2,3 -dihydropyrazine electrochemical reduction

In a series of detailed studies, Armand and coworkers have examined the electrochemical reduction of pyrazines (72CR(C)(275)279). The first step results in the formation of 1,4-dihydropyrazines (85), but the reaction is not electrochemically reproducible. The 1,4-dihydropyrazine is pH sensitive and isomerizes at a pH dependent rate to the 1,2-dihydro compound (83). The 1,2-dihydropyrazine then appears to undergo further reduction to 1,2,3,4-tetrahydropyrazine (88) which is again not electrochemically reproducible. Compound (88) then appears to undergo isomerization to another tetrahydro derivative, presumably (8, prior to complete reduction to piperazine (89). These results have been confirmed (72JA7295). 

The fusion of a benzene ring to pyrazine results in a considerable increase in the resistance to reduction and it is usually difficult to reduce quinoxalines beyond the tetrahydroquinoxa-line state (91). Two possible dihydroquinoxalines, viz. the 1,2- (92) and the 1,4- (93), are known, and 1,4-dihydroquinoxaline appears to be appreciably more stable than 1,4-dihydropyrazine (63JOC2488). Electrochemical reduction appears to follow a course anzdogous to the reduction of pyrazine, giving the 1,4-dihydro derivative which isomerizes to the 1,2- or 3,4-dihydroquinoxaline before subsequent reduction to 1,2,3,4-tetra-hydroquinoxaline (91). Quinoxaline itself is reduced directly to (91) with LiAlH4 and direct synthesis of (91) is also possible. Tetrahydroquinoxalines in which the benzenoid ring is reduced are well known but these are usually prepared from cyclohexane derivatives (Scheme 30). 

Armand and coworkers have shown that, while 1,4-dihydropyrazines are the initial products of the electrochemical reduction of pyrazines, they could not be isolated and readily isomerize in solution into 1,2- or 1,6-dihydropyrazines depending on the substitution pattern in the heterocyclic ring (74CJC3971 84MI1). The rate of the isomerization depends on the type of pyrazine as well as the pH and the nature and amount of the cosolvent. 

The electrochemical reduction of pyraz- Similar behaviors were observed for ines in an alkaline hydroorganic medium quinoxaline [246, 247] and pyridopyrazine gives the corresponding 1,4-dihydropyraz- derivatives [248, 249], ines that are easily reoxidizable. Generally, Triazines are reducible in two 2-e steps l,4-dihydropyrazinesisomerizeintol,2-or in slightly acidic media [250], The first 1,6-dihydropyrazines (Scheme 135) [245]. reduction leads to a mixture of two... 

The electrochemical reduction of 2,3-disubstituted 5,6-dihydro-pyrazines (165a) yields the 1,4,5,6-tetrahydropyrazines (166)169 the diimine-enediamine system is thus analogous to the dione-enediol system. It is of interest that the 5,6-dihydropyrazines are somewhat more easily reduced than the pyrazines. 

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). 

Electrochemical reduction of l-methyl-2-oxo-5,6-diphenyl-l, 2-dihydropyrazine has been discussed in Section 6F (1096, 1097). Direct amination of the oxo group appears to be unexplored, and little is known of the action of phosphorus halides except that a number of 1-alkyl-3,5,6-trichloro-2-oxo-l,2-dihydropyrazines has been prepared from 1,4-dialkylpiperazine-2,5-diones and phosphorus pentachloride (853) Section 9A(4)]. 

Electrochemical reductions of 2,3-dihydropyrazines have been investigated (1549, 1567) 2,3-diphenyl-5,6-dihydropyrazine was reported to give 2,3-diphenyl-... 

The electrochemical reduction of pyraz-ines in an alkaline hydroorganic medium gives the corresponding 1,4-dihydropyraz-ines that are easily reoxidizable. Generally, 1,4-dihydropyrazines isomerize into 1,2- or 1,6-dihydropyrazines (Scheme 135) [245]. 

A report of the electrochemical reduction of pyrazine to 1,4-dihydro-pyrazine, and subsequent reductive decomposition of dihydropyrazine, has appeared. ... 

Dihydropyrazines, although the initial reduction product under electrochemical conditions, appear to be unstable, as might be predicted from the fact that they contain eight... 

On the other hand, the pzlT adsorption mode does change with potential. A flat adsorbed cation is predominant at potentials more negative than -300 mV. The end-on adsorbed pziT dominates the SERS spectrum at potentials more positive than -170 mV. Electrochemical SERS is also useful for the in situ study of faradaic processes. The electroreduction of pz was observed at potentials more negative than -900 mV, and the reduction product was identifled as the 1,4-dihydropyrazine cation (DHPz ). 

---