Pyrazine V-Oxides

In the Reissert-Henze reaction, quinoline 1-oxide reacts with benzoyl chloride and potassium cyanide to give 2-cyanoquinoline in good yield (Scheme 30). Pyridine 1-oxides undergo the Reissert-Henze reaction readily when the reaction is carried out in non-aqueous medium using PhCOCl-Me3SiCN (Scheme 31). Pyrimidine /V-oxides and pyrazine /V-oxides also undergo Reissert-Henze reactions. 

Regioselectivity in the chlorination of pyrazine /V-oxides with phosphoryl chloride depends upon the substituent on the C-3 carbon. Thus, 3-aminopyrazine 1-oxide is chlorinated with loss of the /V-oxide oxygen to give 2-amino-3-chloropyrazine as the sole product whereas 3-methoxy and 3-chloropyrazine 1-oxides form approximately equal amounts of 3-chloro- and 6-chloro-2-substituted pyrazines along with a trace of the 5-chloro derivatives. 

The pyrazine mono-iV-oxides show close similarity in their reactions to the pyridine AT-oxides.402-404 In the latter compounds the electronreleasing ability of the iV-oxide function is demonstrated by the activation of the a- and y-ring carbon atoms to electrophilic attack. Pyrazine mono-AT-oxides are predictably less activated to electrophilic substitution, and thus there have been no reports of the successful nitration of pyrazine /V-oxides. The pyrazine ring is, however, activated by the A-oxide function to nucleophilic attack, especially if the positive charge of the N atom is enhanced by formation of an intermediate with an electron acceptor. Thus, phosphoryl chloride treatment of pyrazine 1-oxide yields chloropyrazine391 and similar... 

The only reference to these compounds records the preparation of the furo[3,4-6]pyrazine-/V-oxides (247) from the oximes (246), which were intended to be used to make pyrazines for further elaboration into pteridines (Equation (84)). It is suggested that in an acidic environment the isopropylidene is cleaved thus allowing cyclization to the lactone structure <84JHC657>. 

It is obvious that simple pyrazine /V-oxides cannot undergo O-alkylation or acylation. However, tautomeric N-oxides, for example, (262), can do so. The following examples will illustrate conditions required and results to be expected ... 

Just as pyrazine. V-oxides may be converted into C-halogeno- (Section 4.1.3) or C-acyloxypyrazines (Section 5.5.2.3), so they can afford C-amino-, C-azido-, C-cyano-, or C-alkylthiopyrazines, although such reactions are not well developed yet. The following examples will illustrate such procedures as used in recent literature ... 

Pyrazine /V-oxides undergo several minor reactions, illustrated in the following examples ... 

The preparation of guanidinocarbonylpyrazine A -oxides by ring opening reactions has been described in Section VI11.3A(2), and from alkoxycarbonyl-pyrazine V-oxides in Section 9B.6-Chloro-2-methyl-4//-pyrazino[2,3-[Pg.307]

Proton magnetic resonance techniques have been used for the measurement of rates of hydrogen-deuterium exchange of pyrazine (in CHsOD-CHsONa at 164.6") (591) for a study of protonation of pyrazine (1472) for analysis of the reaction mixture from quatemization of 2-substituted pyrazines with methyl iodide (666) for elucidation or confirmation of the structures of alkylpyrazines obtained by alkylation of pyrazines with aldehydes and ketones in the presence of a solution of an alkali or alkaline earth metal in liquid ammonia, or a suspension of these metals in other solvents (614) for a study of changes in chemical shifts produced on ionization of 2-methyl and 2-amino derivatives of pyrazine in liquid ammonia (665) for characterization of methoxymethylpyrazines (686) for the determination of the position of the A -oxide function in monosubstituted pyrazine V-oxides and the analysis of V-oxidation reactions (838) for a study of the structure of the cations of fV-oxides of monosubstituted pyrazines (1136) and for the determination of the structure of the products of peroxyacetic and peroxysulfuric acid iV-oxidation of phenyl- and chlorophenylpyrazines (733b). 

Pyrazines,/V-oxides 176,196 Pyrazoles 189 Pyridine complexes 314 Pyridines 8, 28, 43. 125, /6S Pyridines, A -oxides 28, 41, 169, 196 Pyridinium salts 171 Pyridols 172 Pyridones 151 Pyridthione.s 31, 172 Pyrimidines 43, 174 Pyrimidines, iV-oxides 174,196 Pyrones /78... 

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