Hammet correlation

Influence of Structural Moieties on Acidity Constants the Hammet Correlation... 

At constant acidity a second-order reaction is observed (first order in each component) (Eq. 5). The rate constants exhibit a Hammet correlation (p = -1.5), and a small isotopic effect is observed (kH/kD 1.51) ... 

For example, the oxidation of l-amino-3-arylguanidines by Ce(IV) was studied by Schelenz et al. (1982) in perchloric acid solutions for a homologous series of 17 substituted compounds at four different temperatures. The predominant products of this eight-equivalent oxidation are nitrogen and 3,6-diarylamino-l,2,3,5-terrazine compounds. For such well-defined systems, the resulting isokinetic and Hammet correlation relations calculated from the kinetic data present significant mechanistic information. 

The conclusions about the influence of azole ring substituents on the tautomeric equilibria are summarized in Table VIII. Although sufficient data are available for pyrazoles and imidazoles, it is difficult to correlate them within any well-defined scheme. The energy differences between pairs of tautomers are generally quite small and attempts to analyze these using, for example, the Taft-Topson model failed [95JCR(S)172]. In the case of mono-substituted compounds, Hammet-type equations... 

Halterman et al. agreed with this proposal to show the selectivity of 5-aryl-5-phenylcyclopentadiene favoring the reactions on the anti side of a more electron rich aromatic system with significant correlation between the Hammet constants for the aromatic substituents and the facial selectivity [19] (Scheme 29). 

In reactivity, the same series of mutagens exhibited positive Hammett correlations for AaiI acid catalysed solvolysis (p — + 0.32) and SN2 reactivity with A-methyl-aniline (p — + 1.7), hydroxide (p — +0.55) and L-cysteine ethyl ester (p — + 1.1), all reactions in which the benzoyloxyl group leaves with electrons and which are therefore accelerated by electron-withdrawing groups. The negative Hammet p-value for... 

In higher acidity, the rate constant may correlate better with (the Hammet-Deyrup acidity scale) than with the stoichiometric concentration of H+. Since nearly all the studies involve hydrolysis reactions, the depletion of the reagent water may be an important consideration also. 

The bipyridines are dibasic, and the two acid dissociation constants Ki and K2, for all the bipyridines have been determined. Typical values are recorded in Table I. There has been considerable interest in the first dissociation constants Ki of 2,2 -bipyridine and substituted 2,2 -bipyridines because of their use as metal complexing agents. In general, the order of relative basic strengths of derivatives of 2,2 -bipyridine is as expected. Electron-attracting substituents reduce the basicity, whereas electron-donating substituents increase the basicity of the molecule. " The dissociation constants of several substituted bipyridines correlate well with the Hammet equation. 2,2 -Bipyridines with an electron-donating substituent at position 4 are monoprotonated at N-1 and not at... 

Regression analysis is currently the most widely used correlative method in drug design. This is because it simplifies problems within a set of compounds by using a limited number of descriptors, notably the Hansch hydrophobic constant n, Hammet constants, or other electronic characteristics of substituents, and the Taft steric constant Eg. 

The same situation is encountered with a,/ -alkynic phosphonium salts in which C(a) carbons are strongly shielded vs C p) carbons 47.8-73.0 vs 119-127 ppm36,97. The linear correlation of the C(a) and C(P) chemical shifts with a para Hammet constant was illustrative of the polarization of the 7r-electron system in the C=C triple bond (Figure 8). In the same sense, the observed C(flt) and C(/J) chemical shifts were used to argue for the existence of either resonance hybrid structures as in the case of enaminophosphonium salts98,99 or incipient ylide contribution40. 

Figure 13.15 Effects of substituents on the base-catalyzed hydrolysis of benzoic acid ethyl esters in ethanoliwater (85 15) at 25°C. Relative reaction rates are correlated with Hammet Oj constants (data from Tinsley, 1979).

Para carbon shieldings, however, clearly follow the pattern described by the cannonical formulae. They may be correlated with the total charge densities Aq, obtained by CNDO calculations, according to eq. 4.14 [387], and with the Hammet a constants, as shown in... 

Possible methods of determining the extent of protonation include absorption spectroscopy at a wavelength for which species with n and fir-1 protons have different extinction coefficients, freezing point depression, and electrical conductivity (15). Of these, we have utilized only spectroscopy, which has the disadvantage that only the equilibrium constants for the most highly protonated states are accessible if, as is usual, the species with low protonation are insoluble. In this method, the extinction coefficient c of the compound is determined as a function of the H2SO4 content in the sulfuric acid solvent and correlated with the Hammet acidity function H0 (18) to give the pKB value of the protonated species,... 

