An Efficient Synthesis Of Phenol Via CuI/8-Hydroxyquinoline ...

Organic Chemistry Portal Abstracts An Efficient Synthesis of Phenol via CuI/8-Hydroxyquinoline-Catalyzed Hydroxylation of Aryl Halides and Potassium Hydroxide

Stefan Maurer, Wei Liu, Xiaojing Zhang, Yongwen Jiang*, Dawei Ma*

*State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200062, P. R. of China, Email: jiangywmail.sioc.ac.cn, madwmail.sioc.ac.cn

S. Maurer, W. Liu, X. Zhang, Y. Jiang, D. Ma, Synlett, 2010, 976-978.

DOI: 10.1055/s-0029-1219548

Abstract

A CuI/8-hydroxyquinoline-catalyzed direct hydroxylation of aryl iodides with KOH takes place at 100˚C in a mixed solvent system providing a broad range of phenols. Aryl bromides are less reactive under these reaction conditions.

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Details

This study presents an efficient method for synthesizing phenols via CuI/8-hydroxyquinoline-catalyzed hydroxylation of aryl halides using potassium hydroxide (KOH). The reaction occurs at 100°C in a mixed solvent system (t-BuOH–DMSO–H2O), yielding phenols with diverse substitution patterns. Aryl iodides are highly reactive under these conditions, achieving excellent yields (up to 98%), while aryl bromides are less reactive, producing lower yields. The optimized reaction conditions include 10 mol% CuI, 20 mol% 8-hydroxyquinoline, 4 equivalents of KOH, and the mixed solvent system, with a reaction time of 48 hours.

The study highlights the critical role of the solvent system and ligand selection in suppressing side reactions and improving yields. Functional groups such as nitro, carbonyl, carboxyl, and hydroxyl are well-tolerated, and ortho-substituted aryl iodides also yield phenols efficiently. However, substrates like methyl esters and nitriles undergo hydrolysis under these conditions. The method provides a cost-effective alternative to palladium-based systems, offering economic and environmental benefits. This protocol expands the scope of copper-catalyzed hydroxylation, enabling the synthesis of phenols with broad applicability in chemical, pharmaceutical, and materials industries.

Key Words

coupling, hydroxylation, 8-hydroxyquinoline, phenols