2- Phenylpyrazine

The Chichibabin amination of phenylpyrazine with N-labeled potassium amide/liquid ammonia gave two products, 3-amino- and 5-amino-2-phenylpyrazine in both products the label is only present in the amino group, and no label was found to be incorporated into the pyrazine ring (82MI1). This result proves that in the aminodehydrogenation of phenylpyrazine, no Sn(ANRORC) mechanism is involved. This result is confirmed by the fact that amination of phenylpyrazine in the presence of the radical scavenger azobenzene, a compound that has been found to prevent the Sn(ANRORC) mechanism in the Chichibabin amination of 4-phenylpyrimidine, still yields both aminopyrazines. 

The simple phenyl-substituted pyrazines do undergo nitration in the phenyl ring for example, 2-phenylpyrazine yields the 4-nitrophenyl derivative (mixed acid), although 5-phenyl-2-pyrazinone forms the 3-nitropyra-zinone under similar conditions (75MI1). However, 2,5-dimethyl-3,6-diphenylpyrazine and its /V,A -dioxide are both reported to be nitrated to give the bis-(3-nitrophenyl) products (55JCS3094). 

Flash pyrolysis of 5,7-diphenyl-2,3-dihydro-1/7-1,4-diazepine (34, R = H) at 700°C in a vacuum afforded 2-phenylpyrazine (35) in 21% yield, after separation from a pyrimidine the methyl substrate (34, R = Me) also gave a small yield of the same product (35) and 6-phenyl-2,3-dihydro-17/-l,4-diazcpine gave some unsubstituted pyrazine.176,1698... 

Phenylpyrazine 4-oxide (52) gave a separable mixture of 2-chloro-... 

Phenylpyrazine 4-oxide (268) gave a separable mixture of 2-acetoxy-6-phenylpyrazine (269), 2-acetoxy-3-phenylpyrazine (270), and 2-acetoxy-5-phenylpyrazine (271) [Ac20, Et3N, reflux, A, 6 h 68, 11, 8% respectively (by NMR), isolated in much lower yields].1575... 

Phenylpyrazine 4-oxide gave a mixture of 2-p-methoxybenzylthio-3-phenylpyrazine (296, R = SCH2C6H4OMe-p), its 5-phenyl isomer, and its 6-phenyl isomer [HSCH2C6H4OMe-p, Et2NCOCl, MeCN, reflux, 6 h 63, 43, 0% (isolated) or likewise with the addition of ZnBr2 21, 38, 41% (estimated by NMR)] 43 also other examples, all with the same thiol.43... 

Phenylpyrazine (44) gave a separable mixture of 5-phenyl- (43) and 3-phenyl-2-pyrazinamine (43a) (KNH2, liquid NH3, 33°C, 24 h —40 and —10%, respectively) the same substrate (44) gave only 2-methylamino-5-phenylpyrazine (45) (KNHMe, MeNH2, 6°C, 3 h 60%).1457... 

Phenyl-2-pyrazinecarboxylic acid 5-Phenyl-2,3-pyrazinediamine 5-Phenyl-2,3-pyrazinedicarbonitrile 5-Phenyl-2,3-pyrazinedicarboximide 5-Phenyl-2,3-pyrazinedicarboxylic acid 5- Phenyl-2,3(1 H, 4//)-pyrazinedione 2-Phenylpyrazine 1,4-dioxide 2-Phenylpyrazine 1-oxide... 

Propyl-2-pyrazinecarboxylic add 2-Propylpyrazine 1,4-dioxide 2-Propylpyrazine 1-oxide 2-Phenylpyrazine 4-oxide... 

The dipole moment of pyrazine 1-oxide has been determined in benzene at 25° as 1.66D, and comparison with those obtained by SMO (simple molecular orbitals) calculations show that agreement is good (748). Other determinations of dipole moment were as follows pyrazine 1-oxide, 1.60 (carbon tetrachloride, 25°) (749) and 1.62 (benzene, 25°) (663) 2,5- and 3,5-dimethylpyrazine 1-oxides, 1.68 and 2.14, respectively (benzene, 25°) (663) 2-phenylpyrazine 1-oxide, 1.39 (benzene, 25°) (733a) and 3-phenylpyrazine 1-oxide, 2.03 (benzene, 25°) (733a). 

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). 

Alkoxypyrazine A-oxides may also be prepared by oxidation of the alkoxypyrazine with peroxyacetic acid. In this way the following have been prepared 3-ethoxypyrazine 1-oxide (100°/20h) (978) 3-(trideuteromethoxy)pyrazine 1-oxide (757l9h) (975) 3-ethoxy-2-methylpyrazine 1-oxide (65-75724h) (978) 3-methoxy-2-phenylpyrazine 1-oxide (55720 h) (817) 3-ethoxy-2,5-dimethyl-pyrazine 1-oxide (56716 h) (872) 3-carbamoyl-2-methoxypyrazine 1-oxide (80720h) (881) and 2-cyano-5-ethoxy-3,6-dimethylpyrazine A-oxide (55720h) (288). 

The diazotization of aminopyrazines has been described in earlier sections. Section V.IH records the preparation of 2-fluoropyrazine from 2-aminopyrazine in fluoroboric acid containing copper powder with sodium nitrite (882, 884) and Section V.ll the preparation of iodopyrazines from some aminopyrazines via isodiazotate salts (30) (887). These salts were assigned the isodiazotate structure, on the basis of their inability to couple with 0-naphthol in alkaline solution (887) and they were characterized by hydrolysis in cold 40% aqueous sulfuric acid to the hydroxypyrazine (887). Section V.I K describes the conversion of aminopyrazines to bromopyrazines (798, 800, 807, 890-892) for example, 2-amino-3-methoxy-carbonylpyrazine with hydrobromic acid, bromine, and sodium nitrite in water gave 2-bromo-3-methoxycarbonylpyrazine (798, 890). The diazotization of aminopyrazines to hydroxypyrazines has been described in Section VI. 1C, to alkoxy-pyrazines in Section V1.3C, and to oxopyrazines in Section V1.9A(5). 2-Amino-pyrazine with isopentyl nitrite in benzene gave 2-phenylpyrazine (45%) and some 2-isopentoxypyrazine and 2,2 -dipyrazinyl amino isomers (1211). 

The nickel-catalyzed cross-coupling reaction of fluoropyrazine and phenylmagnesium bromide was achieved in high yield using commercially available ligands such as dppe, dppp, and dppf to afford 2-phenylpyrazine 1 [10]. The conditions were suitable for the reaction of electron-poor fluorosubstrates and to a lesser extent, for reaction of fluorobenzenes. 

Substituted 2-phenylpyrazines 2 were prepared from 2-chloropyrazine and arylmagne-... 

Phenylpyrazine 4-oxide (52) gave a separable mixture of 2-chloro-3-phenylpyrazine (53), 2-chloro-5-phenylpyrazinc (54), and 2-chloro-... 

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