title: Synthesis of fluorinated carbazoles via C-H arylation catalyzed by Pd/Cu bimetal system and their antibacterial activities.
abstract: An effective intramolecular C-H arylation reaction catalyzed by a bimetallic catalytic system Pd(OAc)2/CuI for the synthesis of fluorine-substituted carbazoles from corresponding N-phenyl-2-haloaniline derivatives under ligand free conditions is demonstrated. The established method is effective for both N-phenyl-2-bromoaniline and N-phenyl-2-chloroaniline, and requires the low loading of Pd(OAc)2 (0.5 mol%). A series of new fluorinated carbazoles were synthesized in excellent yields using the protocol (>83%, 19 examples) and were fully characterized by (1)H, (13)C and (19)F NMR spectral data, HRMS and elemental analysis. All compounds were evaluated for their antibacterial activities against four bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and methicillin-resistant S. aureus with resistance to gentamicin) by serial dilution technique. All tested compounds showed antibacterial activity against three test strains (S. aureus, B. subtilis and MRSA), and most of these compounds displayed pronounced antimicrobial activities against these three strains with low MIC values ranging from 0.39 to 6.25 μg/mL. Among them, compounds 7 and 14 exhibited potent inhibitory activity better than reference drugs meropenem and streptomycin. Three compounds (2, 4 and 5) showed antibacterial activity against E. coli. with MIC values from 12.5 to 25 μg/mL.
authors.affiliation: School of Chemistry and Chemical Engineering and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou, Jiangsu 221116, PR China.
authors.forename: Xianqiang
authors.initials: X
authors.lastname: Kong
authors.affiliation: School of Chemistry and Chemical Engineering and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou, Jiangsu 221116, PR China.
authors.forename: Huizi
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Chemical Engineering and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou, Jiangsu 221116, PR China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Cao
authors.affiliation: Key Laboratory of Biotechnology for Medical Plant of Jiangsu Province, Jiangsu Normal University, Xuzhou, Jiangsu 221116, PR China. Electronic address: zhousl@jsnu.edu.cn.
authors.forename: Shengliang
authors.initials: S
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun, Jilin 130012, PR China.
authors.forename: Guangsheng
authors.initials: G
authors.lastname: Pang
authors.affiliation: School of Chemistry and Chemical Engineering and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou, Jiangsu 221116, PR China. Electronic address: yhshi@jsnu.edu.cn.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects; D005461:Fluorine / Q000737:chemistry*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D002227:Carbazoles; D009942:Organometallic Compounds; D005461:Fluorine; D010165:Palladium; D003300:Copper
keywords: Anti-bacterial activity; Fluorinated carbazole; Intramolecular C–H arylation; Pd/Cu cocatalyst