2- Nitropyrazine

Like 2-aminopyridines and 2-aminopyrimidine, 2-aminopyrazine (39) (Scheme 29) has been converted into the nitroso compound (121) by reaction with dimethyl sulfide and NCS followed by deprotonation of the resulting sulfonium salt with sodium methoxide to the 5, 5-dimethylsulfilimine and then oxidation with MCPBA <82JOC552>. The extremely reactive nitrosopyrazine (121) condenses with 1,3-dienes to give 3,6-dihydro-1,2-oxazines and with aromatic amines in the presence of acid to gives azo compounds, and is smoothly oxidized with ozone or sodium hypochlorite to 2-nitropyrazine (122). Methyl 3-aminopyrazinecarboxylate reacts with thiophosgene to produce the... 

One of the nitro groups of 92 is readily reduced when it is slurried in aqueous ammonium chloride with sodium sulfide monahydrate as the reducing agent, and 2,3,5-triamino-6-nitropyrazine (93) is produced in high yield (74USP3808209). 

Dichloro-3-nitro-2-pyrazinamine (60, R = NH2) gave 2-bromo-5,6-dichloro-3-nitropyrazine (60, R = Br) (Bu CH2ONO, excess CHBr3, reflux, 8 h then more Bu CH2ONO J, reflux, 10 h —50%, crude product mechanism ).1313... 

Bromo-5,6-dichloro-3-nitropyrazine (95) gave 2-chloro-3,5-bis(2-hydrox-yethylamino)-6-nitropyrazine (96) (HOCH2CH2NH2, Et3N, PrOII, <10 —>... 

Chloro-3-dimethylamino-6-nitropyrazine (184) gave 3-dimethylamino-6-nitro-2-pyrazinecarbonitrile (185) (CuCN, Me2NCIIO, 155°C, 18 h 62%).1313... 

Neither nuclear nor extranuclear nitropyrazines are commonly encountered in the pyrazine literature1638 but some have been made, usually with no subsequent use evident. 

A few nitropyrazines have been prepared by primary synthesis (see Chapters 1 and 2). Other routes to nitropyrazines are illustrated in the following examples ... 

Note Pyrazinamines may be converted into the corresponding dimethylsulfimidopyrazines (sometimes called dimethylsulfiliminopyrazines neither name is satisfactory ) as outlined in Section 13.2.5 these derivatives may be oxidized successively to unstable C-nitrosopyrazines and forthwith to nitropyrazines, as illustrated here. 

All the major routes to pyrazinecarbonitriles have been discussed already by primary synthesis in Chapters 1 and 2 by cyanolysis of halogenopyrazines in Sections 4.2.8 and 4.4 by deoxidative cyanation of pyrazine N-oxides in Section 5.5.2.4 by the rare cyanolysis of nitropyrazines in Section 7.1.2 by cyanolysis of trimethylammoniopyrazine salts no recent examples by dehydration of pyrazinecarboxamides in Section 8.4.2 and by passenger introduction of a cyano group in a variety of ways, for example, by cyanoalkylation. 

Acetamido-6-bromo-2-pyrazinecarboxamide 6-Acetamido-5-bromo-2-pyrazinecarboxylic acid 2-Acetamido-5-chloro-3-guanidinocarbonylpyrazine 2-Acetamido-5,6-dichloro-3-nitropyrazine... 

Bromomethyl-3,5,6-trimethylpyrazine 2-Bromo-5-morpholinopyrazine 4-oxide 2-Bromo-5-nitropyrazine... 

Reduction of 2,6-diamino-3,5-dinitropyrazine in dimethylacetamide with hydrogen over platinum oxide (or with sodium sulfide and ammonium chloride in water at room temperature) gave 2,3,5-triamino-6-nitropyrazine (1180), but reduction with hydrogen and 10% palladium on charcoal at 50p.sJ. gave tetraamino-pyrazine (1180). 2-Amino-5hydrochloric acid at reflux gave 2-chloro-5-(3, 3 -dimethylureido)-... 

The brominations of 2-amino-3-carboxypyrazine (804), 2-amino-5-bromo-3-carboxypyrazine (805, 806), and 2-amino-5-bromo-3-methoxycarbonylpyrazine (807) to 2-amino-3,5-dibromopyrazine have been described in Section V.IB (2) nitrations of 2-amino-3-carboxy-5-chloro-6-ethylaminopyrazine to 2-amino-5-chloro-6-ethylamino-3-nitropyrazine (1181) and 2,6-diamino-3,5-dicarboxypyrazine... 

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