Surya K. De - Applied Organic Chemistry

1 Cover

2 Applied Organic Chemistry Applied Organic Chemistry Reaction Mechanisms and Experimental Procedures in Medicinal Chemistry Surya K. De Volume 1

3 Copyright Copyright Author Dr. Surya K. De Supra Sciences San Diego, CA United States Cover Image: © enot‐poloskun/Getty All books published by Wiley‐VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate. Library of Congress Card No.: applied for British Library Cataloguing‐in‐Publication Data A catalogue record for this book is available from the British Library. Bibliographic information published by the Deutsche Nationalbibliothek The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at < http://dnb.d-nb.de >. © 2021 WILEY‐VCH GmbH, Boschstr. 12, 69469 Weinheim, Germany All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law. Print ISBN: 978‐3‐527‐34785‐8 ePDF ISBN: 978‐3‐527‐82815‐9 ePub ISBN: 978‐3‐527‐82817‐3 oBook ISBN: 978‐3‐527‐82816‐6

4 Preface Preface Organic chemistry is a constantly developing and expanding field of science because of its infinite research and application possibilities. Clear understanding of organic chemistry concepts, including the mechanistic aspects of organic reactions, helps chemists design drug molecules with the power to save human lives. This textbook is targeted to advanced undergraduates and postgraduate students in all areas of organic, bioorganic, pharmaceutical, and medicinal chemistry. Professional researchers may utilize it as a handbook due to its references to original literature, recent reviews, and application of named reactions and reagents frequently used in organic synthesis. This book also covers, step by step, the mechanism of selected reactions that are part of undergraduate and postgraduate curricula. The definition of each named reaction with its original reference(s), i.e. the first one or others if applicable, current reviews, and their applications (sourced from Journal of Medicinal Chemistry and others) are also included. Heterocyclic compounds have important biological activities, so the nomenclature and application of heterocyclic compounds have been summarized in Chapter 9. In addition, Chapter 12 presents preliminary concepts regarding solution‐phase and solid‐phase peptide syntheses. For synthetic stand points, common organic reagents and functional groups transformation are discussed in Chapters 13–16. References included in this book are available on PubMed ( https://www.ncbi.nlm.nih.gov/pubmed ) or https://pubs.acs.org . The experimental procedure of each reaction can be found on Google Patents ( http://patents.google.com ). I would like to express great thanks to Dr. Ramkrishna De (Vertex Pharmaceuticals) for reviewing the manuscript and providing valuable suggestions. Also, Dr. Maloy Kumar Parai provided some assistance in preparing the manuscript. I would like to express great thanks to Wiley editors Dr. Anne Brennführer, Dr. Frank Weinreich, Ms. Katherine Wong, as well as their staffs Ms. Pinky Sathishkumar, Ms. Abisheka Santhoshini who helped me to complete this book. Finally, I wish to thank my family members for their continual understanding and support. I welcome and, in fact, earnestly request readers to notify me of any suggestions for improving this book. Surya K. De San Diego, CA, USA March 2020

5 About the Book About the Book This book is unique in that it covers most reactions that are the syllabus of undergrascapduate and postgraduate students. The reaction mechanisms are shown in details with step‐by‐step explanation of the processes. Most of the reactions' applications and experimental procedures are also given. Professional researcher may utilize it as a handbook due to its references to original literature, recent reviews, and application of named reactions and reagents frequently used in organic synthesis.

6 About the Author About the Author Surya K. De received his BS degree from Midnapore College and his PhD degree from Jadavpur University. His first book, Cancer & You: What Everyone Needs to Know About Cancer and Its Prevention , was published in 2018. He has published over 100 peer‐reviewed papers in reputed international journals, covering a broad array of specialized topics in science, and he holds 15 US patents for his inventions. Due to Dr. De's abundant research contributions in the areas of cancer, metabolic diseases, organic and medicinal chemistry, and neuroscience, he earned the distinction of Fellow of the Royal Society of Chemistry (London, UK) in 2010; he was subsequently awarded the status of Chartered Chemist in 2011. Furthermore, he is an elected alternate councilor in the American Chemical Society (San Diego section). Dr. De resides in San Diego, California, where he loves the scenic coastline and sunny skies.

7 Acknowledgments Acknowledgments The author would like to extend his gratitude to the original publishers for experimental procedures for granting permission to use in this book. The publishers include the American Chemical Society, Elsevier, the Royal Society of Chemistry, John Wiley & Sons, Wiley VCH‐Verlag, Thieme, and the Japan Institute of Heterocyclic Chemistry. I would like to thank all inventors for patent literatures cited in this book.

8 List of Abbreviations References List of Cooling Baths Further Reading

9 1 Rearrangement Reactions Baeyer–Villiger Oxidation or Rearrangement Dakin Oxidation (Reaction) Bamberger Rearrangement Beckmann Rearrangement Benzilic Acid Rearrangement Baker–Venkataraman Rearrangement Claisen Rearrangement Eschenmoser–Claisen Rearrangement Ireland–Claisen Rearrangement Johnson–Claisen Rearrangement Overman Rearrangement Cope Rearrangement Curtius Rearrangement Demjanov Rearrangement Tiffeneau–Demjanov Rearrangement Fries Rearrangement Favorskii Rearrangement Fischer–Hepp Rearrangement Hofmann Rearrangement (Hofmann degradation of amide) Hofmann–Martius Rearrangement Lossen Rearrangement Orton Rearrangement Pinacol–Pinacolone Rearrangement Rupe Rearrangement/Meyer–Schuster Rearrangement Schmidt Rearrangement or Schmidt Reaction Wagner–Meerwein Rearrangement Wolff Rearrangement Arndt–Eistert Homologation or Synthesis Zinin Rearrangement or Benzidine and Semidine Rearrangements References Dakin Oxidation or Reaction Bamberger Rearrangement Beckmann Rearrangement Benzilic Acid Rearrangement Baker–Venkataraman Rearrangement Claisen Rearrangement/Eschenmoser–Claisen Rearrangement/Ireland–Claisen Rearrangement/Johnson–Claisen Rearrangement/Overman Rearrangement Cope Rearrangement Curtius Rearrangement Demjanov Rearrangement Tiffeneau–Demjanov Rearrangement Fries Rearrangement Favorskii Rearrangement Fischer–Hepp Rearrangement Hofmann Rearrangement (Hofmann Degradation of Amide) Hofmann–Martius Rearrangement Lossen Rearrangement Orton Rearrangement Pinacol–Pinacolone Rearrangement Rupe Rearrangement/Meyer–Schuster Rearrangement Schmidt Rearrangement or Schmidt Reaction Wagner–Meerwein Rearrangement Wolff Rearrangement Arndt–Eistert Homologation or Synthesis Zinin Rearrangement or Benzidine and Semidine Rearrangements