Preface ...................................................... XVII
About European Cooperation in COST Chemistry Programs ......... XIX
List of Authors ............................................. XXIII
1. Microwave-Material Interactions and Dielectric
Properties, Key Ingredients for Mastery of Chemical
Microwave Processes .......................................... 1
Didier Stuerga
1.1. Fundamentals of Microwave-Matter Interactions .............. 1
1.1.1. Introduction ........................................ 2
1.1.2. The Complex Dielectric Permittivity ................. 9
1.1.3. Dielectric Properties and Molecular Behavior ....... 29
1.2. Key Ingredients for Mastery of Chemical Microwave
Processes ................................................. 43
1.2.1. Systemic Approach .................................. 43
1.2.2. The Thermal Dependence of Dielectric Loss .......... 45
1.2.3. The Electric Field Effects ......................... 46
1.2.4. Hydrodynamic Aspects ............................... 49
1.2.5. Thermodynamic and Other Effects of Electric
Fields ............................................. 51
1.2.6. The Athermal and Specific Effects of Electric
Fields ............................................. 52
1.2.7. The Thermal Path Effect: Anisothermal Conditions ... 54
1.2.8. Hot Spots and Heterogeneous Kinetics ............... 56
References ..................................................... 57
2. Development and Design of Laboratory and Pilot Scale
Reactors for Microwave-assisted Chemistry ................... 62
Bernd Ondruschka, Werner Bonrath, and Didier Stuerga
2.1. Introduction .............................................. 62
2.2. Basic Concepts for Reactions and Reactors in Organic
Synthesis ................................................. 63
2.3. Methods for Enhancing the Rates of Organic Reactions ...... 64
2.4. Microwave-assisted Organic Syntheses (MAOS) ............... 66
2.4.1. Microwave Ovens and Reactors - Background .......... 67
2.4.2. Scale-up of Microwave Cavities ..................... 72
2.4.3. Efficiency of Energy and Power ..................... 73
2.4.4. Field Homogeneity and Penetration Depth ............ 73
2.4.5. Continuous Tube Reactors ........................... 74
2.4.6. MAOS - An Interdisciplinary Field .................. 74
2.5. Commercial Microwave Reactors - Market Overview ........... 75
2.5.1. Prolabo's Products ................................. 77
2.5.2. CEM's products ..................................... 78
2.5.3. Milestone's Products ............................... 80
2.5.4. Biotage's Products ................................. 84
2.6. Selected Equipment and Applications ....................... 85
2.6.1. Heterogeneous Catalysis ............................ 89
2.6.2. Hyphenated Techniques in Combination with
Microwaves ......................................... 90
2.6.3. Combination of Microwave Irradiation with
Pressure Setup ..................................... 92
2.6.4. Synthesis of Laurydone® ............................ 97
2.6.5. Industrial Equipment Batch or Continuous Flow? ..... 98
2.7. Qualification and Validation of Reactors and Results ..... 101
2.8. Conclusion and Future .................................... 102
References .................................................... 103
3. Roles of Pressurized Microwave Reactors in the
Development of Microwave-assisted Organic Chemistry ........ 108
Thach Le Ngoc, Brett A. Roberts, and Christopher
R. Strauss
3.1. Introduction ............................................. 108
3.2. Toward Dedicated Microwave Reactors ...................... 109
3.2.1. The Continuous Microwave Reactor (CMR) ............ 110
3.2.2. Microwave Batch Reactors .......................... 111
3.3. Applications of the New Reactors ......................... 112
3.3.1. With Low-boiling Solvents ......................... 112
3.3.2. Kinetics Measurements ............................. 113
3.3.3. Core Enabling Technology .......................... 114
3.4. Commercial Release of MBRs and CMRs ...................... 114
3.5. Advantages of Pressurized Microwave Reactors ............. 116
3.6. Applications ............................................. 117
3.6.1. General Synthesis ................................. 117
3.6.2. Kinetic Products .................................. 121
3.6.3. Selective Synthesis of O-Glycofuranosides
and Pyranosides from Unprotected Sugars ........... 121
3.6.4. Synthesis in High-temperature Water ............... 123
3.6.5. Biomimetic Reactions .............................. 125
3.6.6. Indoles ........................................... 126
3.7. Effect of the Properties of Microwave Heating on
