4-Methyl-benzoic acid acidity constant

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. 

Example 4.3. The p value for alkaline saponification of methyl esters of substituted benzoic acids is 2.38, and the rate constant for saponification of methyl benzoate under the conditions of interest is 2 x 10 s . Calculate the rate constant for the hydrolysis... 

We have also correlated rate constants for the reaction of 3- or 4-substituted N,N-dimethylanilines with methyl iodide, 3- or 4-substituted benzoic acids with diphenyldia-zomethane and 3- or 4-substituted benzoyl chlorides with aniline with the MYT equation. The best regression equations obtained are ... 

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... 

The effect of various surfactants, the cationics-eetyl trimethyl ammonium bromide (CTAB), and cetyl pyridinium chloride (CPC), the anionic-sodium lauryl sulfate (SLS), and the nonionic-polysorbate 80 (Tween 80), on the solubility and ionization constants of some sparingly soluble weak acids of pharmaceutical interest was studied (Gerakis et al., 1993). Benzoic acid (and its 3-methyl-, 3-nitro-, and 4-tert-butyl-derivatives), acetylsalicylic acid, naproxen, and iopanoic acid were chosen as model drugs. The cationics, CTAB and CPC, were found to considerably increase th< ionization constant of the weak acidS Ka ranged from-0.21 to-3.57), while the anionic, SLS, showed a negligible effect and the nonionic, Tween 80, generally decreased the ionization constants Solubility of the acids increased in aqueous micellar and in acidiLed micellar solutions. 

One of the first reaction series studied involved triethylamine reacting with a series of methyl esters of substituted benzoic acids. A plot of the logarithm of the rate constant (Infe) versus the logarithm of the acid equilibrium constant (InRa) was linear. " In mathematical form, this is Eq. [2] where m is the slope and b the intercept. 

Protonation becomes a rapid reaction in protic solvents and in the presence of acids, as demonstrated for, e.g., -butyl acrylate in aqueous solution [207], methyl acrylate in EtOH [208], cinnamates in the presence of phenol in DMF [209], and benzaldehyde in ethanolic buffer solution [210]. Rate constants for protonation of aromatic radical anions (anthracene [211], naphthalene, 2-methoxynaphthalene, 2,3-dimethoxynaphthalene) by a number of proton donors including phenols, acetic acid, and benzoic acids in aprotic DMF were found to vary from 5.0 X 10 M- s-> (for anthracene, in the presence of p-chlorophenol) to 6.2 x lO s (for anthracene, in the presence of pentachlorophenol) [212]. For dimedone, PhOH, or PhC02H the rate of protonation depends on the hydrogen-bond basicity of the solvent and increases in the order DMSO < DMF MeCN [213],... 

The ff constants for the 4,6-dimethyl-s-triazinyl group were evaluated by two independent methods (1) from the pK values of m- and p-(4,6-dimethyl-2-triazinyl)benzoic acids (series 10) and (2) from the spectra of 4,6-dimethyl-2-(m-/p-fluorophenyl)triazines (series 9) in various solvents (74JOC2591). That the ff] values in alcoholic media and in DMSO are very close can be accounted for by the low protophilicity of heterocyclic nitrogen atoms of the triazine ring and by their small steric accessibility in the presence of two methyl groups in the ring. At the same time, the polarity of the medium exerts an appreciable effect on the value of the inductive constants (see Table XIII). 

By proceeding stepwise with a series of suitable indicators (Minnick and Kilpatrick, 68) the whole scale of relative acidity for any one solvent can be covered. Kilpatrick and Hears (69) have determined the relative acid strengths of the monosubstituted benzoic acids in the solvents methyl and ethyl alcohol and compared the results with the direct determinations of the equilibrium constants (Elliott and Kilpatrick, 70) for reactions as expressed in equation (23). Difficult extrapolations in equation (22) can be avoided if the indicator and other acid are of the same charge type. Measurements of this type yield relative acid strengths in a particular solvent without any nonthermodynamic assumptions. 

Catalytic supercritical water oxidation is an important class of solid-catalyzed reaction that utilizes advantageous solution properties of supercritical water (dielectric constant, electrolytic conductance, dissociation constant, hydrogen bonding) as well as the superior transport properties of the supercritical medium (viscosity, heat capacity, diffusion coefficient, and density). The most commonly encountered oxidation reaction carried out in supercritical water is the oxidation of alcohols, acetic acid, ammonia, benzene, benzoic acid, butanol, chlorophenol, dichlorobenzene, phenol, 2-propanol (catalyzed by metal oxide catalysts such as CuO/ZnO, Ti02, MnOz, KMn04, V2O5, and Cr203), 2,4-dichlorophenol, methyl ethyl ketone, and pyridine (catalyzed by supported noble metal catalysts such as supported platinum). ... 

