Organic Chemistry: Structure, Mechanism, and Synthesis This Page Intentionally left blank Organic Chemistry: Structure, Mechanism, and Synthesis Robert J Ouellette Professor Emeritus, Department of Chemistry, The Ohio State University And J David Rawn Professor Emeritus, Towson University AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD PARIS • SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Elsevier 525 B Street, Suite 1900, San Diego, CA 92101-4495, USA 225 Wyman Street, Waltham, MA 02451, USA Copyright © 2014 Elsevier 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 or otherwise without the prior written permission of the publisher Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone (+44) (0) 1865 843830; fax (+44) (0) 1865 853333; email: permissions@ elsevier.com Alternatively you can submit your request online by visiting the Elsevier web site at http://elsevier.com/locate/permissions, and selecting Obtaining permission to use Elsevier material Notice No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made Library of Congress Cataloging-in-Publication Data Rawn, J David, 1944Organic chemistry / J David Rawn, Robert J Ouellette – First edition pages cm Includes index ISBN 978-0-12-800780-8 Chemistry, Organic–Textbooks I Ouellette, Robert J., 1938- II Title QD251.3.R39 2014 547–dc23 British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library For information on all Elsevier publications visit our web site at store.elsevier.com Printed and bound in China 14 15 16 17 18 10 9 8 7 6 5 4 3 2 1 ISBN: 978-0-12-800780-8 2013050560 To our families Verweile doch, du bist so schön —Johann Wolfgang von Goethe, Faust This Page Intentionally left blank Contents Acknowledgments Preface xxxiii xxxv Chapter structure and bonding in organic compounds Table of Contents 1.1 Brief review of atomic structure Page Atomic Structure Atomic Orbitals Valence Shell Electrons 1.2 Atomic properties Atomic Radius Electronegativity 1.3 ionic and covalent bonds Ionic Bonds Covalent Bonds Structural Formulas Multiple Covalent Bonds Polar Covalent Bonds 1.4 strategies for writing Lewis structures 1.5 formal charge 1.6 molecular geometry 6 10 11 Bond Lengths Drawing Structures 11 1.7 resonance structures 12 Nonequivalent Resonance Structures 13 1.8 valence shell electron Pair repulsion theory 1.9 dipole moments 15 Determining Charge Separation Bond Polarity and Molecular Geometry 16 1.10 molecular orbital theory 18 Molecular Orbitals 18 1.11 The hydrogen molecule 1.12 bonding in carbon compounds 19 Orbital Hybridization 21 1.13 sp3 hybridization of carbon in methane 1.14 sp3 hybridization of carbon in ethane 1.15 sp2 hybridization of carbon in ethene 1.16 sp hybridization of carbon in ethYne 1.17 effect of hybridization on bond length and bond strength 1.18 hybridization of nitrogen 1.19 hybridization of oxygen 21 12 16 17 20 22 23 25 27 27 30 vii Summary of Orbital Hybridization and Its Relation to VSEPR Theory 32 exercises 33 Chapter Part I: Functional Groups and Their Properties Table of Contents 2.1 INTRODUCTION TO FUNCTIONAL GROUPS: HYDROCARBONS AND HALOALKANES Page 41 Hydrocarbons Haloalkanes 41 2.2 FUNCTIONAL GROUPS THAT CONTAIN OXYGEN 43 Carbon–Oxygen Single Bonds in Alcohols and Ethers Carbon–Oxygen Double Bonds in Aldehydes and Ketones Carbon–Oxygen Bonds in Carboxylic Acids and Esters 43 2.3 FUNCTIONAL GROUPS THAT CONTAIN NITROGEN 2.4 FUNCTIONAL GROUPS THAT CONTAIN sulfur 2.5 STRUCTURAL FORMULAS 2.6 BOND-LINE STRUCTURES 45 Recognizing Structural Features in Complex Molecules 50 2.7 isomers 52 Nomenclature 54 Part II: Identification of Functional Groups by infrared spectroscopy 2.8 SPECTROSCOPY 2.9 infrared sPECTROSCOPY 42 43 44 47 48 49 55 57 The Relation of Vibrational Frequencies and the Masses of Bonded Atoms 57 2.10 IDENTIFYING HYDROCARBONS 2.11 IDENTIFYING OXYGEN-CONTAINING COMPOUNDS 58 The Carbonyl Group Alcohols and Ethers Carboxylic Acids Esters Carboxylic Acid Anhydrides 61 2.12 IDENTIFYING nitroGEN-CONTAINING COMPOUNDS 64 Amines Nitriles 65 2.13 BENDING DEFORMATIONS 66 Alkenes Bending Modes in Aromatic Compounds 66 end-of-chapter exercises 69 61 62 63 63 64 66 66 Chapter Introduction to organic reaction mechanisms Table of Contents 3.1 acid-base reactions viii Page 75 Brønsted-Lowry Acids and Bases Lewis Acids 75 3.2 CHEMICAL EQUILIBRIUM AND EQUILIBRIUM CONSTANTS 78 Le Chatelier’s Principle 79 3.3 pH AND pK VALUES 80 Ka and pKa Kb and pKb Applying pKa Values in Organic Acid-Base Reactions 80 76 81 82 3.4 EFFECT OF STRUCTURE ON ACIDITY 84 Effect of Periodic Trends on Acidity and Basicity Effect of Resonance on Acidity and Basicity Inductive Effects Effect of Hybridization on Acidity 84 3.5 STANDARD FREE ENERGY CHANGES IN CHEMICAL REACTIONS 86 The Standard Free Energy Change and the Equilibrium Constant 86 3.6 ENTHALPY CHANGES IN CHEMICAL REACTIONS 3.7 BOND DISSOCIATION ENERGIES 88 Effect of Electronegativity on Bond Energies Effect of Hybridization on Bond Energies Effect of Multiple Bonds on Bond Energies 89 3.8 INTRODUCTION TO REACTION MECHANISMS 90 Concerted and Multistep Reactions Types of Bond Cleavage 90 3.9 STRUCTURES AND STABILITIES OF CARBON RADICALS, CARBOCATIONS, AND CARBANIONS 91 Carbocations Carbon Radicals Methyl Radical Carbanions 91 3.10 FACTORS THAT INFLUENCE REACTION RATES 94 The Effect of Structure on Reactivity The Effect of Reactant Concentration on Reaction Rates The Effect of Temperature on Reaction Rates The Effect of Catalysts on Reaction Rates 94 3.11 reaction rate theory 97 Reaction Coordinate Diagrams Reaction Coordinate Diagrams and Reaction Mechanisms Catalysis Transition State Structure: The Hammond Postulate 97 3.12 STABILITY AND REACTIVITY end-of-chapter exercises 84 85 85 89 90 90 90 93 93 93 95 95 96 98 100 101 102 103 ix index A Absolute configuration Kahn–Ingold–Prelog System, 252 priority rules, 252–253 R,S system, 252 X-ray crystallography, 251 Acetal formation alcohols protection, 640–641 aldehyde group, 638 carbon–carbon double bond, 638 cyclic acetals synthesis, 638–639 ethers, 638 and ketals, 635–637 selective acetal synthesis, 639–640 synthetic transformations, 638 Acetamidomalonate synthesis, 959–960 Acetoacetate ester synthesis acid hydrolysis, β-keto ester, 784 Claisen condensation, ethyl acetate, 784 dialkylated acetone, 785 Acetylide, 228 Acid–base equilibria, α-amino acids carboxylic acids and amines, 955 ionic form, 955–956 pKa values, 956–957 Acid–base reactions alcohols, 307 Brønsted–Lowry acids and bases, 75–76 Lewis acid, 76–77 Acid-catalyzed nucleophilic addition reactions, 634 Acid chlorides sulfonic acids, 493 synthesis, 1085 Acidity carboxylic acids aromatic, 670–671 inductive effect, 668–669 resonance stabilization, carboxylate ion, 668 structure effect