Patent GB-762041-A (GB)
Title: Novel hydroxy-esters and the manufacture and conversion thereof
Filed: 1954-07-07
Abstract: The invention comprises lower alkyl esters of 3 - hydroxy - 2,6 - dimethyl - 8 - [21.61.61 - tri-methyl - cyclohexene - (11) - yl] - octadien - (4,6)-oic-(1) acid. The lower alkyl groups are those containing from 1 to 4 carbon atoms.  They may be prepared by a process comprising condensing 2 - methyl - 4 - [21.61.61 - trimethyl - cyclohexen - (11) - yl] - buten - (2) - ol(1) with a halogeno-acetic acid lower alkyl ester, either dehydrating the resulting 2.3-epoxy-4-methyl-6-[21.6.61 - trimethyl - cyclohexene - (1) - yl]-hexen - (4) - oic(1) acid ester or the corresponding 3-hydroxy ester by heating in a solvent in the presence of an acidic dehydrating agent and then reducing the lower alkyl ester of 4 - methyl - 6 - [21.61.61 - trimethyl - cyclohexen - (11) - yl] hexadien - (2.4) - oic - (1) acid with lithium aluminium hydride; or reducing the 2.3-epoxy- or 3-hydroxy compound with lithium aluminium hydride and then dehydrating the resulting 4-methyl-6-[21.61.61-trimethylcyclohexen - (11) - yl] - hexen - (4) - diol (1.3) by heating with an acidic dehydrating agent, after first esterifying the primary hydroxy group; oxidizing the resulting 4-methyl-6[21.61.61-trimethyl - cyclohexene - (1)1 - yl] - hexadien - (2.4)-ol-(1) so as to convert the hydroxy-methyl group to an aldehyde group and condensing the resulting 4 - methyl - 6 - [21.61.61 - trimethylcyclohexene - 11 - yl] - hexadien - (2.4) - al - (1) with an a -halogeno-propionic acid lower-alkyl ester.  When the epoxy ester is formed in the first step it can, if desired, be converted into the hydroxy ester by heating it and reducing the resulting keto acid ester.  The first step comprising the condensation of the aldehyde with a halogeno-acetic acid lower-alkyl ester may be brought about, for example, by using zinc or sodium or sodium methylate as condensing agent.  Preferably the condensation is carried out as a Reformatsky reaction using a bromoacetic acid lower-alkyl ester. Alternatively the condensation may be carried out using a chloroacetic acid lower-alkyl ester and sodium methylate in which case the product is an epoxy ester.  The dehydration step which follows may be carried out by heating the hydroxy ester in a solvent such as toluene or xylene in the presence of a p-toluene sulphonic acid. In the example a mixture of 2 - methyl - 4 - [21.61.61 - trimethylcyclohexen - (11) - yl] - buten - (2) - al - (1), bromo-acetic acid ethyl ester and ether is treated with zinc to give a mixture containing 3-hydroxy - 4 - methyl - 6 - [21.61.61 - trimethylcyclohexen - (11) - yl] - hexen - (4) - oic - (1) acid ethyl ester; this ester is heated in toluene solution with p-toluene-sulphonic acid to give 4-methyl - 6 - [21.61.61 - trimethyl - cyclohexen-(11) - yl] - hexadien - (2.4) - oic - (1) acid ethyl ester; this latter ester is dissolved in ether and treated with lithium aluminium hydride to give 4 - methyl - 6 - [21.61.61 - trimethyl - cyclohexen-(11) - yl] - hexadien - (2.4) - ol - (1); this alcohol is treated with manganese dioxide to give 4-methyl - [21.61.61 - trimethyl - cyclohexen - (11) - yl] - hexadien - (2.4) - al - (1); this aldehyde is treated with a -bromo-propionic acid ethyl ester dissolved in ether and zinc to give 2.6-dimethyl-3 - hydroxy - 8 - [21.61.61 - trimethyl - cyclohexen - (11) - yl] - octadien - (4.6) - oic - (1) acid ethyl ester; this ester is treated with p-toluene sulphonic acid to give 2.6-dimethyl-8-[21.61.61-trimethyl - cyclohexen - (11) - yl] - octatrien(2.4.6)-oic-(1) acid ethyl ester; a mixture of this ester and ether is treated with lithium aluminium hydride to give 2.6-dimethyl-8-[21.61.61-trimethyl - cyclohexen - (11) - yl] - octatrien(2.4.6) - ol - 1; and this alcohol is treated with manganese dioxide to convert it to 2.6-dimethyl8 - [21.61.61 - trimethyl - cyclohexen(11) - yl]-octatrien - (2.4.6) - al - (1). Specifications 744,113, 753,552, 753,635, 756,622, 762,067 and 762,068 are referred to.