Copper(0) Catalyzed C-N Coupling Approach for the Synthesis of Thiourea Linked Quinoline Analogues Using Aqueous Media: Rationale and Biological Study

Title:Copper(0) Catalyzed C-N Coupling Approach for the Synthesis of Thiourea Linked Quinoline Analogues Using Aqueous Media: Rationale and Biological Study

Volume: 12 Issue: 4

Author(s): Dhruvin R. Shah, Harshad P. Lakum and Kishor H. Chikhalia

Affiliation:

Keywords: 7-Aminoquinoline, anti-microbial, anti-tuberculosis, copper(0), ligand-free, rational drug design, thiourea, Ullmann C-N coupling.

Abstract: A convergent and facile synthesis of thiourea-based novel 1-(3-nitrophenyl)-3-(7- (substituted phenylamino/piperazino)quinolin-4-yl)thiourea derivatives is presented by approaching copper catalyzed Ullmann reaction. Pliable route was adopted to achieve amination on bioactive 4,7- dichloroquinoline analogous for the first time in which substituted amine/piperazine condensed with C-7 position of quinoline core. Presented C-N coupling reaction precedes fair to good yields. Cu(0) catalyzed synthetic route was also explained by discussing its probable mechanism. On the basis of currently available antimicrobial drugs, we rationalized the title compounds and examined their biological potency. Compound 3i proved to be the most potent antimicrobial derivative (36 mm, 0.39 μg/mL MIC) against B. cereus strain than standard Ciprofloxacin (31 mm, 0.39 μg/mL MIC). Compound 4e showed equipotent antituberculosis (99% inhibition, 6.25 μg/mL MIC) effect against H37Rv strain as compared to Pyrazinamide. Final analogues were characterized by IR, ¹H NMR, ¹³C NMR, mass spectroscopy and elemental analysis.

Cite this article as:

Shah R. Dhruvin, Lakum P. Harshad and Chikhalia H. Kishor, Copper(0) Catalyzed C-N Coupling Approach for the Synthesis of Thiourea Linked Quinoline Analogues Using Aqueous Media: Rationale and Biological Study, Letters in Organic Chemistry 2015; 12 (4) . https://dx.doi.org/10.2174/1570178612666150203005106