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TENTH EDITION
International Student Version
T w. GRAHAM SOLOMONSUnive rsity of South Flurida
C IG . FRYHLEPacific Luth eran University
JOHN WILEY & SONS, INC.
Brief Contents
The Basics Bonding and Mo lecu lar Structure 1
Families of Carbon Compounds Funct ion al Groups, Int ermole cular Forces, and Inf rared (IR)Spectroscopy 53
An Introduction to Organic Reactions and Their Mechanisms Ac ids and Bases 98
l'Jomenclature and Conformations of Alkanes and Cycloalkanes 137
Stereochemistry Chiral Mo lecules 186
lonic Reactions Nucleophilic Substitution and Elimin at ion React ion s of A lky l Halides 230
7 Alkenes and Alkynes I Pro pert ies and Synthesis . Eliminat ion Reacti ons of Alky l Halides 285
Alkenes and Alkynes 11 Add it io n React ions 331
9 Nuclear Magnetic Resonance and Mass Spectrometry Tool s fo r Structure Determ inat ion 385
o Radical Reactions 459
, Alcohols and Ethers Synt hesis and Reacti on s 502
2 Alcohols From Carbonyl Compounds Oxidation-Reduction and O rga nometall ic Co mpounds 548
13 Conjugated Unsaturated Systems 585
14 Aromatic Compounds 632
Reactions of Aromatic Compounds 676
16 Aldehydes and Ketones Nucleophili c Addit ion to the Carbonyl Group 729
17 Carboxylic Acids and Their Derivatives Nucleo phil ic Add it ion-El imi nati on at th e Acyl Carbon 779
18 Reactions at the a Carbon of Carbonyl Compounds Enols and Eno lates 831
19 Condensation and Conjugate Addition Reactions of Carbonyl Compounds Mo re Chemistry of
Enolates 869
20 Amines 911
21 Phenols and Aryl Halides Nucleophi lic Aromatic Subst itut ion 964
Special Topic G Carbon-Carbon Bond-Forming and Other Reactions of Transition MetalOrganometallic Compounds G-1
22 Carbohydrates 1000
23 Lipids 1050
24 Amino Acids and Proteins 1084
25 Nucleic Acids and Protein Synthesis 1131
Answers to Selected Problems A-1
Glossary Gl-1
Photo Credits C-1
Index 1-1
Contents
1 The Basics Bondin g and Mo lecular Structu re 1
1.1 We Are Stardus t 2
1.2 Atomic Structure 2
1.3 The St ruc tura l Theory of Organic Chemistry 5
1.4 Chemical Bonds : The Octet Ru/e 7
1.5 How to Write Le wis Structures 91.6 Exceptions to th e Octet Rule 11
1.7 Formal Charges and How to Ca/cu/ate Them 13
1.8 Re sona nce Theory 15
1.9 Quantum Mechanics and A tomic Structure 20
1.10 Atomic Orbitals and Ele ctron Configuration 21
1.11 MoJecular Orbitals 23
1.12 The Structure of Me thane and Ethane : sp3 Hyb rid ization 2 5
THE CHEMISTRY OF . . . Calcu lated Molecu lar Model s: Electro n Density Surfaces 29
1.13 The Structure of Ethe ne (Ethy lene): sp2 Hyb rid ization 30
1.14 The Structure of Ethyn e (Acetylene): sp Hyb ridization 341.15 A Summary of Im p ortan t Co ncepts that Come from Q uantum Me chanics 36
1.16 Molecular Ge ometry: The Vale nce She ll Ele ctron Pair Re pulsion Mo d el 38
1.17 How to Interpret and Write Str uc tura l Formulas 41
1.1 8 App licatio ns of Basic Princip/ e s 46
Families of Carbon Compounds Functio nal Groups, Intermolecular Forces,
and Infrared (IR) Spectroscopy 53
2.1 Hyd ro carb ons: Re p res ent ativ e A lkanes, A lkenes, Alkyne s, an d A roma tic
Compounds 54
2.2 Polar Co vale nt Bonds 57
THE CHEMISTRY OF . . . Calcu lated Molecular Mod els: Mapsof Elect rostati c Potential 59
2.3 Polar and Nonpolar Mole cu /e s 60
2.4 Funct ion al Groups 62
2.5 A /kyl Halides or Ha/oalkanes 64
2.6 Alcoho/s 65
2.7 Ethers 67
THE CHEMISTRY OF . . . Ethers as Genera l Anesthetics 67
2.8 Amines 68
2.9 Aldehydes and Ketones 69
2.10 Carb oxyl ic Acids, Esters, and Am ides 70
2.11 Nitriles 72
2.12 Summary of Imp o rtan t Fami lie s of Org anic Compounds 722.13 Physical Properties and Mole cular Struc ture 73
THE CHEMISTRY OF . . . Fluorocarbons and Tefl on 78
2.14 Sum ma ry of A ttrac tive Elec tric Force s 82
THE CHEMISTRY OF . . . O rganic Templ ates Eng ineered to Mi mic Bone Growth 82
2.15 fnfrared Spectroscopy: A n Instrum en tal Method for Detecting Functional
Groups 83
2.16 /nterp reting IR Spectra 87
2. 17 A p p /icatio ns of Basic Princip/es 92
Contents
An Introduction to Organic Reactions and The ir MechanismsAcids and Bases 98
