Dissociation constant aromatic acids

Determination of the dissociation constants of acids and bases from the change of absorption spectra with pH. The spectrochemical method is particularly valuable for very weak bases, such as aromatic hydrocarbons and carbonyl compounds which require high concentrations of strong mineral acid in order to be converted into the conjugate acid to a measurable extent. 

Hammen equation A correlation between the structure and reactivity in the side chain derivatives of aromatic compounds. Its derivation follows from many comparisons between rate constants for various reactions and the equilibrium constants for other reactions, or other functions of molecules which can be measured (e g. the i.r. carbonyl group stretching frequency). For example the dissociation constants of a series of para substituted (O2N —, MeO —, Cl —, etc.) benzoic acids correlate with the rate constant k for the alkaline hydrolysis of para substituted benzyl chlorides. If log Kq is plotted against log k, the data fall on a straight line. Similar results are obtained for meta substituted derivatives but not for orthosubstituted derivatives. 

The physical properties of cyanoacetic acid [372-09-8] and two of its ester derivatives are Hsted ia Table 11 (82). The parent acid is a strong organic acid with a dissociation constant at 25°C of 3.36 x 10. It is prepared by the reaction of chloroacetic acid with sodium cyanide. It is hygroscopic and highly soluble ia alcohols and diethyl ether but iasoluble ia both aromatic and aUphatic hydrocarbons. It undergoes typical nitrile and acid reactions but the presence of the nitrile and the carboxyUc acid on the same carbon cause the hydrogens on C-2 to be readily replaced. The resulting malonic acid derivative decarboxylates to a substituted acrylonitrile ... 

Analogous plots for many other reactions of aromatic compounds show a similar linear correlation with the acid dissociation constants of the corresponding benzoic acids. 

The next step in the development of the extrathermodynamic approach was to find a suitable expression for the equilibrium constant in terms of physicochemical and conformational (steric) properties of the drug. Use was made of a physicochemical interpretation of the dissociation constants of substituted aromatic acids in terms of the electronic properties of the substituents. This approach had already been introduced by Hammett in 1940 [14]. The Hammett equation relates the dissociation constant of a substituted benzoic acid (e.g. meta-chlorobenzoic acid) to the so-called Hammett electronic parameter a ... 

Hirayama, N., Maruo, M., and Kuwamoto, T., Determination of dissociation constants of aromatic carboxylic acids by ion chromatography, /. Chromatogr, 639, 333, 1993. 

Generally, the results of the measurements indicated that, where dissociation constants were determined by conductometry and also potentiometric titration, they were in agreement with each other further, KHX is low, e.g., about 10 4-10 6moll 1 for aromatic sulphonic acids and 10 13-10 16 moll-1 for carboxylic acids, Xhx2 is high, e.g., 102-104, and KBis low again, e.g., 10 5-10 6 for aliphatic amines and 10 10 for aromatic amines. 

The retention times of neutral non-ionized compounds can be predicted by the above calculation method, but those of ionized compounds are also very important. The inclusion of the dissociation constant in the calculation made it possible to predict the retention times of ionized aromatic acids.25,26 The dissociation constant was calculated by the method proposed by Perrin et al.27... 

The agreement between the observed and predicted k values of aromatic acids was within 10%. The correlation coefficient was 0.954 (n = 32). An error of greater than 10% for 3-hydroxy-2-naphthoic acid and 2-hydroxybenzoic acid was attributed mainly to an error in their K.A values.25 The partition coefficient, logP, and dissociation constant, pKA, of analytes can be obtained by simple calculations and by computational chemical calculations, and thus the retention time can be predicted in reversed-phase liquid chromatography. 

Smdies of the thermal degradation of several aromatic acids have been reported. Phthalic acid (80), but not isophthalic acid (81) or terephthalic acid (82), decomposes via dehydration to its anhydride at 140-160 °C. However, (81) and (82) and benzoic acid are thermally stable below 200 °C. Dissociation constants of all 19 isomers of methyl-substimted benzoic acids (83) have been measured in methanol and DMSO. From the pA a values, the substiment effects of the methyl groups were calculated and tentatively divided into polar and steric effects. Also, in the case... 

