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Microwaves in Organic and Medicinal Chemistry

Microwaves in Organic and Medicinal Chemistry

C. Oliver Kappe, Alexander Stadler, Raimund Mannhold (Series Editor), Hugo Kubinyi (Series Editor), Gerd Folkers (Series Editor)

ISBN: 978-3-527-60655-9

Jan 2006

422 pages

Select type: O-Book

Description

The authors of this guide are experts on the use of microwaves for drug synthesis as well as having much experience in teaching courses held under the auspices of the American Chemical Society and the IUPAC.
In this handy source of information for any practicing synthetic chemist they focus on common reaction types in medicinal chemistry, including solid-phase and combinatorial methods. They consider the underlying theory, latest developments in microwave applications and include a variety of examples from recent literature, as well as less common applications that are equally relevant for organic and medicinal chemists.
An indispensable reference for researchers with an affinity to modern methods.
Preface.

Personal Foreword.

1. Introduction: Microwave Synthesis in Perspective.

1.1 Microwave Synthesis and Medicinal Chemistry.

1.2 Microwave: Assisted Organic Synthesis (MAOS) – A Brief History.

1.3 Scope and Organization of the Book.

2. Microwave Theory.

2.1 Microwave Radiation.

2.2 Microwave Dielectric Heating.

2.3 Dielectric Properties.

2.4 Microwave Versus Conventional Thermal Heating.

2.5 Microwave Effects.

2.5.1 Thermal Effects (Kinetics).

2.5.2 Specific Microwave Effects.

2.5.3 Non-Thermal (Athermal) Microwave Effects.

3. Equipment Review.

3.1 Introduction.

3.2 Domestic Microwave Ovens.

3.3 Dedicated Microwave Reactors for Organic Synthesis.

3.4 Multimode Instruments.

3.4.1 Milestone s.r.1.

3.4.2 CEM Corporation.

3.4.3 Biotage AB.

3.4.4 Anton Paar GmbH.

3.5 Single-Model Instruments.

3.5.1 Biotage AB.

3.5.2 CEM Corporation.

3.6 Discussion.

4. Microwave Processing Techniques.

4.1 Solvent-Free Reactions.

4.2 Phase-Transfer Catalysis.

4.3 Reactions Using Solvents.

4.3.1 Open-versus Closed-Vessel Conditions.

4.3.2 Pre-Pressurized Reaction Vessels.

4.3.3 Non-Classical Solvents.

4.4 Parallel Processing.

4.5 Scale-Up in Batch and Continuous-Flow.

5. Starting with Microwave Chemistry.

5.1 Why Use Microwave Reactors?

5.2 Translating Conventionally Heated Methods.

5.2.1 Open and Closed Vessels?

5.2.2 Choice of Solvent.

5.2.3 Temperature and Time.

5.2.4 Microwave Instrument Software.

5.3 Reaction Optimization and Library Generation – A Case Study.

5.3.1 Choice of Solvent.

5.3.2 Catalyst Selection.

5.3.3 Time and Temperature.

5.3.4 Reinvestigation by a “Design of Experiments” Approach.

5.3.5 Optimization for Troublesome Building Block Combinations.

5.3.6 Automated Sequential Library Production.

5.4 Limitations and Safety Aspects.

6. Literature Survey Part A: General Organic Synthesis.

6.1 Transition Metal-Catalyzed Carbon-Carbon Bond Formations.

6.1.1 Heck Reactions.

6.1.2 Suzuki Reactions.

6.1.3 Sonogashira Reactions.

6.1.4 Stille Reactions.

6.1.5 Negishi, Kumada, and Related Reactions.

6.1.6 Carbonylation Reactions.

6.1.7 Asymmetric Allylic Alkyations.

6.1.8 Miscellaneous Carbon-Carbon Bond-Forming Reactions.

6.2 Transition Metal-Catalyzed Carbon-Heteroatom Bond Formations.

6.2.1 Buchwald-Hartwig Reactions.

6.2.2 Ullmann Condensation Reactions.

6.2.3 Miscellaneous Carbon-Heteroatom Bond-Forming Reactions.

6.3 Other Transition Metal-Mediated Processes.

6.3.1 Ring Closing Metathesis.

6.3.2 Pauson-Khand Reactions.

6.3.3 Carbon-Hydrogen Bond Activation.

6.3.4 Miscellaneous Reactions.

6.4 Rearrangement Reactions.

6.4.1 Claisen Rearrangements.

6.4.2 Domino/Tandem Claisen Rearrangements.

6.4.3 Squaric Acid-Vinylketene Rearrangements.

6.4.4 Vinylcyclobutane-Cyclohexene Rearrangements.

