3- Hydroxy-2,5-diphenylpyrazine methylation

Hydroxy-2,5-diphenylpyrazine, methyl iodide, and methanol and some potassium hydroxide heated in a sealed tube at 100° for 10 hours formed the methiodide of 1 -methyl-3,6-diphenyl-2-oxo-l, 2-dihydropyrazine (1104) [3-hydroxy-... 

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). 

When 2-hydroxy-3,5-diphenylpyrazine 1-oxide was heated under reflux with an excess of acetic anhydride, a crystalline triacetoxy compound was obtained which was thought to have an open chain structure [AcO-CH=CPh-N=CPh-C(OAc)=N-OAc], but when the 2-hydroxypyrazine-l-oxide was boiled with a mixture of acetic anhydride and acetic acid, 2,6-diacetoxy-3,5-diphenylpyrazine was obtained (873) which was hydrolyzed by potassium hydrogen carbonate in methanol to 2,6-dihydroxy-3,5-diphenylpyrazine (873). 2-Hydroxy-5-methyl-3-phenylpyrazine 1-oxide behaved differently and when refluxed with acetic anhydride gave 5-acetoxymethyl-2-hydroxy-3-phenylpyrazine (100) and 2-hydroxy-3-methyl-5-phenylpyrazine 1-oxide similarly gave 3-acetoxymethyl-2-hydroxy-5-phenylpyrazine (873). When 2- l-hydroxy-2 -methylpropyl)-5-isobutylpyrazine 1-oxide was heated with a mixture of acetic anhydride and sodium acetate on a water bath 2-(l -acetoxy-2 -methylpropyl)-5-isobutylpyrazine 1 oxide was obtained (760a). 

The mass spectra of pyrazine, methylpyrazine, 2,5- and 2,6-dimethylpyrazine have been reported.106 The base peak in the mass spectrum of tetramethylpyrazine corresponds to the loss of two molecules of methyl cyanide.107 The mass spectra of 2,5-bis(p-fluorophenyl)-3,6-diphenylpyrazine,108 2-hydroxy-3- alkylpyrazines, and their N- and O-methyl derivatives have also been reported.30... 

Chloro-3-methylpyrazine (101,535) and 2-chloro-5-phenylpyrazine (363, 365a, 377, 824, 825) have been prepared from the corresponding hydroxy compound and phosphoryl chloride, 2-chloro-6-methylpyrazine from 2-hydroxy-6-methylpyrazine and phosphoryl chloride with one drop of dimethylformamide (681), and 2-benzyl(or s-butyl, isobutyl, or isopropyl)-3phosphoryl chloride with a trace of concentrated sulfuric acid (80). 2-Chloro-6-methyl-3-propyl- (826), 3[Pg.99]

Section II.7 describes some ring closures of the C-C-N-C-C, N-C-C-N-C-C, and N-C-C-N-C-C-N systems to give hydroxypyrazines (248, 365a, 477, 479, 480-483) more information can be found in reference 1054. Newbold and Spring (89) described the reaction of 2-bromo-A -(r-methyl-2 -oxopropyl)propionamide with ethanolic ammonia to give 2-hydroxy-3,5,6-trimethylpyrazine and Masaki et al. (551) have described the reaction of A -leucyl-6>-benzyIhydroxylamine (2) with phenacyl bromide in methanol saturated with ammonia to give 3-hydroxy-2-isobutyl-5-phenylpyrazine and 2,5-diphenylpyrazine. 

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)]. 

Hydroxy-2 3-diphenylpyrazine (and its lV-4-methyl derivative) are electro-chemically reduced to the 5,6-dihydro derivatives which isomerize to the 3,6-... 

Dimethylaminoethyl)pyrazine was quaternized by methyl iodide to give 2-(2 -trimethylammonioethyl)pyrazine iodide (48) (which with aqueous sodium hydroxide gave 2-vinylpyrazine) (657) and 2-hydroxy-3-nitro-5,6-diphenylpyrazine... 

The title compounds are stable tautomers of the corresponding 2-hydroxypyrazine 1-oxides, and in fact l-acetoxy-2(lH)-pyrazinones, not 2-acetoxypyrazine A -oxides, are obtained on treatment with acetyl chloride in the presence of pyridine at room temperature <87JHC187>. Nevertheless, these compounds resemble the N-oxides in most of their reactions. Representative examples are deoxidative acetoxylation and chlorination. Treatment of l-hydroxy-3,5-diphenyl-2(l//)-pyr-azinone (100) with a refluxing mixture of acetic anhydride and acetic acid affords 2,6-diacetoxy-3,5-diphenylpyrazine (101), which is deacetylated with potassium hydrogen carbonate to give 2,6-dihydroxy-3,5-diphenylpyrazine (102) (or tautomer) (Scheme 23) <7UCS(C)2977>, Acetoxylation of a methyl substituent occurs exclusively and then that of the pyrazine ring is suppressed completely. 

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