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Published on: April 9, 2018
Mechanochemical Electron Donor-Acceptor (EDA)-Complex-Mediated Thioetherification Reaction via Site-Selective C-H
Roshan I Patel1, Barakha Saxena1, Anuj Sharma1
1Department of Chemistry, Laboratory for Light Assisted and Mechanochemical Practices, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
This study introduces a new method for making thioethers using ball milling and an electron donor-acceptor (EDA) complex strategy. This approach enables efficient C-H functionalization for C-S bond formation in medicinal chemistry.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- Thioether synthesis is crucial in medicinal chemistry.
- Existing methods often require harsh conditions or lack site-selectivity.
Purpose of the Study:
- To develop a novel, efficient, and site-selective method for thioether synthesis.
- To utilize mechanochemistry and nonphotochemical electron donor-acceptor (EDA) complex activation.
Main Methods:
- Employing a mechanochemical approach using ball milling.
- Utilizing aryl iodonium salts (acceptor) and potassium thiolate salts (donor) to form an EDA complex.
- Investigating the reaction mechanism through mechanistic studies.
Main Results:
- Achieved site-selective C-H functionalization for C-S bond formation.
- Demonstrated broad substrate scope including aromatic, heteroaromatic, and pharmaceutical derivatives.
- Obtained desired thioether products with excellent efficiency and regioselectivity.
- Confirmed the involvement of an EDA complex and a radical pathway.
Conclusions:
- The developed protocol offers a straightforward and versatile platform for thioether synthesis.
- The combination of mechanochemistry and EDA-complex activation is effective for C-S bond formation.
- This method holds potential for applications in medicinal chemistry and drug discovery.
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