Micro Reaction Technology in Organic Synthesis

Transcription

1 Micro Reaction Technology in Organic Synthesis Charlotte Wiles and Paul CRC Press Taylor & Francis > Group Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business

2 Preface Acknowledgments Authors Abbreviations xiii xv xvii xix Chapter 1 Introduction to Micro Reaction Technology What Is Micro Reaction Technology? Fabrication/Construction of Micro Reactors Glass Devices Silicon Devices Polymeric Devices Metallic Devices Ceramic Devices Reactor to World Interface Manipulation of Reactants and Products within Flow Reactors Mixing within Micro Reactors Flow Types within Biphasic Systems Advantages of Micro Reaction Technology Process Safety Novel Reaction Conditions Reduced Waste Generation On-Site Chemical Processing Disadvantages of Micro Reactors Handling of Insoluble Materials Process Intensification In Situ Reaction Monitoring Raman Spectroscopy In Situ Analysis by FTIR Spectroscopy Nuclear Magnetic Resonance Detection Chromatographic Techniques Development of Sensors for Process Monitoring Commercial Availability of Continuous Flow Reactor Technology Outlook 31 References 31 Chapter 2 Micro Reactions Employing a Gaseous Component Gas-Phase Micro Reactions Gas-Phase Oxidations 38 v

3 VI Contents Hydrogenation Reactions within Microstructured Reactors Dehydration and Dehydrogenation Reactions Fischer-Tropsch Synthesis Synthesis of Methylisocyanate in a Micro Reactor Gas-Liquid-Phase Micro Reactions Continuous Flow Chlorination Reactions Continuous Flow Fluorination Reactions Ozonolysis within Micro Reactors Biphasic Carbonylations Transfer Hydrogenations under Continuous Flow Conditions Miscellaneous Biphasic Micro Reactions Gas-Liquid-Solid Micro Reactions Triphasic Oxidations under Flow Conditions Carbonylations Using Solid-Supported Catalysts Hydrogenations within Continuous Flow Reactors Slurry-Based Micro Reactions Miscellaneous Triphasic Micro Reactions 69 References 70 Chapter 3 Liquid-Phase Micro Reactions Nucleophilic Substitution C-C Bond Formation: Acylation Reactions C-C Bond Formation: Alkylation Reactions Enantioselective C-C Bond-Forming Reactions C-0 Bond Formation: Esterification Reactions C-0 Bond Formation: Etherification Reactions C-O Bond Formation: Epoxide Hydrolysis C-N Bond Formation: Alkylation Reactions C-N Bond Formation: Acylation Reactions C-N Bond Formation: Arylation Reactions C-N Bond Formation: Azidation Reactions C-N Bond Formation: Synthesis of Hydroxamic Acids C-N Bond Formation: Aminolysis of Epoxides C-F Bond Formation Electrophilic Substitution C-C Bond Formation C-N Bond-Forming Reactions: Nitration Reactions C-Hetero Bond-Forming Reactions: Halogenations under Flow 130

4 vii C-Hetero Bond-Forming Reactions: Diazotizations under Flow C-Hetero Bond-Forming Reactions: Sulfonations under Flow Nucleophilic Addition C-C Bond Formation: Aldol Reaction/Condensation C-C Bond Formation: Knoevenagel Condensation C-C Bond Formation: Michael Addition C-C Bond Formation: Diels-Alder Reaction C-C Bond Formation: Horner-Wadsworth-Emmons C-C Bond Formation: Enantioselective Examples C-Hetero Bond Formation: Aza-Michael Addition C-Hetero Bond Formation: Alkylation of Amines C-Hetero Bond Formation: Synthesis of Triazoles C-Hetero Bond Formation: Addition of Hydrazine to Carbonyl Compounds Elimination Reactions Dehydration Reactions Dehalogenations: Tris(Trimethylsilyl)Silane- Mediated Reductions Oxidations Oxidations: Inorganic Oxidants Oxidations: Swern-Moffat Oxidation Oxidations: TEMPO-Mediated Oxidations Oxidations Using Oxone Oxidations: Epoxidations under Flow Conditions Oxidation: Deprotection of Amines Reductions Transition Metal Free Reductions Dibal-H Reductions Metal-Catalyzed Cross-Coupling Reactions Suzuki-Miyaura Reaction Heck Reaction Sonogashira Reaction Other Metal-Catalyzed Coupling Reactions Rearrangements Claisen Rearrangement Newman-Kwart Rearrangement Hofmann Rearrangement 193

