Download Organic Chemistry

SIXTH EDITION
Organic Chemistry
Robert Thornton Morrison
Robert Neilson Boyd
New York University
Prentice Hall, Englewood Cliffs, New Jersey 07632
Contents
Preface xxiii
Acknowledgments
xxvii
PART ONE
The Fundamentals
/
Structure and Properties
1.1
1.2
1.3
1.4
1.5
1.6
1.7
1.8
1.9
1.10
1.11
1.12
1.13
1.14
1.15
1.16
1.17
1.18
1.19
1.20
1.21
Organic chemistry 7
The structural theory 3
The chemical bondbefore 1926 4
Quantum mechanics 5
Atomic Orbitals 6
Electronic connguration. Pauli exclusion principle 8
Molecular Orbitals 9
The covalent bond 9
Hybrid Orbitals: s/> 77
Hybrid Orbitals: sp2 13
Hybrid Orbitals: sp3 15
Unshared pairs of electrons 7 7
Intramolecular forces 20
Bond dissociation energy. Homolysis and heterolysis 21
Polarity ofbonds 23
Polarity ofmolecules 23
Structure and physical properties 26
Melting point 27
Intermolecular forces 28
Boiling point 30
Solubility 31
V
CONTENTS
1.22
1.23
Acids and bases
Isomerism 36
Methane
2.1
2.2
2.3
2.4
2.5
2.6
2.7
2.8
2.9
2.10
2.11
2.12
2A3
2.14
2.15
2.16
2.17
2.18
2.19
2.20
2.21
2.22
2.23
2.24
2.25
2.26
2.27
2.28
2.29
2.30
3.4
3.5
3.6
3.7
3.8
3.9
3.10
Energy of Activation.
Transition
State
Hydrocarbons 39
Structure of methane 40
Physical properties 41
Source 41
Reactions 42
Oxidation. Heat of combustion 42
Chlorination: a Substitution reaction 43
Control of chlorination 44
Reaction with other halogens: halogenation 44
Relative reactivity 45
Reaction mechanisms 45
Mechanism of chlorination. Free radicals 46
Chain reactions 48
Inhibitors 49
Heat of reaction 50
Energy of activation 57
Progress of reaction: energy changes 52
Rate of reaction 55
Relative rates of reaction 58
Relative reactivities of halogens toward methane 59
An alternative mechanism for halogenation 61
Structure of the methyl radical. jp 2 Hybridization 64
Transition State 65
Reactivity and development of the transition State 67
Chlorofluorocarbons and the ozone shield 69
Molecular formula: its fundamental importance 72
Qualitative elemental analysis 72
Quantitative elemental analysis: carbon, hydrogen, and
halogen 73
Empirical formula 74
Molecular weight. Molecular formula 74
Alkanes
3.1
3.2
3.3
33
Free-Radical
Substitution
Classification by structure: the family 77
Structure ofethane 78
Free rotation about the carbon-carbon Single bond.
Conformations. Torsional strain 79
Propane and the butanes 83
Conformations of n-butane. Van der Waals repulsion
Higher alkanes. The homologous series 86
Nomenclature 87
Alkyl groups 88
Common namesof alkanes 90
IUPAC names of alkanes 90
CONTENTS
3.11
3.12
3.13
3.14
3.15
3.16
3.17
3.18
3.19
3.20
3.21
3.22
3.23
3.24
3.25
3.26
3.27
3.28
3.29
3.30
3.31
3.32
3.33
3.34
4
vii
Classes of carbon atoms and hydrogen atoms 92
Physical properties 92
Industrial source 94
Industrial source vs. laboratory preparation 96
Preparation 97
The Grignard reagent: an organometallic Compound 99
Coupling of alkyl halides with organometallic Compounds 707
Reactions 702
Halogenation 704
Mechanismof halogenation 706
Orientation of halogenation 707
Relative reactivitiesof alkanestoward halogenation 709
Ease ofabstraction of hydrogen atoms. Energy of activation 770
Stability of free radicals 777
Ease offormation of free radicals 113
Transition State for halogenation 775
Orientation and reactivity 114
Reactivity and selectivity 775
Non-rearrangement of free radicals. Isotopic tracers 776
Combustion 775
The greenhouse efFect 779
Pyrolysis: cracking 720
Determination ofstructure 727
Analysisof alkanes 722
Stereochemistry I. Stereoisomers
4.1
4.2
4.3
4.4
4.5
4.6
4.7
4.8
4.9
4.10
4.11
4.12
4.13
4.14
4.15
4.16
4.17
4.18
4.19
4.20
4.21
4.22
Stereochemistry and stereoisomerism 725
Isomer number and tetrahedral carbon 726
Optical activity. Plane-polarized light 725
The Polarimeter 725
Specific rotation 729
Enantiomerism: the discovery 750
Enantiomerism and tetrahedral carbon 757
Enantiomerism and optical activity 755
Prediction of enantiomerism. Chirality 755
The chiral center 755
Enantiomers 756
The racemic modification 755
Optical activity: a closer look 759
Configuration 140
Specification of configuration: R and S 140
Sequence rules 141
Diastereomers 144
Meso structures 146
Specification ofconfiguration: morethan one chiral center 148
Conformational isomers 149
Reactions involving stereoisomers 750
Generation of a chiral center. Synthesis and optical activity 757
viii
CONTENTS
4.23
4.24
4.25
4.26
4.27
4.28
5
Alkyl Halides
5.1
5.2
5.3
5.4
5.5
5.6
5.7
5.8
5.9
5.10
5.11
5.12
5.13
5.14
5.15
5.16
5.17
5.18
5.19
5.20
5.21
5.22
5.23
5.24
6
Reactionsofchiralmolecules. Bond-breaking 153
Reactionsofchiral molecules. Relating configurations 154
Optical purity 156
Reactions of chiral molecules. Generation of a second chiral
center 756
Reactions of chiral molecules with optically active reagents.
