PROCEDEU PENTRU PREPARAREA UNOR P-HALOFENIL-2-PIROLIDINONE

摘要

1350582 Substituted phenyl-2-pyrrolidinones UCB SA 21 July 1971 [24 July 1970] 35948/70 Heading C2C Novel substituted phenyl-2-pyrrolidinones of the general formula wherein R is a halogen atom, an alkyl, haloalkyl, alkenyl, alkynyl or alkoxy radical having up to 5 carbon atoms, or a nitro, amino or hydroxyl group; R 1 is an alkyl, alkenyl or alkynyl radical having up to 5 carbon atoms or an optionally ring-substituted aryl or aralkyl radical, R 2 is a hydrogen atom or a C 1-5 alkyl or aryl radical, R 3 is a hydrogen atom, an alkyl, alkenyl or alkynyl radical having up to 7 carbon atoms, or a cycloalkyl or aralkyl radical and n is 1, 2 or 3, and the cis- and trans-stereoisomers, racemates and optically-active isomers thereof are prepared (a) by cyclizing a 4-aminobutyric acid or an alkyl ester thereof of the general formula H(R 3 )N-A-COOX, wherein X is a hydrogen atom or a C 1-4 alkyl group and A is a trimethylene chain substituted by (R) n -phenyl, R 1 and R 2 radicals; (b) by hydrolysing a 2- iminopyrrolidine of the general formula (c) by reacting, at elevated temperature, a lactone of the general formula with a compound of the general formula R 3 NH 2 ; (d) by cyclizing, in the presence of an alkaline condensation agent, a halobutyramide of the general formula Hal-S-CONH(R 3 ), wherein Hal is a halogen atom; (e) by thermally decarboxylating a 2-pyrrolidinone-3-carboxylic acid of the general formula (f) when R 3 is other than a hydrogen atom, by reacting the corresponding compound in which R 3 is a hydrogen atom with a compound of the general formula R 3 -Hal in the presence of an alkaline condensation agent; (g) when R is a nitro group in the para-position, by nitrating the corresponding compound in which R is a hydrogen atom; (h) when R is an amino group in the para-position, by reducing the corresponding compound in which R is a nitrogroup in the para-position; (i) when R is a halogen atom in the para-position, by diazotizing the corresponding compound in which R is an amino group in the para-position in an aqueous medium with an alkali metal nitrite in the presence of a hydrohalic acid at 0-5‹ C. and subjecting the resulting diazonium salt to a Sandmeyer reaction in the presence of Cu powder or a cuprous halide; and (j) when R is a hydroxyl group in the paraposition, by diazotizing the corresponding compound in which R is an amino group in the paraposition in an aqueous medium with an alkali metal nitrite in the presence of a hydrohalic acid at 0-5‹ C. and heating the aqueous solution of the resulting diazonium salt; followed optionally by separating resulting diastereo isomer mixtures into the cis- and trans-components thereof or separating resulting racemates into the optically-active isomers thereof. 4-Aminobutyric acids and alkyl esters thereof of the second general formula above are prepared by catalytically hydrogenating the corresponding 3-cyanopropionic acid or alkyl ester thereof (prepared by reaction of the corresponding acetonitrile and bromoacetic acid or alkyl ester thereof in the presence of sodium hydride). Ethyl 3 - p - chlorophenyl - 4 - nitropentanoate is prepared by reaction of nitroethane, ethyl pchloro-cinnamate and a 35% solution of trimethylbenzyl - ammonium hydroxide in methanol. Pharmaceutical compositions having effects on the central nervous system comprise, as active ingredient, a substituted phenyl-2-pyrrolidinone of the first general formula above, in admixture with a solid or liquid pharmaceutical diluent or carrier.