2,7‐Dimethyl‐4,5,9,10‐tetraazapyrene (VI) was synthesized by the catalytic hydrogenation of 4,4′‐dimethyl‐2,2′,6,6′‐tetranitrobiphenyl (IIa) with W‐2 Raney nickel in the presence of alkali. 4,4′‐Dicarbomethoxy‐2,2′,6,6′‐tetranitrobiphenyl (IIc) under similar conditions in neutral medium gave 4,4′‐dicarbomethoxy‐2,2′,6,6′‐tetraaminobiphenyl (IV) which on oxidation gave 2,7‐dicarbomethoxy‐4,5,9,10‐tetraazapyrene (V). 2,7‐Dimethyl‐, 2,7‐dimethoxy‐, and 2,7‐diacetamido‐4,5,9,10‐tetraazapyrene di‐N‐oxides (III a,b,c) were obtained by catalytic reduction of the corresponding 4,4′‐disubstituted‐2,2′,6,6′‐tetranitrobiphenyls with W‐7 Raney nickel in the presence of alkali. Compound VI on oxidation with hydrogen peroxide gave the di‐N‐oxide (IIIa).

No abstract

No abstract

Pyrazino[2, 3-dlpyridazine (I) w a s synthesized by two different routes. 5.8-Dihydroxypyrazino[2,3-d]pyridazine (IV) was converted to 5,8-dichloropyrazino[2,3-d]pyridazine (V) and 5,8-dibromopyrazino[2,3-d]pyridazine (Va). When V w a s treated with various benzyl mercaptans and alkoxides the corresponding disubstituted derivatives were obtained. Compound V when allowed to react with a r o m a t i c a m i n e s gave 5,8-bisaminopyrazino[2,3-d]pyridazines, however, with aliphatic a m i n e s only mono substituted products w e r e obtained substituted in the 8 -position.The reaction of pyrazine-2,3-dinitrile with hydrazine gave 5,8-diaminopyrazino[2,3-d]pyridazine (X).In the pyrazino[2,3-d]pyridazine (I) ring system only two compounds have previously been reported in the literature namely 5 , 8 -dihydroxyp,yrazino-[2,3-d]pyridazine (IV) (1,2) and 5,U-bis(P-methoxyphenyl)pyrazino[2,3-d]pyridazine (3). T h i s ring is of interest because of the close structural similarity to the pteridine ring system. The title compound (I) was synthesized by two different methods. These w e r e (a) condensation of 4,5-diaminopyridazine (II) (4) with glyoxal in methanol (5) and (b) by dehalogenation of 5 , 8dichloropyrazino[2,3dpyridazine (V) with palladium on charcoal. 2-Methylpyrazino-[ 2 , 3dlpyridazine (111) w a s similarly prepared by allowing I1 to react with pyruvaldehyde.Compound N w a s prepared by a slight modification of Hammerich's procedure (2) by using hydrazine dihydrochloride and water (6) instead of hydrazine hydrate and acetic acid. Similarly Jones' procedure (1) w a s also modified since in o u r hands e r r a t i c results w e r e obtained. We have allowed dimethylpyrazine-2,3-dicarboxylate to react with hydrazine hydrate in methanol under reflux for a longer period of time and the insoluble hydrazonium s a l t w a s dissolved in water and IV w a s precipitated by acid ( 7 ) .Compound N failed to give the diacetate as w a s the case with 5,8-dihydroxypyridino[2,3-d ]pyridazineobserved by Gheorghiu (8), but it gave the monoacetate (ma). Similarly, a monotosylate (IVb) w a s obtained when IV w a s treated with P-toluenesulfonyl chloride in pyridine. The spectroscopic data suggest that IVa and IVb exist in the keto forms. 5 ,U-Dichloropyrazin0[2,~djpyridazine w a s obtained when IV was allowed to r e a c t with a mixture of phosphorus oxychloride and phosphorus pentachloride ( 9 ) . Similarly the 5 , 8dibromopyrazino[2,3 -d ]pyridazine w a s the product when IV w a s treated with phosphorus oxybromide and bromine (10). When V was treated with sodium alkoxides the corresponding 5,U -dial koxypyrazino[ 2 ,Sd] py ridazines (VIa-c) w e r e obtained in good yields (11). Attempts to p r e p a r e 5,8-dimercaptopyrazino[2,3-d]pyridazine CHO 8 1 I CHO Ill 5 4 I Pd -C /Hp CI V OH OH 0-R IVO, R -CHsCOb. R -Tosyl

The synthesis of 5‐chloro‐8‐(ω‐dialkylaminoalkylamino)pyrazino[2,3‐d]pyridazine (II) proceeded smoothly when 5,8‐dichloropyrazino[2,3‐d]pyridazine (I) was allowed to react with ω‐dialkylaminoalkylamines. Similarly, the reaction of 5,8‐dichloropyrido[2,3‐d]pyridazine (IV) with ω‐dialkylaminoalkylamines gave the two expected products 8‐chloro‐5‐(ω‐dialkylaminoalkylamino)pyrido[2,3‐d]pyridazine (V) and 5‐chloro‐8‐(ω‐dialkylaminoalkylamino)pyrido[2,3‐d]pyridazine (VI) in a 2:3 ratio. 4,7‐Dichloroimidazo[4,5‐d]pyridazine (XII) was found to be much less reactive towards nucleophilic substitutions and more vigorous conditions resulted in disubstituted products (XIII). 7‐Chloroimidazo[4,5‐c]pyridazine (XVIII) was also found to be much less reactive towards nucleophilic substitution. In both of these cases one of the imidazole nitrogen atoms was blocked by a tetrahydropyranyl group which increased the reactivities and led to the desired monosubstituted products XVII from XII and in the latter case the expected products (XIX).