Electrophilicity correlation with Hammett

The distinction between electrophilic and electron-transfer mechanisms of addition reactions to vinyl double bonds of ArX—CH=CH2 (X = S, O, Se) has been achieved by studying substituent effects. Specifically, the effects of meta and para substituents on the rates of electrophilic additions correlated with Hammett radical cations correlates with statistical tests. The ofclcctrophilicj/o-1 (FT) dichotomy is in accord with the conventional paradigm for cr/cr+ correlations and further support has been found by ah initio calculations. Interestingly, the application of this criterion to the reactions of aryl vinyl sulfides and ethers with tetracyanoethylene indicates that cyclobutanes are formed via direct electrophilic addition to the electron-rich alkene rather than via an electron-transfer mechanism.12... 

The effect of substituents on the rate constant for reaction of H with benzene was also examined. Correlation with Hammett s substituent constants was possible and showed that the hydrogen atom behaves as a slightly electrophilic reactant (Neta, 1972a, and references therein see also Brett and Gold, 1971, 1973 and photochemical studies by Pryor et al., 1973). 

Addition of OH to olefinic and aromatic compounds is also very rapid usually k = 109-1010 M -1 s"1. Despite the high rates, a reasonable correlation with Hammett s substitutent constants was obtained for the series of substituted benzenes and demonstrated the electrophilic behaviour of OH in its addition to aromatic compounds (Neta and Dorfman, 1968). 

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 ... 

The electrophilic character of n-perfluoroalkyl radicals was confirmed by a correlation of the rates of addition of the n-C8F17 radical to a series of para-substituted styrenes with Hammett o values, as shown in Fig. 3. The p value is negative (-0.53), as would be expected for an electrophilic reactant [115]. 

There are principally two different approaches of correlating experimental rate data of electrophilic substitution with reactivity indices (1) Correlating the index with the rate data of a given reaction, e.g. bromination. For example, a satisfying correlation of Dewar reactivity numbers with the log of rate constants of the bromination of benzene, naphthalene (1- and 2-position), biphenyl (4-position), phenanthrene (9-position), and anthracene (9-position) has been observed [55]. In correlations of this type the reactivity index corresponds to the reactivity constant in the Hammett equation while the slope of the linear correlation corresponds to the reaction constant (see also Sect. 3) (2) correlating the index with experimental a values. 

The numerous reactions and physical properties that can be correlated with electronic substituent constants suggest that they reflect a basic mechanism for the effect of the substituent on the reaction or the property. Many reactions were correlated by the Hammett equation, such as electrophilic (4, 31, 32, 33), nucleophilic (4, 34) and radical (35, 36, 37). Spectroscopic properties, such as infrared and ultraviolet absorption frequencies and intensities (38). nuclear magnetic resonance shifts of various nuclei, e.g., -H, F, (39), and mass spectroscopic ionization... 

An example of a quantitative SMR study correlating electronic properties and catalytic parameters is provided by the glutathione conjugation of para-substituted l-chloro-2-nitro-benzene derivatives (183). The values of log/j2 (second order rate constant of the nonenzy-matic reaction) and log (enzymatic reaction catalyzed by various glutathione transferase preparations) were correlated with the Hammett resonance cr value of the substrates, a measure of their electrophilicity. Regression equations with positive slopes and values in the range 0.88-0.98 were obtained. These results quantitate the influence of substrate electrophilicity on nucleophilic substitutions mediated by glutathione, be they enzymatic or nonenzymatic. 

From the results summarized in Table I, apparently the Brpnsted relationship will hold for all combinations of nucleophiles and electrophiles. Because, as pointed out previously, the Hammett equation is really a special case of the Brpnsted relationship, all the legion of nucleophile-electrophile, rate-equilibrium Hammett correlations that have been studied also fall under the scope of the Brpnsted relationship. For example, nucleophilicities of ArO , ArS , ArC(CN)2 , and the other families listed in footnote c of Table I have generally been correlated by the Hammett equation, where the acidities of benzoic acids in water are used as a model for substituent interactions with the reaction site (a), and the variable parameter p is used to define the sensitivity of the rate constants to these substituent effects. The Brpnsted equation (equation 3) offers a much more precise relationship of the same kind, because this equation does not depend on an arbitrary model and allows rate and equilibrium constants to be measured in the same solvent. Furthermore, the Brpnsted relationship is also applicable to families of aliphatic bases such as carboxylate ions (GCH2C02 ), alkoxide ions (GCH20 ), and amines (GCH2NH2). In addition, other correlations of a kinetic parameter (log fc, AGf, Ea, etc.) can be included with various thermodynamic parameters (pKfl, AG°, Eox, etc.) under the Brpnsted label. 

Attempts to relate the efficiency of inhibition with the Hammett— Taft equation were soon abandoned in favour of more accurate correlations with Brown s electrophilic substituent constants, o+, as given by [43]... 

The migratory reductive elimination process is consistent with the kinetic data reported for C-C reductive elimination from c/5-PdMe(C6H4-p-Y)(PEt2Ph)2 complexes (Scheme 9.5) [16], The rate constants exhibit a good Hammett correlation with Ojt values of Y, which are synthetic parameters introduced by Yukawa and Tsuno for isolating resonance effects. On the other hand, no correlation was observed with o or Op values. Positive sign of the p value (-1-3.2) indicates a major contribution of tt-electrophilicity of aryl ligand in the C-C bond formation. 

The rate of reaction of indole and 3-methylindole have been measured with a series of substituted benzenediazonium ions and give Hammett correlations with p of +3.4 and +3.8, respectively. The 3-methyl derivatives are about an order of magnitude slower. The second order kinetics, are consistent with a classical electrophilic substitution mechanism [7]. 

Rate data for the ozonolysis of a series of substituted styrenes in CCI4 at 25°C are summarized in Table 6.14. Do the data show a linear Hammett correlation with either tr, cr, or meta substituents in all three correlations.) If so, what is the value of p at 25°C What do these results suggest about the reaction mechanism Specifically, does the addition of ozone appear to be electrophilic or nucleophilic in nature ... 

The cyclobutane intermediate is not an irreversible sink for the catalyst, but remains reversibly linked to the catalytic cycle. In this mechanistic scenario, the enantioselectivity of the reaction does not depend on the difference of the activation energies for the electrophilic attack on the two diastereotopic faces of the enamine intermediate and is controlled, according to the Curtin—Hammett principle, by the relative stability and reactivity of the diastereomeric intermediates (cyclobutane and enamine of the Michael adduct) downstream in the catalytic cycle [58, 60]. A very recent detailed mechanistic study of another reaction catalyzed by diarylproUnol sdyl ethers, the a-chlorination of aldehydes by iV-chlorosuccinimide, also suggests that the stereochemical outcome of this process is not determined by the transition state of the electrophilic attack to the enamine, but instead is correlated with the relative stability and reactivity of the diastereomeric 1,2-addition products from the resulting iminium intermediate [60]. 

Hammett correlations also permit some insight into the reactivity and selectivity of electrophiles in aromatic substitution reactions. In general, the standard Hammett O substituent constant gives poor correlations with reactions involving electrophilic... 

Direct fluorination of aromatics is not a preparatively important reaction because it can occur with explosive violence. Mechanistic studies have been done at very low temperatures and with low fluorine concentrations. For toluene, the fp and fm values are 8.2 and 1.55, respectively, indicating that fluorine is a very unselective electrophile. The p value in a Hammett correlation with o- is -2,45. Thus, fluorination exhibits the characteristics that would be expected for a very... 

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