hybridization, 85 inductive effects, 85 periodic trends, 84 resonance, 84 Activation energy, 95 Acyclic compounds, 124–125 Acylation, ketones with esters diethyl carbonate reaction, enolate anion, 779 nonenolizable esters, 778 Acyl groups and carboxylic acids acid chloride and acid anhydride, 661 amide, 660 bonding, 660 formic acid, resonance structures, 659 lactones and lactams, 661 methanoic acid, 659 retanoic acid, 659 thioester, 661 Acylium ion, 425 Adams catalyst, 179 Addition polymerization chain branching, 998–999 chain length regulation, 998 stereochemistry, 1003–1005 termination steps, 997–998 Addition reactions, alkenes anti addition, 196 carbenes, 208–210 carbocations, 196–197, 201–203 characteristics, 195–197 dihydroxylatin, 212–213 epoxidation, 210–212 halogens (see Halogen addition, alkene) hydration, 204–205 hydrogen halides, 197–199 Markovnikov’s rule, mechanistic basis, 199–200 ozonolysis, 214–215 syn addition, 196 Alcohol reactivity acid anhydrides, 717 acid chlorides, 717 esters, 717 penicillins and cephalosporins, 718–719 Alcohols acid-base reactions, 307 and alkanes, boiling points, 294 alkyl halides synthesis, 310 boiling points and solubilities, 293, 294 carbonyl compounds reduction, 514–518 classification, 287 esters, 492–497 functionalized hydrocarbons, 287–288 Grignard reagents, 518–521 haloalkanes, 497–500 indirect hydration methods, 509–514 methanol structure, 294 nomenclature, 290–292 oxidation, 500–504 reactions, 306, 491–492 solubility, water, 295 solvents, 295 substitution reactions, 308–309 synthesis, 507–509, 1083–1084 thiols and thioethers, 521–523 vicinal diols reactions, 504–506 VSEPR theory, 293 Aldehydes and ketones acetals (see Acetal formation) acid-and base-catalyzed carbonyl addition reactions, 633–635 boiling points, 601 carbonyl compounds hydration, 630–633 carbonyl group, 595–597 condensation reactions α carbon atom, 747–750 conjugation, α-β-unsaturated, 765–766 α halogenation reactions, 754–758 keto-enol equilibria, 750–752 cyanohydrins formation, 630 description, 629 1189 Aldehydes and ketones—continued electron density map, acetone, 601 IUPAC names, 598–599 nitrogen compounds, 643–646 nomenclature, 597–599 oxidation-reduction reactions, 603–606 physical properties, 600–602 solubility, 601–602 solvents, 602 spectroscopy, 614–616 stabilities, 629 synthesis, carbonyl compounds, 606–613 thioacetals and thioketals, 641–643 Wittig reaction (see Wittig reaction) Aldol condensation, aldehydes aldehydes, 761–762 intramolecular, 763–765 mixed, 763 Aldol-type condensations, acid derivatives biochemical condensation reactions, 782–784 Knoevenagel condensation, 781 Reformatskii reaction, 782 Alkanes boiling points, 143–144 bond dissociation energies, 145–147 branched alkanes, 112 carbon atoms, classification, 113 conformations, 119–126 densities, 144 names, 112 nomenclature, 114–117 normal alkane, 112 quaternary carbon, 113 solubility, 144 synthesis, 1083 Alkenes boiling points, 176–177 bond lengths and bond energies, 165–166 β-carotene, 164 catalytic hydrogenation, 181–182 classification, 166 conjugated polyenes, 164 copolymerization, 999–1000 cycloalkenes, 163 density, 175 ethene, 163, 165 geometric isomerism, 168–170 heats of hydrogenation, 183–184 IUPAC names, 173–174 muscalure, 163 nomenclature, 173 polarity, 175–176 polyenes, 163 reduction, 178–181 stability, 177–178 steric effect and stability, 178 synthesis, 1083 unsaturation number, 167–168 Alkoxymercuration, 542 Alkyl alkyl ethers, 536 Alkyl alkyl sulfides, 556 Alkylation, enolate ions acetophenone, KH reaction, 760 dialkylation, 759 1190 β-diketones, 760 nucleophilic substitution, 759 strong bases, 759 Alkylation of amines, 813–814 Alkyl group, 112, 427 Alkyl halides dehydration reactions (see Dehydration) dehydrohalogenation reactions (see Dehydrohalogenation) elimination reactions, 310–311 synthesis, 1083 Alkyl radicals, stabilities, 145–147 Alkynes chemical properties, 226 classification, 224 electrophilic addition reactions, 231–233 hybridization, bond length and bond energies, 224–225 hydrogenation, 228–230 IUPAC names, 227 occurrence and uses, 223–224 physical properties, 225–226 synthesis, 234–235, 1083 terminal, acidity, 228 Alkynide, 228 Allylic systems bromine, 370, 371 carbocations, 367–369 C—H bond energy, 370 free radicals, 369–370 Hückel molecular orbitals (see Hückel molecular orbitals) reaction catalyzed, NBS, 371–373 and vitamin E, 373–375 Amides reduction, 817 synthesis, 1085 Amines acid and base properties, 821 alkylation, alkyl halides, 813–814 amides reduction, 817 azides reduction, 816 basicity (see Basicity, amines) bonding and structure, 804–805 classification, 805–806 common names, 806–807 elimination reactions, 821 Gabriel synthesis, 814–816 imines reduction, 816–817 melting points and boiling points, 808–809 nitriles reduction, 817 nitro compounds reduction, 817–818 nucleophilicity, 821 odor and toxicity, 809–810 oxidation reactions, 822 pyridine, 806 solubility, water, 809 spectroscopy, 828–830 substitution reactions, 821 synthesis, 1085 systematic names, 807–808 trimethylamine, 806 α-Amino acids acetamidomalonate synthesis, 959–960 acetylation, 962–963 acid–base equilibria, 955–957 chirality, 953 chiral synthesis (see Chiral synthesis, α-amino acids) esterification, α-carboxyl group, 961–962 α-halocarboxylic acids, 958–959 isoionic points, 957, 958 reductive amination, 959 side chain, 953 Strecker synthesis, 959 structures at pH 7, 953, 954 titration, 958 Ammonium salts solubility, 813 1,2-and 1,4-Electrophilic addition reactions 3-bromo-1-butene, 380 HBr, 379 kinetic control, 380 nonconjugated alkadienes, 379 nucleophilic bromide ion, 380 thermodynamic control, 380–382 Anhydrides, synthesis, 1085 Anilines acid-base properties, 846–847 pKa values, 847 Anti addition, 196 Antiaromatic compounds antibonding orbitals, 405 atomic orbitals, 405 benzene’s MOs, 405 cyclobutadiene, 406, 407 cycloheptatrienyl anion, 406 cycloheptatrienyl cation, 406 cyclopentadienyl anion, 406 cyclopropenium ion, 406 symmetric and antisymmetric, 405 Arene oxides, 554, 555 Arenes and aromaticity and antiaromatic compounds, 405–407 aromatic compounds, 397–398 benzene covalent structure, 398–401 heterocyclic aromatic compounds, 407–409 Hückel rule, 401–404 polycyclic aromatic compounds, 409–411 Aromatic compounds bonding and structure, 843–844 bond polarity, 844–845 Aromatic hydrocarbons, synthesis, 1083 Aryldiazonium salts, 861–862 Aryl halides carbon–halogen bond, 843 conversion, grignard and organolithium reagents, 848–849 nucleophilic substitution, 849 synthesis, 1083 Atomic properties atomic radius, electronegativity, 3–4 Atomic structure, organic compounds atomic number, electron configurations, first and second period