Greener and scalable mechanosynthesis of bis(3-indolyl)methane as an example of versatile pharmaceutical scaffold: Is the mechanochemical technique a metal-free process?

Abstract

The metal-free feature of mechanosynthesis of bis(3-indolyl)methane derivatives using poly(4-vinyl pyridine), a commercially available functional polymer, by ball mill technique at ambient conditions was studied. The condensation of various carbonyl compounds with two indoles smoothly proceeded, and pure products were easily isolated in high to excellent yields. Poly(4-vinylpyridine) exhibited high recyclability without any loss of catalytic activity or change in the chemical structure. The influence of polymer M̅W with a certain PDI on the mechanosynthesis of BIMs was investigated. In addition, the effect of the ball and jar with zirconium oxide material was studied on the rate and yield of the BIMs synthesis process. The method was scalable and generated minimal hazardous wastes. Some merits of the current methodology are such as the good to high yields for various carbonyl compounds and avoiding the use of toxic, expensive, and metal-containing catalysts with a tedious process of preparation, separation, and purification.

Graphical abstract

Keywords:

• Environmental protection
• multicomponent reaction
• solid-phase synthesis
• sustainable chemistry

Acknowledgments

The authors are thankful to Sari Agricultural Sciences and Natural Resources University, Iran, and the Universiti Malaya, Malaysia, for the partial support of this work.

Author contributions

Hoda Fahim: Methodology, Investigation, Data collection, Data curation; Peyman Mihankhah: Investigation, Data collection, Writing-original draft; Nader Ghaffari Khaligh: Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Validation, Writing - review & editing.

Disclosure statement

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

Additional information

Funding

This work was partially supported by a Research [Grant ST018-2022 and RU003-2021] from the Universiti Malaya, Kuala Lumpur, Malaysia.