2.3- Dihydroxy-5-methylpyrazine

The irans-benzylidene derivative (188), obtained as the major product of condensation of 3-methylpiperazine 2,5-dione and benzaldehyde in the presence of acetic anhydride, undergoes photoisomerization to the cis isomer (191) on irradiation in methanol. Both isomers have been converted into tetrahydropyrazine imino ethers (189) and (192) by treatment with triethyloxonium fluoroborate. The trans compound reacts more slowly and gives a lower yield of imino ether and this is attributed to steric hindrance. Compounds 188 and 191 are de-acetylated on treatment with methanolic 2 N potassium hydroxide. The trans and cis isomers (187) and (190), so produced are converted into 3-benzyl-2,5-dihydroxy-6-methylpyrazine (144) when heated at 100° with sodium hydroxide.384 Treatment of the dichloroacetyl derivative of phenylalanine with methylamine gives l-methyl-3-benzylidenepiperazine 2,5-dione with the stereochemistry shown.384a... 

Some chlorinations have been reported with thionyl chloride. 23-Dicyano-5,6-dihydroxypyrazine refluxed with thionyl chloride in pyridine was reported to give 23-dichloro-5,6-dicyanopyrazine (862) and 2-hydroxy-3-nitro-5,6-diphenyl-pyrazine with thionyl chloride gave 2-chloro-3-hydroxy-5,6-diphenylpyrazine (817, 841) but with thionyl chloride and pyridine it gave the betaine of 2-hydroxy-5,6-diphenyl-3-pyridiniopyrazine chloride (5) (863), which was hydrolyzed in acid to 2,3-dihydroxy-5,6-diphenylpyrazine (863). No product could be isolated from 2-methylpyrazine when refluxed with thionyl chloride (864). 1,4-Dimethylpiperazine-... 

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-... 

In 23-dihydroxypyrazine and derivatives Honzl (853), from measurements of infrared spectra in chloroform and ultraviolet spectra in aqueous alcohol, has proposed that 5,6-dichloro-l-cyclohexyl-3-hydroxy-2-oxo-l, 2-dihydropyrazine (pA in water 4.66, 5.66) exists in the form (48). The p.m.r. spectra of some 5- and 6-methyl- and 5- and 6-phenyl-2,3-dihydroxypyrazines have been reported (483). In the 2,5-dihydroxypyrazine series, the infrared spectrum (Nujol) of 2-benzyl-3,6-dihydroxy-5-methylpyrazine has been interpreted as indicating that the major tautomeric form present in the solid state was the dihydroxy form (49), but the ultraviolet spectrum in ethanol was considered consistent with the coexistence of the dihydroxy (49) and oxo-hydroxy form, for example, (50), Although the structure (51) has been proposed for 3-butyl-2,5-dihydroxypyrazine (1092), the evidence in favor of this structure is inconclusive. 

Methylation of 2-hydroxy-3-7V-phenylcarbamoylpyrazine with dimethyl sulfate and potassium carbonate in boiling acetone gave l-methyl-2-oxo-3-A -phenylcarbamoyl-1,2-dihydropyrazine and the 3-(A -methyl-Af-phenylcarbamoyl) analogue was prepared likewise (1055). Similar methylation of 2-hydroxy-3-(o-methylaminophenyl)pyrazine produced 1 -methyl-3-(o-methylaminophenyl)-2-oxo-1,2-dihydropyrazine (1055). A series of 24iydroxy-3-(a-hydroxybenzyl)pyrazines has been methylated with dimethyl sulfate in aqueous sodium hydroxide to the 2-methoxy analogues (1045) and 2-benzyl-3,6-dihydroxy-5-methylpyrazine with diethyl sulfate and sodium ethoxide formed 2-benzyl-3,6-diethoxy-6-methylpyrazine (1066). 

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