Sept., 1942
REARRANGEMENT OF ~6,1i-DIBROMOPREGNAN-3(~)-OL-2o-ONE
2093
(CONTRIBUTION FROM THE SCHOOL O F CHEMISTRY AND PHYSICS O F THE PENNSYLVANIA STATE COLLEGE]
Sterols. CLII. Rearrangement of 16,17-Dibromopregnan-3(p)-ol-ZO-one' BY RUSSELLE. MARKER,R. B. WAGNER AND EMERSON L. WITTBECKER During the course of our recent studies of bro- composition with that obtained by similar treatmopregnan-20-keto compounds, we found that ment of 17,21-dibromopregnan-3(P)-ol-20-one ace17,2l-dibromopregnan-3(~)-ol-20-one acetate2 tate. Although the reaction of the latter with alunder vigorous alkali treatment yields 3@)- coholic potash is similar to a reaction reported hydroxy- A17-20-pregnen-21-oic acid. We now by FaworskiiJ4who obtained P,P'-dimethylacrylic we find that 16,17-dibrornopregnan-3(~)-01-20-oneacid from 3-methyl-1,3-dibromo-2-butanone, acetate undergoes a rearrangement to give this have been unable to find in the literature any same product and the corresponding methyl ester. analogous rearrangement for a,P-dibromo keBromination of 16-pregnen-3(P)-ol-20-one ace- tones. Whereas a,P-dibromo ketones are known tate (I) in acetic acid solution gives a good yield to hydrolyze to a,@-diketones,i t was impossible of the 16,17-dibromide (11). That the formation for our compound to take such a course. The unsaturated acid (IV) is converted to the of the latter was not attended by any rearrangement was shown by the simple debromination of unsaturated methyl ester (111) by diazomethane the product (11) with methanolic sodium iodide in ether. This methyl ester (111) is identical with to give the original olefinic compound (I) in almost the ester isolated in the neutral fraction of this quantitative yield. The debromination was ef- reaction. The ester was not found by us in our fected equally well with boiling pyridine. Since previously described rearrangement2 of the 17,21the dibromo compound (11) was easily converted dibromo compound, and its isolation here may to 3(@)-hydroxy-A17-20-pregnen-21-oicacid (IV) have an important bearing on any mechanism under exactly the same conditions as those re- which might be proposed. Catalytic hydrogenation of the acid (IV) with quired for the formation of IV from 17,21-dibromopregnan-3(P)-ol-2O-one acetate2 it was neces- Adams catalyst gave a lower melting saturated sary to show that these two dibromo compounds acid which was identified by composition and were really different. For this purpose, 16,17- physical properties as 3(P)-hydroxypregnan-21-oic dibromopregnan-3 (P)-ol-20-one acetate (11) was acid, previously described by u s 2 Similar hydrorefluxed with potassium acetate in acetic acid genation of the unsaturated methyl ester (111) solution. The product isolated was 16-pregnen- followed by alkaline hydrolysis gave the same 3(P)-ol-20-one acetate (I). Similar treatment of saturated acid. Both the saturated and the un17,21-dibromopregnan-3(P)-ol-20-one acetate has saturated (111) methyl esters, acetylated and unbeen previously shown3 to give 21-bromo-16- acetylated, agree in melting points and properties pregnen-3(P)-ol-20-one acetate. Thus the 16,17- with the corresponding esters obtained by subsedibromide is readily debrominated to give the ole- quent treatment of the acid from the rearrangefinic compound, whereas the 17,21-dibromide ment of the 17,21-dibromide acetate. The satuloses hydrobromic acid under the same conditions rated methyl ester depresses the melting point of to give an unsaturated monobromide. The pe- the methyl ester of 3(/3)-hydroxy-l7-methyl-etioculiar reactivity of the 16,17-dibromide is further cholanic acid obtained from the reaction of 17shown by its action with hydrogen and palladium- bromopregnan-3(P)-ol-20-one with alcoholic pobarium sulfate catalyst in the presence of dioxane tassium bicarbonates5 and pyridine to give compound I. I n order to furnish additional proof of the idenWhen 16,17 - dibromopregnan - 3(P) - 01 - 20-one tity of this unsaturated acid (IV) it was oxidized acetate (11) is treated with a boiling solution of by ozonolysis in chloroform to give etio-cholanmethanolic potassium hydroxide, i t gives a mix- 3(P)-ol-17-one (V) which was isolated as the semiture of 3(p)-hydroxy-A17-20-pregnen-21-oicacid carbazone. Acid hydrolysis of the latter gives the (IV) and the corresponding methyl ester (111). free hydroxy-ketone (V) which was the same as The unsaturated acid agrees in properties and the compound described before. ( 1 ) Original manuscript received July 16, 1941. (2) Marker, Crooks and Wagner, THIS JOURNAL, 64, 817 (1942). (3) I b t d , 64, 213 (1942).
(4) Fnworskii, J . Russ. Phys.-Chcm., 44, 1358 (1913); J . p r a k i . Chcm., [2] 88, 658 (1913). ( 5 ) Marker and Wagner. THIS JOURNAL, 64, 216 (1942).
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