page_title: Madelung synthesis
section_title: Synthetic applications
hierarchical_section_title: Madelung synthesis / Synthetic applications
caption_attribution_description: English: Synthesis of 2,6-diphenyl-1,5-diaza-1,5-dihydro-s-indacene
context_page_description: The Madelung synthesis is a chemical reaction that produces indoles by the intramolecular cyclization of N-phenylamides using strong base at high temperature.The Madelung synthesis was reported in 1912 by Walter Madelung, when he observed that 2-phenylindole was synthesized using N-benzoyl-o-toluidine and two equivalents of sodium ethoxide in a heated, airless, reaction. Common reaction conditions include use of sodium or potassium alkoxide as base in hexane or tetrahydrofuran solvents, at temperatures ranging between 200–400 °C. A hydrolysis step is also required in the synthesis. The Madelung synthesis is important because it is one of few known reactions that produce indoles from a base-catalyzed thermal cyclization of N-acyl-o-toluidines. The overall reaction for the Madelung synthesis follows.
context_section_description: The Madelung synthesis has many important applications in chemistry, biochemistry, and industrial chemistry. This reaction served useful in synthesizing, with an 81% yield, the architecturally complex tremorgenic indole alkaloid (-)-penitrem D, a molecule naturally produced by ergot fungus that causes various muscular and neurological diseases in livestock. Because this toxin ultimately causes significant economic problems in the livestock industry, understanding how to synthesize and easily decompose alkaloid (-)-penitrem D is of great importance. Nonetheless, the synthesis of such a complex molecule was, by itself, an incredible feat. 
   
  
  Another facet through which the Madelung synthesis has served useful is in the synthesis of 2,6-diphenyl-1,5-diaza-1,5-dihydro-s-indacene, from 2,5-dimethyl-1,4-phenylenediamine. 
   This synthesis was performed without modification to the Madelung synthesis, using sodium ethoxide base at a temperature of 320 – 330 °C. This indacene has shown to be an organic light-emitting diode that may have important applications for low-cost light displays in commercial industry.
caption: Madelung synthesis of 2,6-diphenyl-1,5-diaza-1,5-dihydro-s-indacene
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