Atnaujinkite slapukų nuostatas

Micro Reaction Technology in Organic Synthesis [Kietas viršelis]

(Chemtrix BV, The Netherlands),
  • Formatas: Hardback, 466 pages, aukštis x plotis: 234x156 mm, weight: 1010 g, 141 Tables, black and white; 327 Illustrations, black and white
  • Išleidimo metai: 15-Mar-2011
  • Leidėjas: CRC Press Inc
  • ISBN-10: 1439824711
  • ISBN-13: 9781439824719
  • Formatas: Hardback, 466 pages, aukštis x plotis: 234x156 mm, weight: 1010 g, 141 Tables, black and white; 327 Illustrations, black and white
  • Išleidimo metai: 15-Mar-2011
  • Leidėjas: CRC Press Inc
  • ISBN-10: 1439824711
  • ISBN-13: 9781439824719
While continuous processes have found widespread application within chemical production, members of the research and development communities have historically favored the centuries old technique of iterative batch reactions. With the exception of combinatorial and microwave chemistry, little had been done to change the way that synthetic chemists conduct their research. However, todays synthetic chemist is under increasing pressure to discover and deliver compounds quickly, with an eye on devising scalable synthetic methodologies.

An up-to-date account of recent developments in continuous flow organic synthesis, Micro Reaction Technology in Organic Synthesis is a useful resource for those both new to, and actively researching within, the field of micro reaction technology.











Written by chemists for chemists, key synthetic information takes precedence over technological details Highlights the advantages and disadvantages of the technology, giving the reader an idea of where future research needs to be targeted Presents a comprehensive collection of synthetic reactions that have been investigated over the past decade, therefore is a one-stop resource to the reactions and techniques that have been investigated so far

With an ever increasing number of commercial flow reaction platforms available, this book highlights the current state of the technology with the vision that more synthetic chemists will embark upon flow chemistry programs of research, facilitating the identification of novel synthetic methodologies the potential to be scaled directly to production.

Recenzijos

"Although there have been several books devoted to Micro Reaction Technology over the past decade, there has not been a volume focussed on the needs of the organic chemist. This excellent new book fulfils that gap." Trevor Laird, in Organic Process Research, March 2011

"In contrast to some of the other books available on this subject, this is clearly a book written by chemists for chemists. In a relatively short and easy-to-follow introductory chapter, the fundamentals of micro reaction technology, including fabrication of devices, pumping and mixing issues, and advantages/disadvantages, are explained with the synthetic chemist in mind. In each of tile sub chapters, the reader is pointed toward appropriate key references, review articles, or other books that provide further details on the subject." American Chemical Society, 2011

