Patent GB-494773-A (GB)
Title: Process for the manufacture of compounds of the cyclopentano-polyhydrophenanthrene series
Filed: 1937-05-06
Abstract: Compounds of the cyclopentanopolyhydrophenanthrene series which have a side chain in the molecule are subjected to a cracking process by heating the compound to a temperature considerably above its melting point and even at or near its boiling point, distilling off only the more volatile constituents of the reaction mixture and isolating the desired cracking products from the undistilled residue.  By this process at least a part of the side chain is split off leaving a residue with the ring system unattacked.  As starting materials there may be used compounds of the general formula <FORM:0494773/IV/1> where x is hydrogen, oxygen, a hydroxyl group, or a group which on hydrolysis is converted into a hydroxyl group, such as an ether, ester or halogen group.  y is hydrogen or a methyl group, z is a methyl group.  R is a substituted or unsubstituted, saturated or unsaturated hydrocarbon residue.  Rings A and B may contain one or more double bands, and in particular ring A may be aromatic.  If x is hydroxyl water may be split out to give the corresponding anhydro compound which may also be used as a starting material. Starting materials mentioned include sterol compounds such as cholestene, dihydrocholesterol, tetrahydrostigmasterol, dihydrositosterol, tetrahydroergosterol, coprosterol and its ethers, epi-dihydrocholesterol, cholestenone, cholestanone, dihydro-cholesterol-methyl ether, bisdihydrocholesteryl-ether, and their acetates.  The most favourable results are obtained by operating on sterol ethers.  The preferred temperature range is from 280-400 DEG  C.  In general the distillation of the lighter constituents is observed to commence at about 280-300 DEG  C.  The operation may be conducted in the presence of diluents such as hydrocarbons, or catalysts such as finely divided metals or salts such as finely divided nickel, palladium, platinium, cuprous chloride or aluminium chloride.  The side chain is usually in the case of the sterols split off in the form of iso-octane or iso-octene.  It is desirable to start with carefully purified materials to avoid the occurence of side reactions.  The most favourable cracking temperature for any given compound is determined by initial trial experiments.  In some cases it is advantageous to use a low vacuum to carry away the split products, or a stream of inert gas may be used for this purpose.  In examples: (1) cholestene is heated to about 350 DEG  C. in a distilling flask with a low side tube.  The material is heated so that slow boiling takes place and a ring of refluxing liquid is formed just under the point of attachment of the side tube. Iso-octane, and octane pass over leaving a residue which contains the ring system unattacked; (2) dihydrocholesterol-methyl-ether is treated as in example (1) to give a mixture of 3-methoxy-androstene and 3-methoxy-androstane.  In place of the methyl ether, other ethers such as methoxymethyl ether, dinitrophenyl ether or trinitrophenyl ether may be used; (3) bischolesteryl ether is treated as in example (1); (4) a mixture of epi-dihydrocholesterol and finely divided cuprous chloride is slowly heated to about 360 DEG  C. to give after the octane-octene mixture has been driven off a residue consisting mainly of 3-hydroxy-androstane and 3-hydroxy androstene.  This is separated from unchanged starting material by crystallization from acetone; (5) cholestanone and an equal amount of a high boiling hydrocarbon such as phenanthrene are heated to the boiling point of the mixture for about 10 hours, under the conditions of example (1). From the residue the 3-keto-androstene is separated from the hydrocarbon by crystallization from methyl alcohol.