Tmultimedia he website found at www.whfreeman.com/vollhardtschore5e is a learning tool that focuses on molecular visualizations “Animations” and “Animated Mechanisms” are two features of this interactive website that are integrated seamlessly with the textbook using media icons and descriptive text “Animations” allow students to view motion, three dimensions, atomic and molecular interactions, and chemical reactions at the atomic level Topics focus on orbitals and hybridization “Animated Mechanisms” allow students to view molecular interactions visually as structural formulas and in a ball-and-stick format Topics include chemical reactivity and structures and bonding The following is a list of selected “Animations” and “Animated Mechanisms” found in this textbook Molecular Visualizations, Text Reference Stereospecific bromination of 2-butenes p 512 (Ch 12) Hydroboration–oxidation p 521 (Ch 12) p 27 (Ch 1) Oxacyclopropanation p 525 (Ch 12) p 34 (Ch 1) Ozonolysis p 529 (Ch 12) p 34 (Ch 1) Radical hydrobromination of 1-butene p 532 (Ch 12) Radical allylic halogenation p 606 (Ch 14) p 35 (Ch 1) Addition of HBr to 1,3-butadiene p 614 (Ch 14) p 35 (Ch 1) Diels-Alder cycloaddition (endo rule) p 630 (Ch 14) Electrophilic aromatic p 37 (Ch 1) sulfonation of benzene p 698 (Ch 15) p 105 (Ch 3) Electrophilic aromatic substitution of benzenamine (ortho vs meta vs para) p 729 (Ch 16) p 141 (Ch 4) Electrophilic aromatic substitution of p 143 (Ch 4) benzoic acid (ortho vs meta vs para) p 732 (Ch 16) pp 225, 226, 228, Acetal formation p 781 (Ch 17) 236 (Ch 6) The Wittig reaction p 794 (Ch 17) Nucleophilic substitution (SN1) pp 825, 826 (Ch 18) of (CH3)3CBr with HOH pp 253, 254 (Fig 7-2), Aldol condensation–dehydration Robinson annulation p 840 (Ch 18) 255 (Ch 7) Esterification p 878 (Ch 19) Elimination (E2) reaction of Amide hydrolysis p 929 (Ch 20) 2-chloro-2-methylpropane p 266 (Ch 7) Hofmann rearrangement p 934 (Ch 20) Reduction of pentanal with Reductive amination p 973 (Ch 21) sodium borohydride p 297 (Ch 8) The Mannich reaction p 977 (Ch 21) Reduction of cyclobutanone Benzylic nucleophilic substitution pp.1004,1005(Ch 22) with lithium aluminum hydride p 300 (Ch 8) Nucleophilic aromatic substitution p 1015 (Ch 22) Formation of Grignard reagent Nucleophilic aromatic from 1-bromobutane p 304 (Ch 8) substitution via benzynes p 1019 (Ch 22) Reaction of Grignard reagent with The Claisen condensation p 1062 (Ch 23) acetaldehyde to give 2-hexanol p 307 (Ch 8) Alcohol dehydration p 336 (Ch 9) Cyclic hemiacetal formation by glucose p 1102 (Ch 24) Carbocation rearrangement p 337 (Ch 9) Methyl glycoside formation p 1114 (Ch 24) Electrophilic addition of HCl The Strecker synthesis p 1200 (Ch 26) to propene p 506 (Ch 12) Merrifield synthesis of peptides p 1219 (Ch 26) Fig 1-5, 1s orbital Fig 1-7, px orbital; py orbital; pz orbital Fig 1-16, sp hybrids Fig 1-17, sp2 hybrids Fig 1-18, sp3 hybrids and methane orbitals Fig 1-19, ethane orbitals Fig 1-21, ethene and ethyne orbitals Chlorination of methane Fig 4-9, cyclohexane potential energy diagram Fig 4-11, cyclohexane ring flip Nucleophilic substitution (SN2) p 25 (Ch 1) Organic Chemistry The , Fifth Edition eBook is a complete online version of the respected textbook This next generation eBook offers students substantial savings and provides a rich learning experience by taking full advantage of the electronic medium This online version of Organic Chemistry integrates all of the existing student media resources and adds features unique to the eBook The eBook also offers instructors unparalleled flexibility and customization options not previously possible with any printed textbook All of the student media that accompany Organic Chemistry were developed specifically for the book There is no extraneous material that does not directly support and integrate with the concepts and art program of the textbook The genius of the eBook is that it puts these unique resources right at the students’ fingertips as they read the text—making the integration of the media and text much more seamless than was possible before Key features of the Organic Chemistry eBook include: ◆ Easy access from any Internet-connected computer via a standard Web browser ◆ Quick, intuitive navigation to any section or subsection, as well as any printed book page number ◆ Integration of all student website animated tutorials and activities ◆ In-text self quiz questions ◆ In-text links to all glossary entries ◆ Interactive chapter summary exercises ◆ Text highlighting, down to the level of individual phrases ◆ A bookmarking feature that allows for quick reference to any page ◆ A powerful Notes feature that allows students or instructors to add notes to any page ◆ A full glossary and index ◆ Full-text search, including an option to also search the glossary and index ◆ Automatic saving of all notes, highlighting, and bookmarks Additional features for instructors: ◆ Custom Chapter Selection: Instructors can choose the chapters that correspond to their syllabus, and students will get a custom version of the eBook with the selected chapters only ◆ Instructor Notes: Instructors can choose to create an annotated version of the eBook with their notes on any page Once a student enters their eBook, they will see the instructor’s version ◆ Custom Content: Instructor notes can include text, web links, and even images, allowing instructors to place any content they choose exactly where they want it ◆ Online Quizzing: The online quizzes from the student website are integrated into the eBook For more information, please visit www.ebooks.bfwpub.com About the Authors K Peter C Vollhardt was born in Madrid, raised in Buenos Aires and Munich, studied at the University of Munich, got his Ph.D with Professor Peter Garratt at the University College, London, and was a postdoctoral fellow with Professor Bob Bergman (then) at the California Institute of Technology He moved to Berkeley in 1974 when he began his efforts toward the development of organocobalt reagents in organic synthesis, the preparation of theoretically interesting hydrocarbons, the assembly of novel transition metal arrays with potential in catalysis, and the discovery of a parking space Among other pleasant experiences, he was a Studienstiftler, Adolf Windaus medalist, Humboldt Senior Scientist, ACS Organometallic Awardee, Otto Bayer Prize Awardee, A C Cope Scholar, Japan Society for the Promotion of Science Prize Holder, and recipient of the Medal of the University Aix-Marseille and an Honorary Doctorate from The University of Rome Tor Vergata He is the current Chief Editor of Synlett Among his more than 290 publications, he treasures especially this textbook in organic chemistry, translated into ten languages Peter is married to Marie-José Sat, a French artist, and they have two children, Paloma (b 1994) and Julien (b 1997), whose picture you can admire on p 168 Neil E Schore was born in Newark, New Jersey, in 1948 His education took him through the public schools of the Bronx, New York, and Ridgefield, New Jersey, after