Patent GB-437953-A (GB)
Title: Process for the manufacture of acridine derivatives
IPC: C07D219/10
Filed: 1934-05-04
Abstract: 9-Aminoacridines substituted in the amino group by basic substituents of the type defined in the parent Specification and containing in the 6-position a halogen atom or an alkyl group and in the 2-position an alkylmercapto group are prepared (a) by reacting upon such acridine derivatives as contain as a reactive substituent in the 9-position a halogen, alkoxy, aryloxy, mercapto, substituted mercapto or sulpho group, a halogen atom or an alkyl group in the 6 - position and an alkylmercapto in the 2-position with a base or salt thereof which contains at least two nitrogen atoms at least one of which is in a primary or secondary amino group; (b) by reacting an acridine derivative as in (a) with a base or salt thereof which contains at least two nitrogen atoms, one of which is substituted by an acyl residue, and splitting off the acyl residue by saponification; (c) by reacting an acridine as in (a) with an aminoalcohol or with an aminohalogen alkyl compound and further reacting the product with ammonia or a primary or secondary amine, if necessary after the esterification of the hydroxy group to give a basically substituted 9-amino derivative; (d) by reacting an acridine derivative as specified in (a) except that the 6-position is occuped by a nitro or amino group and/or the 2-position by a mercapto group, so as to introduce a basic radicle in 9-position and then converting the 6-nitro (with prior reduction) or amino group to a halogen substituent by a Sandmeyer process and/or the 2-mercapto to an alkylmercapto group by alkylation; (e) by subjecting a diphenylamine-6-carboxylic acid amide basically substituted in the amide group and containing in the 3-position a halogen atom or an alkyl group or a nitro or amino group and in the 4<1>-position an alkylmercapto or mercapto group to ring closure, a nitro or amino group in the 6-position and a mercapto group in the 2-position being converted into halogen and alkylmercapto respectively by the processes referred to in (d). The basic residue attached to the 9-amino group may contain one or more nitrogen atoms, also ether or thioether linkages or hydroxy groups and may be aliphatic, isocyclic, or heterocyclic in character.  In examples: (1) 2.4-dichlorobenzoic acid is condensed with 4-aminothiophenolmethylether, the product ring-closed and chlorinated to give 2 - methylmercapto - 6.9-dichloracridine; this is condensed with a -diethylamino - d  - aminopentane, a -diethylamino-d -aminobutane, b -diethylaminoethoxyethylamine, b  - diethylaminoethylmercaptoethylamine; (2) 2.4-dichlorbenzoic acid is condensed with 4-aminothiophenolethylether, the product ring-closed and chlorinated to give 2-ethylmercapto-6.9-dichloracridine which is condensed with a -diethylamino-d -aminopentane, and with a -diethylamino-g -aminopropane; (3) 4-methyl-2-chlorbenzoic acid is condensed with 4-aminothiophenol methylether, the product ring-closed and chlorinated to give 2-methylmercapto - 6 - methyl - 9 - chloracridine which is condensed with a -diethylamino-d -aminopentane, a -diethylamino-b .b -dimethyl-g -aminopropane and with a  - diethylamino - e -aminopentane; 2-butylmercapto-6.9-dichloracridine (prepared by condensing 4-butylmercapto-1-aminobenzene with 2.4-dichlorbenzoic acid and ring-closing and chlorinating the product) is condensed with a -diethylamino-d -aminopentane; 2-isooctylmercapto-6.9-dichloracridine (prepared by condensing 4-isooctylmercapto-1-aminobenzene with 2.4-dichlorbenzoic acid and ring-closing and chlorinating the product) is condensed with a -diethylamino-d -aminopentane.  Most of these compounds are isolated in the form of their salts with organic acids (picric, citric, methylene-disalicylic acids).  Samples have been furnished under Sect. 2 (5) of the following products: (I) 2-methylmercapto - 6 - chloro - 9 - (p - aminomethylphenyl)-aminoacridine prepared by condensing 2-methylmercapto-6.9-dichloracridine with phenol and the resulting 9-phenoxy derivative with N-(4-aminobenzyl) - acetamide; the product is saponified by means of hydrochloric acid; (II) 2-methylmercapto-6-chloro-9-(p-diethylaminoethyloxyphenyl) - aminoacridine prepared by reacting 2-methylmercapto-6.9-dichloracridine with phenol and 4-aminophenylhydroxyethylether, treating the product with thionyl chloride and then with diethylamine; (III) the same product as (II) prepared by condensing 4-aminothiophenol-methylether with 4-nitro-2-chlorbenzoic acid, ring-closing and chlorinating to give 2 - methylmercapto - 6 - nitro - 9 - chloracridine, reacting this with 4-aminophenyldiethylaminoethylether, reducing the product with iron in acetic acid, diazotizing and finally treating this diazo body with cuprous chloride; (IV) 2-methylmercapto-6-chloro-9-(p-diethylaminoethylmercaptophenyl -aminoacridine prepared by condensing 4-aminothiophenol-methylether with 2.4-dichlorbenzoic acid, treating the product with phosphorus pentachloride and condensing the product with 4-aminothiophenyldiethylaminoethylether; the acid amide product obtained is ring-closed by heating with phosphorus oxychloride. Specification 267,169, [Class 2 (iii)], also is referred to. N-(4-aminobenzyl)-acetamide is prepared by reducing the corresponding nitro derivative with iron in acetic acid. 4-Aminophenylhydroxyethylether is prepared by reacting potassium 4-nitrophenolate with chlorethylalcohol and reducing with iron in acetic acid.  4-Aminothiophenol-diethylaminoethylether is prepared by boiling 4.4<1>-dinitrodiphenyl-disulphide with alcoholic sodium ethylate, condensing the product with diethylaminoethylchloride and reducing by means of iron in acetic acid.