ORGANIC CHEMISTRY AS A SECOND LANGUAGE, 5e Second Semester Topics DAVID KLEIN Johns Hopkins University VP AND DIRECTOR DIRECTOR EDITOR EDITORIAL ASSISTANT EDITORIAL MANAGER CONTENT MANAGEMENT DIRECTOR CONTENT MANAGER SENIOR CONTENT SPECIALIST PRODUCTION EDITOR COVER PHOTO CREDITS Laurie Rosatone Jessica Fiorillo Jennifer Yee Chris Gaudio Judy Howarth Lisa Wojcik Nichole Urban Nicole Repasky Bharathy Surya Prakash © Africa Studio/Shutterstock, © Lightspring/Shutterstock, © photka/Shutterstock, Flask - Norm Christiansen This book was set in 9/11 Times LT Std Roman by SPi Global and printed and bound by Quad Graphics Founded in 1807, John Wiley & Sons, Inc has been a valued source of knowledge and understanding for more than 200 years, helping people around the world meet their needs and fulfill their aspirations Our company is built on a foundation of principles that include responsibility to the communities we serve and where we live and work In 2008, we launched a Corporate Citizenship Initiative, a global effort to address the environmental, social, economic, and ethical challenges we face in our business Among the issues we are addressing are carbon impact, paper specifications and procurement, ethical conduct within our business and among our vendors, and community and charitable support For more information, please visit our website: www.wiley.com/go/citizenship Copyright © 2020, 2016, 2012, 2006, 2005 John Wiley & Sons, Inc All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning or otherwise, except as permitted under Sections 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923 (Web site: www.copyright.com) Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030-5774, (201) 748-6011, fax (201) 748-6008, or online at: www.wiley.com/go/permissions Evaluation copies are provided to qualified academics and professionals for review purposes only, for use in their courses during the next academic year These copies are licensed and may not be sold or transferred to a third party Upon completion of the review period, please return the evaluation copy to Wiley Return instructions and a free of charge return shipping label are available at: www.wiley.com/go/returnlabel If you have chosen to adopt this textbook for use in your course, please accept this book as your complimentary desk copy Outside of the United States, please contact your local sales representative ISBN: 978-1-119-49391-4 (PBK) ISBN: 978-1-119-49390-7 (EVAL) LCCN: 2019030971 The inside back cover will contain printing identification and country of origin if omitted from this page In addition, if the ISBN on the back cover differs from the ISBN on this page, the one on the back cover is correct CONTENTS CHAPTER 1.1 1.2 1.3 1.4 Introduction to Aromatic Compounds Nomenclature of Aromatic Compounds Criteria for Aromaticity Lone Pairs CHAPTER 2.1 2.2 2.3 2.4 2.5 2.6 AROMATICITY IR SPECTROSCOPY 11 Vibrational Excitation 11 IR Spectra 13 Wavenumber 13 Signal Intensity 18 Signal Shape 19 Analyzing an IR Spectrum 26 CHAPTER NMR SPECTROSCOPY 33 3.1 Chemical Equivalence 33 3.2 Chemical Shift (Benchmark Values) 36 3.3 Integration 41 3.4 Multiplicity 44 3.5 Pattern Recognition 46 3.6 Complex Splitting 48 3.7 No Splitting 49 3.8 Hydrogen Deficiency Index (Degrees of Unsaturation) 50 3.9 Analyzing a Proton NMR Spectrum 53 3.10 13 C NMR Spectroscopy 57 CHAPTER 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 4.9 ELECTROPHILIC AROMATIC SUBSTITUTION 60 Halogenation and the Role of Lewis Acids 61 Nitration 65 Friedel–Crafts Alkylation and Acylation 67 Sulfonation 74 Activation and Deactivation 78 Directing Effects 80 Identifying Activators and Deactivators 89 Predicting and Exploiting Steric Effects 99 Synthesis Strategies 106 iii iv CONTENTS CHAPTER 5.1 5.2 5.3 5.4 Criteria for Nucleophilic Aromatic Substitution 112 SN Ar Mechanism 114 Elimination–Addition 120 Mechanism Strategies 125 CHAPTER 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 KETONES AND ALDEHYDES 127 Preparation of Ketones and Aldehydes 127 Stability and Reactivity of C===O Bonds 130 H-Nucleophiles 132 O-Nucleophiles 137 S-Nucleophiles 147 N-Nucleophiles 149 C-Nucleophiles 157 Exceptions to the Rule 166 How to Approach Synthesis Problems 170 CHAPTER 7.1 7.2 7.3 7.4 7.5 7.6 7.7 NUCLEOPHILIC AROMATIC SUBSTITUTION CARBOXYLIC ACID DERIVATIVES 176 Reactivity of Carboxylic Acid Derivatives 176 General Rules 177 Acid Halides 181 Acid Anhydrides 189 Esters 191 Amides and Nitriles 200 Synthesis Problems 209 CHAPTER ENOLS AND ENOLATES 217 8.1 Alpha Protons 217 8.2 Keto-Enol Tautomerism 219 8.3 Reactions Involving Enols 223 8.4 Making Enolates 226 8.5 Haloform Reaction 229 8.6 Alkylation of Enolates 232 8.7 Aldol Reactions 236 8.8 Claisen Condensation 242 8.9 Decarboxylation 249 8.10 Michael Reactions 256 CHAPTER 9.1 9.2 9.3 9.4 9.5 9.6 AMINES 263 Nucleophilicity and Basicity of Amines 263 Preparation of Amines Through