Benzene derivatives side-chain reactions

Although the application of the Hammett equation to side-chain reactions of disubstituted benzene derivatives (1) is relatively straightforward, the introduction of a heteroatom somewhere in the aromatic... 

The Hammett equation is the best-known example of a linear free-energy relationship (LFER), that is, an equation which implies a linear relationship between free energies of reaction or activation for two related processes48. It describes the influence of polar meta-or para-substituents on reactivity for side-chain reactions of benzene derivatives. 

The symbol k or K is the rate or equilibrium constant, respectively, for a side-chain reaction of a meta- or para-substituted benzene derivative, and k° or K° denotes the statistical quantity (intercept term) approximating to k or K for the parent or unsubstituted compound. The substituent constant a measures the polar (electronic) effect of replacing H by a given substituent (in the meta- or para-position) and is, in principle, independent of the nature of the reaction. The reaction constant p depends on the nature of... 

Quite early on (p. 361) in this discussion of linear free energy relationships consideration was restricted to the side-chain reactions of m- and p-substituted benzene derivatives. The reactions of o-substituted benzene derivatives, and indeed of aliphatic compounds, were excluded because of the operation of steric and other effects, which led to non-linear, or even to apparently random, plots. 

The Hammett equation is the best-known and most widely studied of the various linear free energy relations for correlating reaction rate and equilibrium constant data. It was first proposed to correlate the rate constants and equilibrium constants for the side chain reactions of para and meta substituted benzene derivatives. Hammett (37-39) noted that for a large number of reactions of these compounds plots of log k (or log K) for one reaction versus log k (or log K) for a second reaction of the corresponding member of a series of such derivatives was reasonably linear. Figure 7.5 is a plot of this type involving the ionization constants for phenylacetic acid derivatives and for benzoic acid derivatives. The point labeled p-Cl has for its ordinate log Ka for p-chlorophenylacetic acid and for its abscissa log Ka for p-chloroben-zoic acid. The points approximate a straight line, which can be expressed as... 

The partial rate factors af and /3f for the a- and /3-positions of thiophene have been calculated for a wide range of electrophilic reactions these have been tabulated (71 AHC(13)235, 72IJS(C)(7)6l). Some side-chain reactions in which resonance-stabilized car-benium ions are formed in the transition states have also been included in this study. A correspondence between solvolytic reactivity and reactivity in electrophilic aromatic substitution is expected because of the similar electron-deficiency developed in the aromatic system in the two types of reactions. The plot of log a or log /3f against the p-values of the respective reaction determined for benzene derivatives, under the same reaction conditions, has shown a linear relationship. Only two major deviations are observed mercuration and protodemercuration. This is understandable since the mechanism of these two reactions might differ in the thiophene series from the benzene case. 

Hammett, 1940) for the correlation of side-chain reactions of m- and -substituted benzene derivatives has been reviewed by Jaffe (1953), van Bekkum, Verkade, and Wepster (1959), and Pal m (1961). The two parameters are a, the substituent constant, and p, the reaction constant. A typical reaction which obeys eq. (1) is the methanolysis of... 

Other side-chain reactions of benzene derivatives also obey this simple relationship with good precision. Accordingly, the equation has proved very useful in the solution of a variety of problems involving structure, mechanism, and reactivity. 

The extension of the Hammett equation to poly-substituted benzene derivatives has been made for side-chain reactions (Jafife, 1953). The essential features of these treatments are the assumptions that the contribution of each substituent is constant and that the influences of the substituents are simply additive. This postulate is usually cited as the additivity principle. In the case of electrophilic substitution, assuming additivity, the equation may be written... 

Aromatic Substitutions Using Organometallic Reagents 790 17-14 Addition Reactions of Benzene Derivatives 796 Mechanism 17-9 The Birch Reduction 797 17-15 Side-Chain Reactions of Benzene Derivatives 798... 

Similar correlations between rate and equilibrium constants exist for various other side-chain reactions of benzene derivatives. The magnitude of p, which is called the reaction constant, is the slope of the line and varies with the reaction. The sign of p can be positive or negative according to whether the reaction rate is increased or decreased by the withdrawal of electrons. 

The symbol A or /Ts the rate or equilibrium constant, respectively, for a side-chain reaction of a meta- or para-substituiQd benzene derivative, and k or denotes the statistical... 

However, another type of reactions of benzene derivatives was studied by in-situ IR spectroscopy as well, viz. the side-chain alkylation of alkylbenzenes, for instance of toluene, over basic zeolite catalysts such as M -X zeolites (M=Na, K, Rb, Cs) [901,902]. The intermediate conversion of methanol to formaldehyde turned out to be crucial for the side-chain alkylation as well as a strong polarization of the methyl group of toluene, the preferential adsorption of toluene, and a sufficient basicity, i.e., base strength of the catalyst. Related to these IR studies of side-chain alkylation of toluene were in-situ IR spectroscopic investigations of the decomposition of methanol over basic zeolites (M+-X, M =Na+, K+, Rb, Cs+ Na-ZSM-5 and Cs-ZSM-5 [903]). It was shown that over weakly basic zeolites (Na-ZSM-5, Cs-ZSM-5) dimethyl ether was formed from methanol, whereas over more strongly basic X-type zeolites formaldehyde was produced, which is an indispensable intermediate for the side-chain reaction (vide supra). 

Another type of benzannulation, which might be related to the benzannulation of conjugated enynes, is the Pd-catalyzed cyclotrimerization of 1,3-diynes (Scheme 1,3-Diynes cyclotrimerize in the presence of a Pd catalyst to give 1,3.5-trisubstituted benzene derivatives. In this reaction, too, the regioselectivity is perfectly controlled as shown in Scheme 4, and other products were never isolated. The reaction of various diynes is summarized in Table 7. Some functional groups such as olefins and ether linkages may be present in the side chain. An example for the cross-cyclotrimerization of a diyne and an aUcyne has also been reported (Scheme... 

The work of Hammett and others in the early 1930s led to the formulation of the best known linear free energy relationship, the Hammett equation, which describes the influence of polar meta- or para-substituents on the side-chain reactions of benzene derivatives. This equation, its refinement in various ways, and its elaboration in the form of multiparameter extensions are the subjects of Section 2. 

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