Fundamentals (eBook)

Fundamentals

Ferenc Darvas, Volker Hessel, György Dorman (Herausgeber)

eBook Download: PDF | EPUB

2014 | 1. Auflage
313 Seiten
Walter de Gruyter GmbH & Co.KG (Verlag)
978-3-11-028916-9 (ISBN)

Infos

Broader theoretical insight on organic reactions in driving them 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. Our book provides a comprehensive discussion on the theoretical foundation of flow chemistry.

Ferenc Darvas, Florida Int.Uni., Miami, USA; Volker Hessel, TU Eindhoven,The Netherlands; György Dorman, ThalesNano, Budapest, Hungary

Inhalt

Preface 5
About the editors 13
Abbreviations 17
Part I Introduction and outlook 19
1 Introduction and outlook 21
Part II Theoretical foundations 25
2 Fundamentals of Flow Chemistry 27
2.1 Fundamentals of chemical reactions 27
2.1.1 Thermodynamic requirements for reaction 27
2.1.2 Kinetic requirements for a reaction 28
2.1.3 Reaction order and kinetics 30
2.1.4 Diffusion control 31
2.1.5 Kinetic versus thermodynamic control 31
2.1.6 Competing reactions 33
2.1.7 Initiation and termination of chemical reactions 33
2.1.8 Exotherm and endoterm reactions 34
2.1.9 How to accelerate an organic chemical reaction. Shifting the equilibrium towards product formation 34
2.2 Batch versus flow reactions 38
2.2.1 Performing chemical reactions in batch and flow 41
2.2.2 Multistep reactions in batch and flow 44
2.2.3 The dimensions of batch (flask) and flow (micro) reactors 44
2.2.4 Mixing in batch versus microreactors 45
2.2.5 Mass transfer in batch and flow 46
2.2.6 Temperature control in batch and flow 47
2.2.7 Heterogeneous catalytic reactions in batch and flow 50
2.3 Introduction to the basics of microfluidics 52
2.3.1 Electroosmotic (electrokinetic) flow (EOF) 52
2.3.2 Hydrodynamic (pressure-driven) pumping 54
2.3.3 Segmented flow 55
2.3.4 Centrifugal pumping 56
2.3.5 Laminar and turbulent flow regimes, the Reynolds number 56
2.3.6 Axial dispersion versus radial dispersion (Bodenstein and Peclet Numbers) 59
2.3.7 Mixing versus reaction rate–Damköhler Number 59
2.3.8 Heat transfer in flow 60
2.3.9 Flow rates in microreactors 61
2.4 Microreactors in general 62
2.4.1 General properties of flow reactors 62
2.4.2 Major flow reactor configurations 65
2.5 Essentials of reaction planning and realization in continuous flow 67
2.5.1 Classification of chemical reactions based on reaction kinetics 67
2.5.2 Flash chemistry 68
2.5.3 High-resolution reaction time control 69
2.5.4 Novel process windows 70
2.5.5 Process intensification 73
3 Principles of controlling reactions in flow chemistry 77
3.1 Introduction 77
3.2 Reactions in a flow microreactor 77
3.2.1 Reaction time in a batch reactor 77
3.2.2 Residence time control in a flow reactor 78
3.2.3 Why micro? 80
3.3 High-resolution reaction time control of reactions in flow 86
3.3.1 The principle 86
3.3.2 Example 1: Phenyllthiums bearing alkoxycarbonyl groups 88
3.3.3 Temperature–residence time map 90
3.3.4 Example 2: Control of isomerization. Aryllithiums bearing a nitro group 94
3.4 Space integration of reactions 95
3.4.1 The concept 95
3.4.2 Example 3: Synthesis of disubstituted benzenes from dibromobenzene 96
3.4.3 Example 4: Synthesis of TAC-101 97
3.4.4 Linear integration and convergent integration 98
3.4.5 Example 5: Synthesis of unsymmetrically-substituted photochromic diarylethenes. Convergent integration 99
3.4.6 Example 6: Integration of lithiation and cross-coupling 100