elements, Hund’s rule, periods and groups, principal quantum numbers., 2s and 2p oribtals, subshell, valence shell electrons, Azides reduction, 816 Azo compounds, 862–864 B Base-catalyzed nucleophilic addition reactions, 634–635 Basicity amines description, 810 deuterium exchange, 811 diethylamine, 810 heterocyclic amines, 811–812 order, 810 carboxylic acid derivatives, 705–706 Benzene bicyclic structure, 398 C6H5Br, 398 equivalent hydrogen atoms, 399 Kekulé based structure, 398 Lewis structure, 398 resonance energy, 400–401 resonance theory, 399 Benzene derivatives, nomenclature, 417–419 Benzyne structure, 852–853 Biochemical condensation reactions, 782–784 Biochemical reactions, epoxides acid-catalyzed, 550 biochemical, 554–556 description, 549 nucleophiles, 549–550 regioselectivity, 550–552 stereochemistry, 552–554 Bond cleavage types, 90–91 Bond dissociation energies electronegativity, 89 hybridization, 90 multiple bonds, 90 Bonding in proteins, amino acids disulfide bonds, 979 α-helix, 977 hydrophobic interactions, 980 β-pleated sheets, 977–978 structure, 976, 977 Bond–line structures complex molecules, 50–52 drawing rules, 49 rings of carbon atoms, 49 Branching point, 112 Bromine addition, mechanism, 207 Bromochlorofluoromethane, 242–243 Bromochloromethane, 243 Brønsted–Lowry acids and bases, 75–76 1,3-Butadiene bond length, 366 molecular orbitals, 363–365 rotation, 366–367 Butane alkane isomers, 114 eclipsed conformation, 123 gauche conformation, 122 planar arrangement, 122 rotational barrier, 123–124 torsional angle, 122 van der Waals repulsion, 123 C Carbanions, 93–94 Carbenes addition, alkenes carbenoid species, 209–210 1191 Carbenes addition, alkenes—continued and carbocation, structure, 208 dichlorocarbene formation, 208–209 stereospecificity, 209 Carbenoid species, 209–210 Carbocation rearrangement reactions 1,2-hydride shift, 202 1,2-methide shift, 202–203 rearrangement, 202 Carbocations, 91–92 Carbohydrates biosphere, 907 classification, 907–908 disaccharides, 926–931, 940–941 glycosides, 923–926 human blood group antigens, 941–943 monosaccharides (see Monosaccharides) polysaccharides, 931–933 α Carbon, acid derivatives alkylation, esters, 774 α bromination, 774–776 deuterium exchange, 773–774 α Carbon atom, aldehydes and ketones acidity, α hydrogens, 747–748 enolates formation, 748–749 enolates reactions, 749 Carbon–carbon bonds, synthesis, 1085–1086 Carbon compounds bonding σ and π bonds, 20 orbital hybridization, 21 Carbon-13 NMR spectroscopy 2-butanol, 475 characteristics, 475 chemical shifts, 476 1-cis-3-cis-5-trimethyl-cyclohexane, 478 1-cis-3-trans-5-trimethylcyclohexane, 478 counting carbon atoms, 477 2-methyl-1-propanol, 476 2-methyl-2-propanol, 477 proton-decoupled spectra, 476 proton decoupling, 476 Carbon–oxygen bonds carboxylic acids and esters, 44–45 double bonds, aldehydes and ketones, 43–44 single bonds, alcohols and ethers, 43 Carbon radicals, 93 Carbonyl compounds reduction alcohols, 514 aldehydes and ketones, 507 alkenes, 514 hydride reduction, 515–516 lithium aluminum hydride and sodium borohydride, 515, 517 metal hydrides, 514–515, 517 synthesis acid chlorides, reduction, 610–611 acid derivatives reactions with organometallic reagents, 612 alcohols oxidation, 606–607 alkenes ozonolysis, 607–608 alkynes hydration, 608–609 esters, reduction, 611 Friedel–Crafts acylation, 607 Gatterman–Koch synthesis, 607 nitriles, 613 vicinal diols, oxidative cleavage, 608 1192 Carbonyl group acetone, 595 aldehydes and ketones, naturally occurring, 597 carbon–oxygen bond length, 596 carbonyl compounds, 596–597 formaldehyde, 595–596 Carboxylate anions basic solution, 671 separation and purification, 671–672 soaps and detergents, 672–674 water, 671 α-Carboxyl group esterification, 961–962 Carboxylic acid derivatives ammonia and amines, 719–720 basicity, 705–706 hydrolysis, 712–716 infrared spectroscopy, 725–728 NMR spectroscopy, 728–730 nomenclature, 699–702 nucleophilic acyl substitution, 706–712 organometallic reagents, 724–725 physical properties, 702–705 reaction of alcohols, 717–719 reduction, 721–723 Carboxylic acids acidity, 668–671 and acyl groups, 659–661 carboxylate anions (see Carboxylate anions) conversion to acyl halides, 681–682 to esters, 682–684 decarboxylation (see Decarboxylation reactions) esterification mechanism, 684–685 nomenclature, 661–664 nucleophilic acyl substitution, 680–681 physical properties, 665–667 reduction, LiAlH4 and diborane, 676–677 spectroscopy, 686–690 synthesis, 674–676, 1084, 1085 Catalysis, 100–101 Catalytic hydrogenation homogeneous, 180 regioselectivity, 180 stereochemistry, 181 stereoselective, 181–182 Chelate, 540 Chemical equilibrium and equilibrium constants, 78–79 Chemical kinetics Hammond postulate, 1080 interpretation, rate constants, 1077–1078 order and molecularity, 1074–1075 pseudo first-order reactions, 1073–1074 rate law, first-order reactions, 1071–1072 second-order reactions, 1072–1073 steady-state approximation, 1075–1077 transition state, 1078–1079 Chemical methods, monosaccharides chain extension, aldoses, 936–937 osazone formation, 935–936 oxidation and optical activity, 935 periodate oxidation, 933–935 proteins and lipids, 933 Wohl degradation, aldoses, 937 Chemical shift delta scale, 457 deshield, 461 electronegativity effects, 461 π electrons, effects, 461 equivalent hydrogens, 458 hydrogen atoms, 462 local magnetic field, 456 nucleus, shielding, 456 operating radio frequency and, 457 Chirality, monosaccharides aldoses, 909–911 glyceraldehyde, 908 ketoses, 912–914 Chiral molecules, 242–243 Chiral synthesis, α-amino acids description, 961 structure, (R,R)-degphos, 961 Chlorination, alkane activation energy, halogenation, 152 enthalpy changes, halogenation reactions, 151–152 hyperconjugation, 153–154 reactivity and selectivity, 153 reactivity and statistical factors, 150 regioselectivity, 148–149 Claisen condensation acylation, ketones with esters, 778–779 description, 772, 776 Dieckmann condensation, 777–778 mixed, 778 steps, 776–777 thioesters, 779–781 Claisen rearrangement, 896–897 Competing substitution and elimination reactions primary haloalkanes, 349–350 secondary haloalkanes, 350–351 tertiary haloalkanes, 348–349 Concerted and multistep reactions, 90 Condensation polymers description, 1005 types, monomers, 1005–1006 Condensation reactions, carbonyl compounds aldehydes and ketones (see Aldehydes and ketones, condensation reactions) aldol condensation, 760–765, 781–784 alkylation, enolate ions, 758–760 α carbon, acid derivatives, 773–776 Claisen condensation (see Claisen condensation) conjugate addition, 766–769 β-dicarbonyl compounds, 784–787 enolization, 753–754 α hydrogen atoms, acid derivatives, 770–773 Michael condensations, acid derivatives, 