Pschorr-Hoppe indole synthesis

Indole Ring Synthesis From Natural Products to Drug Discovery, First Edition. Gordon W. Gribble. 2016 John Wiley Sons, Ltd. Published 2016 by John Wiley Sons, Ltd. 

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Table 1 Applications of the Pschorr-Hoppe Indole Synthesis... 

In 1910 Robert Pschorr and Gerhard Hoppe reported the synthesis of indole via the reaction of o-nitrophenylace-tonitrile with tin foil and concentrated hydrochloric acid to give initially o-aminophenylacetonitrile. Subsequent treatment with sodium in boiling ethanol afforded indole (Scheme 1, equation 1) [1], The starting o-nitrophenylace-tonitrile was synthesized from o-nitrophenylacetic acid in a few steps. Although this simple synthesis of indole is first attributed to Pschorr and Hoppe, it was Makosza who greatly extended it by means of his vicarious nucleophilic substitution (VNS) of hydrogen as an efficient route to the prerequisite o-nitrophenylacetonitriles, as presented in Chapter 43. 

Without reference to Pschorr and Hoppe, Steven in 1925, in the context of a new aldehyde synthesis, prepared indole in 55% yield from o-nitrophenylacetonitrile using anhydrous stannous chloride and gaseous hydrogen chloride (Scheme 2, equation 1) [2]. The reduction of the nitrile proceeds to form initially the aldimine stannic chloride complex ([RCH=NH HClJ SnCl ), which can be isolated. 

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