Fig. 8. Selected examples of aromatic donor molecules that form complexes with HRP C. The apparent dissociation constant for complex formation with the resting state plant enzyme is given (original references should be consulted for details of solution conditions and error estimations). (1) 2-Naphthohydroxamic acid (228) (2) benzhydroxamic acid (228) (3) 2-hydroxybenzhydroxamic acid (salicyUiydroxamic acid) (228) (4) benzhy-drazide (228) (5) cyclohexylhydroxamic acid (228) (6) 4-methylphenol (p-cresol) (192) (7) 2-methoxyphenol(guaiacol) (192) (8) indole-3-propionic acid(24i) (9)p-coumaric acid (238) (10) aniline (243).

Similar expressions have been obtained for the particular cases of mono-protic acids and bases, diprotic acids and bases, and zwitterions (207, 208), and in each case the data conformed well to Eq. (111). It has also been shown (207) that the acid dissociation constants can be determined by using reversed phase chromatography. The pIK, values of 10 aromatic acids calculated from chromatographic data by employing Eq. (91) were... 

Singlet excited state acid dissociation constants pK can be smaller or greater than the ground state constant pK by as much as 8 units. Phenols, thiols and aromatic amines are stronger acids upon excitation, whereas carboxylic acids, aldehydes and ketones with lowest >(71, ) states become much more basic. Triplet state constants pKr are closer to those for the ground state. Forster s cycle may be used to determine A pK =pK —pK) from fluorescence measurements if proton transfer occurs within the lifetime of the excited molecule. 

Organic functional groups exert characteristic electronic effects upon other groups to which they are attached. The quantitative expression of such effects can sometimes be correlated by linear Gibbs energy relationships. The best known of these is the Hammett equation, which deals with the transmission of electronic effects across a benzene or other aromatic ring. Consider the acid dissociation constants of three classes of compounds ... 

In addition to influencing the rate of a reaction, pH may also control the products where alternate or sequential pH-dependent reactions take place. An example of this type of reaction is the chlorination of phenol. Lee and Morris (37) have shown that the chlorination of phenol proceeds by the stepwise substitution at the 2, 4, and 6 positions of the aromatic ring. The rate of each of these reactions depends on the product of phenate or chlorophenate anion and the hypochlorous acid concentrations. Since each phenolic compound has a slightly different acid dissociation constant, the species of chlorophenols that are formed depend on the pH of the solution. 

Typically in aromatic systems, the inductive effect is transmitted about equally to the meta and para positions. Consequently, am is an approximate measure of a substituent s inductive effect whereas crp gives an approximate measure of a substituent s resonance effect. Consider the dissociation of benzoic acids in water. This process is assigned a reaction constant p of 1. The reaction is illustrated using Sub to represent a substituent. 

Affinities between NOSs and BH4 are stronger than those between aromatic amino acid hydroxylases and BH4, so the purified NOS from animal tissues still contain 0.2-0.5 BH4 molecules per heme moiety [128]. BH4 tightly binds to endothelial and neural NOSs with dissociation constants in the nanomolar range, and this binding is reported to stabilize the dimeric structure of NOS [129-131], whereas aromatic amino acid hydroxylases do not have BH4 in the proteins. BH4 functions as a one electron donor to a heme-dioxy enzyme intermediate. The BH4 radical remains bound in NOS and is subsequently reduced back to BH4 by an electron provided by the NOS reductase domain [128]. 

Tables 4 and 5 include several electron adducts of aromatic and olefinic carboxylic acids. The dissociation constants of these radicals are generally much higher than those of the parent acids because of the additional charge. It appears that one should not compare the value of 12-0 for the electron adduct (C6H5C02H) with pK = 4-2 for C6HsC02H. Instead, a comparison of the first pA = 5 3 for the conjugate acid of the electron adduct (C6HsC02H2)" seems more suitable. Similarly pK for the conjugate acid of the electron adduct of the C6HsC(OH)OCH3 (5-5) is comparable to that of the acid or...

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