Ionization constants, benzoic acids

About twenty years ago McDaniel and Brown (28) published their noclassic compilation of (j and Op constants based on the ionization constants of the corresponding benzoic acids. Since that time considerable numbers of new determinations of substituted benzoic acid ionization constants have appeared. As ffR constants are readily determined from Equation 80, it seemed worthwhile... 

For the purpose of systematizing kinetic and equilibrium data, for literally hundreds of reactions, it is desirable to have a single reference series for all. Hammett adopted as the standard the acid ionization constants for substituted benzoic acids in aqueous solution at 25 °C. This choice was fortunate because the compounds are stable and for the most part readily available. Also, their pA"a s can easily and precisely be measured for nearly every substituent. Thus, one constructs a plot according to either of the following equations, in which Eq. (10-4) constitutes a further example ... 

The cr-constants (Jaffe, 1953) are based on benzoic acid ionization data of greatly variable quality (McDaniel and Brown, 1958). In some cases the uncertainty in the pKA values introduces an uncertainty of + 0.1 unit in the Hammett cr-constants. To avoid the inclusion of this doubt in the cr+-constants only the thermodynamically based [Pg.88]

Sections 3.3.1 and 4.2.1 dealt with Bronsted acid/base equilibria in which the solvent itself is involved in the chemical reaction as either an acid or a base. This Section describes some examples of solvent effects on proton-transfer (PT) reactions in which the solvent does not intervene directly as a reaction partner. New interest in the investigation of such acid/base equilibria in non-aqueous solvents has been generated by the pioneering work of Barrow et al. [164]. He studied the acid/base reactions between carboxylic acids and amines in tetra- and trichloromethane. A more recent compilation of Bronsted acid/base equilibrium constants, determined in up to twelve dipolar aprotic solvents, demonstrates the appreciable solvent influence on acid ionization constants [264]. For example, the p.Ka value of benzoic acid varies from 4.2 in water, 11.0 in dimethyl sulfoxide, 12.3 in A,A-dimethylformamide, up to 20.7 in acetonitrile, that is by about 16 powers of ten [264]. 

The solvent isotope effect in the decarboxylation of 2,4-dihydroxy-benzoic acid is ( atcoohJhjO /( ArcooD)D,o = 6.25. The solvent isotope effect on the acid ionization constant of 2,4-dihydroxybenzoic acid has been determined separately, by potentiometric methods ... 

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. 

The relation between the constant of the para acid and that of the ortho or meta acid varies with the nature of the substituent. While p-nitrobenzoic acid is a slightly stronger acid than m-nitro-benzoic acid, the constant of p-chlorobenzoic acid is only about one-half that of the meta acid. The case of p-hydroxybenzoic acid is a striking one while o-hydroxybenzoic acid and m-hy-droxybenzoic acid are more highly ionized than benzoic acid, the constant of the para acid is less than half that of benzoic acid. A satisfactory explanation of such facts as these would, no doubt, materially advance organic chemistry. The effect of a phenyl radical on a carboxyl group in a side-chain, is shown by the constants for phenylacetic acid, hydrocinnamic acid, and cinnamic acid. 

Acid ionization constant of the substituted benzoic acid in water at 25°. 

Hammett plots. For phenylacetic acid ionization constants and for benzoic acid in ethanol. Data to generate these plots were taken from Bright W. L., and Briscoe, H. T. "The Acidity of Organic Acids in Methyl and Ethyl Alcohols." J. Phys. Chem., 37,787 (1933), and Dippy, J. F., and Williams, F. R. "Chemical Composition and Dissociation Constants of Mono-Carboxylic Acids. Part I. Some Substituted Phenylacetic Acids." /. Chem. Soc., 161 (1934). 

The best-known equation of the type mentioned is, of course, Hammett s equation. It correlates, with considerable precision, rate and equilibrium constants for a large number of reactions occurring in the side chains of m- and p-substituted aromatic compounds, but fails badly for electrophilic substitution into the aromatic ring (except at wi-positions) and for certain reactions in side chains in which there is considerable mesomeric interaction between the side chain and the ring during the course of reaction. This failure arises because Hammett s original model reaction (the ionization of substituted benzoic acids) does not take account of the direct resonance interactions between a substituent and the site of reaction. This sort of interaction in the electrophilic substitutions of anisole is depicted in the following resonance structures, which show the transition state to be stabilized by direct resonance with the substituent ... 

Table 19 3 lists the ionization constants of some substituted benzoic acids The largest effects are observed when strongly electron withdrawing substituents are ortho to the carboxyl group An o nitro substituent for example increases the acidity of benzoic acid 100 fold Substituent effects are small at positions meta and para to the carboxyl group In those cases the values are clustered m the range 3 5-4 5... 