Preface xiii
Acknowledgments xv
Authors xvii
Abbreviations xix
Chapter 1 Introduction to Micro Reaction Technology
1(36)
1.1 What Is Micro Reaction Technology?
1(1)
1.2 Fabrication/Construction of Micro Reactors
2(2)
1.2.1 Glass Devices
2(1)
1.2.2 Silicon Devices
3(1)
1.2.3 Polymeric Devices
3(1)
1.2.4 Metallic Devices
3(1)
1.2.5 Ceramic Devices
4(1)
1.2.6 Reactor to World Interface
4(1)
1.3 Manipulation of Reactants and Products within Flow Reactors
4(3)
1.3.1 Mixing within Micro Reactors
5(1)
1.3.2 Flow Types within Biphasic Systems
6(1)
1.4 Advantages of Micro Reaction Technology
7(4)
1.4.1 Process Safety
7(1)
1.4.2 Novel Reaction Conditions
8(1)
1.4.3 Reduced Waste Generation
9(2)
1.4.4 On-Site Chemical Processing
11(1)
1.5 Disadvantages of Micro Reactors
11(2)
1.5.1 Handling of Insoluble Materials
12(1)
1.6 Process Intensification
13(1)
1.7 In Situ Reaction Monitoring
14(10)
1.7.1 Raman Spectroscopy
14(2)
1.7.2 In Situ Analysis by FTIR Spectroscopy
16(5)
1.7.3 Nuclear Magnetic Resonance Detection
21(1)
1.7.4 Chromatographic Techniques
22(1)
1.7.5 Development of Sensors for Process Monitoring
23(1)
1.8 Commercial Availability of Continuous Flow Reactor Technology
24(7)
1.9 Outlook
31(1)
References
31(6)
Chapter 2 Micro Reactions Employing a Gaseous Component
37(40)
2.1 Gas-Phase Micro Reactions
37(7)
2.1.1 Gas-Phase Oxidations
38(3)
2.1.2 Hydrogenation Reactions within Microstructured Reactors
41(1)
2.1.3 Dehydration and Dehydrogenation Reactions
42(1)
2.1.4 Fischer-Tropsch Synthesis
43(1)
2.1.5 Synthesis of Methylisocyanate in a Micro Reactor
43(1)
2.2 Gas-Liquid-Phase Micro Reactions
44(16)
2.2.1 Continuous Flow Chlorination Reactions
44(1)
2.2.2 Continuous Flow Fluorination Reactions
45(1)
2.2.3 Ozonolysis within Micro Reactors
45(3)
2.2.4 Biphasic Carbonylations
48(7)
2.2.5 Transfer Hydrogenations under Continuous Flow Conditions
55(2)
2.2.6 Miscellaneous Biphasic Micro Reactions
57(3)
2.3 Gas-Liquid-Solid Micro Reactions
60(10)
2.3.1 Triphasic Oxidations under Flow Conditions
61(1)
2.3.2 Carbonylations Using Solid-Supported Catalysts
62(1)
2.3.3 Hydrogenations within Continuous Flow Reactors
63(3)
2.3.4 Slurry-Based Micro Reactions
66(3)
2.3.5 Miscellaneous Triphasic Micro Reactions
69(1)
References
70(7)
Chapter 3 Liquid-Phase Micro Reactions
77(144)
3.1 Nucleophilic Substitution
77(36)
3.1.1 C-C Bond Formation: Acylation Reactions
77(1)
3.1.2 C-C Bond Formation: Alkylation Reactions
78(5)
3.1.3 Enantioselective C-C Bond-Forming Reactions
83(2)
3.1.4 C-O Bond Formation: Esterification Reactions
85(4)
3.1.5 C-O Bond Formation: Etherification Reactions
89(1)
3.1.6 C-O Bond Formation: Epoxide Hydrolysis
90(1)
3.1.7 C-N Bond Formation: Alkylation Reactions
90(3)
3.1.8 C-N Bond Formation: Acylation Reactions
93(5)
3.1.9 C-N Bond Formation: Arylation Reactions
98(1)
3.1.10 C-N Bond Formation: Azidation Reactions
99(3)
3.1.11 C-N Bond Formation: Synthesis of Hydroxamic Acids
102(1)
3.1.12 C-N Bond Formation: Aminolysis of Epoxides
