Jamison / Koch Science of Synthesis: Flow Chemistry in Organic Synthesis

1. Auflage 2018
ISBN: 978-3-13-242334-3
Verlag: Thieme
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 590 Seiten, ePub

The aim of this work is to convey the practice, power, and potential of flow chemistry to a larger audience.

An emerging and strengthening trend is that flow chemistry is much more than the adaption of batch processes to flow systems. Rather, flow chemistry offers a new paradigm in the way we think about chemical synthesis. This volume demonstrates the enabling power of continuous flow to access new reaction types and different chemistry space and, to this end, it has been compiled by a team of pioneers and leaders, who present both the practical and conceptual aspects of this rapidly growing field. Included are the principles of reactor design, automation, and separations/purifications in flow systems, applications in photochemistry, electrochemistry, gaseous systems, immobilized reagents and catalysts, and multistep processes. The synthesis of peptides, carbohydrates, and pharmaceuticals is covered and several chapters give insight into the use of flow in an industrial context.

Zielgruppe

Wissenschaftler

Autoren/Hrsg.

Jamison, Timothy

Koch, Guido

Fachgebiete

• Naturwissenschaften Chemie Physikalische Chemie Elektrochemie, Magnetochemie
• Naturwissenschaften Chemie Physikalische Chemie Chemische Reaktionen, Katalyse
• Naturwissenschaften Chemie Chemie Allgemein Pharmazeutische Chemie, Medizinische Chemie
• Naturwissenschaften Chemie Organische Chemie
• Naturwissenschaften Chemie Physikalische Chemie Nuklearchemie, Photochemie, Strahlenchemie

Inhaltsverzeichnis

1 Introduction
2 Flow Chemistry System Design and Automation
3 Separation and Purification in the Continuous Synthesis of Fine Chemicals and Pharmaceuticals
4 Flow Photochemistry in Organic Synthesis
5 Electrosynthesis in Continuous Flow
6 Hazardous Reagents in Continuous-Flow Chemistry
7 Very Fast Reactions and Extreme Conditions
8 Gaseous Reagents in Continuous-Flow Synthesis
9 Immobilized Reagents and Multistep Processes
10 Intermolecular Transition-Metal-Catalyzed C-C Coupling Reactions in Continuous Flow
11 Immobilized Catalysts for Asymmetric Reactions
12 Pushing the Limits of Solid-Phase Peptide Synthesis with Continuous Flow
13 The Controlled Synthesis of Carbohydrates
14 Continuous-Flow Syntheses of Active Pharmaceutical Ingredients
15 Flow Chemistry in the Pharmaceutical Industry