Resolution 158
Reactions of chiral molecules. Mechanism of free-radical
chlorination 760
Nucleophilic Aliphatic
Homolytic and heterolytic chemistry 765
Relative ratesofcompeting reactions 766
Structure. The functional group 767
Classification and nomenclature 765
Physical properties 769
Preparation 770
Reactions. Nucleophilic aliphatic Substitution 772
Nucleophilic aliphatic Substitution. Nucleophiles and leaving
groups 775
Rate of reaction: efFect of concentration. Kinetics 777
Kinetics of nucleophilic aliphatic Substitution. Second-order and
first-order reactions 7 78
Nucleophilic aliphatic Substitution: duality of mechanisms 7 79
The SN2 reaction: mechanism and kinetics 757
The SN2 reaction: stereochemistry. Inversion of
configuration 182
The SN2 reaction: reactivity. Steric hindrance 755
The SNI reaction: mechanism and kinetics. Rate-determining
step 755
Carbocations 797
Structure of carbocations 7 93
The SNI reaction: stereochemistry 194
Relative stabilities of carbocations 7 96
Stabilization of carbocations. Accommodation of Charge. Polar
effects 799
The SNI reaction: reactivity. Ease of formation of
carbocations 200
Rearrangement of carbocations 203
S„,2 BS. V
208
Analysisof alkyl halides 277
Alcohols and Ethers
6.1
6.2
6.3
6.4
6.5
Substitution
Introduction 275
Structure of alcohols 214
Classification of alcohols 274
Nomenclature of alcohols 275
Physical properties of alcohols 275
CONTENTS
ix
6.6
6.7
6.8
6.9
6.10
6.11
6.12
6.13
6.14
6.15
Industrial source 218
Fermentation of carbohydrates 219
Fuel from carbohydrates. Carbon dioxide balance 279
Ethanol 221
Preparation of alcohols 222
Reactionsof alcohols 224
Alcohols as acids and bases 227
Reaction of alcohols with hydrogen halides. Acid catalysis
Formation ofalkyl sulfonates 233
Oxidationof alcohols 235
6.16
6.17
6.18
6.19
6.20
6.21
6.22
6.23
Structure and nomenclature of ethers 23 7
Physical properties of ethers 238
Industrial sources of ethers. Dehydration of alcohols
Preparation of ethers 240
Preparation of ethers. Williamson synthesis 241
Reactionsof ethers. Cleavageby acids 242
Analysisof alcohols 243
Analysisof ethers 244
229
ETHERS
7
Role of the Solvent
7.1
12
7.3
7.4
7.5
7.6
7.7
7.8
7.9
7.10
8
Secondary
Bonding
Role of the solvent 249
Secondary bonding 250
Solubility: non-ionic solutes 252
Solubility: ionic solutes. Protic and aprotic solvents. Ion pairs 254
The SNI reaction: role of the solvent. Ion-dipole bonds 258
The SN2 reaction: role of the solvent. Protic and aprotic
solvents 261
The SN2 reaction: phase-transfer catalysis 264
SN2 VS. SNI: effect of the solvent 267
Solvolysis. Nucleophilic assistance by the solvent 268
The medium: a message 271
Alkenes I. Structure and Preparation
8.1
8.2
8.3
8.4
8.5
8.6
8.7
8.8
8.9
8.10
8.11
8.12
8.13
8.14
238
Elimination
Unsaturated hydrocarbons 273
Structure ofethylene. The carbon-carbon double bond 273
Propylene 276
Hybridization and orbital size 276
The butylenes 277
Geometrie isomerism 279
Higher alkenes 282
Namesof alkenes 282
Physical properties 283
The organic chemistry of vision 285
Industrial source 287
Preparation 287
Dehydrohalogenation ofalkyl halides: 1,2-elimination 290
Kinetics of dehydrohalogenation. Duality of mechanism 293
