Electrochemical reduction of pyrazine

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). 

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. 

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

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). 

One study that could have synthetic utility is the electrochemical reduction of thieno[2,3-6]py-razines, such as the parent molecule (68) to the corresponding tetrahydro compound (69) (Equation (23)) <91JOC4840>. Thieno[3,4- ]pyrazine, as well as the oxygen analogues of both compounds, behave similarly. 

The redox chemistry of pyrazines has long been of interest to organic chemists. The chemical and electrochemical reduction of compounds (44) and (45) are reported in a comparative study. 

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). 

The electrochemical reduction of several pyrazines has been reported (125,702, 703, 1096, 1097, 1190, 1549, 1567). Many of these reductions involve unstable... 

The electrochemical reduction of pyrido[2,3-h]pyrazines bearing methyl or phenyl substituents in the 2/3-positions has been studied in hydroorganic or aprotic media.35 The 1,4-dihydro compounds thus formed then in most cases isomerize to give the 1,2-, 3,4-, or 5,8-dihydro compounds. 

The electrochemical reduction of 2,3-diphenylpyrido[3,4-6]pyrazine yields 1,4-dihydro derivatives which isomerize to give 1,2- or 3,4-dihydro compounds. These can then be reduced at the electrode to afford the 1,2,3,4-tetrahydro derivative.35... 

The electrochemical reduction of pyrazino[2,3-(t]pyrazines has also been studied... 

Polarographic reduction of the parent gave a value for the half-wave potential (E1/2 = -0.85 v) which is intermediate between the values for quinoxaline ( 1/2 =-1.09 v) and pteridine ( 1/2 =-0.52 v). The electrochemical reduction of substituted pyrido[2,3-fc]pyrazines has been the subject of a recent study. Along with other fused pyrazine systems, the... 

Recently electrochemical reduction of pyrido[2,3-h]pyrazines has been shown to give l,2-(or possibly 3,4-)dihydro derivatives. These partially reduced compounds are isolated in good yield under controlled conditions. It is suggested that 1,4-dihydro compounds are initially formed, and these rapidly isomerize before they can be isolated. 

Electrochemical reduction of the drnuclear pyrazine [Cp IrCl(/Lt-L)ItClCp ] ions [L = bpip and bxip 785] proceeds via the paramagnetic intermediates [Cp IrCl(/it-L)IrClCp ] (L = bpip) or [Cp Ir( -L)IrClCp ] (L = bxip) and [Cp Irl(/r-L)ItCp ]. The main difference between bpip and bxip systems is the destabilization of the chloride complexes through the bxip ligand for reasons of steric interference." ... 

The biologically active relatives of folic acid and biopterin are the tetrahydro compounds with a reduced pyrazine ring. Reduction to this level occurs rapidly in vivo. The corresponding electrochemical process is well illustrated by reduction of the N-methylated analogue 28 [95], Reduction to the 5,8-dihydro stage is a reversible two-electron and two-proton process. The product rapidly tautomerises to the... 

Figure 10 shows SER spectra of pyrazine adsorbed on a silver electrode at applied potentials more negative than -900 mV vs. SCE. The pz features vanish as the potential becomes negative, and new bands due to a pz electrochemical reduction product can be observed. Figure 10 is a good example of the use of the SERS technique as a tool to monitor in situ faradaic processes. The reduction of pz is a well characterized process. 

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