Abbrc-3,3-Ethy~ory-~~drostme-l7_onc
and utronc 3-methyl ether were subjected to cIJ&er~ coodauatio~~ with ethyl acetate and aifluoroacan~c. 7-h~ a101 aatatea of lCtri!?uoroaceyl duintiva undawnt hydrogxolysis with the formation of trithorocthyl CO~~~UII&.
UV and 1R
spaxrd data and other cvidcncz are cited in support of the proposed structure.
ACYUTIONS of the steroid nucleus at position 16 by means of a Claiscn reaction arc described. In the course of this work, results were encountered which motivated further investigations by one of us (M.H.), the results of which have been incorporated in a number of patents.'** In preliminary studies, the 3-ethylene glycol ketal (Ia) of 4-aodrostene-3,17diooe (Chart I) was treated with ethyl acetate and gave the lbacctyl derivative (Ib) which is soluble in dilute sodium hydroxide. The W mx at 279 rnp shifted to 3055 rnp upon addition of alkali, in accordance with the proposed @diketone structure. Autylation with acetic anhydride and pyridioe produced a mixture of the aatoxy compounds (Ic and VI), as evidenced by examination of the NMR spectrum, despite the established preference to locate double bonds in an exocyclic rather than eadocyclic position relative to a five membered ring. Similarly, atrone methyl ether reacted with ethyl aatate in the presence of sodium methoxide to give the &dikctone (IIIa).
When the k&I Ia was trifluoroacetylatcd, a sparingly soluble sodium salt of the @-diketone (Id) was obtained. The UV absorption of the free trifluoroaatyl compound exhibited peaks at 238-5 and 306 rnp which indicate that it exists largely, if not completely, in the en01 form (Id') rather than the keto form (Id'). In the trifluoroacetyl derivative IIIb and others obtained later,' a very high enol content has also been observed, which must be due to the electronegative character of the trifluoromethyl group. On the other hand, the ketonic quality of these compounds is not completely absent, since they react with hydraxine to form pyrazole derivatives.* Treatment of the sodium salt of Id with hot acetic anhydride gave an enol acetate formulated as Ie, in which (as in the other trifluoro enol acetate IIId described below) the double bond is cxocyclic. Similar treatment of the potassium salt of the 2-t+ fluoroaatyl derivative of testosterone gave the dienol acctatc (IV), while treatment of l