One-pot sequential multi-component reaction: Synthesis of 3-substituted indoles

Abstract

Here, we have developed a 3-component one-pot sequential approach to 3-substituted indoles. The main advantages of this process are step economy, reduced waste, and operational simplicity. The method involves in situ generation of 3-indolylalcohols from the reaction of indoles and aldehydes in the presence of base. Further, nucleophilic substitution of 3-indolylalcohols with various nucleophiles affords 3-substituted indole derivatives. The reaction does not requires any hazardous and expensive metal catalyst. In addition, the reaction is carried out in (1:1) ethanol–water which is considered as environmentally benign solvent. On the other hand, nonsequential 3-component reaction results in the formation of unwanted bisindolylmethanes.

Graphical Abstract

Keywords:

• Alkylideneindolenine intermediate
• 3-indolylalcohol
• one-pot
• sequential transformation
• 3-substituted indole

Acknowledgements

We acknowledge Dr. S. Karmakar for collecting single-crystal X-ray data and the Sophisticated Analytical Instrumentation Facility (SAIF), Gauhati University, for use of the single-crystal X-ray diffractometer. We acknowledge Gauhati University, Indian Institute of Technology, Guwahati and National Chemical Laboratory, Pune for the NMR and Mass spectral facility.

Additional information

Funding

MLD is thankful to Science and Engineering Research Board (SERB), India [Grant No. SB/FT/CS-073/2014] for the financial support under “Fast Track” Scheme. PKB is also thankful to SERB, India [Grant No. SB/FT/CS-100/2012] for the financial support. PJB and BD acknowledge MHRD, Govt of India, for research fellowship under the TEQIP-III Project.