A Q&A Approach to Organic Chemistry A Q&A Approach to Organic Chemistry Michael B. Smith First edition published 2020 by CRC Press 6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-2742 and by CRC Press 2 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN © 2020 Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, LLC Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume respon- sibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. 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ISBN: 978-0-367-22427-1 (hbk) ISBN: 978-0-429-27484-8 (ebk) Typeset in Times by Deanta Global Publishing Services, Chennai, India Contents Preface ...................................................................................................................................................... ix Common Abbreviations ............................................................................................................................xi Author .....................................................................................................................................................xiii Part A A Q&A Approach to Organic Chemistry 1 Orbitals and Bonding....................................................................................................................... 3 1.1 ORBITALS ............................................................................................................................. 3 1.1.1 Atomic Orbitals ......................................................................................................... 3 1.1.2 Electron Confguration .............................................................................................. 5 1.1.3 Molecular Orbitals .................................................................................................... 5 1.2 BONDING .............................................................................................................................. 6 1.2.1 Ionic Bonding ............................................................................................................ 6 1.2.2 Covalent Bonding ...................................................................................................... 7 1.3 HYBRIDIZATION ............................................................................................................... 12 1.4 RESONANCE ...................................................................................................................... 15 END OF CHAPTER PROBLEMS ...................................................................................................18 2 Structure of Molecules ................................................................................................................... 19 2.1 BASIC STRUCTURE OF ORGANIC MOLECULES ........................................................ 19 2.1.1 Fundamental Structures .......................................................................................... 19 2.1.2 Structures with Other Atoms Bonded to Carbon ................................................... 22 2.2 THE VSEPR MODEL AND MOLECULAR GEOMETRY ............................................... 23 2.3 DIPOLE MOMENT ............................................................................................................. 25 2.4 FUNCTIONAL GROUPS .................................................................................................... 26 2.5 FORMAL CHARGE ............................................................................................................ 28 2.6 PHYSICAL PROPERTIES ................................................................................................... 28 END OF CHAPTER PROBLEMS .................................................................................................. 32 3 Acids and Bases .............................................................................................................................. 33 3.1 ACIDS AND BASES ........................................................................................................... 33 3.2 ENERGETICS ...................................................................................................................... 35 3.3 THE ACIDITY CONSTANT, K ......................................................................................... 38 a 3.4 STRUCTURAL FEATURES THAT INFLUENCE ACIDITY .......................................... 40 3.5 FACTORS THAT CONTRIBUTE TO MAKING THE ACID MORE ACIDIC ............... 45 END OF CHAPTER PROBLEMS .................................................................................................. 48 4 Alkanes, Isomers, and Nomenclature .......................................................................................... 49 4.1 DEFINITION AND BASIC NOMENCLATURE ............................................................... 49 4.2 STRUCTURAL ISOMERS .................................................................................................. 50 4.3 IUPAC NOMENCLATURE ................................................................................................ 52 4.4 CYCLIC ALKANES ............................................................................................................ 57 END OF CHAPTER PROBLEMS .................................................................................................. 58 v vi Contents 5 Conformations .................................................................................................................................61 5.1 ACYCLIC CONFORMATIONS ...........................................................................................61 5.2 CONFORMATIONS OF CYCLIC MOLECULES ............................................................. 67 END OF CHAPTER PROBLEMS .................................................................................................. 75 6 Stereochemistry .............................................................................................................................. 