Carboxy hydroxypyrazines

Many derivatives of carboxy chloropyrazines have been prepared by the action of phosphoryl chloride on the corresponding hydroxypyrazine. In this way were prepared 2-chloro-3-methoxycarbonylpyrazine (371, 423, 836), 2-chloro-3-methoxycarbonyl-5,6-diphenylpyrazine (but the corresponding hydroxy compound did not react with phosphorus tribromide) (837), and 3-chloro-2-methoxycarbonyl-... 

Section II.S includes the cleavage of pteridines and related ring systems to yield hydroxypyrazines (375, 420, 429, 433-434, 440, 441,445,448,449). Additional data are given in references 372,907,1052 and 1053. 2-Amino-6-(p-fluorophenyl)-4-hydroxypteridine with 4A sodium hydroxide at 170 gave 3-carboxy-5-(p-fluorophenyl)-2-hydroxypyrazine, and a similar preparation of the isomeric 6-(p-fluorophenyl)pyrazine was also described (347). 

Diacetyl-3,6-dibenzylpiperazine-2,5-dione (15) reacted with sulfur in dimethyl-formamide and triethylamine to form, after hydrolytic removal of the acetyl groups, 3-benzyl-6-benzylidenepiperazine-2,5-dione (16) (1068). 2-Chloro-5-hydroxy-3,6-dimethylpyrazine heated with solid potassium hydroxide gave 3-hydroxy-2,5-dimethylpyrazine (312), and 2-chloro-6-hydroxy-3,5-diphenylpyrazine with an excess of methanolic sodium methoxide at 150° formed 2-hydroxy-3,5-diphenylpyrazine (873). Decarboxylation of 2-carboxy-3-hydroxypyrazine gave 2-hydroxypyrazine (420) and in this way 24iydroxy[2- C]pyrazine (823) and 2-hydroxy[l- N]pyrazine (822) have been prepared. 

Amino-3-cyano-5-methylpyrazine 1,4-dioxide (91) refluxed for several minutes with acetic anhydride formed 3-acetamido-2-cyano-5-hydroxy-6-methylpyrazine 1-oxide (92) (24%) (532) and 2-acetoxymethyl-5-methylpyrazine 1,4-dioxide refluxed with acetic anhydride afforded a mixture of2,5-di(acetoxymethyl)pyrazine 1-oxide, with some 2,5-diacetoxymethylpyrazine and a monoxide of 2-acetoxy-methyl-5-methylpyrazine (625). 2-Formylpyrazine hydrate 1,4-dioxide with aqueous sodium hydroxide or bicarbonate at < 37° in an unusual reaction gave 3-carboxy-pyrazine 1-oxide mixed with 5 [Pg.188]

The preparation of arylazo derivatives from hydroxypyrazines has been described in Section VI.6E and from l,4,6-trimethyl-3-methylene-2-oxo-l,2,3,4-tetrahydro-pyrazine to give l,4,6-trimethyl-2-oxo-3-phenykzomethylene-l,23,4-tetrahydro-pyrazine in Section VI.9B. In addition to these reactions Princivalle (1122) reports that 2reacted with benzenediazonium chloride and p-toluenediazonium chloride by elimination of the carboxy group para to the hydroxy group and coupling to form 2-hydroxy-3,6-dimethyl-5-phenyl-azo(and p-tolueneazo)pyrazines, respectively (1122), identical to those prepared from 3-hydroxy-2,5 -dimethylpyrazine. 

Amino-5-carboxypyrazine in anhydrous dimethylformamide with triethyl-amine and ethyl chloroformate and then diethyl glutamate and stirred at room temperature gave 2-amino-5-(l, 3 -diethoxycarbonylpropyl)carbamoylpyrazine (24) (1244). Similarly a mixture of 2-carboxypyrazine and triethylamine in methylene dichloride with ethyl chloroformate and morpholine gave 2-( -morpholinocarbonyl)-pyrazine (1351). 2-Carboxy-3-hydroxypyrazine refluxed with phosphorus tris(A-methylanilide) in toluene gave 2-hydroxy-3-(A-methyl-A-phenyIcarbamoyl)pyrazine (1055), and 2-hydroxy-3-(A -methyl-A -p-tolylcarbamoyl)pyrazine was prepared similarly (1055). Tetracarboxypyrazine heated with sulfur tetrafluoride (SF4) at 150° gave tetra(trifluoromethyl)pyrazine (899). 

Carboxy-3-hydroxypyrazine refluxed with phosphorus tri(Af-methylanilide) in toluene gave 2-hydroxy-3-(A -methyl-A -phenyl)carbamoylpyrazine, and 2-hydroxy-... 

Carbamoylpyrazine in dogs and humans is hydrolyzed to 2-carboxypyrazine and then converted to 2-carboxy-5-hydroxypyrazine (1400) and a combined gas chromatographic-mass spectroscopic technique has been described for the simultaneous determination of 2-carbamoylpyrazine, 2-carboxypyrazine, and 2-carboxy-... 

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). 

Formylpyrazine hydrate dioxide in alkaline solution (with or without hydrogen peroxide) formed a mixture of 3-carboxypyrazine 1-oxide and 5-carboxy-2-hydroxypyrazine 1-oxide (739), and it formed derivatives with 2,4-dinitrophenyl-hydrazine, semicarbazide, or hydroxylamine (739). 

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