Microreactors in Organic Synthesis and Catalysis

Thomas Wirth3527318690, 9783527318698

This one-stop reference is the first book on this emerging and rapid developing field with a focus on synthesis and catalysis. As such, it covers all aspects from academia and industry in a clearly structured way. Leading experts provide the background information as an initial aid for newcomers to the field, while chapters on different reaction types and industrial applications make this an equally vital resource for specialists.

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Table of contents :
Microreactors in Organic Synthesis and Catalysis……Page 4
Contents……Page 8
Preface……Page 14
List of Contributors……Page 16
1.1 Manufacturing Techniques for Metals……Page 18
1.1.1 Etching……Page 19
1.1.2 Machining……Page 21
1.1.3 Generative Method: Selective Laser Melting (SLM)……Page 23
1.1.4 Metal-Forming Techniques……Page 24
1.1.5 Assembling and Bonding of Metal Microstructures……Page 26
1.2 Ceramic Devices……Page 29
1.2.1 Joining and Sealing……Page 31
References……Page 32
2.1 How Microreactors are Constructed……Page 36
2.2 Glass as Material……Page 37
2.3 Silicon as Material……Page 39
2.5 Structuring by Means of Masked Etching in Microsystems Technology……Page 41
2.6 Etching Technologies……Page 43
2.6.1 Anisotropic (Crystallographic) Wet Chemical Etching of Silicon (KOH)……Page 44
2.6.2 Isotropic Wet Chemical Etching of Silicon……Page 46
2.6.3 Anisotropic Dry Etching of Silicon……Page 47
2.6.4 Isotropic Wet Chemical Etching of Silicon Glass……Page 48
2.6.5 Photostructuring of Special Glass……Page 49
2.7.1 Drilling, Diamond Lapping, Ultrasonic Lapping……Page 51
2.7.2 Micropowder Blasting……Page 52
2.7.3 Summary……Page 54
2.8.2 Silicon Direct Bonding (Silicon Fusion Bonding)……Page 55
2.9 Establishing Fluid Contact……Page 56
References……Page 58
3.1 Introduction……Page 60
3.2.1 Geometries……Page 61
3.2.2 Constructional Materials and Their Properties……Page 62
3.3.1 Fluid Flow……Page 63
3.3.2 Fluid Delivery……Page 65
3.3.3 Mixing Mechanisms……Page 66
3.5.1 Overview……Page 67
3.5.2 Unstable Intermediates Fast and Exothermic Reactions……Page 68
3.5.4.1 Sustainability Agenda……Page 69
3.5.4.2 Point-of-Demand Synthesis……Page 70
References……Page 71
4.1.1 Acid-Promoted Reactions……Page 76
4.1.2 Base-Promoted Reactions……Page 79
4.1.3 Condensation Reactions……Page 81
4.1.4 Metal-Catalyzed Reactions……Page 85
4.1.5 Photochemical Reactions……Page 87
4.1.6 Electrochemical Reactions……Page 92
4.1.7.2 Grignard Exchange Reaction……Page 97
4.1.7.4 Phenyl Boronic Acid Synthesis……Page 98
References……Page 99
4.2.1 Introduction……Page 101
4.2.2 Concepts in Flow Mode Synthesis……Page 102
4.2.3.1 On-Bead Synthesis……Page 103
4.2.3.2 Solution-Phase Synthesis……Page 104
4.2.3.3 Library Synthesis in Flow……Page 106
4.2.3.4 Heterocycle Synthesis……Page 107
4.2.4 Introduction to Monoliths……Page 110
4.2.5.1 Reduction……Page 112
4.2.5.2 Oxidation……Page 116
4.2.5.3 Cross-Coupling Reactions……Page 117
4.2.5.4 Olefin Metathesis……Page 122
4.2.6.1 Hydrolytic Kinetic Resolution……Page 124
4.2.6.2 Organometallic Additions……Page 125
4.2.6.3 Enantioselective Diels–Alder Reactions……Page 126
4.2.6.5 Cyclopropanation……Page 127
4.2.6.7 β-Lactam Synthesis……Page 128
4.2.6.8 Asymmetric Chlorination……Page 129
4.2.7 Multistep Synthesis……Page 130
4.2.8 Conclusions and Outlook……Page 134
References……Page 135
4.3.1 Introduction……Page 139
4.3.2 Background……Page 140
4.3.3 Kinetics of Biphasic Systems……Page 141
4.3.4 Biphasic Flow in Microchannels……Page 142
4.3.5 Surface–Liquid and Liquid–Liquid Interactions……Page 144
4.3.6 Liquid–Liquid Microsystems in Organic Synthesis……Page 149
4.3.7 Conclusions and Outlook……Page 154
References……Page 155