the Scale-up of Methods in Pressurized Reactors .......... 127
3.8. Software Technology for Translation of Reaction
Conditions ............................................... 129
3.9. Conclusion ............................................... 131
Acknowledgments ............................................... 132
References .................................................... 132
4. Nonthermal Effects of Microwaves in Organic Synthesis ...... 134
Laurence Perreux and Andre Loupy
4.1. Introduction ............................................. 134
4.2. Origin of Microwave Effects .............................. 135
4.3. Specific Nonthermal Microwave Effects .................... 137
4.4. Effects of the Medium .................................... 141
4.4.1. Polar Solvents .................................... 141
4.4.2. Nonpolar Solvents ................................. 143
4.4.3. Solvent-free Reactions ............................ 146
4.5. Effects Depending on Reaction Mechanisms ................. 147
4.5.1. Isopolar Transition-state Reactions ............... 148
4.5.2. Bimolecular Reactions Between Neutral
Reactants Leading to Charged Products ............. 152
4.5.3. Anionic Bimolecular Reactions Involving
Neutral Electrophiles ............................. 153
4.5.4. Unimolecular Reactions ............................ 154
4.6. Effects Depending on the Position of the Transition
State Along the Reaction Coordinates ..................... 155
4.7. Effects on Selectivity ................................... 156
4.8. Some Illustrative Examples ............................... 157
4.8.1. Bimolecular Reactions Between Neutral Reactants ... 157
4.8.2. Bimolecular Reactions with One Charged Reactant ... 184
4.8.3. Unimolecular Reactions ............................ 198
4.8.4. Some Illustrative Examples of Effects on
Selectivity ....................................... 204
4.9. Concerning the Absence of Microwave Effects .............. 209
4.10.Conclusions: Suitable Conditions for Observation of
Specific MW Effects ...................................... 210
References .................................................... 212
5. Selectivity Under the Action of Microwave Irradiation ...... 219
Antonio de la Hoz, Angel Diaz-Ortiz, and Andres Moreno
5.1. Introduction ............................................. 219
5.2. Selective Heating ........................................ 220
5.2.1. Solvents .......................................... 220
5.2.2. Catalysts ......................................... 223
5.2.3. Reagents; Molecular Radiators ..................... 230
5.2.4. Susceptors ........................................ 232
5.3. Modification of Chemoselectivity and Regioselectivity .... 233
5.3.1. Protection and Deprotection of Alcohols ........... 233
5.3.2. Electrophilic Aromatic Substitution ............... 236
5.3.3. Synthesis and Reactivity of Heterocyclic
Compounds ......................................... 241
5.3.4. Cycloaddition Reactions ........................... 247
5.3.5. Polymerization .................................... 252
5.3.6. Miscellaneous ..................................... 257
5.4. Modification of Stereo and Enantioselectivity ............ 264
5.5. Conclusions .............................................. 272
Acknowledgments ............................................... 273
References .................................................... 273
6. Microwaves and Phase-transfer Catalysis .................... 278
Andre Loupy, Alain Petit, and Dariusz Bogdal
6.1. Phase-transfer Catalysis ................................. 278
6.2. Synthetic Applications of Phase-transfer Processes ....... 281
6.2.1. O-Alkylations ..................................... 281
6.2.2. N-Alkylations ..................................... 293
6.2.3. C-Alkylations of Active Methylene Groups .......... 297
6.2.4. Alkylations with Dihalogenoalkanes ................ 300
6.2.5. Nucleophilic Addition to Carbonyl Compounds ....... 302
6.2.6. Deprotonations .................................... 307
6.2.7. Miscellaneous Reactions ........................... 309
6.3. Conclusion ............................................... 322
References .................................................... 322
7. Microwaves and Ionic Liquids ............................... 327
Nicholas E. Leadbeater and Hanna M. Torenius
7.1. Introduction ............................................. 327
7.2. Ionic Liquids in Conjunction with Microwave Activation ... 330
7.2.1. Synthesis of Ionic Liquids Using Microwave
Heating ........................................... 330
7.2.2. Reactions Using Microwave Irradiation and Ionic
Liquids as Solvents and Reagents .................. 333
