Intramolecular nucleophilic aromatic rearrangement

Intramolecular nucleophilic aromatic rearrangement. General scheme ... 

Smiles rearrangement Intramolecular nucleophilic aromatic rearrangement of activated aromatic substrates. 416... 

Excited-state intramolecular nucleophilic aromatic substitutions are known as photo-Smiles rearrangements. Ealier, these were reported for 2,4-dinitrophenyl ethers and. v-lriazinyl ethers32. The exploratory33 and mechanistic34 studies on photo-Smiles rearrangements of p-(nitrophenoxy)- >-anilinoalkanes were carried out (equation 28). 

Smiles rearrangement. Intramolecular nucleophilic aromatic substitution in alkaline solution resulting in the migration of an aromatic system from one heteroatom to another. 

The Smiles rearrangement occurs via an intramolecular nucleophilic aromatic substitution as shown below. ... 

This reaction was first reported by Fischer and Jourdan in 1883. It is a synthesis of indole derivatives by the treatment of aryl hydrazones coupled from aromatic hydrazines and ketones or aldehydes with either a mineral or Lewis acid. Therefore, it is generally known as the Fischer indole synthesis. In addition, it is also referred to as Fischer cyclization, Fischer indole cyclization, Fischer indole reaction, Fischer indolization, Fischer reaction, and Fischer indole annulation. Although the mechanism has been extensively studied, the one formulated by Robinson and Robinson is now generally accepted. It involves the following steps (a) initial acid-catalyzed tautomerization of an aromatic hydrazone to an ene-hydrazine, b) a [3,3]-sigmatropic rearrangement of ene-hydrazine to a M-imine intermediate, (c) re-aromatization to aniline, d) intramolecular nucleophilic attack to form aminal, and (e) extrusion of an ammonia to afford the indole. 

Despite both intramolecular and intermolecular mechanisms for the Chapman rearrangement having been postulated [28], it is the intramolecular one that has been confirmed by crossover experiments and isotopic labeling studies [29]. It has also been observed that the rearrangement follows first-order kinetics involving a nucleophilic aromatic substitution step [30]. 

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