Tetraazanaphthalene

Armarego et have determined the infrared spectra of the four parent pyridopyrimidinos (148) in the solid phase as KBr discs, and have comiiared them with other di-, tri-, and tetraazanaphthalenes. Thirteen in-plane skeletal vibrations and ten CH bending vibrations... 

Fig. 3. Ultraviolet spectra of 1,4,6,8-tetraazanaphthalene in water. (A) Anhydrous neutral species, (B) hydrated cation, and (C) hydrated neutral species.

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. 

T. Rowan, H. C. S. Wood, and P. Hemmerich, Proc. Chem. Soc. 260 (1961). 52a Calculated by subtracting 2.7 (due to the base-weakening effect produced by removal of foiu methyl groups) from the pK (— 0.02) of 2,3,6,7-tetramethyl-1,4,5,8-tetraazanaphthalene, which forms an anhydrous cation. 15... 

Similar analyses of 2-methyl-, 2,3-dimethyl-, 2,3,6-trimethyl-, and 2,3,6,7-tetramethyl-l,4,5,8-tetraazanaphthalene showed that all the neutral species were anhydrous. Whereas the cations (in aqueous solution) of the 2-methyl and 2,3-dimethyl derivatives were predominantly ( > 95%) hydrated, the 2,3,6-trimethyl cation had only a trace of hydrated species and that of the 2,3,6,7-tetramethyl derivative was anhydrous. ... 

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-... 

Some of the scatter within the groups is undoubtedly due to differences in bond order and also to whether or not the nitrogens are located in the same ring. Nevertheless, some striking exceptions are apparent in which the pA values are much higher than expected. These include quinazoline, 1,3,5-, 1,3,7-, 1,3,8-, and 1,4,6-triazanaph-thalene, pteridine, and 1,4,5,8-tetraazanaphthalene. In all these cases, covalent hydration of the cation has been shown to occur, so the measured pA values are, in fact, equilibrium values involving both hydrated and anhydrous species. The hydrated species are, without... 

The two most reactive types of derivatives are expected to be the 4-Le-l,3,6,8- and 4-Le-l,2,3,6-tetraazanaphthalenes 456 and 457. Of the twenty-two possible ring systems, ten are known in aromatic form, and nucleophilic substitution has been carried out on only four of these. Covalent hydration has been observed in the pteri-dines and in 1,4,6,8-tetraazanaphthalenes. 

The great advance in the capacity of modern computers has contributed to a major expansion in the detail of theoretical investigations of small molecules and also an expansion of the size of systems suitable for study. Pteridine chemistry has aspects of both. In small molecule work, it is important to establish the appropriateness of a number of possible basis sets for ab initio calculations to yield useful results. For vibrational spectra of pteridines and related tetraazanaphthalenes, the B3LYP/6-31G basis set has been reported to give the best correlation between theory and experiment but the smaller 4-31G basis set also gave acceptable results <2000PCA7386>. Calculations relevant to... 

Irradiation of 2,3,6,7-tetracyano-l,4,5,8-tetraazanaphthalene 106 at low temperature results in isomerization to a product identified as 107. The latter is reconverted into 106 upon exposure to visible light <2003CPL(375)605>. By comparison, attempts to prepare all-carbon analogues of 107 result only in the formation of naphthalenes. The dianion 108 has been used as a ligand to link two bis(molybdenum) units <2006IC767>. 

Both chlorines in 79 are easily replaced by nucleophiles, as shown for the preparation of 2,3,6,7-tetracyano-l,4-dithiinopyrazine (80) by the action of disodium dimercaptomaleonitrile (80USP4199581). Cyclization of DAMN with 79 is reported to give a 90% yield of 2,3,6,7-tetracyano-l,4-dihydro-1,4,5,8-tetraazanaphthalene (81), which can be oxidized to 82. Ammonia in dimethylformamide gave the diamine (53) (Scheme 30) (78MI1). 

Increasing numbers of nitrogen atoms increase not only the kinetic susceptibility toward attack but also the thermodynamic stability of the adducts. Reversible covalent hydration of C = N bonds has been observed in a number of heterocyclic compounds (76AHC(20)117). Pyrimidines with electron-withdrawing groups and most quinazolines show this phenomenon of covalent hydration . Thus, in aqueous solution the cation of 5-nitropyrimidine exists as (164) and quinazoline cation largely as (165). These cations possess amidinium cation resonance. The neutral pteridine molecule is covalently hydrated in aqueous solution. Solvent isotope effects on the equilibria of mono- (166) and dihydration (167) of neutral pteridine as followed by NMR are near unity (83JOC2280). The cation of 1,4,5,8-tetraazanaphthalene exists as a bis-covalent hydrate (168). 

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