1Topics in Heterocyclic Chemistry

Series Editor: R. R. Gupta

Editorial Board:

D. Enders · S. V. Ley · G. Mehta · A. I. MeyersK. C. Nicolaou · R. Noyori · L. E. Overman · A. Padwa

Topics in Heterocyclic ChemistryRecently Published and Forthcoming Volumes

Bioactive Heterocycles IVolume Editor: S. EguchiVolume 6, 2006

Heterocyclic Marine ProductsVolume Editor: H. KiyotaVolume 5, 2006

QSAR and Molecular Modeling Studiesin Heterocyclic Drugs IIVolume Editor: S. P. GuptaVolume 4, 2006

QSAR and Molecular Modeling Studiesin Heterocyclic Drugs IVolume Editor: S. P. GuptaVolume 3, 2006

Heterocyclic Antitumor AntibioticsVolume Editor: M. LeeVolume 2, 2006

Microwave-Assisted Synthesis of HeterocyclesVolume Editors: E. Van der Eycken, C. O. KappeVolume 1, 2006

Microwave-Assisted Synthesisof Heterocycles

Volume Editors: Erik Van der Eycken, C. Oliver Kappe

With contributions by

F. Almqvist · P. Appukkuttan · M. C. Bagley · T. BessonE. Chorell · S. Crosignani · M. Erdélyi · E. Van der EyckenN. Kaval · B. Linclau · M. C. Lubinu · B. U. W. MaesN. Pemberton · M. Rodriquez · M. Taddei · V. Thiéry

123

The series Topics in Heterocyclic Chemistry presents critical reviews on “Heterocyclic Compounds”within topic-related volumes dealing with all aspects such as synthesis, reaction mechanisms, structurecomplexity, properties, reactivity, stability, fundamental and theoretical studies, biology, biomedicalstudies, pharmacological aspects, applications in material sciences etc. Metabolism will be also includedwhich will provide information useful in designing pharmacologically active agents. Pathways involvingdestruction of heterocyclic rings will also be dealt with so that synthesis of specifically functionalizednon-heterocyclic molecules can be designed.The overall scope is to cover topics dealing with most of the areas of current trends in heterocyclicchemistry which will suit to a larger heterocyclic community.As a rule contributions are specially commissioned. The editors and publishers will, however, alwaysbe pleased to receive suggestions and supplementary information. Papers are accepted for Topics inHeterocyclic Chemistry in English.In references Topics in Heterocyclic Chemistry is abbreviated Top Heterocycl Chem and is cited asa journal.

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ISSN 1861-9282ISBN-10 3-540-30983-7 Springer Berlin Heidelberg New YorkISBN-13 978-3-540-30983-3 Springer Berlin Heidelberg New YorkDOI 10.1007/11497363

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Series Editor

Prof. R. R. Gupta

10A, Vasundhara ColonyLane No. 1, Tonk RoadJaipur-302 018, Indiarrg_vg@yahoo.co.in

Volume Editors

Prof. Erik Van der Eycken

K. U. LeuvenDepartment of ChemistryLaboratory for Organic SynthesisCelestijnenlaan 200FB-3001 Heverlee, BelgiumErik.VanderEycken@chem.kuleuven.be

Prof. C. O. Kappe

Institute of Organic ChemistryKarl-Franzens UniversityHeinrichstr. 28A-8010 Graz, Austriaoliver.kappe@uni-graz.at

Editorial Board

Prof. D. Enders

RWTH AachenInstitut für Organische ChemieD-52074, Aachen, Germanyenders@rwth-aachen.de

Prof. Steven V. Ley FRS

BP 1702 Professorand Head of Organic ChemistryUniversity of CambridgeDepartment of ChemistryLensfield RoadCambridge, CB2 1EW, UKsvl1000@cam.ac.uk

Prof. G. Mehta FRS

DirectorDepartment of Organic ChemistryIndian Institute of ScienceBangalore- 560 012, Indiagm@orgchem.iisc.ernet.in

Prof. A.I. Meyers

Emeritus Distinguished Professor ofDepartment of ChemistryColorado State UniversityFort Collins, CO 80523-1872, USAaimeyers@lamar.colostate.edu

Prof. K.C. Nicolaou

ChairmanDepartment of ChemistryThe Scripps Research Institute10550 N. Torrey Pines Rd.La Jolla, California 92037, USAkcn@scripps.eduandProfessor of ChemistryDepartment of Chemistry and BiochemistryUniversity of CaliforniaSan Diego, 9500 Gilman DriveLa Jolla, California 92093, USA