77 6.1 CHIRALITY ........................................................................................................................ 77 6.2 SPECIFIC ROTATION ........................................................................................................ 81 6.3 SEQUENCE RULES ............................................................................................................ 83 6.4 DIASTEREOMERS ............................................................................................................. 87 6.5 OPTICAL RESOLUTION ................................................................................................... 89 END OF CHAPTER PROBLEMS .................................................................................................. 90 7 Alkenes and Alkynes: Structure, Nomenclature, and Reactions .............................................. 93 7.1 STRUCTURE OF ALKENES ............................................................................................. 93 7.2 NOMENCLATURE OF ALKENES ................................................................................... 95 7.3 REACTIONS OF ALKENES .............................................................................................. 98 7.4 REACTION OF ALKENES WITH LEWIS ACID-TYPE REAGENTS ......................... 107 7.4.1 Hydroxylation ........................................................................................................ 107 7.4.2 Epoxidation ............................................................................................................111 7.4.3 Dihydroxylation .....................................................................................................113 7.4.4 Halogenation ..........................................................................................................114 7.4.5 Hydroboration ........................................................................................................117 7.5 STRUCTURE AND NOMENCLATURE OF ALKYNES ............................................... 122 7.6 REACTIONS OF ALKYNES ............................................................................................ 124 END OF CHAPTER PROBLEMS ................................................................................................ 129 8 Alkyl Halides and Substitution Reactions ..................................................................................133 8.1 STRUCTURE, PROPERTIES, AND NOMENCLATURE OF ALKYL HALIDES ........133 8.2 SECOND-ORDER NUCLEOPHILIC SUBSTITUTION (S 2) REACTIONS ................ 134 N 8.3 OTHER NUCLEOPHILES IN S 2 REACTIONS .............................................................143 N 8.4 FIRST-ORDER SUBSTITUTION (S 1) REACTIONS .....................................................151 N 8.5 COMPETITION BETWEEN S 2 vs. S 1 REACTIONS .................................................. 156 N N 8.6 RADICAL HALOGENATION OF ALKANES ............................................................... 158 END OF CHAPTER PROBLEMS .................................................................................................162 9 Elimination Reactions ...................................................................................................................165 9.1 THE E2 REACTION ...........................................................................................................165 9.2 THE E1 REACTION ...........................................................................................................172 9.3 PREPARATION OF ALKYNES ........................................................................................176 9.4 SYN ELIMINATION ..........................................................................................................178 END OF CHAPTER PROBLEMS ................................................................................................ 180 10 Organometallic Compounds ........................................................................................................183 10.1 ORGANOMETALLICS ......................................................................................................183 10.2 ORGANOMAGNESIUM COMPOUNDS .........................................................................183 10.3 ORGANOLITHIUM COMPOUNDS .................................................................................185 10.4 BASICITY ...........................................................................................................................187 10.5 REACTION WITH EPOXIDES .........................................................................................188 10.6 OTHER METALS ...............................................................................................................188 END OF CHAPTER PROBLEMS ................................................................................................ 190 Contents vii 11 Spectroscopy ..................................................................................................................................191 11.1 THE ELECTROMAGNETIC SPECTRUM .......................................................................191 11.2 MASS SPECTROMETRY ................................................................................................. 192 11.3 INFRARED SPECTROSCOPY (IR) ................................................................................. 196 11.4 NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY (nmr) ................................. 201 END OF CHAPTER PROBLEMS .................................................................................................215 12 Aldehydes and Ketones. Acyl Addition Reactions .....................................................................219 12.1 STRUCTURE AND NOMENCLATURE OF ALDEHYDES AND KETONES .............219 12.2 REACTION OF ALDEHYDES AND KETONES WITH WEAK NUCLEOPHILES ...... 221 12.3 REACTIONS OF ALDEHYDES AND KETONES. STRONG NUCLEOPHILES ........ 230 12.4 THE WITTIG REACTION ................................................................................................ 