3.1 Reactions and Their Mechanisms 99
3.2 Acid-Base Reactions 101
3.3 Lewis Acids and Bases 102
3.4 Heterolysis of Bonds to Carbon : Carbocation s and Carbanions 104
THE CHEMISTRY OF .. . HOMOs and LUMOs in Reactions 105
3.5 How to Use Curved Arrows in Iflustrating Reactions 106
3.6 The Strength of Bransted-Lowry Acids and Bases: Ka and pKa 109
3.7 How to Predict the Outcome of Acid-Base Reactions 113
3.8 Relationships between Structure and Acidity 115
3.9 Energy Changes 119
3.10 The Relationship between the Equilibrium Constant and the Standard Free -EnergyChange, L'.G o 120
3.11 The Acidity of Carboxylic Acids 121
3.12 The Effect of the Solvent on Acidity 125
3.13 Organic Compounds as Bases 126
3.14 A Mechanism for an Organ ic Reaction 127
3.15 Acids and Bases in Nonaqueous Solutions 128
3.16 Acid-Base Reactions and the Synthesis of Deuterium- and Tritium-Labeled
Compounds 130
3.17 Applications of Basic Principles 131
Nomenclature and Conformations of Alkanes and Cycloalkanes 137
4.1 Introduction to Alkanes and Cycloalkanes 138
THE CHEMISTRY OF . .. Petroleum Refining 139
4.2 Shapes of Alkanes 140
4.3 IUPAC Nomenclature of A lkanes, Alkyl Halides, and Alcoho/s 142
4.4 How to Name Cycloalkanes 149
4.5 Nomenclature of Alkenes and Cycloalkenes 151
4.6 Nomenclature of Alkynes 154
4.7 Physical Properties of Alkanes and Cycloalkanes 154
THE CHEMISTRY OF .. . Pheromones: Communication by Mean s of Chemicals 156
4 .8 Sigma Bonds and Bond Rotation 157
4.9 Conformational Analysis of Butane 160
THE CHEMISTRY OF ... Muscle Action 162
4 .10 The Relative Stabilities of Cycloalkanes: Ring Strain 162
4.1 1 Conformations of Cyclohexane: The Chair and the Boat 163
THE CHEM ISTRY OF . .. Nanoscale Motors and Molecular Switches 166
4.12 Substituted Cyclohexanes: Axial and Eq uatorial Hydrogen Groups 167
4.13 Disubstituted Cycloalkanes: Cis-Trans Isomerism 171
4.14 Bicyclic and Polycyclic Alkanes 175
THE CHEMISTRY OF . . . Elemental Carbon 176
4.15 Chemical Reactions of Alkanes 177
4 .16 Synthesis of Alkanes and Cycloalkanes 177
4 .17 How to Gain Structural Information from Mo/ecular Fo rm ulas and the Index ofHydrogen Deficiency 178
4.19 Applications of Basic Principles 181
PLUS See SPECIALTO prC A: 13C NMR Spectr os copy - A Practi cal Introd uct ion in WileyPWS
Contents
5 Stereochemistry Chira l Moleeu les 186
5.1 Chirafity and Stereoch emistry 186
5 .2 Isomerism: Constitutionallsomers and Stereoisomers 188
5.3 Enantiom e rs and Chiral Molecules 190
5.4 A Single Chirality Center Causes a Moleeule to Be Chiral 191
THE CHEMISTRY OF . . . l.ife 's Molecular Handedness 193
5.5 More about the Biofogical Jmportanc e of Chirality 194
5.6 How to Test for Chirality: Planes of Symmetry 195
5.7 Nam ing Enantiomers: The R,S-System 196
5.8 Properties of Enantiomers: Optical Activity 20 1
5.9 The Origin of Optical Activity 205
5.10 The Synthesis of Chiraf M olecules 207
5 .11 Chiral Drugs 209
THE CHEMISTRY OF . .. Selective Binding of Drug Enant iomers to Left- and
Right-Handed Coiled DNA 21 1
5.12 Molecules with More than One Chirality Center 211
5.13 Fischer Proje ct ion Formufas 215
5 .14 Stereois om erism of Cyclic Compounds 217
5.15 Relating Configurations through Reactions in Whi ch No Bonds to the Ch irality
Center A re Broken 219
5.16 Separation of Enantiomers: Resolution 223
5.17 Compounds with ChiraJity Centers Other than Carbon 224
5.18 ChiraJ Mo Jec uJes th at Do Not Possess a ChiraJity Center 224
6 lonic Reactions Nucleophilic Substitut ion and Elimination React ions of A lkyl
Halides 230
6 .1 Organic Halides 231
6 .2 Nucle ophilic Substitution Reaction s 233
6.3 Nucleophiles 234
6.4 Leaving Groups 237
6. 5 Kine tics of a Nucie ophiJic Substitut ion Reacti on : An SN2 Reaction 237
6.6 A Mechan ism for the SN2 Reaction 238
6.7 Transition State Theory: Free-Energy Diag ram s 240
6 .8 The Stereochemistry of SN2 Reactions 243
6 .9 The Re action of tert-Butyl Chloride with Hydroxide Ion: An SN 1 Reaction 246
6.10 A Me chanism for th e SN1 Re action 247
6.11 Carb ocation s 248
6 .12 The Stereochemistry of SN1 Rea ctions 251
6 .13 Factors Affecting the Rates of SN1 and SN2 Reac tions 254
