2-Chloro-3-methyl-5-phenylpyrazine

Chloro-3-methyl-5-phenylpyrazine 1-oxide (44) gave 2,6-dichloro-3-methyl-5-phenylpyrazine (45) (POCl3, 80°C, 30 min 93%) analogues likewise.57... 

Chloro-3-methyl-5-phenylpyrazine 4-oxide 2-Chloro-3-methyl-6-phenylpyrazine 4-oxide 2-Chloro-5-methyl-3-phenylpyrazine 1-oxide 2-Chloro-5-methyl-3-phenylpyrazine 4-oxide 2-Chloro-5-methyl-6-phenylpyrazine 4-oxide 2-Chloro-6-methyl-3-phenylpyrazine 1-oxide 2-Chloro-6-methyl-3-phenylpyrazine 4-oxide... 

Chloro-3-methylpyrazine (101,535) and 2-chloro-5-phenylpyrazine (363, 365a, 377, 824, 825) have been prepared from the corresponding hydroxy compound and phosphoryl chloride, 2-chloro-6-methylpyrazine from 2-hydroxy-6-methylpyrazine and phosphoryl chloride with one drop of dimethylformamide (681), and 2-benzyl(or s-butyl, isobutyl, or isopropyl)-3phosphoryl chloride with a trace of concentrated sulfuric acid (80). 2-Chloro-6-methyl-3-propyl- (826), 3[Pg.99]

Many chloropyrazines have been prepared from hydroxypyrazines by reaction with mixed phosphorus pentachloride-phosphoryl chloride as follows 2-hydroxy-pyrazine to 2-chloropyrazine (818), 2-hydroxy-3-phenylpyrazine to 2-chloro-3-phenylpyrazine (535), 2-hydroxy-6-methyl- and 5-hydroxy-23-[Pg.102]

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). 

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-,... 

Mcthyl-5-phenyl-2(l//)-pyrazinone (4) gave 2-chloro-3-methyl-5-phenylpyra-zine (5) (P0C13,175°C, sealed, 18 h 92% beware of pressure within the tube even when cooled ) 57 such a sealed reaction also converted 5-chloro-3-phcnyl-2( l//)-pyrazinone into 2,5-dichloro-3-phenylpyrazine (6) (185°C, 5 h 92%).1382... 

Chloro-3-methoxy-6-methoxymethyl-1 -phenyl-2n //)-pyrazinone 5-Chloro-6-methoxy methyl-1,3-diphenyl-20 //)-pyrazinone 2-Chloro-6-methoxy-3-methyl-5-phenylpyrazine 2-Chloro-6-methoxy-5-methyl-3-phenylpyrazine 5-Chloro-3-methoxy-6-methyl-l-phenyl-2( 1 //t-pvTa/ini iie... 

Dichloropyrazines have also been prepared from the corresponding hydroxy compounds as follows 2,3-dihydroxypyrazine with phosphoryl chloride containing pyridine (481, 757) [see Schneller and May (828) re the use of phenylphosphonic dichloride at 150-170°] 2,3-dihydroxypyrazine and its methyl, dimethyl, phenyl, diphenyl, and 5-methy 1-6-phenyl derivatives with phosphoryl chloride (483, 829) [N.B. error in work of Minovici and Bente (830)] 2-chloro-5-hydroxypyrazine with phosphoryl chloride (831) 2-chloro-6-hydroxypyrazine with phosphoryl chloride at reflux for 6hours (832) and 2,5-dihydroxy-3-phenylpyrazine and3,5-dihydroxy-2-phenylpyrazine with phosphoryl chloride at 180-200° (829). 

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) 2dimethyl 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). 

The following alkoxypyrazines have been prepared from the corresponding dichloropyrazines and alkoxide ions 2,3-dimethoxy-5,6-dimethyl(and diphenyl) (797) 2,3-dibenzyloxy (sodium benzyl oxide in benzyl alcohol at reflux for 24 hours (883)] [but 23-dichloropyrazine with sodium hydride and benzyl alcohol in xylene gave l,4-dibenzyl-2,3-dioxo-l,2,3,4-tetrahydropyrazine)(988)] 2-chloro-5-methoxy (838) 2,5-diethoxy-3,6-dimethyl (872) 2methanolic sodium methoxide refluxed for 2 h) 2,5-dimethoxy-3-phenyl (817) 2-chloro-5-methoxy(and ethoxy)-3,6-diphenyl (817) 2,5-dimethoxy-3,6-dimethyl (and diisopropyl) (844) 2,5-dimethoxy-3-isopropyl-6-methyl (methanolic potassium methoxide at reflux for 6 days) (844) 2(5)-s-butyl-3-chloro-6-ethoxy-5(2)-isobutyl (93) 2-chloro-6-methoxy (838, 883) 2,6-dimethoxy (reflux for 8h) (832) 2,6-diethoxy (reflux for 14 h) (883) 2-benzyloxy-6-chloro (1 equiv. of sodium hydride and benzyl alcohol in benzene at reflux) (832) 2,6-dibenzyloxy (5 equiv. of sodium benzyloxide in benzene at reflux gave 70%) (832) and 3,5-dimethoxy-2-methyl (535). 

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-... 

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