Phenylacetic acids dissociation

The slope of the Hammett plot (p) does not bear a simple relationship with the transition-state structure (relative to ground state) because the model and the reaction or equilibrium in question are usually entirely dissimilar. Even the phenylacetic acid dissociation constants are not strictly comparable with those of benzoic acids because the polar effect is transmitted via different routes. 

Further data from the polarography and cyclic voltammetry in dimethylformamide are given in Table 5.1 for a series of overall two-electron processes leading to cleavage of a benzyl-heteroatom bond. The first electron transfer step is of the dissociative electron transfer type leading to a benzyl radical. This radical is reduced firrther, at the working potential, to the benzyl carbanion. The carbanion fi om benzyl chlorides, esters, ethers, sulphides, sulphones and quaternary ammonium salts can be trapped by carbon dioxide to form phenylacetic acid [2]. Reac-... 

The decreases in the pK of phenylacetic acid occasioned by replacement of the meta-hydrogen with Cl or N02 are -0.18 and -0.34, respectively, substantially less than for the benzoic acids. On the other hand, for the phenols the differences amount to -0.90 and -1.53, much greater than for the benzoic acids. The Hammett equation asserts that for reactions such as the dissociation of protons from phenylacetic acids or from phenols, the changes in AG occasioned by meta substitutions are proportional to the o values, i.e., to the changes in AG for the standard reaction - dissociation of a proton from benzoic acid.1, J... 

If we now examine the effect of substituents on another reaction, for example acid dissociation of phenylacetic acids (Equation 2.10), we can anticipate that the... 

Equation 6 of Chapter 3 can be applied to the dissociation of benzoic and phenylacetic acids (Scheme 1) and since Cp = Cp = -1 and e/ = c, = 0 the value of d is dlQAl, this is qualitatively acceptable for phenylacetic acid owing to the increase in distance between reaction centre and substituent d compared with that d) in benzoic acid. 

The parameters cr , cTp, and (7"p are for the dissociation constants of m-, / -substituted benzoic acids and of p-substituted phenols, fr m and o p are for the solvolyses of m- and p-substituted phenyldime-thyl carbinyl chloride in 90% acetone-water. 0° is for the reaction of hydroxide ion with the ethyl esters of substituted phenylacetic acids. 

Hammett also observed that substituents have a similar effect on the dissociation of other organic acids and bases. Consider the dissociation of phenylacetic acids ... 

Kq or K o represent equilibrium constants for unsubstituted compounds and K or K, for substituted compounds. Values for the abscissa are calculated from the dissociation constants of unsubstituted and substituted benzoic acid. Values for the ordinate are obtained from another organic acid or base with identical patterns of substitution, in this case phenylacetic acid. 

These constants were evaluated by the dissociation of meta-substituted phenylacetic acids and esters and were defined for a selected group of m-XC(,H4— substituents which exhibit a precise linear free energy relationship. Their values are independent of whether the process is rate or equilibrium, the solvent and reaction conditions. 

Comparison of the Hammett p values for phenylacetic acid ( + 0.47) and benzoic acid (-I-1.00) dissociation constants provides us with a measure of the transmission of the methylene group (0.47) compared with direct coupling. The ratio (0.47) is remarkably constant for attenuation of the polar effect down a methylene side chain and essentially the same value is obtained for the reaction of phenylacetic and... 

Fig. 9. Correlation of the dissociation constants of phenylacetic acids with sigma.

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). 

Lateral validation of CoMFA models with classic QSAR models was performed by comparing the informative content of PLS components (from CoMFA) with classic QSAR descriptors (e.g., Hammett s ct constant) for the dissociation constants of benzoic and phenylacetic acids. This approach, useful in comparing CoMFA to classical QSARs, could be routinely used in CoMFA studies. Kim s work illustrates the principle that classical QSAR should always be performed to complement CoMFA studies (see also final remarks). 

Hammett found, for example, that the nitro group has a stabilising effect on other dissociation reactions such as those of phenylacetic acid. He then proposed a quantitative relationship to account for such findings... 

Fiala G, Stetter KO, Jannasch HW, Langworthy TA, Madon J (1986) Staphylothermus marinus sp. nov. represents a novel genus of extremely thermophilic submarine heterotrophic archaebacteria growing up to 98 °C. Syst Appl Microbiol 8 106-113 Fischer A, Mann BR, Vaughan J (1961) Influence of pressure on the Hammett reaction constant dissociation of benzoic acids and phenylacetic acids. J Chem Soc 1961 1093-1097... 

Andraos, J., Chiang, Y, Kresge, A.J., PojarKefF, I.G., Schepp, N.P., and Wirz, J., The a-Cyano-a-Phenylacetic Acid Keto-Enol System. Flash Photolytic Generation of the Enol in Aqueous Solution and Determination of the Keto-Enol Equilibrium Constants and Acid Dissociation Constants Interrelating All Keto and Enol Forms in that Medium, /. Am. Chem. Soc., 116, 73, 1994. 

We can contrast primary and secondary isotope effects on equilibria, if we consider the ionization of phenylacetic acid. Carboxylic acids deutcrated in the hydroxyl group are characteristically less dissociated in water than the parent acids. Thus, for the two reactions ... 

Scheme 1 Dissociation of phenylacetic and benzoic acids having the same effective charge...

In the aniline and phenol equilibria, the hydrogen ion dissociates and removes one atom from the phenyl ring, whereas in the benzoic acid equilibrium two atoms are removed. Thus, substituents are able to exert a greater effect on the dissociation in aniline and phenol than in benzoic acid and the value of p is >1. In phenylacetic and phenylpropionic acids, the hydrogen ion dissociates and removes three and four atoms, respectively, from the phenyl ring. Substituents exert a lesser effect on the equilibrium in this case than on the benzoic acid... 

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