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Synthesis of 1‐hydrazinopyridazino[4,5‐ b ]quinoxaline and related compounds
Author(s) -
Vega A. Onge,
Gil M. J.,
FernándezAlvarez E.
Publication year - 1984
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570210505
Subject(s) - quinoxaline , chemistry , hydrazine (antidepressant) , reagent , medicinal chemistry , phenylhydrazine , aldehyde , nitrous acid , acetic acid , sodium dithionite , organic chemistry , catalysis , chromatography
This paper describes the synthesis of 1‐hydrazinopyridazino[4,5‐ b ]quinoxaline ( 10 ), tetrazolo[4,3‐ b ]pyridazino[4,5‐ b ]quinoxaline ( 11 ) and some 1,2,4‐triazolo[4,3‐ b ]pyridazino[4,5‐ b ]quinoxalines 13 . Starting with 2‐ethoxycarbonyl‐3‐methylquinoxaline 1,4‐dioxide ( 1 ), 1,2‐dihydro‐1‐oxopyridazino[4,5‐ b ]quinoxaline ( 5 ) was prepared by three different ways: (a) chlorination of 1 in acetic acid gave 2‐ethoxycarbonyl‐3‐dichloromethylquinoxaline 1,4‐dioxide, which reacts with an excess of hydrazine to give about 60% of 5 ; (b) oxidation of 1 with selenium dioxide gave 90% of 2‐ethoxycarbonyl‐3‐formylquinoxaline 1,4‐dioxide ( 3 ), which reacts with hydrazine to give 5 (63%); (c) compound 3 was treated with hydrazine to give 1,2‐dihydro‐1‐oxopyridazino‐[4,5‐ b ]quinoxaline 1,4‐dioxide ( 4 ) (70%), which by reduction with sodium dithionite gave 5 (80%). Compound 5 reacts with phosphorus pentasulfide or the Lawesson reagent to give 1,2‐dihydro‐1‐thiocarbonylpyridazino[4,5‐ b ]quinoxaline ( 9 ), which treated with hydrazine gave 5 (80%). This last compound reacts with nitrous acid to give 11 . Some hydrazones 12 from 10 are described. Heating the aldehyde hydrazones 12a,c,d with dimethylsulfoxide some 1,2,4‐triazolo[4,3‐ b ]pyridazino[4,5‐ b ]quinoxalines 13 were obtained. Compound 13a was also obtained in the reaction of 10 with benzoyl chloride. Reaction of 3 with phenylhydrazine gave 1,2‐dihydro‐1‐oxo‐2‐phenylpyridazino[4,5‐ b ]quinoxaline ( 6 ). Reactions of 5 with acetic anhydride and dimethylsulfate gave, respectively, 1‐acetoxypyridazino[4,5‐ b ]quinoxaline ( 8 ) and 1,2‐dihydro‐1‐oxo‐2‐methylpyridazino‐[4,5‐ b ]quinoxaline ( 7 ). All the compounds were characterized by elemental analysis and 1 H‐nmr spectra. Compounds 5 and 10 showed antihypertensive activity in rats.