Pyrazines, reduced

Derivatives of 1,2-, 1,4-, 2,3-, and 2,5-dihydropyrazine are known, but the structures of these compounds are not easy to establish because of the tendency of dihydropyrazines to isomerize, dimerize, and oxidize. Dihydro structures are stabilized by groups such as alkoxycarbonyl and phenyl 1,4-dihydro-2,3,5,6-tetraethoxycarbonyl-pyrazine and 2,3-dihydro-5,6-diphenylpyrazine are relatively stable compounds. 

These compounds are formed by addition of lithium alkyls to alkylpyrazines, followed by hydrolysis (see Section V,A). They readily oxidize to pyrazines on exposure to air. Some early examples of 1,4-dihydropyrazines have recently been shown to have 1,2-dihydro structures.384  

4-dihydropyrazine formed by reduction of pyrazine with lithium and trimethylsilyl chloride, spontaneously decomposes on exposure to air.384b 

Mager and Berends found that tetraethoxycarbonylpyrazine (161) undergoes partial catalytic hydrogenation to give the tetrahydro-pyrazine (162) which spontaneously oxidizes in air to give the 1,4-dihydro derivative (163).365 Compound 163 is more conveniently 

Methylated 1,4-dihydropyrazines (1,2,4-tri-, 1,2,4,5-tetra-, and 1,2,4,6-tetramethyl) as well as imidazolines have been isolated from the reaction of sucrose with methylamine at high temperatures (120°-260°), for prolonged reaction periods (18 hours) and in the presence of ammonium phosphate as catalyst. 1,4-Dihydropyrazines are also isolated from the reaction of sucrose and ethanolamine sucrose-ammonia interaction yields a wide range of pyrazines and imidazoles.369-372 

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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... 

Among the four isomers of dihydropyrazines, the 2,3-dihydro isomers are most explored because these reduced pyrazines have been easily prepared by condensation of 1,2-diamines and 1,2-dicarbonyl compounds. This class of compounds is unexpectedly unstable resulting in dimerization at room temperature. Thus, 2,3-dihydropyrazine 97 (R = = Me) gradually dimerizes to form tricyclic system 98, fused with two tetrahydropyrazine units... 

When DISN reacts with electron-rich styrenes such as p-methoxystyrene, good yields of reduced pyrazines 117, often accompanied by their oxidized forms, are obtained. However, reaction with electron-deficient styrenes like p-fluorostyrene give the 2-amino-3-(2-arylaziridin-l-yl)maleonitriles (118) (72JA3242 84JOC813). 

Conformations. Calculations have been made of the preferred conformations for 1,4-dihydropyrazine,456, 1080 1,2,3,4-tetrahydropyrazine,100 piperazine (and several alkyl derivatives),1079 and the (reduced) pyrazine ring in several biologically important di- and tetrahydropteridines.100... 

Although nuclear C-nitrosopyrazines can be made, they appear to be too unstable for isolation and characterization as such in contrast, many N-nitrosated derivatives of piperazine or other partially reduced pyrazines are quite stable. 

Note The Rh-catalyzed C-acylation of reduced pyrazines with carbon monoxide and ethylene appears to offer considerable potential for further development. l-Methyl-4-(pyridin-2-yl)piperazine (292) gave l-methyl-3-propionyl-4-(pyridin-2-yl)-l,4,5,6-tetrahydropyrazine (293) [Rh4(CO)12, PhMe, H2C=CH2 J, to 10 atm, CO l to 15 atm, 25°C, autoclave then 160°C, 20 h 85%] several N-alkyl/aryl homologues were made similarly.1404... 

Piperazine (or 2,6- Aqueous solution over reduced Pyrazine (79%) (or 2,6- 468... 

Pratt (36) in 1957 published a comprehensive review which included reduced pyrazines (di- and tetrahydropyrazines, piperazines, and piperazinones), and the literature prior to 1957 is generally not further examined. 

Author(s) (Total References Cited) Year Published Reduced Pyrazines Reviewed Refs. 

This volume summarizes published pyrazine chemistry with emphasis on syntheses, properties, and reactions of pyrazines and pyrazine iV-oxides (Chapters 1-X). Treatment of theoretical aspects is minimal. Although not strictly relevant. Chapter XI is presented as a summary of earlier reviews and more recent literature of reduced pyrazines (including piperazines). The literature recorded in Beilstein to 1929 and Chemical Abstracts through 1978 (Volume 89) has been covered together with selected references to 1980. Whereas every reasonable effort has been made to incorporate most significant material, no attempt has been made to include all relevant data. Tables have been incorporated in the text to extend the range of examples. 

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