Synthesis of Symmetric Bis(N-alkylaniline)triarylmethanes via Friedel-Crafts-Catalyzed Reaction between Secondary Anilines and Aldehydes

Rafael F A Gomes; Jaime A S Coelho; Raquel F M Frade; Alexandre F Trindade; Carlos A M Afonso

doi:10.1021/acs.joc.5b01875

Synthesis of Symmetric Bis(N-alkylaniline)triarylmethanes via Friedel-Crafts-Catalyzed Reaction between Secondary Anilines and Aldehydes

J Org Chem. 2015 Oct 16;80(20):10404-11. doi: 10.1021/acs.joc.5b01875. Epub 2015 Oct 5.

Authors

Rafael F A Gomes¹, Jaime A S Coelho¹, Raquel F M Frade¹, Alexandre F Trindade¹, Carlos A M Afonso¹

Affiliation

¹ Instituto de Investigação do Medicamento (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon , Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.

PMID: 26402221
DOI: 10.1021/acs.joc.5b01875

Abstract

The first general protocol for the preparation of symmetric triarylmethanes bearing secondary anilines by ytterbium-catalyzed Friedel-Crafts reaction of hetero(aryl) aldehydes and secondary anilines is reported. Mechanistic studies indicated that the iminium ion intermediate is the electrophilic partner. The reaction is greatly accelerated by high pressure (9 kbar) and showed a broad substrate scope on the hetero(aryl) aldehyde. The new triarylmethanes exhibited activity against HT-29 cancer cell lines, with the best result scoring an IC50 of 1.74 μM.

Publication types

Research Support, Non-U.S. Gov't