Patent GB-650302-A (GB)
Title: Improvements in and relating to the production of straight chain conjugated polyene esters and acids
IPC: C07C403/00
Filed: 1947-02-01
Abstract: <FORM:0650302/IV (b)/1> Polyene acids and esters of the formula <FORM:0650302/IV (b)/2> where R is a hydrocarbon radical and R1 is H or a hydrocarbon radical, are obtained by treating with a catalyst having an acidic character under the reaction conditions, either the b g -isomer, probably <FORM:0650302/IV (b)/3> or the corresponding b -hydroxy-a b -dihydroacid or ester <FORM:0650302/IV (b)/4>  The product of the reaction is an equilibrium mixture from which the desired acid or ester may be removed and the residue treated again. The starting material may comprise a mixture of the conjugated acids or esters with or without the hydroxy compound. The process is especially applicable to the production of compounds in which R is a b -unsaturated cyclohexene radical or isoprenologue thereof, e.g. those shown in Figs. 3 and 7.  The esterifying group R1 may be methyl, ethyl, phenyl, benzyl, octyl, palmityl, stearyl or allyl. Suitable acidic catalysts are iodine, phosphoric acid, phosphorus trichloride, phosphorus oxychloride, formic acid, oxalyl chloride, dimethylaniline hydriodide, p-toluene-sulphonic acid and zinc chloride +acetic acid; sulphuric acid is less suitable.  The reaction may be carried out in a solvent such as benzene, toluene, xylene, acetic acid, acetone, carbon tetrachloride, petroleum ether or mixtures of these, according to the solubility of the catalyst. Ethers such as isopropyl ether are less suitable.  Reaction temperatures may range from room temperature to reflux temperature. The reaction time may vary from 5 minutes to 1 day, according to the catalyst used, but may be reduced by adding a small amount of the hydroxy compound, e.g. 10-20 per cent.  Tables are given showing the reaction conditions and yields using various catalysts and solvents. The desired product may be separated from the reaction mixture by (1) distillation, preferably under reduced pressure; (2) solvent extraction, the a b -compounds being more soluble in polar solvents such as aqueous methanol, aqueous ethanol and dimethyl - sulpholane; or (3) chromatography on a mild adsorbent, e.g. sodium aluminium silicate.  When the product is an ester, it may be subsequently hydrolysed to the free acid.  The process may be used for the synthesis of vitamin A as follows: b -ionone is condensed with a haloacetate in the presence of zinc or magnesium to give a mixture which is treated according to the process of the invention to give a good yield of the ester (Fig. 3).  This is reduced with a hydride such as aluminium hydride or lithium aluminium hydride to the corresponding alcohol, which is then condensed with acetone in the presence of an aluminium or magnesium alkoxide to give the C18 ketone (Fig. 5).  This is again condensed with a haloacetate and zinc or magnesium, and the resultant mixture treated according to the process of the invention to isolate vitamin A acid ester (Fig. 7).  Reduction of this with lithium aluminium hydride gives vitamin A (Fig. 9), which may be esterified if desired.  Examples are given of these steps in the synthesis.  According to the Provisional Specifications, R may be an aliphatic or cycloaliphatic radical, or combination of these, saturated or unsaturated, and the formula of the product is given as <FORM:0650302/IV (b)/5> where X is or contains a carboxyl group or the corresponding ester group.  It is stated that the esterifying group is preferably unsaturated, allyl, crotonyl and phenyl being specified.