which he completed a B.A with honors in chemistry at the University of Pennsylvania in 1969 Moving back to New York, he worked with Professor Nicholas Turro at Columbia University, studying photochemical and photophysical processes of organic compounds for his Ph.D thesis He first met Peter Vollhardt when he and Peter were doing postdoctoral work in Professor Robert Bergman’s laboratory at Cal Tech in the 1970s Since joining the U C Davis faculty in 1976, he has taught organic chemistry to more than 10,000 nonchemistry majors, winning three teaching awards, and has published over 80 papers in various areas related to organic synthesis Neil is married to Carrie Erickson, a microbiologist at the U C Davis School of Veterinary Medicine They have two children, Michael (b 1981) and Stefanie (b 1983), both of whom carried out experiments for this book ORGANIC CHEMISTRY This page intentionally left blank O RGANIC C HEMISTRY Structure and Function FIFTH EDITION K PETER C VOLLHARDT University of California at Berkeley NEIL E SCHORE University of California at Davis W H FREEMAN AND COMPANY New York Publishers: Susan Finnemore Brennan, Craig Bleyer Senior Acquisitions Editor: Clancy Marshall Senior Marketing Manager: Krista Bettino Developmental Editor: David Chelton Media Editor: Victoria Anderson Associate Editor: Amy Thorne Photo Editor: Cecilia Varas Photo Researcher: Elyse Reider Cover Designer: Cambraia Fernandes Text Designer: Blake Logan Project Editor: TechBooks Illustrations: Network Graphics Illustration Coordinator: Bill Page Production Coordinator: Susan Wein Composition: TechBooks Printing and Binding: RR Donnelley EAN: 9780716799498 Library of Congress Cataloging-in-Publication Data Vollhardt, K Peter C Organic chemistry : structure and function.— 5th ed / K Peter C Vollhardt, Neil E Schore p cm Includes index ISBN 0-7167-9949-9 Chemistry, Organic—Textbooks I Schore, Neil Eric, 1948– II Title QD251.3.V65 2007 547—dc22 2005025107 ©2007 All rights reserved Printed in the United States of America First printing W H Freeman and Company 41 Madison Avenue New York, NY 10010 Houndmills, Basingstoke RG21 6XS, England www.whfreeman.com CONTENTS Preface: A User’s Guide to Organic Chemistry: Structure and Function Structure and Bonding in Organic Molecules 1-1 The Scope of Organic Chemistry: An Overview Chemical Highlight 1-1 Saccharin: One of the Oldest Synthetic Organic Compounds in Commercial Use 1-2 Coulomb Forces: A Simplified View of Bonding 1-3 Ionic and Covalent Bonds: The Octet Rule 1-4 Electron-Dot Model of Bonding: Lewis Structures 1-5 Resonance Forms 1-6 Atomic Orbitals: A Quantum Mechanical Description of Electrons Around the Nucleus 1-7 Molecular Orbitals and Covalent Bonding 1-8 Hybrid Orbitals: Bonding in Complex Molecules 1-9 Structures and Formulas of Organic Molecules Chapter Integration Problems Important Concepts Problems Structure and Reactivity: Acids and Bases, Polar and Nonpolar Molecules 2-1 Kinetics and Thermodynamics of Simple Chemical Processes 2-2 Acids and Bases; Electrophiles and Nucleophiles Chemical Highlight 2-1 Stomach Acid and Food Digestion 2-3 Functional Groups: Centers of Reactivity 2-4 Straight-Chain and Branched Alkanes 2-5 Naming the Alkanes 2-6 Structural and Physical Properties of Alkanes 2-7 Rotation about Single Bonds: Conformations Chemical Highlight 2-2 “Sexual Swindle” by Means of Chemical Mimicry 2-8 Rotation in Substituted Ethanes Chapter Integration Problems Important Concepts Problems xx 14 19 23 29 32 38 41 45 46 51 52 58 59 66 69 71 76 79 79 83 87 89 90 vi CONTENTS Reactions of Alkanes: Bond-Dissociation Energies, Radical Halogenation, and Relative Reactivity 3-1 Strength of Alkane Bonds: Radicals 3-2 Structure of Alkyl Radicals: Hyperconjugation 3-3 Conversion of Petroleum: Pyrolysis Chemical Highlight 3-1 Petroleum and Gasoline: Our Main Energy Sources 3-4 Chlorination of Methane: The Radical Chain Mechanism 3-5 Other Radical Halogenations of Methane 3-6 Chlorination of Higher Alkanes: Relative Reactivity and Selectivity 3-7 Selectivity in Radical Halogenation with Fluorine and Bromine 3-8 Synthetic Radical Halogenation 3-9 Synthetic Chlorine Compounds and the Stratospheric Ozone Layer Chemical Highlight 3-2 Chlorination, Chloral, and DDT 3-10 Combustion and the Relative Stabilities of Alkanes Chapter Integration Problems Important Concepts Problems Cycloalkanes 4-1 Names and Physical Properties of Cycloalkanes 4-2 Ring Strain and the Structure of Cycloalkanes 4-3 Cyclohexane: A Strain-Free Cycloalkane 4-4 Substituted Cyclohexanes 4-5 Larger Cycloalkanes 4-6 Polycyclic Alkanes 4-7 Carbocyclic Products in Nature Chemical Highlight 4-1 Cubane Derivatives with Potential as Explosives: Octanitrocubane Chemical Highlight 4-2 Cholesterol: How Is It Bad and How Bad Is It? Chemical Highlight 4-3 Controlling Fertility: From “the Pill” to RU-486 Chapter Integration Problems Important Concepts Problems 96 97 100 101 104 105 110 112 116 118 119 119 122 124 126 127 131 132 134 139 144 148 149 151 151 155 156 158 161 162 INDEX Prelog, Vladimir, 177 Primary amine, 784–785 carbon, 72 hydrogen, 72–73, structure, 1207 Priority of substituents, R,S nomenclature, 178 Prismane, 666 Product, Progesterone, 156–157, 299 Progestin, 156 Proline, 1193t 1,2-Propadiene (allene), 610 Propagation, in radical reactions, 536 Propane, 66 chlorination of, 113–114 conformational analysis of, 83 Propanedioic acid See malonic acid 1,2,3-Propanetriol (glycerol, glycerine), 368 Propanoic (propionic) acid, 68t 2-Propanol, 68t [2.2.2]Propellane, 48 Propenal (acrolein), 624–625 Propenenitrile (acrylonitrile), 537, 585, 983 Propenoic (acrylic) acid, 584 2-Propenyl system, 602, 605 allylic halides, nucleophilic substitution, 607–609 allylic halogenation, radical, 606 anion, 603 cation, 603 molecular orbitals of, 604 organometallic reagents of, 609 radical, 603 resonance in, 604 Propyl group, 72 Propylhexedrine (Benzedrex), 960 2-Propynyl group, 562 Prostacyclin, 38, 888 Prostaglandin, 459, 840 Protein, 1191 See also Polypeptide fibrous, 1209 globular, 1209, 1249 Protecting group, 356, 357, 743, 1115 acetals as, 782–783 for alcohols, 356–357, 743, 1115 for aldehydes and ketones, 782–783 See Acetal for amino acids, 1216 in DNA synthesis, 1235–1237 in polypeptide synthesis, 1216 for sugars, 1115 thiols as, 784 Protic solvents, 236, 260, 290 Proton, Protonation, 290 of alcohols, 290 of alkanenitriles, 939 of alkenes, 505–506 of alkynes, 585 of amines, 966 of 1,3-butadiene, 614 of carboxylic acid derivatives, 866, 913 of carboxylic acids, 866 of enolate ions, 816 of organometallic reagents, 305 of pyridine, 1161 of pyrrole, 1158 reversible, 509–510 see also Acid; Acidity; Deprotonation; Electrophilic addition; Nucleophilic addition Proton relaxation time, 404 Prozac (Fluoxetin), 956, 960, 985 Pteridine, 1169–1170 See 1,3,5,8Tetraazanaphthalene Pyramidal, 14, 958 Pyran, 1103 Pyranose, 1103, 1105 Pyrazine, 1161 See 1,4 Diazabenzene Pyridazine, 1161 See 1,2Diazabenzene Pyridine, 1160–1162 basicity of, 1161 electronic structure of, 1160–1161 