6 .14 Organic Synthesis: Functi on al Group Transformations Using SN2 Rea ctions 264
THE CHEMISTRY OF ... Bio log ical Methylat ion: A Bio log ical Nucieop hilic Subst it ut ionReact ion 266
6. 15 Elimination Reactions of Alkyl Halid es 268
6 .16 The E2 Reaction 269
6.17 The El Reaction 271
6.1 8 How to De te rm ine whether Substitution or Elimination Js Favored 273
6 .19 Overall Summary 276
7 Alkenes and Alkynes I Prop erties and Synthesis. Eliminat ion React ion s of
Alkyl Halides 285
7. 1 Introd uction 286
7.2 The (E)-(Z) System for Des ignating Alkene Diastereomers 286
7. 3 Relative Stabilit ies of Alkenes 288
Contents
7 .4 Cycloalkenes 290
1.5 Synthesi s of A lken es via Elim inat ion Re actions 291
7.6 Dehyd rohalo g en ation of Alkyl Halid e s 291
7 .7 Acid- Catalyz ed Dehydration of Alcohols 297
7.8 Carbocation Stability and the Occ urrenc e of Molecu/ar Rearrangem ents 303
7.9 The A cid ity of Term inal Alk ynes 307
7 .10 Synthe sis o f Alkyn e s by Elimin ation Reaction s 308
7 .11 Rep lace m ent of the Acetylenic Hydrog en Atom of Terminal Al kyn e s 310
7 .12 A lkylatio n of A lkynide An ions: Some Ge neral Principles of Stru ctu re
and Reactivity Illustrated 312
7.13 Hydro gen at ion of A lkenes 313
THE CHEMISTRY OF . . . Hydroge nation in the Foo d Indust ry 3137 .14 Hydrogenat io n: The Fun ct ion of th e Catalys t 314
7.15 Hydro ge nat ion of A/kyn e s 315
7.16 An Introdu ction to O rganic Synthesis 317
THE CHEMISTRY OF .. . From the Inorganic to the O rganic 321
Alkenes and Alkynes 11 Add it ion React ions 331
8.1 Addition Reactions of Alkene s 332
8.2 Ele ct rop hilic Addition of Hydrog e n Halid e s to A lke nes: Mechanism and
Markovn ikov's Rule 334
8.3 Stereochemistry of the lo nic Addition to an A lkene 339
8.4 Addition of Sulfuric Acid to A /ke nes 340
8.5 Addition of Water to Alken es : A cid- Catalyzed Hyd ration 340
8.6 Alcohol s from A lken e s th rou g h Oxymerc uration-Demercuratio n: Markovnikov
Addition 344
8.7 Alcohols from A lke nes throu gh Hyd rob oration-Oxid ation : A nti- Markovnikov Sy n
Hydratio n 347
8.8 Hydrobo ratio n: Synthesis of A lkylboranes 347
8.9 Oxidation and Hyd rolysis of A/k ybo ran e s 350
8.10 Summary of Alkene Hyd ration Me thod s 353
8.11 Protonolysis of A lkyb ora nes 353
8.12 Elect rop hilic Addition of Brom ine and Ch lorine to A lken es 354
THE CHEMISTRY OF . . . The Sea: A Treasury of Biol ogi cally Active Natural
Products 357
8.13 Stereo specific Re actions 358
8.14 Halohyd rin Formation 359
8.15 Divalent Carbon Compounds: Carbenes 36 1
8.16 Oxida tions of Al ken e s: Syn 1,2-Dihydroxylation 363
THE CHEMISTRY OF . . . Catalyt ic Asym metr ie Dih ydroxylation 3658.17 Ox idative Cleavage of Alken e s 365
8.1 8 Electrop hilic Addition of Bromine and Chlorine to A lkyn es 368
8.19 Addition of Hydrog e n Halide s to A lkyn es 369
8.20 Oxida tive Clea vage of Alk ynes 370
8.21 How to Plan a Synthesis: So me Approac hes and Exam pl e s 370
9 Nuclear Magnetic Resonance and Mass Spectrometry Tools for
Structure Determination 385
9. 1 Introdu ction 386
9 .2 Nu clear Magn etic Re sonan ce (N MR) Spec troscopy 386
9.3 How to Interpre t Proton NMR Sp e ctra 392
9.4 Nu clea r Sp in: The O rigin of the Sig nal 395
9.5 Dete cting the Signal: Fourie r Trans form NMR Spectrom eters 397
9.6 Shie /d ing and Deshie ld ing of Proton s 399
Contents
9 .7 The Chemical Shift 400
9 .8 Chemical Shift Equi valent an d Nonequivalent Proto ns 401
9 .9 Signal Splitting: Spin -Spin Coupling 405
9.10 Proton NMR Spectra and Rate Processes 415
9.11 Carb on-7 3 NMR Sp ectroscopy 417
9 .12 Two-Di m ension al (20) NMR Tech nique s 422
THE CHEMISTRY OF . . . Magnetie Resonanee Imaging in Me d ieine 425
9.13 A n Introduction to Mass Spectrometry 426
9.14 Formation of Ions: Elect ron Im p act lonizat ion 427
9.15 Depict ing the Molecu/ar Ion 427
9.16 Fragmentatio n 428
9.17 How to Determine Mole cu/ar Fo rm u/as and MolecuJar Weights Using Mass
Spectrometry 435
9.18 Mass Sp e ctrom ete r Instrument Desig ns 440
9.19 GC/MS Analysis 442
9.20 Mass Sp e ctrom e try of Biom o lec ule s 443
10 Radical Reactions 459
