3-Ethoxy-2,5-dimethylpyrazine

Dimethoxy(or diethoxy)-3,6-dimethylpyrazine 1,4-dioxide with phosphoryl chloride have been shown to give 2,5-bis(chloromethyl)-3,6-dimethoxy(or diethoxy)-pyrazine (756), 3-ethoxy-2,5-dimethylpyrazine 1-oxide gave 2-chloro-5-ethoxy-... 

The following alkoxypyrazine Af-oxides have been prepared from the corresponding chloropyrazine A-oxides and sodium alkoxide in the appropriate alcohol (unless otherwise specified) 3-methoxypyrazine 1-oxide (838) 2-methoxypyrazine 1-oxide (no details (838) 3-ethoxypyrazine 1-oxide (978) 3-ethoxy-2-methylpyrazine 1-oxide (potassium hydroxide in ethanol) (978) 3-ethoxy-2,5-dimethylpyrazine 1-oxide (sodium ethoxide or potassium hydroxide in ethanol) (872, 978) and 3-methoxy-2,5-dimethylpyrazine 1-oxide (588). 

Alkoxypyrazine A -oxides may be hydrolyzed with acid to hydroxypyrazine A -oxides. Some examples are the hydrolysis of 3-ethoxy-2,5-dimethylpyrazine 1-oxide at reflux with 3 A hydrochloric acid to give 3-hydroxy-2,5-dimethylpyrazine 1-oxide (872) 2,5-diethoxy-3,6-dimethylpyrazine 1,4-dioxide with 2N hydrochloric acid at 70° gave 2-ethoxy-5-hydroxy-3,6-dimethylpyrazine 1,4-dioxide and 2,5-dibenzyloxy-3,6-dimethylpyrazine 1,4-dioxide similarly treated but at room temperature gave the 2-benzyloxy analogue (842), but with lOAf hydrochloric acid at room temperature it gave 2,5-dihydroxy-3,6-dimethylpyrazine 1,4-dioxide (842). 

Reactions of C-alkoxypyrazine A-oxides with phosphoryl chloride have been described in Section V.IG (756, 817, 838, 872, 881). For example, 3-ethoxy-2,5-dimethylpyrazine 1-oxide refluxed with phosphoryl chloride for 10 minutes gave 2-chloro-5-ethoxy-3,6-dimethylpyrazine and 2-chloromethyl-3-ethoxy-5-methyl-pyrazine (872). 

Ethoxy-3,6-dimethylpyrazine 5-Ethoxy-3,6-dimethyl-2-pyrazinecarbonitrile 5-Ethoxy-3,6-dimethyl-2-pyrazinecarbonitrile 1/4-oxide... 

Ethoxy-3,6-dimethylpyrazine 4-oxide 5-Ethoxy-l,3-dimethyl-2(177)-pyrazinone 2-Ethoxy-3,6-diphenylpyrazine... 

Other alkoxy dechlorinations were 2-chloro-5-ethoxy-3,6-dimethylpyrazine (872) and 2-amino-6-chloro-3,5-dicyanopyrazine (484) with ethoxide ion 5-chloro-... 

Ethoxypyrazine 1-oxide refluxed with 40% alcoholic hydrogen chloride yielded 2-ethoxy-5-hydroxypyrazine (1069). Ultraviolet irradiation of 2,5-dimethyl-pyrazine 1-oxide in water afforded 3-hydroxy-2,5-dimethylpyrazine (10%) and 2,5-diphenylpyrazine 1-oxide in benzene gave 3-hydroxy-2,5-diphenylpyrazine (3%) (742). A small yield of 2-ethyI-5-hydroxy-3,6-dimethylpyrazine has been isolated as by-product from the reaction of 2,5-dimethylpyrazine with ethyllithium in ether (615). 

Diniethylpiperazine-2,5-dione (34) on treatment with triethyloxonium fluoroborate in dichloromethane gave 5-ethoxy-l,3-dimethyl-2-oxo-l, 2,3.6-tetrahydropyrazine which was oxidized by DDQ in dry benzene to 5-ethoxy-l 3 dimethyl-2-oxo-l,2-dihydropyrazine (35) (1067). l,3,6-Trimethylpiperazine-2,5-dione similarly treated gave three products, one of which was assigned the structure 5-methoxy-l 3,6-trimethyl-2-oxo-l, 2-dihydropyrazine 3-benzyl-5-methoxy-l, 6-dimethyl-2-0X0-1,2-dihydropyrazine was also prepared similarly (1078). When 3,6-diethoxy-2,5"dimethyl-2,5-dihydropyrazine was refluxed with lead tetraacetate in dry benzene it gave a mixture of 2,5-diacetoxy-3,6-diethoxy-2,5-dimethyl-2,5-dihydropyrazine (36) (4 parts) and 2,5-diethoxy-3,6-dimethylpyrazine (1 part) (1068). 

