Lake Como 2|4 October 2011 - CHIMICA Oggi/Chemistry Today
Lake Como 2|4 October 2011 - CHIMICA Oggi/Chemistry Today Lake Como 2|4 October 2011 - CHIMICA Oggi/Chemistry Today
Segmented fl ow reactor: effi ciently develop chemical reactions using fl ow systems Jan K. Hughes a , Werner Zinsser b a Accendo Corporation, 3762 S. Carson Avenue, Tucson, AZ 85730-2544, USA b Zinsser Analytic GmbH, Eschborner Landstrasse 135, 60489 Frankfurt, Germany Over the past three years, the use of continuous flow reactors for organic chemical reactions has been on the rise as these systems enable extreme reaction conditions (300 °C and 150 Bar), which are not easily obtained using traditional laboratory equipment. Although continuous flow systems broaden the types of chemistries one can pursue, they have three major limitations when used for chemical development (screening and optimization) and library production: the minimum amount of reagent for each experiment/compound is very high, experimental throughput is very low and accurate reaction kinetic information is difficult to obtain. POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER 5555555555555555555555555555 Meso scale fl ow reactions for reaction screening and optimization Kristin Price a , Joel Hawkins a , Neal Sach b , Terry D. Long c a Pfi zer Global Research and Development, Pfi zer Inc., Central Research Division, Eastern Point Road, Groton, CT 06340, USA b Pfi zer Global Research and Development, La Jolla site, Pfi zer Inc.,10777 Science Center Drive (CB6/2243), San Diego, CA 92121, USA c Accendo Corporation, 3762 S. Carson Avenue, Tucson, AZ 85730-2544, USA Flow reactors have proven to be a useful tool for organic chemistry as they enable the pursuit of extreme reaction conditions (300 °C and 150 Bar). There are a variety of commercially available continuous flow systems, which are primarily used for the synthesis of large scale quantities of starting material (gram) or product (kilogram). Until recently, flow systems were not generally used to explore new reaction conditions as in chemical screening and optimization or to make compound libraries as they require more reactant than needed for analysis or biochemical screening and they generally have low (poor) experimental throughput. POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER 6666666666666666666666666 For flow systems to become more widely used as a tool for organic chemistry these limitations must be removed and one solution is the adoption of segmented flow systems. We explain how segmented flow works and how as little as 20 µL of reactant can be used per experiment, experimental throughput can be as high as ten times faster than that continuous flow systems and how extremely accurate reaction kinetic data is obtained. We review a meso-scale segmented flow reactor, commercialized by Accendo Corporation, for reaction screening and optimization where we were able to screen new conditions with small microliter amounts of reactant in high temperature conditions and compared these results with those performed in a microwave system. In addition, we describe chemical optimizations using design of experimentation (DOE) protocols and then using the optimized conditions and the segmented flow automated system for the synthesis of a 36 compound matrix library, which was done three times at three temperatures in order to dramatically increase the number of successfully synthesized compounds. 25 Lake Como 2|4 October 2011
Continuous fl ow chemistry in multi-phase systems Dieter Most, Ian Grayson, Marco Lerm, Heidi Grön, Klaus Stadtmüller Evonik Degussa GmbH, Rodenbacher Chaussee 4, 63457 Hanau-Wolfgang, Germany The application of continuous processing in the manufacture of fine chemicals can lead to problems where there are multiple phases in the process, or when a phase has to be removed from the process in order to ensure complete reaction or the suppression of side reactions. Two examples are given where this problem has been solved on laboratory and pilot scale. In the first example (gas/liquid/gas removal) a photochlorination was performed in a loop reactor. This process had been operated on a production scale for several years for the manufacture of a product for the electronics industry. Impurity formation during the chlorination meant that an extensive purification of the downstream product was required, involving multiple distillation and recrystallisation steps. Key to a purer downstream product was found to be the continuous removal of the HCl by-product from the photochlorination step by a nitrogen purge, while maintaining a continuous chlorination (1). The improved quality of the intermediate allowed a subsequent 4-step continuous distillation process to be employed for the isolation of the downstream product. In the second example (gas/liquid/solid) an air oxidation of a pharmaceutical intermediate was followed by acidification and isolation of the crystallised product. A spiral wound oscillating flow reactor was used, with three sequential sections (air oxidation, cooling and acidification) (2). In comparison with the batch process, where variable amounts of polymeric impurities were formed due to the long residence times, a purer crystalline product was isolated directly from the reactor. POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER 7 (1) Performance of modular SiC-ceramic microreactors for severe environments