Palladium-catalysed amination of electron-deficient or relatively-rich benzo[b]...

• Author(s): Queiroz, Maria João R. P. ; Begouin, Agathe ; Ferreira, Isabel C. F. R. ; Kirsch, G. ; Calhelha, Ricardo C. ; Barbosa, Sandra ; Estevinho, Letícia M.
• Date: 2004
• Persistent ID: http://hdl.handle.net/1822/2015
• Origin: RepositóriUM - Universidade do Minho
• Subject(s): Amination; Antimicrobial activity; Benzothiophenes; Diarylamines; Fluorescence; Palladium
• Document Type: Article
• Language: English

Description

Several diarylamines in the benzo[b]thiophene series were prepared by palladium catalyzed amination of ethyl 3-bromobenzo[b]thien-2-yl carboxylate with anilines and 5-aminoindole, in good to high yields using Pd(OAc)2, BINAP, Cs2CO3 in toluene. The presence of the ester group in the position 2 of the benzo[b]thiophene moiety increases the yields and lowers the heating times when compared with reactions using 3-bromobenzo[b]thiophene. When aminopyridines, instead of anilines, were used the ligand and the solvent need to be changed to XANTHPHOS and dioxane in the amination reaction. From 2-aminopyridine a one pot C-N coupling and intramolecular cyclization involving the nitrogen of the pyridine, with lost of ethanol, occurred giving an interesting fluorescent tetracyclic heteroaromatic compound. The antimicrobial activity, the minimal inhibitory concentration (MIC) and structure-activity relationships (SAR) were evaluated. A selectivity with low MICs was observed against Bacillus Cereus and good results were also obtained against Candida albicans. The acids obtained by hydrolysis of the ester group, as non proteinogenic alpha,beta-unsaturated beta-amino acids can be incorporated in a peptide chain to induce conformational constraints.