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Fischer Synthesis: History
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Contributor: Helena Kang

In the organic-synthesis taxonomy, Fischer synthesis denotes the Fischer indole synthesis, an acid-catalyzed conversion of an arylhydrazone into an indole. The arylhydrazone is normally formed by condensation of an arylhydrazine with an aldehyde or ketone. Dedicated reviews define the Fischer reaction as acid-promoted indole formation from an arylhydrazone [1]. Mechanistic studies describe tautomerization to an enehydrazine, carbon–carbon bond-forming rearrangement, cyclization, and ammonia elimination to establish the aromatic indole nucleus [2]. The nitrogen attached to the aryl group becomes the indole nitrogen, whereas the carbonyl substrate determines the substituents introduced into the five-membered ring. The process requires an arylhydrazone capable of enehydrazine formation and is therefore distinct from Madelung, Bartoli, and Larock indole syntheses, which use different precursors and bond-forming steps. Fischer glycosidation and Fischer esterification share the chemist's name but are separate reactions and are not included in this concept.

  • Fischer indole synthesis
  • arylhydrazone
  • enehydrazine rearrangement
  • indole

Organic Chemistry Synthesis Methods • Organic Chemistry • Chemistry • Physical Sciences

References

  1. B. Robinson; The Fischer Indole Synthesis. Chem. Rev. 1963, 63, 373-401, 10.1021/cr60224a003.
  2. Brian Robinson; Studies on the Fischer indole synthesis. Chem. Rev. 1969, 69, 227-250, 10.1021/cr60258a004.
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