10.1 Introdu ction : How Rad icals Fo rm and Ho w Th ey React 460
10.2 Homolytic Bond Disso ciation Energie s (DW ) 461
10.3 Reaction s of A lkanes with Halog en s 465
10.4 Chlo rination of Metha ne : Me chanism of Re action 467
10.5 Chlorination of Methane: Energ y Changes 470
10.6 Halogenation of Higher Alkanes 477
10 .7 The Geometry of Al kyl Radicals 480
10 .8 Reactions that Generate Tetrahedral Chirality Centers 481
10 .9 Rad ical Ad ditio n to Al ke nes: The A nti-Marko vnik ov Ad dition of Hydrog enBromid e 484
10 .10 Rad ical Polym e rization of Alkenes: Chai n-Gro wth Polyme rs 486
10.11 Other Imp ortan t Radical Reactions 490
THE CHEMISTRY OF ... Calicheamiein 1', 1: A Rad ieal Device for Slicing t he Baekboneof DN A 492
THE CHEMISTRY OF ... Antioxidants 494
THE CHEMISTRY OF .. . Ozone Dep leti on and Ch lorofluo rocarbons (CFCs) 495
PlUDS See SPECIAL TOPIC B: Chain-Growth Polymers in WileyPLUS
11 Alcohols and Ethers Synthesis and Reaetions 502
11.1 Structure and Nom e nclature 503
11 .2 Physical Prop erties of Alcoho/s and Ethers 505
11.3 Imp ortant A lco ho/s and Eth ers 507
THE CHEMISTRY OF . . . Ethanol as a Biofuel 508
11.4 Synthesis of Alcoho/s from A lkenes 509
11 .5 Re action s of A lco ho /s 511
11 .6 A lcoho /s as Acids 513
11.7 Con ve rsion of A lcoho/s into Alkyl Halides 514
11 .8 Al ky l Halid e s from the Re actio n of A lcoho/s with Hydrog e n Halid es 514
11.9 A lkyl Halid e s from the React ion of A lco ho/s with PBr] or SOCI2 517
11 .10 Tosylates, Mesylates, and Triflates: Leaving Group Derivat ives of Alco ho/s 518THE CHEMISTRY OF . . . Al kyl Phosphates 52 1
11.11 Sy nthesis of Ethe rs 522
11.12 Re actions of Ethers 527
11.13 Ep oxid e s 528
THE CHEMISTRY OF . . . The Sharpl ess Asymmetrie Epoxidat ion 529
Content s
11.14 Reactions of Epoxid es 531THE CHEMISTRY OF . . . Epoxide s, Carcinogen s, and Bio logi cal Oxidation 533
11.15 Anti 1,2-Dihydroxy/ation of Alkenes via Epoxid es 535THE CHEMISTRY OF .. . Environmentally Friendly Al kene Oxidation Method s 537
11.16 Crown Ethers 537THE CHEMISTRY OF .. . Transport Anti b ioti cs and Crown Eth ers 539
11.17 Summary of Reaction s of Alkenes, Alcoh ols, and Ethe rs 540
12 Alcohols From Carbonyl Com pounds Oxidat ion-Reduction and
Organom etalli c Compounds 548
12.1 Structure of the Carbonyl Group 549
12.2 Oxidation-Reduction Reaction s in Organ ic Chem istry 55012.3 Alcohols by Reduct ion of Carbonyl Compounds 552
THE CHEMISTRY OF ... Alcohol Dehydrogenase - A BiochemicalHydride Reagent 554
THE CHEMISTRY OF ... Stereosel ecti ve Reductions of Carbo nyl Groups 555
12.4 Oxidation of Alcoh ols 55712.5 Organ ometallic Compounds 561
12.6 Preparation of Organ olithium and Organomagn esium Compounds 56212.7 Reactions of Organ olithium and Organ omagnesium Compounds 56312.8 Alcoho/s from Grignard Reagents 566
12.9 Protecting Groups 575
PLUo See the First Review Problem Set in WileyPLUS
13 Conjugated Unsaturated Systems 585
13.1 Introduct ion 586
13.2 Allylic Substitution and the Allyl Radical 586THE CHEMISTRY O F . . . All ylic Brominat ion 590
13.3 The Stability o f the Allyl Radical 59013.4 The Allyl Cation 59413.5 Resonance The ory Revisited 595
13.6 Alkadienes and Polyunsaturated Hydrocarbon s 599
13.7 1,3-Butadiene: Electron Delocalization 60013.8 The Stability of Conjugated Dienes 60213.9 Ultraviolet-Visible Spectroscopy 604
THE CHEMISTRY OF . . . The Photochem istry of Vision 609
13.10 Electrophific Attack on Conjugated Dienes: 1,4 Addition 61213.11 The Diels-Alder Reaction: A 1,4-Cycloaddition Reaction of Dienes 616
THE CHEMISTRY OF . . . Mole cule s with the Nobel Prize in Their Synth etic Lineage 620
14 Aromatic Compounds 632
14.1 The Discovery of Benzene 63314.2 Nomenclature of Benzene Derivatives 634
14. 3 React ions of Benzene 63714.4 The Kekule Structure for Benzene 63814.5 The Thermodynamic Stability of Benzene 63914.6 Modern Theo ries of the Structure of Benzene 64014.7 Hückel's Rule: The 4n + 2 11" Electron Rufe 64314.8 Other Aromatic Compounds 651
THE CHEMISTRY OF . .. Nanot ubes 655
14.9 Hete rocylic Aromati c Compou nds 655