4.4.2.1 Contacting with Continuous Phases……Page 156
4.4.2.2 Falling-Film Microreactor……Page 157
4.4.2.3 Contact with Disperse Phases……Page 163
4.4.3.1 Direct Fluorination of Aromatics……Page 172
4.4.3.2 Oxidations of Alcohols, Diols and Ketones with Fluorine……Page 177
4.4.3.3 Photochlorination of Aromatic Isocyanates……Page 178
4.4.3.4 Monochlorination of Acetic Acid……Page 179
4.4.3.5 Sulfonation of Toluene……Page 180
4.4.3.6 Photooxidation of α-Terpinene and Cyclopentadiene……Page 182
4.4.3.7 Reactive Carbon Dioxide Absorption……Page 184
4.4.4.1 Cyclohexene Hydrogenation over Pt/Al(2)O(3)……Page 186
4.4.4.2 Hydrogenation of p-Nitrotoluene and Nitrobenzene over Pd/C and Pd/Al(2)O(3)……Page 187
4.4.4.3 Hydrogenation of α-Methylstyrene over Pd/C……Page 189
4.4.5.1 Asymmetric Hydrogenation of Cinnamic Acid Derivatives……Page 190
4.4.5.2 Asymmetric Hydrogenation of Methylacetamidocinnamate……Page 193
4.4.7 Conclusions and Outlook……Page 195
References……Page 196
4.5.1 General Introduction……Page 200
4.5.2.1 Protein and DNA Analysis……Page 201
4.5.2.2 DNA Amplifications……Page 205
4.5.2.3 Enzyme-Linked Immunoassays……Page 206
4.5.2.4 Other Diagnostic Applications……Page 209
4.5.3 Biocatalysis……Page 210
4.5.3.1 Enzyme Kinetics in Microreactors……Page 211
4.5.3.2 Biocatalyzed Synthesis in Microreactors……Page 213
4.5.3.3 Complex Catalysis in Microbioreactors……Page 221
4.5.4 Conclusions……Page 222
References……Page 223
5.1 Mission Statement from Industry on Impact and Hurdles……Page 228
5.2.1 Peptide Synthesis……Page 229
5.2.2 Hantzsch Synthesis……Page 232
5.2.3 Knorr Synthesis……Page 233
5.2.4 Enamine Synthesis……Page 234
5.2.6 Wittig Reaction……Page 235
5.2.7 Polyethylene Formation……Page 236
5.2.8 Diastereoselective Alkylation……Page 237
5.2.9 Multistep Synthesis of a Radiolabeled Imaging Probe……Page 238
5.3.1 Nitration of Substituted Benzene Derivatives……Page 240
5.3.2 Phenyl Boronic Acid Synthesis……Page 241
5.3.4 Desymmetrization of Thioureas……Page 243
5.3.6 Ester Hydrolysis to Produce an Alcohol……Page 245
5.3.9 (S)-2-Acetyl Tetrahydrofuran Synthesis……Page 246
5.3.10 Synthesis of Intermediate for Quinolone Antibiotic Drug……Page 247
5.3.11 Domino Cycloadditions in Parallel Fashion……Page 248
5.3.13 Methyl Carbamate Synthesis……Page 250
5.3.14 Newman–Kuart Rearrangement……Page 251
5.3.15 Ring-Expansion Reaction of N-Boc-4-Piperidone……Page 252
5.3.16 Grignard and Organolithium Reagents……Page 253
5.4.1 Hydrogen Peroxide Synthesis……Page 255
5.4.2 Diverse Case Studies at Lonza……Page 257
5.4.3 Polyacrylate Formation……Page 259
5.4.4 Butyl Lithium-Based Alkylation Reactions……Page 260
5.4.5 German Project Cluster 2005……Page 262
5.4.7 Development for Liquid/Liquid and Gas/Liquid Fine-Chemicals Production……Page 263
5.4.8 Development of Pharmaceutical Intermediates Production by Ozonolysis and Halogenation……Page 264
5.4.9 Industrial Photochemistry……Page 267
5.4.11 Japanese Project Cluster 2002……Page 268
5.4.12 Pilot Plant for MMA Manufacture……Page 269
5.4.13 Grignard Exchange Reaction……Page 270
5.4.14 Halogen–Lithium Exchange Pilot Plant……Page 271
5.4.15 Swern–Moffat Oxidation Pilot Plant……Page 273
5.4.17 Polycondensation……Page 274
5.4.18 Friedel–Crafts Alkylation……Page 276
5.4.19 H(2)O(2) Based Oxidation to 2-Methyl-1,4-Naphthoquinone……Page 277
5.4.20 Direct Fluorination of Ethyl 3-Oxobutanoate……Page 278
5.4.21 Propene Oxide Formation……Page 279
5.4.22 Diverse Industrial Pilot-Oriented Involvements……Page 281
5.4.23 Production of Polymer Intermediates……Page 282
5.4.24 Synthesis of Diazo Pigments……Page 283
5.4.25 Nitroglycerine Production……Page 285
5.4.26 Fine-Chemical Production Process……Page 286
5.4.27 Grignard-Based Enolate Formation……Page 287
5.5 Challenges and Concerns……Page 288
References……Page 289
Index……Page 294