CONTENTS
8.15
8.16
8.17
8.18
8.19
8.20
8.21
8.22
8.23
8.24
8.25
8.26
The E2 mechanism 294
Evidence for the E2 mechanism. Kinetics and absence of
rearrangements 294
Evidence for the E2 mechanism. Isotope effects 295
Evidence for the E2 mechanism. Absence of hydrogen
exchange 297
Evidence for the E2 mechanism. The element effect 299
The E2 reaction: orientation and reactivity 300
The El mechanism 303
Evidence for the El mechanism 304
The El reaction: orientation 306
Elimination: E2 vs. El 308
Elimination vs. Substitution 308
Dehydration ofalcohols 310
9 Alkenes IL Reactions of the Carbon-Carbon Double Bond
Electrophilic and Free-Radical Addition
9.1
9.2
9.3
9.4
9.5
9.6
9.7
9.8
9.9
9.10
9.11
9.12
9.13
9.14
9.15
9.16
9.17
9.18
9.19
9.20
9.21
9.22
9.23
9.24
9.25
9.26
9.27
Reactions of alkenes 317
Reactions at the carbon-carbon double bond. Addition 317
Hydrogenation. Heat ofhydrogenation 323
Heat ofhydrogenation and stabilityof alkenes 326
Addition of hydrogen halides. Markovnikov's rule. Regioselective
reactions 327
Addition of hydrogen bromide. Peroxide effect 330
Addition ofsulfuricacid 331
Addition of water. Hydration 332
Electrophilic addition: mechanism 332
Electrophilic addition: rearrangements 334
Electrophilic addition: orientation and reactivity 335
Addition of halogens 339
Mechanism of addition of halogens 340
Halohydrin formation: addition of the elements of hypohalous
acids 342
Addition of alkenes. Dimerization 343
Addition of alkanes. Alkylation 344
Oxymercuration-demercuration 346
Hydroboration-oxidation 347
Orientation ofhydroboration 348
Mechanism ofhydroboration 349
Free-radical addition. Mechanism of the peroxide-initiated
addition ofHBr 351
Orientation of free-radical addition 352
Other free-radical additions 355
Free-radical polymerization of alkenes 356
Hydroxylation. Formation ofl,2-diols 357
Cleavage: determination of structure by degradation.
Ozonolysis 358
Analysisof alkenes 360
xi
CONTENTS
10 Stereochemistry II. Stereoselective and Stereospecific
Reactions
10.1
10.2
10.3
10.4
10.5
10.6
10.7
11
Organic chemistry in three dimensions 36 7
Stereochemistry of addition of halogens to alkenes. syn- and antiaddition 368
Mechanism of addition of halogens to alkenes 372
Stereochemistry of the E2 reaction. syn- and antt'-elimination 377
Stereospecific reactions 381
Stereoselectivity vs. stereospecificity 382
A look ahead 383
Conjugation and Resonance
11.1
11.2
11.3
11.4
11.5
11.6
11.7
11.8
11.9
11.10
11.11
11.12
11.13
11.14
11.15
11.16
11.17
11.18
11.19
11.20
11.21
11.22
11.23
11.24
11.25
11.26
Dienes
The carbon-carbon double bond as a substituent 387
Free-radical halogenation of alkenes: Substitution vs.
addition 388
Free-radical Substitution in alkenes: orientation and
reactivity 390
Free-radical Substitution in alkenes: allylic rearrangement 392
Symmetry of the allyl radical 393
The theoryof resonance 394
The allyl radical as a resonance hybrid 395
Stability of the allyl radical 397
Orbital picture of the allyl radical 397
Using the resonance theory 399
Resonance stabilization of alkyl radicals. Hyperconjugation 401
The allyl cation as a resonance hybrid 402
Nucleophilic Substitution in allylic Substrates: SNI . Reactivity.
