Patent GB-657508-A (GB)
Title: Manufacture of hydrophenanthrene carboxylic acids and esters thereof
IPC: C07C61/39
Filed: 1948-08-27
Abstract: Hydrophenanthrene - 2 - carboxylic acids or esters, of which the ring A (containing the 5 : 6 : 7 : 8-positions) is aromatic and the ring structure contains at most one further double bond, and which are unsubstituted in the 7-position but may contain hydrocarbon radicals in the 1- and 2-positions, are manufactured by: (a) eliminating the 7-substitutent from corresponding compounds containing a free or substituent from corresponding compounds containing a free or substituted hydroxy group in the 7-position; or (b) removing the keto group from a 1-keto-hydrophenanthrene-2-carboxylic acid or ester of which the ring A is aromatic and the ring structure contains at most one further double bond and which is unsubstituted in the 7-position but may contain a hydrocarbon radical in the 2-position, and, if desired, introducing a hydrocarbon radical into the 2-position; or (c) ring-closing a 1-(31 : 41-dihydronaphthyl-11)-butane unsubstituted in the 61-position but containing in the 3-position a free or esterified carboxyl group and in the 4-position an oxy- or oxo-group and, if desired, in the 3- or 4-positions one or more hydrocarbon radicals; or (d) reacting a 3 : 4-dihydro-1-ethenyl- or -ethinyl-naphthalene, unsubstituted in the 6-position, with an a  : b -ethylenic monocarboxylic acid or ester, or the former with propiolic acid, b -ethylpropiolic acid or an ester thereof.  In all cases double bonds in ring B or C or in a side chain may be simultaneously or subsequently hydrogenated, at least one always being hydrogenated when the initial product contains two in rings B and C.  Hydrocarbon radicals which may be present in the 1- and 2-positions in the final products are preferably of the aliphatic resins such as alkyl (e.g. methyl, ethyl or propyl), alkenyl (e.g. allyl), alkinyl (e.g. ethinyl) or aralkyl (e.g. benzyl).  The elimination of the free or substituted hydroxy group (e.g. a hydroxy group esterified with an aliphatic or aromatic acid or etherified with an aliphatic or aromatic alcohol) according to (a) may be effected by reduction, especially hydrogenation in the presence of a heavy metal catalyst and an alkali or an alkaline compound of an alkaline-earth metal. The removal of the keto group according to (b) may be brought about by means of hydrogen which is nascent or is produced by electrolytic or biochemical methods or is catalytically activated, or by reaction with an organo-metal compound with introduction of a hydrocarbon radical, followed by elimination of the tertiary hydroxy group formed.  Subsequent introduction of a hydrocarbon radical into the 2-position may be effected by the action of the appropriate halide in the presence of sodium triphenylmethyl.  The ring closure according to (c) may be effected by the action of concentrated inorganic acids or chlorides or oxides of phosphorus, alone or in the presence of a solvent.  The diene synthesis according to (d) may be carried out in the presence or absence of a solvent, at a more or less raised temperature, if desired in the presence of an inert gas, suitable ethylenic acids or esters being acrylic, methacrylic, crotonic, isocrotonic, angelic, tiglic, a  : g -dimethylcrotonic, and a -methyl-b -vinylacrylic acids and their esters.  Esterified carboxyl groups in the products may be hydrolysed, whilst free acids may be esterified (e.g. directly with diazomethane or diazoethane or indirectly by way of their halides or salts) or converted into salts (e.g. alkali- or alkaline-earth metal or ammonium salts).  The products are useful as medicaments or intermediates therefor. Examples illustrate the alternative processes as applied to the production of dl- and d-1-ethyl-2-methyl-1 : 2 : 3 : 4 : 9 : 10 : 11 : 12-octahydrophenanthrene-2-carboxylic acid, dl-1 : 2-dimethyl-and dl-1-ethyl-2-methyl-1 : 2 : 3 : 4 : 9 : 10-hexahydrophenanthrene - 2 - carboxylic acid, and 1 : 2 : 3 : 4 : 9 : 10 : 11 : 12-octahydrophenanthrene-2-carboxylic acid.  The Specification as open to inspection under Sect. 91 comprises also the manufacture of other functional derivatives (e.g. amides or nitriles) of the acids, and the use in process (a) of starting materials containing in the 7-position a substituent convertible into a hydroxy group, e.g. an amino group (which may be eliminated by diazotization followed by boiling) or a halogen atom (which may be eliminated by reduction). This subject-matter does not appear in the Specification as accepted.