The halogenation of alcohols under mild conditions expedited by the presence of substoichiometric amounts of thiourea additives is presented. The amount of thiourea added dictates the pathway of the reaction, which may diverge from the desired halogenation reaction toward oxidation of the alcohol, in the absence of thiourea, or toward starting material recovery when excess thiourea is used. Both bromination and chlorination were highly efficient for primary, secondary, tertiary, and benzyl alcohols and tolerate a broad range of functional groups. Detailed electron paramagnetic resonance (EPR) studies, isotopic labeling, and other control experiments suggest a radical-based mechanism. The fact that the reaction is carried out at ambient conditions, uses ubiquitous and inexpensive reagents, boasts a wide scope, and can be made highly atom economic, makes this new methodology a very appealing option for this archetypical organic reaction.
|Number of pages||11|
|Journal||Journal of Organic Chemistry|
|State||Published - 16 Oct 2020|
Bibliographical noteHighlight Information:
Featured in Org. Chem. Highlights: Functional Group Interconversion (https://www.organic-chemistry.org/Highlights/2021/28June.shtm) and in Org. Chem. Portal Abstracts: https://www.organic-chemistry.org/abstracts/lit7/577.shtm.
The Israel Science Foundation is gratefully acknowledged for an individual ISF grant 2316/19 (OR) that funded this research. The Open University and Ben-Gurion University of the Negev are greatly acknowledged for partial financial support. We thank Prof. Doron Pappo for his valuable comments and mechanistic insight into this manuscript.
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