electrophilic aromatic substitution of, 1164 nuclear magnetic resonance of, 1161 nucleophilic substitutions in, 1165 pyridinium salts from, 1161 synthesis of (Hantzsch synthesis), 1162 Pyridinium chlorochromate (PCC), 302–303 Pyridinium salts, 1161, 1166 Pyrimidine See 1,3Diazabenzene, 1161, 1170 Pyridoxine (Vitamin B6), 1147 Pyrolysis, 101 of alkanes, 101–102 of hexane, 101 and petroleum, 101, 103 of quaternary ammonium salts, 975 See Hofmann elimination and radicals, 102 Pyrrole, 1153–1158 basicity of, 1158 electronic structure, 1154 electrophilic aromatic substitution, 1156–1157 preparation of (Paal-Knorr synthesis), 1155 protonation of, 1158 resonance structure of, 1154 Q Quanta, 389 Quantized, 24, 389 Quantum mechanics, 18, 23–24, 32 Quartets in NMR, 458–459 Quaternary ammonium salt, 970, 975 in Hofmann elimination, 975 pyrolysis, 975 synthesis, 970 see also Ammonium salt Quaternary carbon, 72, 430 Quaternary structure, 1211, 1222 Quinazoline, 1170 See 1,3Diazanapthalene Quinine, 1171 Quinoline, 573, 1148, 1167 Quinomethane, 1026–1027 Quinoxaline, 1170 See 1,4Diazanapthalene R R,S nomenclature, 178, 373 Racemate, 189, 193, 194, 201 from cationic intermediates, 255 from radical intermediates, 195–196 Racemic mixture, 176, 178, 194 See racemate Racemization, 176–177, 662, 819 of ketones, 819 Radiation, electromagnetic, 3, 24, 388–389 Radical allylic substitution, 606 Radical anion, 535, 574, 1031–1032 Radical chain mechanism, 105 See also Radical reaction I-19 Radicals, 97 stability of, 98–100 formation of, 97 steric crowding, 101 see also Pyrolysis; Radical reaction, 100 Radical reaction, 97 additions to alkenes, 535 additions to alkynes, 579 chain mechanism, 105 halogenations, 105–119 initiation step, 106 initiators in, 532–533 mechanism of, 532 propagation step, 532 regioselectivity in, 113–116, 531 termination step, 109 Radiotracer, 1113 Raney, Murray, 502 Raney nickel, 502, 784, 790, 970, 1158 Rate constant, 56–57 Rate law, 57, 224 Rate-determining step, 252–253 Reactant Reaction, kinetic and thermodynamic control, of 614 Reaction coordinate, 55 Reaction intermediate, Reaction mechanism, See Mechanism of reaction Reaction rates, 56–57 Rearrangement, 337 of alkenes, 833 of carbocations, 337 by alkyl shifts, 341 by hydride shifts, 337 by electrocyclic reactions, 632–636 of enols to ketones or aldehydes, 816 Hofmann, 933–934 McLafferty, 772 mutarotation, 1105–1107 in protein sequencing, 1216 Receptor site, enzyme, 198 Redox reactions, 296, 319, 1033–1034 Reducing sugars, 1107–1108 Reduction, 295 of aldehydes and ketones, 296–301 of alkanenitriles, 940 of alkanoyl halides, 917 of alkenes, 501–503 of alkylmercury compounds, 516 of alkynes 573–574 of amides, 932–933, 975 of azides, 971 I-20 INDEX Reduction (cont.) of carbon monoxide, 293 of carboxylic acids, 882 of esters, 923–924 of haloalkanes, 305 by hydrazine (WolffKishner), 789–791 of imines, 972–974 by lithium, 366 of nitriles, 940 one-electron, 574–576, 1034 of oxacyclopropanes, 359 of ozonides, 529–530 by potassium, 692 by sodium, 574–575, 592t of sugars, 1110 of thioacetals, 784 by zinc amalgam (Clemmensen), 739 see also Hydrogenation; Hydride reagent Reductive amination, 972–974 Regioselectivity, 359 in Baeyer-Villiger oxidations, 796 in E2 reactions, 478 in electrophilic reactions, 724–727 in halonium ion opening, 514 in hydroborations, 520 in radical reactions, 531 Remsen, Ira, Relative reactivity, 96 Replication of DNA, 1227 Residue, amino acid, 1204 Resolution, 201 of enantiomers, 194, 201 with (ϩ)tartaric acid of amine, 189 Resonance, 19, 387 acceptance from benzene, 723 in acylium cations, 705 in aldehydes and ketones, 861–862 allylic, 604 in [18]annulene, 689 in anthracene, 684 in benzene, 666 in benzenediazonium cation, 1038 benzylic, 1002–1003 in carbonyl group, 767 in carboxylate ion, 864 in carboxylic acid derivatives, 910 in carboxylic acids, 863 in cycloheptatrienyl cation, 691 in cyclohexadienyl cations, 693 in cyclopentadienyl anion, 691 in diazomethane, 23 donation to benzene, 723 in enamines, 823 in enolates, 864 hybrid, 20 in hydrazone anion, 790 in imidazole, 1198 in iminium ions, 785 increased acidity of a-hydrogens, 62 in indole, 1159 in naphthalene, 682 in nuclear magnetic resonance, 387, 391 in phenanthrene, 684 in phenoxide ion, 1011 in protonated carboxylic acid, 866 in pyridine, 1161 in pyrrole, 1154 in substituted benzenes, 722 in ␣,-unsaturated aldehydes and ketones, 833 in ylides, 792 Resonance energy, 669 Resonance forms, 19–22 guidelines for drawing, 22 Resonance hybrid, 20 Restriction endonucleases, 1231 Restriction enzymes, 1231, 1238 Resveratrol, 1013 Retention of configuration, 229, 261, 521 Retinal, 814, 832 Retinal isomerase, 832 Retinol, 619, 832 See Vitamin A Retronecine, 978 Retrosynthetic analysis, 312 Reverse polarization, 305, 1078 Reversible protonation, 509–510 Reverse sulfonation, 697 Rhodopsin, 832 Riboflavin (vitamin B2), 1169 Ribonucleic acid See RNA, 1097 Ribose, 1097 Ribosome, 930, 1229–1230 Ring current, 674 Ring fusion carbon, 149 Ring fusion substituent, 149 Ring strain, 134 in cycloalkanes, 134–139 effect of, on cyclization rates in cyclic ether synthesis, 352 limits of, 150 in oxacyclopropane openings, 359 and reactvity of heterocyclopropanes and butanes, 1149 Ring system, 149 bicyclic, 149 see also Benzene; Cycloalkane; Heterocycle; Polycyclic benzenoid hydrocarbon Ring-closure reactions, 353, 542, 633 in acid-catalyzed dehydration of diols to cyclic ethers, 584 in alkene halogenations to cyclic halonium ions, 512 in alkene mercurations, 518 in alkene oxidations to oxacyclopropanes, 513, 524 in carbene additions to alkenes, 522 in cyclic anhydride formation, 876 in dithiol oxidations, 366 of geranyl pyrophosphate, 642 in Hantzsch pyridine synthesis, 1162 in hemiacetal formation in sugars, 780 in imide formation, 881 in intramolecular aldol condensations, 830 in intramolecular FriedelCrafts alkylations, 753 in intramolecular hemiacetal and acetal formation, 780 in intramolecular Williamson ether synthesis, 351 in lactam formation, 881 in lactone formation, 798 in Paal-Knorr synthesis of heterocylopentadienes, 1155 in Wittig reaction, 794 Ring-opening reaction, 137, 358 of cyclic acetals, 783 of cyclic anhydrides, 919 of cyclic halonium ions, 512 of cyclic mercurinium ions, 518 of furan, 1158 of imides, 972, 1199 of lactones, 922 in nucleophilic attack on heterocycles, 1149 of ozonides, by reducing agents, 529 ozonolysis of cycloalkenes, 531 in Wittig reaction, 794 RNA, 1191 messenger RNA, 1192 nucleotides in, 1223–1225 in protein synthesis, 1228 transfer RNA, 1229 Robinson annulation, 839–841 Rotamer See Conformational isomer, 82 Rotational energy, 82 Royal purple dye, 1042 Rubber, 638 Ruff degradation, 1117 Ruff, Otto, 1117 RU-486, 156 S S, 178, 373 See R,S nomenclature Saccharides 1097 See also Sugar Saccharin, Salicylic acid, 858, 1023, 1027, 1172 Sandmeyer, Traugott, 1039 Sandmeyer reaction, 1039 Saponification, 884 See also Hydrolysis Saturated hydrocarbon See Alkane Saturation, 474 Saytzev, Alexander M., 478 Saytzev rule, 478 Schiff