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Ring expansion of steroid oxetanes into dihydrooxazines

Andrea Hajnal, János Wölfling and Gyula Schneider

Department of Organic Chemistry, Jozsef Attila University, H-6720 Szeged, Dom ter 8., Hungary

Acid nitriles yield acylamino derivatives with all organic compounds forming carbocations in strongly acidic media. This reaction recognised by Ritter and coworkers1-3 results in vicinal trans-acylaminohydroxy compounds in the case of steroid epoxides.4-6

The ring cleavage of steroid epoxides was extended to the oxetan epimers condensed to ring D. This method provided possibilities for the preparation of a,g-acylaminohydroxysteroids.

The 16b,17b-epoxymethylene-3-methoxyestra-1,3,5(10)-triene (1) was reacted with aliphatic and aromatic nitriles in the presence of equivalent amounts of HBF4-diethyletherate. A dihydrooxazine-HBF4 salt condensed to the sterane skeleton was found to be formed instead of the expected a,g-acylaminohydroxysteroid.

Employing the appropriate nitriles, the derivatives 2a-f were thus prepared. The bases (3a-f) can be liberated from the salts formed with an aqueous solution of NaHCO3.

The stability of the bases are widely different. Compound 2a transforms relatively readily into the corresponding 16b-acylaminomethyl-3-methoxy-17b-hydroxy-estra-1,3,5(10)-triene (4a) on the effect of the NaHCO3 solution. In contrast, the analogous compounds 2b-f proved to be stable even in the presence of alkali alcoholates.

The structure of dihydrooxazine steroids and their conversion products were established by spectroscopic methods. Authentic samples for verification purposes were also synthesised.

The Ritter reaction of the epimeric compound 5, however, leads to cleavage of the oxetane ring followed by stabilisation of the carbocation developed via the Wagner-Meerwein rearrangement. Under such conditions, the attack by the nitrile function does not take place and 16a-hydroxymethyl-17b-methyl-18-nor-3-methoxyestra-1,3,5(10),13(14)-tetraene (6) is formed.


  1. J.J. Ritter and P.P. Minieri, J.Am.Chem.Soc., 1948, 70, 4045.
  2. J.J. Ritter and J. Kalish, J.Am.Chem.Soc., 1948, 70, 4048.
  3. L.I. Krimen and D.J. Kota, Organic Reactions, J. Wiley, New York 1969, 17, 213.
  4. S. Julia and G. Bourgery, C. R. Acad. Sci., (C) 1967, 264, 333.
  5. G. Bourgery, J.J. Frankel, S. Julia and R.J. Ryan, Tetrahedron, 1972, 28, 1377.
  6. Gy. Schneider and B. Schönecker, Acta Chim. Acad. Sci. Hung., 1977, 95, 321.