Patent GB-741419-A (GB)
Title: Manufacture of basic ethers
IPC: C07D295/092
Filed: 1952-05-26
Abstract: The invention comprises compounds of the general formula <FORM:0741419/IV(a)/1> in which X is -CO- or -CH2- R1 represents an alkyl radical of up to 4 carbon atoms and R2 is an aminoalkyl or mono- or dialkylaminoalkyl radical or an alkyl radical which is substituted by a nitrogen atom which forms part of a heterocyclic ring and their acid addition salts.  It comprises also the preparation of these compounds by esterifying or etherifying a compound of the above general formula in which R1 or R2 is hydrogen with a monohydric alkanol of up to 4 carbon atoms, or with a compound containing an aminoalkyl or mono or dialkylaminoalkyl or an alkyl radical substituted by a nitrogen atom forming part of a heterocyclic ring, respectively. The starting material for this process may be prepared by esterifying or etherifying 4-hydroxybenzophenone - 2 - carboxylic acid or 41-hydroxy - diphenylmethane - 2 - carboxylic acid. The etherification of the phenolic hydroxy group may be effected by reacting the alkali or alkaline earth metal phenolate with a reactive ester such as the halide, sulphonic acid ester, sulphuric acid ester or alkyl sulphuric acid ester of the appropriate basically substituted aliphatic alcohol.  Basic ethers of the above general formula in which X represents CH2 may be made by reduction of the corresponding compound in which X represents CO, e.g. by reaction with zinc dust and ammonia.  Basic ethers of the above general formula in which R2 represents an aminoethyl group may be made by reacting an ester of 41-hydroxybenzophenone-2-carboxylic acid or 41-hydroxydiphenylmethane - 2 - carboxylic acid with chloracetonitrile and reducing the cyanomethyl compound obtained by means of hydrogen in methanolic solution in the presence of a catalyst such as Raney nickel.  In examples: (1) 41-hydroxybenzophenone - 2 - carboxylic acid methyl ester is treated with b -piperidinoethyl chloride in the presence of potassium carbonate to give 41-b -piperidinoethoxy-2-carbomethoxy - benzophenone hydrochloride; (2) 4 - hydroxybenzophenone - 2 - carboxylic acid ethyl ester is reacted with b -piperidinoethyl chloride to give 41-b -piperidino-ethoxybenzophenone-2-carboxylic acid ethyl ester hydrochloride; (3) 41-hydroxybenzophenone-2-carboxylic acid butyl ester is treated with b -piperidinoethyl chloride to give 41-b -piperidinoethoxy - (2) - carbobutoxy - benzophenone which is purified as its oxalate and converted into the citrate; (4) 41-hydroxybenzophenone-2-carboxylic acid ethyl ester is reacted with b -diethylaminoethyl chloride to give 41-b -diethylaminoethoxy - 2 - carbethoxy - benzophenone hydrochloride; (5) 41-hydroxy-diphenylmethane-2-carboxylic acid methyl ester is reacted with b -piperidinoethyl chloride to give 41 - b  - piperidinoethoxy - 2 - carbomethoxy - diphenylmethane hydrochloride; (6) 41 - hydroxy - diphenylmethane - 2 - carboxylic acid ethyl ester is reacted with b -piperidinoethyl chloride to give 41-b -piperidinoethoxy - 2 - carbethoxy - diphenylmethane which is purified via the oxalate and converted to the citrate; (7) 41-hydroxy-benzophenone-2-carboxylic acid ethyl ester is reacted with b -pyrrolidinoethyl chloride to give 41 - b  - pyrrolidinoethoxy - 2 - carbethoxy-benzophenone hydrochloride; (8) 41-hydroxy-benzophenone-2-carboxylic acid ethyl ester is heated with chloracetonitrile and the resulting 41 - cyanomethoxy - 2 - carbethoxy - benzophenone is treated with hydrogen and Raney nickel to give 41-aminoethoxy-2-carbethoxy-benzophenone which is isolated as the oxalate; and (9) 41-hydroxy-benzophenone-2-carboxylic acid ethyl ester is reacted with chloromethylimidazoline hydrochloride to give 41-imidazolinomethoxy - 2 - carbethoxy - benzophenone isolated as the oxolate and (10 41-hydroxy-benzophenone-2-carboxylic acid is converted into its sodium derivative and reacted with b -piperidinoethyl chloride to give 41-b -piperidinoethoxy - carboxy - (2) - benzo-phenone separated as the internal salt which is esterified to the corresponding 2-carbethoxy compound.