base, 785 Schiff, Hugo, 785 Schrödinger, Erwin, 23 Secondary amine, 788 carbon, 72 hydrogen, 72 structure, of proteins, 1207–1211 Second-order reaction, 56–57 Selectivity, 112 See also Regioselectivity Self-ionization constant of water, 59 Semicarbazide, 787t Semicarbazone, 787t Semiquinone radical anion, 1031 Sequencing, 1211 of DNA, 1231 of polypeptides, 1211–1216 Serine, 1193t Sevin (1-naphthyl-Nmethylcarbamate), 936 INDEX Sex hormone, 156, 357 Shielding, 396 Sibutramine (Meridia), 961 Sickle-cell anemia, 1211 Sigma () bond, 31 overlap in vs pi bond, 452 Sildenafil citrate (Viagra), 1147 Simmons, Howard E., 523 Simmons-Smith reagent, 523 Simple sugar, 780, 1097 Singlets in NMR, 407 Skew configuration, 80, 141 Skew-boat configuration, 141 Smalley, Richard E., 680 Smith, Ronald D., 523 SN1 reaction, 252–259, 261 carbocation stability and, 258–259 E1 reaction in relation to, 262–263 effect of nature of leaving group on, 256–257 of nucleophile on, 257 kinetics of, 252 mechanism of, 252–253 potential energy diagram of, 254 2-propenyl system and, 608 of secondary and tertiary alcohols, 335 SN2 reactions and, 258 solvent effects, 256 stereochemistry of, 255 substrate structure and rate of, 258–259 transition state of, 256 see also Nucleophilic substitution SN2 reaction, 226 effect of nature of leaving group on, 231–232 of nucleophile on, 232–235 kinetics of, 223–226 mechanism, 223–229 potential energy diagram, 228 of primary alcohols, 335 relative reaction rates, 233, 236t solvent effects, 235–236 specific enantiomer synthesis using, 228–229 stereochemistry of, 226–227 substrate structure and rate of, 237, 239–242 transition state of, 228 see also Nucleophilic substitution Snails, edible, 173 Soaps and detergents, 483, 884, 885 Sodium amide, 291, 570, 966 Sodium borohydride, 296–297, 519, 1110 Sodium cyanoborohydride, 973 Solid-phase synthesis of polypeptides, 1219 Solubility in water of alcohols, 287–290 of alkanes, 289t of amines, 959 of haloalkanes, 289t Solvation, 234 and nucleophilicity, 234–235 and anion size, 235 Solvent, 236 alcohols as, 288–290 aprotic and protic, 236 effect on SN1 reaction, 256 effect on SN2 reaction, 236 ethers as, 304 hydrogen bonding and, 236 polar, 235–236 for NMR, 394 see also specific solvents Solvolysis, 250–252, 257–258, 262, 340 of haloalkanes, 250, 335 kinetics, 252 mechanism, 252–254 see also SN1 reaction Sondheimer, Franz, 688 Sonogashira coupling, 582 Soot, 680–681 Sorbic acid, 615 D-Sorbitol, 1110–1111, 1124 Spectrometer, 389 schematic diagram of, 394 Spectroscopy, 388 infrared (IR), 388 mass, 446 nuclear magnetic resonance (NMR), 387 types of, 387 UV-visible, 643–646 Spectrum, 388 D-Sphingosine, 1150 sp orbital, 33 sp2 orbital, 33 sp3 orbital, 35 Specific rotation, 175 Spinach, 859 Spin, electron, 28 Spin, nuclear, 391 Spin states, 391–392 Spin-spin coupling, 408 Spin-spin splitting, 407 of alkyl groups, 412t complications of, 415 Squalene, 1067 Stabilized ylides, 792 See also Wittig reaction Staggered conformation, 80 Staphylococcus, 930 Starch, 1096 State of equilibrium, 52 Statistical product ratio, 113 Stem chain, 73 Stereocenter, 172–173, 177–178 description of configuration of, 177–179 effect of in reactions, 193–198 multiple, 186–192 See also Diastereomer in sugars, 1098 Stereochemistry, 159t, 192 in chemical reactions, 192–201 of SN1 reaction, 255 of SN2 reaction, 228 Stereoisomerism, 168, 169 constitutional isomerism, 168 of cycloalkanes, 133 of sugars, 1098 Stereoperception, 181 Stereoselective, 200 Stereospecific, 226 Steric hindrance, 83 Steroid, 154–155 Stille coupling, 582 Stomach acid, 59 Stork, Gilbert, 840 Strategic disconnection, 313 See also Synthesis Strecker, 1200–1203 Strecker synthesis of amino acids, 1201 Streptomycin, 1132 Structural isomer, 38 See also Isomer Strychnine, 310, 1171 Styrene, 535t, 640, 668, 1219 Substituent, 2, 36, 39, 73 and acidity effects, 865t Substitution reaction, See also Electrophilic aromatic substitution; Nucleophilic substitution Substrate, Succinic acid, 858, 876 See Butanedioic acid Succinimide, 881 See Butanimide Sucrose, 1122 Sugar, 1096 acetal formation, 1115 as aldoses and ketoses, 1097 amino sugars, 830, 1132 I-21 anomerism of, 1103 biosynthesis, 1118–1119 chain lengthening, 1116 chain shortening, 1116 classification by chain length, 1097 complex, 1097, 1122–1127 cyclic, 1102–1105 stereochemistry of, 1102 hemiacetal formation in, 1102 D and L classification of, 1098 establishing relative configuration of, 1116 esterification of, 1112 Kiliani-Fischer synthesis of, 1117 mutarotation in, 1105–1107 oxidation of, 1107–1109 polyfunctional reactions of, 1107 reducing, 1110–1111 reaction with amine derivatives, 1111–1112 reduction, 1110 Ruff degradation of, 1117 simple, 1097 stereochemistry of, 1098–1101 see also Polysaccharide Sugar substitutes, 1124–1125 Sulfadiazine, 371, 698 Sulfa drug, 698 Sulfalene (Kelfizina), 698 Sulfamethoxazole (Gantanol), 698 Sulfide (thioether), 364 naming of, 364 nucleophilicity of, 365 reactions, 364–366 synthesis, 365 Sulfide bridge, in proteins, 366 Sulfonamide, 371, 698 Sulfonate ester, 342, 349 Sulfonation, 696–699 aromatic, blocking by, 696 of benzene, 696–698 reversible, 697–698 Sulfone, 366 Sulfonic acid, 342, 366, 698 Sulfonium ions, 365 Sulfonyl chloride, 345, 366, 698 Sulfonyl group, 722–723 Sulfoxide, 366 Sulfur trioxide, 696–697, 699 Sulfur, valence expansion and, 366 Sulfuric acid, 696–697 Sulfuryl chloride, 129 I-22 INDEX Super Glue, 537 Superhelix, 1209 Superoxide, 1034 Surfactants, 885 Suzuki coupling, 582 Symmetry chemical shift equivalence and, 401 chirality and, 172 NMR spectroscopy and, 404 plane of, 172, 173 rotational, 401 Syn addition, 503 and catalytic hydrogenation, 502–504 and hydroboration, 520 for delivery of oxygen in epoxidation, 525 Syn dihydroxylation, 527 using osmium tetroxide, 526–528 using potassium permanganate, 529 Synthesis, evaluating efficiency of, 316 identifying disconnections in, 312–315 methodology in, 311–312 pitfalls in, 316 Synthesis gas, 293–294 Synthetic nucleic acid, 1225 Synthetic strategy, 312 Systematic nomenclature (IUPAC), 71 T Talose, 1100 Tartaric acid, 189, 201–203, 1120 Tautomers, 577, 816 enol and keto, 816–818 Tautomerism, 577 Tautomerization, 816 Taxol, 152–153 Teflon (polytetrafluoroethene), 535, 537 Temperature, 53 kinetic energy and, 56 reaction rates and, 57 Terephthalic acid, 867, 1007 See 1,4 Benzenedicarboxylic acid Terminal alkene, 399, 448 Termination, in radical reactions, 109 Terpene, 152 ␣-Terpinene, 483 ␣-Terpineol, 483 acid-catalyzed dehydration of, 483 Tertiary amine, 957 carbon, 72 hydrogen, 72 structure, in proteins, 1207 Testosterone, 156–157, 357 Tetraazabenzene, 1161 1,3,5,8-Tetraazanapthalene (Pteridine), 1168–1170 Tertracene (naphthacene), 682 Tetracyanoethene (TCNE), 625t, 627 Tetrazole, 1236 Tetrahedral intermediate, 871, 873, 875 Tetrahedral structure, 35 Tetrahedral symmetry, 35 Tetrahedrane, 150 Tetrahydrofolic acid, 1168–1169 Tetrahydrofuran See also Oxacyclopentane, 346 1,2,3,4-Tetrahydroisoquinoline, 1171 Tetrahydrothiophene See also