103(6)
3.1.13 C-F Bond Formation
109(4)
3.2 Electrophilic Substitution
113(23)
3.2.1 C-C Bond Formation
113(13)
3.2.2 C-N Bond-Forming Reactions: Nitration Reactions
126(4)
3.2.3 C-Hetero Bond-Forming Reactions: Halogenations under Flow
130(3)
3.2.4 C-Hetero Bond-Forming Reactions: Diazotizations under Flow
133(3)
3.2.5 C-Hetero Bond-Forming Reactions: Sulfonations under Flow
136(1)
3.3 Nucleophilic Addition
136(22)
3.3.1 C-C Bond Formation: Aldol Reaction/Condensation
136(3)
3.3.2 C-C Bond Formation: Knoevenagel Condensation
139(3)
3.3.3 C-C Bond Formation: Michael Addition
142(2)
3.3.4 C-C Bond Formation: Diels-Alder Reaction
144(2)
3.3.5 C-C Bond Formation: Horner-Wadsworth-Emmons
146(2)
3.3.6 C-C Bond Formation: Enantioselective Examples
148(1)
3.3.7 C-Hetero Bond Formation: Aza-Michael Addition
149(2)
3.3.8 C-Hetero Bond Formation: Alkylation of Amines
151(1)
3.3.9 C-Hetero Bond Formation: Synthesis of Triazoles
152(5)
3.3.10 C-Hetero Bond Formation: Addition of Hydrazine to Carbonyl Compounds
157(1)
3.4 Elimination Reactions
158(5)
3.4.1 Dehydration Reactions
158(2)
3.4.2 Dehalogenations: Tris(Trimethylsilyl)Silane-Mediated Reductions
160(3)
3.5 Oxidations
163(10)
3.5.1 Oxidations: Inorganic Oxidants
163(1)
3.5.2 Oxidations: Swern-Moffat Oxidation
164(3)
3.5.3 Oxidations: TEMPO-Mediated Oxidations
167(1)
3.5.4 Oxidations Using Oxone
168(1)
3.5.5 Oxidations: Epoxidations under Flow Conditions
168(4)
3.5.6 Oxidation: Deprotection of Amines
172(1)
3.6 Reductions
173(2)
3.6.1 Transition Metal Free Reductions
173(1)
3.6.2 Dibal-H Reductions
173(2)
3.7 Metal-Catalyzed Cross-Coupling Reactions
175(12)
3.7.1 Suzuki-Miyaura Reaction
175(2)
3.7.2 Heck Reaction
177(6)
3.7.3 Sonogashira Reaction
183(2)
3.7.4 Other Metal-Catalyzed Coupling Reactions
185(2)
3.8 Rearrangements
187(11)
3.8.1 Claisen Rearrangement
187(4)
3.8.2 Newman-Kwart Rearrangement
191(2)
3.8.3 Hofmann Rearrangement
193(2)
3.8.4 Fisher Indolization
195(1)
3.8.5 Curtius Rearrangement
196(1)
3.8.6 Dimroth Rearrangement
197(1)
3.9 Multistep/Multicomponent Liquid-Phase Reactions
198(13)
3.9.1 Multicomponent Synthesis of Heterocycles
198(1)
3.9.2 Multistep Synthesis of 1,2,4-Oxadiazoles
199(2)
3.9.3 Continuous Flow Synthesis of Ibuprofen
201(2)
3.9.4 Cation-Mediated Sialylation Reactions
203(2)
3.9.5 Oligosaccharide Synthesis
205(1)
3.9.6 Synthesis of Indole Alkaloids Using Metal-Coated Capillary Reactors
206(1)
3.9.7 Iododeamination under Flow
206(3)
3.9.8 Radical Additions under Flow
209(2)
3.10 Summary
211(1)
References
211(10)
Chapter 4 Multi-Phase Micro Reactions
221(68)
4.1 Nucleophilic Substitution
221(4)
4.1.1 C-O Bond-Forming Reactions: Esterifications
221(3)
4.1.2 C-N Bond-Forming Reactions: Azidations
224(1)
4.2 Electrophilic Substitution
225(2)
4.2.1 Brominations
225(1)
4.2.2 Phosgene Synthesis
226(1)
4.3 Nucleophilic Addition
227(14)
4.3.1 C-C Bond-Forming Reactions: Knoevenagel Condensation
227(2)
4.3.2 C-C Bond-Forming Reactions: Michael Additions