14.10 Aromatic Compounds in Biochemistry 65714.11 Spectroscopy of Aromatic Compounds 660
Contents
THE CHEMISTRY OF . .. Sunscreen s (Catchi ng the Sun's Rays and What
Happens to Them) 664
15 Reactions of Aromatic Compounds 676
15.1 Efectroph ilic Aromatic Substitution Reaction s 67715 .2 A General Mechanism for Electrophilic Aromatic Substitution 67815.3 Halogenation of Benzene 68015.4 Nitration of Benzene 68115.5 Sulfonation of Benzene 68215.6 Friedel-Crafts Alkylation 68415.7 Friedel-Crafts A cyJation 68515.8 Limitations of Friede l-Crafts Reacti ons 68 7
15.9 Synthetic Applications of Friedel-Crafts Acylation s: The Clemmensen
Reduction 69015.10 Substituents Can Affect Both the Reactivity of the Ring and the Orientation
of the Incom ing Group 69 1
15.1 1 How Substituent s Affect Electrophilic Aromatic Substitution : A CIoser Look 69715.12 React ion s of the Side Chain of A lkylbenzene s 706
THE CHEMISTRY OF lodine Incorporation in Thyroxine Biosynthesis 707
THE CHEMISTRY OF Indu strial Styrene Synthe sis 709
15.13 Alkenylbenzenes 71215.14 Synthetic App/ications 71415.15 AJlyJic and Benzylic Halide s in Nucle op hilic Substitution Reactions 71715.16 Reduction of Aromatic Compounds 719
16 Aldehydes and Ketones Nucleophi lic Addition to the Carbonyl Group 729
16.1 Introduction 73016 .2 Nomenclature of Aldehydes and Keton es 73016 .3 Physicaf Properties 732
THE CHEMISTRY OF . .. A ldehydes and Ketones in Perfumes 733
16.4 Synthesis of Aldehydes 73316.5 Synthesis of Ketones 73816.6 Nucl eophilic Addition to the Carbo n-Oxygen Double Bond 74116.7 The Addition of Alcoh ols: Hemiacetals and Acetals 74416.8 The Addition of Primary and Secondary Amines 751
THE CHEMISTRY OF .. . A Very Versatile Vitamin , Pyridoxine (Vitamin B6) 753
16 .9 The Addition of Hydro gen Cyan ide: Cyanohydrins 755
16. 10 The Addition of Ylides: The W itt ig Rea ction 75716.11 Oxydation of Aldehydes 761
16.12 Chemical Analyse s for Aldehydes and Ketones 76116.13 Spectro scopic Properties of Aldehydes and Ketones 76216.14 Summary of Aldehyde and Ketone Addition Reactions 765
17 Carboxylic Acids and Their Derivatives Nucleoph ilic
Addition-Elimination at the Acyl Carbon 779
17 .1 Introduction 780
17.2 Nomenclature and Physical Properties 78017.3 Preparation of Carboxylic Acids 78917 .4 A cyl Substitution: Nucleophi/ic Addition-Elimination at the Acyl Carbon 79217 .5 Acyl Ch/orides 79417.6 Carboxylic A cid Anhydrides 79617.7 Esters 79717.8 Amides 804
Contents
THE CHEMISTRY OF ... Penicillins 81117.9 Derivatives of Carbonic Acid 812
17.10 Decarboxylation of Carboxylic Acids 814
17.11 Chem ical Tests for Acyl Compounds 816
17.12 Polyes ters and Polyamides: Step -Growth Polymers 817
17.13 Summary of the Reactions of Carboxy/ic Ac ids and Their Derivatives 818
Reactions at the a Carbon of Carbonyl Compounds Enols and
Enolates 831
18.1 The Acidity of the Cl' Hyd rog ens of Carbonyl Compounds: Enolate Anions 832
18.2 Keto and Enol Tautomers 833
18.3 Reactions via Enols and Eno /ate s 834
THE CHEMISTRY OF . . . Chloroform in Drinking Water 839
18.4 Lithium Enolate s 841
18.5 Enolates of ß -Dicarbonyl Co mpounds 844
18.6 Synthesis of Methyl Ketones: The A cetoacetic Ester Snythesis 845
18.7 Syn thesi s of Subs tituted A ce tic A cid s: The Malonic Este r Syn th esis 850
18.8 Further Reactions oi Active Hydrogen Compounds 853
18.9 Synthesis of Enamine s: Stark Enam ine React ions 85418.10 Summary of Enolate Chemistry 857
PLUQS See SPECIAL TOPIC C: Step-Growth Polymers in WileyPLUS
19 Condensation and Conjugate Addition Reactions of CarbonylCompounds More Chem istry of Eno lates 869
19.1 Introduction 870
19.2 The Claisen Condensation : The Synthesis of ß-Keto Este rs 870
19.3 ß -Dicarbony/ Compounds by A cy lat ion of Ke ton e Eno/at e s 875
19.4 Aldol React ions: Addition of Enolat e s and Eno /s to Aldehydes
and Ketones 876
THE CHEMISTRY OF . . . A Retro -A ldol Reaction in Glyco lysis-Div iding Assets toDouble the ATP Yield 878
19.5 Crossed A ld o l Condensations 882
19.6 Cycl izations via Aldol Condensations 888
19.7 Additions to Cl',ß-Unsaturated Aldehyd es and Ket ones 889
