Simple continuous flow synthesis of 3-indolyl naphthoquinone using acid catalysts

Abstract

The batch and continuous flow processes for the synthesis of 2-(3-indolyl)-1,4-naphthoquinone catalyzed by trifluoroacetic acid are reported. Continuous flow synthesis shows more efficient than batch synthesis. The flow system was easily assembled from commercially available tubing, a simple 3-way connector, and a set of peristaltic pumps. Using this system, a range of indoles and 1,4-naphthoquinone could be smoothly transformed under mild reaction conditions to the desired 2-(3-indolyl)-1,4-naphthoquinones in good to excellent yields and in short reaction times. Using the reactor greatly improved safety and additionally facilitated easy scaled up of the reaction.

Graphical Abstract

Keywords:

• Conjugate addition
• flow synthesis
• trifluoroacetic acid
• 1,4-naphthoquinone
• indole

Acknowledgments

We would like to thank the Faculty of science, Mahasarakham University (Grant year 2020) to Aekkaphon Mokkarat for his PhD research project, and the Thailand Research Fund (TRF), Mahasarakham University for their joint support through the Royal Golden Jubilee Ph.D. (RGJ-PHD) Program for financial support. We would like to express our gratitude to the Center of Excellence for Innovation Chemistry (PERCH-CIC), Ministry of Higher Education, Science, Research, and Innovation for instrument in this research. We would like to Laboratory Equipment Center and Department of chemistry, Mahasarakham University for their facilities during the research.

Disclosure statement

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

Additional information

Funding

This research was funded by the Royal Golden Jubilee PhD (RGJ-PHD) Scholarship Program, Thailand, Grant number PHD/0127/2558, and the Faculty of Science, Mahasarakham University, Thailand, Grant year 2020.