Effect of Substituents on Substrate Reactivity

Contrary to the above expectations, the bromination of anisole (Tee and Bennett, 1984) and of phenols (Tee and Bennett, 1988a) in the presence of a-CD is not strongly retarded, so that some form of catalysis must occur. In some cases, actual rate increases are observed in spite of the several complexations that reduce the free reactant concentrations. Analysis of the effects of substituents on the kinetics leads to the conclusion that the catalysis by a-CD most probably results from reaction of CD-bound bromine with free substrate (12a) and that the a-CD-Br2 complex is 3-31 times more reactive than free Br2 towards phenols and phenoxide ions (cf. Tee et al., 1989). For the kinetically equivalent reaction of the substrate CD complex with free bromine (12b), the rate constants (A 2 ) for phenols do not correlate sensibly with the nature and position of the substituents, and for three of the phenoxide ions they have unrealistically high values, greater than 10u m 1 s . 

The effects of substituents on the form of the substrate reacting is nicely shown by comparison of the rate profiles for 9.27 and 9.33. 4-Pyri-done (9.27) exchanges as the free base even at H0 -10, whereas for its 2,6-dimethyl derivative (9.33), the reaction takes place mainly via the conjugate acid at // -— 3.5. 1,2,6-Trimethyl-4-pyridone (9.35) shows the changeover at even lower acidity (H0 -— 2.7). At high acidity, 9.33, 9.35, and 4-methoxy-2,6-dimethylpyridine (9.36) all react at similar rates and show similar dependence of rate upon acidity. This indicates that all react as the conjugate acids of type 9.37, and excludes the unlikely alternative 9.38. [In [68JCS(B)866], curve C of Fig. 3 refers to 4-methoxy-2,6-dimeth-ylpyridine, and not as stated]. At lower acidity the similarity in rate persists for 9.33 and 9.35, but 9.36 is much less reactive. Hence, the 4-pyridone 9.33 reacts as such and not as the 4-hydroxypyridine tautomer. 

The measured data also were used (700) in a quantitative representation of the effect of structure on the reactivity and adsorptivity of substrates by means of the Taft-Pavelich equation (22). The adsorption data suffered from a larger scatter than the rate data. No substrate or substituent could be detected that would fail to satisfy completely the correlation equations. In the correlation of the initial reaction rates and relative adsorption coefficients the parameter p was negative, while the parameter S was positive. In correlations of the reaction rates obtained by the hydrogenation of a similar series of substrates on the same catalyst in a number of solvents, the parameters p and had the same sign as in the hydrogenation in solvent-free systems, while in the correlation of the adsorption coefficients the signs of the parameters p and in systems with solvents were opposite to those in solvent-free systems. This clearly indicates that solvents considerably affect the influence of the structure of substrates on their reactivity. 

A similar approach has been chosen also in the evaluation of the effect of solvents on the reactivity and adsorptivity of unsaturated substrates. Parameters of solvents, formally resembling those of substituents used in the evaluation of the effect of structure, were defined. These parameters adequately described the effect of solvents on the course of hydrogenation in systems of similar compounds, but became unsatisfactory for other model series. A detailed analysis of these parameters revealed that they could not be freed from the effect of the structure of substrates, which obviously is the cause of their nontransfertibility. 

A dependence on [H+]" in the observed rate law suggests that TiOH + is the reactive reducing species. The reaction rates do not vary over a large range and show little correlation with the electronic effects of substituents on the substrates. This is explained by a balance between the ease of co-ordination to Ti " and the ease of electron transfer. 

Taft began the LFER attack on steric effects as part of his separation of electronic and steric effects in aliphatic compounds, which is discussed in Section 7.3. For our present purposes we abstract from that treatment the portion relevant to aromatic substrates. Hammett p values for alkaline ester hydrolysis are in the range +2.2 to +2.8, whereas for acid ester hydrolysis p is close to zero (see Table 7-2). Taft, therefore, concluded that electronic effects of substituents are much greater in the alkaline than in the acid series and. in fact, that they are negligible in the acid series. This left the steric effect alone controlling relative reactivity in the acid series. A steric substituent constant was defined [by analogy with the definition of cr in Eq. (7-22)] by Eq. (7-43), where k is the rate constant for acid-catalyzed hydrolysis of an orr/to-substituted benzoate ester and k is the corresponding rate constant for the on/to-methyl ester note that CH3, not H, is the reference substituent. ... 

Silyl ethers are among the most frequently used protective groups for the alcohol function. This stems largely from the fact that their reactivity (both formation and cleavage) can be modulated by a suitable choice of substituents on the silicon atom. Both steric and electronic effects are the basic controlling elements that regulate the ease of cleavage in multiply functionalized substrates. In plan-... 

It is a common understanding that the spatial arrangements of the substituents of a molecule have an crucial effect on whether an enzyme can accept the compound as a substrate. The effect of configuration on the difference of reactivities of enantiomers may be evaluated, as the two enantiomers can be separated and treated as individual starting materials and their products. In fact, promising models of enzyme-substrate interactions have been proposed that permit successful interpretation of the difference of reactivities between a given pair of enantiomers [29,30]. On the other hand, analysis of the reactivity of the conformational isomers of a substrate is rather difficult,because conformers are readily interconvertible under ordinary enzymatic reaction conditions. 

With information available regarding the quantitative effects of the heteroatoms on the reactivity of various systems, the correlation of the effects of heteroatoms on different reactions and different substrates could be examined. Mutual interactions with substituents and other het-... 

The effect of a substituent on the reactivity of a particular centre may be quantified in terms of the partial rate factor, The partial rate factor is defined as the rate of substitution at a given position relative to that in any one position in benzene itself. Partial rate factors may be calculated by treating an equimolar mixture of benzene and the substituted benzene with insufficient reagent to complete the reaction. Analysis of the products will then show which substrate has reacted with more of the reagent and at which centre. 

Quite a considerable number of papers deal with the effect of structure of olefinic substrates on their reactivity in the catalytic hydrogenation 65). Lebedev 66) attempted a generalization of the problem. His conclusion that the rate of hydrogenation of olefins decreases in the order monosubstituted - symmetric disubstituted - asymmetric disubstituted - trisubstituted tet-rasubstituted ethylene derivatives is called the Lebedev rule. Campbell 67) supplemented it by demonstrating that the rate of hydrogenation decreases with the number and size of substituents on carbon atoms of the double bond, cis isomers are usually hydrogenated more quickly than trans isomers, and olefins containing the terminal double bond are more reactive than those with the double bond inside the chain. 

In the case of foliol (16) the incubation with G. fujikuroi brought about the hydroxylation of the hexocyclic methylene with the formation of a 16p-Me and 16a-OH system (F) [114]. In these papers, hypotheses are formulated on the effect of the different substituents on the reactivity of the substrates [112-114],... 

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