Carbamoylpyrazines oxidation

Tetramethyl-2,4,5,7-tetraoxo-1,2,3,4,5,6,7,8-octahy dropyrim ido[5,4.g ]-pteridine 10-oxide NaOH 3,5 -Bismethy lamino-2,6-bismethylcarbamoylpyrazine 1-oxide and 2-carboxy-3,5-bismethylamino-6miethyl-carbamoylpyrazine 1-oxide 462... 

Aminopyrazine 1-oxide has been prepared from 3-carbamoylpyrazine 1-oxide with sodium hypobromite (108, 547a), and the interaction of iminodiacetonitrile ... 

Reduction of 2-carbamoylpyrazine in ethanol over palladium-charcoal at atmospheric pressure gave 2-carbamoylpiperazine (870, 1269, 1352), and the 2-carbamoyl-3-carboxy (1269) and 2,3-dicarbamoyl (1269, 1352) analogues were prepared similarly, but 2,3-dicarboxypyrazine imide gave 50% 2,3-dicarboxy-1,4,5,6-tetrahydropyrazine imide (1269). 2-Hydroxy-3-V-phenylcarbamoylpyrazine oxidized with hydrogen peroxide in acetic acid at 50° for 96 hours did not give an 7V-oxide but only a tar and 2,3-dihydroxypyrazine (1055). 

Carboxypyrazine A -oxides have been prepared by hydrolysis of carbamoyl- and alkoxycarbonylpyrazine A(-oxides as follows (reagent and conditions) 2-carbamoyl-pyrazine 1-oxide (10% NaOH/reflux/12h) (838) 3-carbamoylpyrazine 1-oxide (10% NaOH/reflux/30 min) (1266, cf. 838) 3-A(-acetylcarbamoylpyrazine 1-oxide (10% NaOH/heat) (1057) 3-morpholinocarbonylpyrazine 1-oxide (18% HQ/reflux/ 8h) (870) 2-hydroxy-5-methoxycarbonylpyrazine 1-oxide 2.5N NaOH/20-25°/ 20min) (739) 3-hydroxy-5-methoxycarbonylpyrazine 1-oxide (KOH/22 /2h gave 3-carboxy-5-hydroxypyrazine 1-oxide, which interfered with the growth of Streptococcus faecium Escherichia coli at 6 x lO and 4 x 10" M, respectively) (1035) 2-amino-3-benzyloxycarbonyl-5-methyIpyrazine 1-oxide 2N NaOH/reflux/ 30min) (365c) and 2-amino-5-chloro-3-methoxycarbonylpyrazine 1-oxide 2.5N NaOH/heat) (876,1222). 

Carboxy-3-(o-carboxyphenyI)-5,6-diphenylpyrazine A -oxide was deoxygenated by stannous chloride (399) and 2-carboxy-3,5-bis(methylamino)-6-A -methyl-carbamoylpyrazine 1-oxide with sodium dithionite in aqueous ethanol at 90° for 3 hours (462). 

CARBAMOYLPYRAZINE A-OXIDES AND RELATED COMPOUNDS (HYDRAZIDES, GUANIDINOCARBONYL COMPOUNDS, ETC.)... 

Carbamoylpyrazine A-oxides are also prepared from the corresponding esters. 3-Methoxycarbonylpyrazine 1-oxide with ammonium hydroxide at reflux gave 3-carbamoylpyrazine 1-oxide (1266) and similarly with hydroxylamine gave 3-N-hydroxy carbamoylpyrazine 1-oxide (1266). 2-Amino-5-chloro-3-methoxycarbonyl-pyrazine 1-oxide with methylamine gave 2-amino-5-chloro-3-A-methylcarbamoyl-pyrazine 1-oxide (876). 

Cyanopyrazine 1-oxide and 3-cyanopyrazine 1-oxide each with alkaline 3% hydrogen peroxide at 55° gave 2-carbamoylpyrazine 1-oxide and 3-carbamoyl-pyrazine 1-oxide, respectively (838). 3-Amino-2-cyanopyrazine 1-oxide refluxed with trifluoroacetic anhydride in triHuoroacetic acid for 5 hours gave 3-amino-2-carbamoylpyrazine 1-oxide (538), and 2-amino-3-cyano-5-methylpyrazine 1-oxide with sulfuric acid (d. 1.8) at 100° gave 2-amino-3-carbamoyl-5-methylpyrazine 1-oxide (1255). 2-Amino-6-chloro-3-cyano-5-methylpyrazine 1-oxide with 0.5N sodium hydroxide at room temperature for 48 hours formed a mixture of 2-amino-3-cyano-6-hydroxy-5-methylpyrazine 1-oxide (56%) and 2-amino-3-carbamoyl-6-chloro-5-methylpyrazine 1-oxide (22%)(533). 3-7V-Acetylcarbamoylpyrazine 1-oxide was hydrolyzed by hot 10% sodium hydroxide to 3-carboxypyrazine 1-oxide (1057). 

Oxidation of 2-carbamoylpyrazine with hydrogen peroxide in acetic acid gave a mbcture containing mainly 3-carbamoylpyrazine 1-oxide (138, 575, 757, 839, 840,... 

Hydrolyses of carbamoylpyrazine A -oxides to carboxypyrazine IV-oxides have been described in Section 8A(2), deoxygenation and chlorination of carbamoylpyrazine A -oxides (A -unsubstituted carbamoyl compounds gave the nitrile) in Section V.IG, and deoxygenation of carbamoylpyrazine A -oxides (which also contained amino groups) in Section VIII.3C(4). In addition, 4-methyl-2-A -methyl-A -phenylcarbamoyl-3-oxo-3,4-dihydropyrazine 1-oxide refluxed with aqueous ethanolic sodium dithionite gave 4-methyl-2-Af-methyl-Af-phenylcarbamoyl-3-oxo-3,4-dihydropyrazine (1137), and 3,5-bis(methylamino)-3-A -methylcarbamoyl-pyrazine 1-oxide was deoxygenated by heating at 190-200° and 0.25 mm (462). 

Various bicyclic heterocycles have been prepared from carbamoylpyrazine V-oxides 2-amino-5-chloro-3-7V-methyIcarbamoylpyrazine 1-oxide refluxed with triethyl orthoformate and acetic anhydride gave 6-chloro-3-methyl-4-oxo-3,4-dihydropteridine 8-oxide (1222) 2-amino-3-carbamoyl-5-methyl(or phenyl)pyrazine 1-oxide with triethyl orthoformate, or with ethyl chloroformate followed by cyclization of the intermediate urethane, gave 6-methyl(or phenyl)-4-hydroxy-pteridine 8-oxide (537). 

The oxidations of 2-amino-3-cyanopyrazine 1-oxides to the 1,4-dioxides are described in Section VIII.3A(4) and deoxygenations of some 2-amino-3-cyano-pyrazine 1-oxides and 1,4-dioxides with phosphorus trichloride or sodium dithionite in Section VIII.3C(4). Deoxygenation and chlorination of aminocyanopyrazine 1-oxides are reported in Section V.IG, and deoxygenation and acetoxylation or alkoxylation of 2-amino-3-cyano-5-methylpyrazine 1,4-dioxide in Section VIII.3C(5). Hydrolysis of cyanopyrazine Y-oxides to carbamoylpyrazine Af-oxides are given in Section 10A(3) and ring closure reactions of 2-amino-3-cyanopyrazine 1-oxides to pteridine 8-oxides in Section V11I.3C(3). 

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