A Mild, Efficient Approach for the Synthesis of 1,5-Disubstituted Hydantoins

Francesca Olimpieri, Maria Cristina Bellucci, Alessandro Volonterio, Matteo Zanda

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

An efficient and straightforward two-step procedure for the synthesis of N-1 alkyl/aryl-substituted hydantoins was developed, starting from easily available starting materials. The procedure envisages a highly regiospecific domino condensation/aza-Michael (nucleophilic substitution)/O -> N acyl migration between activated alpha,beta-unsaturated carboxylic acids or alpha-haloaryl acetic acids, respectively, and N-tert-butyl- or N-tritylcarbodiimides, leading to the regioselective formation of hydantoins bearing the tertiary alkylic substituent in the 3-position, followed by selective removal the substituent. This process avoids the use of harsh reaction conditions and toxic reagents and is high yielding. A detailed study of the influence of the structure of the reactants on the reaction outcome is presented. A wide variety of final products having a primary, secondary, cyclic and aryl substituent at the N-1 position were successfully synthesized by this method, ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Original languageEnglish
Pages (from-to)6179-6188
Number of pages10
JournalEuropean Journal of Organic Chemistry
Issue number35
Early online date2 Nov 2009
DOIs
Publication statusPublished - Dec 2009

Keywords

  • Domino reactions
  • Regioselectivity
  • Nitrogen heterocycles
  • solid-phase synthesis
  • alpha,beta-unsaturated carboxylic-acids
  • substituted hydantoins
  • pharmacological characterization
  • antiarrhythmic activity
  • acyl migration
  • cleavage step
  • binding-site
  • carbodiimides
  • derivatives

Cite this

A Mild, Efficient Approach for the Synthesis of 1,5-Disubstituted Hydantoins. / Olimpieri, Francesca; Bellucci, Maria Cristina; Volonterio, Alessandro; Zanda, Matteo.

In: European Journal of Organic Chemistry, No. 35, 12.2009, p. 6179-6188.

Research output: Contribution to journalArticle

Olimpieri, Francesca ; Bellucci, Maria Cristina ; Volonterio, Alessandro ; Zanda, Matteo. / A Mild, Efficient Approach for the Synthesis of 1,5-Disubstituted Hydantoins. In: European Journal of Organic Chemistry. 2009 ; No. 35. pp. 6179-6188.
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AB - An efficient and straightforward two-step procedure for the synthesis of N-1 alkyl/aryl-substituted hydantoins was developed, starting from easily available starting materials. The procedure envisages a highly regiospecific domino condensation/aza-Michael (nucleophilic substitution)/O -> N acyl migration between activated alpha,beta-unsaturated carboxylic acids or alpha-haloaryl acetic acids, respectively, and N-tert-butyl- or N-tritylcarbodiimides, leading to the regioselective formation of hydantoins bearing the tertiary alkylic substituent in the 3-position, followed by selective removal the substituent. This process avoids the use of harsh reaction conditions and toxic reagents and is high yielding. A detailed study of the influence of the structure of the reactants on the reaction outcome is presented. A wide variety of final products having a primary, secondary, cyclic and aryl substituent at the N-1 position were successfully synthesized by this method, ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

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