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Synlett 2020; 31(08): 797-800
DOI: 10.1055/s-0039-1690832
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 2,4-Disubstituted Imidazoles via Nucleophilic Catalysis

Dmitrii A. Shabalin
a   A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky St, Irkutsk 664033, Russian Federation
,
Jay J. Dunsford
b   School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK
,
Simbarashe Ngwerume
b   School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK
,
Alexandra R. Saunders
b   School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK
,
Duncan M. Gill
c   Department of Chemical Sciences, University of Huddersfield, Queensgate Huddersfield, HD1 3DH, UK
,
Jason E. Camp  ∗
b   School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK
c   Department of Chemical Sciences, University of Huddersfield, Queensgate Huddersfield, HD1 3DH, UK
d   Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK   eMail: j.e.camp@hud.ac.uk
› InstitutsangabenWe gratefully acknowledge the financial support received from the Engineering and Physical Sciences Research Council (EPSRC, postdoctoral associateship for J.J.D. through First-Grant EP/J003298/1), a ­Pfizer Summer Research Fellowship (A.R.S.), the University of Nottingham (S.N.) and the Royal Society of Chemistry for a Researcher Mobility Grant (D.A.S.).
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Publikationsverlauf

Received: 07. Januar 2020

Accepted after revision: 31. Januar 2020

Publikationsdatum:
18. Februar 2020 (online)

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Abstract

A convergent, microwave-assisted protocol for the synthesis of disubstituted NH-imidazoles via nucleophilic catalysis is described. The substituted imidazoles are accessed via the intramolecular addition of a variety of amidoxime substrates to activated alkynes followed by a thermally induced rearrangement of the in situ generated O-vinylamid­oxime species. The unprotected imidazoles contain an aryl group at the 2-position as well as an ester moiety at the 4-position.

Key words

nucleophilic catalysis - imidazole - heterocycles - microwave - 19F NMR - rearrangement

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1690832.
  • Supporting Information
 

  • References and Notes


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  • 16 2,4-Disubstituted Imidazoles 4; General Procedure An oven-dried microwave vial was loaded with the desired amidoxime 2 (0.66 mmol) and DABCO (7.4 mg, 0.066 mmol), then methyl propiolate (55 mg, 0.66 mmol) in dry DMF (3 mL) was added under a nitrogen atmosphere. The reaction mixture was subjected to a two-stage microwave irradiation sequence (Stage 1: 80 °C, 15 min; Stage 2: 240 °C, 2 min). The mixture was concentrated under reduced pressure and the obtained residue dissolved in EtOAc (20 mL), washed with H2O (2 × 10 mL) and dried over anhydrous Na2SO4. The residue after solvent evaporation was purified by flash column chromatography on silica gel (PE/EtOAc) to afford the desired imidazole 4.
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