Synthesis of N-Aryl and N-Heteroaryl gamma-, delta-, and epsilon-Lactams Using Deprotometalation-Iodination and N-Arylation, and Properties Thereof

Rim Amara (1) , Ghenia Bentabed-Ababsa (1) , Madani Hedidi (1) , Joseph Khoury (2) , Hacan Awad (2) , Ekhlass Nassar (3) , Thierry Roisnel (4) , Vincent Dorcet (4) , Floris Chevallier (4) , Ziad Fajloun (2) , Florence Mongin (4)

1 Université d'Oran 1 Ahmed Ben Bella [Oran]
2 LU - Lebanese University [Beirut]
3 Université Ain Shams
4 ISCR - Institut des Sciences Chimiques de Rennes

Xanthone, thioxanthone, fluorenone, benzophenone, 2-benzoylpyridine, dibenzofuran, and dibenzothiophene were deprotonated using a base prepared in situ from MCl2TMEDA (M = Zn or Cd; TMEDA =N,N,N,N-tetramethylethylenediamine) and lithium 2,2,6,6-tetramethylpiperidide in a 1:3 ratio, as demonstrated by subsequent iodolysis. The different aryl halides were involved as partners in the N-arylation of pyrrolidin-2-one. In the presence of copper(I) iodide and tripotassium phosphate, and using dimethyl sulfoxide as solvent, the reactions could be performed in yields ranging from 40 to 70%. Most of the products were tested for their antimicrobial, antifungal, antioxidant, and cytotoxic (MCF-7) activity.

Keywords: C-N bond formation; deprotonative metalation; lactam; aromatic compound; antimicrobial activity; antifungal activity

Domains: Chemical Sciences

Rim Amara, Ghenia Bentabed-Ababsa, Madani Hedidi, Joseph Khoury, Hacan Awad, et al.. Synthesis of N-Aryl and N-Heteroaryl gamma-, delta-, and epsilon-Lactams Using Deprotometalation-Iodination and N-Arylation, and Properties Thereof. Synthesis: Journal of Synthetic Organic Chemistry, 2017, 49 (19), pp.4500-4516. ⟨10.1055/s-0036-1590798⟩. ⟨hal-01614770⟩