GB720198A - Manufacture of new dioxopiperidines - Google Patents

Abstract

The invention comprises 2 : 6-dioxopiperidines of the general formula <FORM:0720198/IV (b)/1> (wherein R1 represents an aliphatic hydrocarbon residue of 1-3 carbon atoms, R2 represents a phenyl residue which is unsubstituted or substituted by a halogen atom, and R3 represents hydrogen or an aliphatic hydrocarbon residue of 1-3 carbon atoms), which may be prepared from 2-R1, R2-disubstituted pentane-1:5-diacids or their functional derivatives (e.g. by reacting the acids or their functional derivatives, e.g. halides, with ammonia or amines, or by intramolecular acylation, by the action of condensing agents, of the monoamides of the acids or their functional derivatives, which may be formed in situ, e.g. from the mono- or di-nitriles or nitrile esters, or by heating the diamides, diammonium salts or mononitrile ammonium salts of the acids). When the product is unsubstituted in the 1-position, an aliphatic hydrocarbon residue may be subsequently introduced there, e.g. by the action of reactive esters of alcohols or of aliphatic diazo compounds (preferably in the presence of condensing agents capable of converting the dioxopiperidines into metal derivatives, e.g. alkali or alkaline-earth metals or their amides, hydrides, hydrocarbons or alcoholates). The products are useful as anticonvulsive agents. In examples: (1) 2-phenyl-2-ethylpentane-1 : 5-diacid 1-mononitrile is heated with glacial acetic acid and concentrated sulphuric acid to produce 3 - phenyl - 3 - ethyl - 2 : 6 - dioxopiperidine; (2) 2-phenyl-2-isopropylpentane-1 : 5-diacid 1-mononitrile similarly yields 3-phenyl-3-isopropyl-2 : 6-dioxopiperidine; (3) the 1-mononitrile in (1) is replaced by the 1-monoamide; (4) the product of (1) is warmed with sodamide in toluene and the product heated with methyl iodide under pressure, producing 1 - methyl - 3 - phenyl - 3 - ethyl-2 : 6-dioxopiperidine; (5) n-propyl bromide similarly gives 1 - n - propyl - 3 - phenyl - 3-ethyl - 2 : 6 - dioxopiperidine; (6) 2 - p - chlorophenyl - 2 - ethylpentane - 1 : 5 - diacid 5-monomethyl ester 1-mononitrile is heated with glacial acetic acid and 85 per cent sulphuric acid to form 3-p-chlorophenyl-3-ethyl-2 : 6-dioxopiperidine; (7) 2-phenyl-2-methylpentane-1 : 5-diacid 5-monomethyl ester 1-mononitrile similarly yields 3-phenyl-3-methyl-2 : 6-dioxopiperidine; (8) the product of (6) is methylated as in (4) except that dioxan is used instead of toluene as solvent. The aliphatic hydrocarbon residue may also be an unsaturated radical, e.g. allyl. 2 - Phenyl - 2 - ethyl - and - 2 - isopropylpentane - 1 : 5 - diacid 1 - mononitriles are obtainable by condensing a -phenylbutyronitrile or a -phenyl-b -methylbutyronitrile with methyl acrylate and hydrolysing the resulting monomethyl ester mononitriles. 2 - p - Chlorophenyl - 2 - ethyl - and 2 - phenyl-2 - methyl - pentane - 1 : 5 - diacid 5 - monomethyl ester 1-mononitriles are obtainable similarly (but omitting the hydrolysis) from a -(p - chlorophenyl) - butyronitrile and a -phenylpropionitrile respectively.