3.4.7 Example 7: Anionic polymerization of styrene and synthesis of block copolymers with a silicon core 103
3.4.8 Example 8: Anionic block copolymerization of styrene and methyl methacrylate 106
3.5 Summary 107
4 Technology overview/Overview of the devices 113
4.1 General aspects 113
4.2 Pumps for liquid handling 114
4.2.1 Syringe pump 114
4.2.2 Piston pump 115
4.2.3 Other pumps 116
4.3 Mass-flow controllers 117
4.4 Heating/cooling of the reaction zone 117
4.5 Back-pressure regulators 118
4.6 Mixers 119
4.6.1 Modular mixers 120
4.6.2 In-line mixers 121
4.7 Reactors 123
4.7.1 Coil reactors 124
4.7.2 Chip reactors 126
4.7.3 Packed-bed or fixed-bed reactors 127
4.8 Miscellaneous techniques 130
4.8.1 Tube-in-tube reactor 130
4.8.2 Segmented flow biphasic reactions 131
4.8.3 Falling film reactors 134
4.8.4 Flow microwave reactors 135
4.8.5 UV reactors 136
4.8.6 Working with supercritical CO2 137
4.9 Assembling and using a flow reactor 138
4.10 Commercially available systems for the laboratory use 141
5 From batch to continuous chemical synthesis – a toolbox approach 159
5.1 Chemical process development and scale-up challenges 159
5.1.1 Batch synthesis: Current profile of the pharmaceutical and fine-chemical industry 159
5.1.2 Flow chemistry and microreactor technology: a viable alternative? 160
5.1.3 Modularized process intensification – use the right tool at the right place 161
5.2 Reaction categories based on rate 164
5.2.1 Type A reactions 164
5.2.2 Type B reactions 164
5.2.3 Type C reactions 165
5.3 Reacting phases 165
5.3.1 Single phase systems – mix-then-reside 165
5.3.2 Liquid-liquid systems – mix-and-reside versus active mixing 166
5.3.3 Gas-liquid systems – use of pressure 168
5.3.4 Liquid-solid systems 168
5.4 Summary 168
Part III Lab and teaching practise 173
6 Experimental procedures for conducting organic reactions in continuous flow 175
6.1 Flow chemistry calculations 175
6.1.1 Reaction and microreactor temperature 175
6.1.2 Determination of flow rates 175
6.1.3 Example calculation 176
6.2 Wittig reaction in a continuous-flowmicroreactor 177
6.2.1 Continuous-flow design 177
6.2.2 Basic experiment 178
6.2.3 Optimization experiment 179
6.3 Swern–Moffatt oxidation in a continuous-flow microreactor 181
6.3.1 Continuous-flow design 181
6.3.2 Basic experiment 182
6.3.3 Optimization experiment 184
6.3.4 Optimization experiment on a different substrate 185
6.4 Synthesis of silver nanoparticles in a continuous-flow microreactor 186
6.4.1 Continuous-flow design 187
6.4.2 Basic experiment 187
6.4.3 Optimization experiment 190
6.5 1,2,3-triazole synthesis in continuous flow with copper powder and additives 190
6.5.1 Continuous-flow design 191
6.5.2 Basic experiment 192
6.5.3 Optimization experiment 192
6.6 Heterogeneous catalytic deuteration with D2O in continuous flow 194
6.6.1 Continuous-flow design 194
6.6.2 Basic experiment 195
6.6.3 Optimization experiment 196
6.7 Aldol reaction in a continuous-flow microreactor 196
6.7.1 Continuous-flow design 197
6.7.2 Basic aldol experiment 197
6.7.3 Aldol reaction optimization 198
6.8 Prilezhaev epoxidation in a continuous-flow microreactor 199
6.8.1 Continuous-flow design 199
6.8.2 Basic epoxidation experiment 200
6.9 Peptide catalyzed stereoselective reactions in a continuous-flow reactor 202
6.9.1 Continuous-flow design 204
6.9.2 Basic aldol experiment 204
6.9.3 Reaction optimization 205
