Heteroaromatic hydration

It is a simple matter to determine an ionization constant and also to predict its magnitude. When these values do not agree, and if ringopening has been carefully excluded, the likelihood of covalent hydration must be considered. Equilibria encountered during the determination of the ionization constant of a hydrating heteroaromatic base are shown in the following diagram. Similar equilibria exist for... 

Of all the heteroaromatic compounds that have been examined qualitatively and quantitatively for covalent hydration, the pteridines constitute the largest series. Most of the quantitative relationships which were used in earlier discussions were first derived for the hydroxypteridines. Also most of the known examples of hydration in anions were found in this series. 

Thus far, this section has been concerned with the explanation of the factors responsible for the covalent hydration of heteroaromatic substances. Heteroethylenic substances (e.g. the dihydropyridines. 

The electronic effects (8+ on carbon and S on nitrogen) that favor the hydration of heteroaromatic molecules and of Schiff bases to give Dimroth bases are the same as those that would favor the ringopening of the hydrated heteroaromatic molecules and cleavage of the C—bond in Dimroth compounds. 

An understanding of covalent hydration is essential for all who work with heteroaromatic compounds containing doubly bonded nitrogen atoms. As chemists become more aware of the circumstances in which hydration occurs, and the means for detecting it, many new examples will probably be discovered and many puzzling discrepancies solved. Many of the values for ionization constants and ultraviolet spectra which are in the literature refer to partly hydrated equilibrium mixtures and should be replaced by values for the pure substances. 

Covalent Hydration in Nitrogen Heteroaromatic Compounds II. Quantitative Aspects... 

Our next step was to assess whether the methodology used to calculate hydration free energy differences for simple carbonyl-containing compounds9 was suitable for heteroaromatic bases. Since our drug design strategy entailed analysis of purine riboside hydration, a series of azanaphthalenes was initially selected for analysis in part because of their structural similarity to purines and in part because of the extensive... 

Table 1 Hydration free energies of heteroaromatic compounds (kcal/mol) ...

Sulfonated poly(arylene ether)s have shown promise for durability in fuel cell systems, while poly-(styrene)- and poly(imide)-based systems serve as model systems for studying structure-relationship properties in PEMs because their questionable oxidative or hydrolytic stability limits their potential application in real fuel cell systems. Sulfonated high performance polymer backbones, such as poly(phe-nylquinoxaline), poly(phthalazinone ether ketone)s, polybenzimidazole, and other aromatic or heteroaromatic systems, have many of the advantages of poly-(imides) and poly(arylene ether sulfone)s and may offer another route to advanced PEMs. These high performance backbones would increase the hydrated Tg of PEMs while not being as hydrolytically sensitive as poly(imides). The synthetic schemes for these more exotic macromolecules are not as well-known, but the interest in novel PEMs will surely spur developments in this area. 

Becker et al.174 find that the photoproduct of cytidine-3 -phosphate is the photohydrate. The quantum yield is dependent on the pH, and is higher for the neutral form than for the acidic form. Albert176 has published a review article on nonphotolytic hydration of the C=N bond in many heteroaromatic substances, a reaction similar in many respects to photohydration of the pyrimidines. Shapiro and Klein175 report that cytidine and cytosine are deaminated at 95°C by a variety of aqueous buffers. The reaction is pH sensitive. 

In heterocyclic chemistry it can be misleading to speak of covalent addition to mean both a product of an addition reaction, such as the hydration of a neutral substrate (i.e., transformation of pteridine to the 4-hydroxydihydro derivative),20 and a product of an attachment reaction, such as the reaction of the hydroxide ion with the ring carbon of a heteroaromatic cation.21... 

Covalent Hydration in Nitrogen-Containing Heteroaromatic Compounds I, Qualitative Aspects A. Albert and W. L. F. Armarego, Adv. Heterocycl. Chem., 1964, 4, 1-42. Covalent Hydration in Nitrogen Heteroaromatic Compounds II, Quantitative Aspects D. D. Perrin, Adv. Heterocycl. Chem., 1964, 4, 43-73. 

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