Rapid Catalyst Screening by a Continuous-Flow Microreactor Interfaced with Ultra-High-Pressure Liquid Chromatography

被引：30

作者：

Fang, Hui ^{[1
]}

Xiao, Qing ^{[1
]}

Wu, Fanghui ^{[1
]}

Floreancig, Paul E. ^{[1
]}

Weber, Stephen G. ^{[1
]}

机构：

[1] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2010年 / 75卷 / 16期

基金：

美国国家科学基金会;

关键词：

FRIEDEL-CRAFTS REACTION; MICRO REACTORS; COMBINATORIAL LIBRARIES; ORGANIC-SYNTHESIS; BRONSTED ACIDS; CHEMISTRY; OPTIMIZATION; DISCOVERY; EPOXIDES; SCALE;

D O I：

10.1021/jo100981e

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A high-throughput screening system for homogeneous catalyst discovery has been developed by integrating a continuous-flow capillary-based microreactor with ultra-high-pressure liquid chromatography (UHPLC) for fast online analysis. Reactions are conducted in distinct and stable zones in a flow stream that allows for time and temperature regulation. UHPLC detection at high temperature allows high throughput online determination of substrate, product, and byproduct concentrations. We evaluated the efficacies of a series of soluble acid catalysts for an intramolecular Friedel-Crafts addition into an acyliminium ion intermediate within 1 day and with minimal material investment. The effects of catalyst loading, reaction time, and reaction temperature were also screened. This system exhibited high reproducibility for high-throughput catalyst screening and allowed several acid catalysts for the reaction to be identified. Major side products from the reactions were determined through off-line mass spectrometric detection. Er(OTf)(3), the catalyst that showed optimal efficiency in the screening, was shown to be effective at promoting the cyclization reaction on a preparative scale.

引用

页码：5619 / 5626

页数：8

共 63 条

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