VI Editorial Board

Prof. Ryoji Noyori NL

PresidentRIKEN (The Institute of Physical and Chem-ical Research)2-1 Hirosawa, WakoSaitama 351-0198, JapanandUniversity ProfessorDepartment of ChemistryNagoya UniversityChikusa, Nagoya 464-8602, Japannoyori@chem3.chem.nagoya-u.ac.jp

Prof. Larry E. Overman

Distinguished ProfessorDepartment of Chemistry516 Rowland HallUniversity of California, IrvineIrvine, CA 92697-2025leoverma@uci.edu

Prof. Albert Padwa

William P. Timmie Professor of ChemistryDepartment of ChemistryEmory UniversityAtlanta, GA 30322, USAchemap@emory.edu

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Preface to the Series

Topics in Heterocyclic Chemistry presents critical accounts of heterocyclic com-pounds (cyclic compounds containing at least one heteroatom other than car-bon in the ring) ranging from three members to supramolecules. More thanhalf of the more than 10000 compounds listed in Chemical Abstracts are hete-rocyclic compounds. The branch of chemistry dealing with these heterocycliccompounds is called heterocyclic chemistry, which is the largest branch ofchemistry and as such the chemical literature appearing every year as researchpapers and review articles is vast and can not be covered in a single volume.

This series in heterocyclic chemistry is being introduced to collectivelymake available critically and comprehensively reviewed literature scatteredin various journals as papers and review articles. All sorts of heterocycliccompounds originating from synthesis, natural products, marine products,insects, etc. will be covered. Several heterocyclic compounds play a significantrole in maintaining life. Blood constituents hemoglobin and purines, as well aspyrimidines, are constituents of nucleic acid (DNA and RNA). Several aminoacids, carbohydrates, vitamins, alkaloids, antibiotics, etc. are also heterocycliccompounds that are essential for life. Heterocyclic compounds are widely usedin clinical practice as drugs, but all applications of heterocyclic medicines cannot be discussed in detail. In addition to such applications, heterocyclic com-pounds also find several applications in the plastics industry, in photographyas sensitizers and developers, and the in dye industry as dyes, etc.

Each volume will be thematic, dealing with a specific and related subjectthat will cover fundamental, basic aspects including synthesis, isolation, pu-rification, physical and chemical properties, stability and reactivity, reactionsinvolving mechanisms, intra- and intermolecular transformations, intra- andintermolecular rearrangements, applications as medicinal agents, biologicaland biomedical studies, pharmacological aspects, applications in material sci-ence, and industrial and structural applications.

The synthesis of heterocyclic compounds using transition metals and us-ing heterocyclic compounds as intermediates in the synthesis of other organiccompounds will be an additional feature of each volume. Pathways involving thedestruction of heterocyclic rings will also be dealt with so that the synthesis ofspecifically functionalized non-heterocyclic molecules can be designed. Eachvolume in this series will provide an overall picture of heterocyclic compounds

X Preface to the Series

critically and comprehensively evaluated based on five to ten years of literature.Graduates, research students and scientists in the fields of chemistry, pharma-ceutical chemistry, medicinal chemistry, dyestuff chemistry, agrochemistry,etc. in universities, industry, and research organizations will find this seriesuseful.

I express my sincere thanks to the Springer staff, especially to Dr. MarionHertel, executive editor, chemistry, and Birgit Kollmar-Thoni, desk editor,chemistry, for their excellent collaboration during the establishment of thisseries and preparation of the volumes. I also thank my colleague Dr. MahendraKumar for providing valuable suggestions. I am also thankful to my wife Mrs.Vimla Gupta for her multifaceted cooperation.

Jaipur, 31 January 2006 R.R. Gupta

Preface to Volume 1

The domestic microwave oven is one of the magnificent inventions used in thekitchen that contributes to simplifying the lives of many people, as the timefor “cooking” an acceptable meal can be reduced to the time it takes to defrostand heat vacuum-packed food, altogether consuming less than half an hour.

It all started almost 60 years ago when P. Spencer, studying high-powermicrowave sources for radar applications, observed the melting of a chocolatebar in his pocket; at least that is the story told. The first patent in this field wasfiled by him in 1946 and one year later the first commercial microwave ovenappeared on the market. We had to wait until 1955 for domestic models, butby 1976 almost 60% of US households already had a microwave oven.

