2-Hydrazinocarbonyl-6- pyrazine

Formylpyrazine has been prepared by the McFadyen-Stevens method. 2-(2 -Benzenesulfonylhydrazino)carbonylpyrazine heated with sodium carbonate at 150-170° gave formylpyrazine (isolated as its thiosemicarbazone) (138), also obtained as distillate when the reactants were heated at 120°/3mm (1201), but Fand and Spoerri (1323), from the attempted reaction with sodium carbonate in ethylene glycol at 160°, were unable to isolate 2-formylpyrazine instead 2-(2 -pyrazinoyl-hydrazinocarbonyl)pyrazine, 2-carboxypyrazine, and other products were obtained. 

The antitubercular activity of 2-carbamoylpyrazine and biological activity of pyrazines generally has been mentioned in Section 1.4. Certain pyrimidinyl derivatives of 2-carbamoylpyrazine have been shown to have lower toxicity and rather greater in vitro activity against Mycobacterium tuberculosis than 2-carbamoylpyrazine (1388), and the antitubercular activity of some extranuclear )V-substituted carbamoylpyrazines also showed a higher activity than 2-carbamoylpyrazine (1201). When tested on mice in vivo, 2-carbamoyl-5-methoxypyrazine and 2-hydrazino-carbonylpyrazine had less antitubercular activity than did 2-carbamoylpyrazine (1098) the antitubercular activities in a series of hydrazinocarbonyl-, carbamoyl-, and thiocarbamoylpyrazines have been examined and compared (1399). 

The amino group of hydrazides react with aldehydes and ketones. For example, 2-hydrazinocarbonylpyrazine refluxed with acetone-ethanol gave 2-isopropylidene-hydrazinocarbonylpyrazine (51) [which was reduced in methanol over palladium-charcoal to 2-(2 -isopropylhydrazinocarbonyI)pyrazine] (1366,1428,1429). Other references to similar reactions include the following reactions 2-hydrazinocarbonylpyrazine with p-acetamidobenzaldehyde (138) 4-hydroxy-, 4-hydroxy-3-methoxy-and 2-carboxy-3,4-dimethoxybenzaldehydes (1319) furfural (1201) and pyruvic acid (1201) 2-amino-3-hydrazinocarbonylpyrazine with acetone and benzaldehyde (1214) and 2-hydrazinocarbonyl-5,6-dimethyl-3-methylaminopyrazine with acetone (428). 

Hydrazinocarbonylpyrazine condensed with 4-cyanopyridine to give 2-[5 -(pyridin-4"-yl)-l//-r,2, 4 -triazol-3 -yl]pyrazine (S3) (1430), cyanoethylation of 2-hydrazinocarbonylpyrazine with cyanoethylene gave 2- 2 -[2 -(cyanoethyl)-hydrazino]carbonyl pyrazine (1317), and 2-[r-(isopropylidenehydrazinocarbonyl)-hydrazinocarbonyl]-5-methyl-3-methylaminopyrazine (54) heated with Raney nickel in ethanol gave 2-carbamoyl-5-methyl-3-methylaminopyrazine (428). 

---