Intramolecular amination hydrazone reactions

As a specific kind of intramolecular amination, one can consider the oxidative cyclization of arylhydrazones of benzazolyl-2-ketones by the action of N-bromosuccinimide (67AG272) [Eq. (22)]. This reaction occurs most easily for hydrazones of benzimidazoles, and this process is more difficult in the case of benzothiazoles weakly basic hydrazones of benzo-xazolyl-2-ketones do not take part in this conversion. 

Anodic oxidation of azomethine, hydrazone, oxime, formazane, and semicarbazone structures has been used to initiate the intramolecular cyclization [119] under formation of heterocycles like triazoles [126,127], oxadiazoles [128,129], triazolinones [129], benzoxa-zoles [130,131], benzimidazoles [130,131], pyrazoles [132], indazoles [133], furoxanes [134], and tetrazolium salts [135] (see Chapter 18). Some of these reactions can be performed advantageously by indirect electrolysis using tris(4-bromophenyl)amin or 2,3-dihydro-2,2-dimethylphenothiazine-6(l/7)-one as mediators [119,136]. Two examples are given in Eqs. (19) and (20). 

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. 

The Mannich reaction and its variants have been reviewed, mainly focussing on asymmetric catalysis thereof. Catalytic, enantioselective, vinylogous Mannich reactions have also been reviewed, covering both direct and silyl dienolate methods. Another review surveys Mannich-type reactions of nitrones, oximes, and hydrazones. A pyrrolidine-thiourea-tertiary amine catalyses asymmetric Mannich reaction of N-Boc-imines (e.g. Ph-Ch=N-Boc) with ethyl-4-chloro-3-oxobutanoate to give highly functionalized product (16). Addition of triethylamine leads to one-pot intramolecular cyclization to give an 0-ethyl tetronic acid derivative (17). ... 

Lam and Raghavendra have also highlighted the synthesis of 1,2,3-triazoles through an intramolecular cyclization of a diazo intermediate that was generated from the Bamford-Stevens reaction between a tosyl hydrazone and abase. Polystyrene sulfonyl hydrazide 74 was treated with 1,1-dichloroacetone in THF to yield polymer-bound a-dichloro carbonyl sulfonylhydrazone 75 (Scheme 12.19). Alternative reaction of 74 with 1,1,1-trichloroace-taldehyde and pyridine derivatives yielded resin 76 and 77. When treated with excess amine,... 

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