NOTES
1374 Semicarbazones of
a,B-Unsaturated steroids
20-Keto-
BY HANSREICHA N D RAYMOND W. COLLISS*
Some time ago Klyne and co-workers2 isolated A16-allopregnen-3(/3)-01-20-one sulfate from pregnant mare’s urine and reported that the free ketoalcohol failed t o give a semicarbazone. However, three semicarbazones of 16,17-unsaturated 20-ketosteroids are described in the literature : A16-pregnene-3,20-dione disemicarbazone, A16-pregnen-3(/3)-01-20-onesemicarbazone4and A16-pregnen-3(P)01-20-one acetate seniicarbazone.4 These sernicarbazones were prepared “by treatment with semicarbazide acetate under the usual conditions.” In the present experiments we have studied the conditions under which semicarbazones of A“j-20 ketosteroids are formed, and have prepared three additional compounds of this type. We found that the reaction of A5,16-pregnadien-3(/3)-01-20-one,its acetate and A1~-allopregnen-3(cr)01-20-one acetate with semicarbazide acetate in ethanol was incomplete after refluxing for 1.5 hours. The crude reaction products showed maximum ab,sorption a t 240 inp (starting material) and only an inflection between 260 and 270 n i p . When the ketosteroids were refluxed with the same semicarbazide acetate solution for 24 hours, the crude reaction products as well as the crystals isolated from them showed only a single maximum a t 267 mp. The same was the case when the reaction was carried out a t room temperature in the presence of pyri d i ~ ~ e A. ~ similar absorption maximum was found by Lt-ettstein8 for the semicarbazone of A5J~-16-methylpregnadien-3(~)-ol-20-one acetate. Since displacement to longer wave lengths is usually observed in passing from the carbonyl compound to its semi~arbazone,~ the absorption maximum a t 267 inp indicates that riorinal semicarbazones of 16,17-unsaturated 20-ketosteroids were formed. ‘This maximum excludes the formation of a pyrazoline derivative as well as the addition of one mole of semicarbazide to the quite reactive Alfi-double In the latter case there would result a saturated ketone which should show only a band of low intensity with a maximum in the region of 280300 mpt9while pyrazoline derivatives show nearly the same absorption maxima as the parent ketones.1° I n contrast to the slow forination of semicarbazones of 15,17-unsaturated PO-ketosteroids the corresponding saturated ketones and those with a hy(1) This investigation was supported in part by research grants from the National Cancer Institute of the National Institutes of Health, Public Health Service. and from Cibn Pharmaceutical Products, Inc., Summit, K. J. (2) W.Klyne, B. Schachter and G. F.Marrian, Bioihem. J . , 43, 231 i 1948). (3) R . E . Marker and E. Rohrmann, THIS JOURNAL, 62, 518 (1940). (4) R. E. Marker and E. Rohrmann, ibid., 62, 521 (1940). ( 5 ) J. D. Dutcher and 0. Wintersteiner, i b i d . , 61, 1992 (1939). (6) A. Wettstein, Helw. Chim. Acta, 27, 1803 (1944). (7) I. K. Evans and A. E. Gillam, J . Chem. Soc., 565 (1943). ( 8 ) D. K.Fukushima and T. F. Gallagher, THISJOURNAL, 72, 2306 (1950). (9) L. F. Vieser and M . Iiieser, “Satural Products Related to Phenanthrene,” 3rd ed , Krinhnl
