Patent GB-477400-A (GB)
Title: Manufacture of new enol derivatives containing the sterol nucleus
IPC: C07J9/00
Filed: 1936-05-29
Abstract: 3-Keto compounds containing a sterol nucleus are converted into the corresponding enol derivatives by treatment with an acylating-agent in the presence or absence of an acid binding - agent for a long period.  Suitable acylating-agents are organic or inorganic halides or anhydrides.  The reaction time varies with the temperature, being from about 5 hours at 160 DEG  C. to 40 hours at 80--100 DEG  C.  In cases where the parent materials contain a hydroxyl group in addition to the 3-keto group, the acylation must be continued for a period substantially longer than that which is sufficient to acylate the hydroxyl group.  When an organic halide is used as the acylating-agent, either or both the enol ester and its halide can be produced.  Reaction in an open vessel so that the hydrogen halide can escape, favours the formation of the ester, whereas reaction in a closed vessel favours the formation of the halide.  In examples: (1) D <4>,<5>-cholestenone-(3) is boiled with benzoyl chloride in benzine solution for 40 hours.  If desired, the solvent may be omitted and pyridine may be present.  In a similar manner the enol ester of D <1>,<2>cholestenone may be formed; (2) cholestenone is heated in a bomb tube to 100 DEG  C. for 22 hours to give the enol-benzoate; (3) cholestenone is heated with acetyl chloride in a bomb tube for 16 hours at 100 DEG  C.  The product consisting of cholestenone enol-acetate is recrystallized from alcohol and hexane; (4) D <4>,<5>-androstenedione-(3 : 17) is heated in benzine solution at 100 DEG  C. for 40 hours, to give the mono-ester of androstene dione, enolized in the 3-position; (5) similar to example (1) using a larger amount of benzoyl chloride; (6) D <4>,<5>-androstene-dione(3 : 17) is boiled with acetic anhydride and fused potassium acetate for 45 hours; after working up in the usual way the corresponding enol mono-acetate is obtained; (7) testosterone benzoate is converted into the corresponding 3-enol benzoate by boiling with benzoyl chloride in benzine solution for 44 hours; (8) testosterone is converted into the 3-enol acetate by treatment with acetic anhydride and potassium acetate as in example (6).  Cholestenone may be treated similarly to give the corresponding enol-acetate.  Similar results are obtained by using as the acylating-agent an acetic acid halide such as acetyl chloride or bromide, or a ketene such as ketene itself; (9) testosterone propionate is treated with acetic anhydride and potassium acetate as in example (6) to give the 3-enol acetate of testosterone-17-propionate.  Similarly, the 3-enol propionate of testosterone 17-acetate can be obtained from testosterone acetate; (10) testosterone, or testosterone-17-propionate is converted into the 3-enol-propionate by heating with propionic anhydride for 5 hours.  In a similar manner there can also be prepared normal or mixed di-esters of testosterone with other acids such as formic acid, n-butyric acid, iso-butyric acid, valeric acid, or palmitic acid. Corresponding enol-esters can be obtained for example from androstane-dione-(3 : 17), androstane-ol-(17)-one-(3), D <1>,<2> - androstene - dione, D <1>,<2>-cholestenone, D <1>,<2> - androstene - ol - 17 - one-(3); (11) progesterone is converted into the corresponding 3-enol acetate by heating with anhydrous sodium acetate and acetic anhydride for 40 hours; (12) progesterone is converted into the 3-enol-propionate by heating with propionic anhydride and anhydrous sodium propionate for five hours.  In a similar manner, other end esters of progesterone can be prepared such as the butyrates, valerates, stearates, or the benzoate; (13) the 3-enol butyrate of testosterone-17-acetate is prepared by heating testosterone acetate with anhydrous sodium-n-butyrate and n-butyric anhydride in benzine solution. Similarly, from testosterone propionate the -3-enol-n-butyrate may be obtained.  From the corresponding testosterone butyrates there are also similarly obtained the 3-enol acetate of testosterone-17-n-butyrate, the 3-enol acetate of testosterone-17-isobutyrate and the 3-enol propionate of testosterone-17-isobutyrate.  From testosterone acetate there is also similarly obtained the 3-enol benzoate of testosterone - 17 - acetate.  In an analogous manner, 3-keto-compounds containing a sterol nucleus which occur in the suprarenal cortex such as 21-oxyprogesterone and esters thereof can be converted into their enol derivatives such as acetates, propionates, and acetate-propionates.