Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

Paola Vitale; Luciana Cicco; Ilaria Cellamare; Filippo M Perna; Antonio Salomone; Vito Capriati

doi:10.3762/bjoc.16.158

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

Beilstein J Org Chem. 2020 Aug 5:16:1915-1923. doi: 10.3762/bjoc.16.158. eCollection 2020.

Authors

Paola Vitale¹, Luciana Cicco¹, Ilaria Cellamare¹, Filippo M Perna¹, Antonio Salomone^{2

3}, Vito Capriati¹

Affiliations

¹ Dipartimento di Farmacia-Scienze del Farmaco, Università di Bari "Aldo Moro", Consorzio C.I.N.M.P.I.S., Via E. Orabona 4, I-70125 Bari, Italy.
² Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Prov.le Lecce-Monteroni, 73100 Lecce, Italy.
³ Dipartimento di Chimica, Università di Bari "Aldo Moro", Via E. Orabona 4, I-70125 Bari, Italy.

Abstract

We report that phenacyl azides are key compounds for a regiodivergent synthesis of valuable, functionalized imidazole (32-98% yield) and pyrimidine derivatives (45-88% yield), with a broad substrate scope, when using deep eutectic solvents [choline chloride (ChCl)/glycerol (1:2 mol/mol) and ChCl/urea (1:2 mol/mol)] as environmentally benign and non-innocent reaction media, by modulating the temperature (25 or 80 °C) in the presence or absence of bases (Et₃N).

Keywords: deep eutectic solvents; imidazoles; phenacyl azides; phenacyl halides; pyrimidines.

Grants and funding

This work was carried out under the framework of the national PRIN project “Unlocking Sustainable Technologies Through Nature-inspired Solvents (NATUREChem) (grant number: 2017A5HXFC_002) financially supported by the University of Bari “A. Moro” (codes: SFARMA.RicercaLocale.Vitale Fondi Ateneo 17-18, PernaF.18 FondiAteneo15-16, VitaleP.18 FondiAteneo15-16), the University of Salento, the Interuniversity Consortium C.I.N.M.P.I.S., and the Ministero dell’Università e della Ricerca (MIUR-PRIN).