THE CHEMISTRY OF . .. Calicheamicin 'Yl1 Activation for Cleavage of DNA 894
19.8 The Mannich Re action 894
THE CHEMISTRY OF . . . A Suic ide Enzyme Substrate 89 5
19.9 Summary of Impo rtant Rea ct ions 897
p~QS See SPECIAL TOP IC 0: Thiols, Sulfur Ylides, and Disulfides in WileyPLUS
PLUQS See SPECIAL TOPIC E: Thiol Esters and Lip id Biosynthesis in WileyPLUS
20 Amines 911
20.1 Nomenclature 912
20.2 Phys ical Prop erti es and St ructure of Amines 913
20.3 Basicity of Amines: Amine Safts 915
THE CHEMISTRY OF . .. Biolo gically Important Amines 922
20.4 Preparation of Amines 924
20.5 Reaction s of Am ines 933
20.6 Reactions of Amines with Nitrous Aci d 935THE CHEMISTRY OF . . . N-Nitrosoami nes 936
20.7 Replacement React ions of Are nediazonium Salts 937
20.8 Coupling Reaction s o f Arenediazon ium Safts 941
)
Contents
20 .9 Reactions of Am ines with Su lfony l Ch lorides 943
THE CHEMISTRY OF . • • Che motherapy and Sulfa Drugs 944
20 .10 Synthesis of Sulfa Drug s 947
20.11 Analysis of Amin es 947
20.12 Elim inations Involving A mm onium Compounds 949
20.13 Summary of Preparations and Reactions o f Amines 950
PLUS See SPECIAL TOPIC F: Alkalo ids in Wi/eyPLUS
21 Phenols and Aryl Halides Nucleophi lic Aromatic Sub stitution 964
21.1 Structu re and Nom e nclature of Phenols 965
21.2 Naturally Occurring Phe nols 966
21 .3 Physical Properties of Phenols 966
21.4 Synthesis of Pheno ls 967
21.5 Reactions o f Phe nols as Acids 969
21.6 Other Reacti ons of the O-H Group of Phe no ls 972
21.7 C1eavage o f Alkyl Aryl Ethers 973
21 .8 Reactions of the Ben zen e Ring of Phen ols 973
THE CHEMISTRY OF ... Polyketide An ticancer Antibiotic Bio syn thesis 975
21.9 The Claise n Rearrang ement 977
21.10 Quino nes 978
THE CHEMISTRY OF .. . The Bombard ier Beet le's Noxio us Spray 979
21.11 Aryl Halides and Nu cleophilic Aromatic Subs titution 980
THE CHEMISTRY OF • • • Bacterial Dehalogenation of a PCB Deri vative 983
21.12 Spectrosco p ic A nalysis of Phen ols and A ryl Halides 988
THE CHEMISTRY OF . • • Aryl Halid es: Their Uses and Environ mental Concerns 989
PLUoS See the Second Review Problem Set in Wi/eyPLUS
SPECIAL TOPIC G: Carbon-Carbon Bond-Forming and Other Reactions of Transition
Metal Organometallic Compounds G-1--..PLUS See SPECIAL TOPIC H: Electrocyclic and Cycloaddition Reactions in Wi/eyPLUS
22 Carbohydrates 1000
22 .1 Introduction 1001
22.2 Monosaccharide s 1004
22.3 Mutarotat ion 1009
22.4 Glycoside Formation 1010
22.5 Other Reactions of Mon osaccharides 1013
22 .6 Oxida tion Reactions of Monosaccharide s 1016
22 .7 Reduction of Monosaccharide s: Aldito/s 1022
22 .8 Reaction s of Mon osaccharide s with Phenylhydrazine: Osazones 1022
22 .9 Synthesis and Degra dation of Mon osaccharides 1023
22 .10 The D Family of Aldoses 1025
22.11 Fischer's Proo f of the Con fig uration of D-(+ )-G/ucose 1027
22.12 Disaccharides 1029
THE CHEMISTRY OF ••• A rtifi cial Sweetener5 (How Sweet It 15) 1032
22.13 Polysaccharide s 1033
22 .14 Othe r Biolog ically Important Sugars 1037
22.15 Suga rs That Contain Nitroge n 1038
22 .16 G/yco lip ids and G/ycoproteins of the Cell Surface: Cell Recognition and theImmune System 1040
22 .17 Carbohydrate Antibiotics 1042
22 .18 Summary of Reactions of Carbohyd rates 1042
Contents
23 Lipids 1050
23.1 Int roduction 105123.2 Fatty Acids and Triacylglyce rols 1052
THE CHEMISTRY OF .. . O lestra and Other Fat Substitutes 1055
THE CHEMISTRY OF . . . Self-Assembled Mon olaye rs- Li pid s in Materials Science andBioengineering 1060
23.3 Terpenes and Te rp enoids 1061
23.4 Steroids 106423.5 Prostaglandins 1073
23.6 Phosph olip ids and Cell Membrane s 1074
THE CHEMISTRY OF . . . STEALTH® Liposomes fo r Drug Delivery 107723.7 Waxes 1078
24 Amino Acids and Proteins 1084
24.1 Introduct ion 1085
24.2 Amino A cids 1086
24.3 Syn thesis of er -A m ino A cids 1092
24.4 Polype ptid e s and Prote ins 109424.5 Prima ry Structure of Polypeptide s and Prot e ins 109724.6 Exam ples of Polypeptide and Protein Prim ary Struc ture 1101
THE CHEMISTRY OF . . . Sickle -Ce ll Anemia 110324.7 Polypep tide and Protein Synthes is 110424.8 Secondary, Tertiary, and Quate rnary Structure of Pro te ins 111024.9 Introduc tion to Enzymes 111524.10 Lyso zyme: Mode of A ction of an Enzyme 1116