5 3.8.4 Fisher Indolization Curtius Rearrangement Dimroth Rearrangement Multistep/Multicomponent Liquid-Phase Reactions Multicomponent Synthesis of Heterocycles Multistep Synthesis of 1,2,4-Oxadiazoles Continuous Flow Synthesis of Ibuprofen Cation-Mediated Sialylation Reactions Oligosaccharide Synthesis Synthesis of Indole Alkaloids Using Metal-Coated Capillary Reactors Iododeamination under Flow Radical Additions under Flow Summary 211 References 211 Chapter 4 Multi-Phase Micro Reactions Nucleophilic Substitution C-O Bond-Forming Reactions: Esterifications C-N Bond-Forming Reactions: Azidations Electrophilic Substitution Brominations Phosgene Synthesis Nucleophilic Addition C-C Bond-Forming Reactions: Knoevenagel Condensation C-C Bond-Forming Reactions: Michael Additions C-C Bond-Forming Reactions: Henry Reaction C-C Bond-Forming Reactions: Diels-Alder C-C Bond-Forming Reactions: Benzoin Condensation C-C Bond-Forming Reactions: Trifluoromethylation under Continuous Flow C-C Bond Formation: Aldol Reaction C-N Bond Formation: Cycloaddition Reactions C-O Bond-Forming Reactions: Acetalizations C-S Bond-Forming Reactions: Thioacetalizations Elimination Reactions Dehydration Reactions Dehydration Reactions Oxidation Reactions Catalytic Oxidations Epoxidations 247

6 ix 4.6 Metal-Catalyzed Cross-Coupling Reactions Suzuki-Miyaura Reaction Heck Coupling Reactions Other Metal-Catalyzed Coupling Reactions Rearrangements Enantioselective Reactions Chemically Promoted Reactions Enzymatic Enantioselective Micro Reactions Multistep/Multicomponent Reactions Independent Multistep Flow Reactions Integrated Multistep Sequences Reagents and Scavengers in Series Combined Chemical and Biochemical Catalysis "Catch and Release" Strategies under Continuous Flow Casein Kinase I Inhibitor Synthesis Summary 281 References 283 Chapter 5 Electrochemical and Photochemical Applications of Micro Reaction Technology Electrochemical Synthesis under Continuous Flow Electrochemical Oxidations Electrolyte-Free Electroorganic Synthesis Electrochemical Reductions Electrolyte-Free Reductions under Flow Summary Photochemical Synthesis under Continuous Flow Photocycloadditions under Continuous Flow Photodecarboxylative Addition Photocyanation Photochemical Halogenations Nitrite Photolysis under Flow Conditions Photochemical Dimerization Photosensitized Diastereo Differentiation Multiphase Photochemical Reactions Photocatalytic Reductions Photocatalytic Oxidation Reactions Photocatalytic Alkylation Reactions Photocatalytic Cyclizations Gas-Liquid Transformations Gas-Liquid-Solid Reactions Summary 321 References 321

7 X Contents Chapter 6 The Use of Microfluidic Devices for the Preparation and Manipulation of Droplets and Inorganic/Organic Particles Droplet Formation Using Continuous Flow Methodology Polymerization of Droplets under Flow Preparation of Inorganic Nanoparticles under Continuous Processing Conditions Formation of Organic Particles within Continuous Flow Devices The Use of Micro Reactors for the Postsynthetic Manipulation of Organic Compounds Mixed Particle Formation Microencapsulation of Active Pharmaceuticals Summary 341 References 343 Chapter 7 Industrial Interest in Micro Reaction Technology MRT in Production Environments Synthesis of Fine Chemicals Using Micro Reactors Synthesis of Carbamates under Continuous Flow Conditions Production-Scale Synthesis of Ionic Liquids Scalable Technique for the Synthesis of Diarylethenes Continuous Flow Synthesis of Light-Emitting Materials (2,5-Dimethyl-l#-Pyrrol-l-yl)Ethanol Synthesis Synthesis of Pigments under Flow Conditions Production of Thermally Labile Compounds under Flow Conditions Peracetic Acid Production Using an On-Site Microprocess The In Situ Synthesis and Use of Diazomethane Synthesis of Pharmaceuticals and Natural Products Using Continuous Flow Methodology Ciprofloxacin and Its Analogs Synthesis of Pristane Synthesis of Imatinib under Flow Conditions Synthesis of Aspirin and Vanisal Sodium Synthesis of Suberoylanilide Hydroxamic Acid Synthesis of Rimonabant and Efaproxiral Using AlMe Continuous Flow Synthesis of Sildenafil Synthesis of 6-Hydroxybuspirone A Key Step in the Synthesis of (rac)-tramadol 373

8 xi Claisen Rearrangement to Afford 2,2-Dimethyl-2#-l-Benzopyrans Synthesis of a 5HT, B Antagonist Serial Approach to a Novel Anticancer Agent Using Flow Reactors Synthesis of Grossamide under Flow Conditions Synthesis of the Natural Product (+)-Oxomaritidine Synthesis of Furofuran Ligans Synthesis of Small Doses of Radiopharmaceuticals Summary 384 References 384 Chapter 8 Microscale Continuous Separations and Purifications Introduction Liquid-Liquid Extractions Side-by-Side (Stratified) Contacting Three-Phase Microextractions Segmented Flow Fluorous Phase Extractions Comparison of Liquid-Liquid Extraction Efficiencies Gas-Liquid Separation Membrane Separators Microfluidic Distillations Solvent Exchange and Solvent Removal The Use of Scavenger Resins for Product Purification under Flow Trace Metal Removal Removal of Unreacted Starting Materials Continuous Flow Resolutions Biocatalytic Resolutions Chemical Racemization Product Isolation Antisolvent Precipitation Lysozyme Crystallization Solution Crystallization Summary 421 References 421 Index 427