Electrophilic substitution regioselectivity

Effect of substitutents on regioselectivity of electrophilic substitution in Hve-membered heterocycles... 

Selenophene, a colourless liquid, which, in contrast to thiophene, has an unpleasant smell, has mp -38°C and bp 110°C and is insoluble in water. Selenophene undergoes electrophilic substitution reactions typical of furan and thiophene. It reacts faster than thiophene but much more slowly than fiiran. Substitution occurs regioselectively in the 2- or 2,5-positions. 

Carbazole reacts with electrophiles faster than benzene. Substitution occurs regioselectively in the 3-position, e.g. in the Vilsmeier-Haack formylation. 

Lithiation reactions involving lV-methyl-3-substituted indoles are sometimes useful for introducing electrophiles regioselectively to C2. Comins [77] and Adam [78] reported regioselective C2-lithiations of indole substrates containing... 

Just as there is a marked difference m how methyl and tnfluoromethyl substituents affect the rate of electrophilic aromatic substitution so too there is a marked difference m how they affect its regioselectivity... 

The regioselectivity of substitution like the rate is strongly affected by the sub stituent In the following several sections we will examine the relationship between the structure of the substituent and its effect on rate and regioselectivity of electrophilic aro matic substitution... 

Why IS there such a marked difference between methyl and trifluoromethyl substituents m their influence on electrophilic aromatic substitution s Methyl is activating and ortho para directing trifluoromethyl is deactivating and meta directing The first point to remember is that the regioselectivity of substitution is set once the cyclohexadienyl cation intermediate is formed If we can explain why... 

The regioselectivity of substitution in furan is explained using a resonance descrip tion When the electrophile attacks C 2 the positive charge is shared by three atoms C 3 C 5 and O... 

Sections How substituents control rate and regioselectivity m electrophilic aro 12 10-12 14 matic substitution results from their effect on carbocation stability An electron releasing substituent stabilizes the cyclohexadienyl cation inter mediates corresponding to ortho and para attack more than meta... 

In view of the overall increased reactivity of furan compared with thiophene it would be anticipated that furan would be less regioselective in its reactions with electrophiles than thiophene. Possible reasons for the high regioselectivity of furan in electrophilic substitution reactions include complex formation between substrates and reagents and the ability of heteroatoms to assist in the stabilization of cationic intermediates (80CHE1195). 

What is the effect of a substituent on the regioselectivity of electrophilic aromatic substitution ... 

Would you expect the substituent —N(CH3)3 to more closel resemble —NfCHj), or —NO, in its effect on rate and regioselectivity in electrophilic aromatic substitution Why ... 

Section 12.15 When two or more substituents aie present on a ring, the regioselectivity of electrophilic aiomatic substitution is generally controlled by the directing effect of the more powerful activating substituent. 

As for regioselectivity in the electrophilic substitution reactions, we have assumed that introducing a methoxy group to the 1 position of indole nucleus might alter its positional reactivity. 

---