Pyrazines nitration

Allen, F. H., Kennard, 0., and Taylor, R., Systematic analysis of structural data as a research technique in organic chemistry, Acc. Chem. Res., 16, 146-153 (1983). Vranka, R. G., and Amma, E. L., Metal ion-aromatic complexes. II. The crystal structure of the 1 1 silver nitrate-pyrazine complex, Inorg. Chem., 5, 1020-1025 (1966). Kubel, F, and Strahle, J., Crystal structure of polymeric bis(dismethyl-glyoximato)pyrazine iron (II), Z Naturforsch. B, 38, 258-259 (1983). 

Classic A/-heterocychc ligands, eg, bipyridyl (bipy), terpyridyl, imidazole, pyrazine, phenanthroline, piperazine (including alkyl- and aryl-substituted derivatives), and polypyrazol-l-yl-borates (bis, tris, and tetra), have all been found to coordinate Th(IV) chlorides, perchlorates, and nitrates. The tripodal hydrotris(pyrazolyl)borates, HBPz, have been used to stabilize organometaHic complexes (31). Bis-porphyrin Th(IV) "sandwich" complexes have been... 

Electrophilic substitution reactions of unsubstituted quinoxaline or phenazine are unusual however, in view of the increased resonance possibilities in the transition states leading to the products one would predict that electrophilic substitution should be more facile than with pyrazine itself (c/. the relationship between pyridine and quinoline). In the case of quinoxaline, electron localization calculations (57JCS2521) indicate the highest electron density at positions 5 and 8 and substitution would be expected to occur at these positions. Nitration is only effected under forcing conditions, e.g. with concentrated nitric acid and oleum at 90 °C for 24 hours a 1.5% yield of 5-nitroquinoxaline (19) is obtained. The major product is 5,6-dinitroquinoxaline (20), formed in 24% yield. 

Conflicting reports on the nitration of phenazine have appeared, but the situation was clarified by Albert and Duewell (47MI21400). The early work suggested that 1,3-dinitroph-enazine could be prepared in 66% yield under standard nitration conditions however, this proved to be a mixture of 1-nitrophenazine and 1,9-dinitrophenazine (24). As with pyrazines and quinoxalines, activating substituents in the benzenoid rings confer reactivity which is in accord with valence bond predictions thus, nitration of 2-methoxy- or 2-hydroxy-phenazine results in substitution at the 1-position. 

Cerium(IV) ammonium nitrate in methanol has been used to oxidize phenazine to the mono-N-oxide (41) in good yield (75JCS(P1)1398), but no other reports on the application of this reagent to the pyrazine or quinoxaline series have appeared. 

Imidazolidine, 4,5-dichloro-l,3-diacetyl-imidazo[4,5-6]pyrazine synthesis from, 5, 646 Imidazolidine, 1,3-dimethyl-conformation, 5, 355 Imidazolidine, diphenyl-dehydrogenation, 5, 427 Imidazolidine, 2-imino-1-substituted nitration, 5, 427... 

The adverse properties of red beet preparations are without doubt, their high nitrate content, their unpleasant smell due to pyrazine derivatives and geosmin with a low odor threshold, and finally the risk of carry-over of earth-bound germs. - " Since nitrate has been associated with nitrite and nitrosamine formation, the latter exhibiting cancer-inducing properties, procedures have been developed to reduce the nitrate content of red beet preparations. This has been achieved by microbial denitrification. - ... 

Pyrazine and pyrimidine heterocycles, like pyridine, are electron deficient and need the presence of an activating/electron-releasing group to allow efficient electrophilic nitration to occur. An example of this strategy is seen during the synthesis of 2,6-diamino-3,5-dinitropyrazine (ANPz) (183) where one of the chloro groups of 2,6-dichloropyrazine (180) is substituted for a... 

It is to be expected that furo[2,3-ft]pyrazines would show an appreciably lower reactivity in electrophilic substitution than benzo[fe]furans. Bromination of 2-phenylfuro[2,3-6]pyrazine requires high temperatures and long reaction times the substitution takes place in position 3. By contrast, nitration occurs mainly in the phenyl group. Reaction with peracids easily provides the N-7 monoxide. This is to be expected since quantum mechanical calculations (HMO, PPP, CNDO) all predict a higher charge density at N-7 compared with N-5. 

It has been observed that when an aqueous solution of pyrazine was added to an excess of silver nitrate solution, a precipitate of shiny white platelets formed immediately. If the order was reversed, however, and silver nitrate was added to an excess of pyrazine, the precipitate was formed only very slowly and after cooling. In each case, the precipitate was found to be Ag(pyrazine)N03 and the solubility product was determined as 2.3 x 10-4.103... 

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