LiO t Bu-promoted synthesis of bis(3-indolyl)methanes by the alkylation of indoles with alcohols under air

Hai Yen Nguyen; Thu Hue Tran; Ha Nam Do; Dang Van Do; Quoc-Anh Ngo; Nguyen Quyet Tien; Truong Thi Thanh Nga; Hien Nguyen; Tran Quang Hung; Tuan Thanh Dang

doi:10.1039/d3ra07115d

LiO t Bu-promoted synthesis of bis(3-indolyl)methanes by the alkylation of indoles with alcohols under air

RSC Adv. 2024 Jan 11;14(4):2341-2345. doi: 10.1039/d3ra07115d. eCollection 2024 Jan 10.

Authors

Hai Yen Nguyen¹, Thu Hue Tran¹, Ha Nam Do¹, Dang Van Do¹, Quoc-Anh Ngo^{2

3}, Nguyen Quyet Tien², Truong Thi Thanh Nga², Hien Nguyen⁴, Tran Quang Hung^{2

3}, Tuan Thanh Dang¹

Affiliations

¹ Faculty of Chemistry, VNU-Hanoi University of Science 19 Le Thanh Tong Hanoi 10000 Vietnam.
² Insitute of Chemistry, Vietnam Academy of Science and Technology (VAST) 18 Hoang Quoc Viet, Cau Giay Hanoi 10000 Vietnam.
³ Graduate University of Science and Technology, Vietnam Academy of Science and Technology (VAST) 18 Hoang Quoc Viet, Cau Giay Hanoi 10000 Vietnam.
⁴ Faculty of Chemistry, Hanoi National University of Education 136 Xuan Thuy, Cau Giay Hanoi 10000 Vietnam.

Abstract

Bis(3-indolyl)methanes (BIMs) are known for their important bioactivities, which include anti-cancer, anti-inflammatory, antibacterial, and antioxidant properties. In this study, we are disclosing a metal catalyst-free synthesis of BIMs in high yields via the alkylation reaction of indoles and alcohols in the presence of lithium tert-butoxide base. Notably, oxygen in air played an important role as an oxidant for the facilitation of this transformation. Interestingly, unactivated aliphatic alcohols could be successfully used as alkylating reagents in the alkylation reactions of indole. Especially, several chemical intermediates detected by GC-MS gave important information about the mechanism insights. This method demonstrated cost and environmental advantages for the development of green processes.