787–788 Michael reaction, 770 Robinson annulation, 770 Conformations alkanes acyclic compounds, 124–125 barrier to rotation, ethane, 120–121 and biological activity, 125–126 butane, 122–124 conformational analysis, 119 conformers, 119 definition, 119 eclipsed, 119 ethane, 119–120 Newman projection formulas, 120 propane, 121 rotamers, 119 “Sawhorse” representations, 119 staggered, 119 steric hindrance, 121 steric strain, 121 torsional strain, 121 van der Waals radii, 121 van der Waals repulsion, 121 cycloalkanes cyclobutane, 131 cyclohexane, 132–134 cyclopentane, 132 cyclopropane, 131 ethane, 22–23 Conformers, 119 Conjugate addition reactions 1,2-and 1,4-addition reactions, 766–768 organometallic reagents, 769 Conjugated alkenes allylic systems (see Allylic systems) 1,3-butadiene (see 1,3-butadiene) dienes, 357–361 MOs (see Molecular orbitals (MOs)) Conjugated polyenes, 164 Cope rearrangement, 874, 896 Coupling constants dihedral angle, 471–472 long-range coupling, 472–473 Covalent bonds bonding electrons, bonding forces, hydrogen molecule, 5–6 bond length, hydrogen molecule, multiple, 6–7 polar, 7–8 standard enthalpy change, valences, common elements, Cross-linked polymers copolymers, automobiles, 1002 cross-links, addition polymerization, 1001 p-divinylbenzene, 1000 vulcanized polyisoprene, 1001, 1002 Crown ethers, 540 Cyanohydrins, 630 Cyclic bromonium ion, 206–207 Cyclic hemiacetals and hemiketals anomers, 918 α-d-glucopyranose and β-d-glucopyranose, 916–917, 920 furanoses and pyranoses, 916, 918 Haworth projection formulas, 918–919 mutarotation, 919 Cycloaddition reactions antarafacial process, 886 Diels–Alder reaction, 874, 888 dienophile, 874 Lewis acid-Lewis base process, 887 LUMO and HOMO, 887–888 orbital symmetry rules, 889 stereochemistry, 887 suprafacial reactions, 886 symmetry-forbidden thermal addition reaction, 888 thymine dimers, 889–890 1193 Cycloalkanes bridged ring compounds, 126 conformations, 131–134 cyclopropane, structure and bonding, 130 fused ring compounds, 126 geometric isomerism, 126–127 heat formation, 130 nomenclature, 128–129 relative stabilities, 129 spirocyclic compounds, 126 structure and bonding, 130–131 synthesis, 1083 Cycloalkylalkane, 128–129 Cyclohexane boat conformation, 134 chair–chair interconversion, 134 cis-and trans-1,2-dimethylcyclohexanes, 139–140 cis-and trans-1,4-dimethylcyclohexanes, 137–138 compounds with different substituents, 140 conformational energies, 135–136 conformations, cycloalkanes, 132 monosubstituted, 136–137 Newman projection formula, 133–134 twist boat conformation, 135 Cystine, 522 D Decarboxylation reactions acetoacetic acid, 678 biochemical, 679–680 β carbonyl group, 677 Hunsdiecker reaction, 678 malonic acid, 678 Degree of substitution, 166 Dehalogenation, 310 Dehydration alcohols, mechanism, 316–317 aldols, 762 elimination reaction, 311 rearrangements, 317–318 regioselectivity, alcohols, 316 Dehydrobromination, 310 Dehydrohalogenation elimination reaction, 310–311 E1 mechanism, 315–316 E2 mechanism (see E2 mechanism) regioselectivity, 312 stereoelectronic effects, 313–314 Zaitsev’s rule, 312 Delta scale, 457 Deuterium isotope effects, elimination reactions, 347 Diastereomers catalytic hydrogenation, 273 configurations, 257 definition, 255 enantiomers and, 255, 257 nomenclature, 256 stereoselective reaction, 273 Diazotization, 439 β-Dicarbonyl compounds acetoacetate ester synthesis, 784–785 β-keto esters, 784 malonate ester synthesis, 785–786 Dichlorocarbene formation, 208–209 Dichloromethane, 242–243 1194 Dieckmann condensation, 777–778 Diene polymers, 1004–1005 Dienes classification, 357–359 conjugated, 360–361 electrophilic addition (see 1,2-and 1,4-Electrophilic addition reactions) Dihydroxylatin, alkenes glycols, 213 N-methylmorpholine-N-oxide (NMNO), 213 osmium tetraoxide, 213 syn dihydroxylation, 213 vicinal diols, 213 Diisopropyl ether, 536 Dimethyl cyclohexanes, 261–264 Dimethyl sulfoxide (DMSO), 557 Dipole moments average, 17 bond polarity and molecular geometry, 17 charge separation determination, 16 Disaccharides cellobiose, 928 glycosidic bonds, 926 lactose, 928–929 maltose, 926–927 structure, 940–941 sucrose, 929–930 Disubstituted alkyne, 224 Disubstituted cyclobutanes, 261–262 Disubstituted cyclohexanes, 137–141 DMSO See Dimethyl sulfoxide (DMSO) Dynamic processes conformational changes, 473–474 ethanol, NMR spectrum, 474 hydroxyl hydrogens, 474 E The Edman degradation, 972–973 Electrocyclic reactions conrotatory motion, 880–882 Cope rearrangement, 874 cyclobutene, 874 disrotatory motion, 880–882 HOMO and LUMO, 881 photochemical cyclization, 883, 885 rules, 885 thermal cyclization, 4n + 2π systems, 882–884 Electron impact mass spectrometer, 479 Electrophilic addition reactions, alkynes halogens, 232–233 hydration, 233 hydrogen halides, 231–232 Electrophilic aromatic substitution alkylation, 424–425 benzene derivatives, nomenclature, 417–419 directing effects, interpretation, 434–437 electrophilic addition to cyclohexene, 421 Friedel–Crafts acylation, 425–428 functional group modification, 437–440 halogenation, 422 mechanism, 420–421 nitration, 422–423 reaction rates, substituents effect on, 432–434 sigma complex, 420 substituent effects, 429–430 substituted aromatic compounds, 440–442 sulfonation, 423–424 Elimination reactions and competing substitution, 348–351 dehydrohalogenation, 346 deuterium isotope effects, 347 E2 and E1 mechanisms, 346, 347 reaction mechanisms, 346 stereoelectronic effects, 346 steric effect, 347–348 1,2-Elimination reactions, 310 β-Eliminations, 310 E2 mechanism orbital geometry, 315 stereochemistry, elimination reactions, 314 stereoelectronic effects, 313–314 stereoselectivity, 315 steric effects, 315 Enamines alkylation, 823–824 carbinolamine, 822 cyclopentanone reaction, pyrrolidine, 822 secondary amines, preparation, 822–823 Enantiomeric excess, 249 Enantiomers chiral chromatography, 267–268 definition, 243–244 levodopa, 245 physical and chemical properties, 245 resolution, 266 resolving agent, 266 stereospecific, 245 Endergonic reaction, 98 Enolizable hydrogen atom, 773 Enolization cis-2-ally1-3-methylcyclohexanone, 753 enolizable hydrogen atom, 753 (R)-2-methylcyclohexanone enol formation, 753 tautomerization, metabolic reactions, 753–754 Enthalpy changes, chemical reactions, 88–89 Entropy changes, chemical reactions compounds, 1064 stoichiometry and ΔS °rxn, 1064–1065 Epimers, 914–915 Epoxidation, alkenes epoxides, 210 m-chloroperoxybenzoic acid (mCPBA), 210 mechanism, 211–212 peroxyacetic acid, 210 Epoxides reactions, 549–556 synthesis, 548–549, 1084 Erythromycin, 254–255 Ester enolates formation, 772 Esters carbon-carbon double bond, 502 carboxylic acids, 494–495 chromic, 502, 504 lithium aluminum hydride, 517 