Micro-reactor mixing unit interspacing for fast liquid-liquid reactions leading to a generalized scale-up methodology

Abstract The effect of geometrical arrangements of a residence time channel (RTC) positioned in between LL-Rhombus static mixing elements on interphase mass transfer rates is investigated. Four variations of a micro-reactor plate are tested with four immiscible aqueous-organic systems: water coupled with n-butanol, n-hexanol, methyl tert-butyl ether and toluene. The alkaline hydrolysis of 4-nitrophenyl acetate is used to determine the overall volumetric mass transfer coefficient (Kda). For all solvent pairs, the micro-reactor without a RTC has the greatest Kda at a given flow rate due to a greater energy dissipation rate (ɛ) and the fact that drops can re-coalesce leading to reduced advective transfer in the RTC pending the flow regime. An increase in flow rate results in a rise in conversion up to a maximum, after which viscous dissipation impedes further turbulent breakdown of the droplets as they near the Kolmogorov length scale. When the resulting flow is finely dispersed, interphase mass transfer rates no longer depend on reactor geometry but was correlated to the solvent system and rate of energy dissipated. The negative impact of operating at greater ɛ values than at maximum conversion is shown via the required pressure loss to achieve a certain conversion or residence time. Lastly, relevant to production rates in the fine chemical and pharmaceutical industry, an algorithm for scaling a generic mass transfer-limited liquid-liquid reaction at identified optimal operating conditions is presented.

[1]  Neima Brauner,et al.  THE PREDICTION OF FLOW PATTERN MAPS IN MINICHANNELS , 2007 .

[2]  Alastair J. Florence,et al.  Oscillatory flow reactors (OFRs) for continuous manufacturing and crystallization , 2015 .

[3]  Colin L Raston,et al.  Multi-step continuous-flow synthesis. , 2017, Chemical Society reviews.

[4]  V. Parker.  Instantaneous rate constants in physical organic chemistry: application to acyl transfer reactions of p‐nitrophenyl acetate to hydroxide ion , 2006 .

[5]  Jochen Strube,et al.  Development of Micro Separation Technology Modules. Part 1: Liquid‐Liquid Extraction , 2015 .

[6]  Norbert Kockmann,et al.  Scale-up concept of single-channel microreactors from process development to industrial production , 2011 .

[7]  D. Barrow,et al.  Effect of segmented fluid flow, sonication and phase transfer catalysis on biphasic reactions in capillary microreactors , 2008 .

[8]  D. Barrow,et al.  Enhancement of Reaction Rates by Segmented Fluid Flow in Capillary Scale Reactors , 2006 .

[9]  Panagiota Angeli,et al.  Effect of channel size on mass transfer during liquid–liquid plug flow in small scale extractors , 2015 .

[10]  J. T. Davies,et al.  Drop sizes of emulsions related to turbulent energy dissipation rates , 1985 .

[11]  Floris P. J. T. Rutjes,et al.  Fast Scale-Up Using Microreactors: Pyrrole Synthesis from Micro to Production Scale , 2011 .

[12]  Klavs F. Jensen,et al.  Scalability of mass transfer in liquid-liquid flow , 2014 .

[13]  Dominique M. Roberge,et al.  From Batch to Continuous Chemical Synthesis—A Toolbox Approach , 2014 .

[14]  T. Makita,et al.  Volumetric properties of 1-alkanols at temperatures in the range 298–348 K and pressures up to 40 MPa , 1989 .

[15]  Dominique M. Roberge,et al.  Liquid–Liquid Mass Transfer in an Oscillatory-Flow Mesoscale Coil Reactor without Baffles , 2016 .

[16]  Neima Brauner,et al.  The prediction of dispersed flows boundaries in liquid–liquid and gas–liquid systems , 2001 .

[17]  P. Seeberger,et al.  The Hitchhiker's Guide to Flow Chemistry ∥. , 2017, Chemical reviews.

[18]  Dominique M. Roberge,et al.  On the scale-up of micro-reactors for liquid–liquid reactions , 2016 .

[19]  María José Nieves-Remacha,et al.  Hydrodynamics of Liquid–Liquid Dispersion in an Advanced-Flow Reactor , 2012 .

