2.5- Diphenylpyrazine reduction

Reductive debenzylation. 2-Benzyloxy-3,6-diisobutyl-5-methoxypyrazine 4-oxide (21) gave 3,6-diisobutyl-5-methoxy-2(l//)-pyrazinone 4-oxide (22) (H2, Pd/C, EtOH, h 90% structure confirmed by X-ray analysis) 310 2,5-dibenzy-loxy-3,6-diphenylpyrazine likewise gave 5-hydroxy-3,6-diphenyl-2(l//)-pyrazinone (23) (43%).82... 

Diphenylpyrazine gave dimethyl 2,3-diphenyl-l,4-dihydro-l,4-pyrazinedicar-boxylate (68) (Me02CCl, electrolytic reduction 15% for details see original).785... 

Having obtained and described a suitable sample, the next stage is to analyse the material for the presence of cathinone and cathine. In addition to these drugs, other structurally similar compounds found in the C. edulis plant include norephedrine (3). It is well accepted that cathinone is converted into this compound by the process of enzymatic reduction. Furthermore, the oxidation product, 1-phenyl-1,2-propanedione (4), and the cathinone dimer, 3,6-dimethyl-2,5-diphenylpyrazine (5), may also be identified. These, however, are reported to form as artefacts of the isolation and analytical processes [6]. 

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). 

Dihydroxy-5,6-diphenylpyrazine refluxed with aqueous hydrazine hydrate gave 2-hydrazino-3-hydroxy-5,6-diphenylpyrazine, which was also obtained by heating 2-hydroxy-3-nitro-5,6-diphenylpyrazine with aqueous hydrazine (1124). Distillation of the compound claimed by Japp and Knox (317) to be 3-hydroxy-2,5-diphenylpyrazine (317, cf. 282) with zinc dust produced 2,5-diphenylpyrazine (317) reduction of the former with hydriodic acid and red phosphorus at 200 for 6 hours gave what was regarded as 2,5-diphenyl-3,4-dihydropyrazine (317). 

Electrochemical reduction of 5-methoxy-2 -diphenylpyrazine produced a 1,6-dihydro derivative which isomerized to the electrochemically reducible 3,6-dihydro derivative (1097). 

These effects are produced mostly by phenylpropanolamines present in the leaves. These include cathinone [4] (5 -a-aminopropiophenone), cathine [5] [(-)-IS, 2S-norpseudoephedrine] and (-) -IR, 2S-norephedrine (8). These substances have pharmacological properties similar to those of amphetamine [6] (81), as they induce the release and inhibit the uptake of dopamine and norepinephrine in CNS (82). In addition to the known phenylpropylamines, the presence of other amines such as meracathine, pseudomeracathine and meracathinone have been identified (83, 84). Cathinone, being a ketoamine base, is extremely unstable and, in particular, it can be transformed into (+)-norpseudoephedrine and (-)-norephedrine by an enzymatic reduction. It can also be oxidized to give 1-phenyl-l,2-propandione, while the cathinone dimers, such as 3,6-dimethyl-2,5-diphenylpyrazine are purely artifacts of the isolation (85). 

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