Triazanaphthalenes covalent hydration

Covalent hydration has been demonstrated in the following families of compounds 1,6-naphthyridines, quinazolines, quinazoline. 3-oxides, four families of l,3,x-triazanapththalenes, both l,4,x-triazanaphthalenes, pteridines and some other tetraazanaphthalenes, and 8-azapurines these compounds are discussed in that order. In general, for any particular compound (e.g. 6-hydroxypteridine) the highest ratio of the hydrated to the anhydrous species follows the order cation > neutral species > anion. In some cases, however, anion formation is possible only when the species are hydrated, e.g. pteridine cf. 21 and N-methyl-hydroxypteridines (Section III, E, 1, d). Table V in ref. 10 should be consulted for the extent of hydration in the substances discussed here. 

In all the examples studied, the difference in the free energy between the anhydrous and hydrated species is 4 kcal/mole or less. ° Both electron deficiency and resonance stabilization are necessary for covalent hydration to be measurable. The necessity for electron deficiency is clearly shown in the following examples. The cation of 1,4,5-triazanaphthalene is anhydrous, but the cation of 1,4,5,8-tetraazanaphthalene is predominantly hydrated. 1,6-Naphthyridine cation is anhydrous, whereas the cations of the 3- and 8-nitro derivatives are predominantly hydrated. Also, the percentages of the hydrated form in the neutral species of 2-hydroxy-1,3-diaza-, 1,3,8-... 

Reversible covalent hydration across C=N bonds occurs in a number of nitrogen-containing heterocycles, including pteridine and its 2- and 6-hydroxy derivatives, quinazoline (as the cation), and 1,4,6-triazanaphthalene (as the cation). Among bases giving this reaction, the neutral molecule exists predominantly as the anhydrous form, whereas the cation contains an increased proportion of the... 

Very few values are known for anhydrous organic bases which can undergo covalent hydration, so that, in general, and for such systems cannot be calculated using Eqs. (12) and (13). However, in cases where the pA of the hydrated species can be measured, Eq. (14) can be used to obtain an approximate estimate of K, the equilibrium ratio of hydrated to anhydrous neutral molecules. This treatment has been applied to quinazoline, the nitroquinazolines, and some triazanaphthalenes. 

Of the fourteen possible triazanaphthalenes, ten are known in aromatic form, and nucleophilic displacements are reported for nine of these. Covalent hydration has been observed with 1,3,5-, 1,3,6-, 1,3,7-, 1,3,8-, and 1,4,6-triazanaphthalenes. ... 

The 6-amino derivative of 1,4,6-triazanaphthalene (455) is similarly hydrolyzed with 5N alkali (140°, 3 hr). Covalent hydration of the 2-0X0 derivative has been observed. ... 

Covalent hydrates can undergo ring opening especially in acidic media, for example the triazanaphthalene (178 — 179). 

Covalent hydrates can undergo ring opening especially in acidic media, for example, the triazanaphthalene (196 197). 1,2,4,5-Tetrazines 198 are hydrolyzed with a base to give aldehyde hydrazones, RCH=NNHCOR. Polyaza rings suffer complete hydrolytic ring cleavage. 1,2,3-Benzotriazines are easily converted into derivatives of 2-aminobenzaldehyde. 

Triazanaphthalenes. Part II. Covalent Hydration in 1,4,6-Triazanaphthalenes. (With G. B. Barlin.)... 

Heterocyclic compounds that have water bound covalently across a C=N bond behave as secondary alcohols. When subjected to very gentle oxidative conditions, they are converted into the corresponding 0x0 compounds. Potassium permanganate in 0. IN sodium hydroxide at room temperature has been used to oxidize 2- and 6-hydroxypteri-dine to 2,4- and 6,7-dihydroxypteridine, respectively. In contrast, 4-hydroxypteridine was not attacked by this reagent even at 100°. Hydrogen peroxide in acid solution was used to oxidize quinazoline quinazoline 3-oxide 1,3,5-, 1,3,7-, and 1,3,8-triazanaphthalene and pteridine (which hydrate across the 3,4-double bond in the... 

---