Patent GB-321968-A (GB)
Title: Process for the manufacture of halogen substituted aminobenzoic acid alkamine esters
Filed: 1928-07-23
Abstract: 321,968. Williams, W. P., (Schering- Kahlbaum Akt.-Ges.). July 23, 1928. Samples furnished. Halogenated aminobenzoic acid alkamine esters are prepared either by halogenating an aminobenzoic acid alkamine ester, or by converting a halogennitrobenzoic acid or halogenaminobenzoic acid by the usual methods. The products possess anaesthetic properties. According to the examples, (1) the diethylaminoethanol ester of 3-iodo-4-aminobenzoic acid is prepared by passing gaseous iodine chloride into a hydrochloric acid solution of p-aminobenzoyl-diethylaminoethanol; the iodine chloride may be employed in solution, or elementary iodine may be used; (2) the addition of bromine water to an aqueous solution of p-aminobenzoyldiethylaminoethanol yields 3: 5-dibromo-4- aminobenzoyl-diethylaminoethanol; (3) by bromination of the product of (1), 3-iodo-5-bromo- 4-aminobenzoyl-diethylaminoethanol is produced; in the same way is effected the halogenation of N-methyl- or ethyl-aminobenzoyl-dimethylamino- or piperidino-ethanol or 1-propanol or -butanol, or of p-aminobenzoyl-ethylfuromethylaminoethanol; thus the bromination of 4-aminobenzoic acid piperidinoethanol ester gives the 3: 5-dibromobody, whilst the chlorination of 4-aminobenzoyl- #-ethoxy-gamma-diethylaminopropanol (prepared by reduction of the reaction product of p-nitrobenzoyl chloride and alpha-oxy-#-ethoxy-gamma-diethylaminopropane) forms the 3: 5-dichloro compound; (4) 2-amino-4-iodobenzoic acid diethylaminoethanol ester is obtained from 2-nitro-4- iodobenzoic acid by treatment with thionyl chloride, interaction of the resulting acid chloride with diethylaminoethanol followed by reduction with stannous chloride; the same product results from the treatment of 4-iodo-2-nitrobenzoyl-#-chlorethanol (prepared from 4-iodo-2- nitrobenzoyl chloride and ethylene chlorhyrin) with diethylamine and subsequent reduction; by use of piperidine instead of diethylamine, 2- amino-4-iodobenzoic acid piperidinoethanol ester is obtained; (5) 2-bromo-4-aminobenzoic acid diethylaminoethanol ester is prepared in the same manner as (4) above from 2-bromo-4-nitrobenzoic acid ; (6) 3 : 5-dibromo-4-aminobenzoic acid diethylaminoethanol ester is produced from 3 : 5- dibromo-4-aminobenzoic acid by treatment with ethylene chlorhydrin and interaction of the resulting chlorethyl ester with diethylamine; the coiresponding methylamino body is obtained by starting with 3: 5-dibromo-4-methylaminobenzoic acid, which is prepared by methylating 3 : 5-dibromo-4-aminobenzoic acid with methyl iodide either directly or after acylation of the acid, say with p-toluenesulphonic acid, and subsequent saponification; (7) 3-iodo-4-aminobenzoic acid diethylaminoethanol results when 3-iodo-4-aminobenzoic acid or its methyl ester (obtained by esterification of the acid, say with methyl alcohol and hydrochloric acid) is heated with diethylaminoethanol, hydrochloric acid being present when the amino acid is used; the same product is also obtained when the silver salt of 3-iodo-4- aminobenzoic acid is decomposed with #-diethylaminoethyl halide; (8) 4-iodo-3-aminobenzoyl-diethylaminoethanol is prepared from 4-aminobenzoic acid by diazotization, treatment with potassium iodide, nitration conversion of the 4- iodo-3-nitro-benzoic acid into its chloride by means of thionyl chloride, interaction with diethylaminoethanol and finally reduction with tin and hydrochloric acid. The products are obtained in the form of their salts, usually the hydrochloride or hydrobromide but also including the lactate, tartrate, citrate, borate and sulphate; from these, the free bases may be prepared by treatment with alkali.