Electrophilic addition inductive effect

Electrophilic substitution of a disubstituted benzene ring is governed by the same resonance and inductive effects that affect monosubstituted rings. The only difference is that it s now necessary to consider the additive effects of two different groups. Tn practice, this isn t as difficult as it sounds three rules are usually sufficient. 

The carbonyl group also possesses electrophilic properties at the carbon atom and nucleophilic properties at the oxygen atom. Nucleophilic attack of the carbonyl group is favored if this is attached to an aromatic ring (inductive effect) and there is also a methoxy or phenolic OH group present in the 4-position. Changing a neutral reaction medium by proton addition has the same effect. 

A very similar situation is encountered in the electrophilic addition of unsymmetrical adducts (e.g. HBr) to vinyl halides (e.g. CH2=CHBr), where the inductive effect of halogen controls the rate, but relative mesomeric stabilisation of the carbocationic intermediate controls the orientation, of addition (p. 185). 

For the cycloreduction of keto-enones, competitive 1,4-reduction in response to the reduced electrophilicity of the carbonyl partner is observed. Diones are more susceptible to addition by viture of inductive effects and the relief of di-... 

In addition, due to the proximity and inductive effect of the indoline nitrogen, a metalation strategy provides for a facile synthesis of 7-bromoindoline, as well as other 7-substituted indolines. Thus, Iwao and Kuraishi find that IV-Boc-indoline (22) is smoothly lithiated at C-7 to give 7-lithio 23. Quenching 23 with suitable electrophiles gives 7-haloindolines 24-26, and quenching with tri-n-butylstannyl chloride affords the corresponding tin derivative in 65% yield [31]. 

It is well known that not all attempts to explain the reactivity of individual positions in electrophilic substitution reactions have been successful. There are three main lines along which attempts have been made to remove discrepancies between theory and experiment (for a summary, see ref. 147) (1) introduction into the HMO treatment of additional empirical parameters (inductive effect), (2) invoking the addition-elimination mechanism, and (3) invoking different reactivity of the protonated and unprotonated forms. 

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... 

Bromination of allylic positions cannot be achieved specifically by using elementary bromine, unless electrophilic addition to the rc-bond (Eq. 18) is unfavorable because the substituents have a high negative inductive effect. Efficiency of electrophilic addition of Br2 may also be diminished by steric effects. In addition to these secondary thermal reactions, the specificity of photochemical brominations of allylic positions using Br2 will also suffer from the competing (radical) addition of Br to the double bond (Eq. 19) [31]. 

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]... 

The effects of the cr—JT interaction on the ground-state properties of allyltrimethylmetal compounds are paralleled by the effect on reactivity towards electrophilic reagents. Mayr demonstrated that allyltrialkylsilanes, allyltrialkyl-germanes, and trialkylstannanes react with diphenylcarbenium ions at rates 105,5.6 x 105, and 109, respectively, relative to propene.158 The reaction rates were also found to be sensitive to the inductive effects of the other substituents attached to the metal. A theoretical evaluation of the factors determining the regiochemistry and stereochemistry of electrophilic addition to allylsilanes and other allyl systems is reported by Hehre et al.159 They predict a preference for electrophilic attack anti with respect to the silane substituent, a prediction that is supported by many experimental studies.82,160... 

Like hydrates, hemiacetals are not favored at equilibrium and, in general, cannot be isolated. The equilibrium is shifted in their favor by the inductive effects of electron-withdrawing groups, similar to the case of hydrates. In addition, the equilibrium is shifted in their favor if the alcohol nucleophile and carbonyl electrophile are part of the same molecule as in the following example ... 

---