Benzoic acids, dissociation

Provided that the influence of the water-ethanol composition on the reaction involving addition of hydroxide ions to benzaldehydes can be characterized by any parameter Yj (the application of Y- used for benzoic acid dissociations in ethanol-water mixtures (28) might be doubtful), application of the relation pYt - pyo = C(Yi - Y0) would indicate that the value of C (0.638) for benzoic acids (28) and —0.573 for anilines (29) is close to zero for the benzaldehyde reaction (4). 

When added to a suspension, benzoic acid dissociates, with the benzoate anion adsorbing onto the suspended drug particles. This adsorption alters the charge at the surface of the particles, which may in turn affect the physical stability of the suspension. ... 

The Hammett equation is often employed even though the reaction under investigation is not similar to the reference benzoic acid dissociation. Effective charge cannot be obtained directly from equation (7) (Chapter 3) but can be obtained from the Hammett p values as shown for the example given below. 

The a values are always those determined from the ionization of substituted benzoic acids, but the p values are different for each substrate type and also for each reaction type because they reflect the sensitivity of the substrate to the electronic effect of the substituent. With p > 1, the ionization or reaction rate is more sensitive to substituent s electronic effects than is the ionization of benzoic acids. With p < 1, electron-withdrawing groups will increase the equilibrium constant or rate, but less than in benzoic acid dissociation. A negative p indicates that electron-donating groups increase the reaction constant. In consideration of reaction rates, a small r often indicates that the reaction involves either radical intermediates or some other pathway that requires little charge separation. 

The degree of dissociation decreases with increasing electrolyte concentration. With the dissociation constant for benzoic acid, K = 6.25 10 , the degree of benzoic acid dissociation in solution, with the concentration of 1.25 10 mol/L used as an example, is calculated to be a = 0.2. Therefore, such a solution contains 2.5 10 mol/L of oxonium and benzoate ions. Comparing such a benzoic acid solution with a sodium benzoate solution of the concentration c = 2.5 10 mol/L, an almost identical elution behavior for inorganic anions is observed. 

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. 

Figure 3-8 a) The dissociation of substituted benzoic acids (X = substituent), and b) the hydrolysis of benzoic acid methyl esters. 

Chemical Equilibria. In many cases, mass transfer between two Hquid phases is accompanied by a chemical change. The transferring species can dissociate or polymerize depending on the nature of the solvent, or a reaction may occur between the transferring species and an extractant present in one phase. An example of the former case is the distribution of benzoic acid [65-85-0] between water and benzene. In the aqueous phase, the acid is partially dissociated ... 

The influence of NH., and CO, on the chromatographic behaviour of benzoic acid and its derivatives (o-, m-, p-hydroxybenzoic, nitrobenzoic, aminobenzoic, chlorobenzoic acids) was studied. The work was carried out by means of upgoing TLC on Sorbfil plates. Isopropanol- and ethyl acetate-containing water-organic eluents were used as mobile phases in the absence or presence of gaseous modifiers in the MP. The novel modification of TLC has been found to separate benzoic acids with different values of their dissociation constants more effectively than water-organic mobile phases. 

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

Fig. 4.2. Conelation of acid dissociation constants of benzoic acids with rates of alkaline hydrolysis of ethyl benzoates. [From L. P. Hammett, J. Am. Chem. Soc. 59 96 (1937).]...

The numerical values of the terms a and p are defined by specifying the ionization of benzoic acids as the standard reaction to which the reaction constant p = 1 is assigned. The substituent constant, a, can then be determined for a series of substituent groups by measurement of the acid dissociation constant of the substituted benzoic acids. The a values so defined are used in the correlation of other reaction series, and the p values of the reactions are thus determined. The relationship between Eqs. (4.12) and (4.14) is evident when the Hammett equation is expressed in terms of fiee energy. For the standard reaction, o%K/Kq = ap. Thus,... 

A pKa of 3.6 means that p-(trifluoromethyl)benzoic acid is stronger than benzoic acid, whose pKa is 4.19. Thus, the trifluoromethyl substituent favors dissociation by helping stabilize the negative charge. Trifluoromethyl must therefore be an electron-withdrawing, deactivating group. 