Allylic rearrangement 404
Stabilization of carbocations: the resonance effect 406
Nucleophilic Substitution in allylic Substrates: SN2 407
Nucleophilic Substitution in vinylic Substrates. Vinylic
cations 407
Dienes: structure and properties 409
Stability of conjugated dienes 410
Resonance in conjugated dienes 411
Resonance in alkenes. Hyperconjugation 413
Ease of formation of conjugated dienes: orientation of
elimination 414
Electrophilic addition to conjugated dienes. 1,4-Addition 414
1,2- vs. 1,4-Addition. Rate vs. equilibrium 417
Free-radical polymerization of dienes. Rubber and rubber
Substitutes 419
Isoprene and the isoprene rule 421
Analysisof dienes 421
12 Alkynes
12.1
12.2
12.3
Introduction 425
Structure ofacetylene. The carbon-carbon triple bond
Higher alkynes. Nomenclature 428
425
xii
CONTENTS
12.4 Physicalpropertiesofalkynes 428
12.5
Industrial source of acetylene 429
12.6
Preparationofalkynes 429
12.7
Reactionsofalkynes 430
12.8
Reduction of alkenes 433
12.9
Electrophilic addition to alkynes 434
12.10 Hydration of alkynes. Tautomerism 435
12.11 Acidity of alkynes. Very weak acids 436
12.12 Reactions of metal acetylides. Synthesis of alkynes 438
12.13 Formation of carbon-carbon bonds. Role played by
organometallic Compounds 439
12.14 Analysis of alkynes 440
13 Cyclic Aliphatic Compounds
13.1
13.2
13.3
13.4
13.5
13.6
13.7
13.8
13.9
13.10
13.11
13.12
13.13
13.14
13.15
13.16
13.17
13.18
13.19
13.20
13.21
13.22
13.23
13.24
13.25
14
Open-chain and cyclic Compounds 443
Nomenclature 443
Industrial source 446
Preparation 447
Reactions 448
Reactions of small-ring Compounds. Cyclopropane and
cyclobutane 449
Baeyer strain theory 450
Heats of combustion and relative stabilities of the
cycloalkanes 450
Orbital picture of angle strain 453
Factors affecting stability of conformations 454
Conformations of cycloalkanes 455
Equatorial and axial bonds in cyclohexane 460
Stereoisomerism of cyclic Compounds: eis and trans isomers 463
Stereoisomerism of cyclic Compounds. Conformational
analysis 466
Stereochemistry of elimination from alicyclic Compounds 471
Carbenes. Methylene. Cycloaddition 473
Addition of substituted carbenes. 1,1 -Elimination 476
Cyclic ethers 478
Crown ethers. Host-guest relationship 4 78
Epoxides. Structure and preparation 481
Reactions of epoxides 482
Acid-catalyzed cleavage of epoxides. awft'-Hydroxylation 483
Base-catalyzed cleavage of epoxides 485
Orientation of cleavage of epoxides 485
Analysis of alicyclic Compounds 487
Aromaticity
14.1
14.2
14.3
14.4
Benzene
Aliphatic and aromatic Compounds 493
Structure of benzene 494
Molecular formula. Isomer number. Kekule structure 494
Stability of the benzene ring. Reactions of benzene 497
CONTENTS
14.5
14.6
14.7
14.8
14.9
14.10
14.11
14.12
14.13
xiii
Stability of the benzenering.Heats of hydrogenation and
combustion 498
Carbon-carbon bond lengths in benzene 499
Resonance structure of benzene 500
Orbital pictureof benzene 501
Representation ofthe benzene ring 503
Aromatic character. The Hückel 4w + 2 rule 504
Nomenclature of benzene derivatives 508
Polynuclear aromatic hydrocarbons. Naphthalene 510
Quantitative elemental analysis: nitrogen and sulfur 575
15 Electrophilic Aromatic Substitution
15.1
15.2
15.3
15.4
15.5
15.6
15.7
15.8
15.9
15.10
15.11
15.12
15.13
15.14
15.15
15.16
15.17
15.18
15.19
15.20
15.21
Introduction 577
Effect of substituent groups 579
Determination of orientation 520
Determination of relative reactivity 527
Classification of substituent groups 522
Orientation in disubstituted benzenes 522
Orientation and synthesis 524
Mechanism of nitration 525
Mechanism of sulfonation 527
Mechanism of Friedel-Crafts alkylation 528
Mechanism of halogenation 529
Desulfonation. Mechanism of protonation 529
Mechanism of electrophilic aromatic Substitution: a
summary 530
Mechanism of electrophilic aromatic Substitution: the two
steps 557
Reactivity and orientation 535
Theory of reactivity 536
Theory of orientation 538
Electron release via resonance 540
Effect of halogen on electrophilic aromatic Substitution 542
