Pyrido pyrazin

The final chapter by Istvan Hermecz (Chinoin, Ltd., Budapest, Hungary) deals with bicyclic systems containing one ring junction nitrogen and one heteroatom and their benzologs, i.e. pyrido-oxazines, pyrido-thiazines, pyrido-pyridazines, pyrido-pyrazines, pyrido-pyrimidines and their analogs. Much of this material has not been reviewed for forty years, during which time immense advances have occurred. 

Both the possible non-bridgehead pyridopyrazines, pyrido[2,3-f ]pyrazine (386) and pyrido[3,4-f ]pyrazine (387), are well known, the numbering being as shown. In the older literature they may be known as pyridino-2, 3 -2,3- and -3, 4 -2,3-pyrazines, as 1,4,5- and 1,4,6-triazanaphthalenes, or as 5- and 6-azaquinoxalines respectively. Some derivatives may also be referred to and numbered as deazapteridines, or as deaza derivatives of various natural products (see Section 2.15.16.3). Of the benzo fused systems, representatives of one angular (388) and two linear (389) and (390) derivatives of the [2,3-f ] system are known, but only the linear benzo fused [3,4-6] system (391). 

The stereochemistry and conformational behaviour of 2,3-dimethyl-l,2,3,4-tetrahy-dropyrido[2,3-f ]pyrazine and some related compounds have been studied, as have the corresponding pyrido[3,4-f ]pyrazine derivatives (67JOC1378, 60JA3762). 

The europium shift NMR spectra of both parents have also been studied (710MR(3)575), as has the nematic liquid crystal behaviour of pyrido[2,3-f ]pyrazine (760MR(8)155). 

IR spectroscopy has also been used in structural problems in 2- and 3-hydroxypyrido[3,4-f ]pyrazines (63JCS5156), in 8-oxopyrido[2,3-f ]pyrazine-7-acids (73MI21501) and in the pyrido[3,4-f ]quinoxaline field (74JCS(P1)1965). IR spectra were recommended for the distinction of isomeric products in the Isay reaction (Section 2.15.15.6.1) (71TH21500) UV spectra were not satisfactory. The Raman spectra of a number of 1- and 3-deazaflavin analogues have been recorded and discussed (80BBA(623)77). 

No systematic study of the mass spectra of pyridopyrazines has been noted, but those of 2,3-dialkyl and 2,3-diaryl derivatives have been recorded 750MS97), and mass spectrometry has been used in the elucidation of problems in the reactions of pyrido[2,3-f ]pyrazines with amide ion (including use of and derivatives) (79JHC305), and of pyrido[2,3-f ]pyrazinium salts with indoles (78ZOR431). The mass spectra of some 1-deazaflavins have been recorded (74JCS(P1)1965). 

The tautomerism of some deaza analogues of riboflavin has been studied (77TL2551). The tautomerism of 3-ethoxalylmethyl- and 3-acetonyl-pyrido[2,3-f ]pyrazin-2-ones is fully discussed in (71TH21500 p. 68)... 

Protonation of pyrido[2,3-f ]pyrazine occurs normally without covalent hydration, although the 2-hydroxy derivative did show such behaviour (63JCS5737). The pyrido[3,4-f)]pyrazine parent base does show the phenomenon, although the exact structure of the covalent hydrate seemed to be in doubt between protonated (392) and (397). The issue was resolved in favour of the former by NMR (79JHC301, 75AG356). The 3-hydroxy derivative also shows hydration effects, as does the 7-amino cation (63JCS5166). 

An unusual addition of acetoacetic acid to pyrido[2,3-Z>]pyrazin-2(l//)-one (400) to give (eventually) the 3-acetonyl derivative (401) was postulated (71TH21500) to occur via a cyclic transition state, and the similar addition of oxalacetic ester may occur via a related mechanism. 

Both 2- and 3-methyl groups in pyrido[2,3-Z ]pyrazines are acylated by ethyl oxalate (71TH21500). They give (preferentially 3-) styryl derivatives with aromatic aldehydes and oximes with pentyl nitrite. 

Nitro groups have been reduced to amino groups, whilst amino groups in the 3- and 6-positions of pyrido[2,3-f ]pyrazines and in the 5-position of the [3,4-f ] isomers have been hydrolyzed to the corresponding hydroxy derivatives with alkali. Protected amino groups have been liberated by hydrolysis or reduction in deazapteridine syntheses. 

H-Pyrido[2,l-i]purine-9-carboxylic acid, 7-oxo-methyl ester, 5, 566 Pyrido[2,3-6]pyrazine, amino-nucleophilic attack, 3, 253 Pyrido[2,3-h]pyrazine, 6-chloro-reactions... 

E rido[2,3-b]pyrazine, 2,3-dihydroxy-chlorination, 3, 251 Pyrido[2,3-b]pyrazine, 6-hydroxy-formation, 3, 251... 

Pyrido[3,4-b]pyrazine, 2-hydroxy-IR spectra, 3, 249 Pyrido[3,4-b]pyrazine, 3-hydroxy-IR spectra, 3, 249 structure, 3, 254 Pyrido[3,4-6]pyrazine, methyl-... 

Pyrido[l,2-a]pyrazin-5-ium salts — see 2-Azaquinolizinium salts E rido[2,3-b]pyrazinium salts mass spectra, 3, 250... 

Pyrido[2,3-b]pyrazin-8-one-7-carboxylic acids H NMR, 3, 249 Pyrido[2,3-b]pyrazinones alkylation, 3, 250... 

Pyrido[2,3-h]pyrazin-3- and -2-ones exhibit temperature-dependent equilibria in DMSO-dg solution ( H NMR studies), with gradual increase in the proportion of the imino forms 173b and 174b as the temperature increases, although the enamino forms 173a and 174a remain predominant (97JHC773). 

Chemistry of pyrido[2,l-c]-l,4-oxazines, pyrido[2,l-c]-l,4-thiazines, pyrido-[l,2-(2]pyrazines, and their benzologs 98AHC(71)145. 

Chemistry of pyrido[l,2-<2]pyrazines and their benzologs 98AHC(71)145. 

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