It has been pointed out [52] that there is a correlation between the Hammet S (Tpara constants of the apical substituents and the redox potentials of the corresponding iron clathrochelates. Meanwhile, such a correlation is observed only inside the two groups of complexes with (a) OH, OCH3, F, Cl, and Br and (b) CH3, CsHs, and i-C4H9 substituents. No reasons are given for the existence of two groups of complexes. In spite of the fact that the cyclic voltammetry evidence indicates that the Fe +/ + couple is quasi-reversible, the electrolytic oxidation has failed to isolate stable iron(III) complexes [52]. 

The electrochemical behaviour of the ribbed-functionalized iron(II) [65, 68] and ruthenium(II) [78] clathrochelates with alkylamine, thioaryl, thioalkyl, phenoxyl and crown ether substituents in a-dioximate fragments was characterized by E1/2 values for Fe3+/2+ and Ru3+/2+ couples (Table 37). The Tomes criterion values of most complexes exhibited reversible or quasi-reversible anodic processes. Moreover, the quasi-reversible oxidation processes are accompanied by the formation of insoluble products followed by passivation of the working electrode. The Ev2 values depend on the electron-donating properties of the substituents in the ribbed fragments. The correlations of E1/2 values for Ru3" 2+ and Fe + 2+ couples with these substituents Hammet s Opara constants were observed in Refs. 65, 68, and 78. These correlations are rather qualitative, but they enable one to conclude that ruthenium complexes are less sensitive to the change of substituents in dioximate fragments. There was no correlation between the Em values and the inductive Taft s (cr,) constants for substituents in dioximate fragments. 

A good agreement between the Oi values and Hammet s constants is observed in some cases (Fig. 56). For sepulchrate and sarcophaginate cobalt(III)/cobalt(II) pairs with apical amino, methyl, and chlorine substituents, the Log/en values correlate with inductive constants of these substituents (Fig. 56). 

In principle, extrathermodynamic relationships that deviate from the simple Hammett equation (equation 8) can be treated by equation 14. The major problem is the determination of the different sets of o s, (e.g., set and 0 set) in a way that will indeed reflect their relation to independent properties. An example of such a procedure is the separation of polar and steric effects (10). The need for such a separation arose when a nearly complete lack of correlation was observed between substituent effects represented by the Hammet a constants and the rates for alkaline hydrolysis of aliphatic systems (12). Inspection of the structures indicated that the proximity of the substituents to the reaction site was a common feature. The steric interaction between R and X had to be considered separately from the electronic effects. Polar substituent constants were thus defined as the difference between the rate constants of base and acid catalyzed hydrolysis of esters. From the structural similarity of the transition states for these reactions (equation 15) it was assumed that the difference in their charge reflects only the polar effect of the substituent... 

Acid-base properties of oxide surfaces are employed in many fields and their relationship with PZC has been often invoked. Adsorption and displacement of different organic molecules from gas phase was proposed as a tool to characterize acid-base properties of dry ZnO and MgO [341]. Hammet acidity functions were used as a measure of acid-base strength of oxides and some salts [342]. Acidity and basicity were determined by titration with 1-butylamine and trichloroacetic acid in benzene using indicators of different pAg. There is no simple correlation between these results and the PZC. Acid-base properties of surfaces have been derived from IR spectra of vapors of probe acids or bases, e.g. pyridine [343] adsorbed on these surfaces. The correlation between Gibbs energy of adsorption of organic solvents on oxides calculated from results obtained by means of inverse gas chromatography and the acceptor and donor ability of these solvents was too poor to use this method to characterize the donor-acceptor properties of the solids [344],... 

The propensity for C-N vs. N-H activation correlates well with substituent Hammet parameters groups that increase the basicity of aniline increase the relative rate of N-H activation, suggesting that nucleophilic attack by the amine at an empty d /dy orbital of Ta(silox)3 preceeds oxidative addition. On the other hand, electron-withdrawing substituents decrease the rate of N-H activation and increase the rate of C-N activation, similarly to the effects observed on electrophilic aromatic substitution. Nucleophilic attack by the filled d a orbital of Ta(silox)3 is expected to occur at the arylamine ipso carbon preceding C-N oxidative addition. The carbon-heteroatom cleavages can be accomodated by mechanisms using both electrophilic and nucleophilic sites on the metal center. 

Thiazole exhibits a H NMR spectrum of first order. Table 3 lists the relevant chemical shifts for which a relationship exists with the calculated 7t-electron densities on the respective carbon atoms (to which the protons are bonded). Simple correlations were observed in other cases. For instance, a satisfactory linear relationship between the experimental S values and the calculated 7t-electron densities was found for bromothiazoles <84H(22)1077>. Correlations between the experimental d values of some substituted thiazoles and the Cp Hammet constants have been also reported <85SUL17>. 

Figure 11. Correlation of triboelectric charging with electronegativity, as measured by Hammet sigma function. (Reproduced from Ref. 66. Copyright 1975, American Chemical Society.)...

The rates of substituted benzaldehydes are correlated by a Hammet LFER with p = +3.76. 

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