229(1)
4.3.3 C-C Bond-Forming Reactions: Henry Reaction
230(2)
4.3.4 C-C Bond-Forming Reactions: Diels-Alder
232(1)
4.3.5 C-C Bond-Forming Reactions: Benzoin Condensation
232(2)
4.3.6 C-C Bond-Forming Reactions: Trifluoromethylation under Continuous Flow
234(1)
4.3.7 C-C Bond Formation: Aldol Reaction
234(3)
4.3.8 C-N Bond Formation: Cycloaddition Reactions
237(3)
4.3.9 C-O Bond-Forming Reactions: Acetalizations
240(1)
4.3.10 C-S Bond-Forming Reactions: Thioacetalizations
241(1)
4.4 Elimination Reactions
241(1)
4.4.1 Dehydration Reactions
241(1)
4.4.2 Dehydration Reactions
242(1)
4.5 Oxidation Reactions
242(8)
4.5.1 Catalytic Oxidations
243(4)
4.5.2 Epoxidations
247(3)
4.6 Metal-Catalyzed Cross-Coupling Reactions
250(11)
4.6.1 Suzuki-Miyaura Reaction
250(2)
4.6.2 Heck Coupling Reactions
252(3)
4.6.3 Other Metal-Catalyzed Coupling Reactions
255(6)
4.7 Rearrangements
261(1)
4.8 Enantioselective Reactions
262(10)
4.8.1 Chemically Promoted Reactions
262(4)
4.8.2 Enzymatic Enantioselective Micro Reactions
266(6)
4.9 Multistep/Multicomponent Reactions
272(9)
4.9.1 Independent Multistep Flow Reactions
272(1)
4.9.2 Integrated Multistep Sequences
272(2)
4.9.3 Reagents and Scavengers in Series
274(1)
4.9.4 Combined Chemical and Biochemical Catalysis
274(3)
4.9.5 "Catch and Release" Strategies under Continuous Flow
277(3)
4.9.6 Casein Kinase I Inhibitor Synthesis
280(1)
4.10 Summary
281(2)
References
283(6)
Chapter 5 Electrochemical and Photochemical Applications of Micro Reaction Technology
289(36)
5.1 Electrochemical Synthesis under Continuous Flow
289(13)
5.1.1 Electrochemical Oxidations
290(6)
5.1.2 Electrolyte-Free Electroorganic Synthesis
296(2)
5.1.3 Electrochemical Reductions
298(1)
5.1.4 Electrolyte-Free Reductions under Flow
299(2)
5.1.5 Summary
301(1)
5.2 Photochemical Synthesis under Continuous Flow
302(10)
5.2.1 Photocycloadditions under Continuous Flow
303(4)
5.2.2 Photodecarboxylative Addition
307(1)
5.2.3 Photocyanation
307(1)
5.2.4 Photochemical Halogenations
308(1)
5.2.5 Nitrite Photolysis under Flow Conditions
309(2)
5.2.6 Photochemical Dimerization
311(1)
5.2.7 Photosensitized Diastereo Differentiation
312(1)
5.3 Multiphase Photochemical Reactions
312(9)
5.3.1 Photocatalytic Reductions
313(1)
5.3.2 Photocatalytic Oxidation Reactions
314(1)
5.3.3 Photocatalytic Alkylation Reactions
315(1)
5.3.4 Photocatalytic Cyclizations
316(1)
5.3.5 Gas-Liquid Transformations
317(4)
5.3.6 Gas-Liquid-Solid Reactions
321(1)
5.3.7 Summary
321(1)
References
321(4)
Chapter 6 The Use of Microfluidic Devices for the Preparation and Manipulation of Droplets and Inorganic/Organic Particles
325(22)
6.1 Droplet Formation Using Continuous Flow Methodology
325(5)
6.1.1 Polymerization of Droplets under Flow
328(2)
6.2 Preparation of Inorganic Nanoparticles under Continuous Processing Conditions
330(2)
6.3 Formation of Organic Particles within Continuous Flow Devices
332(4)
