Micro Reaction Technology in Organic Synthesis

by Wiles; Charlotte

• ISBN13: 9781439824719
• ISBN10: 1439824711
• Edition: 1st
• Format: Hardcover
• Copyright: 2011-03-15
• Publisher: CRC Press

Summary

A valuable resource for the modern synthetic chemist, this broadly applicable book addresses the multidisciplinary field of micro reaction technology from novel research technique to a synthetic approach capable of changing the way chemists perform reactions. Concise and informative, it discusses the theory of process-intensification and continuous flow purifications, describes the advantages of miniaturization of organic reactions, and offers expert insight into micro reaction technology and the opportunity to increase the efficiency of organic reactions on a broad scale.

Table of Contents

Preface	p. xiii
Acknowledgments	p. xv
Authors	p. xvii
Abbreviations	p. xix
Introduction to Micro Reaction Technology	p. 1
What Is Micro Reaction Technology?	p. 1
Fabrication/Construction of Micro Reactors	p. 2
Glass Devices	p. 2
Silicon Devices	p. 3
Polymeric Devices	p. 3
Metallic Devices	p. 3
Ceramic Devices	p. 4
Reactor to World Interface	p. 4
Manipulation of Reactants and Products within Flow Reactors	p. 4
Mixing within Micro Reactors	p. 5
Flow Types within Biphasic Systems	p. 6
Advantages of Micro Reaction Technology	p. 7
Process Safety	p. 7
Novel Reaction Conditions	p. 8
Reduced Waste Generation	p. 9
On-Site Chemical Processing	p. 11
Disadvantages of Micro Reactors	p. 11
Handling of Insoluble Materials	p. 12
Process Intensification	p. 13
In Situ Reaction Monitoring	p. 14
Raman Spectroscopy	p. 14
In Situ Analysis by FTIR Spectroscopy	p. 16
Nuclear Magnetic Resonance Detection	p. 21
Chromatographic Techniques	p. 22
Development of Sensors for Process Monitoring	p. 23
Commercial Availability of Continuous Flow Reactor Technology	p. 24
Outlook	p. 31
References	p. 31
Micro Reactions Employing a Gaseous Component	p. 37
Gas-Phase Micro Reactions	p. 37
Gas-Phase Oxidations	p. 38
Hydrogenation Reactions within Microstructured Reactors	p. 41
Dehydration and Dehydrogenation Reactions	p. 42
Fischer-Tropsch Synthesis	p. 43
Synthesis of Methylisocyanate in a Micro Reactor	p. 43
Gas-Liquid-Phase Micro Reactions	p. 44
Continuous Flow Chlorination Reactions	p. 44
Continuous Flow Fluorination Reactions	p. 45
Ozonolysis within Micro Reactors	p. 45
Biphasic Carbonylations	p. 48
Transfer Hydrogenations under Continuous Flow Conditions	p. 55
Miscellaneous Biphasic Micro Reactions	p. 57
Gas-Liquid-Solid Micro Reactions	p. 60
Triphasic Oxidations under Flow Conditions	p. 61
Carbonylations Using Solid-Supported Catalysts	p. 62
Hydrogenations within Continuous Flow Reactors	p. 63
Slurry-Based Micro Reactions	p. 66
Miscellaneous Triphasic Micro Reactions	p. 69
References	p. 70
Liquid-Phase Micro Reactions	p. 77
Nucleophilic Substitution	p. 77
C-C Bond Formation: Acylation Reactions	p. 77
C-C Bond Formation: Alkylation Reactions	p. 78
Enantioselective C-C Bond-Forming Reactions	p. 83
C-O Bond Formation: Esterification Reactions	p. 85
C-O Bond Formation: Etherification Reactions	p. 89
C-O Bond Formation: Epoxide Hydrolysis	p. 90
C-N Bond Formation: Alkylation Reactions	p. 90
C-N Bond Formation: Acylation Reactions	p. 93
C-N Bond Formation: Arylation Reactions	p. 98
C-N Bond Formation: Azidation Reactions	p. 99
C-N Bond Formation: Synthesis of Hydroxamic Acids	p. 102
C-N Bond Formation: Aminolysis of Epoxides	p. 103
C-F Bond Formation	p. 109
Electrophilic Substitution	p. 113
C-C Bond Formation	p. 113
C-N Bond-Forming Reactions: Nitration Reactions	p. 126
C-Hetero Bond-Forming Reactions: Halogenations under Flow	p. 130
C-Hetero Bond-Forming Reactions: Diazotizations under Flow	p. 133
C-Hetero Bond-Forming Reactions: Sulfonations under Flow	p. 136