Thiacyclopentane, 1148 Tetramethylammonium bromide, 970 N,N,N’,N’-tetramethyl-1,2ethanediamine (TMEDA), 609 Tetrose, 1097 Theobromine, 1171 Thermal isomerization, 452–453, 633 Thermodynamic control, 52 in acid-catalyzed dehydrations, 509 Thermodynamic stability, 85, 475 Thermodynamics, 52 Thia- as prefix, 1148 Thiacyclopentane (tetrahydrothiophene), 1148 Thiamine, 1080, 1118–1119 Thiamine pyrophosphate (TPP), 1118–1119 Thiazole, 1078 Thiazolium ion catalysis, 1082, 1118–1119 Thiazolium salts, 1082, 1118 Thiol, 364 acetal formation with, 784 acidity of, 364 boiling points, 364t hydrogen bonding in, 364 naming of, 364 oxidation, 366 radical additions to alkenes, 532 reactions of, 365 sulfonium salts from, 365 synthesis, 365 Thiol-disulfide redox reaction, 366 Thiol ester, 886 Thionyl chloride, 344–345, 705 Thiophene, 1148 electronic structure, 1153–1154 electrophilic aromatic substitution, 1156–1157 preparation of, 1155–1156 Raney nickel desulfurization of, 784 Threonine, 1192, 1193t Threose, 1099–1100 Thromboxane, 38, 888–889, 1023 Thymine, 1223 Tollens, Bernard, 797 Tollens’s test, 1107 Toluene (methylbenzene), 67, 724 benzylic halogenation, 1003 deprotonation, 1006 electrophilic bromination, 724–725 electrophilic nitration and sulfonation, 724–725 ortho-, meta-, para-attack on, 725–726 reactivity of in electrophilic aromatic substitutions, 725–726 2,4,6-trinitro- See TNT Torsional angle, 82 Torsional energy, 82 Torsional strain, 82 Tosylate (p-toluenesulfonate), 231, 1004 See also 4Methylbenzenesulfonate ion Total synthesis of organic molecules, 312 See also Synthesis Trans configuration, 133 in cycloalkanes, 133 Trans fatty acid (TFA), 887 Transaminase, 1202–1203 Transannular strain, 140 Transcription, 1228 Transesterification, 921–924 Transfer RNA (tRNA), 1229 Transferase, 1130 Transferrin, 1192 Transition, electronic, in UVvis spectrum, 389 Transition metal catalysis, 308 Transition state (TS), 55 diastereomeric, 197 early and late, 112 Translation, 1228 Transpeptidase, 930 Tremorine, 587 Triazabenzene (triazine), 1161 Tricarboxylic acid (TCA) cycle 1,1,1-Trichloro-2,2-bis(4chlorophenyl)ethane (DDT), 119 Triflate ion See also Trifluoromethanesulfonate ion, 231 (Trifluoromethyl)benzene, 726–728 Trifluoromethanesulfonate (triflate) ion, 231 Trifluoromethyl group, 621 Triglycerides, 368, 925 Trigonal structure, 13, 33 Trigonal symmetry, 20 Trimethylamine, 69t, 958, 966, 970, 980 1,3,5-Trimethylbenzene (mesitylene), 668 Trimethylene diradical, 136–137 Trinitrotoluene (TNT), 151, 731 Tripeptide, 1204–1205 Triplets, in NMR, 417, 420 Trisaccharide, 1098 Trivial name, 71 Trypsin, 1214, 1215t Tryptophan, 1159 Turpentine, 152 Twist- (or skew-) boat conformation, 141 Two-dimensional (2D) NMR, 428–429 Tylenol, 721, 1023 Tyrosine, 1193, 1196 U Ubiquinone, 1033 Ultraviolet-visible spectroscopy, 388–390, 602, 642–646 of aldehydes and ketones, 770 of aromatic compounds, 674 interpretation, 644–646 Unimolecular dehydration See E1 reaction Unimolecular elimination See E1 reaction Unimolecular nucleophilic substitution, 252 see also SN1 reaction ␣,-unsaturated aldehydes and ketones, 814 preparation, 825–826 properties, 832 INDEX resonance in, 833 cis- and trans-retinal as, 832 ␣,-unsaturated aldehyde and ketone reactions addition of organolithium reagents, 837 of C–O double bond, 837 conjugate additionalkylation, 837, 839 of cuprates, 837 of enolate ions (Michael and Robinson annulations), 839–840 of hydrogen cyanide, 836 of oxygen and nitrogen nucleophiles, 835–836 halogenation, 834 imine condensations, 834 reduction of C–C double bond, 834 ␣,-unsaturated aldehyde and ketone synthesis, 824 by aldol condensation, 825–831 by oxidation of allylic alcohols, 774 Unsaturated compound, 447 Unselective, 114 Uracil, 1223 Urea, 3, 911, 928 Urethane (carbamic ester), 928–929 Uridylic acid, 1225 V Valence electrons, 8–10, 13 Valence shell electron pair repulsion (VSEPR), 14 Valence shell expansion, 17, 22, 366 Valine, 1193t, 1201 Valium See Diazepam, 1147 Vancomycin, 930–931 Van der Waals, Johannes D., 77 Van der Waals forces, 77 Van’t-Hoff, Jacobus H., 189 Viagra, 1147 See Sildenafil citrate Vibrational excitation, 389, 460 See also Infrared spectroscopy Vibrational mode, 461 Vicinal diol, 526, 1109, 1115 from alkenes, 410, 526–527 cleavage by periodic acid, 1109–1110 cyclic acetal formation from, 1115 from epoxides, 526 Vicinal coupling constants in NMR, 410 Vicinal dihydroxylation, 526–527 Vicinal dihaloalkanes, 510–515, 570–571 dehydrohalogenation of, 570–571 Vicinal haloalcohol and haloether, 513–514 Vicinal hydrogen, and E2 reactions, 478 Villiger, Victor, 795 Vinegar, and acetic acid, 856 Vinyl chloride, 535, 537 Vinyl group, 450 Visible spectroscopy, 389, 602, 642–643 Vision, chemistry of, 814, 832 Vitamin A (retinol), 619, 645, 794 oxidation, 794 Vitamin B1, 1080, 1118–1119 See Thiamine Vitamin B2, 1169 See Riboflavin Vitamin B6, 1147 See Pyridoxine Vitamin B12 (cobolamin), 1147 Vitamin C, 1036–1037, 1115 Vitamin E, 93, 1035–1037 Volhard, Jacob, 883 W Wacker process, 540 Water bonding in, 36 electron-dot structure, 11 hydrogen bonding in, 288–289 as leaving group, 334–335 molecular-orbital picture of, 36 self-ionization constant of, 60 Watson, James D., 1226 Watson and Crick model for DNA, 1226–1227 Wave equation, 24 Wave function, 24 phase, 25 Wavelength (), 24, 389, 460, 642 Wavenumber, 389 Waxes, 103, 924–927 Weight control, 960 Williamson, Alexander, W., 349 Williamson ether synthesis, 349–354 intramolecular, 351–354 with phenols, 1022 with phenylmethyl halides, protection of alcohols, 1008 with sugars, 1112–1113 see also Nucleophilic substitution; SN2 reaction Willstätter, Richard, 687 I-23 Wintergreen flavor, 669 Wittig, Georg, 792 Wittig reaction, 792–795 mechanism of, 794 phosphonium salt synthesis, 792 ylide formation, 792 Wöhler, Friedrich, Wolff, Ludwig, 789 Wolff-Kishner reduction 789–791 Woodward, Robert B., 636 Woodward-Hoffmann rules, 636–638 X Xanthopterin, 1168 X-ray diffraction, 39, 177 Xylene, 668, 675 Xylitol, 1124 Xylose, 1100, 1121 Y -yl as suffix, 72 -ylene as suffix, 447 Ylide formation of phosphorous, 792–793 Z Zantac, 59 Zelinsky, Nicolai, 883 Zeolite catalyst, 102, 367 Zidovudine (AZT), 1147, 1225 Ziegler, Karl, 538 Ziegler-Natta catalyst, 538–540 Ziegler-Natta polymerization, 539–540 Zigzag notation, 39, 766 Zinc amalgam, 739–740 in ozonolysis, 529–530 Zwitterion, 793 This page intentionally left blank TEXT REFERENCES FOR COMPOUND CLASSES AND FUNCTIONAL GROUPS Compound class Functional group Alkanes A A O C OC OH A A Haloalkanes A O C OX A Alcohols A O C O O OH A Ethers A A O C O O OC O A A Thiols A O C O S OH A Alkenes G D CP C G D Alkynes Aromatics O C q C OH Properties 2-6 to 2-8, 3-1, 3-10, 4-2 to 4-6 6-1 Preparations 8-7, 11-9, 12-2, 13-6, 17-10, 18-8, 21-10 3-4 to 3-8, 9-2, 9-4, 12-3, 12-5, 12-6, 12-13, 13-7, 14-2, 19-12 Reactions 3-3 to 3-10, 8-6, 19-5 Compound class Preparations Reactions 17-2, 17-3, 18-1, 23-1 8-6, 12-12, 13-7, 13-8, 15-13, 16-5, 17-4, 17-6 to 17-9, 17-11, 18-1, 18-4, 20-2, 20-4, 20-6, 20-8, 22-2, 22-8, 23-1, 23-2, 