6.4 The Use of Micro Reactors for the Postsynthetic Manipulation of Organic Compounds
336(2)
6.5 Mixed Particle Formation
338(3)
6.5.1 Microencapsulation of Active Pharmaceuticals
338(3)
6.6 Summary
341(2)
References
343(4)
Chapter 7 Industrial Interest in Micro Reaction Technology
347(40)
7.1 MRT in Production Environments
347(2)
7.2 Synthesis of Fine Chemicals Using Micro Reactors
349(14)
7.2.1 Synthesis of Carbamates under Continuous Flow Conditions
350(1)
7.2.2 Production-Scale Synthesis of Ionic Liquids
351(2)
7.2.3 Scalable Technique for the Synthesis of Diarylethenes
353(1)
7.2.4 Continuous Flow Synthesis of Light-Emitting Materials
354(2)
7.2.5 2-(2,5-Dimethyl-1H-Pyrrol-1-yl)Ethanol Synthesis
356(1)
7.2.6 Synthesis of Pigments under Flow Conditions
357(1)
7.2.7 Production of Thermally Labile Compounds under Flow Conditions
358(2)
7.2.8 Peracetic Acid Production Using an On-Site Microprocess
360(2)
7.2.9 The In Situ Synthesis and Use of Diazomethane
362(1)
7.3 Synthesis of Pharmaceuticals and Natural Products Using Continuous Flow Methodology
363(19)
7.3.1 Ciprofloxacin and Its Analogs
363(1)
7.3.2 Synthesis of Pristane
363(3)
7.3.3 Synthesis of Imatinib under Flow Conditions
366(2)
7.3.4 Synthesis of Aspirin and Vanisal Sodium
368(1)
7.3.5 Synthesis of Suberoylanilide Hydroxamic Acid
369(1)
7.3.6 Synthesis of Rimonabant and Efaproxiral Using AlMe3
370(2)
7.3.7 Continuous Flow Synthesis of Sildenafil
372(1)
7.3.8 Synthesis of 6-Hydroxybuspirone
372(1)
7.3.9 A Key Step in the Synthesis of (rac)-Tramadol
373(1)
7.3.10 Claisen Rearrangement to Afford 2,2-Dimethyl-2H-1-Benzopyrans
373(2)
7.3.11 Synthesis of a 5HT1B Antagonist
375(3)
7.3.12 Serial Approach to a Novel Anticancer Agent Using Flow Reactors
378(1)
7.3.13 Synthesis of Grossamide under Flow Conditions
378(1)
7.3.14 Synthesis of the Natural Product (±)-Oxomaritidine
378(3)
7.3.15 Synthesis of Furofuran Ligans
381(1)
7.4 Synthesis of Small Doses of Radiopharmaceuticals
382(2)
7.5 Summary
384(1)
References
384(3)
Chapter 8 Microscale Continuous Separations and Purifications
387(40)
8.1 Introduction
387(1)
8.2 Liquid-Liquid Extractions
387(16)
8.2.1 Side-by-Side (Stratified) Contacting
388(4)
8.2.2 Three-Phase Microextractions
392(3)
8.2.3 Segmented Flow
395(3)
8.2.4 Fluorous Phase Extractions
398(3)
8.2.5 Comparison of Liquid-Liquid Extraction Efficiencies
401(2)
8.3 Gas-Liquid Separation
403(4)
8.3.1 Membrane Separators
403(1)
8.3.2 Microfluidic Distillations
403(4)
8.4 Solvent Exchange and Solvent Removal
407(3)
8.5 The Use of Scavenger Resins for Product Purification under Flow
410(3)
8.5.1 Trace Metal Removal
410(1)
8.5.2 Removal of Unreacted Starting Materials
411(2)
8.6 Continuous Flow Resolutions
413(5)
8.6.1 Biocatalytic Resolutions
415(1)
8.6.2 Chemical Racemization
416(2)
8.7 Product Isolation
418(3)
8.7.1 Antisolvent Precipitation
418(2)
8.7.2 Lysozyme Crystallization
420(1)
8.7.3 Solution Crystallization
420(1)
8.8 Summary
421(1)
References
421(6)
Index 427
Charlotte Wiles, Paul Watts