Aromatic pyrazine ring, production

In many instances the primary reaction product is a dihydropyrazine and aromatization may be required as a final step. In addition, many pyrazines are prepared by the structural modification of a preformed pyrazine ring and hence would be classified as a reaction of the ring rather than a ring synthesis such processes are discussed more fully in Section 2.14.2. 

Another way to prevent any dissociation of cyclization products obtained by the diaddition reactions is their conversion into aza-aromatic compounds. Oxidation of cycloadducts by permanganate in acetone yields condensed pyrazine derivatives containing, of course, no ring junction hydrogen atoms. Several examples of condensed systems obtained by this method are shown in Scheme 53. 

Ring systems containing two heteroatoms tend to feature less in the vapor-phase literature. This is partly because of the greater reactivity (i. e. reduced aromaticity) of these heterocyclic compounds. In addition, there has been less commercial incentive to develop catalyzed processes for these smaller-volume niche products. As an example, both pyrimidine (26) [51] and pyrazine (27) [52] can be made by catalyzed vapor-phase methods they can also be recovered from the pyri-dine- ff-picoline reaction. In principle, pyrimidine and pyrazine could then serve as platforms-much like pyridine does-for preparing a wide range of derivatives. The market for these derivatives is, however, best met by traditional convergent syntheses in the liquid phase. 

Attempted oxidation of the 3-oxo compound 96 with potassium permanganate resulted only in ring breakdown. Nevertheless a solution of this reagent in acetone is commonly used to oxidize compounds such as the dihydro derivative 97 to the aromatic system without further oxidation occurring. Oxidation of the tetrahydro oxo compound 98 with potassium permanganate in 2M sodium hydroxide solution at room temperature gives the 2-oxo compound 99. This compound is sensitive to oxidation, and the use of iodine has been recommended for this conversion. If alkaline potassium ferricyanide is used, the product formed is the dioxo derivative 100. The dioxo compound is also obtained from l,2-dihydro-2-oxo- or 3,4-dihydro-3-oxopyrido[2,3-b]pyrazine under the same conditions. Recently ferric chloride has been used to aromatize a series of dihydropyrido[2,3-b]pyrazines. ... 

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