3-Methoxycarbonylpyrazine 1-oxide

Pd-catalyzed carbonylation of 2-chloropyrazine 1-oxide failed, whereas that of 3-chloropyrazine 1-oxide (40) proceeded without deoxygenation of the IV-oxide function to give 3-methoxycarbonylpyrazine 1-oxide (73). This observation was in accord with the failure of Stille reactions of 2-chloropyrazine 1-oxide [9,18]. 

Amino-2prepared from 2-amino-3-cyanopyrazine 1-oxide by reflux with acetic acid-acetic anhydride followed by ready deacetylation by refluxing in methanol (538), and in a similar manner 3-amino-2-ethoxycarbonyl-5-hydroxypyrazine has been prepared from 2-amino-3-ethoxycarbonylpyrazine 1 -oxide through 3-acetamido-2-ethoxycarbonyl-5 ydroxy-pyrazine (538), and 2-amino-3-carbamoyl-6-hydroxy-5-methylpyrazine from 2-amino-3-cyano-5-methylpyrazine 1-oxide (538). The preparation of 24 ydroxy-6-methoxycarbonylpyrazine (10) has been claimed from 3-methoxycarbonylpyrazine 1-oxide with acetic anhydride followed by hydrolysis (1057) [cf. Nov Cek et al. (839), who claim it to be the 5-isomer, and Foks (744)]. 

Aminopyrazine was oxidized by hydrogen peroxide in acetic acid at 20° to 3-aminopyrazine 1 -oxide and at 50° for 15 hours to 2-aininopyrazine 1,4-dioxide (51%) (also obtained by similar oxidation of 3-aminopyrazine 1-oxide) (1189). m-Chloroperoxybenzoic acid was also used for the oxidation of 2-aminopyrazine to its 1-oxide (1258). The following aminopyrazine TV-oxides have been prepared by oxidation (reagent and conditions) 2-amino-3-methoxycarbonylpyrazine 1-oxide (m-chloroperoxybenzoic acid in chloroform at reflux) (880, 1222) 2-amino-5-chloro-3-methoxycarbonyl(and methylcarbamoyl)pyrazine 1-oxide (m-chloroperoxybenzoic acid in chloroform at reflux) (1222) 2-amino-5-bromo-3-methoxycarbonylpyrazine 1-oxide (wperoxyacetic acid) (906) 2-amino-3-bromo-5,6-dimethylpyrazine 1-oxide (peroxyacetic acid) (907) and 2,3-bis(pyridin-2 -yl)pyrazine 1,4-dioxide (hydrogen peroxide in sulfuric acid at room temperature) (754). 

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). 

Carboxypyrazine 1-oxide heated in a sealed tube at 60° with methanol and a little thionyl chloride (870, 1266), or refluxed in methanol with thionyl chloride until the acid dissolved (3 hours) (839), gave 3-methoxycarbonylpyrazine 1-oxide, and the ethyl ester was prepared similarly (839,1266). 3-Carboxypyrazine 1-oxide with diazomethane also gave 3-methoxycarbonylpyrazine 1-oxide (1266). 

Alkoxycarbonylpyrazine 7V-oxides have been prepared by esteriflcation of the corresponding acids. 3-Methoxycarbonylpyrazine 1-oxide was prepared from 3methanol with a little thionyl chloride in a sealed tube at 60° (the ethyl ester was prepared similarly) (739, 1266) and also from... 

Acetoxylative deoxygenations are as follows. 3-Methoxycarbonylpyrazine 1-oxide refluxed with acetic anhydride for 30 hours gave 2-acetoxy-6-methoxy-carbonylpyrazine (838), but Novdcek et al. (839) claim that the product (prepared with acetic anhydride at 160°) after hydrolysis with water was 2-hydroxy-5( )-methoxycarbonylpyrazine and 2-amino-3-ethoxycarbonylpyrazine 1-oxide refluxed with acetic acid-acetic anhydride gave 3-acetamido-2-ethoxycarbonyl-5-hydroxypyrazine (538). 

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). 

Methoxycarbonylpyrazine 1-oxide refluxed with 50% hydrazine hydrate gave... 

Hydrolysis of 2,6-diacetoxy-3,5-diphenylpyrazine (9) (from 2-hydroxy-3,5-diphenylpyrazine 1 -oxide by refluxing with acetic acid-acetic anhydride) with potassium hydrogen carbonate in methanol gave 2,6-dihydroxy-3,5-diphenylpyrazine (873), and 2-acetoxy-6-methoxycarbonylpyrazine (from 3-methoxycarbonyl-pyrazine 1-oxide with acetic anhydride) with methanolic hydrogen chloride gave 2-hydroxy-6 -methoxycarbonylpyrazine (838). 

Alkoxycarbonylpyrazines have been oxidized to alkoxycarbonylpyrazine Af-oxides as follows 2-ethoxycarbonylpyrazine with perhydrol gave 3-ethoxy-carbonylpyrazine 1-oxide (575) 2-amino-3-methoxycarbonylpyrazine refluxed with m-chloroperoxybenzoic acid in chloroform gave 2-amino-3-methoxycarbonyl-pyrazine 1-oxide (876,880,1222) the 5-bromo (808, 877,878, 1222) and 5-chloro (875, 876, 879, 1222) derivatives were prepared similarly and some 3-ethoxy-carbonylpyrazine 1-oxides have been prepared by oxidation (reagent not stated) of... 

For the pyrazine A -oxides, there is a table for each substituent type, and compounds are listed (once only) at the first opportunity. For example, 2-amino-6-chloromethyl-3-cyanopyrazine 1-oxide is listed in Table A.31 (aminopyrazine A -oxides) and 2-hydroxy-5-methoxycarbonylpyrazine 1-oxide in Table A.32 (carboxypyrazine A -oxides). 

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