Patent GB-607289-A (GB)
Title: Improvements in processes for producing substituted acridines
IPC: C07D219/12
Filed: 1945-04-24
Abstract: 2 - Methoxy - 6 - chloro - 9 - [o  - (unsymmetricaldialkylamino) polymethyleneamino] acridines of the general formula <FORM:0607289/IV(b)/1> wherein R and R1 are different saturated hydrocarbon radicals and the sum of the carbon atoms in R and R1 does not exceed 10 and n is an integer between 2 and 5 inclusive, are prepared by reacting a secondary amine of the general formula <FORM:0607289/IV(b)/2> with an aldehyde and a cyanide or with an o -chloroalkylcyanide or with an alkylene cyanide to yield an aminonitrile of the general formula <FORM:0607289/IV(b)/3> which is reduced to a diamine of the formula <FORM:0607289/IV(b)/4> and then condensed with 2-methoxy-6 : 9-dichloroacridine.  In the example, acridines of the above general formula are prepared from the diamines specified below and are converted into their dihydrochloride, dihydrobromide, sulphate, nitrate, phosphate, lactate and propionate salts. Diamines of the general formula <FORM:0607289/IV(b)/5> wherein R and R1 have the above significance, are prepared by reducing aminonitriles of the general formula <FORM:0607289/IV(b)/6> e.g. by treating an ether-ammonia solution of the nitrile with hydrogen under heat and pressure or by treating an alcohol solution of the nitrile with metallic sodium.  In examples (1) to (33), diamines of the above general formula are prepared and in particular 2-(methyl-n-propylamino)-, 2 - (methyl - 11 - methylbutyl - amino)-, 2 - (ethyl - 11 - methylbutylamino)-, 2 - (ethyl-11-methylhexylamino-, 2-(sec.-butyl-n-propylamino)-, 2 - (n - propyl - 11 - ethylpropyl - amino)-, 2 - (n - propyl - 11 p  - methylbutylamino)-, 2-(isopropyl-sec.-butylamino)-, 2-(sec.-butyl - isobutylamino)-, 2 - (methylcyclopentylamino)-, 2 - (methylcyclohexylamino)-, 2 - (ethylcyclo - pentylamino)-, 2 - (n - propylcyclopentylamino)-and 2 - (sec. - butyl - cyclopentylamino) - ethylamines, 3 - (methylisobutylamino)-, 3 - (methyl - cyclopentylamino)-, 3-(methyl-n-propylamino)-, 3 - (n - butyl - sec. - butylamino)-, 3 - (methyliso - propylamino)-, 3 - (ethylisopropylamino)-, 3-(methyl - sec. - butylamino)-, 3 - (n - propyl - iso - propylamino)-, 3 - (n - butyl - n - propylamino)-, 3 - (sec. - butyl - n - propylamino)-, and 3 - (ethylcyclohexylamino) - propylamines, 4 - (methyl - n - propylamino)- and 4-(methylethylamino)-butylamines and 5-(methyl-n-propylamino)-pentylamine.  Aminonitriles of the general formula <FORM:0607289/IV(b)/7> , wherein R and R1 have the significance indicated above, are prepared by the methods outlined above.  In examples (1) to (33), aminonitriles of the above general formula are prepared and in particular methyl-n-propylamino-, methyl-11 - methylbutylamino-, ethyl - 11 - methylbutylamino-, ethyl-1-methylhexylamino-, sec.-butyl-n-propylamino-, n-propyl-1-ethylpropylamino-, n-propyl-1-methylbutylamino-, isopropyl-sec.-butylamino-, sec.-butyl-isobutylamino-, methylcyclopentylamino-, methylcyclohexylamino-, ethyl-cyclopentylamino-, n-propylcyclopentylamino- and sec.-butylcyclopentylamino-acetonitriles, 3 - (methylisobutylamino)-, 3 - (methylcyclopentylamino)-, 3-(methyl-n-propylamino)-, 3 - (n - butyl - sec. - butylamino)-, 3 - (methylisopropylamino)-, 3 - (ethyl - isopropylamino)-, 3 - (methyl - sec. - butylamino)-, 3 - (n - propyl - isopropylamino)-, 3 - (n - butyl - n - propylamino)-, 3 - (sec. - butyl - n - propylamino)- and 3 - (ethylcyclohexylamino) - propionitriles, 4 - (methyl - n - propylamino)- and 4 - (methylethylamino)-butyronitriles and 5 - (methyl - n - propylamino) - valeronitrile.  Secondary amines for the formula <FORM:0607289/IV(b)/8> , wherein R and R1 have the above significance, are prepared by reacting a primary amine containing one desired R or R1 substituent 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 catalyst such as Raney nickel.  In examples (2), (3) and (7) to (28) inclusive, the following secondary amines are prepared: methyl-isobutyl-, methylcyclopentyl-, methylethyl-, n-butyl-sec.-butyl-, methylisopropyl-, ethylisopropyl-, methyl-sec.-butyl-, n-propylisopropyl-, n - butyl - n - propyl-, sec. - butyl - n - propyl-, ethylcyclohexyl-, methyl - 1 - methyl - butyl-, ethyl - 1 - methylbutyl-, sec. - butyl - n - propyl-, n - propyl - 1 - ethylpropyl-, n - propyl - 1 - methylbutyl-, isopropyl-sec.-butyl-, sec.-butyl-isobutyl-, methylcyclopentyl-, methylcyclohexyl-, ethylcyclopentyl-, n - propylcyclopentyl- and sec.-butyl-cyclopentyl-amines.  Specification 423,735 is referred to. The Specification as open to inspection under Sect. 91 refers to the preparation of 5-(methyl-n-propylamino)-pentylamine by hydrolysing 5-methyl - n - propylaminobenzoyl - n - pentylamine which is prepared by heating 5-benzoylamino-chloropentane and methyl-n-propylamine. This subject-matter does not appear in the Specification as accepted.ALSO:2-Methoxy-6-chloro-9-[o -(unsymmetrical-dialkylamino) polymethyleneamino] acridines of the general formula <FORM:0607289/IV (c)/1> wherein R and R1 are different saturated hydrocarbon radicals and the sum of the carbon atoms in R and R1 does not exceed 10 and n is an integer between 2 and 5 inclusive, are prepared by reacting a secondary amine of the general formula <FORM:0607289/IV (c)/2> with an aldehyde and a cyanide or with an o -chloroalkylcyanide or with an alkylene cyanide to yield an aminotrile of the general formula <FORM:0607289/IV (c)/3> which is reduced to a diamine of the formula <FORM:0607289/IV (c)/4> and then condensed with 2-methoxy-6 : 9-dichloroacridine.  In the examples, acridines of the above general formula are prepared (see Group IV (b)).