Leseproben

Abstracts
2 Flow Chemistry System Design and Automation
C. W. Coley, J. Imbrogno, Y. Mo, D. A. Thomas, and K. F. Jensen Organic chemistry performed in continuous-flow equipment, flow chemistry, has emerged as a complementary tool to traditional batch synthesis. This chapter describes typical components of a flow chemistry platform (e.g., pumps, mixers, reactors, and separators), reviews reaction engineering fundamentals as they apply to flow chemistry (e.g., mixing, dispersions, mass and heat transfer), summarizes laboratory and production reactors for single-phase, multiphase, thermal, photochemical, and electrochemical reactions, and describes strategies for separation with a focus on extraction. The chapter also reviews systems for multistep reactions along with integrated flow platforms comprising flow reactors, analytics, and computer control for automation, screening, and optimization. Keywords: flow chemistry • fluid delivery • pumps • laboratory reactor • commercial reactor • photochemistry • electrochemistry • multiphase reactions • extraction • multistep reactions • automation • reaction screening • reaction optimization 3 Separation and Purification in the Continuous Synthesis of Fine Chemicals and Pharmaceuticals
M. O'Mahony, S. Ferguson, T. Stelzer, and A. Myerson Of use to both chemists and chemical engineers working in flow synthesis, this chapter provides a summary of separation and purification operations that can be applied to flow synthesis reaction streams. Both single and biphasic separations for the liquid phase are detailed. Separation and purification by continuous crystallization of a solid phase is covered. Continuous solid–liquid separation and drying technologies for the isolation of a fine-chemical or pharmaceutical product are also reviewed. Keywords: flow chemistry • continuous separation • pharmaceuticals • nanofiltration • membrane extractors • continuous crystallization • integrated continuous manufacturing • continuous solid–liquid separation • filtration • continuous filtration • continuous isolation and drying 4 Flow Photochemistry in Organic Synthesis
R. Telmesani, A. C. Sun, A. B. Beeler, and C. R. J. Stephenson Performing photochemical reactions in flow has helped increase their efficiency, scalability, and utility. These efforts have brought photochemistry back to prominence as a powerful tool for synthesis. This chapter outlines the most important procedures and flow setups that can be used to perform photochemical transformations. Examples include ultraviolet-light-driven photocycloadditions and reactions with reagents such as singlet oxygen and transition-metal catalysts. Applications of visible-light photoredox catalysis in continuous-flow systems are discussed in the context of late-stage fluorination, natural product synthesis, alkyl–aryl cross coupling, and lignin fragmentation. Keywords: photochemistry • flow chemistry • photocycloaddition • singlet oxygen • photochemical rearrangements • polymer modification • immersion well • fluorination • photoredox catalysis • perfluoroalkylation • natural product synthesis • lignin 5 Electrosynthesis in Continuous Flow
A. A. Folgueiras-Amador and T. Wirth Organic electrosynthesis is recognized as a green enabling methodology to perform reactions in an efficient and straightforward way. Electrons are used as the reagent to form anionic and cationic radical species from neutral organic molecules, achieving oxidations and reductions and replacing toxic and dangerous reagents. Within this field, the use of microreactors in continuous flow is particularly compatible with electrochemistry because of the convenient advantages of flow over batch, including: (i) low loading or no supporting electrolyte at all, due to the small distance between electrodes, providing significant advantages in downstream processing; (ii) high electrode surface-to-reactor volume ratio; (iii) short residence time; and (iv) improved mixing effects. In this chapter, the most relevant electrochemical flow reactors and electrochemical transformations performed in continuous flow are presented and discussed. Keywords: flow electrosynthesis • electrochemical microreactors • flow chemistry • electrochemistry • anodic oxidations • cathodic reductions • divided cells • undivided cells 6 Hazardous Reagents in Continuous-Flow Chemistry
R. W. Hicklin, A. E. Strom, E. D. Styduhar, and T. F. Jamison Continuous-flow technology enables the use of hazardous reagents and the safe handling of hazardous intermediates. This chapter focuses on the application of continuous-flow techniques in reactions involving reactive organometallic reagents, hazardous nitrogen- and halogen-based reagents, oxidants, and toxic low-molecular-weight reagents. Keywords: continuous-flow chemistry • hazardous reagents • diazo compounds • halogenation • explosive reagents • pyrophoric reagents • acutely toxic reagents • reactive organometallic reagents • toxic low-molecular-weight reagents • oxidation 7 Very Fast Reactions and Extreme Conditions
H. Kim and J. Yoshida Microreaction technology represents a powerful and unique tool for the control of extremely fast reactions and reactions under extreme conditions. In this chapter, fast flow reactions such as Swern–Moffatt oxidations, diisobutylaluminum hydride reductions, reactions involving organolithiums and organomagnesiums, and Friedel–Crafts alkylations are presented. Moreover, this chapter also covers examples of reactions performed under extreme reaction conditions of high temperature and high pressure, which cannot be easily conducted in flasks. Keywords: fast reactions • unstable intermediates • organolithiums • extreme conditions • high temperature • high pressure • flow chemistry • microreactors • flash chemistry 8 Gaseous Reagents in Continuous-Flow Synthesis
M. O'Brien and A. Polyzos Although reactive gases facilitate a wide range of important synthetic transformations, their use is often not straightforward. Significant safety issues arise from the highly mobile nature of gases, both in terms of the rapidity with which they can spread throughout the laboratory and also because of the frequent need to use pressurized containment. Additionally, as surface-area-to-volume ratios tend to decrease as reactor dimensions are increased, gas–liquid transformations carried out in batch mode are often accompanied by scale-dependent performance. This chapter highlights some of the benefits that continuous flow chemistry can bring to gas–liquid synthetic chemistry. A number of flow chemical reactor systems are described, including microfluidic devices which enhance the mechanical mixing of gas and liquid phases, as well as systems based on the use of gas-permeable membrane materials. Keywords: gas–liquid • flow chemistry • falling film • cyclone • H-Cube • Teflon AF-2400 • tube-in-tube • biphasic flow • microfluidic • membranes 9 Immobilized Reagents and Multistep Processes
S. V. Ley, D. L. Browne, and M. O'Brien Multistep continuous-flow processing enables the direct preparation of complex chemical materials from simple input streams through a series of complexity-adding reaction steps. The use of polymer-supported reagents can greatly facilitate this process through the inline hosting of reagents or catalysts, the scavenging of spent materials or impurities, or even the temporary hosting of reactive intermediates prior to their reaction and release from the support. This chapter provides a comprehensive overview of such polymer-supported techniques. Keywords: polymer-supported reagents • multistep flow synthesis • natural products • pharmaceutical agents • catch and release 10 Intermolecular Transition-Metal-Catalyzed C—C Coupling Reactions in Continuous Flow
C. Bottecchia and T. Noël This chapter provides an up-to-date collection of prominent examples of intermolecular transition-metal-catalyzed C—C coupling reactions performed in continuous-flow systems. The advantages offered by flow technology for the implementation of traditional cross-coupling methods are discussed. Moreover, recent examples of the successful application of flow reactors for C—H functionalization strategies (including C—H activation and dual photoredox transition-metal catalysis) are reviewed. Keywords: transition-metal catalysis • cross coupling • Suzuki–Miyaura coupling • Negishi coupling • Mizoroki–Heck coupling • carbonylative coupling • continuous flow • C—H functionalization • dehydrogenative coupling • C—H activation • dual catalysis 11 Immobilized Catalysts for Asymmetric...