2,5- Dimethyl-3- -pyrazines

A comparison of ortho vs. para direct deactivation by a methoxy group has been made by Karmas and Spoerri in 2,3-dibromo-5,6-dimethyl- and 2,5-dibromo-3,6-dimethyl-pyrazine. The former gives monomethoxy-debromination with one equivalent of methanolic methoxide (65°, 6 hr) and disubstitution via 198 with excess reagent for a longer time (10 hr). In contrast, the isomeric 2,5-dibromo compound gave only monosubstitution, forming 199, under the latter conditions. 

Fluorobenzene to fluorodihydrocatechol and fluorocatechol Conversion of 2,5-dimethyl pyrazine to 5-metyl pyrazine-2-carboxylic acid, conversion of 5-ethyl-2-methyl pyridine to... 

Pyrazino[2,3-d]pyridazine-5,8-dione (104) can be prepared from either pyrazine-2,3-dicarboxylic acid anhydride (212) or dimethyl pyrazine-2,3-dicarboxylate (213) by reaction with hydrazine hydrochloride or hydrazine hydrate, respectively. The preparation based... 

Methyl- and 2,6-dimethylpyrazines with DMAD in acetonitrile yield the corresponding azaindolizines (249),351 whereas 2,5-dimethyl-pyrazine gives a 1 3-molar adduct less the elements of acetonitrile. This adduct, originally described as an azepine,336 is probably the cyclo-butaindolizine 251,337 and could be formed via 250 by cycloaddition of DMAD across the dihydropyrazine ring and elimination of acetonitrile. 

IsobutyI-3-methoxy-5,6-dimethyl- pyrazine C4H9 OCH3 CH3 CHj... 

Trimethyl pyrazine 3-ethyl 2,5-dimethyl pyrazine FIG. 8 Flavor compounds in roasted flaxseed observed by Meyers et al. (2004). 

To sum up, the flavor constituents of plain and roasted cashew nuts are reported here for the first time. The mild flavor of cashew nuts can be attributed to the carbonyls, esters and lactones, especially to 5-heptene-2-one and 1,3-propanediol diacetate. Upon roasting, 2,6-dimethyl pyrazine, 2,6-diethyl pyrazine and the furanone are formed in larger amounts and from flavor profile also these compounds are likely to play a significant role in the characteristic aroma of roasted cashew nuts. 

A Diels-Alder approach to varenicline was recently published by Dr. Reddy s Laboratories. Entry to a key bicyclic intermediate is achieved by an iodide-catalyzed Diels-Alder reaction of tetrabromo dimethyl pyrazine (47) with excess norbomadiene. Dihydroxylation of 48, oxidative cleavage, and reductive amination prepares N-p-methoxybenzyl varenicline (50), which is deprotected under transfer hydrogenation conditions to give varenicline (1) in 10% yield for the sequence.47 This approach continues the theme of building the piperidine of 1 through olefin oxidative cleavage and reductive amination, but by doing so late in the sequence however, the approach... 

Polarographic studies on pyrazine and methylpyrazines indicate that 1 4-dihydropyrazines are the products of reduction. The reduction of pyrazine itself at the dropping mercury electrode proceeds reversibly. The substitution of methyl groups makes the reduction more difficult with an increased number of methyl groups an increased tendency toward irreversible reduction is noted.102-104 The half-wave reduction potentials for pyrazine, methylpyrazine, 2,6-dimethyl-pyrazine, and tetramethylpyrazine are 2.17, 2.23, 2.28, and 2.50 eV, respectively. Pyrazine is thus more easily reduced than pyridine which has a half-wave potential of 2.76 eV, and less easily reduced than quinoxaline which has a half-wave potential of 1.80 eV.105... 

Pyrazine 1-oxide, 2-methylpyrazine 4-oxide, and 2,6-dimethyl-pyrazine 4-oxide are unreactive toward acetic anhydride, but 2,5-dimethylpyrazine 1-oxide, 2,6-dimethylpyrazine 1-oxide, and 2,3,5,6-tetramethylpyrazine 1-oxide react to give 2-acetoxymethyl derivatives. The following mechanism (Scheme 44) is consistent with the observation that an acetoxymethyl derivative is only formed when a methyl group is adjacent to the AT-oxide function.407 However, in... 

