The core advantages and driving factors of continuous flow technology

Continuous Flow Technology (CFT) realizes the whole process continuity of chemical reactions through microchannel reactors, fixed beds and other equipment, and its core advantages lie in process intensification and precise control, which is significantly different from traditional batch production. Continuous flow microreactors can effectively solve user pain points:

Increased safety: small microreactor hold-up (typically < 100 mL) for safe handling of high-risk reactions (e.g., nitrification, diazotization)

Breakthrough in efficiency: the mass and heat transfer rates are increased by 10-100 times, and the reaction time is shortened from hours to minutes or even seconds

Consistent quality: Horizontal push flow characteristics eliminate amplification effect, and the yield deviation from laboratory to industrial production is <5%

Green manufacturing: reduce solvent consumption by 30%-70%, and reduce carbon emissions by more than 50%.

Key technology classification and application scenarios of continuous flow technology in pharmaceutical production

According to the characteristics of the reaction system, continuous flow technology can be divided into the following types:

1. Gas-liquid reaction system

Application case: Carbonylation reactions involving CO/CO₂, such as continuous synthesis of paroxetine intermediates (yield 92%, purity > 99%)

Technological breakthrough: Tube-in-tube gas loading device for efficient gas-liquid mixing

2. Solid-liquid reaction system

Case Study: Palladium-Catalyzed Suzuki Coupling Reaction with Catalyst Life Extended to Over 500 Hours (Conventional Kettle < 50 Hours)

Innovative design: SiliaCat-DPP-Pd fixed-bed reactor with palladium residue < 30 ppb

3. Gas-liquid-solid reaction system

Application case: Continuous hydrogenation reaction system, integrated water electrolysis hydrogen production technology to replace high-pressure hydrogen cylinders

Extended application: deuterated drug synthesis, by replacing heavy water to achieve the precise introduction of deuterium atoms

4. Liquid-liquid reaction system

Case Study: Bucherer-Bergs Reaction Synthesis of Hydantoins with a Yield of 95% (70% in Traditional Kettle)

High-pressure intensification: Reaction time reduced to 10 minutes at 120 °C at 20 bar

5. Multi-phase integrated system

Innovative model: The SPS-FLOW system developed by Wu Jie's team at the National University of Singapore combines continuous flow and solid-phase synthesis to achieve six-step fully automated production of Prexasertib (65% total yield)

Derivatization potential: synthesis of 23 tetrazoloid derivatives (43%-70% yield) through modular substitution reaction steps