2-Ethoxy-5- -3,6-dihydropyrazine

Diethoxy-3,6-dihydropyrazine (188) and 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine (189) gave 2-ethoxy-5,8-bis(trifluoromethyl)-3,4-dihydropyrazino[2,3-dlpyridazine (190) by loss of N2 and EtOH from an intermediate Diels-Alder adduct (CCLj, reflux, 1 h 72%).708... 

As in the research work of Vivet et al., new bicyclic sila-heterocycles were synthesized by Handmann et al. <2000ZNB133, 2000JOM19>. Compound rac-164 underwent a thermally induced cyclization reaction to give rac-7-ethoxy-2,2-dimethyl-2,3,5,7a-tetrahydro-177-3a,6,-sila-inden-4-one 9a (Equation 27). The crystal stmcture of 9a and kinetic studies of the cyclization reaction have also been reported. Starting from 3,6-ethoxy-2,5-dihydropyrazine 163, metallation with 1 molar equivalent of -butyllithium and subsequent treatment with 1 molar equivalent of the bis(chloromethyl)silane produced compound 164 in 50% yield. Pleating neat 164 at 120 °C gave the crystalline 9a in almost quantitative yield. 

Diniethylpiperazine-2,5-dione (34) on treatment with triethyloxonium fluoroborate in dichloromethane gave 5-ethoxy-l,3-dimethyl-2-oxo-l, 2,3.6-tetrahydropyrazine which was oxidized by DDQ in dry benzene to 5-ethoxy-l 3 dimethyl-2-oxo-l,2-dihydropyrazine (35) (1067). l,3,6-Trimethylpiperazine-2,5-dione similarly treated gave three products, one of which was assigned the structure 5-methoxy-l 3,6-trimethyl-2-oxo-l, 2-dihydropyrazine 3-benzyl-5-methoxy-l, 6-dimethyl-2-0X0-1,2-dihydropyrazine was also prepared similarly (1078). When 3,6-diethoxy-2,5"dimethyl-2,5-dihydropyrazine was refluxed with lead tetraacetate in dry benzene it gave a mixture of 2,5-diacetoxy-3,6-diethoxy-2,5-dimethyl-2,5-dihydropyrazine (36) (4 parts) and 2,5-diethoxy-3,6-dimethylpyrazine (1 part) (1068). 

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). 

A large number of 2-alkyl-3-methoxypyrazines has been isolated from raw vegetables (59, 60, 64, 65, 69, 80, 1099), bell peppers (60,61) and gambanum oil (49). 2-Isobutyl-3-methoxypyrazine is already finding commercial use as a flavoring material (368) and 2-ethoxy-3-methylpyrazine may be used for pineapple flavor (981). The odor characteristics (367, 368, 976, 977) and structure (977) of some alkoxy alkylpyrazines have been examined. 3-Guanidino-6-hydroxymethyl-l-methyl-2-oxo-l,2-dihydropyrazine has been isolated from seeds of Stizolobium hassjoo and on mild alkaline hydrolysis gave 3-hydroxy-6-hydroxymethyl-l -methyl-2-oxo-l, 2-dihydropyrazine (1060). 

Ethoxy-l,3-dimethyl-2-oxo-l,2-dihydropyrazine has been shown to undergo ready cycloaddition reactions even with nonactivated double bonds (1067), and also rapidly reacts with oxygen on exposure to air. 

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... 

Ethoxy-5-hydroxy-3,6-dihydropyrazine coupled with 2,3,4,6-tetra-Q-acetyl-... 

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). 

Reactions of piperazine-2,5-diones with phosphorus pentachloride and phosphorus pentabromide have been described in Sections V.ID and V.IF, respectively. Aromatic aldehydes condense with 3-methylpiperazine-2,5-dione in the presence of acetic anhydride to form mainly mono-A -acetyl derivatives of trans-3-arylidene-6-methylpiperazine-2,5-diones (e.g., 96, R = Ac) (1066). In these products the acetyl group was shown to be attached to position 1 and the 4,5-amide group was found to be sterically hindered. Photolysis formed the cis isomers. Both isomers were deacetylated with methanolic potassium hydroxide (1066). Condensation of 1,4-diacetylpiperazine-2,5-diones with aldehydes has been applied to the synthesis of unsymmetrical 3,6-diarylidenepiperazine-2,5-diones and the reaction has been extended to l,4-diacetyl-3,6-dimethylpiperazine-2,5-diones (1624). Treatment of (96, R = H) with triethyloxonium tetrafluoroborate in dichloromethane gave the monoimino ether, 5-benzylidene-6-ethoxy-3-hydroxy-2-methyl-2,5-dihydropyrazine (97) (1066). l-Methylpiperazine-2,5-dione similarly treated gave 5-ethoxy-l-methyl-2-oxo-l,2,3,6-tetrahydropyrazine (which was condensed with anthranilic acid at 150° to 2-methyl-l,2-dihydropyrazino[2,l-fi]quinazoline-3(4/0.6-dione (98) (1625), and l,4-dimethylpiperazine-2,5-dione gave 5-ethoxy-l,4-dimethyl-2-oxo-1,2,3,4-tetrahydropyrazine and 5,5-diethoxy-l,4-dimethylpiperazin-2-one (1626). 

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