The marked activation of the iV-oxide function on the chlorine atom of 2-chloropyrazine 4-oxide and 2-ehloro-3,6-dimethylpyrazine 4-oxide is also demonstrated by the milder conditions under which these compounds react with ammonia and amines compared with chloro-pyrazine and 2-chloro-3,6-dimethyl pyrazine, respectively. Although 2-chloropyrazine 4-oxide undergoes the expected displacement reaction with ammonia on heating at 115°-120° for 2.5 hours, reaction at 140° for 16 hours gives 2,3-diaminopyrazine, possibly as a result of an addition-elimination reaction on the initially formed 2-amino-pyrazine 4-oxide (Scheme 47).417... 

Alkaline hydrolysis of the di-A-oxide of 2,5-dichloro-3,6-dimethyl-pyrazine (215) readily yields the monohydroxamic acid (216), but the second chlorine atom is inert. Both chlorine atoms in compound 215 may be displaced by ethoxide or benzyloxide ion. Acid treatment of the dibenzyloxy-1,4-dioxide (217) yields compound 218 which with... 

The important aroma compounds of roasted cumin are the pyrazines, their various alkyl derivatives - particularly, 2,5- and 2,6-dimethyl pyrazine - and also substituted pyrazines 2-alkoxy-3-alkylpyrazines ... 

Chloro-3,6-diethylpyrazine (119, R = H) gave 2,5-diethyl-3-methylpyrazine (118) [Me3Al, Pd(PPh3)4, dioxane—C6H14, A, reflux, 2 h 88%] 280 2,5-dichloro-3,6-diethylpyrazine (119, R = Cl) gave 2,5-diethyl-3,6-dimethyl-pyrazine (120) (likewise but reflux, 4 h 93%) 280 and many homologues and their TV-oxides were made similarly.280,282... 

Dimethyl-3-(pent-l-enyl)pyrazine gave 2-(l,2-epoxypentyl)-3,6-dimethyl-pyrazine (ClC6H4C03H-m, CH2C12, 45°C, 4 h 81%).868... 

Dimethylpyrazine 1-oxide (280) gave 2-acetoxymethyl-3-methylpyrazine (281) (neat Ac20, reflux, 30 min 77%) 1272 the isomeric 2,6-dimethyl-pyrazine 1-oxide gave a separable mixture of 2-acetoxymethyl-6-methylpyrazine (282, R = Ac) and 2-hydroxymethyl-6-methylpyrazine (282, R = H), the latter arising presumably by hydrolysis during the work up (neat Ac20, reflux, 1 h 40 and 12%, respectively).1307... 

Key to Figures 16 and 17 1, Pyrazine 2, 2-Methylpyrazine 3, 2,6-Dimethyl-pyrazine 4, Quinoxaline 5, 2-Methylquinoxaline 6,, 4-Diazabicyclo, 2,2 -octane 7, Pyridine 8, Dioxan 9, Tetramethylammonium bromide 10, Tetror ethylammonium bromide 11, Tetrcq>ropylaminonium bromide 12, Tetrabutyl-ammonium bromide 13, n-propanol. 

Gastaldi (286) first described this synthesis, in which an a-hydroxyimino ketone was treated with aqueous sodium bisulfite saturated with sulfur dioxide, and the bisulfite compound treated with potassium cyanide followed by hydrolysis with hydrochloric acid. By this procedure, Gastaldi prepared 2,5-dicyano-3,6-dimethyl-pyrazine from hydroxyiminoacetone, and 2,5-dicyano-3,6-diphenylpyrazine and some 3-cyano-2,5-diphenylpyrazine from hydroxyiminoacetophenone. He proposed a reaction mechanism involving the intermediate compounds (21) and (22). Sharp and Spring (287) used the same procedure to prepare 2,5-dicyano-3,6-diethyl-pyrazine from ethyl hydroxyiminomethyl ketone. 

Sucrose and aqueous /3-aminopropionitiile 2 ethyl- and 2,5-dimethyl pyrazine and other pyrazines 508... 

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