Acids, aromatic ionization constants

The aromatic acids resemble closely in chemical properties the acids derived from the paraffins, and yield similar derivatives. On account of the negative nature of the phenyl radical they are stronger than the fatty acids. The ionization constant of benzoic acid, CgHb.COOH, for example, is 0.0060, while that of acetic acid is 0.0018. 

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 ionization constants of a series of hindered polynuclear aromatic acids have been determined by Newman and Boden (1961). Two factors are held to affect the acidic strength of such acids the decrease of solvation and the inhibition of resonance due to steric effects. Solvation of an ion should be an acid-strengthening factor and if steric factors decrease the amount of anion solvation, the acid should be correspondingly weaker. The resonance factor only comes into play with aromatic (or unsaturated) acids. Here resonance would involve transfer of... 

Ionization Constants of some Aromatic Acids (Newman and Boden, 1961). See Fig. 4 for the numbering scheme... 

The reason for employing alternative treatments to ortho-substituted aromatic molecules is that changes in rate or ionization constants mediated by meta or para substituents are mostly changes in or because substitution does not affect AS or AS". Ortho substituents affect both enthalpy and entropy the effect on entropy is noteworthy because entropy is highly sensitive to changes in the size of reagents and substituents as well as degree of solvation. Bolton et al. examined the ionization of substituted benzoic acids and measured accurate values for AG, and A S... 

Some less reliable H bond interpretations of dissociation data have been made. For example, Dippy (526) proposed that a G—H- -O bond from 7 carbon to C=0 formed a ring in C4-Cg acids, to account for the fact that their ionization constants do not fall as rapidly as do those of C2 and Cs acids. A case in aromatic compounds is given by Arnold and Sprung (64). Some later work (907) makes use of the same idea to explain the Ka of a partially fluorinated valeric acid, (CF8(GH2)sGOOH). This scheme of H bonding hzis not been substantiated, and there is still controversy—the discussion at the end of one of Katch2ilsky s papers is illustrative (1089). 

In the aromatic series it has also been shown that the electron-withdrawing effect of the azido substituent is similar to those of the bromo and iodo groups. Smith, Hall and Kan have recorded the ionization constants of the ortho-, meta- and />ara-azidobenzoic acids and azidoanilines (Table 3) and from the Hammett-Burkhardt relationship these authors derived values for the constant of the azido... 

Define Hammett s constant for aromatic carboxylic acids and comment on the relationship of this constant with both ionization constant (K) and acid strength... 

A major breakthrough in theoretical organic chemistry resulted from the work of Hammett, around 1935. He derived Eqs. (3) and (4) to describe equilibrium constants K and rate constants k of various aromatic compounds by a certain reaction constant p, which depends on the reaction, and by substituent parameters a, which only depend on the nature of the substituents X of the corresponding aromatic compounds, based on hydrogen as a reference substituent p values are based on the ionization constants of substituted benzoic acids [9] ... 

The ionization-constants of a few aromatic acids are given below. The student will find it of interest to study the figures in connection with properties of the aromatic compounds which have been described, in the way exemplified above in the case of the dinitrobenzenes. 

U.v. spectroscopy gives evidence for the protonated species PhAsOsHj in aqueous perchloric acid solutions of phenyl- and substituted phenyl-arsonic acids. Ionization-constant data for a number of aromatic arsonic acids enable the calculation of Hammett a-values for the substituents — As03H2, — AsOgH", and —AsOg, and pK values have been obtained for solutions in dimethylformamide and dimethyl sulphoxide, showing that, relative to water, the solvents have a differentiating action. ... 

The basis of the extiathermodynamic approach is simple. Consider any property such as the heat of formation. The effect, for instance, of an amino group in benzene is assumed to be the same as its effect in any aromatic compound (e.g. toluene or any of the xylenes). The principle is best illustrated for the ionization constant of carboxylic acids in a number of solvents ... 

Hammett s reaction constants p for various aromatic parent compounds were obtained by letting p = 1 for the ionization constant of benzoic acid in an aqueous solution. Based on this assumption, values of p have been extensively tabulated (Jaffe, 1953 McDaniels and Brown, 1958 Wells, 1968 Shorter, 1982). His constants tr for different substituents to these aromatic parent compounds are also included in these references, along with exact procedures for finding the correct values. 

The use of a Hammett substituent constants in QSAR analyses has been prominent since the early studies by Hansch and Fujita (1964) in medicinal chemistry. The electron-withdrawing/releasing potency of substituents on an aromatic system has been formalized by the Hammett equation (Hammett, 1940). The relative reactivities among homologous series of compounds under defined conditions - for example, the logarithms of the rate and equilibrium constants for the hydrolysis of substituted benzoic acid esters (rate constant k) and the ionization constants (K) of the corresponding acids, were found to be linearly related ... 

Aromatic amines are considerably weaker bases than aliphatic amines. Compare, for example, values of for aniline and cyclohexylamine. The ionization constant for the conjugate acid of aniline is larger (the smaller the value of the weaker the base) than that for cyclohexylamine by a factor of 10 . 

Infrared spectra, of primary and secondary amines 17, 111-113 d-a Interaction 706 Intramolecular inversion, in nitroso-amide decomposition 449 in nitrous acid deaminations 469 Ionization constants, of aliphatic amino acids 221-223 of aminophenols 226 of aromatic amino acids 223-226 of nitrogen bases 227, 228... 

B. The Ionization Constants of Aromatic Amino Carboxylic Acids. ... 

Fluorescence Lifetimes and Quantum Yields (4> ) without Acids, Quenching Rate Constants (k, and Ionization Potentials (Ip ) in the Excited State of Aromatic Compounds at 300 K... 

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 ... 

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. 

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... 

---