233 END OF CHAPTER PROBLEMS ................................................................................................ 235 Part B A Q&A Approach to Organic Chemistry 13 Oxidation Reactions ..................................................................................................................... 239 13.1 OXIDATION REACTIONS OF ALKENES ..................................................................... 239 13.2 OXIDATION OF ALKENES: EPOXIDATION ................................................................244 13.3 OXIDATIVE CLEAVAGE: OZONOLYSIS....................................................................... 247 13.4 OXIDATIVE CLEAVAGE. PERIODIC ACID CLEAVAGE OF 1,2-DIOLS ................... 250 13.5 OXIDATION OF ALCOHOLS TO ALDEHYDES OR KETONES .................................251 END OF CHAPTER PROBLEMS ................................................................................................ 255 14 Reduction Reactions ..................................................................................................................... 257 14.1 CATALYTIC HYDROGENATION ................................................................................... 258 14.2 DISSOLVING METAL REDUCTION: ALKYNES .........................................................264 14.3 HYDRIDE REDUCTION OF ALDEHYDES AND KETONES ..................................... 265 14.4 CATALYTIC HYDROGENATION AND DISSOLVING METAL REDUCTIONS. ALDEHYDES AND KETONES ....................................................................................... 269 END OF CHAPTER PROBLEMS ................................................................................................ 273 15 Carboxylic Acids, Carboxylic Acid Derivatives, and Acyl Substitution Reactions ............... 275 15.1 STRUCTURE OF CARBOXYLIC ACIDS ....................................................................... 275 15.2 PREPARATION OF CARBOXYLIC ACIDS ................................................................... 280 15.3 CARBOXYLIC ACID DERIVATIVES ............................................................................ 283 15.4 PREPARATION OF ACID DERIVATIVES ..................................................................... 290 15.5 HYDROLYSIS OF CARBOXYLIC ACID DERIVATIVES ............................................ 301 15.6 REACTIONS OF CARBOXYLIC ACIDS AND ACID DERIVATIVES ........................ 305 15.7 DIBASIC CARBOXYLIC ACIDS ......................................................................................310 END OF CHAPTER PROBLEMS .................................................................................................312 16 Benzene, Aromaticity, and Benzene Derivatives ........................................................................315 16.1 BENZENE AND NOMENCLATURE OF AROMATIC COMPOUNDS ........................315 16.2 ELECTROPHILIC AROMATIC SUBSTITUTION ..........................................................319 16.3 SYNTHESIS VIA AROMATIC SUBSTITUTION ...........................................................335 16.4 NUCLEOPHILIC AROMATIC SUBSTITUTION ........................................................... 337 16.5 REDUCTION OF BENZENE AND BENZENE DERIVATIVES ................................... 344 16.6 POLYCYCLIC AROMATIC COMPOUNDS AND HETEROAROMATIC COMPOUNDS ................................................................................................................... 347 END OF CHAPTER PROBLEMS .................................................................................................353 viii Contents 17 Enolate Anions and Condensation Reactions ............................................................................ 357 17.1 ALDEHYDES, KETONES, ENOLS, AND ENOLATE ANIONS .................................. 357 17.2 ENOLATE ALKYLATION ................................................................................................361 17.3 CONDENSATION REACTIONS OF ENOLATE ANIONS AND ALDEHYDES OR KETONES.................................................................................................................... 366 17.4 ENOLATE ANIONS FROM CARBOXYLIC ACIDS AND DERIVATIVES ................ 372 END OF CHAPTER PROBLEMS ................................................................................................ 383 18 Conjugation and Reactions of Conjugated Compounds........................................................... 385 18.1 CONJUGATED MOLECULES ......................................................................................... 385 18.2 STRUCTURE AND NOMENCLATURE OF CONJUGATED SYSTEMS .................... 387 18.3 REACTIONS OF CONJUGATED MOLECULES ............................................................391 18.4 THE DIELS–ALDER REACTION ................................................................................... 393 18.5 [3+2]-CYCLOADDITION REACTIONS .......................................................................... 401 18.6 SIGMATROPIC REARRANGEMENTS .......................................................................... 403 18.7 ULTRAVIOLET SPECTROSCOPY ..................................................................................406 END OF CHAPTER PROBLEMS ................................................................................................ 409 19 Amines ............................................................................................................................................413 19.1 STRUCTURE AND PROPERTIES ....................................................................................413 19.2 PREPARATION OF AMINES ...........................................................................................416 19.3 REACTIONS OF AMINES ............................................................................................... 420 19.4 HETEROCYCLIC AMINES ............................................................................................. 424 END OF CHAPTER PROBLEMS ................................................................................................ 