Pyrazino pyrazines, covalent

Pyrazino[2,3-6]pyrazines are known to undergo covalent hydration (63JCS4304). In aqueous solution the cation of the parent pyrazino[2,3 -b ]pyrazine (137) exists as the covalently dihydrated form (43) (66JCS(C)999). 

The UV spectra of pyrazino[2,3-6]pyrazine and several methyl-substituted derivatives have been studied, especially with respect to covalent hydration (Section 7.4.12.2.).243 The unsubstituted pyrazino[2,3-6]pyrazine itself in water at 20 °C (pH 7) has the strongest absorptions at 308, 315, and 322 nm (logs 4.16, 4.15, and 4.26).243 244... 

NMR chemical shifts for pyrazino[2,3-fr]pyrazine and pyrazino[2,3-6]quinoxaline and their covalent hydration products are also available245,247 and the ESR spectrum of pyrazino[2,3- >]pyrazine has been discussed in connection with MO calculations.18 248,249... 

The pA value of pyrazino[2,3-6]pyrazine and its methyl-substituted derivative is strongly influenced by covalent hydration of the compounds during the measurement (see Section 7.4.12.2.).148,243... 

As in some other diazinodizines covalent hydration is also observed in pyrazino[2,3-h]pyrazines.148,243,245,247 Thus, pyrazino[2,3-6]pyrazine in aqueous solution reversibly adds two molecules of water with formation of cation 3.247... 

In aqueous solution the cations of the parent heterocycle and its 2-methyl and 2,3-dimethyl derivatives are covalently hydrated. The neutral molecules are anhydrous. The tri- and tetramethyl derivatives are not hydrated either as neutral species or as cations. These conclusions were reached on the basis of acidity constant measurements and ultraviolet studies and confirmed by PMR spectroscopy. The PMR spectra show that hydration occurs by the addition of two molecules of water to give cations of formula 4. Substitution by a methyl group at either of the sites of hydration renders the cation completely anhydrous. Moreover the introduction of methyl groups to give compound 4 (R = Me) reduces the extent of hydration. Thus the cations of pyrazino[2,3-h]pyrazine and its 2-methyl derivative are completely hydrated in aqueous solution, whereas the protonated 2,3-dimethyl compound exists as a 3 1 mixture of the dihydrate and the anhydrous species. 

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