Patent GB-799361-A (GB)
Title: Acridine compounds and the preparation thereof
Inventor: BOWMAN RALPH EDWARD
IPC: C07D219/10
Filed: 1956-02-15
Abstract: The invention comprises acridine-10-oxides of the general formula <FORM:0799361/IV (b)/1> and acid addition salts thereof, wherein R represents a divalent alkyl or hydroxyalkyl radical containing 2 to 5 carbon atoms, R1 and R2 are the same or different and each represent hydrogen or a normal or branched chain alkyl or hydroxy-alkyl radicals containing 2 to 8 carbon atoms or taken together with the nitrogen atom to which they are attached represent a saturated heterocyclic radical, and Y represents hydrogen or chlorine, or a methyl, phenyl or nitro group in the 2- or 3-position, and the preparation thereof by condensing the corresponding 6,9 - dichloroacridine - 10 - oxide with an aminoalkylamine of the general formula <FORM:0799361/IV (b)/2> or an acid addition salt thereof, R1 and R2 having the above significance, the said amine or acid addition salt being in excess of that required for the reaction or the condensation being carried out in the presence of an anhydrous organic solvent.  It is preferable to use substantially equivalent quantities of reactants.  Phenols, aliphatic alcohols, aliphatic ketones, aliphatic ethers, cyclic ethers and hydrocarbons are suitable solvents.  The desired acridine-10-oxide may be recovered in its free base form by neutralizing the hydrochloride salt initially produced by the condensation reaction.  When R1 and R2 together with the nitrogen atom to which they are attached represent a saturated heterocyclic group.  The group may be a piperidino, morpholino, hexamethyleneimino, piperazino or pyrrolidino group.  Suitable 6,9-dichloroacridine-10-oxide reactants are 3,9-dichloro-, 3,6,9-trichloro-, 3,9-dichloro-6-methyl-, 6,9 - dichloro - 2 - phenyl-, and 6,9-dichloro - 3 - nitro - acridine - 10 - oxides.  In the examples the following compounds are prepared: 3,6 - dichloro - 9 - (4 - diethylamino - 1 - methylbutylamino)-acridine 10-oxide dihydrochloride and the corresponding 9-(5-piperidinopentylamino)-, 9 -(3 - piperazinopropylamino)-, and 9 - (3 - piperidinopropylamino) - compounds, 6 - chloro - 9 - (4 - diethylamino - 1 - methylbutylamino - 3 - methylacridine 10 - oxide dihydrochloride and the corresponding 2-phenyl compound, 3 - chloro - 9 - (4 - diethylamino - 1 - methylbutylamino) acridine 10-oxide dihydrochloride and the corresponding 9-(5-pyrrolidinopentylamino) compound, 2,21 - [3 - (3,6 - di - chloro - 9 - acridinylamino) propylimino) diethanol, and 2 - [4 - (6 - chloro - 3 - nitro - 9 - acridinylamino) - 4 - methylbutyl]ethylaminoethanol 10-oxide dihydrochloride.  Starting compounds.  3,6,9 - Trichloro-, 3,9-dichloro-, 3,9 - dichloro - 6 - methyl-, 2 - phenyl-6,9 - dichloro- and 3 - nitro - 6,9 - dichloro-acridine 10-oxides are prepared by treating the corresponding free chloro-substituted acridines with perbenzoic acid in chloroform at room temperature.  3,9 - Dichloro - 6 - methyl-, 2-phenyl - 6,9 - dichloro- and 3 - nitro - 6,9 - dichloro-acridine are prepared by reacting 2,4-dichlorobenzoic acid and m-toluidine, 4-aminodiphenyl and m-nitroaniline to form 4-chloro-N-(m - tolyl) - anthranilic acid, 4 - chloro - N - (41-diphenyl) - anthranilic acid, and 4 - chloro - N - (m-nitrophenyl)-anthranilic acid respectively, and then treating these compounds with phosphorus oxychloride.