Patent GB-791350-A (GB)
Title: 4,4-disubstituted-5-oxohexanoic acids and derivatives thereof
IPC: C07C59/84
Filed: 1955-07-13
Abstract: The invention comprises compounds of the general formula <FORM:0791350/IV (b)/1> and salts thereof wherein R is a mononuclear aryl radical and R1 is a mononuclear aralkyl radical.  R and R1 may contain as substituents halogens or alkyl, alkoxy, nitro, carboxy or hydroxyalkyl groups.  Such compounds are obtained by a process in which an a -arylacetone is converted to an a -aryl-a -aralkylacetone by aralkylation, the product thus formed is converted to the corresponding 4-aryl-4-aralkyl-5-oxohexanenitrile by cyanoethylation and the nitrile then is hydrolysed to 4-aryl-4-aralkyl-5-oxohexanoic acid. If desired, the acid is converted to a salt, ester, amide, enol-lactone or cyclohexanedione.  Aralkylation may be effected by reacting the appropriate phenylacetone with an aralkyl halide in the presence of an alkali metal hydroxide or tertiary alkoxide. Cyanoethylation can be effected by treating the a -aryl-a -aralkylacetone with acrylonitrile in the presence of a solvent such as tertiary butyl alcohol, acetonitrile or 1,4-dioxane and a catalyst such as benzyltrimethylammonium hydroxide or potassium hydroxide. Conversion of the acid to its salts or esters is carried out in the usual way.  The acid is converted to the corresponding 4 - aryl - 4 - aralkyl - 5 - hydroxy-5-hexenoic acid lactone by reaction with isopropenyl acetate.  The lactone heated with an amine gives the amide of the 4-aryl-4-aralkyl-5-oxohexanoic acid.  With a disubstituted amino-alkanol it gives the corresponding disubstituted amino-alkyl hexanoate.  Esters of 4-aryl - 4 - aralkyl - 5 - oxohexanoic acids on treatment with a basic catalyst such as a sodium alkoxide give the corresponding 4-aryl-4-aralkyl-1,3-cyclohexanediones.  These latter compounds can also be prepared by condensation of a 1-aryl - 1 - aralkyl - 2 - propanone with b  - propiolactone in the presence of a condensing agent such as potassium tertiary butoxide.  The 4-aryl-4-aryl-5-oxohexanoic acids, as their brucine salts can be resolved into their optical isomers.  Examples describe the preparation by the above general methods of 1-aryl-1-aralkyl-2-propanones, 4 - aralkyl - 4 - aryl - 5 - oxohexa - nenitriles, 4 - aralkyl - 4 - aryl - 5 - oxohexanoic acids, alkyl esters and basic esters of such acids, 4 - aralkyl - 4 - aryl - 1,3 - cyclohexanediones, 4 - aralkyl - 4 - aryl - 5 - hydroxy - 5 - hexenoic acid lactones, and amides of 4-aryl-4-aralkyl-5-oxohexanoic acids.  In specific compounds the aralkyl radical is selected from benzyl, o-, m- or p-chlorobenzyl, o-fluorobenzyl, o-bromobenzyl, 2,4-, 3,4- or 2,6-dichlorobenzyl, 3,4,5-trichlorobenzyl, o- or m-methylbenzyl, 2,4,6-trimethylbenzyl, p-propylbenzyl, p-ethoxybenzyl, o-methoxybenzyl, and (in the propane and nitrile) m-cyanobenzyl radicals.  The aryl radicals are selected from phenyl, o- or p-chlorophenyl, 3,4-dichlorophenyl, 3,4,5-trichlorophenyl, m-methylphenyl, p - ethylphenyl and o-, m- or p-methoxyphenyl radicals.  As basic esters, specific 2 - dimethylaminoethyl, 2 - diethylaminoethyl, 3 - diethylaminopropyl, 4 - di - methylaminobutyl, and 3-diethylamino-1-butyl esters are prepared.  In examples: (72) and (73) 4-(o-chlorobenzyl)-4-phenyl-5-oxohexanoic acid is resolved as its brucine salt into its optical isomers; (74) levo-4-(o-bromo-benzyl)-4-phenyl-5-oxohexanoic acid is prepared similarly; (76) levo methyl 4-(o-chloro-benzyl)-4-phenyl-5-oxohexanoate is prepared by esterification of the corresponding acid.