nitric, sulfuric and phosphoric acid, 492–493 oxyacid, 492 phosphate and pyrophosphate, 495–497 synthesis and formation, 491, 1085 Ester synthesis, 854–855 Estradiol, 234 Ethane conformations, 119–121 sp3 hybridization, 22–23 Ethanoic acid, 81 Ethers nomenclature, 536–538 physical properties, 538–541 polyether antibiotics, 541–542 protecting group, 547–548 reactions, 545–547 spectroscopy, thiols and sulfides, 557–560 structure, 535–536 synthesis, 542, 854, 1084 Williamson ether synthesis, 543–545 Ethyne, structure and bonding, 225 Exergonic reaction, 98 F FGI See Functional group interconversion (FGI) First law of thermodynamics enthalpy changes, 1059–1060 heat of combustion, 1060 state functions, 1057 statement, 1058 temperature and zeroth law, 1058 Fischer esterification, 684 Fischer projection formulas, 249–250 Formal charge, 10–11 Free energy composition of system, 1065 enthalpy and entropy, 1066 equilibrium constant and standard free energy changes, 1067–1068 exergonic and endergonic, 1066 Gibbs free energy, 1066 standard free energy changes, 1067 Friedel–Crafts acylation acyl cations, 425–426 acylium ion, 425 benzene alkylation, 424 definition, 425 limitations, 427–428 secondary alkyl halides, 425 Fuming sulfuric acid, 423 Functional group interconversion (FGI), 587 Functional group modification acyl group to alkyi group, conversion, 438 alkyl side chain oxidation, 437–438 amino group to diazonium ion, conversion, 439–440 nitro group to amino group, reduction, 439 Functional groups bond-line structures, 49–52 description, 41 hydrocarbons and haloalkanes, 41–42 IR spectrum (see Infrared spectroscopy) isomers, 52–54 nitrogen containing, 45–47 oxygen containing, 43–45 structural formulas, 48–49 sulfur containing, 47–48 G Gabriel synthesis description, 815 dipolar resonance forms, 814 1195 Gabriel synthesis—continued N-alkyl phthalimide product, 815 phthalimide, 814 resonance stabilization, conjugate base, 814 Gem diol, 502 Geminal dihalide, 234–235 Geometric isomerism alkenes, 169 cis and trans isomers, 169 configurations, 169 cycloalkenes, 170 E,Z system, 170–171 sequence rules, 171–172 stereoisomers, 169 Gilman reagent cross-coupling, 570 description, 570 oxidative addition and reductive elimination, 572–573 preparation, 570–571 reactions, 571–572 Glyceraldehyde, 249–250 Glycols dihydroxylation, 213 synthesis, 1084 Glycosides alcohols, 923 α and β anomers, 924–925 cyclic precursors, acetals, 926 oxocarbocation, 924 GPCR See Guanine protein coupled receptor (GPCR) Grignard reagents acetylenic alcohols, 520–521 acidic hydrogen atoms, 518–519 alcohols, 508, 518, 519 description, 518 limitations, 519–520 polar carbon-magnesium bond, 518 protect acidic groups, 520 THF, 518 Guanine protein coupled receptor (GPCR), 964 H Haloalkanes alcohols, 497 boiling points and densities, 293 functionalized hydrocarbons, 287–288 nomenclature, 288–290 nucleophilic substitution reactions, 298–304 organometallic compounds, 295–297 phosphorus tribromide, 499–500 reactions, 297–298 thionyl chloride, 498–499 α-Halocarboxylic acids, 958–959 Halogen addition, alkene bromine addition, mechanism, 207 cyclic bromonium ion, 206–207 halohydrins formation, 207–208 mechanism, 206–207 rearrangement reactions, 206 stereochemistry, 206 vicinal, 205 α-Halogenation reactions, aldehydes and ketones acid-catalyzed, 755–756 base-catalyzed, 757 1196 chlorine and bromine, 754 haloform reaction, 757–758 Halohydrins formation, 207–208 Hammond postulate, 101 Haworth projections, pyranose and furanose, 918–919 Heat of hydrogenation, 228–229 Heats of formation (kJ mole-1010221) acids and esters, 1022 alcohols, 1022 aldehydes and ketones, 1022 alkanes, 1021 alkenes, 1021 alkynes, 1022 amines, 1022 aromatic hydrocarbons, 1022 cycloalkenes, 1021 cyclolkanes, 1021 dienes, 1022 ethers, 1022 substituted cyclolkanes, 1021 sulfur compounds, 1022 Hell–Volhard–Zelinsky reaction, 774–775 Hemoglobin, 984–985 Hess’s law, 1061 Heteroatoms, 111 Heterocyclic amines, 811–812 Heterocyclic aromatic compounds description, 407 furan and thiophene, 408 imidazole, 408, 409 niacin, pyridoxine and thiamine, 408 nitrogen atom, 409 pyridine resembles benzene, 407 pyrrole, 408 tagamet, 408 valence electrons, 407 Heterocyclic compounds, 111 Heterogeneous reaction, 96 Heterolytic cleavage, 91 Highest occupied molecular orbital (HOMO) 1,3-butadiene, 363–365 and LUMO, 386, 387 Hinsberg test, 825 H NMR and 13C NMR chemical shifts (ppm), 1025 Hofmann elimination, 826–828 Hofmann rearrangement mechanism, 819–820 primary amides, 818 HOMO See Highest occupied molecular orbital (HOMO) Homogeneous catalytic hydrogenation, 180 Homolytic cleavage, 90–91 Hückel molecular orbitals allyl carbocation, 375, 376 allylic oxidation and marijuana metabolism, 378–379 antisymmetric, 375 carbon–chlorine bond, 377 C-2 atom, 375 electron configurations, 375, 377 nonbonding, 375, 376 pentadienyl radical, 377 primary alcohols, 378 Hückel rule aromatic ions, 402–404 aromaticity, 401 description, 401 heterocyclic aromatic compounds, 401 nonaromatic and antiaromatic cyclic polyenes, 401–402 unusual stability and unique reactivity, 401 Human blood group antigens, 941–943 Hunsdiecker reaction, 678 Hybridization bond length and strength, 27 nitrogen, 27–30 oxygen, 30–32 Hydrate formation, constants, 631 Hydration, alkenes dehydration and, 204 oxonium ion, 204 regiospecific, 204 reversibility, 204–205 1,2-Hydride shift, 202 Hydrocarbons alkanes, 111 classes, 111 and haloalkanes, 41–42 identification, 58–60 saturated, 111 unsaturated, 111 Hydrogenation Adams catalyst, 179 alkenes, stability, 228–230 alkynes, 228–230 anti addition, 229–230 catalytic (see Catalytic hydrogenation) heats, structural effects, 183–184 Raney nickel, 179 regioselective, 180 syn addition, 229 α-Hydrogen atoms, acid derivatives acidity, 770–772 enolates, β-dicarbonyl compounds, 772–773 ester enolates formation, 772 Hydrogen halide addition alkyl chlorides, synthesis, 199 electrophilic addition, 197 Markovnikov’s rule, 198 regiospecificity, 197–198 Hydrogen molecule antibonding orbital, 20 bonding and antibonding molecular orbitals, 20 energy vs internuclear separation, 19 Hydrolysis acid chlorides and anhydrides, 712 amides, 713–714 chloramphenicol, 715–716 esters, 713 nitriles, 714–715 phenacetin, 716 Hyperconjugation, 153–154 I Imines reduction, 816–817 Indirect hydration methods description, 509 hydroboration–oxidation, 511–514 oxymercuration–demercuration, 509–510 Inductive effects hydration reactions, 632 substituents, 432–433 Infrared spectroscopy absorption values, 58 acetamide and N-methylacetamide, 727–728 acetyl chloride, 726–727 benzonitrile, 725–726 ethyl acetate, 726 1-methylcylcopentene, 57 relation, vibrational frequencies, 57–58 Internal alkyne, 224 