Summary
2,4-Dialkyl-5(4H)-oxazolones are well-recognized intermediates in some aminolysis reactions in peptide synthesis. Using the MOPAC molecular orbital programs, detailed geometric and energetic characteristics of the elementary reaction pathways for the additions of water and ammonia to 2-methyl-5(4H)-oxazolone have been determined at the AM1 level. The results demonstrate that the additions must be parsed into a two-step mechanism involving formation of the α-hydroxyimine followed by tautomerization to the parent N-acetylamino acid or amide.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bodanszky, M., Klausner, Y.S. and Ondetti, M.A., Peptide Synthesis, 2nd ed., Interscience, New York, NY, 1976, pp. 85–136.
Kemp, D.S., In Gross, E. and Meienhofer, J. (Eds.) The Peptides, Vol. 1 (Analysis, Synthesis, Biology), Academic Press, New York, NY, 1979, pp. 315–383.
Benoiton, N.L., Kemp, D.S., In Gross, E. and Meienhofer, J. (Eds.) The Peptides, Vol. 5 (Analysis, Synthesis, Biology), Academic Press, New York, NY, 1983, pp. 217–284.
Chen, F.M.F., Kuroda, K. and Benoiton, N.L., Synthesis (1979) 230.
Chen, F.M.F., Kuroda, K. and Benoiton, N.L., Synthesis (1978) 928.
Chen, F.M.F. and Benoiton, N.L., Can. J. Chem., 65 (1987) 619.
Dewar, M.J.S., Zoebisch, E.G., Healy, E.F. and Stewart, J.J.P., J. Am. Chem. Soc., 107 (1985) 3902.
Dewar, M.J.S., Int. J. Quantum Chem., Quantum Chem. Symp., 22 (1988) 557.
Dannenberg, J.J., J. Phys. Chem., 92 (1988) 6869.
Fabian, W.M.F., J. Comput. Chem., 4 (1983) 369.
Higgins, D. and Thomson, C., J. Comput. Chem., 9 (1988) 212.
Lee, I., Cho, J.K. and Lee, B-S., J. Chem. Soc. Perkin Trans. II, (1988) 1319.
Marcos, E.S., Maraver, J.J., Chiara, J.L. and Gómez-Sánchez, A., J. Chem. Soc. Perkin Trans. II, (1988) 2059.
Dannenberg, J.J. and Vinson, L.K., J. Phys. Chem., 92 (1988) 5635.
Galera, S., Llunch, J.M., Oliva, A. and Bertran, J., J. Mol. Struct. (Theochem), 40 (1988) 101.
Stewart, J.J.P., MOPAC: A General Molecular Orbital Package, modified by Eger, M., to suit IBM/370-compatible scalar computers utilizing VS/FORTRAN version 4.1.4. or higher compilers, 1988, QCPE 459.
Koller, J. and Hadzi, D., J. Mol. Struct. (Theochem) 200 (1989) 233.
Bell, R.A., Faggiani, R., Lock, C.J.L. and McLeod, R.A., Can. J. Chem., 63 (1985) 3618.
Harmony, M.D., Laurie, V.W., Kuczkowski, R.L., Schwendeman, R.H., Ramsay, D.A., Lovas, F.J., Lafferty, W.J. and Maki, A.G., J. Phys. Chem. Ref. Data, 8 (1979) 645.
Harmony, M.D., Laurie, V.W., Kuczkowski, R.L., Schwendeman, R.H., Ramsay, D.A., Lovas, F.J., Lafferty, W.J. and Maki, A.G., J. Phys. Chem. Ref. Data 8 (1979) 647.
Clementi, E. and Popkie, H., J. Chem. Phys., 57 (1972) 1077.
Barlett, R.J., Shavitt, I. and Purvis, G.D., J. Chem. Phys., 71 (1979) 281.
Yeo, G.A. and Ford, T.A., J. Mol. Struct. 141 (1986) 331.
IUPAC-IUB Commission on Biochemical Nomenclature, Biochemistry, 9 (1970) 3471.
CRC Handbook of Chemistry and Physics, 51st ed., The Chemical Rubber Co., Cleveland, OH, 1971, pp. E-51–53.
JonesIII, F.M. and Arnett, E.M., Prog. Phys. Org. Chem., 11 (1974) 263.
Srivastava, R. and Smith, B.D., J. Phys. Chem. Ref. Data, 16 (1987) 219.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ciarkowski, J., Chen, F.M.F. & Benoiton, N.L. Reaction mechanisms in peptide synthesis. Part 1. Semiquantitative characteristics of the reactivity of 2-methyl-5(4H)-oxazolone with water and ammonia in the gas phase and weakly polar media. J Computer-Aided Mol Des 5, 585–597 (1991). https://doi.org/10.1007/BF00135316
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00135316