1.4- Diacetyl-1,4-dihydropyrazine

Dihydropyrazines are readily reoxidized to pyrazines and are difficult to isolate309 reduction of 192 in aprotic medium in the presence of acetic anhydride gives l,4-diacetyl-l,4-dihydropyrazine,297,310 which is the first stable 1,4-dihydropyrazine isolated. Reductive carboxylation of 192 in DMF, followed by alkylation, is also expected to produce a stable 1,4-dihydropyrazine. 

Ethylenediamine and diacetyl gave 2,3-dimethyl-5,6-dihydropyrazine (183) (Et20, 5 — 20°C, 15 h 67%) homologues likewise.1282, cf-473 However, when KOH was included in the condensation medium, the main product was the tricyclic spiro entity (184), formed by a rational mechanism and confirmed in structure by X-ray analysis.120... 

A theoretical/NMR study of keto-enol tautomerism in 2-(2-methoxycarbony-lacetyl)pyrazine (277/278) and other similarly substituted azines has been undertaken the foregoing pyrazine exists in its enolic form (278) to the extent of 35% in deuterochloroform.411 l,4-Diacetyl-l,4-dihydropyrazine (279) gave the persistent radical cation (279) + on one-electron oxidation (cyclic voltammetry in MeCN— Bu4NC104).167... 

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... 

It has been claimed (25) that 2,3-diphenyl-5,6-dihydropyrazine when heated with acetic or benzoic anhydride gives a derivative of the 1,4-dihydropyrazine ring system, but this has been shown by Chen and Fowler (1562) to be in error [the products have been shown to be 1,4-diacetyl(or dibenzoyl)-5,6-diphenyl-l,2,3,4-tetrahydropyrazine (26, R = Me or Ph), respectively, together with 23-diphenyl-pyrazine]. Hexamethyl-2,3-dihydropyrazine cannot undergo oxidation to a pyrazine, but it rapidly dimerized in air in the presence of hydrochloric acid to give compound (27, X = Cl) (also prepared as the iodide with iodine in ether) (1550). 

The 1,4-dihydropyrazine ring system was first characterized by Chen and Fowler using n.m.r. (1562). Slow addition of acetyl chloride to 2,3-diphenyl-5,6-dihydro-pyrazine in benzene containing two equivalents of pyridine gave l,4-diacetyl-2,3-diphenyl-1,4(dihydropyrazine (46) (30%) together with l,4-diacetyl-5,6-diphenyl-1,2,3,4-tetrahydropyrazine and 2,3-diphenylpyrazine (1562, cf. 25). 

Catalytic hydrogenation of 1,4-diacetyl-2,3-diphenyl-1,4-dihydropyrazine (46) over palladium-charcoal resulted in the rapid uptake of 1 mol of hydrogen with formation of 1,4-diacetyl-5,6-diphenyl-l, 2,3,4-tetrahydropyrazine (55) this addition of only one equivalent of hydrogen under these conditions is characteristic of a... 

Hydrolysis of l,4-diacetyl-2,3-diphenyl-l,4-dihydropyrazine with potassium hydroxide in ethylene glycol produced 2,3-diphenylpyrazine (probably formed by air oxidation of the dihydropyrazine) (1562). l,4-Dimethyl-2,6-diphenyl-l,4-dihydropyrazine reacts with methanol to give 2-methoxy-1,4-dimethyl-3,5-diphenyl-1,2,3,4-tetrahydropyrazine (57) (1536). 

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). 

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... 

Ethyienediamine and diacetyl gave 2,3-dimethyl-5,6-dihydropyrazine (183) (Et2O, 5 20°C, 15 h 61%), homologues likewise.However, when... 

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