THE CHEMISTRY OF ... Carbon ic Anhydrase: Shutt ling the Protons 111924.11 Serine Proteases 1120
24.12 Hemoglobin: A Conjuga te d Protein 1122THE CHEMISTRY OF . . . Some Catalytic Antibodi es 1123
24.13 Purificat ion and Analysis of Polypeptid es and Pro teins 112524.14 Proteom ics 1126
25 Nucleic Acids and Protein Synthesis 1131
25.1 Introduc tion 1132
25 .2 Nu cle otides and Nu cle o sid es 1133
25. 3 Laboratory Syn th es is of Nucleosides and Nu cle otide s 1137
25.4 De oxyrib onucleic Acid: DNA 113925.5 RNA and Protein Syn th esi s 114625 .6 Deter mini ng the Base Se quence of DNA: Th e Cha in-Termi nating
(Dideox ynucleotid e) Meth od 115525.7 Lab orato ry Synthesis of Of igonu cle otid es 1157
25 .8 The Polym erase Chain Rea ction 1158
25.9 Sequenc ing of the Hum an Gen ome: A n Instruction Bo ok for the Mole cule sof Life 1162
Answers to Sele cted Problems Ä-1
Glossary GL-1
Photo Credits C-1
Index 1·1
xviii Contents
Chapt er 3
Reaction of Water with Hydrogen Chloride: The Use of
Curved Arrows 107
Reaction of tert-Butyl Alcohol with Concentrated Aqueous
HCI 127
Chapter 6
Mechanism for the SN2 Reaction 239
The Stereochemistry of an SN2 Reaction 245
Mechanism for the SNl Reaction 248
The Stereochem istry of an SN1 Reaction 252
Mechanism for the E2 Reaction 270
Mechanism for the El Reaction 272
Chapter 7
E2 Elimination Where There Are Two Axial ßHydrogens 296
E2 Elimination Where the Only Axial ß Hydrogen Is from a
Less Stable Conformer 296
Acid-Catalyzed Dehydration of Secondary or Tertiary
Alcohols: An El Reaction 301
Dehydration of a Primary A lcohol : An E2 Reaction 302
Formation of a Rearranged Alkene during Dehydration of a
Primary Alcohol 306
Dehydroha logenation of vic-Dibromides to Form
Alkynes 309
The Dissolving Metal Reduction of an Alkyne 316
Chapter 8
Addition of a Hydrogen Halide to an Alkene 335
Addition of HBr to 2-Methylpropene 337
lonic Addition to an Alkene 339
Acid-Catalyzed Hydration of an Alkene 341
Oxymercuration 345
Hydroboration 349
Oxidation of Trialkylboranes 351
Addition of Bromine to an Alkene 356
Addition of Bromine to cis- and trans-2-Butene 359
Halohydrin Formation from an Alkene 360
Ozonolysis of an Alkene 368
Chapter 10
Hydrogen Atom Abstraction 461
Radical Addition to a 1T Bond 461
Radical Chlorination of Methane 468
Radical Halogenation of Ethane 477
The Stereochemistry of Chlorination at C2 of
Pentane 481
The Stereochemistry of Chlorination at C3 of
(5)-2-Chloropentane 482
Anti-Markovnikov Addition 485
Radical Polymerization of Ethene 487
Chapter 11
Conversion of an Alcohol into a Mesylate (an Alkyl
Methanesulfonate) 520
Intermolecular Dehydration of Alcohols to Form an
Ether 522
The Williamson Ether Synthesis 523
Ether Cleavage by Strong Acids 527
Alkene Epoxidation 529
Acid-Catalyzed Ring Opening of an Epoxide 531
Base-Catalyzed Ring Opening of an Epoxide 531
Chapter 12
Reduction of Aldehydes and Ketones by Hydride
Transfer 554
Chromate Oxidations: Formation of the Chromate
Ester 559
The Grignard Reaction 566
Chapt er 15
Electrophilic Aromatic Bromination 680
Nitration of Benzene 682
Sulfonation of Benzene 683
Friedel-Crafts Alkylation 684
Friedel-Crafts Acylation 687
Benzylic Halogenation 710
Birch Reduction 720
Chapter 16
Reduction of an Acyl Chloride to an Aldehyde 736
Reduction of an Ester to an Aldehyde 737
Reduction of a Nitrile to an Aldehyde 737
Addition of a Strong Nucleophile to an Aldehyde or
Ketone 742
Acid-Catalyzed Nucleophilic Addition to an Aldehyde or
Ketone 742
Hemiacetal Formation 744
Acid-Catalyzed Hemiacetal Formation 745
Base-Catalyzed Hemiacetal Formation 746
Hydrate Formation 746
Acid-Catalyzed Acetal Formation 748
Imine Formation 751
Enamine Formation 754
Cyanohydrin Formation 755
The Wittig Reaction 758
Chapter 17
Acyl Substitution by Nucleophilic Addition-
Elimination 792
Synthesis of Acyl Chlorides Using Thionyl Chloride 795
Acid-Catalyzed Esterification 798
Base-Promoted Hydrolysis of an Ester 801
DCC-Promoted Amide Synthesis 807
Acidi c Hydroly sis of an Amide 808
