GB438659A - Manufacture of substituted amides of aliphatic-aromatic acids - Google Patents

Abstract

Amides of phenylated acetic acids, which contain an amine-nitrogen attached to the amide-nitrogen by an alkylene residue, are prepared by (1) reacting a phenylated acetic acid with an aliphatic diamine or triamine containing at least one free amino-hydrogen and having an alkyl- or cycloalkyl-amino group; (2) causing a metal compound of a phenylated acetic acid amide to react with a reactive ester of an aliphatic alkyl- or cycloalkyl-amino-alcohol; (3) treating a phenylated acetic acid with an aliphatic amino-alcohol and reacting the product with an alkyl- or cycloalkyl-amine in presence of a dehydrogenating catalyst; (4) causing a metal compound of a phenylated acetic acid amide to react with an alkylene dihalide or halogenhydrin and treating the product with an alkyl- or cycloalkyl-amine. The products may be converted into the corresponding quaternary ammonium compounds. The amides and their ammonium compounds possess therapeutic properties. Examples describe the preparation of (1) a a a -diphenyloxyacetic acid-2-diethylaminoethylamide by heating the methyl ester of the acid with 2-diethylaminoethylamine; the product may be converted into the quaternary compounds by means of methyl iodide or dimethyl sulphate; (2) diphenylacetic acid-2-dimethylaminoethylamide by treating diphenylacetic acid with thionyl chloride and heating the product with 2 - dimethylamino - ethylamine; (3) phenylacetyl-2-diethylaminoethylamide from phenylacetyl chloride and 2-diethylamino-ethylamine; (4) diphenylacetic acid-2-diethylaminoethylamide from the corresponding acid and amine, or by heating diphenylacetic acid amide with sodamide and adding chlorethyldiethylamine; its methochloride and methiodide are described; (5) diphenylacetic acid-3-diethylaminopropylamide by reacting diphenylacetic acid chloride with diethylamino-propylamine; its methochloride and methiodide are described; (6) a a -diphenyl-a -oxyacetic acid-2 : 2-dimethyl-3-diethylaminopropylamide by treating a a -diphenyl - a - acetoxyacetyl chloride with 2 : 2-dimethyl - 3 - diethylaminopropylamine and saponifying the product; (7) tropic acid-2-diethylamino-ethylamide by interaction of acetyltropic acid chloride with 2-diethylaminoethylamine, followed by saponification; (8) diphenylacetic acid-N-2-diethylaminoethyl-N-benzylamide from the acid chloride and N-2-diethylaminoethyl - N - benzylamine; (9) triphenylacetic acid - 2 - diethylaminoethylamide from the acid chloride and 2-diethylamino-ethylamine; (10) diphenylacetic acid - 2 - diethylaminoethylamide by first reacting diphenylacetic acid or an ester thereof with aminoethanol, then treating the resulting oxyethylamide with phosphorus pentachloride to give the chlorethylamide, and finally heating with diethylamine; the oxyethylamide may also be prepared by the action of an ethylene halogenhydrin or an alkali or alkaline earth metal compound of diphenylacetic acid amide; similarly, the chlorethylamide may be obtained by reacting the same metal compound with ethylene chlorobromide; the final product may also be obtained by direct reaction of diphenylacetic acid-2-oxyethylamide with diethylamine in presence of nickel and an inert solvent at a raised temperature under pressure. The following additional products are referred to: acetylbenzilic acid-2-diethylaminoethylamide, a - phenyl - a - methoxyacetic acid - 2-diethylaminoethylamide, a -phenyl-a a -diethylacetic acid-2-diethylaminoethylamide, mandelic acid - 2 - diethylaminoethylamide, phenylacetic acid-2-piperidinoethylamide and its methiodide, diphenylacetic acid-2-piperidinoethylamide, and diphenylacetic acid-di-(2-piperidinoethyl)-amide. Specifications 219,304, 294,582, [both in Class 2 (iii)], and 368,590 are referred to. The Provisional Specifications describe the invention with reference to the production of the substituted amides of aliphatic-aromatic acids in general. In addition, the first Provisional Specification refers to hydrocinnamic acid and phenyl-lactic acid as acid components, describes the preparation of dihydrocinnamic acid-2-diethylaminoethylamide from the acid and the amine, and mentions diphenyleneoxyacetic acid-2-diethylaminoethylamide in the list of products.