2- Bromo-5-phenylpyrazine

Bromo-3-methyl-5-phenylpyrazine 5-Bromomethyl-6-phenyl-2,3-pyrazine-... 

Aminopyrazine with bromine in acetic acid gave 2-amino-3,5-dibromopyrazine (804, 810, 811), also obtained from bromination of 2-amino-3-bromopyrazine in aqueous hydrobromic acid (806, 807), and 5-amino-2,3-dimethylpyrazine with bromine in acetic acid gave 2-amino-3-bromo-5,6-dimethylpyrazine (812). 2-Amino-5-phenylpyrazine with bromine and pyridine in chloroform at 20 gave 2-amino-3-bromo-5-phenylpyrazine (365a), and 2-amino-3-chloropyrazine with 20% hydrobromic acid and bromine gave 2-amino-5-bromo-3-chloropyrazine (806,807). 

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-... 

Bromo-3-methoxycarbonylpyrazine with 2,3-dimethylaniline in refluxing toluene gave 2-(2, 3 -dimethylphenyl)amino-3-methoxycarbonylpyrazine (950) [hydrolysis of this product with sodium hydroxide in ethanol gave 2-carboxy-3-(2, 3 -dimethylphenyl)aminopyrazine, which was also obtained by treatment of l-(2, 3 -dimethylphenyl)lumazine with sodium hydroxide in refluxing ethanol (950)]. 3-Bromo-2-hydroxy-5-phenylpyrazine with ammonium hydroxide and copper at 150° gave 3-amino-2-hydroxy-5-phenylpyrazine (365a). Replacement of the iodo substituent from 2-amino-5-iodo-3,6-dimethylpyrazine has been effected with ammonium hydroxide (887). 

Amino-5-bromo-3-carbamoylpyrazine heated with trifluoroacetamide and sodium ethoxide (or butoxide) gave 6-ethoxy(or butoxy)-4-hydroxy-2-trifluoro-methylpteridine (49) (987) and 2-chloro-3-pyridiniopyrazine chloride with methoxide ion gave 2,3-dimethoxypyrazine (765). 2-Amino-3-bromo-5-phenyl-pyrazine with sodium methoxide in methanol at 134° for 8 hours formed 2-amino-3-methoxy-5-phenylpyrazine (365a) and 3-bromo-2-hydroxy-5-phenylpyrazine similarly treated gave 2-hydroxy-3-methoxy-5-phenylpyrazine (365a). 

Displacement of the chloro substituent from pyrazines by the cyano group has not been satisfactorily accomplished (866), but many cyanopyrazines have been prepared from the bromo analogues. Karmas and Spoerri (866) prepared 11 cyanopyrazines with mono-, di-, or trialkyl or phenyl substituents from the corresponding bromo compounds and cuprous cyanide in refluxing dry 4-picoline, but the procedure was not suitable for the preparation of 2-cyanopyrazine (866). It was prepared in 29% yield when the reaction was performed in pyridine (866). Another preparation of 2-cyano-3-phenylpyrazine from the bromo analogue has also been reported (1024). 

Section II.7 describes some ring closures of the C-C-N-C-C, N-C-C-N-C-C, and N-C-C-N-C-C-N systems to give hydroxypyrazines (248, 365a, 477, 479, 480-483) more information can be found in reference 1054. Newbold and Spring (89) described the reaction of 2-bromo-A -(r-methyl-2 -oxopropyl)propionamide with ethanolic ammonia to give 2-hydroxy-3,5,6-trimethylpyrazine and Masaki et al. (551) have described the reaction of A -leucyl-6>-benzyIhydroxylamine (2) with phenacyl bromide in methanol saturated with ammonia to give 3-hydroxy-2-isobutyl-5-phenylpyrazine and 2,5-diphenylpyrazine. 

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). 

This convenient indirect process involves conversion of a pyrazinone into the conesponding trimethylsiloxypyrazine, and thence (with phosphorus halide) into the required halogenopyrazine. For example, 5-phenyl-2(lH)-pyrazinone afforded crude 2-phenyl-5-trimethylsiloxypyrazme (neat McsSiNHSiMe , ClSiMc, reflux, 30 min) that reacted with an appropriate phosphorus halide to furnish 2-bromo-(neat PBrj, 150 (1 1 h 77% overall), 2-chloro- (neat PCI5, 2(X) C. 1 h 40%), or 2-iodo-5-phenylpyrazine (PI3, CI2CHCH2CI, reflux, 24 h 12%) homologues were made similarly. ... 

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