Automated Multitrajectory Method for Reaction Optimization in a Microfluidic System using Online IR Analysis

An automated multitrajectory optimization platform with continuous online infrared (IR) monitoring is presented. The production rate of a Paal–Knorr reaction is maximized within a constrained temperature and residence time design space. The automated platform utilizes a microreactor system to carry out optimizations with low material requirements and implements a micro IR flow cell for continuous online monitoring of reaction conversion. The approach to steady state at each set of reaction conditions is assessed continuously before the objective function is evaluated and reactor conditions move to the next set point. Several optimization algorithms are tested for their performance on a complex objective terrain. Each function comes to agreement on the optimal conditions but requires a significantly different number of experiments to reach the final conditions. Additionally, multiple objective functions are compared to analyze the trade-off between production rate and conversion.

[1]  Schaefer Mechtilde,et al.  Computer Controlled Chemical Micro-Reactor , 2006 .

[2]  S. Ley,et al.  Continuous Preparation of Arylmagnesium Reagents in Flow with Inline IR Monitoring , 2012 .

[3]  W. Kuo,et al.  Synthesis and photophysical properties of pyrrole/polycyclic aromatic units hybrid fluorophores. , 2010, The Journal of organic chemistry.

[4]  D. Anthony,et al.  Intermediates in the Paal-Knorr synthesis of pyrroles , 1991 .

[5]  Klavs F Jensen,et al.  An integrated microreactor system for self-optimization of a Heck reaction: from micro- to mesoscale flow systems. , 2010, Angewandte Chemie.

[6]  G. Balme,et al.  Pyrrole syntheses by multicomponent coupling reactions. , 2004, Angewandte Chemie.

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

[8]  Volker Hessel,et al.  Organic Synthesis with Microstructured Reactors , 2005 .

[9]  W. Valentine,et al.  Intermediates in the Paal-Knorr synthesis of pyrroles. 4-Oxoaldehydes. , 1995, Chemical research in toxicology.

[10]  Philipp Rudolf von Rohr,et al.  Transparent silicon/glass microreactor for high-pressure and high-temperature reactions , 2008 .

[11]  Ryan L. Hartman,et al.  Deciding whether to go with the flow: evaluating the merits of flow reactors for synthesis. , 2011, Angewandte Chemie.

[12]  L. Knorr.  Einwirkung des Diacetbernsteinsäureesters auf Ammoniak und primäre Aminbasen , 1885 .

[13]  Volker Hessel,et al.  Chemical microprocess technology—from laboratory-scale to production , 2004 .

[14]  Klavs F. Jensen,et al.  Kinetic and Scale-Up Investigations of Epoxide Aminolysis in Microreactors at High Temperatures and Pressures , 2011 .

[15]  Klavs F Jensen,et al.  Integrated microreactors for reaction automation: new approaches to reaction development. , 2010, Annual review of analytical chemistry.

[16]  Klavs F. Jensen,et al.  Silicon-Based Microchemical Systems: Characteristics and Applications , 2006 .

[17]  Ryan L Hartman,et al.  Microchemical systems for continuous-flow synthesis. , 2009, Lab on a chip.

[18]  Klavs F. Jensen,et al.  Aminolysis of Epoxides in a Microreactor System: A Continuous Flow Approach to β-Amino Alcohols , 2010 .

[19]  Dana Kralisch,et al.  Assessment of the ecological potential of microreaction technology , 2007 .

[20]  S. Kazarian,et al.  Generation of chemical movies: FT-IR spectroscopic imaging of segmented flows. , 2011, Analytical chemistry.

[21]  Nickolas Regalia,et al.  Solution phase synthesis of a library of tetrasubstituted pyrrole amides. , 2006, Journal of combinatorial chemistry.

[22]  S. De.  Ruthenium (III) Chloride as a Novel and Efficient Catalyst for the Synthesis of Substituted Pyrroles Under Solvent-Free Conditions , 2008 .

[23]  Steven V. Ley,et al.  ReactIR Flow Cell: A New Analytical Tool for Continuous Flow Chemical Processing , 2010 .

[24]  Thomas Jochen Schwalbe,et al.  Application Report on Operating Cellular Process Chemistry Plants in Fine Chemical and Contract Manufacturing Industries , 2005 .

[25]  R. J. Boyd,et al.  A density functional theory study of the mechanism of the Paal–Knorr pyrrole synthesis , 2007 .

[26]  H. Löwe,et al.  Chemistry in microstructured reactors. , 2004, Angewandte Chemie.

[27]  Paul Watts,et al.  High-Throughput Organic Synthesis in Microreactors , 2010 .

[28]  A. deMello.  Control and detection of chemical reactions in microfluidic systems , 2006, Nature.

[29]  Paul Watts,et al.  The Application of Microreactors in Combinatorial Chemistry , 2005 .

[30]  A. deMello,et al.  Intelligent routes to the controlled synthesis of nanoparticles. , 2007, Lab on a chip.

[31]  Jonathan P. McMullen,et al.  An Automated Microfluidic System for Online Optimization in Chemical Synthesis , 2010 .

[32]  Cyril Aymonier,et al.  Design and packaging of microreactors for high pressure and high temperature applications , 2010 .

[33]  C. Paal.  Synthese von Thiophen- und Pyrrolderivaten , 1885 .