Discovery of catalysts for amidation and transesterification reactions using fluorescence-based high-throughput screening methods

Abstract

Catalyst development for organic reactions often requires selecting highly active catalysts from numerous candidates, but traditional evaluation of catalyst activity is time-consuming and labor-intensive. To overcome these vulnerabilities, high-throughput screening (HTS) methods using colorimetric or fluorometric responses have been developed, which enable rapid sample processing using relatively inexpensive equipment compared to conventional analytical techniques such as chromatography, mass spectrometry, and nuclear magnetic resonance. In this study, we developed fluorescence-based HTS methods utilizing fluorescent probes to enable rapid catalyst evaluation for organic reactions. Using the developed HTS methods, the most efficient catalysts for amidation and transesterification reactions were identified, and the applicability of these selected catalysts were subsequently verified. Direct amidation of carboxylic acids with amines holds significant importance; therefore, catalytic processes involving boronic acids have undergone extensive investigation. However, studies focused on the amidation of aromatic carboxylic acids remain limited. Various boronic acid catalysts were evaluated for amidation using a new fluorescence-based HTS method that utilized the fluorescence turn-on characteristics of an anthracene-based probe in response to the amidation reaction. Our findings reveal that 2- hydroxyphenylboronic acid, previously deemed inefficient for aliphatic acids, effectively catalyzes the amidation of aromatic acids. The catalysts identified through this method consistently achieved high yields, reaching up to 98% across a broad spectrum of substrates. The development of heterogeneous metal oxide catalysts for transesterification reactions is crucial owing to their seamless reusability and environmental friendliness. In recent years, numerous studies have been conducted on rare-earth oxides, such as lanthanide metal oxides. Various metal oxides were screened for transesterification using another new fluorescence-based HTS method that employed ratiometric fluorescence change of a pyrene excimer probe. Praseodymium (IV) oxide yielded the highest catalytic activity among the prepared metal oxides. Various substrates were successfully transesterified, and biodiesel was also produced in a high yield (90%) from soybean oil through transesterification using the catalyst. The selected catalyst required minimal amounts for the transesterification of various organic substrates (0.7 mol%) and soybean oil (0.8 wt%).