Patent GB-772199-A (GB)
Title: A process for the manufacture of -a,-ß-unsaturated carboxylic acids and esters thereof
IPC: C07C51/09
Filed: 1955-02-11
Abstract: The invention comprises 6-[21:61:61-trimethyl - cyclohexen - (11) - yl] - 4 - methyl - hexadien-(2 : 4)-oic-(1)-acid and a process for preparing it and other a ,b -unsaturated carboxylic acids and esters thereof wherein a b -halogeno-vinyl ether is reacted with an alkali metal amide in liquid ammonia, the resulting solution is reacted with an aldehyde or ketone, the reaction product is hydrolysed to give a secondary or tertiary carbinol, which is treated with an acid to give the a ,b -unsaturated carboxylic acid ester which may finally be hydrolysed to the acid. Specified p-halogeno-vinyl ethers are b -chloro-vinyl methyl or ethyl or phenyl ether and b -bromo-vinyl ethyl ether.  Specified alkali metal amides are lithium, sodium and potassium amides. Specified aldehydes and ketones are propionaldehyde, butyraldehyde, methacrolein, b -methyl-crotonaldehyde, citral, 4 - [21:61:61 - trimethyl - cyclohexen - (11) - yl] - 2 - methyl - buten - 2 - al - (1), benzaldehyde, cinnamaldehyde, acetone, methyl ethyl ketone, diethyl ketone, mesityl oxide, 6 - methyl - heptanone - (2), 5 : 6 - dimethyl - heptanone-(2), pseudoionone, cyclohexanone, 2 : 6 : 6 - trimethyl - cyclohexanone - (1), cyclohexen - (2) - one, 2 : 6 : 6 - trimethyl - cyclohexen-(2) - one - (1), dihydro - betaionone, betaionone, 8 - [21:61:61 - trimethyl - cyclohexen - (11)-yl]-6 - methyl - octatrien - (3 : 5 : 7) - one - (2), acetophenone, acetonyl acetone, octene-(4)-dione-(2 : 7), succinic dialdehyde, 2 : 7 - dimethyl - octatrien - (2 : 4 : 6) - dial - (1 : 8), 2 : 7-dimethyloctadien - (2 : 6) - ine - (4) - dial - (1 : 8), methoxy acetone, levulinic acid, p-dimethylamino- or -hydroxy - benzaldehyde, androsterone and oestrone.  In the process the p-halogeno-vinyl ether is reacted in liquid ammonia with two equivalents of alkali metal amide to give an alkali metal derivative of an ethinyl ether.  The resultant reaction mixture is further reacted with the aldehyde or ketone, to give an alkali metal derivative of a secondary or tertiary carbinol, the quantities being preferably such that each carbonyl group is reacted with a molar equivalent of the alkali metal derivative. When the carbonyl reactant contains free hydroxy or carbonyl groups, an additional molar equivalent of alkali metal amide per hydroxy or carboxy group is used in the first stage.  The reaction product is stable in liquid ammonia and may be hydrolysed to the carbinol without isolation or purification.  The hydrolysis may be carried out by treatment of the mixture with an ammonium salt such as ammonium chloride, followed by evaporation of the ammonia.  The treatment with the acid, which effects a rearrangement of the secondary or tertiary carbinol to an ester of an a ,b -unsaturated carboxylic acid, may be carried out by dissolving the product of the hydrolysis stage in an inert solvent and shaking the resultant solution with a dilute aqueous mineral acid such as sulphuric acid.  The ester can be isolated and may be hydrolysed with dilute aqueous alkali to give the free acid.  In Examples: (1) a solution of sodium amide in liquid ammonia was reacted with b -chloro-vinyl ethyl ether, the mixture being reacted further with 6-methyl-hepten-(5)-one-(2), hydrolysed by the addition of ammonium chloride, the carbinol, i.e. 1-ethoxy-3-hydroxy-3 : 7-dimethylocten-(6)-ine-(1) being isolated and then treated with aqueous sulphuric acid to give the ethyl ester of 3 : 7-dimethyl-octadien-(2 : 6)-oic-(1)-acid from which the acid was obtained by hydrolysis in methanolic sodium hydroxide; (2) as in (1) but reacting lithium amide with b -chloro-vinyl ether and then reacting with 4[21 : 61 : 61 - trimethyl - cyclohexen - (11) - yl]-2-methyl-buten-(2)-al-(1) and not isolating the carbinol, the ethyl ester of 6-[21 : 61 : 61-tri methyl - cyclohexen - (11) - yl] - 4 - methyl - hexadien-(2 : 4)-oic-(1)-acid, the free acid and the methyl ester thereof were obtained; (3) as in (2) but using benzaldehyde, ethyl cinnamate and cinnamic acid were obtained; (4) as in (3) but not isolating the ester the following acids were obtained from the corresponding ketones: 2 : 6 : 6 - trimethyl - cyclohexen - (2) - one - (1) gave [21 : 61 : 61 - trimethyl - cyclohexene - (21) - ylidene]-acetic acid, propionaldehyde gave pentene-(2)-oic-(1)-acid, methyl ethyl ketone gave 3 - methyl - penten - (2) - oic - (1) - acid, acetophenone gave b -methyl-cinnamic acid and dehydro-isoandrosterone acetate gave 3b -hydroxy - pregnadien - [5 : 17(20)]-oic-(21) acid.  Geraniol may be obtained by the reduction with lithium aluminium hydride of 3 : 7-dimethyloctadien-(2 : 6)-oic-(1) acid ethyl ester.