Microwave-assisted synthesis of functionalized carbazoles via palladium-catalyzed aryl C–H activation and study of their interactions with calf-thymus DNA

Abstract

An efficient method is reported to prepare functionalized carbazoles in excellent yields under mild conditions through microwave-assisted Pd-catalyzed aryl C–H activation of 2-iodo-N-arylanilines. The use of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) as a base is found advantageous. Microwave is found beneficial to shorten the reaction time, improve yield, and reduce the amount of base and solvent consumption. Moreover, it offers the access to 4-acetylcarbazole, which was not obtained under conventional heating conditions. Interactions of carbazoles with calf-thymus DNA are investigated by monitoring the change in their photophysical properties. Experimental results hint that the dominant mode of binding of carbazoles with ct-DNA is groove binding in nature and thermodynamically favorable. The highest binding interaction is observed for 4-acetylcarbazole, and the reason behind unequal interactions for different carbazoles can be rationalized by considering the nature and position of functional groups at carbazoles which can affect H-bonding and hydrophobic interactions. Experimental results are in good agreement with molecular docking results.

Graphical Abstract

Microwave-assisted Pd-catalyzed synthesis of carbazoles and their interactions with ct-DNA is reported. Experimental results and docking study hint at groove binding as the dominant binding mode, and 4-acetylcarbazole shows the highest binding interactions.

Keywords:

• Calf-thymus DNA
• carbazole
• C–H activation
• molecular docking
• palladium

Acknowledgments

We thank Professor Hamid Dhimane, Université Paris Descartes, UMR 8601, for ¹H NMR, ¹³C NMR, and HRMS data.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

We thank SERB-DST, New Delhi for financial support under Grant No. SB/FT/CS-066/2013. R.K. is grateful to the Govt. of West Bengal. A.K. and A.R.M. are grateful to the CSIR, New Delhi, India for their fellowships.