First, let us assume that very little [H+] is Formed through dissociation of benzoic acid. This assumption implies that the concentrations of benzoate ion and benzoic acid are very little affected by reaction (42). Assuming this, we see that two of the concentrations in (39) are already specified ... 

The theory of titrations between weak acids and strong bases is dealt with in Section 10.13, and is usually applicable to both monoprotic and polyprotic acids (Section 10.16). But for determinations carried out in aqueous solutions it is not normally possible to differentiate easily between the end points for the individual carboxylic acid groups in diprotic acids, such as succinic acid, as the dissociation constants are too close together. In these cases the end points for titrations with sodium hydroxide correspond to neutralisation of all the acidic groups. As some organic acids can be obtained in very high states of purity, sufficiently sharp end points can be obtained to justify their use as standards, e.g. benzoic acid and succinic acid (Section 10.28). The titration procedure described in this section can be used to determine the relative molecular mass (R.M.M.) of a pure carboxylic acid (if the number of acidic groups is known) or the purity of an acid of known R.M.M. 

There is little information for fluoro-substituted sulfinyl groups. Values of a and ffp for SOCFj based on benzoic acid ionization are 0.63 and 0.69 respectively , compared with values of about 0.52 and 0.49 for SOMe (Table 3). Thus the electronegative fluorine somewhat enhances the electron-attracting influence of the sulfinyl function and makes the order more definitely sulfur lone pair to engage in 7t(pp) conjugation. Values of and ffp for SOCF3 based on anilinium ion dissociation are 0.76 and 1.05 respectively . An increase of 0.13 as between and [Pg.509]

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 ... 

Terabe, S., Yashima, T., Tanaka, N., and Araki, M., Separation of oxygen isotopic benzoic acids by capillary zone electrophoresis based on isotope effects on the dissociation of the carboxyl group, Anal. Chem., 60,1673, 1988. 

If we make the assumption that the reverse of reaction 15.5 is diffusion-controlled and assume that the activation enthalpy for the acyl radicals recombination is 8 kJ mol-1, the enthalpy of reaction 15.5 will be equal to (121 - 8) = 113 kJ mol-1. This conclusion helps us derive other useful data. Assuming that the thermal correction to 298.15 K is small and that the solvation enthalpies of the peroxide and the acyl radicals approximately cancel, we can accept that the enthalpy of reaction 15.5 in the gas phase is equal to 113 kJ mol-1 with an estimated uncertainty of, say, 15 kJ mol-1. Therefore, as the standard enthalpy of formation of gaseous PhC(0)00(0)CPh is available (-271.7 5.2 kJ mol-1 [59]), we can derive the standard enthalpy of formation of the acyl radical Af//°[PhC(0)0, g] -79 8 kJ mol-1. This value can finally be used, together with the standard enthalpy of formation of benzoic acid in the gas phase (-294.0 2.2 kJ mol-1 [59]), to obtain the O-H bond dissociation enthalpy in PhC(0)0H DH° [PhC(0)0-H] = 433 8 kJ mol-1. 

A significant contribution to the uncertainty interval assigned to the O-H bond dissociation enthalpy in benzoic acid comes from the estimate of the activation enthalpy for the radical recombination. The experimental determination of this quantity is not easy because diffusion-controlled recombination rate constants are very high (109 mol-1 dm3 s 1 or larger) [180]. Therefore, most thermochemical data derived from kinetic experiments in solution rely on some similar assumptions. 

Measurements of the dissociation constants of m-nitrobenzoic acid and p-nitrobenzoic acid began with Ostwald in 1889114. However, the first reasonably precise values were obtained by Dippy and coworkers in the nineteen-thirties, as part of an extensive study of the ionization of carboxylic acids by conductimetric methods115. The pKa values in water at 25 °C of m-nitrobenzoic acid and p-nitrobenzoic acid were found to be 3.493 and 3.425, respectively, compared with 4.203 for benzoic acid itself. On the basis of these values Hammett28,116 proposed 0 values of 0.710 for m-NOy and 0.778 for p-NOy (see Section II.A). These a values have commonly been used thereafter, often rounded to 0.71 and 0.78, respectively. 

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