R. Aicher, A. Grimm, A. Krecker, F. Meschke ESK Ceramics GmbH & Co. KG, Max-Schaidhauf Str. 25, D-87437 Kempten, Germany Ceramic Microreactors represent the latest achievement in the development of tools for continuous flow process technology. The material Silicon Carbide is new in the field of reactor equipment. It offers several advantages over conventional materials as it boosts the performance and the efficiency of reactors. Especially the ability to weld plates out of EKasic ® Silicon carbide gives the advantage to manufacture hermetic gas tight microreactor modules. Two family systems are available with 2 types of fully welded mixer modules, 2 types of residence time modules and 1 type of quench module. The EKasic ® ceramic modular systems are ideal to treat or to let react highly corrosive media like in fine chemical synthesis and high exothermic reaction processes. POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER 888888888888888888888888888 M. Lerm, J. Lotz, K. Stadtmüller, EP 2045249 (2) H. Grön, R. Schütte, K. Drauz, K. Stadtmüller, J. I. Grayson, EP 1855788. The advantages on performance are outlined by detailed examples. 26 Lake Como 2|4 October 2011
- Page 1 and 2: in partnership with Organised by La
- Page 3 and 4: AGENDA TUESDAY TUESDAY TUESDAY TUES
- Page 5 and 6: SPEAKER SPEAKER SPEAKER SPEAKER SPE
- Page 7 and 8: SPEAKER SPEAKER SPEAKER SPEAKER SPE
- Page 9 and 10: SPEAKER SPEAKER SPEAKER SPEAKER SPE
- Page 11 and 12: SPEAKER SPEAKER SPEAKER SPEAKER SPE
- Page 13 and 14: SPEAKER SPEAKER SPEAKER SPEAKER SPE
- Page 15 and 16: SPEAKER SPEAKER SPEAKER SPEAKER SPE
- Page 17 and 18: SPEAKER SPEAKER SPEAKER SPEAKER SPE
- Page 19 and 20: SPEAKER SPEAKER SPEAKER SPEAKER SPE
- Page 21 and 22: SPEAKER SPEAKER SPEAKER SPEAKER SPE
- Page 23 and 24: Lake Como 2|4 October 2011 POSTERS
- Page 25: Process intensifi cation under high
- Page 29 and 30: Huisgen cycloaddition to rufi namid
- Page 31: Production of Semiconductor Nanopar
Continuous fl ow chemistry in multi-phase systems<br />
Dieter Most, Ian Grayson, Marco Lerm, Heidi Grön, Klaus Stadtmüller<br />
Evonik Degussa GmbH, Rodenbacher Chaussee 4, 63457 Hanau-Wolfgang, Germany<br />
The application of continuous processing in the manufacture of fine chemicals can lead to problems where there are<br />
multiple phases in the process, or when a phase has to be removed from the process in order to ensure complete reaction<br />
or the suppression of side reactions. Two examples are given where this problem has been solved on laboratory and pilot<br />
scale. In the first example (gas/liquid/gas removal) a photochlorination was performed in a loop reactor. This process had<br />
been operated on a production scale for several years for the manufacture of a product for the electronics industry. Impurity<br />
formation during the chlorination meant that an extensive purification of the downstream product was required, involving<br />
multiple distillation and recrystallisation steps. Key to a purer downstream product was found to be the continuous removal<br />
of the HCl by-product from the photochlorination step by a nitrogen purge, while maintaining a continuous chlorination<br />
(1). The improved quality of the intermediate allowed a subsequent 4-step continuous distillation process to be employed<br />
for the isolation of the downstream product. In the second example (gas/liquid/solid) an air oxidation of a pharmaceutical<br />
intermediate was followed by acidification and isolation of the crystallised product.<br />
A spiral wound oscillating flow reactor was used, with three sequential sections (air<br />
oxidation, cooling and acidification) (2). In comparison with the batch process, where<br />
variable amounts of polymeric impurities were formed due to the long residence times, a<br />
purer crystalline product was isolated directly from the reactor.<br />
POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER<br />
7 (1)<br />
Performance of modular SiC-ceramic microreactors for severe environments<br />
R. Aicher, A. Grimm, A. Krecker, F. Meschke<br />
ESK Ceramics GmbH & Co. KG, Max-Schaidhauf Str. 25, D-87437 Kempten, Germany<br />
Ceramic Microreactors represent the latest achievement in the development of tools for continuous flow process technology.<br />
The material Silicon Carbide is new in the field of reactor equipment. It offers several advantages over conventional<br />
materials as it boosts the performance and the efficiency of reactors.<br />
Especially the ability to weld plates out of EKasic ® Silicon carbide gives the advantage to manufacture hermetic gas tight<br />
microreactor modules. Two family systems are available with 2 types of fully welded mixer modules, 2 types of residence<br />
time modules and 1 type of quench module.<br />
The EKasic ® ceramic modular systems are ideal to treat or to let react highly corrosive media like in fine chemical synthesis<br />
and high exothermic reaction processes.<br />
POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER POSTER<br />
888888888888888888888888888<br />
M. Lerm, J. Lotz, K. Stadtmüller, EP 2045249<br />
(2) H. Grön, R. Schütte, K. Drauz, K. Stadtmüller, J. I. Grayson, EP 1855788.<br />
The advantages on performance are outlined by detailed examples.<br />
26<br />
<strong>Lake</strong> <strong>Como</strong><br />
<strong>2|4</strong> <strong>October</strong> <strong>2011</strong>
Change language