International Union of Pure and Applied Chemistry (IUPAC), 114 Intramolecular aldol condensation reactions five/six-membered ring products, 763 four-and three-membered rings, 764 2-(3-oxobutyl)cyclohexanone), final aldol product, 764–765 Invert soaps, 825–826 Ionic bonds anions and cations, Lewis octet rule, sodium chloride, Ionophores, 541 IR absorptions aldehyde carbonyl stretch, 1023 carboxylic acid carbonyl stretch, 1023 carboxylic acid derivatives, 1023 ester carbonyl stretch, 1023 hydrocarbons, 1023 ketone carbonyl stretch, 1023 O–H, N–H and S–H groups, 1023 Isobutane, 114 Isomeric butenes, 177–178 Isomerizations, monosaccharides D-ribose, 916 enediol, 915 epimers, 914–915 interconversion, aldoses and ketoses, 915 Isomers constitutional isomers, 52, 53 1,2-dichloroethane, 53 nomenclature, 54 stereoisomers, 52 K Keto-enol equilibria, aldehydes and ketones stability, enols, 751–752 tautomerization, 750–751 Ketones, synthesis, 1084 Kiliani–Fischer synthesis, 936 Knoevenagel condensation reaction, 781 Kolbe synthesis, 857, 858 L LCAO See Linear combination of atomic orbitals (LCAO) Le Chatelier’s principle, 79 Lewis acid, 76–77 Lewis structures strategies, writing, valence electrons, 8, Lindlar catalyst, 229 Linear combination of atomic orbitals (LCAO), 18–19, 32 Lowest unoccupied molecular orbital (LUMO) 1,3-butadiene, 363–365 and HOMO, 386, 387 1197 M N Magnesium monoperoxyphthalate (MMPP), 548, 549 Malonate ester synthesis, 785–786 Markovnikov’s rule, mechanistic basis carbocations, 199 Hammond postulate and electrophilic addition, 200 reaction coordinate diagrams, 200 Mass spectrometry alcohols, 482–483 base peak, 480 chlorine and bromine-containing compounds, 481–482 2-chloropropane, 481 description, 478 2,2-dimethylpentane, 481 hydrocarbons, 480 ions production, 479–480 nitrogen-containing compounds identification, 483–484 n-pentane, 480 parent ion, 479 radical cation, 479 m-chloroperoxy-benzoic acid (MCPBA), 548 Meta directors, 430 Methane, sp3 hybridization, 21–22 1,2-Methide shift, 202–203 Methyl carbocation, structure and hybridization, 196–197 Methyl radical, 93 Michael condensations, acid derivatives, 787–788 Michael reaction and Robinson annulation, 770 Mirror image isomers, 243–244 Mixed aldol condensation reactions, 763 Mixed Claisen condensation, 778 MMPP See Magnesium monoperoxyphthalate (MMPP) Molecular geometry average bond lengths, 12 bond lengths, 11 drawing structures, 12 structural formulas and molecular models, 12 Molecular orbitals (MOs) antibonding, 878 atomic orbitals, 18, 19 bonding and antibonding, 1,3-butadiene, 879 1,3-butadiene, 363–365 cycloaddition reactions, 887–888 ethene, 361–362 frontier orbital method, 877 HOMO and LUMO, 877, 879, 880 LCAO, 18–19 sigmatropic rearrangements, 891–896 symmetry-allowed reactions, 362–363, 878 Molozonide, 214–215 Monosaccharides aldoses and ketoses, 907–908 chemical methods, 933–938 chirality, 908–914 cyclic hemiacetals and hemiketals, 916–920 description, 907 determination, ring size, 938–940 glycosidic bonds, 907 isomerizations, 914–916 oxidation, 921–923 reduction, 920–921 Monosubstituted alkyne, 224 Monosubstituted cyclohexanes, 136–137 MOs See Molecular orbitals (MOs) Myoglobin, 983 N-bromosuccinimide (NBS) allylic centers catalyzed, 371 reaction catalyzed, 371–373 NBS See N-bromosuccinimide (NBS) Neoprenes, 164 Newman projection formulas alkanes, 120 cycloalkanes, 133–134 Nitration, 422–423 Nitriles reduction, 817 synthesis, 1085 Nitro compounds reduction, 817–818 Nitrogen containing functional groups amines and nitriles, 46–47 imines, 46 nitriles, 45 Nitrogen hybridization sp-hybridized atom, 29–30 sp2-hybridized atom, 29 sp3-hybridized atom, 28 Nitrogen inversion, amines, 805 N-methylmorpholine-N-oxide (NMNO), 213 NMR spectroscopy See Nuclear magnetic resonance (NMR) spectroscopy Nomenclature alkanes alkyl, 114 alkyl groups names, 116–117 isopropyl group, 116 IUPAC name, 114, 117 normal alkyl groups, 116 parent, 114 suffix, 114 carboxylic acid derivatives acid anhydrides, 699 acid halides, 699 acyl group, 699 amides, 700–701 carboxylate anions, 664 clofibrate, 701–702 common names, 661–662 esters, 700 IUPAC names, 663–664 nitriles, 701 Nonequivalent hydrogen atoms, detecting sets diastereotopic and enantiotopic hydrogen atoms, 7–8 1,2,2-trichloropropane, NMR spectrum, 459 types, 458 Noyori asymmetric reduction, ketones, 583–584 Nuclear magnetic resonance (NMR) spectroscopy carbon-13, 729 electromagnetic radiation, absorption, 455 ethyl acetate, 728–729 field strength, effect, 455 magnetic field strength effect, 455–456 nuclear precession frequency, 456 nuclear spin, 454 precession, 455 resonance, 455 Nucleophilic acyl substitution acid-catalyzed acyl substitution reactions, 707–708 aldehydes and ketones, 707 base-catalyzed acyl substitution reactions, 708 1198 description, 706 haloalkanes, 707 position, 711 reactivities, acyl derivatives, 708–711 Nucleophilic aromatic substitution addition-elimination, 849–851 benzyne structure, 852–853 elimination-addition, 851–852 Nucleophilicity, 333 Nucleophilic substitution acid-base reaction, 333 and basicities, 333 biological SN2 reactions bysulfur-containing, 336 description, 333 nucleophilicity, 333 properties, 333–335 SN1 vs SN2 reactions, 339–345 stereochemistry, 337–339 Nucleophilic substitution reactions, haloalkanes alkynide ions, 299 hydrogen sulfide ion (HS–), 299 iodomethane, 298 leaving group, 298 SN1 reaction mechanism (see SN1 reaction mechanism) SN2 reaction mechanism (see SN2 reaction mechanism) thiolate ions (RS–), 299 O Oligosaccharides, 907, 941–942 Optical activity achiral molecules, 246 chiral molecules, 246 circularly polarized light and optical rotation, 247–248 dextrorotatory and levorotatory isomers, 247 optical isomers, 247 optical purity, 248–249 plane-polarized light, 246 polarimeter, 246 specific rotation, 246–247 Organic acid–base reactions, 75–77, 82 Organic compounds atomic properties, 3–4 atomic structure, 1–3 bonding, carbon compounds, 20–21 dipole moments, 16–17 formal charge, 10–11 hybridization effect, bond length and strength, 27 hydrogen molecule, 19–20 ionic and covalent bonds, 4–8 Lewis structures, 8–10 molecular geometry, 11–12 MOs theory, 18–19 nitrogen hybridization, 27–30 oxygen hybridization, 30–32 resonance structures, 12–14 sp3 hybridization, carbon, 21–23 VSEPR theory, 15–16 Organic nitrogen compounds, 803–804 Organic reaction mechanism acid–base reactions, 75–77 acidity, structure effect, 84–85 bond cleavage types, 90–91 bond dissociation energies, 89–90 carbanions, 93–94 carbocations, 91–92 carbon radicals, 93 chemical equilibrium and equilibrium constants, 78–79 concerted and multistep reactions, 90 enthalpy changes, in chemical reaction, 88–89 methyl radical, 93 pH