A rapid flow strategy for the oxidative cyanation of secondary and tertiary amines via C-H activation

The development of environmentally mild methods for the synthesis of materials and general transformations have been receiving tremendous attention in recent years(1-3), that entails reducing source pollution and hazardous waste generation by the chemical industry(4,5). Additionally, with the increasing world population and the associated upsurge in the demand for materials, the need for chemical production will only swell(6). Therefore, the development of clean, sustainable and environmental-friendly methods for the production of various chemical products is of the utmost importance(7). Importantly, the elaboration of newer technologies and advancements in chemical processing can have added sustenance(8). Engaged in the development of more sustainable protocols(9-13), herein, we demonstrate the use of a simple continuous flow setup in presence of magnetic nano-ferrites (Fe3O4) for the direct oxidative cyanation of the C-H bond comprising secondary and tertiary amines. The product of the direct oxidative cyanation of the C-H bond in secondary and tertiary amines have vast applications(14) as attested by recent research efforts in this area(15-19). This direct oxidative cyanation of the C-H bond in tertiary amines to generate the corresponding a-aminonitriles has been widely studied(20,21), in view of their applications in natural products and nitrogen containing bioactive compounds, namely alkaloids(22-24). An array of metal-based catalytic procedures has been reported for the direct oxidative cyanation of tertiary amines(15-21). Although they lack much to be desired in terms of environmental and economic aspects; most reactions require the use of acetic acid(15,17-21,25). This adds more energy and time requirements, as well as increased waste generation. Newer reports entail the direct utilization of C-H bonds using metals to circumvent the multi-step synthetic procedure. Recently, Varma and co-workers have reported the C-H activation and cyanation of amines using in-house synthesized magnetic graphitic carbon nitride (Fe@g-C3N4)(25). Various amines were exploited using Fe@g-C3N4 under optimized conditions to produce a-aminonitriles in high yield within a reasonable time period. Significantly, the Fe@g-C3N4 catalyst could be recovered and reused repeatedly simply using an external magnet. This paper demonstrates the utility of magnetic nano-ferrites (Fe3O4) under continuous flow conditions to conduct the cyanation of amines within a few minutes (< 10 min) in high yields; enhanced ability to quickly mix the starting materials promotes the faster reaction, quicker optimization, and the formation of selective and desired products under continuous flow conditions. Consequently, various intermediates with diverse potential applications can be synthesized easily and rapidly thus rendering the approach much more advantageous when compared to traditional one-pot synthesis.