Synthesis 2019; 51(21): 4006-4013
DOI: 10.1055/s-0039-1690153
paper
© Georg Thieme Verlag Stuttgart · New York

Direct Access to Highly Functionalised Benzimidazoles and Benzoxazoles from a Common Precursor

Amanda Garrido
a  Laboratoire Synthèse et Isolement de Molécules Bioactives (SIMBA, EA 7502), Université de Tours, Faculté de Pharmacie, Parc de Grandmont, 31 Avenue Monge, 37200 Tours, France   Email: julien.petrignet@univ-tours.fr
,
Pierre-Olivier Delaye
a  Laboratoire Synthèse et Isolement de Molécules Bioactives (SIMBA, EA 7502), Université de Tours, Faculté de Pharmacie, Parc de Grandmont, 31 Avenue Monge, 37200 Tours, France   Email: julien.petrignet@univ-tours.fr
,
François Quintin
a  Laboratoire Synthèse et Isolement de Molécules Bioactives (SIMBA, EA 7502), Université de Tours, Faculté de Pharmacie, Parc de Grandmont, 31 Avenue Monge, 37200 Tours, France   Email: julien.petrignet@univ-tours.fr
,
Mohamed Abarbri
b  Laboratoire Physico-Chimie des Matériaux et des Electrolytes pour l’Energie (PCM2E, EA 6299), Université de Tours, Faculté des Sciences, Parc de Grandmont, 32 Avenue Monge, 37200 Tours, France
,
Pedro Lameiras
c  Institut de Chimie Moléculaire (ICMR CNRS UMR 7312), UFR Sciences Exactes et Naturelles BP 1039, 51687 Reims, France
,
Alain Gueiffier
a  Laboratoire Synthèse et Isolement de Molécules Bioactives (SIMBA, EA 7502), Université de Tours, Faculté de Pharmacie, Parc de Grandmont, 31 Avenue Monge, 37200 Tours, France   Email: julien.petrignet@univ-tours.fr
,
Jérôme Thibonnet
a  Laboratoire Synthèse et Isolement de Molécules Bioactives (SIMBA, EA 7502), Université de Tours, Faculté de Pharmacie, Parc de Grandmont, 31 Avenue Monge, 37200 Tours, France   Email: julien.petrignet@univ-tours.fr
,
Julien Petrignet
a  Laboratoire Synthèse et Isolement de Molécules Bioactives (SIMBA, EA 7502), Université de Tours, Faculté de Pharmacie, Parc de Grandmont, 31 Avenue Monge, 37200 Tours, France   Email: julien.petrignet@univ-tours.fr
› Author Affiliations
The authors are grateful to the French Ministry for Research and Innovation for the financial support.
Further Information

Publication History

Received: 01 July 2019

Accepted after revision: 22 July 2019

Publication Date:
06 August 2019 (eFirst)

Abstract

Benzoxazole and benzimidazole are commonly encountered heterocycles in medicinal chemistry and their functionalisation around 1-, 2-, 5-, and/or 6-positions provides a wide range of molecules of biological interest. In this manuscript, a straightforward preparation of diversely and highly substituted benzimidazoles and benzoxazoles on these positions, from a common starting material, a 3,3-dibromoacrolein, is described. Such acrolein derivatives are almost never described in the literature or used as ‘building-block’ for organic synthesis. The double electrophilicity of this substrate was found to be advantageous for condensation with two equivalents of various 1,2-diaminobenzene or 2-aminophenol derivatives. This one-pot reaction performed under metal-free and mild conditions allows the creation of three new carbon–heteroatom bonds and affords the desired heterocycles.

Supporting Information

 
  • References

  • 1 Dahl SL, Ward JR. Pharmacotherapy 1982; 2: 354
    • 2a Demmer CS, Bunch L. Eur. J. Med. Chem. 2015; 97: 778
    • 2b Zhang H.-Z, Zhao Z.-L, Zhou C.-H. Eur. J. Med. Chem. 2018; 144: 444
    • 3a Bansal Y, Silakari O. Bioorg. Med. Chem. 2012; 20: 6208
    • 3b Rajasekhar S, Maiti B, Balamurali M, Chanda K. Curr. Org. Synth. 2016; 14: 40
  • 4 Derenzini E, Zinzani PL, Cheson BD. Leuk. Lymphoma 2014; 55: 1471
  • 5 Wang S, Dai P, Xu Y, Chen Q, Zhu Q, Gong G. Arch. Pharm. 2015; 348: 595
  • 6 Roche VF. Am. J. Pharm. Educ. 2006; 70: 101
    • 7a Chanda K, Rajasekhar S, Maiti B. Synlett 2017; 28: 521
    • 7b Bakthadoss M, Mushaf M. RSC Adv. 2018; 8: 12152
    • 7c Bakthadoss M, Selvakumar R, Srinivasan J. Tetrahedron Lett. 2014; 55: 5808
    • 7d Nguyen TB, Ermolenko L, Al-Mourabit A. Green Chem. 2013; 15: 2713
  • 8 Shen W, Kohn T, Fu Z, Jiao X, Lai S, Schmitt M. Tetrahedron Lett. 2008; 49: 7284
    • 9a Tao K, Zheng J, Liu Z, Shen W, Zhang J. Tetrahedron Lett. 2010; 51: 3246
    • 9b Fan X, He Y, Zhang X, Guo S, Wang Y. Tetrahedron 2011; 67: 6369
  • 10 For a synthetic application of activated dibromoalkene, see: Taylor R, Beltrán-Rodil S, Edwards M, Pugh D, Reid M. Synlett 2010; 602
    • 11a Roedig A, Degener E. Chem. Ber. 1953; 86: 1469
    • 11b Kundiger DG, Morris GF. J. Am. Chem. Soc. 1958; 80: 5988
    • 11c Roedig A, Manger R, Schodel S. Chem. Ber. 1960; 93: 2294
    • 11d Bovonsombat P, McNelis E. Tetrahedron Lett. 1992; 33: 7705
    • 11e Paterson I, Kan SB, Gibson LJ. Org. Lett. 2010; 12: 3724
    • 11f Kamptmann SB, Brückner R. Eur. J. Org. Chem. 2013; 6584
  • 12 Knochel P, Vu VA, Marek I. Synthesis 2003; 1797
  • 13 McFadden HG, Harris RL. N, Jenkins CL. D. Aust. J. Chem. 1989; 42: 301
  • 14 CCDC 1892877 contains the supplementary crystallographic data for 2a. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
    • 15a Frigerio M, Santagostino M, Sputore S. J. Org. Chem. 1999; 64: 4357
    • 15b Ireland RE, Liu L. J. Org. Chem. 1993; 58: 2899