23-4, 24-5, 24-9, 25-4 8-6, 8-8, 16-5, 17-5 to 17-14, 18-1 to 18-11, 19-5, 19-6, 21-6, 21-9, 22-8, 23-1 to 23-4, 24-4 to 24-7, 24-9, 25-3 to 25-5, 26-2 19-2 to 19-4, 26-1 8-5, 8-6, 17-14, 19-5, 19-6, 19-9, 20-1 to 20-3, 20-5, 20-6, 20-8, 22-2, 23-2, 24-4 to 24-6, 24-9, 26-2, 26-5, 26-6 9-4, 19-4, 19-7 to 19-12, 21-10, 23-2, 24-9, 26-4, 26-6, 26-7 20-1 19-8 15-13, 20-2 Anhydrides O O B B EC H E CH O 20-1 19-8 15-13, 20-3 Esters O f i B H H EC H ECH C O f i 20-1, 20-4, 20-5 7-8, 9-4, 17-13, 19-9, 20-2, 22-5 20-4, 23-1 to 23-3, 26-6 Amides O B C E H EH N A 20-1, 20-6 19-10, 20-2, 20-4, 26-6 20-6, 20-7, 26-5 Nitriles O C qN 20-8 17-11, 18-9, 20-8, 21-10, 22-10, 24-9 17-11, 19-6, 20-8, 21-12, 24-9, 26-2 Amines if EC H EH N A 21-2 to 21-4, 26-1 16-5, 17-9, 18-9, 20-6 to 20-8, 21-5 to 21-7, 21-9, 22-4, 25-2, 25-6, 26-2, 26-5 16-5, 17-9, 18-4, 18-9, 19-10, 20-2 to 20-4, 21-4, 21-5, 21-7 to 21-10, 22-4, 22-10, 22-11, 25-2, 25-3, 26-1, 26-5, 26-6 Aldehydes and ketones 9-5 9-10 11-2 to 11-9, 14-5, 14-11 13-2, 13-3 15-2 to 15-7 8-4 to 8-6, 8-8, 9-8, 9-9, 12-4, 12-6 to 12-8, 12-11, 13-5, 17-6, 17-7, 17-9, 17-11, 18-5, 18-9, 19-11, 20-4, 23-4, 24-6 9-6, 9-7, 12-6, 12-7, 12-10, 12-13, 17-7, 17-8, 18-9, 22-5 6-2, 6-4 to 7-8, 8-5, 8-7, 11-10, 13-9, 14-3, 15-11, 17-12, 19-6, 21-5 9-10, 26-5 7-6 to 7-9, 9-2, 9-3, 9-7, 11-10, 11-11, 12-14, 12-16, 13-4, 13-6 to 13-10, 17-12, 18-5 to 18-7, 21-8 13-4, 13-5 15-8 to 16-6, 22-4 to 22-11, 25-5, 26-7 8-3, 8-6, 9-1 to 9-4, 9-6, 9-7, 9-9, 11-11, 12-6, 15-11, 17-4, 17-7, 17-11, 18-9, 20-2 to 20-4, 22-2, 24-2, 24-5, 24-8 9-8, 9-9, 23-4, 25-2 Alkanoyl halides 9-10, 26-5 8-4, 11-9, 12-2 to 12-16, 13-4, 14-2 to 14-4, 14-6 to 14-10, 15-7, 15-11, 16-4, 18-8 to 18-11, 21-10 13-2, 13-3, 13-5 to 13-10, 17-4 14-7, 15-2, 15-9 to 16-6, 22-1 to 22-8, 22-10, 22-11, 25-4, 25-6, 26-7 Red ϭ nucleophilic or basic atom; blue ϭ electrophilic or acidic atom; green ϭ potential leaving group O B H H EC H H C f i Properties O B H H EC H C CE f i f i Carboxylic acids 8-2, 8-3 Functional group O B C E H EH O O B C E H X Periodic Table of the Elements Relative atomic mass (atomic weight), 1995 IUPAC values; * for these radioactive elements, nuclidic mass of an important isotope 1.00794 1, Ϫ1 2.2 H Oxidation states in compounds: important, most important 6.941 9.012182 2 1.0 Li 24.3050 0.9 11 Na Electronegativity 26 Fe Atomic number Element essential to all biological species investigated Be 22.989770 1.8 1.6 55.845 6, 3, 2, 0, Ϫ2 Element essential to at least one biological species 1.3 12 Mg 39.0983 40.078 44.955910 47.867 50.9415 51.9961 54.938049 4, 5, 4, 3, 2, 6, 3, 2, 7, 6, 4, 3, 2, 0, Ϫ1 6, 3, 2, 0, Ϫ2 0.8 1.0 1.4 1.5 1.6 1.7 20 Ca 21 Sc 22 85.4678 87.62 88.90585 91.224 92.90638 95.94 5, 6, 5, 4, 3, 2, 19 K 0.8 1.0 37 Rb 38 132.90545 Sr 24 Cr 1.3 178.49 180.9479 183.84 6, 5, 4, 3, 2, 223.0197* 226.0254* 0.8 1.8 1.9 26 Fe 27 Co 98.9063* 101.07 102.90550 8, 6, 4, 3, 2, 0, Ϫ2 5, 4, 3, 2, 1, 42 Mo 1.3 2.3 44 Ru 45 Rh 186.207 190.23 192.217 7, 6, 4, 2, Ϫ1 8, 6, 4, 3, 2, 0, Ϫ2 6, 4, 3, 2, 1, 0, Ϫ1 43 Tc 2.4 2.2 72 Hf 73 Ta 74 W 75 Re 76 Os 77 261.1088* 262.1142* 266.1219* 264.1247* (277) 268.1388* 104 Rf 105 Db 106 Sg 107 Bh 108 Hs 109 Mt 138.9055 140.116 140.90765 144.24 146.9151* 150.36 151.964 4, 4, 3 3, La–Lu 0.9 3, 2, 0, Ϫ1 2.2 57 to 71 58.933200 1.6 25 Mn 137.327 0.9 Y V 41 Nb 56 Ba Fr 1.2 39 55 Cs 87 23 40 Zr 0.8 Ti 55.845 Ir 89 to 103 88 Ra Ac–Lr Lanthanides 1.1 1.1 1.1 1.1 1.2 3, 1.2 1.2 57 La 58 Ce 59 Pr 60 Nd 61 Pm 62 Sm 63 Eu 227.0278* 232.0381 231.03588* 238.02891 237.0482* 244.0642* 243.0614* 5, 6, 5, 4, 6, 5, 4, 6, 5, 4, 6, 5, 4, Actinides 1.2 89 Ac 1.3 90 Th 1.3 91 Pa 1.4 92 U 1.4 93 Np 1.3 94 Pu 95 Am 18 4.002602 13 s Block elements d Block elements p Block elements f Block elements 14 15 12.0107 14.0067 15.9994 18.9984032 4, 2, Ϫ4 5, 4, 3, 2, Ϫ3 Ϫ2, Ϫ1 Ϫ1 2.6 B 12 3.0 C N 3.4 O F 39.948 28.0855 30.973761 32.065 35.453 4, Ϫ4 5, 3, Ϫ3 6, 4, 2, Ϫ2 7, 5, 3, 1, Ϫ1 13 Al 14 Si 2.2 15 P 2.6 S 16 3.2 17 18 Ar Cl 58.6934 63.546 65.409 69.723 72.64 74.92160 78.96 79.904 3, 2, 2, 5, 3, Ϫ3 6, 4, Ϫ2 7, 5, 3, 1, Ϫ1 1.9 1.7 1.9 30 Zn 31 Ga 107.8682 112.411 2, 28 Ni 29 Cu 106.42 4, 2, 1.9 2.2 46 Pd 47 Ag 195.078 4, 2, 33 As 114.818 118.710 121.760 4, 5, 3, Ϫ3 1.8 1.7 49 196.96655 200.59 3, 2, 2.5 2.2 32 Ge 48 Cd 2.3 2.0 1.8 2.0 36 Kr 127.60 126.90447 131.293 6, 4, Ϫ2 7, 5, 1, Ϫ1 8, 6, 4, 2.1 2.1 51 Sb 52 204.3833 207.2 208.98038 208.9824* 209.9871* 222.0176* 3, 4, 5, 6, 4, 7, 5, 3, 1, Ϫ1 2.0 2.3 2.0 2.0 53 I 83 Bi 84 Po (281) 272.1535* (285) (284) (289) (288) (292) 110 Ds 111 Rg 112 (113) (114) (115) (116) 157.25 158.92534 162.500 164.93032 167.259 168.93421 173.04 174.967 4, 3 3 3, 3, 1.2 1.2 1.2 64 Gd 65 Tb 66 Dy 67 Ho 68 247.0703* 247.0703* 251.0796* 252.0830* 4, 4, 4, 3 96 Cm 97 Bk 98 Cf 99 Es Er 54 Xe 2.0 82 Pb 1.2 2.6 50 Sn In Te 2.7 81 Tl 1.2 3.0 35 Br 80 Hg Pt 3.0 79 Au 78 83.798 2.6 34 Se 20.1797 10 Ne 1.9 He 4.0 26.981538 1.6 11 17 10.811 2.0 10 16 85 At 1.3 86 Rn 1.0 69 Tm 70 Yb 71 Lu 257.0951* 258.0984* 259.1010* 262.1097* 3 3, 100 Fm 101 Md 102 No 103 Lr Lewis acids/electrophiles: Electron pair acceptors; Lewis bases/nucleophiles: Electron pair donors (2-2) Structure and Bonding 2-3-4 Alkanes and Cycloalkanes Ionic bonds: Formed by transfer of electrons from one atom to another (1-3) IUPAC Nomenclature: Longest continuous chain; numbering: Lowest for first substituent (2-5) Covalent bonds: Formed by electron sharing between two atoms; polar covalent bonds: Between atoms of differing electronegativity (1-3) Alkanes: CnH2nϩ2 hydrocarbons; straight-chain or branched; acyclic; nearly non-polar; weak intermolecular London forces (2-6) Lewis structures: Electron dot descriptions of molecules; resonance forms: Multiple Lewis structures for a molecule; octet rule: Preferred valence electron total for atoms (2 for H) (1-4, 5) Conformations: “Free” rotation about single bonds; staggered 2.9 kcal molϪ1 more stable (lower energy) than eclipsed (2-7, 8) VSEPR: Governs molecular shape and geometry around atoms (1-8) Hybrid orbitals: Explain geometry; sp3: Tetrahedral (109Њ, CH 4); sp2: Trigonal planar (120Њ, BH3 and H2CPCH2); sp: Linear (180Њ, BeH2 and HCqCH) (1-8) bonds: From end-to-end orbital overlap; bonds: From side-by-side orbital overlap (1-8) Constitutional isomers: Different connectivity (1-9) Structure and Reactivity; Acids and Bases Thermodynamics: Govern equilibria; ⌬GЊ ϭ ϪRT ln K ϭ Ϫ1.36 log K (at 25ЊC) (2-1) Cycloalkanes: CnH2n hydrocarbons; n ؍3, 4: Cyclopropane, cyclobutane (strained bond angles); n ؍6: Cyclohexane (most stable, chair conformation); axial (less stable) & equatorial (more stable) substituent positions (4-2, 3) Stereoisomers: Same atom connectivity, different threedimensional arrangement; cis: Two substituents on same ring face; trans: Opposite faces (4-1) Reactions: Few (non-polar, lack functional groups); combustion, halogenation (3-3 to 10) Halogenation: Radical chain mechanism with initiation, propagation, termination steps (3-4) C H ϩ X2 h or ∆ C X ϩ HX X ϭ Cl, Br (DH ЊC H ϩ DHЊX X) Ϫ (DHЊC X ϩ DHЊH X) ϭ ∆HЊ Gibbs free