Replacement of Halogeno Substituents by Amino Groups

Rutner and Spoerri (882, 884) have examined the reactions of 2-fluoropyrazine with amines to give the corresponding aminopyrazines under the conditions indicated as follows 2-amino (28% aqueous ammonium hydroxide at 20° for 3 days) (882, 884) (methanolic ammonia at 20° or anhydrous ammonia in boiling benzene did not react with 2-fluoropyrazine) (884) 2-methylamino (aqueous methanol at 20° for 3 days) (882) 2-piperidino (methanol at 20° for 4 days) (882) 2-benzyIamino (methanol at 20° for 3 days) (882,884) and 2-anilino (130-135° for 9 h) (882). 

Normal nucleophilic substitution reactions of alkyl and aryl chloropyrazines have been examined as follows 2-chloro-3-methyl- and 3-chloro-2,5-dimethyl(and diethyl)pyrazine with ammonia and various amines (535, 679, 680) 2-chloro-3(and 6)-methylpyrazine with methylamine and dimethylamine (681, 844), piperidine and other amines (681, 921) 2-chloro-5(and 6)-methylpyrazine with aqueous ammonia (362) alkyl (and phenyl) chloropyrazines with ammonium hydroxide at 200° (887) 2-chloro-3-methylpyrazine with aniline and substituted anilines (929), and piperazine at 140° (759) 2-chloro-3-methyl(and ethyl)pyrazine with piperidine (aqueous potassium hydroxide at reflux) (930,931) [cf. the formation of the 2,6-isomer( ) (932)] 2-chloro-3,6-dimethylpyrazine with benzylamine at 184-250° (benzaldehyde and 2-amino-3,6-dimethylpyrazine were also produced) (921) 2-chloro-3,5,6-trimethylpyrazine with aqueous ammonia and copper powder at 140-150° (933) and with dimethylamine at 180° for 3 days (934,935) 2-chloro-6-trifluoromethylpyrazine with piperazine in acetonitrile at reflux (759) 2-chloro-3-phenylpyrazine with aqueous ammonia at 200° (535) 2-chloro-5-phenylpyrazine with liquid ammonia in an autoclave at 170° (377) 2-chloro-5-phenylpyrazine with piperazine in refluxing butanol (759) but the 6-isomer in acetonitrile (759) 5-chloro-2,3-diphenylpyrazine and piperidine at reflux (741) and 5-chloro-23-diphenylpyrazine with 2-hydroxyethylamine in a sealed tube at 125° for 40 hours (834). 

2-Chloropyrazine with trimethylamine in benzene at 100° did not give the trimethylammonio compound but gave 2-dimethylaminopyrazine with loss of methyl halide (936). 2-Chloro-5-phenylpyrazine heated with hexamethylphosphoric triamide at 200° for 1 hour gave 2-dimethylamino-5-phenylpyrazine, and similar reactions were observed with 3-chloro-2,5-diethyl-, 3-chloro-2,5-diisobutyl-, 

2- chloro-3,5-diphenyl-, 3-chloro-2,5-diphenyl-, and 5-chloro-2,3-diphenyl-pyrazines (937). 

2-Chloro-3-methylpyrazine with fV-methylaniline at reflux gave 50% 2-methyl- 

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