Patent GB-665254-A (GB)
Title: Process for the manufacture of hydroxyl compounds
Filed: 1949-09-21
Abstract: Hydroxy compounds (which may be of aliphatic, alicyclic, aromatic-aliphatic or heterocyclic nature) are manufactured by hydrogenating splitting of vicinal epoxides by the action of a reactive metal hydride (particularly a dimetal hydride such as an alkali metalaluminium hydride, or also sodium- or lithiumboron hydride), advantageously in an inert anhydrous organic solvent in which the metal hydride is soluble (e.g. diethyl or dibutyl ether or tetrahydrofurane).  The process is applicable particularly in the cyclopentanopolyhydrophenanthrene and polyhydrochrysene series, and especially to the reduction of 2 : 3-, 4 : 5-, 5 : 6-, 11 : 12-, 14 : 15-, 16 : 17-, and 17 : 20-epoxides of steroids. Other reducible substituents present (e.g. oxo, carboxyl or esterified carboxyl groups) may be simultaneously reduced, whilst esterified hydroxy groups may be hydrolysed during the reduction process and can afterwards be re-esterified.  In examples, the following reductions are effected with lithium-aluminium hydride: (1) 3b -acetoxy-16 : 17a - oxido - 20 - keto - 5 - allopregnane to 3b  : 17a  : 20b  - trihydroxy - 5 - allopregnane (also obtainable similarly from the corresponding 3b -hydroxy compound) together with some 3b  : 20b - and 3b  : 20a -diacetoxy-17a -hydroxy-5-allopregnane; (2) 3b  : 21-diacetoxy-16 : 17a -oxido-20-keto-5-allopregane to 3b  : 17a  : 20 : 21-tetrahydroxy - 5 - allopregnane; (3) 3b -acetoxy- or 3b -hydroxy-4b  : 5-oxidocoprostane to 3b  : 5 - dihydroxycoprostane; (4) 3a  - acetoxy - 4b  : 5 - oxidocoprostane to 3a  : 5 - dihydroxycoprostane; (5) 3-keto-4b  : 5-oxidocoprostane to 3a  : 5- and 3b  : 5-dihydroxycoprostane; (6) a -cholesterol oxide acetate to 3b  : 5-dihydroxycholestane; (7) b -cholesterol oxide acetate to 3b : 6b -diacetoxycholestane; (8) 2 : 3a -oxidocholestane to 3a -hydroxycholestane (with some 2 : 3-dihydroxycholestane as by-product); (9) 2 : 3b -oxidocholestane to 2b -hydroxycholestane; (10) 3a -hydroxy-5 : 6a -oxidocholestane to 3a  : 5-dihydroxycholestane; (11) 3a -hydroxy-5 : 6b -oxidocoprostane to 3a : 5-dihydroxycoprostane and 3a  : 6b -dihydroxycholestane, with some 3a  - hydroxycholestane; (12) 2 : 3 - oxidolupane to epilupanol (which is acetylated); (13) 3a -acetoxy-11 : 12b -oxidocholanic acid methyl ester to a triol; (14) the corresponding 11 : 12a -oxide to an isomeric triol; (15) D 16 : 17-3b -acetoxy-14 : 15b  - oxido - 20 - keto - 5 - allopregnene to compounds of the empirical formul C21H32O3 and C21H34O3; (16) 3a -acetoxy-4a  : 5-oxidocholestane to 3a : 5-dihydroxycholestane; (17) 3b  - acetoxy - 4a  : 5 - oxidocholestane to 3b  : 5 - dihydroxycholestane; (19) D 4-17 : 20-oxidopregnenone-3 to a compound containing one double bond and two hydroxy groups.  In example (18), D 16-3b -acetoxy-14 : 15b -oxido-20-keto-5-allopregnene in methanol and chloroform is reduced with a solution of sodium-boron hydride in aqueous dioxane, and the product is oxidized with chromium trioxide in glacial acetic acid to a compound of the empirical formula C23H34O4.  3b -Acetoxy-16 : 17a - oxido - 20 - keto - 5 - allopregnane is obtainable by reaction of D 16-3b -acetoxy - 20 - keto - 5 - allopregnene with benzo-peracid or hydrogen peroxide in glacial acetic acid.  3b - and 3a -Acetoxy-4b  : 5-oxidocoprostane are obtainable by catalytic hydrogenation of 3-keto-4b  : 5-oxidocoprostane followed by acetylation, or preferably by oxidation of D 4-3b - or -3a -acetoxycholestene respectively with peracids.  3-Keto-4b  : 5-oxidocoprostane is obtainable by oxidation of cholestenone with alkaline hydrogen peroxide.  2 : 3-Oxidolupane is obtainable by oxidation of D 2-lupene with benzo-peracid in ether.