Regioselectivity in preparation of unsymmetrically substituted 3-aminoquinoxalin-2(1H )-ones

Abstract

Regioisomer formation has to be considered in the preparation of quinoxalines having different substituents at the 2- and 3-position. Oxalomonoimidic acid dimethyl ester or oxalomonoimidic acid diethyl ester, chloro(methylimino)acetic acid ethyl ester, chloro[(Z )-hydroxyimino]acetic acid ethyl ester and (Z )-2-[(E )-hydroxyimino]acetohydroximoyl chloride were applied to the synthesis of 3-aminoquinoxalin-2(1H )-one derivatives, and the isomer ratio was investigated concerning the reactivity of the ring-closure reagent. The structures of reaction products were identified using ¹H, ¹³C and ¹⁵N NMR techniques. A direct synthesis of quinoxaline-2,3(1H,4H )-dione 3-oximes is described.

References

1. Cs. Gönczi, É. Csikós, E. Sándor, J. Bencze, V. Lakics, P. Molnár, A. Szappanos, B. Podányi, I. Hermecz, G. Héja, S. Báthori, I. Bata, A. Csutor, I. Szvoboda, Zs. Böcskei and I. Ritz, WO9719934, 1997(Chem. Abstr., 1997, 127, 95295c).
2. A. Díaz, M. P. Matia, J. L. Garcia-Navío, J. J. Vaquero and J. Alvarez-Builla, J. Org. Chem., 1994, 59, 8294.
3. (a) See the Experimental section; (b) G. I. Braz, G. B. Myasinkova, A. Ya. Yakubovich and V. P. Bazov, Zh. Obshch. Khim., 1964, 34, 2980 (Chem. Abstr., 1965, 62, 562h).
4. (a) A. McKillop, A. Henderson and P. S. D. Ray, Tetrahedron Lett., 1982, 23, 3357; (b) A. McKillop, S. K. Chattopadhyay, A. Henderson and C. Avendano, Synthesis, 1997, 301.
5. In DMSO-d₆ the tautomeric equilibrium is shifted strongly towards the form indicated in the scheme.
6. A. Bax and M. F. Summers, J. Am. Chem. Soc., 1986, 108, 2093.
7. L. Muller, J. Am. Chem. Soc., 1979, 101, 4481.
8. E. Pretsch, J. Seibl, W. Simon and T. Clerc, Tabellen zur Strukturaufklärung organischer Verbindungen mit spektroskopischen Methoden, Springer, Berlin, Heidelberg, New York, 1981.
9. D. M. Doddrell, D. T. Pegg and M. R. Bendall, J. Magn. Reson., 1982, 48, 323.
10. M. O. Lozinszkij, A. A. Dmitruha and A. G. Bratoljubova, Zs. Organicseszkoj Khim., 1974, 10, 71 (Chem. Abstr., 1974, 80, 108139t).
11. D. Batholomew and I. T. Kay, Tetrahedron Lett., 1979, 2827.
12. L. W. Kissinger and H. E. Ungade, J. Org. Chem., 1958, 23, 1517.
13. A. Koçak and Ö. Bekåroglu, Helv. Chim. Acta, 1984, 67, 1503.
14. X. Gaudiano and X. Ricca, Gazz. Chim. Ital., 1959, 89, 587.
15. Full assignment of the ¹H and ¹³C NMR spectra of the two pure compounds was gained from 2D HMBC spectra, and the carbon–proton coupling constants were determined from proton-coupled ¹³C NMR spectra and from 2D spectra using a modified HSQC pulse sequence.
16. K. E. Kövér, O. Prakash and V. Hruby, Magn. Reson. Chem., 1993, 31, 231.
17. W. Wieker, D. Leibfritz, R. Kerssebaum and W. Bermel, Magn. Reson. Chem., 1993, 31, 287.