5-Methyl-2,3-diphenylpyrazine

Kaftory M, Shteiman V, Lavy T, Scheffer JR, Yang J, Enkelmann V (2005) Discrintination in the solid state photodimerization of l-methyl-5,6-diphenylpyrazin-2-one. Eur J Org Chem 847-853... 

Thermodynamically stable aromatic selenaheterocycles such as selenophene (1), 1,3-selenazole (3), 1,2,5-selenadiazole (5), and 1,2,4-selenadiazole undergo [l,4]cycloaddition followed by spontaneous deselenation, which is a convenient way for construction of nonselenium azaaromatic rings [3, 6, 42], 3,4-Diphenyl-1,2,5-selenadiazole reacted with DMAD to give methyl 2,3-diphenylpyrazine-5,6-dicarboxylate. The similar reaction of 1,2,4-selenadiazoles resulted in pyrimidine -5,6-dicarboxylate, while 2,1,3-benzoselenadiazoles reacted with DMAD to give the quinoxalines [6, 110]. (For deselenation see also Sect. 5.1). 

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... 

Ethylthio-2-pyrazinecarbonitrile 6-Ethylthio-2-pyrazinecarbonitrile 6-Ethylthio-2-pyrazinecarbothioamide 3-Ethylthio-2-pyrazinecarboxamide 6-Ethylthio-2-pyrazinecarboxamide 3-Ethylthio-2-pyrazinecarboxylic acid 6-Ethylthio-2-pyrazinecarboxylic acid 3-Ethylthio-2,5-pyrazinedicarboxamide 2-Ethylthiopyrazine 1-oxide 2-Ethyl-3,5,6-trimethylpyrazine 2-Ethyl-3,5,6-triphenylpyrazine 2-Ethyl-3-vinylpyrazine 2-Ethynyl-3,6-dimethylpyrazine 2-Ethynyl-3-methylpyrazine 2-Fluoro-5,6-dimethoxy-3-methylpyrazine 2- Fluoro- 5,6-dimethoxypyrazine 2-Fluoro-3,6-dimethylpyrazine 2-Fluoro-3-(l-hydroxyethyl)pyrazine 2-Fluoro-3-iodopyrazine 2-Fluoromethyl-5-methyl-3,6-diphenylpyrazine 2- Fluoro- 5-phenylpyrazine 2-Fluoro-3-phenylthiopyrazine... 

Methyl 6-amino-5-cyano-3-methyl-2-pyrazinecarboxylate 1-oxide Methyl 3-amino-5-cyclohexyl-2-pyrazinecarboxylate Methyl 3-amino-6-cyclohexyl-2-pyrazinecarboxylate Methyl 3-amino-6-cyclopropyl-2-pyrazinecarboxylate Methyl 3-amino-5,6-dichloro-2-pyrazinecarboxylate Methyl 3-amino-5-dimethylamino-6-methyl-2-pyrazinecarboxylate Methyl 3-amino-5-dimethylamino-6-phenyl-2-pyrazinecarboxylate Methyl 3-amino-5-dimethylamino-2-pyrazinecarboxylate Methyl 3-amino-5,6-dimethyl-2-pyrazinecarboxylate 2-Methylamino-3,5-diphenylpyrazine 2-Methylamino-3,6-diphenylpyrazine... 

Methyl-5,6-diphenyl-2-pyrazinecarbonitrile Methyl 5,6-diphenyl-2-pyrazinecarboxylate 2-Methyl-5,6-diphenylpyrazine 1-oxide... 

Methyl-5,6-diphenylpyrazine 4-oxide l-Methyl-5,6-diphenyl-2(l//)-pyrazinethione... 

Acetyl-2-carbamoyl-3-methyl-6-phenyl-2,5-dihydropyridazine (115) when heated with potassium hydroxide has been shown to give 2,5-diphenylpyrazine (497), and 2,6-dihydroxymorpholine (116) has been converted smoothly by hydrazine or hydroxylamine in aqueous hydrochloric acid to pyrazine in good yield (28). 

Quaternization of the four dimethylpyrazine A(-oxides and 2,3-diphenylpyrazine 1-oxide with methyl iodide in a sealed tube at 80 gave the 4-methylpyrazinium 1-oxide iodides, but 3-phenyl-, 2,5-diphenyl- and 3,5-diphenylpyrazine 1 -oxides and dimethylpyrazine 1,4-dioxides could not be quaternized. The quaternary salts were reduced by sodium borohydride to A -hydroxypiperazines (766). 

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]

Normal nucleophilic substitution reactions of alkyl and aryl chloropyrazines have been examined as follows 2-chloro-3-methyl- and 3-chloro-2,5-dimethyl(and diethyl)pyrazine with ammonia and various amines (535, 679, 680) 2-chloro-3(and 6)-methylpyrazine with methylamine and dimethylamine (681, 844), piperidine and other amines (681, 921) 2-chloro-5(and 6)-methylpyrazine with aqueous ammonia (362) alkyl (and phenyl) chloropyrazines with ammonium hydroxide at 200° (887) 2-chloro-3-methylpyrazine with aniline and substituted anilines (929), and piperazine at 140° (759) 2-chloro-3-methyl(and ethyl)pyrazine with piperidine (aqueous potassium hydroxide at reflux) (930,931) [cf. the formation of the 2,6-isomer( ) (932)] 2-chloro-3,6-dimethylpyrazine with benzylamine at 184-250° (benzaldehyde and 2-amino-3,6-dimethylpyrazine were also produced) (921) 2-chloro-3,5,6-trimethylpyrazine with aqueous ammonia and copper powder at 140-150° (933) and with dimethylamine at 180° for 3 days (934,935) 2-chloro-6-trifluoromethylpyrazine with piperazine in acetonitrile at reflux (759) 2-chloro-3-phenylpyrazine with aqueous ammonia at 200° (535) 2-chloro-5-phenylpyrazine with liquid ammonia in an autoclave at 170° (377) 2-chloro-5-phenylpyrazine with piperazine in refluxing butanol (759) but the 6-isomer in acetonitrile (759) 5-chloro-2,3-diphenylpyrazine and piperidine at reflux (741) and 5-chloro-23-diphenylpyrazine with 2-hydroxyethylamine in a sealed tube at 125° for 40 hours (834). 

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. 

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). 

Hydroxypyrazine with phosphorus pentasulfide in refluxing pyridine for 45 minutes was readily converted to 2-mercaptopyrazine (46%) (55) (its 1-methyl analogue was prepared similarly) (821,1100) and 5-mercapto-2,3-diphenylpyrazine was prepared likewise (834, 1008). 2-Amino-3-mercaptopyrazine was prepared from 2-amino-3-hydroxypyrazine and phosphorus pentasulflde in refluxing 0-picoline(llOl). 

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)]. 

Other methylations with diazomethane are as follows 2,6-dihydroxy-3,5-diphenylpyrazine formed a mixture of products from which only 2,6-dimethoxy-... 

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-... 

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-... 

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). 

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... 

Carboxy-3-(o-carboxyphenyI)-5,6-diphenylpyrazine A -oxide was deoxygenated by stannous chloride (399) and 2-carboxy-3,5-bis(methylamino)-6-A -methyl-carbamoylpyrazine 1-oxide with sodium dithionite in aqueous ethanol at 90° for 3 hours (462). 

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