6] M. M. Naoum and G. R. Saad, “Solvent Effect on Tautomeric Equilibria and Dipole Moments of Some Alpha Substituted Benzoylacetanilides,” Journal of Solution Chemistry, Vol. 17, No. 1, 1998, pp. 67-76.
[7] R. E. Valters, F. Fülop and D. Korbonits, “Recent Developments in Ring-Chain Tautomerism. II. Intramolecular Reversible Addition Reactions to the C=N, C=N, C=C, and C=C Groups,” Advances in Heterocyclic Chemistry, Vol. 66, 1996, p. 1.
[8] L. Lázár and F. Fülop, “Recent Developments in the Ring-Chain Tautomerism of 1,3-Heterocycles,” European Journal of Organic Chemistry, Vol. 2003, No. 16, 2003, pp. 3025-3042.
[9] L. Lázár, A. Goblyos, F. Evanics, G. Bernáth and F. Fülop, “Ring-Chain Tautomerism of 2-Aryl-Substituted Imidazolidines,” Tetrahedron, Vol. 54, No. 44, 1998, pp. 13639-13644.
[10] A. Goblyos, L. Lázár, F. Evanics and F. Fülop, “Ring-Chain Tautomerism of 2-Aryl-Substituted Imidazolidines,” Heterocycles, Vol. 51, No. 10, 1999, pp. 2431-2438.
[11] K. N. Zelenin, V. V. Alekseyev, I. V. Ukraintsev and I. V. Tselinsky, “2-Substituted Hexahydropyrimidines and Their Tautomerism,” Organic Preparations and Procedures International, Vol. 30, No. 1, 1998, pp. 53-61.
[12] A. Goblyos, L. Lázár and F. Fülop, “Ring-Chain Tautomerism of 2-Aryl-Substituted-Hexahydropyrimidines and Tetrahydroquinazolines,” Tetrahedron, Vol. 58, No. 5, 2002, pp. 1011-1016.
[13] O. Maloshitskaya, J. Sinkkonen, V. V. Ovcharenko, K. N. Zelenin and K. Pihlaja, “Chain-Ring-Chain Tautomerism in 2-Aryl-Substituted Hexahydropyrimidines and 1H-2,3-Dihydroperimidines. Does It Appear?” Tetrahedron, Vol. 60, No. 32, 2004, pp. 6913-6921. j.tet.2004.05.092
[14] J. Sinkkonen, K. N. Zelenin, A. K. Potapov, I. V. Lagoda, V. V. Alekseyev and K. Pihlaja, “Ring-Chain Tautomerism in 2-Substituted 1,2,3,4-Tetrahydroquinazolines A1H, 13C and 15N NMR Study,” Tetrahedron, Vol. 59, No. 11, 2003, pp. 1939-1950.
[15] R. M. Claramunt, C. López, M. D. Santa María, D. Sanz and J. Elguero, “The Use of NMR Spectroscopy to Study Tautomerism,” Progress in Nuclear Magnetic Resonance Spectroscopy, Vol. 49, No. 3-4, 2006, pp. 169-206.
[16] M. T. Barros, C. F. G. C. Geraldes, C. D. Mavcock and M. I. Silva, “A Proton and 13C NMR Study of Keto-Enol Tautomerism of Some β-Ketoamides,” Journal of Molecular Structure, Vol. 142, 1986, pp. 345-349.
[17] S. Laurella, M. González Sierra, J. Furlong and P. Allegretti, “Analysis of Tautomerism in β-Ketobuanamides by Nuclear Magnetic Resonance: Substituent, Temperature and Solvent Effects,” Journal of Applied Solution Chemistry and Modeling, Vol. 1, 2012, pp. 6-12.
[18] C. R. Hauser and C. J. Eby, “Cyclization of β-Ketonitriles or β-Ketoamides with Ketones by Polyphosphoric Acid to Form Substituted 2-Pyridones,” Journal of the American Chemical Society, Vol. 79, No. 3, 1957, pp. 728-731.
[19] S. L. Laurella, C. V. Latorre, R. C. Dietrich, J. J. P. Furlong and P. E. Allegretti, “Tautomeric Equilibria Analysis of β-Ketoamides by Mass Spectrometry,” Journal of Physical Organic Chemistry, Vol. 25, No. 12, 2012, pp. 1365-1373.
[20] Z. Rappoport and S. Biali, “Stable Simple Enols. 9. Solid State Structures and Conformations of Several Simple Enols and Their Keto Tautomers,” Journal of the American Chemical Society, Vol. 105, 1985, pp. 1701-1709.
[21] A. R. Miller, “Sterically Stabilized Enols: A Study Employing the Internal Rotational Barriers of the Destabilized Ketones,” The Journal of Organic Chemistry, Vol. 41, No. 22, 1976, pp. 3599-3602.
[22] E. B. Starikov and B. Nordén, “Entropy-Enthalpy Compensation as a Fundamental Concept and Analysis Tool for Systematical Experimental Data,” Chemical Physics Letters, Vol. 538, 2012, pp. 118-120.
[23] S. H. Gellman, G. P. Dado, G. Liang and B. R. Adams, “Conformation-Directing Effects of a Single Intramolecular Amide-Amide Hydrogen Bond: Variable-Temperature NMR and IR Studies on a Homologous Diamide Series,” Journal of the American Chemical Society, Vol. 113, No. 4, 1991 pp. 1164-1173.
[24] A. Lammermann, I. Szatmári, F. Fülop and E. Kleinpeter, “Interor Intramolecular N···H-O or N-H···O Hydrogen Bonding in 1,3-Amino-α/β-naphthols: An Experimental NMR and Computational Study,” The Journal of Physical Chemistry A, Vol. 113, No. 21, 2009, pp. 6197-6205. 10.1021/jp902731n

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.