Relation to other carbocation reactions 544
Electrophilic Substitution in naphthalene 545
16 Aromatic-Aliphatic Compounds Arenes and Their
Derivatives
16.1
16.2
16.3
16.4
16.5
16.6
16.7
16.8
16.9
16.10
The aromaticringas a substituent 549
Aromatic-aliphatic hydrocarbons: arenes 549
Structure and nomenclature of arenes and their derivatives 557
Physical properties 552
Industrial source of alkylbenzenes 555
Preparation of alkylbenzenes 556
Friedel-Crafts alkylation 557
Mechanism of Friedel-Crafts alkylation 558
Limitations of Friedel-Crafts alkylation 567
Reactions of alkylbenzenes 567
xiv
CONTENTS
16.11 Oxidation of alkylbenzenes 563
16.12 Electrophilic aromatic Substitution in alkylbenzenes 564
16.13 Halogenation of alkylbenzenes: ring vs. side chain 565
16.14 Side-chain halogenation of alkylbenzenes 566
16.15 Resonance stabilization of the benzyl radical 568
16.16 Triphenylmethyl: a stable free radical 5 70
16.17 Stability of the benzyl cation 5 74
16.18 Nucleophilic Substitution in benzylic Substrates 5 75
16.19 Preparation of alkenylbenzenes. Conjugation with the ring 5 76
16.20 Reactionsof alkenylbenzenes 578
16.21 Addition to conjugated alkenylbenzenes 579
16.22 Alkynylbenzenes 580
16.23 Analysisof arenes 580
17
Spectroscopy and Structure
17.1
17.2
17.3
17.4
17.5
17.6
17.7
17.8
17.9
17.10
Determination of structure: spectroscopic methods 585
The mass spectrum 586
The electromagnetic spectrum 589
The infrared spectrum 590
Infrared spectra of hydrocarbons 592
Infrared spectra ofalcohols 594
Infrared spectra ofethers 596
The ultraviolet spectrum 597
The nuclear magnetic resonance (NMR) spectrum 600
NMR. Number of signals. Equivalent and non-equivalent
protons 607
17.11 NMR. Positions of signals. Chemical shift 604
17.12 NMR. Peak area and proton counting 609
17.13 NMR. Splitting of signals. Spin-spin coupling 610
17.14 NMR. Coupling constants 620
17.15 NMR. Complicated spectra. Deuterium labeling 623
17.16 Equivalence of protons: a closer look 625
17.17 Carbon-13 NMR (CMR) spectroscopy 629
17.18 CMR. Splitting 630
17.19 CMR. Chemical shift 634
17.20 NMR and CMR spectra of hydrocarbons 639
17.21 NMR and CMR spectra ofalkylhalides 640
17.22 NMR and CMR spectra of alcohols and ethers. Hydrogen
bonding. Proton exchange 640
17.23 The electron spin resonance (ESR) spectrum 642
18 Aldehydes and Ketones Nucleophilic Addition
18.1
18.2
18.3
18.4
18.5
18.6
Structure 657
Nomenclature 658
Physical properties 660
Preparation 667
Preparation of ketones by Friedel-Crafts acylation 666
Preparation of ketones by use of organocopper Compounds
668
CONTENTS
18.7
18.8
18.9
18.10
18.11
18.12
18.13
18.14
18.15
18.16
18.17
18.18
18.19
Reactions. Nucleophilic addition 669
Oxidation 675
Reduction 677
Addition of Cyanide 678
Addition of derivatives of ammonia 6 79
Addition ofalcohols. Acetal formation 680
Cannizzaro reaction 683
Addition ofGrignardreagents 685
Products of the Grignard synthesis 686
Planning a Grignard synthesis 688
Syntheses using alcohols 692
Limitations of the Grignard synthesis 695
Tetrahydropyranyl (THP) ethers: the use of a protecting
group 696
18.20 Analysisofaldehydesandketones 697
18.21 Iodoformtest 697
18.22 Analysisof 1,2-diols. Periodicacidoxidation 699
18.23 Spectroscopic analysisofaldehydesandketones 700
19 Carboxylic Acids
19.1
Structure 713
19.2
Nomenclature 714
19.3
Physical properties 717
19.4
Saltsof carboxylic acids 775
19.5
Industrial source 719
19.6
Preparation 720
19.7
Grignard synthesis 723
19.8
Nitrile synthesis 724
19.9
Reactions 725
19.10 Ionization of carboxylic acids. Acidity constant 729
19.11 Equilibrium 730
19.12 Acidity of carboxylic acids 732
19.13 Structure of carboxylate ions 733
19.14 Effect of substituents on acidity 735
19.15 Conversion into acid Chlorides 73 7
19.16 Conversion into esters 737
19.17 Conversion into amides 740
19.18 Reduction of acids to alcohols 740
19.19 Halogenation ofaliphatic acids. Substituted acids 741
19.20 Dicarboxylic acids 742
19.21 Analysisof carboxylic acids. Neutralizationequivalent 744
19.22 Spectroscopic analysisof carboxylic acids 745