energy: ⌬GЊ ϭ ⌬HЊ Ϫ T⌬SЊ; enthalpy: ⌬HЊ; exothermic if Ͻ 0; endothermic if Ͼ 0; entropy: ⌬SЊ; measures energy dispersal (disorder) (2-1) Reactivity: F2 Ͼ Cl2 Ͼ Br2 (I2 none); selectivity: Br2 Ͼ Cl2 Ͼ F2 (3-7) Kinetics: Govern rates; first order: Rate ϭ k[A]; second order: Rate ϭ k[A][B] (2-1) Reactivity: Tert Ͼ sec Ͼ prim Ͼ methane COH; follows radical stability due to hyperconjugation (3-6) Reaction coordinate: Graph of energy vs structural change; transition state: Maximum-energy point on reaction coordinate; activation energy: Ea ϭ E (transition state) Ϫ E (starting point) (2-1, 7, 8) Bond-dissociation energy: DHЊ; bond dissociation gives radicals or free atoms (3-1) Brønsted acids: Proton donors; Brønsted bases: Proton acceptors (2-2) Ϫ Strong acids HA: Have weak conjugate bases A ; acidity constant Ka: pKa ϭ Ϫlog Ka; HA acid strength: h for A larger, more electronegative, resonance-delocalized negative charge; g pKa ϭ stronger acid (2-2) Stereoisomers Chiral: Handed; not superimposable on mirror image; enantiomers: Mirror-image stereoisomers; stereocenter: Center of chirality in a molecule, such as a carbon with different groups attached (5-1); nomenclature: R/S system (5-3) Optical activity: Rotation of the plane of polarized light by an enantiomer; racemate (racemic mixture): Optically inactive 1:1 mixture of two enantiomers (5-2) Dehydration: Conc H2SO4 ϩ prim (180ЊC), sec (100ЊC), tert (50ЊC) n alkene; carbocations rearrange (9-2, 3, 7) Diastereomers: Non-mirror image stereoisomers (5-5) Ether synthesis: Williamson, ROϪ ϩ RЈX (RЈ ϭ Me, prim) n RORЈ (9-6) Meso compound: Achiral molecule with multiple stereocenters (5-6) Ether cleavage: RORЈ ϩ HX (X ϭ Br, I) n RX ϩ RЈX (9-8) Resolution: Separation of enantiomers (5-8) 10-11 Spectroscopy 6-7 Haloalkanes Functional group: dϩCOXdϪ; electrophilic C, leaving group XϪ (6-1, 2) Reactions: Nucleophilic substitution (6-2 to 9, 7-1 to 5), elimination (7-6, 7) H C C Nu Subst ϪXϪ NuϪ ϩ H C C X Elim ϪHX D G CP C D G SN2: R ϭ Me Ͼ prim Ͼ sec, backside displacement; SN1: R ϭ tert Ͼ sec, racemization; E2: NuϪ strong base; E1: Side rxn to SN1, rates of SN1, E1 both follow carbocation stabilization by hyperconjugation High-resolution mass spectrometry: Gives molecular formula (11-6, 7) Degree of unsaturation: Gives number of rings ϩ number of p bonds; degree of unsaturation ϭ (Hsat Ϫ Hactual)/2, where Hsat ϭ 2n C ϩ Ϫ nX ϩ nN (11-8) Infrared spectroscopy: Gives bonds and functional groups (11-5) Wavenumber Bond 3650– 3200 3150– 3000 3000– 2840 2260– 2100 1760– 1690 1680– 1620 1500 OOH (s, br) NOH (m, br) qCOH (s) PCOH (m) OCOH (s) CqC (w) CqN (m) CPO (s) CPC (m) Fingerprint w ϭ weak; m ϭ medium; s ϭ strong; br ϭ broad 8-9 Alcohols and Ethers Nomenclature: Alkanol—longest chain containing OH; numbering: Lowest for OH (8-1) dϪ Functional group: dϩCO OOHdϩ; Lewis basic O; acidic H (pKa ϭ 16–18, like H2O), hydrogen bonding (8-2, 3) Preparation: Hydride/Grignard addn to CPO; prim: RCHO ϩ LiAlH4 or H2CPO ϩ RMgX; sec: RRЈCPO ϩ LiAlH4 or RCHO ϩ RЈMgX; tert: RRЈCPO ϩ RЉMgX (8-6, 8) LiAlH4 Hϩ, H2O H C OH G CP O D Nuclear magnetic resonance: Gives hydrogen and carbon signals; chemical shift: Structural environment; integration: Number of H for each signal; splitting: Number of H neighbors (N ϩ rule) (10-4 to 9) Chem shift 9.9–9.5 H type O B OC OH 4.0–3.0 H G D C D G O,Br,Cl 9.5–6.0 5.8–4.6 H H D G CPC D G 2.6–1.6 1.7–0.8 variable G D C D G C P C,O H D alkyl COH OOH NOH 11-12 Alkenes RMgX Hϩ, H2O R C OH Oxidation: Cr(VI) reagents; RCH2OH (prim) ϩ PCC n RCHO (aldehyde); prim ϩ Na2Cr2O7 n RCO2H (carboxylic acid); RRЈCHOH (sec) ϩ Na2Cr2O7 n RRЈCPO (ketone) (8-6) Substitution: Prim, sec ϩ SOCl2, PBr3, P/I2 n RX; tert ϩ HX n RX (9-2 to 4) Nomenclature: Longest chain containing CPC (OH takes precedence); stereochemistry: Cis/trans or E/Z systems (11-1) Functional group: CPC, p bond electron pair nucleophilic, electrophiles add (11-2, 12-3 to 13) Stability: h with increased substitution (R2CPCR2 most stable; H2CPCH2 least stable); trans disubstituted Ͼ cis disubstituted Preparation: Haloalkane ϩ strong base (bulky for prim RX), E2, anti stereospecific, most stable alkene favored (Saytzev rule) except with bulky base (Hofmann rule) (7-7, 11-10) Preparation: Alcohol ϩ conc H2SO4, product mixtures (Saytzev rule) (9-2, 11-11) Hydrogenation: H2 with catalytic Pd or Pt, syn addition n alkane (12-2) Electrophilic addition mechanism: Electrophile adds to less-substituted alkene carbon, nucleophile to more-substituted alkene carbon (12-3) E O Nu ϩ Ϫ Hydrohalogenation: Markovnikov regioselectivity, except HBr ϩ peroxides (ROOR) (12-3, 13) CH3CHPCH2 ϩ H OX CH3CHOCH3 A X X ϭ Cl, Br, l CH3CHPCH2 ϩ HO Br ROOR CH3CHOCH2Br A H Hydration: Markovnikov with aq acid or oxymercuration; anti-Markovnikov with borane (12-4, 7, 8) CH3CHPCH2 CH3CHPCH2 Hϩ, H2O* or Hg2ϩ, H2O; NaBH4 *may rearrange BH3; H2O2, ϪOH CH3CHOCH3 A OH CH3CHOCH2OH A H Halogenation: Anti stereochemistry of addition via cyclic halonium ion (12-5) X X Dihydroxylation: Anti using peroxycarboxylic acid; syn using OsO4 (12-10, 11) Hϩ,H2O C OC HO COC ; ; OH O2 Os O D G CPC D G OsO4 COC ; HO O ; H2S 13 Alkynes Functional group: CqC, two p bonds; qCOH bond acidic (pKa ϭ 25) (13-2) Preparation: Alkene ϩ halogen n 1,2-dihaloalkane (12-5), then double elimination (NaNH2) n alkyne (13-4) OH COC ; Addition: HX, X2 add twice (13-7) Hydration: Hg2ϩ, H2O (Markovnikov) or R2BH, then Ϫ OH, H2O2 (anti-Markovnikov) n enol n ketone or aldehyde via tautomerism (13-7, 8; 18-2) 14 Dienes 1,2- and 1,4-addition to 1,3-dienes: Via delocalized allylic intermediate; kinetic product forms fastest; thermodynamic is more stable (14-6) H2CPCHO CHP CH2 E O Nu Nu A P H2C CHOCHO CH2E 1,2-addn product (usually kinetic) ϩ H2CPCH O CHO CH2E Ϫ Nu ϩ H2C OCH P CHO CH2E ϩ Nu A H2COCH P CHO CH2E 1,4-addn product (often thermodynamic) ; A B C D ϩ A [B C D & O RCO3H & D G CPC D G G CPO D Diels-Alder reaction: Concerted, stereospecific cycloaddition (14-8) & COC & D G C P C ϩ X2 D G X ϭ Cl, Br Reduction: H2, Pt n alkane; H2, Lindlar’s n cis alkene; Na, NH3 n trans alkene; (13-6) CH3CHOCH2E A Nu Nu O3; Zn, CH3CO2H Alkynyl Anions: RCqCH + NaNH2 n RCqC:Ϫ, then RЈX (RЈ ϭ Me, prim) → RCqCRЈ (13-5) more highly substituted CH3CHOCH2E D G CPC D G [ CH3CHPCH2 Ozonolysis: Cleavage using ozone followed by reduction (12-12) 15-16-22 Benzene and Aromaticity Nomenclature: Special common names, ortho/o (1,2), meta/m (1,3), para/p (1,4) for disubstituted (15-1) Alkylbenzenes: F-C alkylation (may rearrange); F-C alkanoylation, then reduction (16-5) OH CH3 H2N Br NO2 3-Nitrobenzenol (m-Nitrophenol) 1-Bromo-2-methylbenzene (o-Bromotoluene) Benzylic reactivity: Halogenation (22-1); oxidation to benzoic acid (22-2) l 4-Iodobenzenamine ( p-Iodoaniline) O P CH2OH C COOH CHO D R H2C D R X2, h or ∆ CHX P Cl, Br Xϭ R Zn(Hg), HCl Clemmensen reduction Phenylmethanol (Benzyl alcohol) Benzenecarboxylic acid (Benzoic acid) Benzenecarbaldehyde (Benzaldehyde) Aromaticity: Special stability, properties, and reactions, based upon Hückel’s rule, 4n ϩ 2p electrons in