3 - -2-pyrazinecarbonyl

Amino or A-BOC-amino pyrazines have been produced by Curtius degradation of pyrazinecarbonyl azides in 7-butanol (Equation 30) <1999JA8783>. 

The most convenient synthesis of halogenopyrazines and -quinoxalines is by halogenation of pyrazinones and quinoxalinones with phosphoryl or other acid halides for example, 5-hydroxy-2-pyrazinecarboxylic acid, rather than 5(477)-pyrazinone-2-carboxylic acid, is chlorinated with phosphorus pentachloride/phosphoryl chloride to afford a 63% yield of 5-chloro-2-pyrazinecarbonyl chloride <1994SL814>. Sato and Narita provided an improved synthesis of various halogenopyrazines in which 2(l//)-pyrazinones were activated with chlorotrimethylsilane to give silyl ethers (Section 8.03.7.3). This procedure is most effective for synthesis of bromopyrazines whose overall yields are 62-81% <1999JHC783>. Bromopyrazine is directly prepared by treatment of 2-(l//)-pyrazinone with phosphoryl... 

Note Pyrazinecarbonyl chlorides are often used as reactive intermediates but they are not always characterized as such. 

Chloro-2-pyrazinecarboxyhc acid (28, R = Cl) gave 6-chloro-2-pyrazinecar-bonyl chloride (29, R = Cl) (SOCl2, PhH, reflux, 90 min 73%) 505 and 6-phenyl-2-pyrazinecarboxylic acid (28, R = Ph) gave 6-phenyl-2-pyrazinecarbonyl chloride (29, R = Ph) (neat SOCl2, reflux, 2 h uncharacterized product).1015... 

Methyl 2-pyrazinecarboxylate (90) gave A -methyl-2-pyrazinecarbohydrazide (89) without any of the. V-m ethyl isomer (91) [MeHNNH2, EtOH, reflux, 12 h 81% the isomer (91) can be made from 2-pyrazinecarbonyl chloride see Section 8.3.2] analogous esters behaved similarly to give, for example, 3-amino-/V -methyl-2-pyrazinecarbohydrazide (71%).1265... 

Chloro-2-pyrazinecarbonyl chloride (126) and 2-pyrazinamine gave 6-chloro-Ar-(pyrazin-2-yl)-2-pyrazinecarboxamide (127) (Et3N, PhH, 20°C, 30 min 85%).505... 

Pyrazinecarbonyl chloride gave 2-(aziridin-l-ylformyl)pyrazine (128) [HN(CH2)2, Et3N, PhH—PhMe, 0 - 20°C, 2 h 66% analogues likewise).8... 

Pyrazinecarbonyl chloride gave Af-methyl-2-pyrazinecarbohydrazide (133) [MeHNNH2, Et20, -35 20°C, slowly 36% the TV -methyl isomer (134)... 

Chloro-2-pyrazinecarbonyl chloride (140, R = Cl) and AKcyclopent- 1-en-1-yl)pyrrolidine gave 2-chloro-3-[2-(pyrrolidin-1 -yl)cyclopent-l-en-1 -ylcar-bonyl]pyrazine (141) (Et3N, CH2C12,--------40°C, N2, 2 h 63%).382... 

Pyrazinedicarbonyl dichloride (144) and cyclohexyl isocyanate gave 3-[a-chloro-a-(cyclohexylimino)acetyl]-2-pyrazinecarbonyl chloride (145) (PhH, 20°C, 1 h then 60°C, 45 min 54%).523 Also other examples.275 1091... 

Pyrazinecarbonyl chloride (146) with benzophenone oxime gave the ester-like... 

Pyrrol-l-yl)-2-pyrazinecarbonyl chloride gave the corresponding azide [sub-... 

Several routes to such derivatives have been covered already by primary synthesis (Chapters 1 and 2), from halogenopyrazines by displacement (Section 4.2.9), from pyrazine carboxylic acids (Section 8.1.2), from pyrazinecarboxylic esters (Section 8.2.2), and from pyrazinecarbonyl halides (Section 8.3.2). The remaining methods of preparation are illustrated in the following examples ... 

Pyrazinecarbonyl azide (165) gave 2-pyrazinecarboxanilide (166) (PhNH2, MeOCH2CH2OMe, 20°C, <12 days 86%).1130... 

Pyrazinecarbonyl azides have been made from pyrazinecarbonyl halides (see Section 8.3.2) but more usually from pyrazinecarbohydrazides with nitrous acid as exemplified here. 

Pyrazinecarbohydrazide (204) and 4-ethoxymethylene-2-phenyloxazolin-5-one (206) gave N,N -bis(2-pyrazinecarbonyl)hydrazine (207) and 4-benzami-dopyrazolin-3-one (208) (dioxane, reflux, 30 min 90% the mechanism of hydrogen removal is discussed).1605... 

Pyrazinecarbonyl azides may be converted into pyrazinamines (see Section 7.3.1) or into pyrazinecarboxamides or pyrazinecarboxanilides (see Section 8.4.1). In addition, two molecules of 3-(pyrrol-l-yl)-2-pyrazinecarbonyl azide (211) in warm water for 15 min have been reported to give /V,/V -bis 3-(pyrrol-l-yl)pyrazin-2-yl]urea (212) in 32% yield.94... 

Several major routes to pyrazine ketones have been covered already by primary synthesis in Chapters 1 and 2, by oxidation of aralkylpyrazines in Section 3.2.4.1, by oxidation of secondary hydroxyalkylpyrazines in Section 5.2.2, from pyrazinecarboxylic esters by the Claisen reaction in Section 8.2.2, from pyrazinecarbonyl halides (using several methods) in Section 8.3.2, and frompyrazinecarbonitriles with a Grignard (or similar reagent) in Section 8.6.2. 

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