New Opportunities for Organic Synthesis with Superheated Flow Chemistry.

ConspectusFlow chemistry has brought a fresh breeze with great promises for chemical manufacturing, yet critical deterrents persist. To remain economically viable at production scales, flow processes demand quick reactions, which are actually not that common. Superheated flow technology stands out as a promising alternative poised to confront modern chemistry challenges. While continuous micro- and mesofluidic reactors offer uniform heating and rapid cooling across different scales, operating above solvent boiling points (i.e., operating under superheated conditions) significantly enhances reaction rates. Despite the energy costs associated with high temperatures, superheated flow chemistry aligns with sustainability goals by improving productivity (process intensification), offering solvent flexibility, and enhancing safety.However, navigating the unconventional chemical space of superheated flow chemistry can be cumbersome, particularly for neophytes. Expanding the temperature/pressure process window beyond the conventional boiling point under the atmospheric pressure limit vastly increases the optimization space. When associated with conventional trial-and-error approaches, this can become exceedingly wasteful, resource-intensive, and discouraging. Over the years, flow chemists have developed various tools to mitigate these challenges, with an increased reliance on statistical models, artificial intelligence, and experimental (kinetics, preliminary test reactions under microwave irradiation) or theoretical (quantum mechanics)