Patent GB-803120-A (GB)
Title: Improvements in the preparation of keto acids
IPC: C07C59/76
Filed: 1955-06-28
Abstract: Delta-keto acids with the general formula R.CO(CH2)3COOH (I) are prepared by subjecting a derivative of 1-acetyl-1-acyl glutaric acid of the formula: <FORM:0803120/IV (b)/1> in which A and B are groups which can be converted into carboxylic groups by hydrolysis, and R is an aliphatic hydrocarbon group, substituted or not, containing at least 4 carbon atoms, either to alkaline hydrolysis or to alkali catalysed alcoholysis followed, after purification of the reaction products if desired, by alkaline hydrolysis, preferably at temperatures between 70 DEG  C. and the boiling point of the mixture. The group R may contain a terminal reactive group, e.g. a double bond, an hydroxy group or a group which on hydrolysis is convertible into an hydroxyl group, such as an acyloxy group or a halogen atom. Groups A and B may be alkoxy carbonyl groups, cyano groups or amide groups.  The reaction is preferably effected with 10-25 per cent soda or potash lye as the hydrolysing agent.  Alternatively the starting material (II) may be treated with an alcohol in the presence of an alkaline catalyst such as an alkali metal alcoholate, an alkali metal hydroxide or ammonia, either at room temperature for some hours or at boiling point for 1/4 to 1/2 hour.  During this treatment the acetyl group is split off, and the product, after purification is desired, is then hydrolysed with aqueous alkali to give the desired keto acid. The derivatives of 1-acetyl-1-acyl glutaric acid (I) used as starting material may be obtained by condensation of an appropriate acid halide with a derivative of 1-acetyl glutaric acid.  The latter may be prepared by condensation of an acetoacetic ester with acrylonitrile, acrylamide or esters of acrylic acid under the influence of alkaline catalysts.  The delta-keto acids (I) may be reduced to hydroxy acids and converted to lactones which are valuable odoriferous compounds.  They can also be converted to fatty acids by total reduction of the keto group.  The keto acids which contain a terminal reactive group, such as an hydroxy group, in the radical R can be converted into macrocyclic lactones.  In examples: (1) methyl 4-keto-3-ethoxy-carbonyl-pentanecarboxylic acid is condensed with decene-9-carboxylic acid chloride in the presence of magnesium, benzene, carbon tetrachloride and ethanol to give methyl 4-keto-3-acetyl - 3 - ethoxycarbonyl - tetradecene - 13-carboxylate which is boiled with methanol and soda lye to give 4-keto-tetradecene-13-carboxylic-acid-(1); the product can be converted into pentadecanolide in accordance with Specification 671,004; (2) to (5) describe similar preparations of the product of (1); (6) methyl-4-keto-3-ethoxycarbonyl-pentane-carboxylate is condensed with hexane carboxylic acid with magnesium as catalyst as in (1), and hydrolysed with soda lye to give 4-keto-decane-carboxylic acid-1; (7) to (14) describe similar preparations of the product of (6) either by alkaline hydrolysis or alkali-catalysed alcoholysis and hydrolysis; (15) 3-ethoxycarbonyl-4-keto-pentane carboxylic acid nitrile is condensed with caproic acid chloride with the aid of magnesium and the product is converted to 4-keto-nonane-carboxylic-acid-1; (16) methyl 4-keto-3-ethoxy-carbonyl-pentanecarboxylate is condensed with heptane carboxylic acid chloride with magnesium as catalyst; boiling the product with ethanol and potassium yields ethyl-4-keto-3-ethoxycarbonyl-pentane carboxylate and ethyl 4-keto-3-ethoxycarbonyl-undecane carboxylate and the latter is hydrolysed with soda lye to yield 4-keto-undecane-carboxylic acid-1; (17) 10-bromo-decane-carboxylic acid chloride is condensed with ethyl 4-keto-3-ethoxycarbonyl-pentane carboxylate with magnesium as catalyst giving ethyl 4 - keto - 3 - acetyl - 3 - ethoxy carbonyl - 14 - bromo - tetradecane - carboxylate which is boiled with soda lye to give 14-hydroxy-4-keto-tetradecane carboxylic acid and 10-hydroxy decane carboxylic acid; the former compound after reduction of the keto group can be cyclized to pentadecanolide.