2- -3-hydroxy-6-methoxypyrazine methylation

Methoxypyrazines (31) have been prepared by diazomethane methylation of 2-hydroxy-3-isobutylpyrazine (60, 311, 367), 2-hydroxy-3-isopropylpyrazine (59, 367), 2-hydroxy-3-propyl(ethyl or hexyl)pyrazine (367), 3-hydroxy-2-isobutyl-5(and 6)methylpyrazine and 2-hydroxy-3-isobutyl-5,6-dimethylpyrazine (368), 2,3-dihydroxypyrazine (832), 2-hydroxy-5-methoxy- and 2,5-dihydroxy-3,6-diphenyl-pyrazine (832), 2-hydroxy-6-methoxy(and benzyloxy)pyrazine (832), 2,6-dihydroxy-3,5-diphenylpyrazine (873), 2,3,5-trifluoro-6-hydroxypyrazine (851), 2-chloro-6-hydroxy-3,5-diphenylpyrazine (873), 2-chloro-6-hydroxy-5-methyl-3-phenylpyrazine (873), 2-chloro-6-hydroxy-3-methyl-5-phenylpyrazine (873), 5,6-dichloro-1 -cyclohexyl-34iydroxy-2-oxo-l, 2-dihydropyrazine (853), 2-chloro-5-hydroxy-3-methoxy-6-methoxycarbonylpyrazine (881), 2-(4 -amino-3, 5 -dibromo-phenylsulfonamido)-3Tiydroxy-6-methoxypyrazine (881), 2-amino-3-hydroxy-... 

Pyrolyses and thermal stabilities of 2-hydroxy-, 2-ethoxy-, and 2-isopropoxy-pyrazines have been studied. 2-Hydroxypyrazine was very stable, but the alkoxy-pyrazines underwent thermal elimination of olefin to yield 2-hydroxypyrazine (668a). Electrochemical reductions of l-methyl-2-oxo-5,6-diphenyl-l,2-dihydro-pyrazine and 54iydroxy(and 5-methoxy)-2,3-diphenylpyrazine are reported to involve the intermediate enamine, for example, 6-hydroxy-1-methyl-2,3-diphenyl-1,4-dihydropyrazine (54) (1096, cf. 1097). When tested on mice 2-carbamoyl-5-methoxypyrazine had less anti tubercular activity than did pyrazinamide (1098). 

Important components of hard cheeses (Gouda type) include some carboxylic acid esters (ethyl butanoate, ethyl hexanoate), as well as carboxylic acids (acetic, butyric, isobutyric, valeric, isovaleric, 2-methylbutyric and caproic acids). Cheeses manufactured using bacteria of the genus Propionibacterium (such as Emmental and Gruyere) contain propionic acid and other lower fatty acids, methyl thioacetate, some oxocarboxylic acids, various alcohols, esters (such as ethyl butanoate), lactones (such as 8-decalactone), amines and other basic compounds (also skatole in addition to aliphatic amines), alkylpyrazines (e.g. 2-sec-butyl-3-methoxypyrazine), 4-hydroxy-2,5-dimethyl-2H-furan-3-one (furaneol), 2-ethyl-4-hydroxy-5-methyl-2H-furan-3-one (homofuraneol) and a range of other compounds. 

Examination of the basic ionization constants (820) and ultraviolet spectra (821, 1081) of 2-hydroxypyrazine and its TV- and D-methyl derivatives (Table VI.1) (820, 821,1082) has revealed that the neutral species of2-hydroxypyrazine exists in aqueous solution as the amide form (46) but, in the absence of a common cation, tautomeric ratios could not be determined (821, 1083). The infrared spectra of 2-hydroxypyrazine in the solid state and in chloroform solution led to a similar conclusion (1084, 1085). Infrared spectra (680) for 2-hydroxy-3-methyIpyrazine and pjn.r. spectra (979,1086) of 2-hydroxy-and 2-methoxypyrazines also indicate that the hydroxy compounds exist in the amide form, and are further supported by MO[Pg.172]

Methylation (666, 912) of 2-methoxypyrazine with methyl iodide in dimethyl sulfoxide at room temperature gave 3-methoxy-l-methylpyrazinium iodide with a rate of methylation relative to pyrazine of 1.05 (666). 2-Methoxypyrazine with tetracyanoethylene oxide gave a small yield of 3 ethoxypyrazinium dicyano-methylide (53) (1094). Alkylation of 2-methoxypyrazine with ethyl methyl ketone in the presence of sodium in liquid ammonia to give 2-s-butyl-6-methoxypyrazine (17%) has been described (614). The reactions of 3-hydroxy-2,5-dimethylpyrazine and alkylhalides have been examined (1095). 

A large number of 2-alkyl-3-methoxypyrazines has been isolated from raw vegetables (59, 60, 64, 65, 69, 80, 1099), bell peppers (60,61) and gambanum oil (49). 2-Isobutyl-3-methoxypyrazine is already finding commercial use as a flavoring material (368) and 2-ethoxy-3-methylpyrazine may be used for pineapple flavor (981). The odor characteristics (367, 368, 976, 977) and structure (977) of some alkoxy alkylpyrazines have been examined. 3-Guanidino-6-hydroxymethyl-l-methyl-2-oxo-l,2-dihydropyrazine has been isolated from seeds of Stizolobium hassjoo and on mild alkaline hydrolysis gave 3-hydroxy-6-hydroxymethyl-l -methyl-2-oxo-l, 2-dihydropyrazine (1060). 

Khydroxypyrazine (which was converted into its jV -dimethyl derivative by treatment with dimethyl sulfate and alkali) gave, on reaction with an excess of ethereal diazomethane a mixture of its N,N-, 0,N-, and 0,0-dimethyl derivatives (58-60) (832). 2-Hydroxy-5-methoxy- and 2,5-dihydroxy-3,6-diphenylpyrazine with ethereal diazomethane gave predominantly 2,5-dimethoxy-3,6-diphenyl-pyrazine and only minor amounts of A -methylated products (832). Methylation of 2-hydroxy-6-methoxypyrazine with ethereal diazomethane produced a mixture of 0- and A -methyl derivatives in which the 0-methyl derivative predominated but the corresponding reaction of 2-benzyloxy-6-hydroxypyrazine gave almost exclusively the 0-methyl derivative (832) [the results of these methylations were correlated with the carbonyl stretching frequency (1103) in the parent lactam (832)]. 

Diazomethane methylation of 3-hydroxy-2,5-diisobutylpyrazine 1,4-dioxide has been shown to give the 4-methoxypyrazine 1-oxide, 2,5-diisobutyl4-methoxy-3-0X0-3,4-dihydropyrazine 1-oxide (96) (843, 980) [and some 3-methoxy-2,5-diisobutylpyrazine 1,4-dioxide (4 l)(980)] 5-s-butyl-3-hydroxy-2-isobutylpyrazine... 

Hashizume, K., Tozawa, K., Endo, M., and Aramaki, I. 2001. 5-Adenosyl-L-methio-nine-dependent 0-methylation of 2-hydroxy-3-alkylpyrazine in wine grapes A putative final step of methoxypyrazine biosynthesis. Biosci. Biotechnol. Biochem. 65 795-801. 

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