426 20 Amino Acids, Peptides, and Proteins ......................................................................................... 429 20.1 AMINO ACIDS .................................................................................................................. 429 20.2 SYNTHESIS OF AMINO ACIDS ......................................................................................435 20.3 REACTIONS OF AMINO ACIDS .................................................................................... 437 20.4 PROTEINS ......................................................................................................................... 441 END OF CHAPTER PROBLEMS ................................................................................................ 447 21 Carbohydrates and Nucleic Acids ............................................................................................... 449 21.1 CARBOHYDRATES ......................................................................................................... 449 21.2 DISACCHARIDES AND POLYSACCHARIDES ............................................................ 457 21.3 SYNTHESIS OF CARBOHYDRATES ............................................................................ 459 21.4 REACTIONS OF CARBOHYDRATES ............................................................................ 461 21.5 NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES .........................................464 END OF CHAPTER PROBLEMS .................................................................................................471 Appendix: Answers to End of Chapter Problems ............................................................................ 473 Index ...................................................................................................................................................... 505 Preface What is organic chemistry? Organic chemistry is the science that studies molecules containing the element carbon. Carbon can form bonds to other carbon atoms or to a variety of atoms in the periodic table. The most common bonds observed in an organic chemistry course are C—C, C—H, C—O, C—N, C—halogen (Cl, Br, I), C—Mg, C—B, C—Li, C—S and C—P. This book is presented in the hope that it will provide extra practice to students taking organic chem- istry for the frst time and also serve as a cogent review to those who need to refresh their knowledge of organic chemistry. This book of questions began life as Organic Chemistry in 1993 to assist those students taking undergraduate organic chemistry and was part of a HarperCollins Outline series that was never completed. My book, along with those other books in the series that were completed, was sold as a reference book rather than a textbook. In 2006, a second edition of Organic Chemistry was published and marketed more or less the same way. The book laid fallow for several years until this version became possible. With this book, published by CRC Press/Taylor & Francis Group, I continue the idea of teach- ing organic chemistry by asking leading questions. A Q&A Approach to Organic Chemistry is intended as a supplement to virtually any organic chem- istry textbook rather than a stand-alone text and it will allow a “self-guided tour” of organic chemistry. Teaching organic chemistry with a Q&A format uses leading questions along with the answers and is presented in a manner that allows a student to refresh and renew their working knowledge of organic chemistry. Such an approach will also be of value to those reviewing organic chemistry for MCATs (Medical College Admission Test); graduate record exams (a standardized test), which is an admissions requirement for many graduate schools); the PCAT (Pharmacy College Admission Test), which identi- fes qualifed applicants to pharmacy colleges before commencement of pharmaceutical education; and so on. This Q&A format was classroom-tested here at the University of Connecticut for many years where one of the earlier versions of this book was used as a supplement. Indeed, the book was not required for purchase and used only on a voluntary basis by students. According to their end-of-semester evaluations, students who wanted or needed additional homework found the book very useful and helpful. Classroom experience and comments from students have been used for the preparation of this new student-friendly book. This book is organized into 21 chapters and will supplement most of the organic textbooks on the market. In all chapters, there are leading questions to focus attention on a principle or reaction and the answer is immediately provided. The organization of the book provides an initial review of fundamental principles followed by reactions based on manipulation of functional groups. The intent in all cases is to provide a focused question about a specifc principle or reaction and the answer immediately follows. There is also a chapter on spectroscopy as well as chapters on amino acid and peptide chemistry and carbohydrate and nucleoside chemistry. Each chapter ends with several homework questions for that chapter, and the answers are provided in an Appendix at the end of the book. I thank all of the organic chemistry students I taught over the years. They provided the inspira- tion for the book as well as innumerable suggestions that were invaluable. I thank Ms. Hilary Lafoe and Ms. Jessica Poile, the Taylor & Francis editors for this book, and also Dr. Fiona Macdonald, the publisher. This book would not have been possible without their interest in chemistry and their help as the book was written. I thank Professor John D’Angelo of Alfred University who provided a very useful and helpful review of the manuscript. I thank PerkinElmer who provided a gift of ChemDraw Professional (Version 18.0.0.231[4318]). All the reactions and fgures were done with ChemDraw except for those images that use molecular models and the artist-rendered drawings. All molecular models were rendered with Spartan’18 software and I thank Warren Hehre and Sean Ohlinger of Wavefunction, ix