The scale-up of continuous biphasic liquid/liquid reactions under super-heating conditions: methodology and reactor design

Mandrelli, Francesca; Buco, Alessia; Piccioni, Lorenzo; Renner, Florian; Guélat, Bertrand; Martin, Benjamin; Schenkel, Berthold; Venturoni, Francesco

doi:10.1039/c6gc02840c

Cited by 13 publications

(9 citation statements)

References 38 publications

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“…First, the continuous reaction‐separation methodology can be used for sought‐after continuous flow multi‐step organic syntheses . Second, the pressurized system allows the reaction to be realized at elevated temperatures up to supercritical conditions which is of recent interest …”

Section: Resultsmentioning

confidence: 99%

Nanofiltration‐Enabled In Situ Solvent and Reagent Recycle for Sustainable Continuous‐Flow Synthesis

et al. 2017

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Solvent usage in the pharmaceutical sector accounts for as much as 90 % of the overall mass during manufacturing processes. Consequently, solvent consumption poses significant costs and environmental burdens. Continuous processing, in particular continuous‐flow reactors, have great potential for the sustainable production of pharmaceuticals but subsequent downstream processing remains challenging. Separation processes for concentrating and purifying chemicals can account for as much as 80 % of the total manufacturing costs. In this work, a nanofiltration unit was coupled to a continuous‐flow rector for in situ solvent and reagent recycling. The nanofiltration unit is straightforward to implement and simple to control during continuous operation. The hybrid process operated continuously over six weeks, recycling about 90 % of the solvent and reagent. Consequently, the E‐factor and the carbon footprint were reduced by 91 % and 19 %, respectively. Moreover, the nanofiltration unit led to a solution of the product eleven times more concentrated than the reaction mixture and increased the purity from 52.4 % to 91.5 %. The boundaries for process conditions were investigated to facilitate implementation of the methodology by the pharmaceutical sector.

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Section: Resultsmentioning

confidence: 99%

Nanofiltration‐Enabled In Situ Solvent and Reagent Recycle for Sustainable Continuous‐Flow Synthesis

et al. 2017

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“…The advanced reactor designs that incorporate multiple CSTRs in a single vessel, thus greatly simplifying and reducing the costs of the CSTR cascades, are essential. For example, the systems demonstrated by Machefer et al [29], Falβ et al [30], and Mandrelli et al [35] incorporate 5-13 CSTRs in a single reactor, enhancing scalability, solid handling, and mixing.…”

Section: Discussionmentioning

confidence: 99%

Continuous stirred tank reactors in fine chemical synthesis for efficient mixing, solids-handling, and rapid scale-up

Cherkasov

Adams²,

Bainbridge³

et al. 2023

React. Chem. Eng.

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“… This methodology suggested how to improve mixing efficiency over that of a conventional slug flow system and led to a practical flow system appropriate for scale-up. Taylor vortices generated by the rotation axis are based on active mixing and strengthen the mixing efficiency independent of the flow rate unlike the passive mixing by a static mixer. − A Taylor vortex flow reactor consists of only a cylindrical tube and a rotation axis, making it easy to clean; this is an essential factor for manufacturing active pharmaceutical ingredients (APIs) under good manufacturing practice . This structure is also resistant to clogging and compatible with continuous crystallization. , Narrow residence time distribution based on the plug flow reactor facilitates continuous crystallization for narrow particle size distribution and precise control of polymorphism .…”

Section: Introductionmentioning

confidence: 99%

Integration of Liquid–Liquid Biphasic Flow Alkylation and Continuous Crystallization Using Taylor Vortex Flow Reactors

Hosoya

Tanaka

Manaka

et al. 2022

Org. Process Res. Dev.

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This work established the integration of a continuous flow reaction and continuous crystallization using Taylor vortex flow reactors. We previously developed liquid–liquid biphasic flow alkylation using a Taylor vortex flow reactor, which is a scalable flow reactor with high mixing efficiency. To maximize the efficiency of this methodology, we evaluated process parameters and instrumental parameters, such as the rotating speed and tilt of the reactor, and optimized the reaction conditions. As a result, the throughput increased more than 20-fold compared to our previous work, and a long-run experiment verified its robustness. Liquid–liquid biphasic flow alkylation, quenching, phase separation, continuous crystallization, and filtration were integrated by using Taylor vortex flow reactors for both the flow reaction and continuous crystallization. The integrated system using two Taylor vortex flow reactors provided the alkylated product continuously from the solution of the starting material.

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The scale-up of continuous biphasic liquid/liquid reactions under super-heating conditions: methodology and reactor design

Abstract: In this paper we explore and propose a methodology for the scale-up of continuous biphasic liquid/liquid reactions under super-heating conditions.

Cited by 13 publications

References 38 publications

Nanofiltration‐Enabled In Situ Solvent and Reagent Recycle for Sustainable Continuous‐Flow Synthesis

Nanofiltration‐Enabled In Situ Solvent and Reagent Recycle for Sustainable Continuous‐Flow Synthesis

Continuous stirred tank reactors in fine chemical synthesis for efficient mixing, solids-handling, and rapid scale-up

Integration of Liquid–Liquid Biphasic Flow Alkylation and Continuous Crystallization Using Taylor Vortex Flow Reactors

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