Reactions of Extranuclear Halogenopyrazines

2-Fluoropyrazine refluxed with aqueous sodium sulfite for 2 hours gave the sodium salt of 2-sulfopyrazine (ca. 70%) (882,884), whereas 2-chloropyrazine with aqueous sodium sulfite at 150° for 12 hours gave only 44% of the desired product (819, 884). 2-Chloro-3-methylpyrazine (71) with magnesium (and a little methyl iodide) in tetrahydrofuran with phenyldimethylchlorosilane (72) gave 2-methyl-3-dimethylphenylsilylpyrazine (73) (929). 

5-Difluoro-3,6-bisheptafluoroisopropylpyrazine (perfluoro-2,5-diisopropyl-pyrazine) subjected to fluorination over a mixture of cobalt trifluoride with calcium fluoride at 156° gave perfluoro-2,5-diisopropyl-3,6-dihydropyrazine (74) (1025). 

Repbcement of Halogeno Substituents by Alkoxy, Hydroxy, and Alkylthio Groups 

The reactions of certain a,o -dichloromethyl- and a,a,0 -trichloromethylpyrazines with alkoxide ions were found to be abnormal. 2-Chloro-3-dichloromethylpyrazine (75) with three equivalents of sodium methoxide in refluxing methanol was found to give a quantitative yield of 3,5-dimethoxy-2-methoxymethylpyrazine (76, R = Me) and the mechanism (75 - 77 78 - 79 76) was proposed (685). The 

2-(Trichloromethyl)pyrazine (80) with three equivalents of methoxide ion in refluxing methanol also underwent an abnormal reaction and gave a quantitative yield of the three isomeric pyrazines 2-dimethoxymethyl-5-methoxypyrazine (75%) (82), 2,3,5-trimethoxy-6-methylpyrazine (15%) (83), and 2,3-dimethoxy-5-methoxymethylpyrazine (10%) (84) (685). Subsequent treatment of (80) with one equivalent of methoxide ion in methanol at 5° gave 2-dichloromethyl-5-methoxypyrazine (81). 

2-Pyrazinecarbaldehyde gave 2-(difluoromethyl)pyrazine (Et2NSF3, CFC13, A, 0 - 20°C, 12 h 39% unstable).630 

4-Diisobutyrylpiperazine gave 1,4-bis(l -chloro-2-methylprop-1 -enyl)piper-azine (POCl3, Me2NCHO, CH2C12, reflux, 30 h 78% presumably via the enolic form of the substrate).1612 

2-Benzyloxy-6-chloromethyl- (227, X = Cl) gave 2-benzyloxy-6-iodomethyl-3-isobutyl-5-methoxypyrazine 4-oxide (227, X = I) (Nal, MeOH, reflux, 4 h  

2-(2-Chloroethyl)- gave 2-(2-bromoethyl)- (NaBr, Me2NCHO, 70°C, 12 h 88%) or 2-(2-iodoethyl)-5-isopropyl-3,6-dimethoxy-2-methyl-2,5-dihydropyrazine (likewise but Nal 88%).1608 

2-o-Bromophenoxypyrazine (230) gave 2-[0-(trimethylsilylethynyl)phenoxy]-pyrazine (231) [Me2SiC=CH, EtsN, Pd(PPh3)2Cl2, Cul, 80°C, sealed, 24 h 54%].369 

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