Basic Hydrolysis of an Amide 808
Acidi c Hydroly sis of a Nitrile 810
Basic Hydrol ysis of a Nitrile 810
Chapter 18
Base-Catalyzed Enoli zati on 835
Acid-Catalyzed Eno lization 835
Base-Promoted Halogenation o f Aldehydes and
Keto nes 837Acid- Catalyzed Halogenat ion of Ald ehyd es and
Keto nes 837
The Haloform React ion 839The Mal oni c Ester Synthesis of Subst ituted Acet ic
Acids 850
Chapter 19
The Claisen Con den sat ion 871
The Dieckmann Cond ensati on 873
The Al dol Addition 877
Dehyd rati on of the A ldol Ad dition Prod uct 879
The Acid- Cat alyzed Aldol React ion 880
A Directed A ldo l Synt hesis Using a Lithi um Enola te 886The Aldol Cycl ization 889
Contents
The Con jugate Additi on of HCN 891
The Conjugate Addition of an Amine 892
The Michae l Addi ti on 892
The Mann ich Reacti on 895
Chapter 20
Al kylati on of NH J 925Red uct ive Amin ati on 928
The Hofmann Rearrang em ent 931
Diazotization 936
Chapter 21
The Kolbe Reacti on 975
The SNAr Mechanism 982The Benzyne Elim inati on-Additi on Mechanism 985
Chapter 22
Form at ion of a Gl ycoside 1011
Hyd roly sis of a Glycoside 1012
Phenylo sazone Formati on 1023
Chapter 24
Formati on of an a- Amino nitr ile during the St recke r
Synthesis 1093
xix
THE CHEMISTRY OF ... SaXES
Chapter 1
Calculated Molecular M od els: Electron Density
Surfaces 29
Chapter 2
Calculated Mole cular Mo del s: Maps of Electrostat icPoten tia l 59
Ethers as General Anestheti cs 67
Fluorocarbon s and Teflon 78
Organic Tem pla tes Eng ineered to Mi mic Bone Growth 82
Chapter 3
HOMOs and LUMOs in Reacti on s 105
Chapter 4
Pet role um Refining 139
Pherom on es: Comm unicati on by Means of Chemica ls 156
Muscle Action 162Nanoscale Motors and Mole cular Switches 166
Elemen tal Carbon 176
Chapter 5
Life's Molecular Hand edness 193
Select ive Bind ing of Drug Enant iomers to Left - and Righ t
Handed Co iled DNA 211
Chapter 6
Biologi cal M et hylati on: A Biologi cal Nucleop hili c
Subst itution Reaction 266
Chapter 7
Hydroge nat ion in the Food Industry 31 3From the lnorgan ic to the O rganic 321
Chapter 8
The Sea: A Treasury of Biol ogi cal ly Activ e Natural
Produ cts 357
Cata lytic Asymmetric Dihyd roxylat ion 365
Chapter 9
Magn eti c Reson ance Imaging in Med icine 425
Chapter 10
Calicheamicin 1'11: A Radica l Device for Slicing th e
Backb one of DNA 492
Ant iox ida nts 494Ozone Depl etion and Chlo rof luorocarbons (CFCs) 495
Chapter 11
Ethanol as a Biofuel 508
Alk yl Phosph ates 521
xx Contents
The Sharpless Asymmetr ie Epoxidat ion 529
Epoxides, Carcinogens , and Biol og ieal
Ox idation 533
Environmentally Friend ly A lkene OxidationMethods 537
Transport Antib iot ies and Crown Ethers 539
Chapter 12
Aleohol Dehydroge nase-A Bioehemieal Hydride
Reag ent 554
Stereo selective Red uct ions of Carbonyl Groups 555
Chapter 13
Allylic Bromination 590
The Photochemistry of Vision 609
Molecules with the Nobel Prize in Their Synthet ic
Lineage 620
Chapter 14
Nanotubes 655
Sunscreens (Catehing the Sun's Rays and What Happens toThem) 664
Chapter 15
lod ine Incorporation in Thyroxine Biosynthesis 707Industr ial Styrene Synthesis 709
Chapter 16
Aldehydes and Ketones in Perfumes 733
A Very Versat ile Vitamin, Pyridoxine (Vitamin B6) 753
Chapter 17
Penicillins 81 1
Chapter 18
Chloroform in Drinking Water 839
Chapter 19
A Retro-A ldol Reaetion in Glyeolysis-Divid ing Assets toDoub le the ATP Yield 878
Cal icheam icin y,' Act ivat ion for Cleavage of DNA 894A Suicide Enzyme Substrate 895
Chapter 20
Biologi cally Important Amines 922N-Nit rosamines 936
Chemotherapy and Sulfa Drugs 944
Chapter 21
Poly ket id e Anti eaneer Antibi oti e Biosynthesis 975
The Bombardi er Beetle's No xious Spray 979
Baeterial Dehalogenati on of a PCB Derivati ve 983
Aryl Halides: Thei r Uses and Environme ntal Co ncerns 989
Chapter 22
Artificial Sweeteners (How Sweet It Is) 1032
Chapter 23
Oles tra and Other Fat Substitutes 1055
Self-Assembled Monolayers-Lipids in Materials Science
and Bioeng ineering 1060
STEALTH® Liposomes for Drug Delivery 1077
Chapter 24
Sickle-Cell Anemia 1103
Carbonic An hydra se: Shuttling the Protons 1119
Some Cata lyt ic Ant ibodies 1123