20 Functional Derivatives of Carboxylic Acids Nucleophilic
Acyl Substitution
20.1
20.2
20.3
Structure 753
Nomenclature 754
Physical properties 754
xv
xvi
CONTENTS
20.4
20.5
Nucleophilic acyl Substitution. Role of the carbonyl group
Nucleophilic Substitution: alkyl vs. acyl 759
20.6
20.7
20.8
Preparationofacid Chlorides 760
Reactionsofacid Chlorides 761
Conversion ofacid Chlorides into acid derivatives
ACID CHLORIDES
762
ACID ANHYDRIDES
20.9
20.10
Preparation ofacid anhydrides 763
Reactions of acid anhydrides 764
AMIDES
20.11
20.12
20.13
20.14
Preparation of amides 766
Reactions of amides 766
Hydrolysisof amides 767
Imides 767
ESTERS
20.15
20.16
20.17
20.18
20.19
20.20
20.21
20.22
20.23
20.24
20.25
21
Carbanions I
21.1
21.2
21.3
21.4
21.5
21.6
21.7
21.8
21.9
21.10
21.11
21.12
22
Preparation ofesters 768
Reactions ofesters 770
Alkaline hydrolysis ofesters 773
Acidic hydrolysis ofesters 776
Ammonolysis ofesters 778
Transesterification 778
Reaction ofesters with Grignard reagents 779
Reduction ofesters 780
Functional derivatives ofcarbonic acid 750
Analysis of carboxylic acid derivatives. Saponification
equivalent 784
Spectroscopic analysis of carboxylic acid derivatives 785
Aldol and Claisen
Condensations
Acidity of a-hydrogens 797
Reactions involving carbanions 799
Base-promoted halogenation of ketones 802
Acid-catalyzedhalogenation of ketones. Enolization 804
Aldol condensation 805
Dehydration of aldol products 807
Use of aldol condensation in synthesis 808
Crossed aldol condensation 809
Reactions related to the aldol condensation 810
The Wittig reaction 811
Claisen condensation. Formation of yS-keto esters 813
Crossed Claisen condensation 816
Amines I. Preparation and Physical Properties
22.1
22.2
22.3
22.4
22.5
Structure 821
Classification 821
Nomenclature 822
Physical properties ofamines
Salts ofamines 823
823
755
CONTENTS
22.6
22.7
22.8
22.9
22.10
22.11
22.12
22.13
22.14
22.15
22.16
22 AI
xvii
Stereochemistry of nitrogen 825
Industrial source 827
Preparation 828
Reductionof nitro Compounds 832
Ammonolysis of halides 832
Reductive amination 834
Hofmann degradation of amides 836
Synthesis of secondary and tertiary amines 836
Heterocyclic amines 837
Hofmann rearrangement. Migration to electron-deficient
nitrogen 838
Hofmann rearrangement. Stereochemistry at the migrating
group 840
Hofmann rearrangement. Timingof the steps 841
23 Amines II. Reactions
23.1
23.2
23.3
23.4
23.5
23.6
23.7
23.8
23.9
23.10
23.11
23.12
23.13
23.14
23.15
23.16
23.17
23.18
23.19
23.20
23.21
Reactions 845
Basicity of amines. Basicity constant 849
Structure and basicity 850
Effect of substituents on basicity of aromatic amines 853
Quaternary ammonium salts. Hofmann elimination 854
E2 elimination: Hofmann orientation. The variable E2 transition
State 855
Conversion of amines into substituted amides 857
Ring Substitution in aromatic amines 860
Sulfonation of aromatic amines. Dipolar ions 862
Sulfanilamide. The sulfa drugs 863
Reactions of amines with nitrous acid 864
Diazonium salts. Preparation and reactions 866
Diazonium salts. Replacement by halogen. Sandmeyer
reaction 869
Diazonium salts. Replacement by —CN. Synthesis of carboxylic
acids 870
Diazonium salts. Replacement by —OH. Synthesis of
phenols 870
Diazonium salts. Replacement by —H 871
Syntheses using diazonium salts 871
Couplingof diazonium salts. Synthesis ofazo Compounds 873
Analysisof amines. Hinsberg test 876
Analysisof substituted amides 877
Spectroscopic analysisof amines and substituted amides 877
24 Phenols
24.1
24.2
24.3
24.4
24.5
Structure and nomenclature 889
Physical properties 890
Salts of phenols 893
Industrial source 893
Rearrangement of hydroperoxides. Migration to electrondeficient oxygen 895
xviii
CONTENTS
24.6
24.7
24.8
24.9
24.10
24.11
24.12
24.13
24.14
24.15
24.16
24.17
Rearrangementofhydroperoxides. Migratory aptitude 896
Preparation 898
Reactions 899
Acidityof phenols 903
Ester formation. Fries rearrangement 905
Ring Substitution 906
Kolbe reaction. Synthesisofphenolicacids 908
Reimer-Tiemann reaction. Synthesis of phenolic aldehydes.
