Flow Chemistry. Volume 2, Flow Chemistry - Applications

The fully up-dated edition of the two-volume work covers both the theoretical foundation as well as the practical aspects. A strong insight in driving a chemical reaction is crucial for a deeper understanding of new potential technologies. New procedures for warranty of safety and green principles are discussed. Vol. 1: Fundamentals. - Filling the gap by covering fundamental reaction principles as well as current applications. - Provides examples of relevant commercial separation, automation, and analytical equipment. - New: Applications in photo-, electrochemistry and nanotechnology. Cover Half Title Also of Interest Flow Chemistry. Volume 2: Applications Copyright Preface Acknowledgments Contents About the editors Contributing authors 1. Photochemical transformations in continuous-flow reactors 1.1 Introduction 1.2 Photochemical versus thermochemical activation of molecules 1.3 Important considerations when performing photochemistry in microreactors 1.4 How to build your own photochemical reactor 1.5 The selection of the right light source 1.6 How flow can make an impact on synthetic organic photochemistry - concrete examples 1.6.1 Homogeneous reaction conditions 1.6.2 Multiphase reaction conditions 1.7 Scale-up of photochemical processes 1.8 Use of automation protocols in combination of photochemical flow reactors 1.9 Summary References 2. Electrochemical processes in flow 2.1 Electrochemical aspects in flow 2.1.1 General electrochemical aspects 2.1.2 Electrolysis in flow 2.1.3 Follow-up conversions 2.1.4 Availability of lab-scale flow electrolyzers 2.2 Design of flow electrolyzers 2.2.1 Industrial narrow gap cells 2.2.2 Membrane/diaphragm-separated electrolyzer cells and plate-frame approach 2.2.3 Gas diffusion electrodes 2.2.4 Electrochemical system design 2.3 Electrochemical processes in flow 2.3.1 Industrial electrochemical processes in flow 2.3.2 Electroconversion of small molecules 2.3.3 Electrosynthesis with high value addition 2.3.4 Electrochemical synthesis of drug metabolites 2.3.5 Paired and consecutive electrolysis 2.4 Strategies for screening and optimization 2.5 Options for industrialization and scale-up References 3. Continuous flow methods for synthesis of functional materials 3.1 Introduction 3.1.1 Flow synthesis of materials and difference from the typical flow synthesis of organic compounds 3.1.1.1 Classifications: size, shape, and form of materials 3.1.2 Material synthesis approach in flow 3.2 Protocols for flow synthesis of materials and various examples 3.2.1 Flow synthesis of metal, metal oxides, and silica particles 3.2.1.1 Metals 3.2.1.2 Microparticles to atomic clusters 3.2.1.3 Nanoclusters/ultra-small nanoparticles 3.2.1.4 Metal oxides and chalcogenides 3.2.1.5 Silica 3.2.2 Nanohybrids 3.2.3 Two-dimensional materials 3.2.4 Catalysts 3.2.5 Porous materials 3.2.6 Mesoporous materials 3.2.7 Quantum dots 3.3 High-throughput continuous flow synthesis of materials 3.4 Challenges and future directions 3.4.1 Challenges associated with separation and purification of the materials (and recent developments in this direction) 3.4.2 Immobilization of materials 3.4.3 Process control 3.4.4 Cleaning of systems 3.5 Summary and recommendations References 4. Polymer synthesis in continuous flow 4.1 Introduction 4.2 Anionic polymerization 4.3 Homogeneous radical polymerization 4.3.1 Atom transfer radical polymerization 4.3.2 Nitroxide-mediated polymerization 4.3.3 RAFT