Patent GB-728527-A (GB)
Title: Improvements in or relating to meta-amino-alkoxy-benzoic acid esters and process formaking same
Filed: 1952-11-27
Abstract: The invention comprises compounds of the formula <FORM:0728527/IV (b)/1> in which R1 and R4 are hydrogen or alkyl groups containing 1 to 8 carbon atoms, R3 is an alkyl group containing from 1 to 16 carbon atoms and R2 is an alkyl group containing 1 to 8 carbon atoms, OR3 being located at one of the positions 2, 5 and 6 on the benzene ring.  The compounds are prepared by alkylating the phenolic group of a compound of formula <FORM:0728527/IV (b)/2> where R is a lower alkyl group (e.g. methyl) and where the phenolic group is in one of the positions 2, 5 and 6, with an alkyl compound having 1 to 16 carbon atoms (preferably a butyl compound, e.g. butyl iodide) to form an alkoxy group, hydrolysing the product to remove R, halogenating the resulting carboxyl group (e.g. with thionyl chloride), reacting the resulting aroyl chloride with an alkylamino-ethanol (e.g. b -diethyl-amino-ethanol) to form a salt of the corresponding alkylamino-ethyl nitro-alkoxybenzoate and reducing the nitro group thereof (e.g. with iron filings) to form the corresponding alkylamino - ethylamino - alkoxy - benzoate salt.  The examples describe the preparation of the hydrochlorides of b -diethylaminoethyl-3 - amino - 2 - butoxy - benzoate, b  - diethylaminoethyl 3 - amino - 5 - butoxy - benzoate, b  - isobutylaminoethyl 3 - amino - 5 - butoxybenzoate, b - n - amylaminoethyl 3 - amino - 5-butoxy - benzoate, b  - ethylaminoethyl 3-amino - 5 - butoxy - benzoate, b  - (n)propylaminoethyl 3 - amino - 5 - butoxy - benzoate, b  - diethylaminoethyl 3 - amino - 6 - butoxybenzoate, b  - diethylaminoethyl 3 - amino - 6-decoxy - benzoate, b  - diethylaminoethyl 3-amino - 6 - cetoxy - benzoate, b  - isobutylaminoethyl 3 - amino - 6 - cetoxy - benzoate, b  - isobutylaminoethyl 3 - amino - 6 - butoxy - benzoate, b  - (n)amylaminoethyl 3 - amino - 6 - butoxy - benzoate, b  - 11 - methylbutylaminoethyl 3 - amino - 6 - butoxy - benzoate, b  - 21-ethylhexylaminoethyl 3 - amino - 6 - butoxybenzoate, b  - dimethylaminoethyl 3 - amino - 6-butoxy - benzoate, b  - 11 - methylheptylaminoethyl 3 - amino - 6 - butoxy - benzoate, and b -diethylaminoethyl 3 - butylamino - 6 - butoxybenzoate.  3 - Nitro - 5 - amino - benzoic acid is prepared by reducing 3,5-dinitro-benzoic acid with ammonium sulphide.  3 - Nitro 5 - hydroxy - benzoic acid is prepared by diazotization and hydrolysis of 3-nitro-5-amino-benzoic acid.  3 - Nitro - salicylic acid is prepared by nitrating salicylic acid.  The methyl esters of 3-nitro-salicylic acid, 3-nitro - 5 - hydroxy - benzoic acid and 3 - nitro-6 - hydroxy - benzoic acid are prepared by refluxing the corresponding acids with methyl alcohol in a stream of dry hydrogen chloride. p   Methyl 3 - nitro - 2 - butoxy - benzoate, methyl 3 - nitro - 5 - butoxy - benzoate and methyl 3-nitro - 6 - butoxy - benzoate are prepared by condensing the corresponding hydroxy compounds with butyl iodide in presence of silver oxide; esters of 3 - nitro - 6 - decoxy - benzoic and 3-nitro - 6 - cetoxy - benzoic acids are similarly prepared.  From these products the corresponding acids are prepared by hydrolysis of the ester group and the corresponding acid chlorides are prepared by subsequent treatment of these acids with thionyl chloride. Alkylaminoethyl 3 - nitro - 2,5 or 6 - alkoxybenzoates are prepared by condensing the corresponding acid chlorides with the appropriate alkylaminoethanol; the following are prepared or described: b  - diethylaminoethyl 3 - nitro-2 - butoxy - benzoate, b  - diethylaminoethyl 3-nitro - 5 - butoxy - benzoate, b  - isobutylaminoethyl 3 - nitro - 5 - butoxy - benzoate, b -(n)propylaminoethyl 3 - nitro - 5 - butoxy - benzoate, b  - diethylaminoethyl 3 - nitro - 6 - butoxybenzoate, b  - diethylaminoethyl 3 - nitro - 6-decoxy - benzoate, b  - diethylaminoethyl 3-nitro - 6 - cetoxy - benzoate, b  - isobutylaminoethyl 3 - nitro - 6 - butoxy - benzoate, b  - isobutylaminoethyl 3 - nitro - 6 - cetoxy - benzoate, b  - (n)amylaminoethyl 3 - nitro - 6 - butoxybenzoate, b  - 11 - methylbutylaminoethyl 3-nitro - 6 - butoxy - benzoate, b  - 21 - ethylhexylaminoethyl 3 - nitro - 6 - butoxy - benzoate, b -dimethylaminoethyl 3 - nitro - 6 - butoxybenzoate and b  - 11 - methylheptylaminoethyl 3-nitro-6-butoxy-benzoate.