Dichlorocarbene 908
Formation ofarylethers 909
Reactions of aryl ethers 911
Analysisof phenols 912
Spectroscopic analysisof phenols 912
25 CarbanionsII Malonic Ester and Acetoacetic Ester Syntheses
25.1
25.2
25.3
25.4
25.5
25.6
25.7
25.8
Carbanions in organic synthesis 923
Malonic ester synthesis of carboxylicacids 924
Acetoacetic ester synthesis of ketones 92 7
Decarboxylation of /j-keto acids and malonic acids 930
Direct and indirect alkylation ofesters and ketones 931
Synthesis of acids and esters via 2-oxazolines 932
Organoborane synthesis of acids and ketones 933
Alkylation ofcarbonyl Compounds via enamines 935
PART TWO
Special Topics
26
Aryl Halides
26.1
26.2
26.3
26.4
26.5
26.6
26.7
26.8
26.9
26.10
26.11
26.12
26.13
26.14
26.15
Nucleophilic Aromatic
Substitution
Structure 943
Physical properties 944
Preparation 946
Reactions 948
Low reactivity of aryl and vinyl halides 949
Structure of aryl and vinyl halides 950
Nucleophilic aromatic Substitution: bimolecular
displacement 952
Bimolecular displacement mechanism for nucleophilic aromatic
Substitution 955
Reactivity in nucleophilic aromatic Substitution 956
Orientation in nucleophilic aromatic Substitution 957
Electron withdrawal by resonance 958
Evidence for the two Steps in bimolecular displacement 959
Nucleophilic Substitution: aliphatic and aromatic 967
Elimination-addition mechanism for nucleophilic aromatic
Substitution. Benzyne 962
Analysis of aryl halides 96 7
xix
CONTENTS
27 a,/?-Unsaturated Carbonyl Compounds Conjugate Addition
21.1
27.2
27.3
21A
27.5
27.6
27.7
21.S
27.9
Structure and properties 971
Preparation 973
Interaction of functional groups 974
Electrophilic addition 974
Nucleophilic addition 976
Comparisonof nucleophilic and electrophilic addition
The Michael addition 979
The Diels-Alder reaction 982
Quinones 984
978
28 Molecular Orbitals. Orbital Symmetry
28.1
28.2
28.3
28.4
28.5
28.6
28.7
28.8
28.9
28.10
Molecular orbital theory 991
Wave equations. Phase 992
Molecular orbitals. LCAO method 993
Bonding and antibonding orbitals 994
Electronic configurationsof somemolecules 996
Aromatic character. The Hückel 4n + 2 rule 1000
Orbital symmetry and the chemical reaction 1004
Electrocyclic reactions 1005
Cycloaddition reactions 1013
Sigmatropic reactions 1019
29 Symphoria Neighbonng Group Effects. Catalysis by
Transition Metal Complexes
29.1
29.2
29.3
29.4
29.5
29.6
29.7
29.8
29.9
Symphoria 1031
Neighboring group eflfects: the discovery. Stereochemistry 1032
Neighboring group eflfects: intramolecular nucleophilic
attack 1035
Neighboring group eflfects: rate of reaction. Anchimeric
assistance 1037
Homogeneous hydrogenation. Transition metal complexes 1042
Stereochemistry of homogeneous hydrogenation:
diastereoselectivity 1046
Stereochemistry of homogeneous hydrogenation:
enantioselectivity 1049
The oxo process 1052
Enzyme action 1054
30 Heterocyclic Compounds
30.1
Heterocyclic Systems
1057
FIVE-MEMBERED RINGS
30.2
30.3
30.4
Structure of pyrrole, furan, and thiophene 1059
Source of pyrrole, furan, and thiophene 1061
Electrophilic Substitution in pyrrole, furan, and thiophene.
