Covalent hydration electron deficiency

Naphthyridines. Part II. Covalent Hydration, Electron-deficiency, and Resonance Stabilization in 1,6-Naphthyridines. 

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-... 

In general, electron-releasing groups (e.g. —NH2, —OH) diminish or prevent covalent hydration by decreasing the electron deficiency in the nucleus. This diminution becomes ineffective if a new kind of stabilizing resonance is facilitated by the substituent, e.g. the urea-type resonance and the 4-aminopyridine-type resonance in 2- and 6-hydroxypteridine, respectively. The reluctance of the anions of these substances to form hydrates is attributed to the stable benzenoid system, e.g. 42, in the anhydrous anion compared with the predominantly lactam form of the neutral species, e.g. 43. 

The added electron deficiency at positions 2 and 5 in the nitro-1,6-naphthyridines together with the resonance stabilization of the hydrated cations (150<—>151 152<—>153) is thus required for covalent hydration. The 3-nitro-1,5-naphthyridine satisfies the first require-... 

The concept of pseudobase formation by heteroaromatic cations is intimately related to the covalent hydration of heteroaromatic molecules16-19 and to Meisenheimer complex formation,20-25 although this relationship has not generally been emphasized in the literature until recently26,27. All such reactions involve the formation of -complexes by nucleophilic addition to electron-deficient aromatic species, and yet, extensive reviews of covalent hydration16-19 and of Meisenheimer complex formation20-25 have neither explicitly recognized their mutual relationship nor considered pseudobase formation. 

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... 

The fundamental aspects of the IR spectra of pteridines have been discussed.31 The NMR spectra of pteridine and its derivatives indicate the marked 7r-electron deficiency, which is reflected in low-field H signals [Pteridine (CDCl3/ppm) 9.80, H4 9.60, H2 9.33, H7 9.15, H6], Covalent hydration causes the signals for the protons in the ring affected to move upfield. These effects are important in the study of covalent hydration.32,33... 

The heterocyclic rings of (benzo)pyridazine systems are electron deficient and thus susceptible to attack by nucleophiles. However, in the absence of a suitable leaving group this is usually unfavoured due to loss of aromaticity. For example, covalent hydration is not observed, though pseudobase formation can occur with subsequent disproportionation to give, for example, phthalazinones and dihy drophthalazines. 

The Lewis acid-base definition focuses on the donation or acceptance of an electron pair to form a new covalent bond in an adduct, the product of an acid-base reaction. Lewis bases donate the electron pair, and Lewis acids accept it. Thus, many species that do not contain El are Lewis acids. Molecules with polar double bonds act as Lewis acids, as do those with electron-deficient atoms. Metal ions act as Lewis acids when they dissolve in water, which acts as a Lewis base, to form an adduct, a hydrated cation. Many metal ions function as Lewis acids in biomolecules. 

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