Development of fluorescent chemosensor for boric acid and application as a high-throughput screening protocol in organic reactions

Abstract

Chemically, boron derivatives have become key chemicals used as final products or intermediates in many pharmaceutical and industrial substances since the development of the Suzuki-Miyaura cross-coupling. Since then, reactions such as Chan-Lam aminations, π-conjugated addition, C-H coupling, and protodeboronation have been developed. The most common by-product of reactions with boron derivatives is boric acid. In this reaction, the concentration of boric acid, a by-product, increases as the reaction progresses. That is, there is a correlation between the yield of the reaction and the amount of boric acid. Therefore, the development of the boric acid measurement method can be a general test method for various reactions using boron derivatives. In particular, the method using a chemosensor is suitable for processing a large number of samples at once, so it is suitable for high-throughput screening. However, there have been no studies based on chemosensors that obtained selectivity for boric acid over boronic acid derivatives. In this dissertation, fluorescence-based chemosensors are designed to solve this problem. Based on the design, four probes were synthesized: junolidine, a fluorophore, and salicylaldehyde imine, a receptor part for boric acid. Among these probes, a probe with high selectivity was selected through the experiment. This study demonstrated that fluorogenic discrimination of boric acid was achieved. This method showed high selectivity for ii boric acid over boronic acid, anions, and cations in optimal conditions. A detection range was obtained for concentrations up to 2 mM with quantitative titration experiments. Interaction studies were performed through NMR spectroscopy, MS spectromerty, and Job’s plot method. As a result, the probe and boric acid are 1:1 complexes. Furthermore, the correlation between the two methods was demonstrated in the actual SuzukiMiyamura cross-coupling was measured, and conversion and yield were analyzed through the classical GC method. In other words, it was proved that high-throughput screening protocol of the reaction was possible through boric acid measurement. It is expected that the developed protocol will contribute to the development of more efficient and more effective boron derivative-related catalysts and reactions