[20]  Jochen Strube,et al.  Development of Micro Separation Technology Modules. Part 2: Distillation , 2015 .

[21]  Norbert Kockmann,et al.  Pressure drop and mixing in single phase microreactors: Simplified designs of micromixers , 2011 .

[22]  D. Donahue,et al.  The Boundary Tension at Water-Organic Liquid Interfaces , 1952 .

[23]  E Bender,et al.  Interfacial tensions in binary and ternary liquid—liquid systems , 1990 .

[24]  R. Stephenson,et al.  Mutual solubilities: water-ketones, water-ethers, and water-gasoline-alcohols , 1992 .

[25]  Dominique M. Roberge,et al.  Microreactor Mixing-Unit Design for Fast Liquid-Liquid Reactions , 2016, Journal of Flow Chemistry.

[26]  Laurent Falk,et al.  Performance comparison of micromixers , 2010 .

[27]  V. Hessel,et al.  Continuous synthesis of tert-butyl peroxypivalate using a single-channel microreactor equipped with orifices as emulsification units. , 2011, ChemSusChem.

[28]  M. Rao,et al.  Densities and Viscosities of Binary Liquid Mixtures of Anisole or Methyl tert-Butyl Ether with Benzene, Chlorobenzene, Benzonitrile, and Nitrobenzene , 2000 .

[29]  María José Nieves-Remacha,et al.  Gas–Liquid Flow and Mass Transfer in an Advanced-Flow Reactor , 2013 .

[30]  I. Rossetti,et al.  Chemical reaction engineering, process design and scale-up issues at the frontier of synthesis: Flow chemistry , 2016 .

[31]  Kai Wang,et al.  Liquid–liquid microflow reaction engineering , 2017 .

[32]  Luigi Vaccaro,et al.  Sustainable flow chemistry: Methods and applications , 2017 .

[33]  T. A. Nijhuis,et al.  Redispersion Microreactor System for Phase Transfer‐Catalyzed Esterification , 2011 .

[34]  A. Berthod,et al.  Water-organic solvent systems in countercurrent chromatography: Liquid stationary phase retention and solvent polarity. , 1993, Talanta.

[35]  C. Xuereb,et al.  Turbulent liquid–liquid dispersion in SMV static mixer at high dispersed phase concentration , 2011 .

[36]  O. Levenspiel.  Chemical Reaction Engineering , 1972 .

[37]  Norbert Kockmann,et al.  Local and overall heat transfer of exothermic reactions in microreactor systems , 2017 .

[38]  J. Hinze.  Fundamentals of the hydrodynamic mechanism of splitting in dispersion processes , 1955 .

[39]  N. Sreekumar,et al.  Liquid-liquid Slug Flow in a Microchannel Reactor and its Mass Transfer Properties - A Review , 2014 .

[40]  C. Radke,et al.  Role of organic solvents on Pa-hydroxynitrile lyase interfacial activity and stability. , 2001, Biotechnology and bioengineering.

[41]  G. Hughmark.  Drop breakup in turbulent pipe flow , 1971 .

[42]  Albert Renken,et al.  Gas–liquid and liquid–liquid mass transfer in microstructured reactors , 2011 .

[43]  Dominique M. Roberge,et al.  Liquid–liquid flow regimes and mass transfer in various micro-reactors , 2016 .

[44]  A. Ricard,et al.  Turbulent Liquid-Liquid Dispersion in Sulzer SMX Mixer , 2010 .

[45]  D. Roberge,et al.  Liquid–liquid mass transfer in a serpentine micro-reactor using various solvents , 2016 .

[46]  E. D. Lavric,et al.  Advanced-Flow™ glass reactors for seamless scale-up , 2009 .

[47]  K. Jensen,et al.  Integrated continuous microfluidic liquid-liquid extraction. , 2007, Lab on a chip.

[48]  Martin D. Johnson,et al.  Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions , 2017, Science.

[49]  Mrityunjay K. Sharma,et al.  Pinched tube flow reactor: Hydrodynamics and suitability for exothermic multiphase reactions , 2017 .

[50]  D. E. Leng,et al.  Immiscible Liquid–Liquid Systems , 2004 .