Flow Chemistry: Volume 1 Flow Chemistry – Fundamentals

Description

"Flow Chemistry fills the gap in graduate education by covering chemistry and reaction principles along with current practice, including examples of relevant commercial reaction, separation, automation, and analytical equipment. The Editors of Flow Chemistry are commended for having taken the initiative to bring together experts from the field to provide a comprehensive treatment of fundamental and practical considerations underlying flow chemistry. It promises to become a useful study text and as well as reference for the graduate students and practitioners of flow chemistry." Professor Klavs Jensen Massachusetts Institute of Technology, USA Broader theoretical insight in driving a chemical reaction automatically opens the window towards new technologies particularly to flow chemistry. This emerging concept promotes the transformation of present day's organic processes into a more rapid continuous set of synthesis operations, more compatible with the envisioned sustainable world. These two volumes Fundamentals and Applications provide both the theoretical foundation as well as the practical aspects. Starts from the principles of this new technology and develops promising applications in a clear and instructive manner Includes numerous illustrations, figures and tables Also available: Volume 2 APPLICATIONS, ISBN: 978-3-11-036707-2 Preface About the editors Abbreviations Part I Introduction and outlook 1 Introduction and outlook Part II Theoretical foundations 2 Fundamentals of Flow Chemistry 2.1 Fundamentals of chemical reactions 2.1.1 Thermodynamic requirements for reaction 2.1.2 Kinetic requirements for a reaction 2.1.3 Reaction order and kinetics 2.1.4 Diffusion control 2.1.5 Kinetic versus thermodynamic control 2.1.6 Competing reactions 2.1.7 Initiation and termination of chemical reactions 2.1.8 Exotherm and endoterm reactions 2.1.9 How to accelerate an organic chemical reaction. Shifting the equilibrium towards product formation 2.2 Batch versus flow reactions 2.2.1 Performing chemical reactions in batch and flow 2.2.2 Multistep reactions in batch and flow 2.2.3 The dimensions of batch (flask) and flow (micro) reactors 2.2.4 Mixing in batch versus microreactors 2.2.5 Mass transfer in batch and flow 2.2.6 Temperature control in batch and flow 2.2.7 Heterogeneous catalytic reactions in batch and flow 2.3 Introduction to the basics of microfluidics 2.3.1 Electroosmotic (electrokinetic) flow (EOF) 2.3.2 Hydrodynamic (pressure-driven) pumping 2.3.3 Segmented flow 2.3.4 Centrifugal pumping 2.3.5 Laminar and turbulent flow regimes, the Reynolds number 2.3.6 Axial dispersion versus radial dispersion (Bodenstein and Peclet Numbers) 2.3.7 Mixing versus reaction rate–Damköhler Number 2.3.8 Heat transfer in flow 2.3.9 Flow rates in microreactors 2.4 Microreactors in general 2.4.1 General properties of flow reactors 2.4.2 Major flow reactor configurations 2.5 Essentials of reaction planning and realization in continuous flow 2.5.1 Classification of chemical reactions based on reaction kinetics 2.5.2 Flash chemistry 2.5.3 High-resolution reaction time control 2.5.4 Novel process windows 2.5.5 Process intensification 3 Principles of controlling reactions in flow chemistry 3.1 Introduction 3.2 Reactions in a flow microreactor 3.2.1 Reaction time in a batch reactor 3.2.2 Residence time control in a flow reactor 3.2.3 Why micro? 3.3 High-resolution reaction time control of reactions in flow 3.3.1 The principle 3.3.2 Example 1: Phenyllthiums bearing alkoxycarbonyl groups 3.3.3 Temperature–residence time map 3.3.4 Example 2: Control of isomerization. Aryllithiums bearing a nitro group 3.4 Space integration of reactions 3.4.1 The concept 3.4.2 Example 3: Synthesis of disubstituted benzenes from dibromobenzene 3.4.3 Example 4: Synthesis of TAC-101 3.4.4 Linear integration and convergent integration 3.4.5 Example 5: Synthesis of unsymmetrically-substituted photochromic diarylethenes. Convergent integration 3.4.6 Example 6: Integration of lithiation and cross-coupling 3.4.7 Example 7: Anionic polymerization of styrene and synthesis of block copolymers with a silicon core 3.4.8 Example 8: Anionic block copolymerization of styrene and methyl methacrylate 3.5 Summary 4 Technology overview/Overview of the devices 4.1 General aspects 4.2 Pumps for liquid handling 4.2.1 Syringe pump 4.2.2 Piston pump 4.2.3 Other pumps 4.3 Mass-flow controllers 4.4 Heating/cooling of the reaction zone 4.5 Back-pressure regulators 4.6 Mixers 4.6.1 Modular mixers 4.6.2 In-line mixers 4.7 Reactors 4.7.1 Coil reactors 4.7.2 Chip reactors 4.7.3 Packed-bed or fixed-bed reactors 4.8 Miscellaneous techniques 4.8.1 Tube-in-tube reactor 4.8.2 Segmented flow biphasic reactions 4.8.3 Falling film reactors 4.8.4 Flow microwave reactors 4.8.5 UV reactors 4.8.6 Working with supercritical CO2 4.9 Assembling and using a flow reactor 4.10 Commercially available systems for the laboratory use 5 From batch to continuous chemical synthesis – a toolbox approach 5.1 Chemical process development and scale-up challenges 5.1.1 Batch synthesis: Current profile of the pharmaceutical and fine-chemical industry 5.1.2 Flow chemistry and microreactor technology: a viable alternative? 