polymerization 4.4 Ring-opening (metathesis) polymerization 4.5 Photopolymerization 4.6 Polymer modification in continuous flow 4.7 Online monitoring of continuous flow polymerizations 4.8 Machine learning in polymer flow synthesis 4.9 Conclusion and outlook References 5. Flow chemistry for nanotechnology 5.1 Introduction to nanotechnology 5.2 Nanomaterials 5.2.1 Size, structure, and size-dependent properties 5.2.2 Introduction to the diverse world of nanomaterials 5.2.2.1 Inorganic nanoparticles 5.2.2.1.1 Carbon structures 5.2.2.1.2 Metal nanoparticles 5.2.2.1.3 Multielement nanoparticles 5.2.2.2 Organic nanoparticles 5.2.2.3 Hybrid nanoparticles 5.2.2.4 Composite nanoparticles 5.3 Principles of nanoparticle synthesis 5.4 Flow chemistry–based nanoparticle synthesis in practice and their application 5.4.1 Synthesis and application of organic nanoparticles 5.4.1.1 Synthesis of drug nanoparticles 5.4.1.2 Synthesis of agrochemical nanoparticles 5.4.1.3 Application of organic nanoparticles 5.4.2 Synthesis and application of inorganic nanoparticles 5.4.2.1 Synthesis of inorganic nanoparticles 5.4.2.2 Application of inorganic nanoparticles 5.4.2.2.1 Coatings 5.4.2.2.2 Sensors 5.4.2.2.3 Biomedical applications 5.4.2.2.4 Heterogeneous catalysis 5.4.3 Synthesis of composite nanoparticles 5.4.3.1 Application of composite nanoparticles 5.4.3.1.1 The future of flow nanotechnology: an outlook References 6. From green chemistry principles to sustainable flow chemistry Objective of this chapter 6.1 Quantitative sustainability assessment and outlook to flow chemistry 6.1.1 Green metrics for use in flow chemistry 6.1.1.1 Green chemistry principles 6.1.2 Green chemistry metrics 6.1.2.1 Basic and simple green metrics 6.2 Flow chemistry and green metrics 6.2.1 Application of green metrics to flow chemistry 6.2.2 Biomass-derived and/or waste-derived alternatives to classic solvents 6.2.3 Biomass-derived solvent production in flow 6.2.3.1 Levulinic acid (LA) 6.2.3.2 GVL 6.2.3.3 2-Methyl-tetrahydrofuran (2-Me-THF) 6.2.4 Flow protocols combining biomass-derived solvents and heterogeneous catalysis 6.2.5 Waste minimization 6.2.5.1 Use of biomass-derived GVL in C–C bond formation via Heck–Mizoroki coupling with heterogeneous catalyst 6.2.5.2 Use of cyclopentyl methyl ether in the multistep flow synthesis of benzoxazoles 6.2.6 Flow-assisted sustainable synthesis of drugs and intermediates 6.2.6.1 Use of 2-Me-THF to reduce the waste associated with the synthesis of drug (Diazepam) 6.2.6.2 Flow synthesis of paroxetine intermediate with a heterogeneous organocatalyst 6.2.7 Critical evaluation to assess the greenness of synthetic procedures References 7. Flow chemistry in fine chemical production 7.1 Introduction 7.2 Advantages of flow technology in chemical production 7.2.1 Cleaner chemistry 7.2.2 Enhanced synthesis 7.2.3 New reactivity patterns 7.2.4 Improved safety 7.3 Flow chemistry in drug discovery 7.3.1 Heterogeneous organometallic catalysis 7.3.2 Homogeneous organometallic catalysis 7.3.3 Multistep and telescoped flow synthesis 7.3.4 Library synthesis 7.3.5 Other technologies applicable to drug discovery 7.3.5.1 Photochemistry 7.3.5.2 Electrochemistry 7.3.5.3 Biocatalysis 7.3.5.4 Microwaves 7.4 Flow chemistry in fragrance and agrochemical production 7.4.2 Agrochemical production 7.4.1 Fragrance production 7.5 Conclusions and outlook References 8. Scale-up of flow chemistry system 8.1 Introduction of scale-up 8.1.1 Scale-up of chemical equipment 8.1.2 Principle of scale-up