3.5- Dimethoxy-2-methylpyrazine

Formylaminopyrazines have been prepared as follows. 2-Amino-3-dimethoxy-methylpyrazine stirred at 0 with acetic formic anhydride gave 2-dimethoxymethyl-3-formamidopyrazine (27) (1075), and 2-amino-3-methylpyrazine similarly treated gave 2-formamido-3-methylpyrazine (1200). 

Optically pure or almost pure a-methyl a-amino acids (alanine derivatives) can be prepared by reacting 5-substituted 2,5-dihydro-3,6-dimethoxy-2-methylpyrazines 1, which are derived from alanine and various amino acids as the chiral auxiliary, with alkylating agents, followed by hydrolysis (see Table 2). 

The composition of the products from the alkylation of lithiated 3,6-dialkoxy-2,5-dihydropy-razines with bis-alkylating reagents depends on the equivalents of electrophile employed. For example, with three equivalents of bis-alkylating electrophiles, (25)-2,5-dihydro-2-isopropyi-3,6-dimethoxy-5-methylpyrazine (I) gives high yields of the 1 1 adducts 2 or 5 with > 97% de2. These products can be further converted to the bicyclic systems (3 and 6. respectively) which, upon hydrolysis, give optically pure cyclic amino acids (4 and 7). Methyloxirane is used as an acid scavenger in order to release the free amino acid zwitterion. 

With chiral racemic oxiranes one enantiomer reacts faster than the other the degree of kinetic resolution is very high for L-valine/alanine-based dialkoxydihydropyrazines. For example, in the reaction of one equivalent of (2.S )-2,5-dihydro-2-isopropyl-3,6-dimethoxy-5-methyl-pyrazine (1, R1 = CH3) with two equivalents of fW-(//,/ )-2,3-dimethyloxirane (R2,R4 = CH3 R = H) virtually only the (2//,3/ )-oxirane enantiomer reacts with the lithiated dihydropyrazine to give exclusively the (l /, 2/, 2 / )-configuratcd adduct i.e., (2/ ,5S)-2,5-dihydro-5-isopropyl-3,6-dimethoxy-2-[(l/ ,2/ )-2-(2-methoxyethoxymethoxy)-l-methylpropyl]-2-methylpyrazine, entry 7. Likewise, kinetic resolution (intramolecular) occurs upon reaction with rac-7-oxabicy-clo[4.1.0]heptane (entry 8). 

Dimethoxy-3-isopropyl- -6-methylpyrazine OCH3 i-C3H7 och3 X u... 

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... 

Isopropylamino-2-pyrazinecarboiiitrile 2-Isopropyl- 3,5-dimethoxy-6-methylpyrazine 2-Isopropyl-3,6-diniethoxy-5-methylpyrazine 2-Isopropyl-3,6-dimethoxy-5-propionylpyrazine 2-Isopropyl-3,6-dimethoxypyrazine... 

Trichloromethyl)pyrazine (80) with three equivalents of methoxide ion in refluxing methanol also underwent an abnormal reaction and gave a quantitative yield of the three isomeric pyrazines 2-dimethoxymethyl-5-methoxypyrazine (75%) (82), 2,3,5-trimethoxy-6-methylpyrazine (15%) (83), and 2,3-dimethoxy-5-methoxymethylpyrazine (10%) (84) (685). Subsequent treatment of (80) with one equivalent of methoxide ion in methanol at 5° gave 2-dichloromethyl-5-methoxypyrazine (81). 

Dimethoxy-2-methoxycarbonylpyrazine boiled with phosphoryl chloride and phosphorus pentachloride gave the acid chloride, which, treated with aqueous hydrazine, gave 2-hydrazinocarbonyl-3,5-dimethoxypyrazine (881). 2-Methoxy-3-methoxycarbonyl-5-methylpyrazine with methylmagnesium iodide in ether gave 3-(l -hydroxy-r-methylethyl)-2-methoxy-5-methylpyrazine (39) (844). Thebromi-nation of 2-amino-5-bromo-3-methoxycarbonylpyrazine in 30% hydrobromic acid to 2-amino-3,5-dibromopyrazine has been described in Section V.IB (2) (807). 

Chlorocarbonyl-2-methoxy-5-methylpyrazine with lithium dimethyl copper reagent in ether gave 3-acetyl-2-methoxy-5-methylpyrazine 2-acetyl-3-methoxy-pyrazine and 2-acetyl-3,6-dimethoxy-5-methylpyrazine were prepared similarly (844), but 2-chlorocarbonyl-3-methoxy-5-methylpyrazine with lithium dimethyl copper in ether gave a mixture of 2-acetyl-3-methoxy-5-methylpyrazine and 2-(l-hydroxy-1-methylethyl)-3-methoxy-5-methylpyrazine (844). 

Acid extraction yielded the following pyrazine derivatives tetramethylpyra-zine, 2,6-diethyl-3-methylpyrazine (47), 2,3-dimethyl-5-ethylpyrazine, 2-methoxy-3-isopropoxy-5-methylpyrazine, and 2,6-dimethoxy-3-isopropoxy-5-methylpyra-zine.38 All structures were confirmed by synthesis. Pyrazine derivatives had previously been isolated from green peas (Pisum sativum).39... 

Boiled chestnut (only) n-Heptane Hexanal 2-Decenal 2-Undecenal n-Tridecane Eicosene 2,5-Dihydro-3-methylfurandione 2-Methoxy-6-methylpyrazine 6,7-Dimethoxy-2H-1 -benzopyran-2-one Mono(2-ethylhexyl) hexanedioate Eicosanoic acid Docos oic acid Heptacosane Cyclotetracosane 1-Docosanol Hexyl acetate 2,3-Dimethylpyrazine 2-Acetylthiazoline ... 

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