Hammett coefficients

Eq. 2 V/S is the volume to surface ratio Phi, the torsion angle between the C2 atom and the B ring o, the Hammett coefficient of the B ring dV, volume difference between substrate and flavonoid dL, length of the C3 side chain (p, dipole moment and C3, C5, and C4 the electron density occurring at these atoms. 

Hammett coefficients for oxidations of 2,6-di-t-butyl-4-X-phenols by t-BuOz in isopentane and Me2(CN)C02 in water are very similar over a temperature range of -40°C to 40°C, suggesting that SARs for other phenols which Table 15.7 lists can be used with moderate reliability to estimate rate constants for oxidations in water. 

Tp = Hammett coefficient, serving as a measure of the ability of the substituent to influence the electron density at the reaction center (tr -values are used for systems which come into contact with positively charged transition states) ... 

The main reaction in MeCN occurs through a base-catalyzed pathway involving formation of a zwitterionic intermediate, equilibrium formation of an anionic intermediate and a rate-limiting proton transfer to base, rate constant kc, followed by a fast leaving-group expulsion. The corresponding reactions in DMSO, however, are found to proceed by both uncatalyzed (via kh) and catalyzed pathways. Similar reactions in benzene show that the Hammett coefficient determined with substituted anilines for the catalyzed path is extremely large (p = —7.7) relative to that for the uncatalyzed path (p = —4.7). The Bronsted fix value (which may, however, be unreliable since the p fa(H20) values are... 

Reaction yields for substituted terephthalic acids are consistent with the Hammett coefficients, such that the more nucleophilic add salt is fevored in the reaction with the electron-poor lead chloride moiety. This is consistent with a nucleophihc attack (probably associative) on the lead atom as being the critical (rate-determining) step. 

In subsequent studies attempting to find a correlation of physicochemical properties and antimicrobial activity, other parameters have been employed, such as Hammett O values, electronic distribution calculated by molecular orbital methods, spectral characteristics, and hydrophobicity constants. No new insight on the role of physiochemical properties of the sulfonamides has resulted. Acid dissociation appears to play a predominant role, since it affects aqueous solubiUty, partition coefficient and transport across membranes, protein binding, tubular secretion, and reabsorption in the kidneys. An exhaustive discussion of these studies has been provided (10). 

C Hansch, RM Muir, T Fujita, PP Maloney, E Geiger, M Streich. The correlation of biological activity of plant growth regulators and chloromycetm derivatives with Hammett constants and partition coefficients. J Am Chem Soc 85 2817-2824, 1963. 

The Hammett equation is said to be followed when a plot of log k against a is linear. Most workers take as the criterion of linearity the correlation coefficient r, which is required to be at least 0.95 and preferably above 0.98. A weakness of r as a statistical measure of goodness of fit is that r is a function of the slope p if the slope is zero, the correlation coefficient is zero. A slope of zero in an LEER is a chemically informative result, for it demonstrates an absence of a substituent... 

If the activity coefficient term on the right of equation (13) stays constant with changing medium, then a linear correlation of log kx with -H0 should follow for the A-l mechanism. The above diagnosis of the A-l mechanism is known as the Zucker-Hammett hypothesis3. 

Kresge and Chiang15 showed that the dependence of rate coefficient upon the Hammett acidity function was not a safe criterion of mechanism and also explained how different dependencies of rate upon acidity function for different compounds could arise. Rate coefficients for detritiation of [3H]-2,4,6-tri-methoxybenzene followed the acidity function h0 in perchloric acid up to 3 M, i.e. k = 0.484 (Ao)1 07. so that a plot of log k versus —H0 would have a slope of 1.07, which implies the A-l mechanism. (New acidity function values479 would make this slope 1.14.) However, the diagnostic value of such a correlation was... 

In this, as in many catalysed reactions, the protonated substrate is postulated as an intermediate, and although the proposed reaction scheme in fact accords with all the known experimental facts it perhaps would be instructive to determine the dependence of the rate coefficient on the Hammett acidity function at high acid concentration and also to investigate the solvent isotope effect kD2JkH20. Both these criteria have been used successfully (see Sections 2.2-2.4) to confirm the intermediacy of the protonated substrate in other acid-catalysed aromatic rearrangements. 

The third approach is based on the correlation of rate coefficients with the Hammett acidity function, and is known as the Hammett-Zucker hypothesis. Although... 

White et al.1A have obtained similar kinetic results for the acid-catalysed rearrangement of N-nitro-N-methylaniline, i.e. a first-order dependence on the nitroamine with a linear H0 plot of slope 1.19 for phosphoric acid, and a deuterium solvent isotope effect of about three, although the results have only been presented in preliminary form. Further, an excellent Hammett a+ correlation was claimed for thirteen para substituted nitroamines which gave a p value of —3.9. Since it is expected that the rate coefficients would correlate with a (rather than different basicities of the amines, the a+ correlation implies that the amino nitrogen is electron-deficient in the transition state,... 

Jaffe (1953)52 showed that while many rate or equilibrium data conform well to the Hammett equation (as indicated by the correlation coefficient), many such data are outside the scope of the equation in its original form and mode of application. Deviations are commonly shown by para-substituents with considerable + Rot — R effect53. Hammett himself found that p-NOz (+ R) showed deviations in the correlation of reactions of anilines or phenols. The deviations were systematic in that a a value of ca. 1.27 seemed to apply, compared with 0.78 based on the ionization of p-nitrobenzoic acid. Other examples were soon discovered and it became conventional to treat them similarly in terms of a duality of substituent constants . 

Hammett s coefficient, in relation with deviation theoor, 71... 

---