. Can. J. Chem. 52,3971 (1974). The electrochemical reduction of several pyrazines in an alkaline hydroorganic medium leads t o 1,4-dihydropyrazines too easily oxidizable to be isolated. These derivatives isomerize into 1,2-or 1,6-dihydropyrazines, the rate of this reaction depending among other things on the p H and on the cosolvent. The different chemical and electrochemical preparations of dihydropyrazines are discussed. It is shown that 3,6-dihydro-2,5-diphenylpyrazine and 1,6-dihydro-2,5-diphenylpyrazine are in thermodynamic equilibrium.JOSEPH ARMAND, KHALED CHEKIR et JEAN PINSON. Can. J. Chem. 52,3971 (1974). La rkduction electrochimique de diverses pyrazines en milieu hydroorganique alcalin fournit des dihydro-1,4 pyrazines, trop oxydables pour pouvoir @tre isolCes. Ces dCrives s'isomkrisent en dihydro-l,2 ou dihydro-1,6 pyrazines avec une vitesse dependant en particulier du p H et de la nature du cosolvant Les differents modes d'obtention, chimiques et electrochimiques des dihydropyrazines sont discutes. I1 est montre que la dihydro-3,6 diphenyl-2,5 pyrazine forme un Cquilibre thermodynamique avec la dihydro-1,6 diphenyl-2,5 pyrazine.The reduction of pyrazines, by the usual chemical reagents, generally leads to hexahydro derivatives, i.e. to piperazines. Few semihydrogenated derivatives, dihydro-and tetrahydropyrazines, are known.The electrochemical reduction of pyrazines in an alkaline hydroorganic medium was investigated to determine the intermediates involved in the reduction of pyrazine5 into piperazines and to find out whether the electrochemical reduction could be of interest for the preparation of dihydro-and tetrahydropyrazines.Besides, a large number of organic compounds of biological or pharmaceutical interest possess the pyrazine ring. Oxido reduction reactions seemingly involving the pyrazine ring often take place in these compounds (1). Therefore there is an additional interest of a detailed knowledge of the electrochemical behavior of pyrazines.This investigation is divided into two parts. This first paper deals with the reduction of pyrazines into dihydropyrazines and with the preparation of dihydropyrazines.As the dihydropyrazines are unstable in acidic medium, this investigation was carried out in alkaline medium. The following pyrazines were investigated: 2,5-diphenylpyrazine (1); 2,3-diphenylpyrazine (2); tetramethylpyrazine (3); 2,5-di-2'-pyridylpyrazine (4); 2,3-di-2'-pyridylpyrazine (5); tetra-2'-pyridylpyrazine (6). I . 2,5-Diphenylpyrazine ( I )Between p H 1 and 13, 1 exhibits a single 2e cathodic wave, its E l l , depends on the pH: Ell, = -0.38 -0.079pH (50% DMF).During the electrolysis of a dilute solution of 1 in a water-DMF medium (0.5 N NaOH; c = 2 x M; E = -1.45 V) an anodic wave appears with an E l i , very close to that of the cathodic wave of 1 (Fig. 1). Then this anodic wave decreases at the expense of another anodic wave, at a less negative potential, and of a cathodic wave, at a potential slightly more negative than that of 1.In a water-methanol medium (80% CH,OH; 0.2...

JOSEPH ARMAND, LINE BOULARES, KHALED CHEKIR, and CHRISTIAN BELLEC. Can. J . Chem. 59, 3237 (1981). The hydrogenation of 2,3-dimethylpyrazino[2,3-blquinoxaline 1 and 2-phenylpyrazino[2,3-b]quinoxaline 2 leads to the corresponding 5,lO-dihydroderivatives 3b and 4b. LiAlH, reduction of 2, of 2.3-dimethyl-6,7-diphenylpyrazino[2,3-b]pyrazne 8 and 2,6,7-triphenylpyrazino[2,3-blpyrazine 9 furnishes the corresponding 1,2,3,4-tetrahydroderivatives 7,10, and 11. NaBH, reduction of 2 leads to a mixture of 4b and 7. In hydroorganic medium 1 and 2 are electrochemically reduced to 36 and 46 with which they form a redox system. Although the synthesis of pyrazino[2,3-blquin-1). The reduction products of 1 and 2 have two oxalines has been investigated (1) neither their amino protons which are readily exchanged by chemical nor their electrochemical reduction has addition of D,O so that the isomeric structures been studied.shown below have to be considered:We report the hydrogenation, the reduction with LiAlH, and NaBH,, and the electrochemical reduction of compounds 1 and 2. Concerning the electrochemical reduction, the presence of two condensed pyrazine rings made possible two reaction paths, either a reduction into a 1,4-(or 5.10-) dihydro derivative as in the case of pyrazines, or a behaviour similar to that of flavines leading to a 1 3 -(or 4, lo-) dihydro compound. HydrogenationIn the presence of Pd/C, hydrogenation of 1 and 2 leads to the dihydro derivatives 3b and 4b, the structures of which were determined by nmr (Table k I A rapid equilibrium on the nmr time scale of the two tautomers 3c and 3c' cannot be excluded on the grounds of the nmr spectrum. However, acetylation gives a diacetylated compound to which the nmr spectrum permits assigning the 1 ,Cdiacetyl-1 ,4-dihydro structure or the 5,lO-diacetyl-5,lOdihydro structure (see Experimental). Thus, the reduction product of 1 must have a plane of symmetry, which rules out structure 3c. Structures 3a and 3b can be discriminated by examination of the chemical shifts. The aromatic protons of 1,2,3,4-tetrahydrophenazine 5 give evidence of a multiplet

The electrochemical reduction of several pyrido[2,3-b]pyrazines in hydroorganic or aprotic media leads to 1,4-dihydro derivatives which can be isolated in some cases. Most of these derivatives isomerize into 1,2-, 3,4-, or 5,8-dihydro compounds. A molecule of alcohol is added to these last compounds in alkaline medium. The electrochemical reduction of 1,2- or 3,4-dihydro derivatives gives 1,2,3,4-tetrahydropyridopyrazines. In hydroorganic media, the 7-bromopyrido [2,3-b]pyrazines give a 1,4-dihydro compound which can either isomerize or debromhydrate. In an aprotic medium, the parent heterocycle is obtained. By electrochemical reduction of pyrido[3,4-b]pyrazines, 1,4-dihydro derivatives can be formed which isomerize. The 1,2- or 3,4-dihydro compounds thus obtained can be reduced at the electrode into 1,2,3,4-tetrahydro derivatives.

Die Elektroreduktion der Pyrazine (I) zu den Piperazinen (VI) wird polarographisch untersucht.

The reduction of pyrazine, quinoxaline and triazine derivatives by titanium(III) chloride leads to di‐ or tetrahydrogenated compounds. High yields of tetrahydro compounds are also obtained through the reduction of quinoxalinium salts. These results are compared with those obtained by electrochemical reduction.