Substitution reactions of indol

Attack at C-3 gives a carbocation that is resonance-stabilized by a nonbonded pair of electrons on the adjacent nitrogen. Attack at C-2 gives a cation in which the positive charge is not adjacent to an atom bearing nonbonded electrons. Any additional resonance contributors disrupt the benzenoid structure in the left ring. Therefore, electrophilic aromatic substitution reactions of indole occur primarily at C-3. 

The reaction of indole 1006 and xanthate 1001 (R = EtO) gave the ethyl l//-indol-2-ylacetate 1007 with high regioselectivity (Equation 237). It is worth noting that electrophilic substitution reactions of indole, including alkylation, occur at C-3 <2003CC2316>. 

An aqueous Friedel-Crafts reaction has also been used in polymer synthesis. The acid-catalyzed polymerization of benzylic alcohol and fluoride functionality in monomeric and polymeric fluorenes was investigated in both organic and aqueous reaction media. Polymeric products are consistent with the generation of benzylic cations that participate in electrophilic aromatic substitution reactions. Similar reactions occurred in a water-insoluble Kraft pine lignin by treatment with aqueous acid. A Bisphenol A-type epoxy resin is readily emulsified in aqueous medium with an ethylene oxide adduct to a Friedel-Crafts reaction product of styrene and 4-(4-cumyl)phenol as emulsifier.Electrophilic substitution reaction of indoles with various aldehydes and ketones proceeded smoothly in water using the hexamethylenetetramine-bromine complex to afford the corresponding Z A(indolyl)methanes in excellent yields.InFs-catalyzed electrophilic substitution reactions of indoles with aldehydes and ketones are carried out in water.Enzymatic Friedel-Crafts-type electrophilic substitution reactions have been reported. ... 

A practical and efficient electrophilic substitution reaction of indoles with a variety of aldehydes was carried out using catalytic trichloro-l,3,5-triazine (10 mol%) in acetonitrile to furnish the corresponding bis(indolyl)methanes 287 in excellent yields (Equation 46) <2004TL7729>. 

In Chap. 3, Sundberg, an indole pioneer and the author of the 1970 classic monograph The Chemistry of Indoles , covers thoroughly Electrophilic Substitution Reactions of Indoles , which is probably the most ubiquitous reaction of indole and one that continues to be extraordinarily useful in synthesis. 

In Chap. 4, Kishbaugh reviews the less well known but emerging Reactions of Indole with Nucleophiles , with a rich collection of both nucleophilic additions to electron-deficient indoles and nucleophilic substitution reactions of indole. 

Zeokarb-225 is a heterogenous, recyclable, eco-benign catalyst for the liquid-phase electrophilic substitution reactions of indoles with aldehydes or indole aldehydes to afford the corresponding bis(indolyl)methanes or tris(indolyl)methanes in good yields (Scheme 2.4). The catalyst is also effective for the synthesis of new diindolyl-carbazolylmethanes in good yields (Magesh et al. 2004). 

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