and pK values, 80–82 reaction rates (see Reaction rates) reactive carbon intermediates, 92 stability and reactivity, 102 standard free energy, chemical reactions, 86–87 Organolithium reagents, 297 Organometallic compounds Grignard reagents, 295–296 organolithium reagents, 297 Organometallic reagents, 724–725 Osazone formation, 935–936 Oxidation, monosaccharides aldaric acids, 922 aldonic acid, 921 Benedict’s solution, 921–922 d-glucuronic acid, 922–923 uronic acid, 922 Oxidation-reduction reactions, carbonyl compounds aldehydes and ketone, 603–604 carbonyl group reduction, 604–605 ethanol, NAD-dependent oxidation, 605–606 Oxonium ion, 204 Oxygen containing functional groups carbon-oxygen bonds, carboxylic acids and esters, 44–45 carbon-oxygen double bonds, aldehydes and ketones, 43–44 carbon-oxygen single bonds, alcohols and ethers, 43 Oxygen hybridization ball-and stick structures, water and methanol, 31 sp2-hybridized oxygen atom, 31–32 sp3-hybridized oxygen atom, 30 Ozonator, 214 Ozonolysis mechanism, 214 molozonide, 214–215 ozonator, 214 reductive and oxidative workup, 215 P Palladium-catalyzed cross-coupling reactions, 573 PCC See Pyridinium chlorochromate (PCC) Peptides amino group, 967 bond synthesis, 968 carboxyl group, 967 description, 963 enkephalins, 965 experimental limitations, 968 Gly-Gly, Gly-Ala and Ala-Gly, 966 GPCR, 964 hormones, 964–965 isomeric tripeptides, 964 N-and C-terminal amino acid residues, 963 nomenclature, 963, 964 physiological functions, 966 polypeptide synthesis, 968 synthesis, requirements, 967 Pericyclic reactions cycloaddition reactions, 874–875, 886–890 description, 873 1199 Pericyclic reactions—continued electrocyclic reactions, 874, 880–886 features, 876–877 molecular orbitals, 877–880 orbital symmetry and Hückle systems, 873 sigmatropic rearrangements (see Sigmatropic rearrangements) Periodate oxidation, 933–935 pH and pK values Ka and pKa, 80–81 Kb and pKb, 81–82 organic acid-base reactions, 82 Phenol–formaldehyde polymers, 1011 Phenols acid–base properties, 845–846 electrophilic substitution, 855 ester synthesis, 854–855 ether synthesis, 854 m-nitrophenol, 847 Phenoxide ions formaldehyde, 856–857 Kolbe synthesis, 857, 858 nucleophilic carbon atom, 856 Phosphorus oxychloride (POCl3), 497 Phosphorus ylides, 646–647 Physical properties acyl halides, 702–703 amides, 704 carboxylic acids boiling points, 665 melting points, 666–667 solubilities, 667 esters, 703–704 ethers dipole moments and boiling points, 538 ethyl ether, 538 polyethers, 539–541 solvents, 539 water solubility, 539 nitriles, 705 polymers crystallinity, 994 description, 991 hydrogen bonding and polymer properties, 993 and London forces, 992 and primary structure, 991 pKa values acyclic carboxylic acids, 1019 alcohols, 1019 benzoic acids, 1019 diarboxylic acids, 1019 hydrocarbons, 1020 α-hydrogen atoms, 1020 inorganic acids, 1019 phenols, 1020 substituted acetic acids, 1019 sulfur compounds, 1020 β-Pleated sheets, 977–978 POCl3 See Phosphorus oxychloride (POCl3) Polyamides, 1009–1010 Polycarbonates description, 1008 Lexan, 1009 Polycyclic aromatic compounds anthracene and phenanthrene, 409, 410 1200 carcinogenic, 410–411 chrysene, π electrons, 410 description, 409 Lewis structure, 409, 410 naphthalene, 409 Polycyclic molecules cis-and trans-decalin, 141 human physiological effects, steroids, 142 solubility, 144 steroid ring system, 141–142 Polyesters cross-links, condensation polymer, 1008 cyclic anhydrides, 1007 Dacron, 1007 description, 1006 synthetic fibers, 1007 transesterification reactions, 1007 Polyether antibiotics cation solvation, 541–542 ionophores, 541 monensin, 541 nonactin, 541 Polymers addition polymerization (see Addition polymerization) elastomers, 994–995 fibers, 996 natural and synthetic, 991 physical properties, 991–994 plastics, 995 polymerization methods, 996–997 Polypeptide synthesis, 968 Polysaccharides amylose and amylopectin, 931 cellulose, 931–932 description, 907 α-d-glucopyranosyl groups, 933 homopolysaccharide starch, 931 Polyurethanes, 1012–1013 Primary carbon, 92 Primary carbon atom, 113 Principle of microscopic reversibility, 205 Prochiral centers, 274–275 Propane, 121 Proteins acid-catalyzed hydrolysis, 970 amino acid derivatives, 971 blocking cystine residues, 974 bonding (see Bonding in proteins, amino acids) covalently modified amino acids, HPLC, 971–972 description, 970 The Edman degradation, 972–973 enzymatic cleavage, polypeptide chains, 975 1GB1 structure, 981 levels of structure, 980 parallel β strands and α-helix, β-α-β arrangement, 981, 982 peptide cleavage, methionine residues, 974 primary structures and evolutionary relationships, 975–976 quatenary structure, 980 ribbon diagram, serotonin receptor, 980, 981 triose phosphate isomerase, 981, 982 Proton NMR spectroscopy, 615 Pyridinium chlorochromate (PCC), 501, 502 Q Quaternary ammonium salts exhaustive methylation, 825 Hofmann elimination, 826–828 invert soaps, 825–826 Quinones coenzyme Q, 859–860 description, 858 reduction potentials, 858, 859 ubiquinone, 860–861 R Racemic mixtures, 249 Radical cation, 479 Reaction coordinate diagrams, 97–100 Reaction rates catalysis, 100–101 endergonic reaction, 98 exergonic reaction, 98 factors, 94–96 Hammond postulate, 101 reaction coordinate diagrams, 97–100 and reaction mechanisms, 98–100 transition state, 97 Reactive carbon intermediates, 92 Reactive intermediates, 92 Reduction acid chlorides, 721 amides, 722 esters, 721–722 monosaccharides, 920–921 nitriles, 722–723 Reductive amination, 959 Reformatskii reaction, 782 Regioselectivity, catalytic hydrogenation, 180 Relative peak areas and proton counting, 463 Resonance effects of substituents, 433–434 Resonance stabilization, 84 Resonance structures carboxylate ion, 13 localized electrons, 12 nonequivalent, 13–14 resonance-stabilized, 12 Retrosynthesis FGI, 587 precursor molecules, 586 synthons, 587 terpinolene, 587–589 Rhodopsin, 503 Robinson annulation, 770 Rotamers, 119 S Sandmeyer reaction, 439–440 Saponification, 508 “Sawhorse” representations, 119 Secondary carbon, 92 Secondary carbon atom, 113 Second law of thermodynamics entropy, probability and information, 1062–1064 Maxwell’s demon, 1063 statement, 1061 Sickle cell hemoglobin, 984–985 Sigma complex, 420 Sigmatropic rearrangements allyl radical, molecular orbitals, 891 antarafacial, 894 Claisen rearrangement, 896–897 Cope rearrangement, 896 description, 875–876 pentadienyl radical, molecular orbitals, 892 suprafacial process, 893, 894 thermal and photochemical rules, 890 vitamin D activation, 894–896 SN1 reaction mechanism carbocation rearrangements, 304 energy profile, 303 unimolecular, 303 SN2 reaction mechanism S-adenosylhomocysteine, 302 biological methylation, 301–302 reaction