Patent GB-630865-A (GB)
Title: Improvements in or relating to the production of compounds having vitamin a activity and the intermediates thereof
IPC: C07C403/00
Filed: 1946-08-20
Abstract: Lithium acetylide is prepared by passing acetylene through liquid ammonia at a temperature below -40 DEG  C. with simultaneous addition of lithium metal.ALSO:Compounds having vitamin A activity are prepared by hydrogenating the acetylenic bond to an ethylenic bond in a compound of the formula <FORM:0630865/IV (b)/1> where X is -OR or <FORM:0630865/IV (b)/2> , R being a hydrocarbon group, and if desired treating with acidic materials to cause allylic rearrangement and splitting off of water.  Alternatively, the compound I is first subjected to a heat treatment to remove water and is then subjected to hydrogenation. If X is <FORM:0630865/IV (b)/3> the group may be hydrolysed to OH.  The acetylenic compound is prepared by treating b -ionone with calcium or lithium acetylide to give a -ethynyl-(b -ionol) which is further reacted with a metal hydrocarbon or hydrocarbon metal halide to form the compound <FORM:0630865/IV (b)/4> where M is a metal and Y is non-existent if the valency of M is one but otherwise is halogen or a hydrocarbon radical.  This compound is then reacted with an ester or an ether of a 1 : 4-halohydrin of isoprene, preferably in the presence of cuprous bromide, to give the desired product.  In examples, a -ethynyl b -ionol, prepared by reacting b -ionone with calcium or lithium acetylide in liquid ammonia, is treated with ethyl magnesium bromide and the resulting organo magnesium bromide is allowed to react with the methyl ether of the 1 : 4-chlorhydrin of isoprene to give an acetylinic compound which is catalytically reduced and dehydrated by heating with glacial acetic acid and p-toluenesulphonic acid to give a vitamin A active compound of the formula <FORM:0630865/IV (b)/5> A similar product is obtained by dehydrating the acetylenic compound before reduction and treating the reduced compound with aqueous caustic potash to effect molecular rearrangement.  As well as the magnesium bromide of a -ethynyl-(b -ionol) the lithium compound, the magnesium chloride and the zinc iodide thereof are prepared and may be used in a similar manner.  Esters of halohydrins of isoprene are prepared by adding an agent capable of yielding a hypohalous acid, e.g. t-butyl hypochlorite, to a solution of isoprene in an organic carboxylic acid.  In an example, 1-chloro-2-methyl-4-acetoxybutene-2 is prepared, admixed with some of the 1 : 2 derivative.  By heating this with calcium bromide or sodium iodide the bromo or iodo compounds are formed.  Ethers of halohydrins of isoprene are prepared by adding an agent capable of yielding a hypohalous acid to a solution of isoprene in a primary or secondary alcohol or a phenol in the presence of a strongly acidic substance such as p-toluenesulphonic acid, stannic chloride or sulphuric acid.  In examples, the pulp of the methyl, ethyl and amyl ethers is described.  Samples have been furnished under Sect. 2 (5) of compounds prepared by (A) catalytic hydrogenation of a vinyl ethynyl carbinol of the formula I wherein X is an acetoxy group, followed by hydrolysis with alcoholic potassium hydroxide; (B) hydrogenation as in (A) followed by treatment with glacial acetic acid in the presence of a trace of p-toluenesulphonic acid to cause rearrangement of the double bonds with splitting off of water and finally hydrolysis of the acetyl group; and (C) heat treatment of the acetoxyvinylethynylcarbinol, catalytic hydrogenation of the product and hydrolysis to remove the acetyl group.