GB861460A - Production of vitamin a aldehyde - Google Patents

Abstract

The invention comprises 1-alkoxy-3 : 7-dihydroxy - 3 : 7 - dimethyl - 9 - (21 : 61 : 61-trimethylcyclohex - 11 - enyl) - nona - 1 : 8-dien-4-ynes and the corresponding 1 : 4 : 8-trienes (the alkoxy groups of which contain up to 10 carbon atoms), the preparation of the former by condensation of a di-magnesium halide of 4-hydroxy-4-methyl-6-(21 : 61 : 61-tri-methylcyclohex - 11 - enyl) - hex - 5 - en - 1 - yne with a 4-alkoxybut-3-en-2-one, the conversion of the 1 : 8-diene-4-ynes into the 1 : 4 : 8-trienes by partial hydrogenation, the conversion of the 1 : 4 : 8-trienes into Vitamin A aldehyde by subjecting them both to hydrolysis and to dehydration in the presence of an acid and, if desired, the conversion of Vitamin A aldehyde to Vitamin A by hydrogenation and the formation of retinylidene acylhydrazones by reaction of Vitamin A aldehyde with an acylhydrazine. The condensation involving the dimagnesium halide may be conducted in a solvent such as an ether and the dihydroxy-1 : 8-dien-4-yne isolated after hydrolysis of the dimagnesium halide compound first formed. Suitable catalysts for the hydrogenation step include Raney nickel and palladium on a carrier, the activity of which may be modulated by the addition of an organic base or lead, the reaction advantageously being effected in a suitable solvent. The hydrolysis and dehydration steps are advantageously effected simultaneously in the presence of an acid such as a mineral acid, formic, acetic or oxalic acid or p-toluene sulphonic acid, which can be used together with a cation exchange material, preferably in an organic solvent and in presence of an organic salt of an alkali metal or a metallic salt such as lithium chloride and an oxidation inhibitor such as tocopherol or hydroquinone. In a modification of this process the dihydroxytriene is treated with diketene to form the diacetoacetate which is then treated with an acid when hydrolysis accompanied by dehydration and de-acidification occurs to form Vitamin A aldehyde. Examples illustrate all the above processes, and the 2 : 4-dinitrophenyl hydrazone of Vitamin A aldehyde is described. In an additional example the 1-methoxy-dihydroxytriene is shaken with 10% sulphuric acid in dioxan in an inert atmosphere to give a product of the probable structure <FORM:0861460/IV (b)/1> which on heating with 2 drops of concentrated hydrochloric acid in dimethylformamide gives Vitamin A aldehyde. U.S.A. Specifications 2,676,990 and 2,676,991 are referred to.