of flow chemistry system 8.2 Scale-up of mixing equipment 8.2.1 Numbering-up of mixing units 8.2.2 Similarity-up of T-junction mixing unit 8.2.3 Fluid distributors in enlarged mixers 8.2.4 Package and connection of mixer 8.3 Scale-up of reaction tubes and channels 8.3.1 Numbering-up of reaction tubes for exothermic reactions 8.3.2 Numbering up of photochemical and electrochemical flow reactors 8.3.3 Fluid distributors of reaction tubes and channels 8.4 Coupling of microequipment and conventional equipment 8.4.1 Integration of micromixer with tubular reactor 8.4.2 Integration of micromixer with packed bed reactor 8.4.3 Integration of micromixer with stirred tank reactor 8.5 Examples of flow chemistry systems in industry or pilot plant 8.5.1 Butyl rubber bromination microreaction system 8.5.2 Nano-calcium carbonate powder preparation reactor 8.5.3 Cyclohexanone-oxime Beckman rearrangement reactor 8.5.4 Bromo-3-methylanisole synthesis reaction system 8.5.5 Food-grade phosphoric acid purification equipment 8.6 Summary References 9. Exothermic advanced manufacturing techniques in reactor engineering: 3D printing applications in flow chemistry 9.1 Introduction to 3D printing applied to flow chemistry 9.2 Classification of 3DP techniques 9.2.1 Vat photopolymerization 9.2.2 Powder-based technologies 9.2.3 Extrusion technologies 9.2.4 Jetting technologies 9.2.5 Other AM technologies 9.3 Applications of 3D printing in flow chemistry 9.4 Future directions: digitalization of reactor design and manufacturing 9.5 Conclusions References 10. Continuous-flow biocatalysis with enzymes and cells 10.1 Introduction 10.2 Considerations for the design of CF biocatalysis procedures 10.2.1 Choice of biocatalysts 10.2.1.1 Single-enzyme or multienzyme-based processes 10.2.1.2 Cell-free or cell-based: advantages and disadvantages 10.2.1.3 Immobilized or not? 10.2.2 Key design criteria 10.2.2.1 Operational parameters 10.2.2.2 Kinetics 10.2.2.3 Choice of reactor 10.2.2.4 Analytical methods and in-process control 10.2.2.5 Optimization of CF reactors with enzymes 10.3 Practical guide to CF biocatalysis 10.3.1 Production of enzymes and cofactors 10.3.2 In situ immobilization 10.3.3 Optimization of reaction under flow conditions 10.3.4 Downstream processing and recycling 10.4 Examples of CF biosynthetic syntheses 10.4.1 Large-scale biocatalysis in CF 10.4.2 Examples of continuous-flow biotransformations 10.4.3 More illustrative examples 10.5 Challenges and future opportunities 10.5.1 Upscaling and integration 10.5.2 On-demand fabrication of bioreactors 10.5.3 Machine learning in continuous monitoring and control References 11. Outlook, future directions, and emerging applications 11.1 Introduction: past, present, and future 11.2 General considerations 11.2.1 Planning to succeed 11.2.2 The right chemistry 11.2.3 Sustainability: cleaner and greener 11.2.4 Safety: protecting the user 11.2.5 Data, data, data 11.3 Current progress 11.3.1 Upstream 11.3.2 Downstream 11.3.3 Feedback and control 11.3.4 Self-optimization 11.4 The future 11.4.1 Integrating batch and flow: A hybridized approach 11.4.2 Mimicking nature: the role of biotransformations 11.4.3 Seeing the future: machine vision 11.4.4 Machine learning 11.4.5 AI: Artificial intelligence 11.4.6 Data collection and storage 11.4.7 Printing the future: 3D printing 11.4.8 High-throughput synthesis: faster is better 11.4.9 Education: teaching the next generation 11.5 Final thoughts References Answers to the study questions Index