7.2.3. Use of Ionic Liquids and Microwaves in
Multicomponent Reactions .......................... 349
7.2.4. Use of Ionic Liquids as Heating Aids .............. 354
7.3. Conclusions .............................................. 357
Abbreviations ................................................. 357
References .................................................... 358
8. Organic Synthesis Using Microwaves and Supported
Reagents ................................................... 362
Rajender S. Varma and Yuhongju
8.1. Introduction ............................................. 362
8.2. Microwave-accelerated Solvent-free Organic Reactions ..... 363
8.2.1. Protection-Deprotection Reactions ................. 364
8.2.2. Condensation Reactions ............................ 372
8.2.3. Isomerization and Rearrangement Reactions ......... 379
8.2.4. Oxidation Reactions - Oxidation of Alcohols
and Sulfides ...................................... 382
8.2.5. Reduction Reactions ............................... 388
8.2.6. Synthesis of Heterocyclic Compounds ............... 391
8.2.7. Miscellaneous Reactions ........................... 401
8.3. Conclusions .............................................. 406
References .................................................... 407
9. Microwave-assisted Reactions on Graphite ................... 416
Thierry Besson, Valerie Thiery, and Jacques Dubac
9.1. Introduction ............................................. 416
9.2. Graphite as a Sensitizer ................................. 418
9.2.1. Diels-Alder Reactions ............................. 418
9.2.2. Ene Reactions ..................................... 423
9.2.3. Oxidation of Propan-2-ol .......................... 425
9.2.4. Thermolysis of Esters ............................. 425
9.2.5. Thermal Reactions in Heterocyclic Syntheses ....... 427
9.2.6. Decomplexation of Metal Complexes ................. 433
9.2.7. Redistribution Reactions between Tetraalkyl or
Tetraarylgermanes, and Germanium Tetrahalides ..... 434
9.2.8. Pyrolysis of Urea ................................. 436
9.2.9. Esterification of Stearic Acid with n-Butanol ..... 437
9.3. Graphite as Sensitizer and Catalyst ...................... 437
9.3.1. Analysis of Two Synthetic Commercial Graphites .... 438
9.3.2. Acylation of Aromatic Compounds ................... 438
9.3.3. Acylative Cleavage of Ethers ...................... 443
9.3.4. Ketodecarboxylation of Carboxylic Diacids ......... 444
9.4. Notes .................................................... 447
9.4.1. MW Apparatus, Typical Procedures, and Safety
Measures .......................................... 447
9.4.2. Temperature Measurement ........................... 448
9.4.3. Mechanism of Retention of Reactants on Graphite ... 449
9.4.4. Graphite or Amorphous Carbon for C/MW Coupling .... 449
9.5. Conclusion ............................................... 450
References .................................................... 451
10.Microwaves in Heterocyclic Chemistry ....................... 456
Jean Pierre Bazureau, Jack Hamelin, Florence Mongin,
and Francoise Texier-Boullet
10.1.Introduction ............................................. 456
10.2.Microwave-assisted Reactions in Solvents ................. 456
10.2.1.Three, Four, and Five-membered Systems with
One Heteroatom .................................... 456
10.2.2.Five-membered Systems with Two Heteroatoms ........ 463
10.2.3.Five-membered Systems with More than Two
Heteroatoms ....................................... 468
10.2.4.Six-membered Systems with One Heteroatom .......... 469
10.2.5.Six-membered Systems with More than One
Heteroatom ........................................ 479
10.2.6.Synthesis of More Complex or Polyheterocyclic
Systems ........................................... 485
10.3.Solvent-free Synthesis ................................... 492
10.3.1.Three, Four and Five-membered Systems with One
Heteroatom ........................................ 492
10.3.2.Five-membered Systems with Two Heteroatoms ........ 499
10.3.3.Five-membered Systems with More than Two
Heteroatoms - Synthesis of Triazoles and
Related Compounds ................................. 506
10.3.4.Six-membered Systems with One Heteroatom .......... 506
10.3.5.Six-membered Systems with More than One
Heteroatom ........................................ 511
10.3.6.Synthesis of More Complex or Polyheterocydic
Systems ........................................... 515
10.4.Conclusion ............................................... 517
References and Notes .......................................... 517
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