coordinate diagram, 300–301 steric hindrance effect, 301 SN1 vs SN2 reactions bysulfur-containing nucleophiles, 336 leaving group, 341–343 nucleophile, 341 solvent, 344–345 substrate structure, 339–341 Solid-phase peptide synthesis CH2Cl group, 969 description, 969 polymer-bound amino acid, 969 Sonogashira reaction, 579–580 Spectroscopy aldehydes and ketones 2-butanone, 616 3-buten-2-one, IR spectrum, 615 C-13 NMR spectroscopy, 616 infrared spectroscopy, 614 proton NMR spectroscopy, 615 amines, 828–829 carboxylic acids carbon-13 NMR, 687–690 infrared, 686–687 proton NMR, 687, 688 electromagnetic radiation, 55 electromagnetic spectrum, 56 ethers, thiols and sulfides, 557–560 features, spectrum, 56 infrared (see Infrared spectroscopy) sp hybridization, ethyne, 25–26 sp2 hybridization, ethene, 23–25 sp3 hybridization ethane, 22–23 methane, 21–22 Spin–spin splitting, NMR spectrum chloroethane, 468 chloroethene, 470 2-chloropropane, 469 coupling constant, 465 definition, 464 doublets, 464 ethyl group and isopropyl group, 467–468 multiple splitting, 469–470 multiplets characteristics, 466 multiplicity, 464 quartets, 464 singlet, 464 1201 Spin–spin splitting, NMR spectrum—continued 1,1,2-tribromo-3,3-dimethylbutane, 464 1,1,2-trichloroethane, 467 vicinal hydrogens, 465 Stability and reactivity, 102 Standard conditions, measurements, 88 Standard free energy, chemical reactions, 86–87 Stereochemistry absolute configuration, 251–253 achiral and chiral, 242 chiral molecules, 242–243 configurations, 241 diastereomers, formation reaction, 273 enantiomers (see Enantiomers) Fischer projection formulas, 250–251 mirror image isomers, 243–244 nonsuperimosable mirror images, 242 non-superimposable objects, 241 nucleophilic substitution reactions carbon atom and the leaving group, 337 SN1 mechanism, 338–339 SN2 mechanism, 337–338 unimolecular reactions, 337 optical activity, 246–249 prochiral centers, 274–275 stereogenic centers (see Stereogenic centers) stereoisomers, 241 superimposable objects, 241 Stereoelectronic effects, elimination reactions, 346 Stereogenic centers alkene bromination, 271–272 chirality and senses, 265–266 cyclic molecules, 260–266 definition, 242 enantiomers and diastereomers, 255–257 equivalent, 257–258 erythromycin, 255 free radical reaction, 269 Markovnikov addition to alkenes, 270–271 nonequivalent, 255 optically active tartaric acids and meso compounds, 258 substitution reaction, 268–269 Stereoisomers, 169, 241 Steric effects hydrates, 631 hydration reactions, 631 regiochemistry, 347–348 Steric hindrance, 121 Steric strain, 121 The Strecker synthesis, 959 Structural formulas condensed, functional groups, 48–49 Structure determination carbon-13 NMR spectroscopy, 474–478 chemical shift, 456–458, 461–462 coupling constants, effects, 471–473 description, 453–454 dynamic processes, 473–474 mass spectrometry, 478–484 nonequivalent hydrogen atoms, detecting sets, 458–460 nuclear magnetic resonance spectroscopy, 454–456 relative peak areas and proton counting, 463 spin-spin splitting, 464–470 1202 Substituent effects, benzene rings reactivity meta directors, 430 orientation effects, 430 ortho and para director, 430 ring substituents effect, 429–430 Substituted aromatic compounds, 440–442 Substitution reactions, alcohols reaction coordinate diagram, 309 reaction mechanisms, 308–309 SN2 and SN1 mechanisms, 309 Sulfhydryl group, 521, 522 Sulfides alkyl alkyl, 556 oxidation, 557 synthesis, 556–557, 1085 Sulfonamides, 824–825 Sulfonation, 423–424 Sulfur containing functional groups, 47–48 Suzuki coupling reaction, 574–576 Syn addition, 196 Syn dihydroxylation, 213 Synthesis acid chlorides, 1085 alcohols, 1083–1084 alkanes, cycloalkanes and aromatic hydrocarbons, 1083 alkyl and aryl halides, 1083 amides, nitriles and amines, 1085 anhydrides, 1085 carbon–carbon bonds, 1085–1086 carboxylic acids functional group modifications, organic, 685–686 Grignard reagents carboxylation, 674–675 hydrolysis of nitriles, 675–676 oxidative methods, 674 epoxides, 1084 esters, 1085 ethers, 1084 glycols, 1084 ketones, 1084 thiols and sulfides, 1085 T TBDMS See Tert-butyldimethylsilyl (TBDMS) Terminal alkene, 166 Terminal alkyne acetylide, 228 alkynide ion, 228 definition, 224 ethyne and, 228 Tert-butyldimethylsilyl (TBDMS), 548 Tertiary carbon, 92 Tetrahy-drocannabinol (THC), 536 Tetrahydrofuran (THF), 518 Thermodynamics ΔH °rxn and ΔS°rxn contributions to ΔG°rxn, 1068–1069 ΔH °rxn estimation, 1060–1061 entropy changes, chemical reactions, 1064–1065 first law, 1057–1060 free energy, 1065–1068 second law, 1061–1064 THF See Tetrahydrofuran (THF) Thioacetals, 641–643 Thioesters Claisen condensation, 779–781 Thioethers, 522–523 Thioketals, 641–643 Thiols description, 521 physical properties, 521 reactions, 521–522 synthesis, 522–523, 1085 Torsional strain, 121 Transition metals elements asymmetric hydrogenation chiral binaphthyl compounds, 582–583 Noyori asymmetric reduction, 583–584 π complexes formation, 569 coordination complex and covalent bond, 567 coordination number and sphere, 567 geometry, 568–569 Gilman reagent (see Gilman reagent) Grubbs reaction, 584–586 Heck reaction, 576–579 ligands, 567 oxidation state, 567 palladium-catalyzed cross-coupling reactions, 573 retrosynthesis (see Retrosynthesis) Sonogashira reaction, 579–580 Suzuki coupling reaction, 574–576 triphenylphosphine, 568 Wilkinson catalyst, 580–582 Transition state, 97 Trimethylene oxides, 537 U α-β-Unsaturated aldehydes and ketones conjugation, 765–766 Unsaturation number, 167–168 V Valence-shell electron-pair repulsion (VSEPR) theory description, 15 geometry, central atom, 16 orbital hybridization, 32 van der Waals Forces (London Forces), 142 van der Waals radii, 121 van der Waals repulsion, 121 Vicinal diols, 213, 504–506 VSEPR theory See Valence-shell electron-pair repulsion (VSEPR) theory W Wilkinson catalyst, 180, 580–582 Williamson ether synthesis cyclization reactions, 544–545 formation, 543 SN2 reaction, 543 tert-butyl methyl ether, 543 Wittig reaction description, 646 mechanism, 647–648 organic synthesis, 648 phosphorus ylides, 646–647 polar aprotic solvents, 646 Wohl degradation, 937 1203 .. .Organic Chemistry: Structure, Mechanism, and Synthesis This Page Intentionally left blank Organic Chemistry: Structure, Mechanism, and Synthesis Robert J Ouellette Professor... verification of diagnoses and drug dosages should be made Library of Congress Cataloging-in-Publication Data Rawn, J David, 194 4Organic chemistry / J David Rawn, Robert J Ouellette – First edition... underlying general principles Understanding mechanisms of organic reactions is the key to understanding organic chemistry How are you going to learn organic chemistry? 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