Electrophilic aromatic substitution inductive effect

Electrophilic substitution, aromatic, 31, 130-167, 381 1,2-ti. 1,4-addition, 195 as addition/elimination, 133 complexing with substituent, 160 deuterium exchange, 131,158 electronic effects in, 148, 158, 159 energetics of, 132, 136 field effect in, 152 hyperconjugation in, 153 inductive effect in, 22,152,153,156, 160... 

A tertiary carbonium ion is more stable than a secondary carbonium ion, which is in turn more stable than a primary carbonium ion. Therefore, the alkylation of ben2ene with isobutylene is much easier than is alkylation with ethylene. The reactivity of substituted aromatics for electrophilic substitution is affected by the inductive and resonance effects of a substituent. An electron-donating group, such as the hydroxyl and methyl groups, activates the alkylation and an electron-withdrawing group, such as chloride, deactivates it. 

Indolmycin, biosynthesis of, 864 Inductive effect. 37, 562 alcohol acidity and. 604 carboxylic acid strength and. 758 electronegativity and, 37 electrophilic aromatic substitution and, 562... 

The effect of monofluorination on alkene or aromatic reactivity toward electrophiles is more difficult to predict Although a-fluonne stabilizes a carbocation relative to hydrogen, its opposing inductive effect makes olefins and aromatics more electron deficient. Fluorine therefore is activating only for electrophilic reactions with very late transition states where its resonance stabilization is maximized The faster rate of addition of trifluoroacetic acid and sulfuric acid to 2-fluoropropene vs propene is an example [775,116], but cases of such enhanced fluoroalkene reactivity in solution are quite rare [127] By contrast, there are many examples where the ortho-para-dueeting fluorine substituent is also activating in electrophilic aromatic substitutions [128]... 

A quantitative description of the reactivity of monosubstituted benzenes to electrophilic substitution based on considerations of inductive effect parameters and con-jugative effect parameters from the 13 C chemical shifts of the aromatic compounds has been proposed.3 MO calculations on the proton migration in the ipso adducts formed in the reaction of CH3+ and SiH3+ with benzene have been described.4 With SiH3+ the ipso adduct is the most stable of possible isomers, whereas for CH3+ the >ara-protonated isomer is the most stable. 

This is so because the methyl substituent can affect the rate and the position of further substitution. A substituent can either activate or deactivate the aromatic ring towards electrophilic substitution and does so through inductive or resonance effects. A substituent can also direct the next substitution so that it goes mainly ortho/para or mainly meta. 

The aromatic ring is deactivated toward electrophilic aromatic substitution by the combined electron-withdrawing inductive effect of electronegative nitrogen and oxygen. The lone pair of electrons of nitrogen can, however, stabilize by resonance the ortho and para substituted intermediates but not the meta intermediate. 

Since Mills and Nixon studied in their original paper hydroxy derivates of fused aromatic systems like /3-hydroxyindan [1], we examined a series of model compounds possessing OH group attached at the /3-position [14], It was found that the hydroxy group exerted overwhelming influence on the electrophilic susceptibility of the aromatic carbons by substantial activation of its ortho positions. However, the free /3 position is the most active one because of the Mills-Nixon effect, which amplifies the OH inductive effect. Hence the selectivity in the electrophilic substitution reactions is governed once again by the MN effect [14]. 

The course of electrophilic aromatic substitution can be represented as shown in Figure 4.12 on the basis of inductive effects of the halogens alone, we would expect the order of reactivity to be X=H > Br > Cl > F. 

An alkyl group activates the ring to electrophilic substitution mainly through an inductive effect and directs attack to the 2- and 4-positions. Examples of these reactions will appear throughout the book in the chapters on functionalized aromatic compounds. 

We have seen that a substituent group affects both reactivity and orientation in electrophilic aromatic substitution by its tendency to release or withdraw electrons. So far, we have considered electron release and electron withdrawal only as inductive effects, that is, as effects due to the electronegativity of the group concerned. 

But certain groups (- rNH2 and OH, and their derivatives) act as powerful activators toward electrophilic aromatic substitution, even though they contain electronegative atoms and can be shown in other ways to have electron-withdrawing inductive effects. If our approach to the problem is correct, these groups must release electrons in some other w than through their inductive effects they are... 

The low reactivity of pyridine toward electrophilic aromatic substitution is due to a combination of factors. Most important is that the electron density of the ring is decreased by the electron-withdrawing inductive effect of the electronegative nitrogen atom. Thus, pyridine has a substantial dipole moment fi = 2.26D), with the ring carbons acting as the positive end of the dipole. Electrophilic attack on the positively polarized carbon atoms is therefore difficult. 

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