Electrophilic aromatic substitution reaction inductive effects

Since pyridine is an aromaric compound, we would expect it to exhibit reactions that are characteristic of aromatic systems. In fact, pyridine undergoes electrophilic aromatic substitution reactions however, the yields are generally quite low, because the inductive effect of the nitrogen atom renders the ring electron poor. High temperatures are required ... 

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 third possible explanation for the reduced reactivity of anisole and phenol compared to that of toluene could be that the former two substrates are deactivated towards electrophilic aromatic substitution by reaction of the alcohol or ether moiety with either the Lewis (BF3) - or Bronsted ( HBFV) acid. In this instance the first equivalent of acid would be consumed by reaction with the oxygen (Scheme 2.4), and the second equivalent effecting protonation of CO. Inductive deactivation of the aromatic ring by the cationic oxygen will result in reduced reactivity of the aromatic system. Since the positive charge resulting from complexation of phenol with BF3 on the phenolic entity could be neutralised by proton loss to the reaction medium, phenol is expected to be more reactive than anisole under the reaction conditions (Scheme 2.4). Additional support for this explanation is provided by the reported isolation of an anisole/HF/BFs complex containing a 1 1 2 ratio of reactants. 

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. 

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]. 

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. 

Kinetics of reacting I R = H, OMe with nucleophiles such as the enol of pentan-2,4-dione aromatic amines , phosphorus derivatives and some reactive aromatic compounds , and relative rates with substituted (cyclohexadienyl)Fe(GO)3 cation have been examined. These behave as classically expected, but in contrast to 1-or 2-OMe, a 3-OMe increases rate through its inductive effect. The kinetics agree with electrophilic substitution with the possible intermediacy of n complexes " . Because aryl (N-diene)Fe(CO)3 complexes can rearrange by dissociation into C-aryl derivatives", intermediates could also involve reaction with an N of an indole or a MeO (oxonium cation) of MeO-aromatics. 

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