2.5- Diethyl-2,5-dihydropyrazine

A mixture of 4 mmol of the alkylated 3.6-dialkoxy-2,5-dihydropyrazine 1 and 32 mL (8 mmol) of 0.25 N hydrochloric acid is stirred at r.t. until a homogeneous solution is obtained (4-30 h). It is then extracted with 1-30 mL of diethyl ether, the ether extract is discharged, and the aqueous phase is evaporated in... 

Hofmann and Schieberle509 also carried out model experiments employing synthetic 1,4-diethyl diquatemary pyrazinium ions with, for example, 2-furfurylthiol, showing that the primary products were 2-(2-furyl)methylthio-l,4-dihydropy-razine, bis[2-(2-furyl)methylthio-l,4-dihydropyrazine], and 2-(2-furyl)methyl-thiohydroxy-l,4-dihydropyrazine. This supports the interpretation of the binding of the thiols as being covalent to pyrazinium intermediates. 

Imidazolines on acid hydrolysis have been shown to give pyrazines (306). Thus 2,2-diethyl4-methylimidazoline-A with dilute hydrochloric acid at 60 gave diethyl ketone (62% of the theoretical) and 2,5-dimethylpyrazine (7%) 2,2-diethyl-4,5-dimethylimidazoline-A gave diethyl ketone (70.2%) and tetramethylpyrazine (20.4%) and 2,2,4-triethyl-5 methylimidazoline-A (41) gave diethyl ketone (84%) and 2,5-diethyl-3,6-dimethyl-3,6-dihydropyrazine (81%) (43). The pyrazines were formed presumably by self-condensation of the amino ketones (42) produced. 

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). 

Honzl (853) has described the preparation of alkyl(or aryl)-2-oxo-l, 2-dihydropyrazines by reaction of A,A -dialkyl(or aryl)piperazine-2,5-diones with phosphorus pentachloride. For example, 1,4-dicyclohexyl(or diethyl)piperazine-2,5-dione (85, R = cyclohexyl, Et) with phosphorus pentachloride in 1,2-dichloroethane gave... 

Irradiation of 2,5-bis(methoxycarbonyl)-3,6-dimethylpyrazine in diethyl ether with a 450-W high-pressure mercury lamp (330 nm) gave two significant photoproducts 2-hydroxy-5-methoxycarbonyl-3,6-dimethylpyrazine and l-(l -ethoxy-ethyl)2,5-dimethoxycarbonyl-3,6-dimethyl-l, 4-dihydropyrazine (74). Similar products were isolated when tetrahydrofuran was used as solvent. Corresponding reactions were observed with 2,5-bis(ethoxycarbonyl)-3,6-dimethylpyrazine, 2,5-diacetyl-3,6-dimethylpyrazine, and 2,5-dibenzoyl-3,6-dimethylpyrazine. The mechanism of these reactions were investigated and the initial stage was found to be... 

Diphenyl-5,6-dihydropyrazine reacts with diethyl fumarate to give diethyl 1,2-diphenyl-1,3-dihydro-3,7-diazabicyclo[2,2,2]octane-5,6-dicarboxylate (31) (1568), and a similar reaction was observed with Af-methylmaleimide (1569). 2,3-Diphenyl-... 

Ethyl 3-ethoxy-a-nitroacrylate with 1,1-diphenylhydrazine in ethanol followed by heating has been shown to give l,4-bis(diphenylamino)-2,5-diethoxycarbonyl-l,4-dihydropyrazine (1586). A small amount of 2,5-dicyano-l,4-bis(dimethylamino)-1,4-dihydropyrazine was obtained from the reaction of 2-chloro-3-(2, 2-dimethyl-hydrazino)propionitrile [(Me)2NNHCH2CH(Cl)CN] with sodium hydride (1587). Hexaalkyl-l,4-dihydropyrazines and other 1,4-dialkyl-1,4-dihydropyrazines can be obtained by thermolysis of the products of reaction of a-(alkylamino)carboxylic acid esters with alkylmagnesium bromide. Thus the reaction of ethyl a-s-butyl-aminopropionate with ethylmapesium bromide, followed by heating in vacuo to 250-300°, gave 2,5-dimethyl-3,6-diethyl-l,4-di-s-butyl-l,4-dihydropyrazine (1588). 

When a solution of diacetyl or 2,3-pentanedione in diethyl ether is slowly added to a solution of ethylene diamine in diethyl ether while maintained at 0 C under an inert gas atmosphere, an extremely exothermic reaction results in 2,3-dimethyl-5,6-dihydropyrazine or... 

A variety of methods exists for the synthesis of optically active amino acids, including asymmetric synthesis [85-93] and classic and enzymatic resolutions [94-97], However, most of these methods are not applicable to the preparation of a,a-disubstituted amino acids due to poor stereoselectivity and lower activity at the a-carbon. Attempts to resolve the racemic 2-amino-2-ethylhexanoic acid and its ester through classic resolution failed. Several approaches for the asymmetric synthesis of the amino acid were evaluated, including alkylation of 2-aminobutyric acid using a camphor-based chiral auxiliary and chiral phase-transfer catalyst. A process based on Schollkopf s asymmetric synthesis was developed (Scheme 12) [98]. Formation of piperazinone 24 through dimerization of methyl (5 )-(+)-2-aminobutyrate (25) was followed by enolization and methylation to give (35.6S)-2,5-dimethoxy-3,6-diethyl-3.6-dihydropyrazine (26) (Scheme 12). This dihydropyrazine intermediate is unstable in air and can be oxidized by oxygen to pyrazine 27, which has been isolated as a major impurity. 

---