Soon engineers and researchers realized that this technique possessed inter-esting applications for food processing, the drying industry, waste remediation,analytical chemistry, etc. Unfortunately organic chemists had to wait until 1986before the first two publications concerning the application of microwaves inorganic synthesis appeared in the literature, independently submitted by thegroups of Gedye and Giguere/Majetich. Since then, the number of publicationsdealing with microwave-assisted organic synthesis (MAOS) has been growingsteadily, having reached today a total of 2000, consisting of regular papers aswell as several review articles and a few books describing the state of the art ofmicrowave-assisted synthesis.

Especially since the appearance on the market at the end of the 1990s of ded-icated single-mode systems, which are ideally suited for performing reactionsunder fully controlled conditions and on a small scale, microwave chemistry isalso steadily finding its way into the labs of the more conservative amongst us.The main difference between conventional heating and microwave irradiationis the way the energy is transferred to the medium: in the former case thisoccurs via classical conduction, while in the latter an almost instantaneoustransfer of energy to the reactants takes place.

There is still some dispute about how microwave irradiation acceleratesreactions. Besides the generally accepted thermal effects, one believes that thereare some specific (but also thermal) microwave effects, such as the formation of“hot spots”. There is still some controversy about the existence of non-thermal(athermal) microwave effects. At the present time, new techniques such as“cooling while heating” are being investigated and the problem of upscaling

XII Preface

for industrial purposes has been tackled with the introduction of continuousand stop-flow microwave systems, although there is certainly still a long wayto go.

In the 1990s the technique of solid-phase organic synthesis (SPOS) becamegenerally popular, but especially in the medicinal chemistry community, forlead detection and lead optimization via combinatorial techniques. The combi-nation with microwave irradiation brought an elegant solution for the problemof the notoriously slower reactions compared to those in solution phase.

The aim of this book is to focus on the application of microwave irradia-tion in different fields of heterocyclic chemistry. As a result we are very proudto present eight selected contributions from eminent scientists in the fieldand one written by one of the editors (EVdE), dealing with different topicsof heterocyclic chemistry. The first chapter describes the synthesis and func-tionalization of 2-pyridones, 2-quinolones and ring-fused 2-pyridones. Anoverview of microwave-assisted multicomponent reactions for the synthesisof heterocycles is given in the second chapter, followed by up-to-date reviewsof the synthesis of sulfur and nitrogen-containing heterocycles in the thirdcontribution, and solid-phase methods for the microwave-assisted synthesisof heterocycles in the fourth. The use of polymer-supported reagents is thor-oughly discussed in the fifth chapter as well as the metal-based carbon–carbonand carbon–heteroatom bond formation for the synthesis and decoration ofheterocycles. The final chapters are devoted to the synthesis of heterocyclesvia microwave-assisted cycloaddition and cyclocondensation reactions and anoverview of 2(1H)-pyrazinone chemistry in solution and on solid support.

On this occasion we would like to thank all authors for sending their excellentcontributions. We also would like to thank Springer for inviting us to be volumeeditors and for their valuable support during the production of this volume.

Heverlee and Graz, January 2006 Erik Van der EyckenC. Oliver Kappe

Contents

Microwave-Assisted Synthesis and Functionalization of 2-Pyridones,2-Quinolones and Other Ring-Fused 2-PyridonesN. Pemberton · E. Chorell · F. Almqvist . . . . . . . . . . . . . . . . . . 1

Microwave-Assisted Multicomponent Reactionsfor the Synthesis of HeterocyclesM. C. Bagley · M. C. Lubinu . . . . . . . . . . . . . . . . . . . . . . . . . 31

Microwave-Assisted Synthesisof Sulfur and Nitrogen-Containing HeterocyclesT. Besson · V. Thiéry . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

Solid-Phase Methodsfor the Microwave-Assisted Synthesis of HeterocyclesM. Erdélyi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79

Synthesis of HeterocyclesUsing Polymer-Supported Reagents under Microwave IrradiationS. Crosignani · B. Linclau . . . . . . . . . . . . . . . . . . . . . . . . . . 129

Transition-Metal-Based Carbon–Carbonand Carbon–Heteroatom Bond Formationfor the Synthesis and Decoration of HeterocyclesB. U. W. Maes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155

Synthesis of Heterocycles via Microwave-Assisted Cycloadditionsand CyclocondensationsM. Rodriquez · M. Taddei . . . . . . . . . . . . . . . . . . . . . . . . . 213

XIV Contents

The Chemistry of 2-(1H)-Pyrazinonesin Solution and on Solid SupportN. Kaval · P. Appukkuttan · E. Van der Eycken . . . . . . . . . . . . . . 267

Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 305

Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307