Patent GB-602351-A (GB)
Title: Processes of making substituted acridines
IPC: C07D219/12
Filed: 1945-06-11
Abstract: 2 - Methoxy - 6 - chloro - 9 - [o  - methyl - o  - disubstituted amino) polymethylene - amino] acridines of the general formula <FORM:0602351/IV(b)/1> wherein R and R1 represent saturated non-tertiary hydrocarbon radicals containing from 1 to 7 carbon atoms and n represents 1 or 2, are prepared by condensing a diamine of the general formula <FORM:0602351/IV(b)/2> , wherein R, R1 and n have the above significance, with 2-methoxy-6 : 9-dichloroacridine.  The resulting substituted acridines may be reacted with an acid to form the corresponding salt.  In examples 1 to 8, substituted acridines of the above general formula are prepared and are reacted to form the corresponding dihydrochloride, dihydrobromide, sulphate, nitrate, phosphate, lactate and propionate salts.  In particular the preparation of 9-[31-methyl-31-(diethylamino) - propylamino]-, 9 - [21 - methyl-21 - (diethylamino) - ethylamino]-, 9 - [31-methyl - 31 - (methyl - n - propylamino)propylamino]-, 9 - [31 - methyl - 31 - (sec. butylisoamylamino)propylamino]-, and 9 - [21 - methyl-21 - isobutylcyclopentylamino) - ethylamino] - 2 - methoxy - 6 - chloro - acridines is described.  Diamines of the general formula <FORM:0602351/IV(b)/3> , wherein R, R1 and n have the above significance are prepared by reducing the corresponding substituted aminoalkylnitriles of the general formula <FORM:0602351/IV(b)/4> , e.g., with hydrogen under heat and pressure or treating a hot alcohol solution of the nitrile with sodium.  In examples 1 to 7, diamines of the above general formula are prepared and in particular, 3 - methyl - 3 - (diethylamino) -, 3 - methyl - 3 - (methyl - n - propylamino) -, and 3 - methyl - 3 - (sec. - butylisoamylamino) - propylamines and 2 - methyl - 2 - (diethylamino)-and 2 - methyl - 2 - isobutylcyclopentylamino)-ethylamines.  Aminonitriles of the general formula <FORM:0602351/IV(b)/5> , are prepared, where R and R1 have the above significance and n is 1, by reacting a secondary amine of the general formula <FORM:0602351/IV(b)/6> and potassium cyanide with an aqueous solution containing the addition product of acetaldehyde and sodium bisulphite, and where R and R1 have the above significance and n is 2, by reacting the above secondary amine with crotonitrile or vinyl-acetonitrile. In examples 1 to 7, aminonitrile of the above general formula are prepared and in particular 3-(diethylamino)-, 3 - methyl - n - propylamino-, and 3 - (sec. - butylisoamylamino) - butyronitriles and 2 - (diethylamino)- and 2-(isobutyl - cyclopentylamino) - propionitriles.  Secondary amines of the general formula <FORM:0602351/IV(b)/7> , wherein R and R1 have the above significance, are prepared by reacting a primary amine containing one of the desired groups R or R1 with hydrogen and an aldehyde or ketone having the carbon skeleton of the other desired R or R1 substituent under pressure and in the presence of a hydrogenation catalyst such as Raney nickel.  In examples 4 and 5 sec.-butylisoamylamine is prepared from isoamylamine and methylethylketone and isobutylcyclopentylamine is prepared from cyclopentanone and isobutylamine.ALSO:2 - methoxy - 6 - chloro - 9 -[o  - methyl -o  - di-substuted amino) polymethylene-amino] acridines of the general formula <FORM:0602351/IV (c)/1> wherein R and R1 represent saturated non-tertiary hydrocarbon radicals containing from 1 to 7 carbon atoms and n represents 1 or 2, are prepared by condensing a diamine of the general formula <FORM:0602351/IV (c)/2> wherein R, R1 and n have the above significance with 2-methoxy-6 : 9-dichloroacridine.  The resulting substituted acridines may be reacted with an acid to form the corresponding salt.  A number of detailed samples are given, (see Group IV (b)).