漫步 · 学术 | Reaction of the Day No. 001

Thiourea-Mediated Halogenation of Alcohols

Amar R. Mohite, Ravindra S. Phatake, Pooja Dubey, Mohamed Agbaria, Alexander I. Shames, N. Gabriel Lemcoff,* and Ofer Reany*

Department of Natural Sciences, The Open University of Israel, Ra’anana 4353701, Israel

—J. Org. Chem. 2020, 85, 12901.

KEYWORDS: Halogenation; alcohol; thiourea; bromination; chlorination; radical

ABSTRACT: 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.

Reaction of 1a with Alternative Additives.

Scope Exploration.

Gram Scale Synthesis of 2e and Recovery of NBS.

Proposed Mechanism of the Bromination of Alcohols in a Reaction Mixture Containing DMTU and NBS.

Summary and Comments:

以色列化学家Reany和Lemcoff发展了一种在温和条件下使用N-卤代丁二酰亚胺和硫脲将脂肪醇直接转化为卤代烃的方法。伯醇、仲醇和叔醇都能以良好到优异的产率进行羟基的卤代反应。该反应在室温下利用稍微过量的NCS或NBS与0.45当量DMTU即可高效地生成相应的卤代烷产物。作者还可以从丁二酰亚胺副产品部分回收NBS（净回收率约为60%)，因此该反应在化学合成工艺研究中有很好的应用前景。

Israel chemists, Reany and Lemcoff, disclosed an elegant method for the direct transformation of aliphatic alcohols into alkyl halides using N-halogenated succinimides and thiourea mediators under mild conditions. A broad substrate scope of primary, secondary, and tertiary alcohols were demonstrated to undergo net halogenfor hydroxyl exchange in good to excellent yields. The reaction utilizes a slight excess of either NCS or NBS in conjunction with substoichiometric DMTU at room temperature to cleanly generate the desired alkyl halide products. Partial (ca. 60% net) recovery of NBS from the succinimide byproduct provides improved sustainability as a feature of this process.