Process intensification in continuous flow organic synthesis with enabling and hybrid technologies

Abstract

Industrial organic synthesis is time and energy consuming, and generates substantial waste. Traditional conductive heating and mixing in batch reactors is no longer competitive with continuous-flow synthetic methods and enabling technologies that can strongly promote reaction kinetics. These advances lead to faster and simplified downstream processes with easier workup, purification and process scale-up. In the current Industry 4.0 revolution, new advances that are based on cyber-physical systems and artificial intelligence will be able to optimize and invigorate synthetic processes by connecting cascade reactors with continuous in-line monitoring and even predict solutions in case of unforeseen events. Alternative energy sources, such as dielectric and ohmic heating, ultrasound, hydrodynamic cavitation, reactive extruders and plasma have revolutionized standard procedures. So-called hybrid or hyphenated techniques, where the combination of two different energy sources often generates synergistic effects, are also worthy of mention. Herein, we report our consolidated experience of all of these alternative techniques.

Continuous Flow Liquid‐Phase Semihydrogenation of Phenylacetylene over Pd Nanoparticles Supported on UiO‐66(Hf) Metal‐Organic Framework

“…Most of the reported materials explored under batch mode have afforded good conversion of PA with excellent selectivity to ST (upto 99.0 %). In contrast to batch operations, the semi‐hydrogenation under continuous flow mode offers excellent benefits in terms of process steps, energy, automation, waste reduction (reduction of E‐factor) etc [28] . In this direction, the materials such as Pt/mpg‐C 3 N 4 , mpg‐C 3 N 4 , Au/γ‐Al 2 O 3 , Pd/PCFs, and Pd/C have been reported for the semi‐hydrogenation of PA in continuous mode (Table 1).…”

“…In contrast to batch operations, the semi-hydrogenation under continuous flow mode offers excellent benefits in terms of process steps, energy, automation, waste reduction (reduction of E-factor) etc. [28] In this direction, the materials such as Pt/mpg-C 3 N 4 , mpg-C 3 N 4 , Au/γ-Al 2 O 3 , Pd/PCFs, and Pd/C have been reported for the semihydrogenation of PA in continuous mode (Table 1). However, the Pt/mpg-C 3 N 4 catalysts fails in achieving the ST selectivity even at high reaction temperature of 150 °C.…”

Analyzing Environmental Impacts of Hypercrosslinked Polymers Produced from Continuous Flow Synthesis for Water Treatment

“…Continuous flow synthesis has been widely employed for process intensification in the production of fine chemicals and pharmaceuticals in the last two decades . Compared with batch reactors, flow reactors possess a higher surface area to volume ratio that improves heat and mass transfers, which enhances reaction kinetics. , Other advantages associated with flow synthesis include ease of scale-up and safer reactions that involve hazardous chemicals or harsh operating conditions …”

From Batch to the Semi-Continuous Flow Hydrogenation of pNB, pNZ-Protected Meropenem

“…From unsaturated organic substrates to heterocycle synthesis and metal-catalyzed chemistry, this technology has played a central role in the development of sustainable multigram preparations that meet the dual requirement of process intensification and reduced production costs. It has proven to be a promising hybrid technique that can link lab-scale investigations and pilot processes, and thus meet industrial challenges [ 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 ]. In addition, the FDA and the European Medicines Agency (EMA) have strongly encouraged the study and implementation of this innovative, sustainable and environmentally friendly technology in API synthesis [ 95 , 96 ].…”