Dicyano-3,6-dimethylpyrazine shaken with sodium ethoxide at room temperature for 10 hours produced 2-cyano-5-ethoxy-3,6-dimethylpyrazine (288). Bromination of 2-methoxy-3-sulfanilamidopyrazine (39) in methanol led to 5-(4 -amino-3, 5 -dibromobenzenesulfonimido)-6-hydroxy-2,3-dimethoxy-2,3,4,5-tetrahydropyrazine (32) which with 2 N sodium hydroxide gave 3-(4 -amino-3, 5 -dibromobenzenesulfonamido)-2-hydroxy-5 nethoxypyrazine (40) (816). The preparation of 2-amino-3,5-dicyano-6-methoxy(and ethoxy)pyrazine from a-(p-toluenesulfonyloxyiminomalononitrile and malononitrile has been described in Section II.7 (484). 2-Methoxycarbonyl(and cyano)-5-pyridiniopyrazine chloride (41) is reported (conditions not stated) to give 2-carboxy(and carbamoyl)-5-methoxypyrazine (765). 

Alkoxypyrazine A-oxides may also be prepared by oxidation of the alkoxypyrazine with peroxyacetic acid. In this way the following have been prepared 3-ethoxypyrazine 1-oxide (100°/20h) (978) 3-(trideuteromethoxy)pyrazine 1-oxide (757l9h) (975) 3-ethoxy-2-methylpyrazine 1-oxide (65-75724h) (978) 3-methoxy-2-phenylpyrazine 1-oxide (55720 h) (817) 3-ethoxy-2,5-dimethyl-pyrazine 1-oxide (56716 h) (872) 3-carbamoyl-2-methoxypyrazine 1-oxide (80720h) (881) and 2-cyano-5-ethoxy-3,6-dimethylpyrazine A-oxide (55720h) (288). 

Cyano-5-ethoxy-3,6-dimethylpyrazine refluxed with 50% sulfuric acid gave 3-hydroxy-2,5-dimethylpyrazine (288) but when refluxed with 5A potassium hydroxide for 10 hours gave 2-carboxy-5-hydroxy-3,6-dimethylpyrazine (288). 

Iminoethers have been hydrolyzed to esters and iminothioethers to thioesters. Some examples follow 2-cyano-3-(C-ethoxy-C-iminomethyl)-5,6-dimethylpyrazine [2-cyano-3-(C-ethoxyformidoyl)-5,6-dimethylpyrazine] (26) in boiling water gave... 

Irradiation of 2,5-bis(methoxycarbonyl)-3,6-dimethylpyrazine in diethyl ether with a 450-W high-pressure mercury lamp (330 nm) gave two significant photoproducts 2-hydroxy-5-methoxycarbonyl-3,6-dimethylpyrazine and l-(l -ethoxy-ethyl)2,5-dimethoxycarbonyl-3,6-dimethyl-l, 4-dihydropyrazine (74). Similar products were isolated when tetrahydrofuran was used as solvent. Corresponding reactions were observed with 2,5-bis(ethoxycarbonyl)-3,6-dimethylpyrazine, 2,5-diacetyl-3,6-dimethylpyrazine, and 2,5-dibenzoyl-3,6-dimethylpyrazine. The mechanism of these reactions were investigated and the initial stage was found to be... 

Cyanopyrazine A -oxides have been prepared from a-amino nitriles and a-hydroxyimino carbonyl compounds as summarized in Section III. 1 (528-530, 532-534, 537, 540, 542). Oxidation of 2-cyanopyrazine with perhydrol gave 3-cyanopyrazine 1-oxide (575), 2-cyano-5-ethoxy-3,6-dimethylpyrazine with 30% hydrogen peroxide in acetic acid at 55° gave 2-cyano-5-ethoxy-3,6-dimethylpyrazine iV-oxide (288), and the oxidations of 2-amino-3-cyanopyrazine 1-oxide (538) and... 

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