SN Reactions 265 Preparation of Amines Through Reductive Amination 268 Acylation of Amines 273 Reactions of Amines with Nitrous Acid 276 Aromatic Diazonium Salts 279 112 CONTENTS CHAPTER 10 10.1 10.2 10.3 10.4 DIELS–ALDER REACTIONS Introduction and Mechanism 282 The Dienophile 285 The Diene 286 Other Pericyclic Reactions 292 Detailed Solutions S-1 Index I-1 282 v CHAPTER AROMATICITY If you are using this book, then you have likely begun the second half of your organic chemistry course By now, you have certainly encountered aromatic rings, such as benzene In this chapter, we will explore the criteria for aromaticity, and we will discover many compounds (other than benzene) that are also classified as aromatic 1.1 INTRODUCTION TO AROMATIC COMPOUNDS Consider the structure of benzene: Benzene Benzene is resonance-stabilized, as shown above, and is sometimes drawn in the following way: This type of drawing (a hexagon with a circle in the center) is not suitable when drawing mechanisms of reactions, because mechanisms require that we keep track of electrons meticulously But, it is helpful to see this type of drawing, even though we won’t use it again in this book, because it represents all six π electrons of the ring as a single entity, rather than as three separate π bonds Indeed, a benzene ring should be viewed as one functional group, rather than as three separate functional groups This is perhaps most evident when we consider the special stability associated with a benzene ring To illustrate this stability, we can compare the reactivity of cyclohexene and benzene: Br2 Br + Enantiomer Br Br2 no reaction Cyclohexene is an alkene, and it will react with molecular bromine (Br2 ) via an addition process, as expected for alkenes In contrast, no reaction occurs when benzene is treated with Br2 , because the stability associated with the ring (of six π electrons) would be destroyed by an addition process That is, the six π electrons of the ring represent a single functional group that does not react with Br2 , as alkenes Understanding the source of the stability of benzene requires MO (molecular orbital) theory You may or may not be responsible for MO theory in your course, so you should consult your textbook and/or lecture notes to see whether MO theory was covered CHAPTER AROMATICITY Derivatives of benzene, called substituted benzenes, also exhibit the stability associated with a ring of six π electrons: R The ring can be monosubstituted, as shown above, or it can be disubstituted, or even polysubstituted (the ring can accommodate up to six different groups) Many derivatives of benzene were originally isolated from the fragrant extracts of trees and plants, so these compounds were described as being aromatic, in reference to their pleasant odors Over time, it became apparent that many derivatives of benzene are, in fact, odorless Nevertheless, the term aromatic is still currently used to describe derivatives of benzene, whether those compounds have odors or not 1.2 NOMENCLATURE OF AROMATIC COMPOUNDS As we have mentioned, an aromatic ring should be viewed as a single functional group Compounds containing this functional group are generally referred to as arenes In order to name arenes, recall that there are five parts of a systematic name, shown here (these five parts were discussed in Chapter of the first volume of Organic Chemistry as a Second Language: First Semester Topics): Stereoisomerism Substituents Parent Unsaturation Functional Group Benzene For benzene and its derivatives, the term benzene represents the parent, the unsaturation AND the suffix Any other groups (connected to the ring) must be listed as substituents For example, if a hydroxy (OH) group is connected to the ring, we not refer to the compound as benzenol We cannot add another suffix (-ol) to the term benzene, because that term is already a suffix itself Therefore, the OH group is listed as a substituent, and the compound is called hydroxybenzene: OH Hydroxybenzene Similarly, other groups (connected to the ring) are also listed as substituents, as seen in the following examples: CH3 Methylbenzene Cl Chlorobenzene NH2 Aminobenzene Many monosubstituted derivatives of benzene (and even some disubstituted and polysubstituted derivatives) have common names Several common names are shown here: ... ORGANIC CHEMISTRY AS A SECOND LANGUAGE, 5e Second Semester Topics DAVID KLEIN Johns Hopkins University VP AND DIRECTOR DIRECTOR EDITOR EDITORIAL ASSISTANT EDITORIAL MANAGER CONTENT MANAGEMENT... analogy: imagine that you have 10 friends, and you know what kind of bakery items they each like to eat every morning John always has a brownie, Peter always has a French roll, Mary always has... is actually a relatively weak base when compared with other very strong bases, such as the amide ion (H2 N− ) or carbanions (C− ) Above, we see an example of a carbanion that is similar in stability