Electrophilic reaction polar effects

We will address this issue further in Chapter 10, where the polar effects of the substituents on both the c and n electrons will be considered. For the case of electrophilic aromatic substitution, where the energetics of interaction of an approaching electrophile with the 7t system determines both the rate of reaction and position of substitution, simple resonance arguments are extremely useful. 

Similarly, carboxylic acid and ester groups tend to direct chlorination to the / and v positions, because attack at the a position is electronically disfavored. The polar effect is attributed to the fact that the chlorine atom is an electrophilic species, and the relatively electron-poor carbon atom adjacent to an electron-withdrawing group is avoided. The effect of an electron-withdrawing substituent is to decrease the electron density at the potential radical site. Because the chlorine atom is highly reactive, the reaction would be expected to have a very early transition state, and this electrostatic effect predominates over the stabilizing substituent effect on the intermediate. The substituent effect dominates the kinetic selectivity of the reaction, and the relative stability of the radical intermediate has relatively little influence. 

The very small p- and m-values observed for the fast bromination of a-methoxystyrenes deserve comment since they are the smallest found for this electrophilic addition. The rates, almost but not quite diffusion-controlled, are amongst the highest. The sensitivity to polar effects of ring substituents is very attenuated but still significant that to resonance is nil. These unusually low p-values for a reaction leading to a benzylic carbocation are accompanied by a very small sensitivity to the solvent. All these data support a very early transition state for this olefin series. Accordingly, for the still more reactive acetophenone enols, the bromination of which is diffusion-controlled, the usual sensitivity to substituents is annulled. 

Correlation analysis of solvent effects on the heterolysis of p-methoxyneophyl tosyl-ate has been performed by using the Koppel-Palm and Kamlet-Taft equations. The reaction rate is satisfactorily described by the electrophilicity and polarity parameters of solvents, but a possible role for polarizability or nucleophilicity parameters was also examined. 

Rates of radical additions to alkenes are controlled mainly by the enthalpy of the reaction, which is the origin of regioselectivity in additions to unsymmetrical systems, with polar effects superimposed when there is a favorable match between the electrophilic or nucleophilic character of the radical and that of the radico-phile. For example, in the addition of an alkyl radical to methyl acrylate (2), the nucleophilic alkyl radical interacts favorably with the resonance structure 3. Polar effects are apparent in the representative rate constants shown in Figure 4.14 for additions of carbon radicals to terminal alkenes. Addition of the electron-deficient or electrophilic rert-butoxycarbonylmethyl radical to the electron-deficient molecule methyl acrylate is 10 times as fast as addition of... 

Polar effects can also be important in atom transfer reactions. 4 In an oft-cited example (Scheme 13), the methyl radical attacks the weaker of the C—H bonds of propionic acid, probably more for reasons of bond strength than polar effects. However, the highly electrophilic chlorine radical attacks the stronger of the C—H bonds to avoid unfavorable polar interactions. As expected, the hydroxy hydrogen remains intact in both reactions. 

This reasoning suggested that thiols might help in circumventing such a limitation on the basis of the strength of the S-H bond (384 kJ/mol in MeSH) and of the electrophilic properties of thiyl radicals. The aforementioned slow reaction would be replaced by a catalytic cycle of reactions, both of which will benefit from favorable polar effects 171... 

Polar effects in radical reactions seem also not quite well understood. There are some attempts to divide radicals into electrophilic and nucleophilic classes (Pryor, 1966 Pryor et al., 1969 Johnston et al., 1966) resembling the pattern of ionic reactants, generally on the basis of the Hammett equation. This classification, however, seems to be alien to the nature of most carbon radicals. In addition reactions (2) the Hammett />-value is usually positive (radical addition to substituted nitrobenzenes Bartlett and Kwart, 1950, 1952 Sinitsyna and... 

Except for extreme cases like this, radical reactions are generally not subject to strong polar effects. From the picture of C—H bonding in Chapter 1, we can deduce that the SOMO of a methyl radical is close to halfway between the local cr and cr orbitals of a C—H bond, so that the interactions should be more or less equally the SOMO with the HOMO and with the LUMO. In agreement, methyl radicals abstracting hydrogen atoms are found to be only marginally electrophilic. 

Despite these complications, the enormous and unique synthetic potential of radical reactions is also obvious. Radicals are highly reactive species and their addition to multiple bonds occurs easily, even with crowded substrates, under mild and essentially neutral conditions. Radical reactions are not generally sensitive to the influence of polar effects and tolerate the presence of functional groups otherwise incompatible with electrophilic and/or nucleophilic reagents. 

In contrast with other electrophilic additions, the peracid epoxidation is syn-stereospecific. With sterically strongly hindered alkenes the reaction takes place on the less sterically hindered side. In other cases, the stereochemistry of the reaction is affected by polar effects or the geometry of the transition state. Important conclusions regarding the mechanism of the reaction can be drawn from the steric pathways in the synthesis of the oxiranes. This has been dealt with comprehensively by Berti, who reviewed the topic up to 1971, with special emphasis on the peracid oxidation. A noteworthy account of the topic of peracid epoxidation is given in a review by Rebek. ... 

After some comments on what was named the medium polarity effect and the medium dielectric constant the authors came to the following conclusions such nucleophilic addition reactions of diphenylmagnesium compounds with ketones and metallation reactions of 1-alkynes have some common features. Apparently, they can both be considered as a special case of aromatic electrophilic substitution, differing from (what the authors named) the classical examples of this reaction, in that the latter one has a more pronounced reagent-like transition state. 

In particular, called resonance polar effect [Taft, 1956] is defined for any benzene derivative where there is no direct conjugation between substituent and reactive it can be considered constant for a particular solvent, therefore expressing resonance interactions between substituent and skeletal group. 6r is usually referred to as the effective resonance constant and of hold for electrophilic and nucleophilic reaction series, respectively. 

Among the various carbon-carbon and carbon-hetero atom bond forming reactions promoted or catalyzed by transition metals, allylic substitution via electrophilic n-allyl-complexes is of utmost importance. Studies focused on the synthetic potential of alkyl or aryl substituted ( n3-allyl)Fe(CO)4 1+) complexes have shown that nucleophilic attack by soft carbon and hetero atom nucleophiles preferentially proceeds regioselectively at the less or syn-substituted allyl terminus.4 Additionally, polar effects on the regioselectivity of this reaction caused by electron-withdrawing functionalities (e.g., CO2R, CONR2) have been examined by the... 

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