Patent GB-444319-A (GB)
Title: The manufacture of quaternary derivatives of heterocyclic compounds
IPC: C07D471/04
Filed: 1934-09-17
Abstract: Quaternary heterocyclic pseudoazimido compounds are prepared by (1) treating a compound in which an aromatic or heterocyclic residue is united to a heterocyclic residue by the pseudoazimido radicle, one or both of the residues containing a nuclear nitrogen atom, with reactive alkyl or aralkyl esters of inorganic acids or their organic substitution products, or (2) oxidizing, e.g. with chromic acid or hydrogen peroxide, a heterocyclic or aromatic-heterocyclic ortho-aminoazo compound containing a nuclear quaternary nitrogen atom.  The products, which may be further substituted by alkyl, alkoxy, halogen, nitro, acylamino or alkylamino groups, possess therapeutic properties.  According to the examples, (1) quinoline-5-diazonium chloride is treated with 6-aminoquinoline, the resulting 6-amino-5 : 5<1> azoquinoline oxidized with chromic acid to give quinoline - 5 : 6 - pseudoazimido - 5<1> - quinoline, which is then converted with dimethyl sulphate into its bis-quaternary methyl-methosulphate; in a similar way are obtained the bis-quaternary methyl-methosulphate or chloromethylate compounds of quinoline - 5 : 6 - pseudoazimido - 6<1>, 7<1> or 8<1>-quinoline, quinoline-5 : 6-pseudoazimido-5<1>-isoquinoline, quinoline - 7 : 8 - pseudoazimido - 7<1>-quinoline, quinaldine-5 : 6-pseudoazimido-6<1>-quinoline and 8 - methoxyquinoline - 5 : 6-pseudoazimido - 6<1> - quinoline; (2) benzene diazonium chloride is combined with 6-amino-quinoline to give 6-amino-5-benzene-azoquinoline, which is then converted into its quarternary compound with dimethyl sulphate and oxidized with aqueous chromic acid to form a compound which is precipitated with sodium iodide as quinolinium-5 : 6-pseudo-azimido-benzene-N-iodomethylate; the oxidation may be effected before the conversion into the quaternary compound; (3) 6-aminoquinoline-chloromethylate is diazotized and coupled with 6-aminoquinoline and the product oxidized with chromic acid to give quinoline-5 : 6 - pseudoazimido - 6<1> - quinoline - chloromethylate; (4) 6-amino-5-(naphthalene-b -azo)-quinoline is obtained by the action of naphthalene-b -diazonium chloride upon 6-amino-quinoline, oxidized to quinoline-5 : 6-pseudoazimido-2<1>-naphthalene by means of chromic acid, and converted into its chloromethylate; (5) the azo compound from diazotized 4-amino-acetanilide and 6-aminoquinoline is oxidized and treated with dimethyl sulphate to form quinoline-5 : 6-pseudoazimido-4<1>-acetylaminobenzene-methylmethosulphate; (6) quinoline-5 : 6 - pseudoazimido - 3<11> - styryl - 2<1> - quinoline is prepared by oxidizing with chromic acid the reaction product of diazotized 2-(3<1>-amino-styryl)-quinoline and 6-aminoquinoline, and converted into its bis-methylmethosulphate.  The samples furnished under Sect. 2 (5) comprise (1 and 2) the mono- and bis-chlormethylates of quinoline-5 : 6-pseudoazimido-4<1>-pyridine, prepared by treating diazotized 4-aminopyridine with 6-aminoquinoline, oxidizing the resulting 6-aminoquinoline-5 : 4<1>-azopyridine with chromic acid, and treating the product first with dimethyl sulphate and then with hydrochloric acid; (3) quinoline-5 : 6-pseudoazimido - 5<1> - benzimidazole bis - chloromethylate, which is obtained by diazotizing 5-aminobenzimidazole and treating it with 6 - aminoquinoline, oxidizing the 6 - amino-quinoline - 5 : 5<1> - azobenzimidazole so formed with chromic acid solution, and treating the product first with dimethyl sulphate and then with hydrochloric acid. 2-(3<1>-Aminostyryl)-quinoline is prepared by boiling quinaldine with 3-nitrobenzaldehyde in the presence of acetic anhydride and reducing the resulting nitro compound.