Hydroxy acids ionization constants

The ionization of hydroxy-substituted benzoic acids is also affected by chelation. If mtramoleculeir H bonding is possible, the carboxylic acid ionization constant is raised due to the stabilization of the anion (265, 114, 273). This is Ulustrated in Table 5-VII. 

Ionization constants of czs-3-substituted acrylic acids have been correlated with the Hammett equation by Hogeveen (58) and by Charton (60). Charton has correlated ionization constants for a number of other c/s-vinylene sets with the Hammett equation (60). Charton and Charton have correlated some cw-vinylene sets with the extended Hammett equation [eq. (2)] (73). Sufficient data are available for twelve sets of cis-vinylene equilibria, of which four sets represent ionization constants of hydroxy compounds (sets 12-1 to 12-4) and eight sets represent ionization constants of carboxylic acids (sets 12-5 to 12-12). All sets have been correlated with eq. (24) and eq. (2). Sets studied are reported in Table XII. Results of the correlations are reported in Table XIII. Sets designated A were correlated with eq. (24), sets designated B were correlated with eq. (2). In the case of the second ionization constant of 2,3,5,6-tetrahydroxy-l,4-benzoquinone (set 12-3), it is uncertain which hydroxyl group ionizes therefore, the value for X = OH was excluded from the correlation. All of the sets 12-1 to 12-4 gave significant correlations with both eq. (24) and eq. (2),... 

The electronegative influence of the thiadiazole system greatly increases the acidity of substituents (Table 2). The effect is further enhanced in the 1-monoxide and 1,1 -dioxide analogues. The ionization constants of 4- and 5-hydroxy-2,l,3-benzothiadiazoles were determined in water <70AC(R)80l>. 

The dione, 3, is a yellow crystalline solid that, despite its strained four-membered ring, is much less reactive than 1,2-benzenedione (ort/w-benzoquinone). It cannot be reduced to a cyclobutadienediol, does not undergo Diels-Alder reactions, and with bromine gives a substitution product rather than addition. The bromo compound so formed hydrolyzes rapidly to a hydroxy compound, 4, which is an extraordinarily strong acid having an ionization constant about 109 times that of benzenol ... 

Table 2 Ionization Constants of Hydroxy Acids in Aqueous Solutions...

The effect of a 5-substituent on the tautomeric equilibrium of 4-pyrimidinones 53 (R1 = Me R2 = H, Me, MeO, COOEt, CONH2, CN R3 = H) was studied using their acidic and basic ionization constants and the results were confirmed by UV spectroscopy (74CPB1239). It was shown that all these compounds exist in aq. solution as an almost equimolar mixture of two oxo forms with the fraction of the hydroxy form not exceeding 4%. 4,6-Dimethyl-2(l//)-pyrimidinone and 6-methyl-4-pyrimidinone exist predominantly in the lactam form in solution (80JST(62)47, 84H(22)2591). 

The pharmacokinetics of nalidixic and hydroxy-nalidixic acids have been studied by several different groups. Takasugi ejt al studied in-situ and in-vitro absorption of nalidixic acid from the gastrointestinal tracts of rats as a function of pH. They reported that the absorption of non-ionized nalidixic acid was faster than the ionized form, with the maximum absorption rate constant found when the drug was administered from a pH=3 buffer solution. The absorption in-sltu was found to be ten times the rate in-vitro, but this was dependent on several factors.(13)... 

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