With One Halogeno and Other Substituents

2-Chloro-6-cyanopyrazine with anhydrous methylamine (940), diethylamine, and other amines in refluxing benzene (941,942), thiomorpholine, and A -methyl- 

2-Cyano-6-methylaminopyrazine was also prepared from the chloro compound with methylamine hydrochloride and sodium hydroxide in aqueous dioxane (945) and 2-cyano-6-(2, 2 -dimethylhydrazino)pyrazine was prepared similarly (945). 2-Chloro-6-cyanopyrazine with methanol (and similarly with ethanol) and triethylamine gave 2-methoxy-6-(C-methoxyformidoyl)pyrazine (32) [see Section 5D(2)], and 2-chloro-6-carbamoylpyrazine with concentrated aqueous ammonia at 170-175° gave 2 -amino-b-carboxypyrazine (744). 2-Chloro-3-cyano-5,6-diphenylpyrazine with ammonium hydroxide and potassium iodide formed 2-amino-3-carbamoyl-5,6-diphenylpyrazine, but on fusion with ammonium acetate it gave 2-amino-3-cyano-5,6-diphenylpyrazine (848). 

Normal nucleophilic substitution occurred on treatment of 2-carbamoyl-3-chloropyrazine with alcoholic methylamine at 130° (423, 836) 2-chloro-3-(4 -morpholinocarbonyOpyrazine with morpholine at reflux in benzene (867) 2 hloro-3-methoxycarbonylpyrazine with methylamine (423, 789, 861), TV-cyclopropyl-A -methylamine in dimethyl sulfoxide at 65° (857) and cyclohexylamine in benzene at reflux (946) 3-chloro-2-methoxycarbonyl-5-phenylpyrazine with alcoholic methylamine at 140° (375) 2-carboxy-3-chloropyrazine with anhydrous ammonia at 100° for 5 hours (947) 2-carbamoyl-6-chloropyrazine with aqueous methylamine at reflux (940) 2-chloro-6-(4 -morpholinocarbonyl)pyrazine (and other amides) and 2-chloro-6-methoxycarbonylpyrazine with morpholine (and other amines) (870, 948, 949) and 2-chloro-6-methoxycarbonylpyrazine with liquid ammonia at 80° (870). 2-Chloro-3-methoxycarbonylpyrazine fused with guanidine carbonate gave 2-amino4-hydroxypteridine and its 7-methyl-, 7-phenyl, and 6,7-diphenyl analogues were prepared similarly (371,375). 

2-Chloro-3-hydroxy-5(and 6)-methylpyrazine with ammonium hydroxide, copper, and cupric chloride at 125° for 15 hours gave 2-amino-3-hydroxy-5(and 6)-methylpyrazine (373, 835), but 2-chloro-5-hydroxy-3,6-dimethylpyrazine was recovered unchanged after treatment with alcoholic ammonia under drastic conditions (312) and 2-chloro-3-hydroxy-5,6-diphenylpyrazine with pyridine and its hydrochloride at reflux gave the betaine (33) from 2-hydroxy-5,6-diphenyl-3-pyridiniopyrazine chloride (863). Replacement of the chloro substituent occurred 

The corresponding diamines were obtained from the following reactions  

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