Patent GB-267169-A (GB)
Title: The manufacture of new products primarily useful as pharmaceutical products
IPC: C07D279/20
Filed: 1925-09-07
Abstract: 267,169. Carpmael, W., (Farbenfabriken vorm. F. Bayer & Co.). Sept. 7, 1925. Acridine, azine, di- and tri-arylmethane, oxazine, quinoline, thiazine, and xanthene derivatives. - Aminoalkylamino-derivatives of these classes of compounds, that is, derivatives which contain amino groups joined through the medium oi aliphatic radicles to aromatic amino groups, are produced either (a) by introducing, by the customary methods, aminoalkyl groups into aromatic amino groups of these classes of compounds, or (b) by synthesizing them, by the customary methods, from intermediate products which contain aminoalkylamino groups. Method (a) can be effected for example by condensing the aromatic amino compounds of the types in question with halogenalkylamines or their substitution products, or by condensing the aromatic amino compounds with reactive aliphatic compounds which contain a further substituent which can be subsequently exchanged for an amino group: thus the aminoacridine &c. may be condensed with a halogenated alcohol or ethyleneoxide and the oxyalkylamino compound converted into the aminoalkylamino-compound in the usual manner. Reactive derivatives of the acridine &c. may also be condensed with aliphatic diamines. The condensation of the aminoacridines &c. with bromethylphthalimide and subsequent removal of the phthalic acid residue is also referred to. The compounds obtained are primarily useful as pharmaceutical pro ducts. The following examples are given : (1) Thiazines are produced by condensing (by means of chromic acid in presence of sodium thiosulphate and zinc chloride (a) p-aminodimethylaniline with N-diethylaminoethylaniline or N-methyl-diethylaminoethylaniline, or (b) dirrethylaniline with p-amino-N-methyl-alpha-dimethylamino - # - methyl - gamma-butylaniline (NH2.C6.H4.- N(CH3).CH(CH3).CH(CH3).CH2.N(CH3)2 or (c) p-aminodimethylaniline with N-methyl-a-dimethylamino-#-methyl-gamma-butylaniline. (2) Triarylmethane derivatives are obtained by (a) condensing tetramethyldiaminobenzhydrol with diethylaminoethylacetylaniline and oxidizing the dye base by means of chloranil in acetic acid: (b) by condensing methyl-diethylaminoethylaniline with benzaldehyde in presence of oxalic acid and oxidizing with chloranil or lead peroxide; (c) by condensing methyl-diethylaminoethylaniline with o-toluic acid in presence of phosphorus oxychloride. (3) Quinoline derivatives are produced from (a) 8-aminoquinoline and diethylaminoethylchloride or a-dimethylamino-#-methyl-gamma-chlorbutane; (b) 6-methoxy-8-aminoquinoline and 1- diethylamino-4-chlorpentane or a-diethylamino- # - oxy - gamma - chlorpropane or 1-di-methylamino- 2-methylbutylene-3 : 4-oxide, (c) 6 - ethoxy- 8-aminoquinoline and a - dimethylamino - #- methyl-gamma-chloro-butane; (d) 4-chlor-2-methyl-6- methoxyquinoline and diethylaminoethyl-methylamine (heated under pressure). (4) An azine derivative is obtained from the nitroso compound of N-methyl-diethylaminoethyl-aniline and mtoluylenediamine. (5) An oxazine is produced from m-oxy-N-diethylamino-ethyl-methyl-aniline and p-nitrosodimethylaniline. (6) A xanthene derivative is obtained from m-oxy-N-diethylaminoethyl-ethyl- or methyl-aniline and phthalic anhydride; the carboxylic acid so obtained is then esterified with ethyl alcohol. (1) An acridine is produced by condensing m-amino-N-diethylaminoethyl-ethyl-aniline with glycerine in presence of zinc chloride and oxalic acid. N-Aminoalkyl-derivatives of aromatic amines are obtained (a) by condensing primary or secondary aromatic amines with halogenalkylamines, (b) by causing a halogenated alcohol or ethylene oxide to act upon an aromatic amine, transforming the oxyalkyl compound so obtained into the corresponding halogenalkyl compound and replacing the halogen by the amino group; (c) by condensing reactive derivatives of aromatic compounds with aliphatic diamines; thus homologues of phenol can be condensed with aliphatic diamines in presence of bisulphite. The production of the following compounds is described:- (1) N-diethylaminoethyl-aniline and N-methyldiethylaminoethyl-aniline from diethylaminoethylchloride and aniline and methylaniline respectively; the first compound yields an acetyl compound with acetic anhydride; the second compound is also produced by treating methylaniline with chlorethylalcohol, exchanging the OH group of the oxyethylmethylaniline for chlorine by means of thionyl chloride, and treating with diethylamine; it yields a nitroso compound with nitrious acid: (2) N-methyl.alpha-dimethylamino-#- methyl-gamma-butylaniline from methylaniline and alphadimethylamino-#-methyl-gamma-chlorbutane: it yields a p-amino-compound by treatment with nitrous acid and reduction of the nitroso compound: (3) m-oxy-N-diethylaminoethyl-methyl- or ethvl-aniline from m-oxy-methyl- or ethyl-aniline and diethylaminoethyl chloride : (4) m-nitro-N-diethylaminoethyl-aniline from m-nitraniline and diethylaminoethylchloride; it yields the corresponding m-amino body by reduction with iron and acetic acid. 1-Diethylamino-4-chlorpentane. - Diethylaminoethylchloride is condensed with acetoacetic ester in presence of sodium alcoholate and the resulting ester saponified with sulphuric acid: the amino ketone so produced is reduced with sodium amalgam and the aminoalcohol treated with thionvl chloride. a-Diethylamino-#-oxy-gamma-chlorpropane is produced by condensing diethylamine hydrochloride with epichlorhydrin in aqueous solution. 1 - Dimethylamino-2-methylbutylene-3 : 4-oxide is obtained by condensing 1-dimethylamino-2- methylbutene-3 with hypochlorous acid and boiling the resulting chlorhydrin with caustic potash. 6-Methoxy- or ethoxy- 8-aminoquinoline is obtained by condensing o-nitro-p-anisidine or onitro-p-phenetidine with glycerine in presence of arsenic acid and sulphuric acid and reducing the 6-methoxy- or ethoxy-8-nitroquinoline so produced. The nitro compound is purified by conversion into the chromate and recrystallizing.