5-Ethyl-2,3-diphenylpyrazine

Ethylthio-2-pyrazinecarbonitrile 6-Ethylthio-2-pyrazinecarbonitrile 6-Ethylthio-2-pyrazinecarbothioamide 3-Ethylthio-2-pyrazinecarboxamide 6-Ethylthio-2-pyrazinecarboxamide 3-Ethylthio-2-pyrazinecarboxylic acid 6-Ethylthio-2-pyrazinecarboxylic acid 3-Ethylthio-2,5-pyrazinedicarboxamide 2-Ethylthiopyrazine 1-oxide 2-Ethyl-3,5,6-trimethylpyrazine 2-Ethyl-3,5,6-triphenylpyrazine 2-Ethyl-3-vinylpyrazine 2-Ethynyl-3,6-dimethylpyrazine 2-Ethynyl-3-methylpyrazine 2-Fluoro-5,6-dimethoxy-3-methylpyrazine 2- Fluoro- 5,6-dimethoxypyrazine 2-Fluoro-3,6-dimethylpyrazine 2-Fluoro-3-(l-hydroxyethyl)pyrazine 2-Fluoro-3-iodopyrazine 2-Fluoromethyl-5-methyl-3,6-diphenylpyrazine 2- Fluoro- 5-phenylpyrazine 2-Fluoro-3-phenylthiopyrazine... 

Gastaldi (286) first described this synthesis, in which an a-hydroxyimino ketone was treated with aqueous sodium bisulfite saturated with sulfur dioxide, and the bisulfite compound treated with potassium cyanide followed by hydrolysis with hydrochloric acid. By this procedure, Gastaldi prepared 2,5-dicyano-3,6-dimethyl-pyrazine from hydroxyiminoacetone, and 2,5-dicyano-3,6-diphenylpyrazine and some 3-cyano-2,5-diphenylpyrazine from hydroxyiminoacetophenone. He proposed a reaction mechanism involving the intermediate compounds (21) and (22). Sharp and Spring (287) used the same procedure to prepare 2,5-dicyano-3,6-diethyl-pyrazine from ethyl hydroxyiminomethyl ketone. 

Refluxing phosphoms tribromide converted 2-bromo-3-hydroxy-5,6-diphenyl-pyrazine and 2-bromo-5-hydroxy-3,6-diphenylpyrazine to the dibromopyrazines 2,3-dichloro-5,6-dimethylpyrazine and 2,5-dichloro-3-phenylpyrazine to the dibromopyrazines (817) 5-chloro-2,3-diphenylpyrazine (and its 6-ethyl derivative) to 5-bromo-2,3-diphenylpyrazine (and its 6-ethyl derivative) (866) and 2-hydroxy-... 

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). 

Methoxypyrazines (31) have been prepared by diazomethane methylation of 2-hydroxy-3-isobutylpyrazine (60, 311, 367), 2-hydroxy-3-isopropylpyrazine (59, 367), 2-hydroxy-3-propyl(ethyl or hexyl)pyrazine (367), 3-hydroxy-2-isobutyl-5(and 6)methylpyrazine and 2-hydroxy-3-isobutyl-5,6-dimethylpyrazine (368), 2,3-dihydroxypyrazine (832), 2-hydroxy-5-methoxy- and 2,5-dihydroxy-3,6-diphenyl-pyrazine (832), 2-hydroxy-6-methoxy(and benzyloxy)pyrazine (832), 2,6-dihydroxy-3,5-diphenylpyrazine (873), 2,3,5-trifluoro-6-hydroxypyrazine (851), 2-chloro-6-hydroxy-3,5-diphenylpyrazine (873), 2-chloro-6-hydroxy-5-methyl-3-phenylpyrazine (873), 2-chloro-6-hydroxy-3-methyl-5-phenylpyrazine (873), 5,6-dichloro-1 -cyclohexyl-34iydroxy-2-oxo-l, 2-dihydropyrazine (853), 2-chloro-5-hydroxy-3-methoxy-6-methoxycarbonylpyrazine (881), 2-(4 -amino-3, 5 -dibromo-phenylsulfonamido)-3Tiydroxy-6-methoxypyrazine (881), 2-amino-3-hydroxy-... 

Amino-3-aminomethylpyrazine and ethyl chloroformate (Et3N/CHQ3) gave 2-amino-3-ethoxycarbonylaminomethylpyrazine (1184) 2-amino-3rA(-benzyl(and butyl)carbamoyl-5,6-diphenylpyrazine refluxed with ethyl chloroformate gave 2-N-benzyl(and butyl)carbamoyl-3-ethoxycarbonylamino-5,6-diphenylpyrazine (455) and 2-amino-3-Af-methylcarbamoyl-5,6-diphenylpyrazine refluxed with ethyl chloroformate for 20 hours gave 2-ethoxycarbonylamino-3-7V-methylcarbamoyl-... 

---