Nucleophilic Addition	p. 136
C-C Bond Formation: Aldol Reaction/Condensation	p. 136
C-C Bond Formation: Knoevenagel Condensation	p. 139
C-C Bond Formation: Michael Addition	p. 142
C-C Bond Formation: Diels-Alder Reaction	p. 144
C-C Bond Formation: Horner-Wadsworth-Emmons	p. 146
C-C Bond Formation: Enantioselective Examples	p. 148
C-Hetero Bond Formation: Aza-Michael Addition	p. 149
C-Hetero Bond Formation: Alkylation of Amines	p. 151
C-Hetero' Bond Formation: Synthesis of Triazoles	p. 152
C-Hetero Bond Formation: Addition of Hydrazine to Carbonyl Compounds	p. 157
Elimination Reactions	p. 158
Dehydration Reactions	p. 158
Dehalogenations: Tris(Trimethylsilyl)Silane-Mediated Reductions	p. 160
Oxidations	p. 163
Oxidations: Inorganic Oxidants	p. 163
Oxidations: Swern-Moffat Oxidation	p. 164
Oxidations: TEMPO-Mediated Oxidations	p. 167
Oxidations Using Oxone	p. 168
Oxidations: Epoxidations under Flow Conditions	p. 168
Oxidation: Deprotection of Amines	p. 172
Reductions	p. 173
Transition Metal Free Reductions	p. 173
Dibal-H Reductions	p. 173
Metal-Catalyzed Cross-Coupling Reactions	p. 175
Suzuki-Miyaura Reaction	p. 175
Heck Reaction	p. 177
Sonogashira Reaction	p. 183
Other Metal-Catalyzed Coupling Reactions	p. 185
Rearrangements	p. 187
Claisen Rearrangement	p. 187
Newman-Kwart Rearrangement	p. 191
Hofmann Rearrangement	p. 193
Fisher Indolization	p. 195
Curtius Rearrangement	p. 196
Dimroth Rearrangement	p. 197
Multistep/Multicomponent Liquid-Phase Reactions	p. 198
Multicomponent Synthesis of Heterocycles	p. 198
Multistep Synthesis of 1,2,4-Oxadiazoles	p. 199
Continuous Flow Synthesis of Ibuprofen	p. 201
Cation-Mediated Sialylation Reactions	p. 203
Oligosaccharide Synthesis	p. 205
Synthesis of Indole Alkaloids Using Metal-Coated Capillary Reactors	p. 206
Iododeamination under Flow	p. 206
Radical Additions under Flow	p. 209
Summary	p. 211
References	p. 211
Multi-Phase Micro Reactions	p. 221
Nucleophilic Substitution	p. 221
C-O Bond-Forming Reactions: Esterifications	p. 221
C-N Bond-Forming Reactions: Azidations	p. 224
Electrophilic Substitution	p. 225
Brominations	p. 225
Phosgene Synthesis	p. 226
Nucleophilic Addition	p. 227
C-C Bond-Forming Reactions: Knoevenagel Condensation	p. 227
C-C Bond-Forming Reactions: Michael Additions	p. 229
C-C Bond-Forming Reactions: Henry Reaction	p. 230
C-C Bond-Forming Reactions: Diels-Alder	p. 232
C-C Bond-Forming Reactions: Benzoin Condensation	p. 232
C-C Bond-Forming Reactions: Trifluoromethylation under Continuous Flow	p. 234
C-C Bond Formation: Aldol Reaction	p. 234
C-N Bond Formation: Cycloaddition Reactions	p. 237
C-O Bond-Forming Reactions: Acetalizations	p. 240
C-S Bond-Forming Reactions: Thioacetalizations	p. 241
Elimination Reactions	p. 241
Dehydration Reactions	p. 241
Dehydration Reactions	p. 242
Oxidation Reactions	p. 242
Catalytic Oxidations	p. 243
Epoxidations	p. 247
Metali¿ Catalyzed Cross-Coupling Reactions	p. 250
Suzuki-Miyaura Reaction	p. 250
Heck Coupling Reactions	p. 252
Other Metal-Catalyzed Coupling Reactions	p. 255
Rearrangements	p. 261
Enantioselective Reactions	p. 262
Chemically Promoted Reactions	p. 262
Enzymatic Enantioselective Micro Reactions	p. 266
Multistep/Multicomponent Reactions	p. 272
Independent Multistep Flow Reactions	p. 272
Integrated Multistep Sequences	p. 272
Reagents and Scavengers in Series	p. 274
Combined Chemical and Biochemical Catalysis	p. 274
"Catch and Release" Strategies under Continuous Flow	p. 277
Casein Kinase I Inhibitor Synthesis	p. 280
Summary	p. 281
References	p. 283
Electrochemical and Photochemical Applications of Micro Reaction Technology	p. 289
Electrochemical Synthesis under Continuous Flow	p. 289
Electrochemical Oxidations	p. 290
Electrolyte-Free Electroorganic Synthesis	p. 296
Electrochemical Reductions	p. 298