The factor 2.48 puts a on the same scale as Hammett s er, and the k0 values are rate constants for acid and base hydrolysis of acetic acid esters (i.e., R is a methyl group in the reference compound). Usually R is an ethyl or methyl group, but in many cases the rate constants do not depend on the nature of R. Equation 8 is based on the fact that acid hydrolysis rates of substituted benzoic acid esters are only slightly affected by the nature of the substituent, but acid hydrolysis rates of aliphatic esters are strongly affected by substituents. These effects were taken to be caused by steric factors thus log(/c//c0)acid defines s. It is reasonable to assume that steric factors affect base-catalyzed rates in the same way. Substituent effects on base hydrolysis of aliphatic compounds are composed of both polar and steric effects, and subtraction of the latter yields a measure of the former. The parameter a is important because it allows one to evaluate substituent effects on aliphatic reaction rates by a formula analogous to the Hammett equation, or by a bivariate relationship, the Taft-Pavelich equation (Pavelich and Taft, 1957) ... 

The alcoholysis equilibrium (K) can be calculated from the respective esterification constants (Ki and K2) of methanol and ethanol with benzoic acid. If benzoic acid is heated with a mixture of methyl and ethyl alcohols, the following equilibriums occur [Eqs. (5) and (6)] ... 

A substituent in the position ortho to the carboxyl group has a marked effect on the ionization of the acid the constant of o-nitrobenzoic acid is one hundred times that of benzoic acid. It is remarkable that even a positive group, like methyl, in the ortho position brings about an increase in the constant the constant for o-toluic acid is twice that of benzoic acid. Such facts as this have not been explained. 

NB Robinson RA, Biggs AI, Ionization constants of p-aminobenzoic acid in aqueous solution at 25°, Ai4st. J. Chem., 10,128-134 (1957). Also reported benzoic acid (4.203) methyl p-aminobenzoate (2.465) efiiyl p-aminobenzoate (2.508) n-propyl p-aminobenzoate (2.487) and n-butyl p-aminobenzoate (2.472). 

CoMFA and related 3D QSAR approaches have been applied to correlate various physicochemical properties. Equilibrium constants of the hydration of carbonyl groups could be explained by a combination of C=0 bond order, steric, and electrostatic fields [1005]. 3D QSAR studies that correlate a, inductive, and resonance parameters of benzoic acids [1015, 1016] as well as pKg values ofclonidine analogs [1017] show that a H " field precisely describes such electronic parameters, e.g. (Jm.p of benzoic acids (n = 49 rpir = 0.976 snr = 0.082 Spress = 0.093). Steric parameters of benzoic acids, like surface area and van der Waals volume can be described by a steric field alone, while values of acetic acid methyl esters need a combination of both steric and electrostatic fields (n = 21 rpix = 0.984 Sfit = 0.133 SpREss = 0.209) [1016]. 

Comings and Briggs (20) studied the extraction of several solutes between benzene and water. For the extraction of benzoic acid, where the distribution favors the benzene, the major resistance to diffusion lay in the water phase. Addition of sodium hydroxide to the water reduced this resistance by causing a rapid chemical reaction, increased the mass-transfer coefficient, and made the effect of benzene rate on the over-all coefficient more pronounced, as would be expected. Similar experiences were obtained in the case of extraction of aniline, but in the case of acetic acid results were contrary to what was expected. The data apparently could be interpreted in terms of Eq. (10.11), with = 0.45 — 0.55,7 = 0 — 0.1, ri = 0.40 — 0.55, T = 0.45 — 0.55. Brinsmade and Bliss (13) extracted acetic acid from methyl isobutyl ketone (core) by water (w all). By making measurements at several temperatures, they were able to investigate the influence of Schmidt number on the rates and by graphical treatment of the data obtained values of the constants of Eq. (10.11) as follows j8 = 1, = 7 = 0,... 

The S. chrysormllus enzyme displays dififerent activities in the presence of a number of different benzene carboxylic acids tested as substrates (Table 2). The value of the equilibrium constant of the adenylate formation reaction, was increased when substituents such as an amino-, hydroxyl-, or methyl-groups in the 4-position were present, compared with benzoic acid alone. The same substituents in the 3-position resulted in a less pronounced response of the enzyme, whereas substituents in the Z-position were... 

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). 

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