Fast Scale-Up Using Microreactors: Pyrrole Synthesis from Micro to Production Scale

A flow chemistry method for the synthesis of pyrroles was developed. The method was optimized in 0.13 to 7 μL microreactors in continuous flow, reaching yields of nearly 100%. Subsequently, the method was scaled up in continuous flow using a 9.6-mL internal volume, glass, microstructured flow reactor, leading to production of a pyrrole derivative at a rate of 55.8 g per hour .

[1]  Floris P. J. T. Rutjes,et al.  Optimizing the Deprotection of the Amine Protecting p-Methoxyphenyl Group in an Automated Microreactor Platform , 2009 .

[2]  M. Orfanopoulos,et al.  Photosensitized oxidations of substituted pyrroles: unanticipated radical-derived oxygenated products. , 2009, The Journal of organic chemistry.

[3]  Ron Wehrens,et al.  Flash chemistry extensively optimized: high-temperature Swern-Moffatt oxidation in an automated microreactor platform. , 2010, Chemistry, an Asian journal.

[4]  H. Schoemaker,et al.  Enzymatic synthesis of optically pure cyanohydrins in microchannels using a crude cell lysate , 2008 .

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

[6]  J. V. Hest,et al.  Flow markers in microreactors: a generally applicable chromatographic method for monitoring flow rates during reactions , 2010 .

[7]  Ilkka Turunen,et al.  Safety Advantages of On-Site Microprocesses , 2009 .

[8]  N. P. Buu‐Hoï,et al.  HYDROXY AND THIOL DERIVATIVES OF 2,5-DIALKYLPYRROLES , 1955 .

[9]  J. V. van Hest,et al.  Continuous flow azide formation: Optimization and scale-up , 2011 .

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

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

[12]  Shahriyar Taghavi-Moghadam,et al.  Microreaction Technology as a Novel Approach to Drug Design, Process Development and Reliability , 2001 .

[13]  A. Vikhansky,et al.  Analysis of a pressure‐driven folding flow microreactor with nearly plug‐flow characteristics , 2009 .

[14]  V. Hessel,et al.  Flow chemistry using milli- and microstructured reactors-from conventional to novel process windows. , 2010, Bioorganic & medicinal chemistry.

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

[16]  Dominique M. Roberge,et al.  Microreactor Technology: A Revolution for the Fine Chemical and Pharmaceutical Industries? , 2005 .

[17]  J C M van Hest,et al.  Enzymatic enantioselective C-C-bond formation in microreactors. , 2008, Biotechnology and bioengineering.

[18]  Ray W.K. Allen,et al.  Numerical characterisation of folding flow microchannel mixers , 2007 .

[19]  Fabrice Renaud,et al.  Facile, Fast and Safe Process Development of Nitration and Bromination Reactions Using Continuous Flow Reactors , 2009 .