Electrolyte-Free Reductions under Flow	p. 299
Summary	p. 301
Photochemical Synthesis under Continuous Flow	p. 302
Photocycloadditions under Continuous Flow	p. 303
Photodecarboxylative Addition	p. 307
Photocyanation	p. 307
Photochemical Halogenations	p. 308
Nitrite Photolysis under Flow Conditions	p. 309
Photochemical Dimerization	p. 311
Photosensitized Diastereo Differentiation	p. 312
Multiphase Photochemical Reactions	p. 312
Photocatalytic Reductions	p. 313
Photocatalytic Oxidation Reactions	p. 314
Photocatalytic Alkylation Reactions	p. 315
Photocatalytic Cyclizations	p. 316
Gas-Liquid Transformations	p. 317
Gas-Liquid-Solid Reactions	p. 321
Summary	p. 321
References	p. 321
The Use of Microfluidic Devices for the Preparation and Manipulation of Droplets and Inorganic/Organic Particles	p. 325
Droplet Formation Using Continuous Flow Methodology	p. 325
Polymerization of Droplets under Flow	p. 328
Preparation of Inorganic Nanoparticles under Continuous Processing Conditions	p. 330
Formation of Organic Particles within Continuous Flow Devices	p. 332
The Use of Micro Reactors for the Postsynthetic Manipulation of Organic Compounds	p. 336
Mixed Particle Formation	p. 338
Microencapsulation of Active Pharmaceuticals	p. 338
Summary	p. 341
References	p. 343
Industrial Interest in Micro Reaction Technology	p. 347
MRT in Production Environments	p. 347
Synthesis of Fine Chemicals Using Micro Reactors	p. 349
Synthesis of Carbamates under Continuous Flow Conditions	p. 350
Production-Scale Synthesis of Ionic Liquids	p. 351
Scalable Technique for the Synthesis of Diarylethenes	p. 353
Continuous Flow Synthesis of Light-Emitting Materials	p. 354
2-(2,5-Dimethyl-lH-Pyrrol-l-y1)Ethanol Synthesis	p. 356
Synthesis of Pigments under Flow Conditions	p. 357
Production of Thermally Labile Compounds under Flow Conditions	p. 358
Peracetic Acid Production Using an On-Site Microprocess	p. 360
The In Situ Synthesis and Use of Diazomethane	p. 362
Synthesis of Pharmaceuticals and Natural Products Using Continuous Flow Methodology	p. 363
Ciprofloxacin and Its Analogs	p. 363
Synthesis of Pristane	p. 363
Synthesis of Imatinib under Flow Conditions	p. 366
Synthesis of Aspirin and Vanisal Sodium	p. 368
Synthesis of Suberoylanilide Hydroxamic Acid	p. 369
Synthesis of Rimonabant and Efaproxiral Using AlMe3	p. 370
Continuous Flow Synthesis of Sildenafil	p. 372
Synthesis of 6-Hydroxybuspirone	p. 372
A Key Step in the Synthesis of (rac)-Trarnadol	p. 373
Claisen Rearrangement to Afford 2,2-Dimethyl-2H-1-Benzopyrans	p. 373
Synthesis of a 5HT1B Antagonist	p. 375
Serial Approach to a Novel Anticancer Agent Using Flow Reactors	p. 378
Synthesis of Grossamide under Flow Conditions	p. 378
Synthesis of the Natural Product (±)-Oxomaritidine	p. 378
Synthesis of Furofuran Ligans	p. 381
Synthesis of Small Doses of Radiopharmaceuticals	p. 382
Summary	p. 384
References	p. 384
Microscale Continuous Separations and Purifications	p. 387
Introduction	p. 387
Liquid-Liquid Extractions	p. 387
Side-by-Side (Stratified) Contacting	p. 388
Three-Phase Microextractions	p. 392
Segmented Flow	p. 395
Fluorous Phase Extractions	p. 398
Comparison of Liquid-Liquid Extraction Efficiencies	p. 401
Gas-Liquid Separation	p. 403
Membrane Separators	p. 403
Microfiuidic Distillations	p. 403
Solvent Exchange and Solvent Removal	p. 407
The Use of Scavenger Resins for Product Purification under Flow	p. 410
Trace Metal Removal	p. 410
Removal of Unreacted Starting Materials	p. 411
Continuous Flow Resolutions	p. 413
Biocatalytic Resolutions	p. 415
Chemical Racemization	p. 416
Product Isolation	p. 418
Antisolvent Precipitation	p. 418
Lysozyme Crystallization	p. 420
Solution Crystallization	p. 420
Summary	p. 421
References	p. 421
Index	p. 427
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