In a series of organic acids of similar type, not much tendency exists for one acid to be more reactive than another. For example, in the replacement of stearic acid in methyl stearate by acetic acid, the equilibrium constant is 1.0. However, acidolysis in formic acid is usually much faster than in acetic acid, due to higher acidity and better ionizing properties of the former (115). Branched-chain acids, and some aromatic acids, especially stericaHy hindered acids such as ortho-substituted benzoic acids, would be expected to be less active in replacing other acids. Mixtures of esters are obtained when acidolysis is carried out without forcing the replacement to completion by removing one of the products. The acidolysis equilibrium and mechanism are discussed in detail in Reference 115. 

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,... 

We take the view of McDaniel and Brown that the Hammett substituent constants should be defined by Eq. (7-22). Table 7-1 lists many of these constants based on the ionization of meta- and para-substituted benzoic acids. 

Reactions that occur with the development of an electron deficiency, such as aromatic electrophilic substitutions, are best correlated by substituent constants based on a more appropriate defining reaction than the ionization of benzoic acids. Brown and Okamoto adopted the rates of solvolysis of substituted phenyldimeth-ylcarbinyl chlorides (r-cumyl chlorides) in 90% aqueous acetone at 25°C to define electrophilic substituent constants symbolized o-. Their procedure was to establish a conventional Hammett plot of log (.k/k°) against (t for 16 /wcra-substituted r-cumyl chlorides, because meta substituents cannot undergo significant direct resonance interaction with the reaction site. The resulting p value of —4.54 was then used in a modified Hammett equation. 

Next we turn to the magnitudes of the p constants. Evidently if p = 0, there is no substituent effect on reactivity. Moreover because p = -I-1.000 by definition for the aqueous ionization of benzoic acids, we have a scale calibration of sorts. Wiberg gives examples of p as a measure of the extent of charge development in the transition state. McLennan" has pointed out that p values must first be adjusted for the transmission factor before they can be taken as measures of charge devel-... 

The ortho effect may consist of several components. The normal electronic effect may receive contributions from inductive and resonance factors, just as with tneta and para substituents. There may also be a proximity or field electronic effect that operates directly between the substituent and the reaction site. In addition there may exist a true steric effect, as a result of the space-filling nature of the substituent (itself ultimately an electronic effect). Finally it is possible that non-covalent interactions, such as hydrogen bonding or charge transfer, may take place. The role of the solvent in both the initial state and the transition state may be different in the presence of ortho substitution. Many attempts have been made to separate these several effects. For example. Farthing and Nam defined an ortho substituent constant in the usual way by = log (K/K ) for the ionization of benzoic acids, postulating that includes both electronic and steric components. They assumed that the electronic portion of the ortho effect is identical to the para effect, writing CTe = o-p, and that the steric component is equal to the difference between the total effect and the electronic effect, or cts = cr — cte- They then used a multiple LFER to correlate data for orrAo-substituted reactants. 

LFER. Consider the rate of base hydrolysis of a series of ethyl benzoates given by d[C2HsOH]/dt = LfdALQ COOQHsHOH"]. Show that a plot of log Jfcx versus log Ka, where Ka is the ionization constant of the parent benzoic acid, should be linear, and relate its slope to that given by a conventional Hammett plot of log k versus a. 

An example of a reaction series in which large deviations are shown by — R para-substituents is provided by the rate constants for the solvolysis of substituted t-cumyl chlorides, ArCMe2Cl54. This reaction follows an SN1 mechanism, with intermediate formation of the cation ArCMe2 +. A —R para-substituent such as OMe may stabilize the activated complex, which resembles the carbocation-chloride ion pair, through delocalization involving structure 21. Such delocalization will clearly be more pronounced than in the species involved in the ionization of p-methoxybenzoic acid, which has a reaction center of feeble + R type (22). The effective a value for p-OMe in the solvolysis of t-cumyl chloride is thus — 0.78, compared with the value of — 0.27 based on the ionization of benzoic acids. 

For sets nos. 1, 2, and 3 of Table XXVII, eq. (1) appears to hold for ionization of ortho substituted benzoic acids (f =. 048 —. 058), with Kj = Pi I= 1.6 . 1. This result is reasonable for field effects transmitted only throu the molecular cavity i.e., the lines of force do not pass through appreciable solvent of high dielectric constant (the solvent is presumably excluded by the close proximity of the CO2H center and the substituent) (36). It is further of interest that eq. (1) fails for the ionization of ortho substituted benzoic acids in solvents of high OH content (sets nos. 4, 5, and 6 of Table XXVII). 

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