A sequential continuous flow synthesis and purification process of calcium dibutyryladenosine cyclophosphate

Calcium dibutyryladenosine cyclophosphate is a widely used cardiovascular drug.The traditional batch synthesis process suffers from long reaction times,tedious operations,and unstable yields.Herein,a sequential continuous flow synthesis combined with a multistage in-line purification process of calcium dibutyryladenosine cyclophosphate was developed.The acylation reaction was completed in a continuous coil reactor at 160℃ in 20 min.And the high toxic solvent pyridine was replaced by acetonitrile.Furthermore,the multistage in-line purification process was integrated into the homemade 3D circular cyclone-type micromixer chip.Combining with the membrane phase separators,the residence time of the purification step was 30 s.The isolated yield of this sequential continuous process was 92%with 99%purity.

Two-step continuous flow process of sodium tanshinone ⅡA sulfonate using a 3D circular cyclone-type microreactor

A sustainable and practical process is presented for the direct synthesis of sodium tanshinone IIA sulfonate(STS).Our approach was inspired by the well-established and industrially applied batch synthetic route for STS production.We constructed a telescoped two-step continuous flow platform.This involved a continuous tanshinone IIA sulfonation and in-line salt formation.For the setup,we constructed a 3D circular cyclone-type microreactor using femtosecond laser micromachining.Compared to the 68%yield for 2 h in batch,the two-step continuous flow had an STS yield of 90%,achieved for a total residence time of<3.0 min under optimal conditions.The proposed continuous flow method vastly simplified the operation and improved procedural safety,while significantly reducing the required acid content and wastewater production.

Computational fluid dynamics simulation and experimental study on mixing performance of a three-dimensional circular cyclone-type microreactor

Microchannels enable the fast and efficient mixing of multiphase fluids.In this study, a millimeter-scale three-dimensional(3D) circular cyclone-type microreactor was designed for the mixing.The flow characteristics and mixing intensity were simulated by computational fluid dynamics simulations at a flow rate range of 12–96 m L/min using a water/ethyl acetate system.In the 3D variable-diameter structure,the microreactor induced paired opposite vortices and abruptly changed the local pressure to achieve a stable turbulent effect within the theoretical range of laminar flow.Tracer injection simulations indicated that sufficient mixing units successfully promote fluid dispersion.Diazo-coupling experiments showed a segregation index of X_S= 0.00,039 within a residence time of 9 s.Extraction experiments on the nbutanol/succinic acid/water system showed that the 3D circular cyclone-type microreactor achieved 100%extraction efficiency(E) in 4.25 s, and the overall volume mass transfer coefficient(K_La) reached 0.05–1.5s^(-1) in 12–96 m L/min.The isolated yield of the phase transfer alkylation and oxidation reactions in the 3D circular cyclone-type microreactor achieved 99% within 36 s, which was superior to the coil microreactor and batch reactor.