The Assembly and Use of Continuous Flow Systems for Chemical Synthesis
The adoption of and opportunities in continuous flow synthesis ('flow chemistry') have increased significantly over the past several years. Continuous flow systems provide improved reaction safety and accelerated reaction kinetics, and have synthesised several active pharmaceutical ingredi...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/114610 https://orcid.org/0000-0002-8601-7799 |
| _version_ | 1811087775636652032 |
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| author | Britton, Joshua Jamison, Timothy F |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Britton, Joshua Jamison, Timothy F |
| author_sort | Britton, Joshua |
| collection | MIT |
| description | The adoption of and opportunities in continuous flow synthesis ('flow chemistry') have increased significantly over the past several years. Continuous flow systems provide improved reaction safety and accelerated reaction kinetics, and have synthesised several active pharmaceutical ingredients in automated reconfigurable systems. Although continuous flow platforms are commercially available, systems constructed 'in-lab' provide researchers with a flexible, versatile, and cost-effective alternative. Herein, we describe the assembly and use of a modular continuous flow apparatus from readily available and affordable parts in as little as 30 min. Once assembled, the synthesis of a sulfonamide by reacting 4-chlorobenzenesulfonyl chloride with dibenzylamine in a single reactor coil with an in-line quench is presented. This example reaction offers the opportunity to learn several important skills including reactor construction, charging of a back-pressure regulator, assembly of stainless-steel syringes, assembly of a continuous flow system with multiple junctions, and yield determination. From our extensive experience of single-step and multistep continuous flow synthesis, we also describe solutions to commonly encountered technical problems such as precipitation of solids ('clogging') and reactor failure. Following this protocol, a nonspecialist can assemble a continuous flow system from reactor coils, syringes, pumps, in-line liquid–liquid separators, drying columns, back-pressure regulators, static mixers, and packed-bed reactors. Keywords: Flow chemistry; Synthetic chemistry methodology |
| first_indexed | 2024-09-23T13:51:47Z |
| format | Article |
| id | mit-1721.1/114610 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:51:47Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1146102022-10-01T17:36:01Z The Assembly and Use of Continuous Flow Systems for Chemical Synthesis Britton, Joshua Jamison, Timothy F Massachusetts Institute of Technology. Department of Chemistry Jamison, Timothy F. Britton, Joshua Jamison, Timothy F The adoption of and opportunities in continuous flow synthesis ('flow chemistry') have increased significantly over the past several years. Continuous flow systems provide improved reaction safety and accelerated reaction kinetics, and have synthesised several active pharmaceutical ingredients in automated reconfigurable systems. Although continuous flow platforms are commercially available, systems constructed 'in-lab' provide researchers with a flexible, versatile, and cost-effective alternative. Herein, we describe the assembly and use of a modular continuous flow apparatus from readily available and affordable parts in as little as 30 min. Once assembled, the synthesis of a sulfonamide by reacting 4-chlorobenzenesulfonyl chloride with dibenzylamine in a single reactor coil with an in-line quench is presented. This example reaction offers the opportunity to learn several important skills including reactor construction, charging of a back-pressure regulator, assembly of stainless-steel syringes, assembly of a continuous flow system with multiple junctions, and yield determination. From our extensive experience of single-step and multistep continuous flow synthesis, we also describe solutions to commonly encountered technical problems such as precipitation of solids ('clogging') and reactor failure. Following this protocol, a nonspecialist can assemble a continuous flow system from reactor coils, syringes, pumps, in-line liquid–liquid separators, drying columns, back-pressure regulators, static mixers, and packed-bed reactors. Keywords: Flow chemistry; Synthetic chemistry methodology United States. Defense Advanced Research Projects Agency 2018-04-09T13:26:44Z 2018-04-09T13:26:44Z 2017-10 2017-08 Article http://purl.org/eprint/type/JournalArticle 1750-2799 1754-2189 http://hdl.handle.net/1721.1/114610 Britton, Joshua, and Timothy F. Jamison. “The Assembly and Use of Continuous Flow Systems for Chemical Synthesis.” Nature Protocols, vol. 12, no. 11, Oct. 2017, pp. 2423–46. https://orcid.org/0000-0002-8601-7799 en_US http://dx.doi.org/doi:10.1038/nprot.2017.102 Nature Protocols Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group Prof. Jamison via Erja Kajosalo |
| spellingShingle | Britton, Joshua Jamison, Timothy F The Assembly and Use of Continuous Flow Systems for Chemical Synthesis |
| title | The Assembly and Use of Continuous Flow Systems for Chemical Synthesis |
| title_full | The Assembly and Use of Continuous Flow Systems for Chemical Synthesis |
| title_fullStr | The Assembly and Use of Continuous Flow Systems for Chemical Synthesis |
| title_full_unstemmed | The Assembly and Use of Continuous Flow Systems for Chemical Synthesis |
| title_short | The Assembly and Use of Continuous Flow Systems for Chemical Synthesis |
| title_sort | assembly and use of continuous flow systems for chemical synthesis |
| url | http://hdl.handle.net/1721.1/114610 https://orcid.org/0000-0002-8601-7799 |
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