Fischer indole synthesis traditional methods

Interestingly, the Fischer indole synthesis does not easily proceed from acetaldehyde to afford indole. Usually, indole-2-carboxylic acid is prepared from phenylhydrazine with a pyruvate ester followed by hydrolysis. Traditional methods for decarboxylation of indole-2-carboxylic acid to form indole are not environmentally benign. They include pyrolysis or heating with copper-bronze powder, copper(I) chloride, copper chromite, copper acetate or copper(II) oxide, in for example, heat-transfer oils, glycerol, quinoline or 2-benzylpyridine. Decomposition of the product during lengthy thermolysis or purification affects the yields. 

Dimethylindole was obtained from phenylhydrazine and butan-2-one, by a one-pot reaction in water (Scheme 9.10, Eq. 1). This is the first example of water as the reaction medium for Fischer indole synthesis, and significantly neither a preformed hydrazone nor addition of acid was required. Also, the decarboxylation of indole-2-carboxylic acid to afford indole is not trivial by traditional methods. However, in water... 

The indole nucleus is a common and important feature of a variety of natural products and medicinal agents.2 The traditional approach for preparing the indole nucleus is the Fischer indole reaction.3 As this reaction has shortcomings, the palladium-catalyzed coupling of ortho-haloanilines is becoming an excellent alternative.4 Recently, the submitters disclosed a new and efficient method for indole synthesis using a palladium-catalyzed annulation between o-iodoanilines and ketones (Scheme I).5... 

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