Reactions of Tautomeric Pyrazinones

The important conversion of pyrazinones into halogenopyrazines has been covered in Section 4.1.1. An unusual aminolytic cyclization has been reported and other reactions are discussed in the subsections that follow. 

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With the exception of those halogenopyrazines made by primary synthesis (see Chapters 1 and 2), most chloropyrazines have been made recently by the reaction of tautomeric pyrazinones with a phosphorus chloride or by the reaction of pyrazine iV-oxides with phosphoryl chloride in contrast, most other halogenopyrazines have been made by direct halogenation or by transhalogenation of chloropyrazines. A single interesting example of the conversion of a methoxy- into a chloropyrazine is included at the end of Section 4.1.1. 

Several rarely used but quite important reactions of tautomeric pyrazinones are typified in the following examples ... 

As already mentioned, hydroxypyrazines exist in tautomeric equilibria with the corresponding pyrazinones which are normally the predominant species in the equilibria. Some of the reactions of hydroxypyrazines are reminiscent of those of phenols they can, for example, be coupled with diazonium salts and brominated and nitrated in either the ortho or para position to the hydroxyl group. Coupling with diazonium salts occurs in neutral or weakly alkaline solution, but if the reaction is carried out in 1 M sodium hydroxide solution, arylation of the pyrazine ring takes place. From hydroxy-pyrazine and benzenediazonium chloride 47% 2-hydroxy-3-phenyl-and 4% 2-hydroxy-3,6-diphenylpyrazine are obtained. 

Leszczynski et al. have shown interest in comparing experimental (matrix isolation) and calculated (B3LYP) IR data (frequency and intensity) to discuss the tautomerism of benzo-annelated pyridonone, pyrazinone, and pyrimidinone (144-148). These equilibria were well reproduced by theoretical calculations carried out at the QCISD and QCISD(T) levels. The combined experimental and theoretical results reveal links between aromaticity and tautomerism. Moreover, a UV-induced phototautomeric reaction transforming the oxo forms into the hydroxy tautomers was observed for all (except 3-hydroxyisoquinoline) studied compounds [144], The interest of Leszczynski in problems related to tautomerism, aromaticity, and proton transfer is also apparent in a study of (lH-aza-hetero-2-ylidene)-acetaldehyde and 2-azahetero-2-yl-ethanol tautomeric pairs [145],... 

Comparison of the ultraviolet absorption and ionization constants of aminopyrazine, methylaminopyrazine, and dimethylaminopyra-zine indicates that aminopyrazine exists as such and not in the tautomeric imino form.147 Aminopyrazines, like their pyridine analogs, form diazonium salts, which readily decompose to the corresponding pyrazinones. For example, nitrous acid treatment of aminopyrazine318 and 2-aminopyrazine-5-carboxylic acid210 gives the corresponding pyrazinones in 30 and 59% yield, respectively. The diazonium salt from aminopyrazine cannot be converted into bromo-pyrazine under the conditions of the Sandmeyer reaction. 

Tautomerism of 2( 1 //j-pyrazinone 57 in low-temperature inert gas matrix has been investigated by means of IR spectroscopy, and the tautomeric equilibrium constant was estimated as KT — 8.6 in the favor of the hydroxy tautomer. The UV-induced phototautomeric reaction has been used to separate the IR spectra of the tautomers (92JPC6250). 

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