a circle of p orbitals (15-2 to 7) Electrophilic aromatic substitution mechanism: Electrophile adds to position favored by groups previously present (directing effects, below), followed by loss of Hϩ (15-8) E Eϩ E H ϩ Five electrophilic aromatic substitutions below, clockwise from bottom right: Sulfonation, nitration, halogenation, Friedel-Crafts (F-C) alkylation, FriedelCrafts alkanoylation (acylation) (15-9 to 13) X NO2 SO3H X2, FeX3 (X ϭ Cl,Br) CH3Cl, AlCl3 CH3 HNO3, H2SO4 CH3COCl, AlCl3 Hϩ, H2O SO3, H2SO4 O CCH3 Directing effects: Ortho/para-directing Go,p include alkyl, aryl, halogen, OOR, ONR2; meta-directing Gm include OSO3H, ONO2, ϾCPO, OCF3, ONR4ϩ (16-2, 3) Activation/deactivation: All Go,p except halogen are activating; halogen and all Gm are deactivating (16-1 to 3) Go,p Go,p Go,p E Eϩ faster than benzene ϩ Eϩ (except Go,p ϭ halogen) ϩ E Gm Gm KMnO4, HOϪ, ∆ Benzenamines: Preparation (16-5); diazotization (22-4, 10, 11) NO2 N2ϩ H2O, ∆ slower than benzene ϩ Eϩ E N2ϩ NH2 Zn(Hg), HCl or H2, Ni or Fe, HCl HNO2, 0ЊC OH Go,p N N CuX, ∆ X X ϭ Cl,Br,CN Go,p Azo dyes Phenols: Acidic (pKa ϭ 10; more acidic with deactivating substituents); phenoxide ϩ RЈX (RЈ ϭ Me, prim) n ether (22-4, 5) 17-18 Aldehydes and Ketones Nomenclature: Alkanal and alkanone—longest chain containing CPO; common: Formaldehyde (methanal), acetaldehyde (ethanal), acetone (propanone) (17-1) Preparation: ROH oxidation (8-6); CPC ϩ O3 (12-12); CϵC hydration (13-7, 8): F-C alkanoylation (15-13) Functional group: dϩCPOdϪ; electrophilic C, NuϪ adds (17-2) Addition: H2O n hydrate, ROH n hemiacetal (both unstable); ROH, H+ n acetal (17-6 to 8) Addition: RNH2 n ϾCPNR; R2NH n enamine (17-9) Deoxygenation: CPO n CH2, Clemmensen (16-5); dithioacetal ϩ Raney Ni (17-8); hydrazone ϩ base, ⌬ (17-10) Wittig: CPO ϩ CH2PPPh3 n CPC (17-12) Aldol: Aldehydes, aldehyde ϩ ketone, intramolecular n a,b-unsaturated aldehyde/ketone (18-5 to 7) O Eϩ CO2H RCH2 HO CH O ϩ RCH2 CH Ϫ OH RCH2 C H H C R O O CH ∆ ϪH2O RCH2 C H C R CH 1,2- vs 1,4-addition: RLi n alcohol (1,2); H2O, ROH, RNH2, R2CuLi (cuprate) n 3-substituted carbonyl product (1,4); Michael addition: Enolate n 1,5dicarbonyl (1,4); Robinson annulation: Intramolecular aldol n 6-membered ring (18-8 to 11) Hydride reduction to amine: RCONHRЈ ϩ LiAlH4 n RCH2NHRЈ (20-6) Cuprate addition: Ketones from halides (20-2) O R O HC O CR Ϫ OH O H 2C ϩ H3C Michael CCH3 H2C O R2CuLi Hϩ, H2O Cl R C R R CR H2CD H2C C Ϫ CH3 Grignard addition: Tert alcohols from esters (20-4) OH, ∆ Robinson O O C O R C OR OH R؆MgX Hϩ, H2O R ϪROH C R؆ R؆ 19-20-23 Carboxylic Acids and their Derivatives Nomenclature: Alkanoic acid—longest chain ending with CO2H; common: Formic (methanoic), acetic (ethanoic), benzoic (benzenecarboxylic) (19-1) Preparation: ROH oxidation; RMgX ϩ CO2; RCN hydrolysis (8-6, 19-6) Functional group: Highly polar, H-bonding (19-2); Lewis basic n dϪOPCOOOHdϩ m acidic (pKa ϭ 4) (19-4); Nu adds to CPO, OH may leave (addition-elimination) (19-7) Claisen condensation: Esters n b-ketoester; 1,7-diester n cyclic b-ketoester (intramolecular: Dieckmann condensation) (23-1) O RCH2 COEt O ϩ RCH2 O CH3 C Reactivity order: Towards NuϪ addition/elimination of leaving group (bold); halides (and anhydrides)–no catalyst needed; esters, amidesOHϩ or ϪOH catalyst required (20-1) R C fast at rt O Cl Ͼ R C O H C OR Ͼ R C ϪEtOH (Et ϭ ethyl) O H C C COEt R ϪOEt; RX ϪOEt; RX O CH3 O R C C H COEt R ϪCO2 O CH3 C CHR R Malonic Ester Synthesis of Carboxylic Acids: Same (23-2) O EtOC O H C COEt ϪOEt; RX ϪOEt; RX O EtOC H O R C COEt R ϪOH, H2O Hϩ, H2O, ∆ ϪCO2 O slow at rt COEt ϪOH, H2O Hϩ, H2O, ∆ Derivatives: RCO2H (acid) ϩ SOCl2 n RCOCl (halide); RCO2H ϩ RЈOH, H+ n RCO2RЈ (ester); RCO2H ϩ RЈNH2, ⌬ n RCONHRЈ (amide) (19-8 to 10) RCH2 Acetoacetic Ester Synthesis of Methyl Ketones: Alkylate, hydrolyze, decarboxylate (23-2) Reduction: LiAlH4 n RCH2OH (19-11) O COEt O ϪOEt Hϩ, H2O O HO C CHR R NHR requires ∆ 21 Amines Hydrolysis: All ϩ excess H2O n RCO2H (acid) (20-2 to 6) Esterification: Halide, ester (transesterification) ϩ excess RЉOH n RCO2RЉ (20-2 to 4) Amide formation: Halide, ester ϩ excess RЈNH2 n RCONHRЈ (20-2 to 4) Hydride reduction to aldehyde: Halide ϩ LiAl(O Bu)3; ester, amide ϩ DIBAL (20-2 to 6) t Hydride reduction to prim alcohol: Halide, ester ϩ LiAlH4 (20-2 to 4) Nomenclature: Alkanamine, follow rules for alcohols, use N- for additional groups on nitrogen; common, alkyl amine (21-1) NH2 CH3NH2 Methanamine (Methyl amine) CH3CH2CHCH3 CH3CH2CH2N(CH3)2 2-Butanamine (sec-Butyl amine) N,N-Dimethyl-1-propanamine (Dimethyl propyl amine) Functional group: Non-planar (pyramidal), sp3 N, inverts easily; Lewis basic, nucleophilic N; NOH m weakly dϩ (pKa ϭ 35) (21-2, 4) Preparation: RX ϩ N3Ϫ n RN3 (azide), then LiAlH4 n RNH2 (primary amine) (21-5) One less carbon: RCONH2 (amide) ϩ Cl2, NaOH n RNH2 (Hofmann) (20-7, 21-7) One more carbon: RX ϩ ϪCN n RCN (nitrile), then LiAlH4 n RCH2NH2 (20-8) Reductive Amination: ϾCPO ϩ NH3, NaBH3CN n ϾCHNH2 (prim amine); ϾCPO ϩ RNH2, NaBH3CN n ϾCHNHR (sec amine); ϾCPO ϩ RRЈNH, NaBH3CN n ϾCHNRRЈ (tert amine) (21-6) ␣-Amino acids: Most have L (S) stereocenter, exist as zwitterions, common names (26-1) ϩH 3N ϩH N COOϪ H same as R O COOϪ ; R H Acid/base properties: At low pH, Hϩ converts COOϪ to CO2H; at high pH, ϪOH converts NH3ϩ to NH2 (26-1) Polypeptides: Contain amino acids linked by amide bonds; amide N trigonal planar, sp2 (26-4) H O N C C HR N C C ; 24 Carbohydrates 26 Amino Acids, Peptides, Proteins, and Nucleic Acids ; Basicity: Amine ϩ Hϩ n ammonium ion (pKa ϭ 10) (21-4) Conventional representations: For D-(ϩ)-glucose (24-1, 2) CHO H HO H H CH2OH O OH OH OH H OH OH HO HO CH2OH OH conformational OH anomeric carbon -D-glucopyranose (cyclic) HO Haworth CH2OH O OH Fischer (open-chain) 25 Heterocycles Nomenclature: Heterocycloalkane; common names for many (25-1) O H N O H N Oxacyclopropane Azacyclopropane Oxacyclopentane Azacyclopentane (Oxirane, epoxide) (Aziridine) (Tetrahydrofuran, THF) (Pyrrolidine) Heteroaromatics: Common names (25-1) O H N Furan Pyrrole S N Thiophene Pyridine RH H O Peptide linkage Bold atoms coplanar Proteins: Polypeptides with polar amino acid side chains in an active site that catalyze biochemical reactions (26-8) Nucleic acids: Polymers made of phosphate-linked sugars bearing the heterocyclic bases adenine (A), guanine (G), cytosine (C), and thymine (T) in DNA or uracil (U) in RNA; contain the genetic code for protein biosynthesis (26-9) ... step H H C H C C C H C H C C H H O C H H H H ł] S C C H C C N H C C O “ ( H H O C H H H N ł [ C H H C H C H C O C S C C C C C C H C H H NH C H C H H H C C H O O Benzylpenicillin Cubane O Saccharin... (Similar to ethyl case) I H 3C ‡ H H − C Br CH3CH2 S (Chiral and optically active) δ− I C H Br δ− I CH3 CH2CH3 Backside displacement B C D CH3 CH2CH3 R (Chiral and optically active; configuration... molecules H3 COCH3 Ethane H2 C H 2C CH2 H 2C CH2 C H2 Cyclohexane We begin with the alkanes, composed of only carbon and hydrogen atoms (“hydrocarbons”) connected by single bonds They lack any functional