Patent GB-740314-A (GB)
Title: Process for the manufacture of substituted 13-methyl-1-keto-perhydrophenanthrenes
IPC: C07D317/72
Filed: 1954-02-03
Abstract: Substituted 1-keto-13-methyl-perhydrophenanthrenes having a trans-anti-trans configuration at positions 11, 12, 13 and 14 are made by subjecting substituted 1-hydroxy-13-methyl5,6,7,8,9,10,13,14 - octahydrophenanthrene having a trans configuration at positions 13 and 14 to catalytic hydrogenation, oxidizing the substituted 1 - hydroxy - 13 - methyl perhydrophenanthrenes so obtained (after transformation of the substituents, if desired) to convert the 1-hydroxy group to 1-keto, and reacting the keto compound with an alkaline agent. The starting material may contain a free or esterified hydroxy group or a keto group (which may be ketolized) in 7- or 8-position, a methyl group in 2-position, and/or a free or esterified hydroxy group in 4-position.  The hydrogenation may be carried out with hydrogen in presence of platinum, palladium, or nickel, and the oxidation with a metal alkoxide or phenoxide or a hexavalent chromium compound.  Any hydroxy groups in 4-, 7-, or 8-position may be protected from oxidation by esterification and the alkaline agent may be an aqueous alcoholic alkali metal hydroxide solution.  In examples, 1,7-diketo-13-methyl-perhydrophenanthrene is obtained from trans-1-hydroxy - 7 - keto - 13 - methyl - 5,6,7,8,9,10, 13,14-octahydrophenanthrene by (1) hydrogenation using Raney nickel, oxidation with chromic anhydride, and treatment with methyl alcoholic potash; (2) conversion to the 1-acetoxy body with acetic anhydride in pyridine, hydrogenation, oxidation with aluminium tert.-butoxide, and treatment with alcoholic potash; (3) reduction with lithium aluminium hydride to the 1,7-dihydroxy body, followed by treatment as in (1); (4) conversion to the 7-ethylenedioxy body with ethylene glycol and treatment as under (1).  Also in examples: (5) trans-1,7-dihydroxy - 2,13 - dimethyl -5,6,7,8,9,10,13,14-octahydrophenanthrene is treated as in (1) or hydrogenated with platinum oxide in acetic acid, any acetoxy groups hydrolysed, and thereafter treated as in (1).  Other products, including triketo bodies, are listed.  1 - Hydroxy - 7 - keto - 13 - methyl - 5,6,7,8,9,10, 13,14 - octahydrophenanthrene and 1,4 - dihydroxy - 7 - keto - 13 - methyl - 5,6,7,8,9,10,13,14-octahydro-phenanthrene are obtained from 9-keto-1-methoxy-or 1,4-dimethoxy-5,6,7,9,10,13-hexahydrophenanthrene by converting to the corresponding enol-ether by treatment with an orthoformic ester in presence of sulphuric acid, hydrogenating in presence of a palladium/calcium carbonate catalyst, hydrolysing in alcoholic aqueous solution in presence of a hydrohalic acid, to give the trans.-7-keto-1-methoxy or 1,4-dimethoxy-13-methyl-5,6,7,8,9, 10,13,14-octahydrophenanthrene, and splitting off the ether groups with aluminium chloride.  The keto groups may be ketalized with ethylene-glycol.  1.4 - Dihydroxy - 8 - keto - 13 - methyl - 5,6,7,8, 9,10,13,14-octahydrophenanthrene is obtained by condensing b -(2,5-dimethoxyphenyl)-ethyl bromide with 4-carbethoxy-3-methyl-cyclohexen(2)-one-(1), hydrolysing and decarboxylating to give b  - [6 - keto - 2 - methyl - cyclohexen 8 (1) - yl]-ethyl-hydroquinone dimethyl ether, ringclosing this to give 8-keto-1,4-dimethoxy-13-methyl - 5,6,7,8,9,10,13,14 - octahydrophenanthrene, and splitting the ether groups with aluminium chloride.  The product may be ketalized with ethylene glycol.  1,7 - Dihydroxy - 2,13 - dimethyl - 5,6,7,8,9,10, 13,14-octahydrophenanthrene is obtained from 1 - hydroxy - 7 - keto - 13 - methyl - 5,6,7,8,9,10, 13,14-octahydrophenanthrene by reduction with sodium boron hydride or lithium aluminium hydride to the corresponding 7-hydroxy compound, reacting the latter with formaldehyde and diethylamine, to give the 2-diethylaminomethyl body, and catalytically hydrogenating the latter.  The product may be oxidized to the 7-keto body and the latter ketalized with ethylene glycol.  1,4,7 - Trihydroxy - 2,13 - dimethyl - 3,5,6,7,8, 9,10,13,14-octahydrophenanthrene may be obtained from 1,7-dihydroxy-2,13-dimethyl-5,6,7, 8,9,10,13,14-octahydrophenanthrene by introduction of a nitroso group, reduction, and diazotization to introduce a further hydroxy group.