5.1.3 Modularized process intensification – use the right tool at the right place 5.2 Reaction categories based on rate 5.2.1 Type A reactions 5.2.2 Type B reactions 5.2.3 Type C reactions 5.3 Reacting phases 5.3.1 Single phase systems – mix-then-reside 5.3.2 Liquid-liquid systems – mix-and-reside versus active mixing 5.3.3 Gas-liquid systems – use of pressure 5.3.4 Liquid-solid systems 5.4 Summary Part III Lab and teaching practise 6 Experimental procedures for conducting organic reactions in continuous flow 6.1 Flow chemistry calculations 6.1.1 Reaction and microreactor temperature 6.1.2 Determination of flow rates 6.1.3 Example calculation 6.2 Wittig reaction in a continuous-flowmicroreactor 6.2.1 Continuous-flow design 6.2.2 Basic experiment 6.2.3 Optimization experiment 6.3 Swern–Moffatt oxidation in a continuous-flow microreactor 6.3.1 Continuous-flow design 6.3.2 Basic experiment 6.3.3 Optimization experiment 6.3.4 Optimization experiment on a different substrate 6.4 Synthesis of silver nanoparticles in a continuous-flow microreactor 6.4.1 Continuous-flow design 6.4.2 Basic experiment 6.4.3 Optimization experiment 6.5 1,2,3-triazole synthesis in continuous flow with copper powder and additives 6.5.1 Continuous-flow design 6.5.2 Basic experiment 6.5.3 Optimization experiment 6.6 Heterogeneous catalytic deuteration with D2O in continuous flow 6.6.1 Continuous-flow design 6.6.2 Basic experiment 6.6.3 Optimization experiment 6.7 Aldol reaction in a continuous-flow microreactor 6.7.1 Continuous-flow design 6.7.2 Basic aldol experiment 6.7.3 Aldol reaction optimization 6.8 Prilezhaev epoxidation in a continuous-flow microreactor 6.8.1 Continuous-flow design 6.8.2 Basic epoxidation experiment 6.9 Peptide catalyzed stereoselective reactions in a continuous-flow reactor 6.9.1 Continuous-flow design 6.9.2 Basic aldol experiment 6.9.3 Reaction optimization 7 Experimental procedures for conducting organic reactions in continuous flow 7.1 Pyrrole synthesis by Paal–Knorr cyclocondensation 7.1.1 Background 7.1.2 The flow process 7.1.3 Experimental procedures 7.2 Diels–Alder Reactions in flow chemistry 7.2.1 Background 7.2.2 The flow process 7.2.3 Experimental procedures 7.3 Copper-catalyzed azide-alkyne cycloaddition in flow using inductive heating 7.3.1 Background 7.3.2 The flow process 7.3.3 Experimental procedures 7.4 Nef Oxidation of nitroalkanes with KMnO 7.4.1 Background 7.4.2 The flow process 7.4.3 Experimental procedures 7.5 Suzuki–Miyaura cross-coupling with palladium-catalysts generated in flow 7.5.1 Background 7.5.2 The flow process 7.5.3 Experimental procedures 7.6 Oxidative amidation of aromatic aldehydes 7.6.1 Background 7.6.2 The flow process 7.6.3 Experimental procedures 7.7 Azide synthesis in flow via diazotransfer 7.7.1 Background 7.7.2 The flow process 7.7.3 Experimental procedures 7.8 Boronic acid/ester synthesis via lithium halogen exchange in a Cryo-Flow Reactor 7.8.1 Background 7.8.2 The flow process 7.8.3 Experimental procedures 7.9 The Ritter Reaction in Continuous Flow 7.9.1 Background 7.9.2 The flow process 7.9.3 Experimental procedures 7.10 Vilsmeier–Haack formylation of electron-rich arenes 7.10.1 Background 7.10.2 The flow process 7.10.3 Experimental procedures 7.11 Appel reaction using monolithic triphenylphosphine in flow 7.11.1 Background 7.11.2 The flow process 7.11.3 Experimental procedures 7.12 Schenck ene reaction in flow using singlet oxygen 7.12.1 Background 7.12.2 The flow process 7.12.3 Experimental procedure 7.13 Chemoenzymatic flow synthesis of cyanohydrins 7.13.1 Background 7.13.2 The flow process 7.13.3 Experimental procedures 7.14 Summary 8 The Microwave-to-flow paradigm: translating batch microwave chemistry to continuous-flow processes 8.1 Microwave chemistry 8.2 Converting microwave to flow chemistry 8.3 Summary 9 Incorporation of continuous-flow processing into the undergraduate teaching laboratory: key concepts and two case studies 9.1 Introduction 9.2 Equipment 9.3 Experiments developed for the undergraduate teaching laboratory 9.4 Development of two new experiments for the undergraduate laboratory 9.4.1 The Biginelli Reaction 9.4.2 The Claisen–Schmidt Reaction 9.5 Summary 9.6 Acknowledgements Answers to the study questions Index