6.4.5 Miscellaneous Rearrangements.

6.5 Diels-Alder Cycloaddition Reactions.

6.6 Oxidations.

6.7 Catalytic Transfer Hydrogenations.

6.8 Mitsunobu Reactions.

6.9 Glycosylation Reactions and Related Carbohydrate-Based Transformations.

6.10 Multicomponent Reactions.

6.11 Alkylation Reactions.

6.12 Nucleophilic Aromatic Substitutions.

6.13 Ring-Opening Reactions.

6.13.1 Cyclopropane Ring-Opening.

6.13.2 Aziridine Ring-Openings.

6.13.3 Epoxide Ring-Opening.

6.14 Addition and Elimination Reactions.

6.14.1 Michael Additions.

6.14.2 Addition to Alkenes.

6.14.3 Addition to Alkenes.

6.14.4 Addition to Nitriles.

6.15 Substitution Reactions.

6.16 Enamine and Imine Formations.

6.17 Reductive Aminations.

6.18 Ester and Amide Formation.

6.19 Decarboxylation Reactions.

6.20 Free Radical Reactions.

6.21 Protection/Deprotection Chemistry.

6.22 Preparation of Isotopically Labeled Compounds.

6.23 Miscellaneous Transformations.

6.24 Heterocycle Synthesis.

6.24.1 Three-Membered Heterocycles with One Heteroaton.

6.24.2 Four-Membered Heterocycles with One Heteroatom.

6.24.3 Five-Membered Heterocycles with One Heteroatom.

6.24.4 Five-Membered Heterocycles with Two Heteroatom.

6.24.5 Five-Membered Heterocycles with Three Heteroatom.

6.24.6 Five-Membered Heterocycles with Four Heteroatom.

6.24.7 Six-Membered Heterocycles with One Heteroatom.

6.24.8 Six-Membered Heterocycles with Two Heteroatom.

6.24.9 Six-Membered Heterocycles with Three Heteroatom.

6.24.10 Larger Heterocyclic and Polycyclic Ring Systems.

7. Literature Survey Part B: Combinatorial Chemistry and High-Throughput Organic Synthesis.

7.1 Solid-Phase Organic Synthesis.

7.1.1 Combinatorial Chemistry and Solid-Phase Organic Synthesis.

7.1.2 Microwave Chemistry and Solid-Phase Organic Synthesis.

7.1.3 Peptide Synthesis and Related Examples.

7.1.4 Resin Functionalization.

7.1.5 Transition Metal Catalysis.

7.1.6 Substitution Reactions.

7.1.7 Multicomponent Chemistry.

7.1.8 Microwave-Assisted Condensation Reactions.

7.1.9 Rearrangements.

7.1.10 Cleavage Reactions.

7.1.11 Miscellaneous.

7.2 Soluble Polymer-Supported Synthesis.

7.3 Fluorous Phase Organic Synthesis.

7.4 Grafted Ionic Liquid-Phase-Supported Synthesis.

7.5 Polymer-Supported Reagents.

7.6 Polymer-Supported Catalysts.

7.6.1 Catalysts on Polymeric Supports.

7.6.2 Silica-Grafted Catalysts.

7.6.3 Catalysts Immobilized on Glass.

7.6.4 Catalysts Immobilized on Carbon.

7.6.5 Miscellaneous.

7.7 Polymer-Supported Scavengers.

8. Outlook and Conclusions.

Index.

"…this book contains many pertinent examples for chemists working in distinct areas such as discovery research or process development." (CHOICE, April 2006)

"…the very well-constructed literature review and the 'how-to' chapters make this a book with a great deal of useful practical information for chemists." (Journal of the American Chemical Society, February 8, 2006)

"...a very enjoyable and interesting book, revealing that no question is too silly to ask." (Chemistry World, 1st February 2006)

"This is a well thought out and nicely constructed book which has been carefully written with its audience in mind. It is more than just a literature review, it is a handbook of "how to do it", which will be extremely useful to the practitioner. In my view, this is now the seminal text for chemists (especially, but not exclusively, medicinal chemists) using microwaves on laboratory scale. I can warmly recommend this book, and would expect it to end up on the shelves in most synthetic organic laboratories." (Organic Process Research & Development)

"...this easy to read work is essential for chemists wishing to learn about the state of the art in microwave-assisted organic synthesis chemistry and will be a handy reference volume for more experienced microwave chemists." (ChemMedChem)