Participation of the cyanide group in the reaction mechanism of benzoxazole formation: Monitoring by continuous flow cell NMR

Benzoxazoles are compounds of considerable interest in the field of organic synthesis. The advancement of materials chemistry has led to the development of new materials with diverse applications, including semiconductors, electroluminescent materials, and functional photoluminescent materials. These compounds exhibit an electronic push-pull phenomenon due to the delocalization of the π system, a characteristic highly desirable for the development of materials with optoelectronic properties, such as organic light-emitting diodes (OLEDs). This study explores the role of the cyanide ion (CN-) in the reaction kinetics between aminophenols (1a-c) and benzaldehydes (2a-c), which serve as imino-precursors (3a-i) in the cyclization process leading to the formation of benzoxazoles (4a-i). The multicomponent synthesis conditions were as follows: one equivalent of Ar-CHO, one equivalent of aminophenol, 10% PhB(OH)₂ dissolved in a minimal amount of methanol, and one equivalent of KCN dissolved in 0.5 mL of distilled water. The total reaction mixture volume was 3 mL, and it was maintained at room temperature and atmospheric pressure for three hours. Real-time monitoring of the reaction was conducted using online NMR with a continuous flow cell on a Magritek Spinsolve 80 MHz proton NMR spectrometer, in conjunction with ATR-FTIR analysis via a Perkin Elmer Spectrum 100 IR spectrometer. Changes in the concentration of the imines (3a-i) indicated that the cyanide ion is involved in the reaction mechanism, following second-order kinetics. This observation suggests that the cyanide ion acts as a reactant in the cyclization process rather than merely as a catalyst.