GB441007A - Process for the manufacture of acridine derivatives - Google Patents

Abstract

Acridine derivatives are prepared by (1) reacting upon acridines containing in the 2-position a halogen atom or an alkyl group and in the 9-position as a reactive substituent halogen, aryloxy-, alkoxy-, mercapto-, substituted mercapto-, or sulphogroup, with a base or salt thereof containing at least two nitrogen atoms at least one of which is in a primary or secondary amino group; (2) reacting upon the acridines specified in (1) with a base or salt thereof containing at least two nitrogen atoms one of the amino groups being substituted by an acyl residue, the latter being subsequently split off by saponification; (3) reacting upon acridines specified in (1) with an amino alcohol or an amino substituted halogen alkyl compound and further reacting the product with ammonia or a primary or a secondary amine, if necessary after esterification of the hydroxyl group; (4) reacting upon acridine derivatives which differ from those specified in (1) by containing a nitro or amino group in 2-position, according to the processes of (1), (2) or (3) followed by reduction if necessary, diazotisation and a Sandmeyer replacement to convert the 2-nitro- or -aminogroup to a 2-halogen substituent; (5) subjecting a diphenylamine-6-carboxylic acid amide basically substituted in the amide group and containing in the 4<1>-position a halogen atom or an alkyl group or a nitro- or acylamino group to ring closure to form the acridine derivative, a nitro- or acylamino group in 2-position then being respectively reduced or saponified, followed by diazotisation and a Sandmeyer replacement to give a 2-halogen derivative. The basic substituents are of the type defined in Specifications 363,392 and 437,953. In examples: (1) 2.9-dichloracridine (prepared from 4<1>-chlordiphenylamine-6-carboxylic acid by ring closure and chlorination) is condensed with a -diethylamino-d -aminopentane, a - diethylamino - b - hydroxy - g - aminopropane a - diethylamino - b - aminoethane, a - dimethylamino - g - aminopropane, a - diethylamino - d - aminobutane, a - diallylamino - b - aminoethane, a - diethylaminoethylthio - g - aminopropane, a - dimethylaminoethoxy - b - aminoethane and a - diethylamino - e - aminopentane; (2) 2 - methyl - 9 - chloracridine (prepared from 4<1>-methyldiphenylamine-6-carboxylic acid by ring closure and chlorination) is condensed with a -diethylamino-d -aminopentane; 2-ethyl-9-chloracridine (prepared analogously to the 2-methyl derivative) may be used instead; (3) 2-bromo-9-chloracridine (prepared from 4<1>-bromdiphenylamine-6-carboxylic acid by chlorinating agents) is condensed with a -diethylamino-d -aminopentane; 2-iodo-9-chloracridine (prepared analogously to the 2-bromo derivative) may be used instead or condensed with a -diethylamino-g -aminobutane or a triamine of the formula <FORM:0441007/IV/1> Samples have been furnished under Sect. 2 (5) of (a) 2-chloro-9-(p-aminomethylphenylamino)-acridine prepared by reacting 2.9-dichloracridine with phenol and the resulting 9-phenoxy derivative with N-(4-aminobenzyl-)acetamide followed by saponification in aqueous hydrochloric acid; (b) 2-chloro-9-(p-diethylaminoethyloxyphenylamino - ) - acridine prepared by condensing 2-chloro-9-phenoxyacridine with 4-aminophenylhydroxyethylether, and boiling the product with thionyl chloride and diethylamine; (c) 2-chloro-9-(a -piperido-g -propylamino)-acridine prepared from 2-nitro-9-chloracridine (obtained by ring closure of 4<1>-nitrodiphenylamine - 6 - carboxylic acid and chlorination) by condensation with g -piperido-a -propylamine, reduction by means of iron in acetic acid, diazotisation and a Sandmeyer replacement with cuprous chloride; (d) 2-chloro-9 - (p - diethylaminoethylmercaptophenylamino-)-acridine prepared by treating 4-chlordiphenylamine-6-carboxylic acid with phosphorus pentachloride and condensing with 4-aminophenyldiethylaminoethylthioether (cf. Specification 437,953) and the product ring-closed by heating with phosphorus oxychloride. Most of these products are isolated in the form of their salts with acids. Specification 267,169, [Class 2 (iii)], also is referred to. a - Diethylaminoethylthio - g - aminopropane is prepared by reacting diethylaminoethylmercaptan with bromopropylphthalimide and saponifying. The triamine of the above formula is prepared by reacting monoethylamine with diethylaminoepihydrin, the product with epichlorhydrin, and finally with ammonia. N-(4-aminobenzyl)-acetamide is prepared by reduction of the corresponding 4-nitro derivative with iron and acetic acid. 4-Aminophenyl-hydroxyethylether prepared by reacting 4-nitrophenol with chlorethyl alcohol and reducing with iron in acetic acid. g -Piperido-a -propylamine is prepared by reacting bromopropylphthalimide with piperidine and saponifying.