7 Experimental procedures for conducting organic reactions in continuous flow 209
7.1 Pyrrole synthesis by Paal–Knorr cyclocondensation 210
7.1.1 Background 210
7.1.2 The flow process 211
7.1.3 Experimental procedures 213
7.2 Diels–Alder Reactions in flow chemistry 214
7.2.1 Background 214
7.2.2 The flow process 214
7.2.3 Experimental procedures 217
7.3 Copper-catalyzed azide-alkyne cycloaddition in flow using inductive heating 218
7.3.1 Background 218
7.3.2 The flow process 220
7.3.3 Experimental procedures 221
7.4 Nef Oxidation of nitroalkanes with KMnO 222
7.4.1 Background 222
7.4.2 The flow process 222
7.4.3 Experimental procedures 224
7.5 Suzuki–Miyaura cross-coupling with palladium-catalysts generated in flow 225
7.5.1 Background 225
7.5.2 The flow process 226
7.5.3 Experimental procedures 228
7.6 Oxidative amidation of aromatic aldehydes 229
7.6.1 Background 229
7.6.2 The flow process 230
7.6.3 Experimental procedures 231
7.7 Azide synthesis in flow via diazotransfer 233
7.7.1 Background 233
7.7.2 The flow process 234
7.7.3 Experimental procedures 235
7.8 Boronic acid/ester synthesis via lithium halogen exchange in a Cryo-Flow Reactor 237
7.8.1 Background 237
7.8.2 The flow process 237
7.8.3 Experimental procedures 240
7.9 The Ritter Reaction in Continuous Flow 241
7.9.1 Background 241
7.9.2 The flow process 242
7.9.3 Experimental procedures 243
7.10 Vilsmeier–Haack formylation of electron-rich arenes 244
7.10.1 Background 244
7.10.2 The flow process 245
7.10.3 Experimental procedures 248
7.11 Appel reaction using monolithic triphenylphosphine in flow 248
7.11.1 Background 248
7.11.2 The flow process 250
7.11.3 Experimental procedures 252
7.12 Schenck ene reaction in flow using singlet oxygen 253
7.12.1 Background 253
7.12.2 The flow process 254
7.12.3 Experimental procedure 257
7.13 Chemoenzymatic flow synthesis of cyanohydrins 259
7.13.1 Background 259
7.13.2 The flow process 260
7.13.3 Experimental procedures 261
7.14 Summary 262
8 The Microwave-to-flow paradigm: translating batch microwave chemistry to continuous-flow processes 269
8.1 Microwave chemistry 269
8.2 Converting microwave to flow chemistry 270
8.3 Summary 275
9 Incorporation of continuous-flow processing into the undergraduate teaching laboratory: key concepts and two case studies 277
9.1 Introduction 277
9.2 Equipment 278
9.3 Experiments developed for the undergraduate teaching laboratory 280
9.4 Development of two new experiments for the undergraduate laboratory 280
9.4.1 The Biginelli Reaction 282
9.4.2 The Claisen–Schmidt Reaction 287
9.5 Summary 291
9.6 Acknowledgements 291
Answers to the study questions 295
Index 309

Produkt-Details

• Erscheint lt. Verlag: 25.8.2014
• Co-Autor: Kaspar Koch, Nicholas E. Leadbeater, Holger Lowe, Arturo Macchi, Istvan M. Mandity, Pieter Nieuwland, Sandor B. Otvos, Patrick Plouffe, Dominique Roberge, Floris Rutjes, Rene Becker, Jun-ichi Yoshida, Marielle M.E. Delville, Melinda Fekete, Ferenc Fulop, Toma Glasnov, Trevor A. Hamlin, Robert K. Harmel, C. Oliver Kappe
• Vorwort: Klavs F. Jensen
• Sprache: englisch
• Themenwelt: Naturwissenschaften ► Chemie ► Analytische Chemie
• Themenwelt: Naturwissenschaften ► Chemie ► Organische Chemie
• Themenwelt: Naturwissenschaften ► Chemie ► Technische Chemie
• Themenwelt: Technik ► Maschinenbau
• Themenwelt: Technik ► Umwelttechnik / Biotechnologie
• ISBN-10: 3-11-028916-4 / 3110289164
• ISBN-13: 978-3-11-028916-9 / 9783110289169