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Synlett 2016; 27(01): 83-87
DOI: 10.1055/s-0035-1560317
letter
© Georg Thieme Verlag Stuttgart · New York

Continuous Synthesis of Hydantoins: Intensifying the Bucherer–Bergs Reaction

Julia L. Monteiro
a   Institute of Chemistry, University of Graz, NAWI Graz, Heinrichstrasse 28, 8010 Graz, Austria
b   Departamento de Química, Universidade Federal de São Carlos, São Carlos, 13565-905, SP, Brazil
,
Bartholomäus Pieber
a   Institute of Chemistry, University of Graz, NAWI Graz, Heinrichstrasse 28, 8010 Graz, Austria
,
Arlene G. Corrêa
b   Departamento de Química, Universidade Federal de São Carlos, São Carlos, 13565-905, SP, Brazil
,
C. Oliver Kappe*
a   Institute of Chemistry, University of Graz, NAWI Graz, Heinrichstrasse 28, 8010 Graz, Austria
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Publikationsverlauf

Received: 15. Juli 2015

Accepted after revision: 22. August 2015

Publikationsdatum:
17. September 2015 (online)

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Dedicated to Professor Steven V. Ley on the occasion of his 70th birthday

Abstract

A continuous Bucherer–Bergs hydantoin synthesis utilizing intensified conditions is reported. The methodology is characterized by a two-feed flow approach to independently feed the organic substrate and the aqueous reagent solution. The increased interfacial area of the biphasic reaction mixture and the lack of headspace enabled almost quantitative conversions within ca. 30 minutes at 120 °C and 20 bar even for unpolar starting materials. In addition, a selective N(3)-monoalkylation of the resulting heterocycles under batch microwave conditions is reported yielding potential acetylcholinesterase inhibitors.

Key words

continuous flow - process intensification - hydantoins - Bucherer–Bergs reaction - microwave-assisted organic synthesis

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1560317.
  • Supporting Information
 

  • References and Notes

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