Reactivity and orientation 1062
CONTENTS
30.5
Saturated five-membered heterocycles
1065
SIX-MEMBERED RINGS
30.6
30.7
30.8
30.9
30.10
30.11
30.12
Structureof Pyridine 7066
Source of Pyridine Compounds 1067
Reactionsof Pyridine 1068
Electrophilic Substitution in Pyridine 7065
Nucleophilic Substitution in Pyridine 7069
Basicity of Pyridine 7077
Reduction of Pyridine 1073
31 Macromolecules. Polymers and Polymerization
31.1
31.2
31.3
31.4
31.5
31.6
31.7
31.8
Macromolecules 7077
Polymers and polymerization 7075
Free-radical vinyl polymerization 7050
Copolymerization 7055
Ionic polymerization. Living polymers 1084
Coordination polymerization 7057
Step-reaction polymerization 7090
Structure and properties of macromolecules 7 093
32 Stereochemistry III. Enantiotopic and Diastereotopic Ligands
and Faces
32.1
32.2
32.3
32.4
32.5
32.6
32.7
Introduction 7707
Biological oxidation and reduction. Ethanol and
acetaldehyde 7707
Biological oxidation and reduction. Deuterium labeling
experiments 7705
Biological oxidation and reduction. Stereochemistry 7704
Enantiotopic and diastereotopic ligands 7707
Enantiotopic and diastereotopic faces 7770
Origin of enantiospecificity 7772
PART THREE
Biomolecules
33 Lipids Fats and Steroids
33.1
33.2
33.3
33.4
33.5
33.6
33.7
33.8
33.9
The organic chemistry of biomolecules 7779
Lipids 7720
Occurrence and composition of fats 7720
Hydrolysisof fats. Soap. Micelles 1124
Fats assourcesofpureacids and alcohols 7725
Detergents 7726
Unsaturated fats. Hardening of oils. Drying oils 7727
Phosphoglycerides. Phosphate esters 7725
Phosphoüpids and cell membranes 7750
xxi
CONTENTS
33.10
33.11
Biosynthesis of fatty acids
Steroids 1134
1132
34 Carbohydrates I. Monosaccharides
34.1
34.2
34.3
34.4
34.5
34.6
34.7
34.8
34.9
34.10
34.11
34.12
34.13
34.14
34.15
34.16
34.17
34.18
34.19
34.20
Introduction 1143
Definition and Classification 1144
(+)-Glucose: an aldohexose 1144
(—)-Fructose: a 2-ketohexose 1146
Stereoisomers of (+)-glucose. Nomenclature of aldose
derivatives 1146
Oxidation. Effect ofalkali 1149
Osazone formation. Epimers 1151
Lengthening the carbon chain of aldoses. The Kiliani-Fischer
synthesis 1152
Shortening the carbon chain of aldoses. The Ruff
degradation 1154
Conversion of an aldose into its epimer 1154
Configuration of (+)-glucose. The Fischer proof 1155
Configurations of aldoses 1160
Optical families. D and L 1162
Tartaricacid 1164
Families of aldoses. Absolute configuration 1166
Cyclic structure of D-(+)-glucose. Formation of glucosides 1168
Configuration about C-1 1173
Methylation 1174
Determination of ring size 1176
Conformation 1178
35 Carbohydrates IL Disaccharides and Polysaccharides
35.1
35.2
35.3
35.4
35.5
35.6
35.7
35.8
35.9
35.10
35.11
35.12
Disaccharides 7755
(+)-Maltose 7755
(+)-Cellobiose 1188
(+)-Lactose 1189
(+)-Sucrose 7797
Polysaccharides 7792
Starch 7793
Structure of amylose. End group analysis
Structure of amylopectin 7795
Cyclodextrins 7795
Structure of cellulose 7200
Reactionsof cellulose 7200
1193
36 Proteins and Nucleic Acids Molecular Biology
36.1
36.2
36.3
36.4
Proteins 7205
Structure ofamino acids 7206
Amino acids as dipolar ions 7205
Isoelectric point ofamino acids 7277
CONTENTS
xxii
36.5
36.6
36.7
36.8
36.9
36.10
36.11
36.12
36.13
36.14
36.15
36.16
36.17
36.18
36.19
36.20
Configurationof natural aminoacids 1212
Preparation of amino acids 1213
Reactionsof aminoacids 1215
Peptides. Geometry ofthe peptide linkage 1215
Determination of structure of Peptides. Terminal residue
analysis. Partial hydrolysis 1217
Synthesisof peptides 1221
Proteins. Classification and function. Denaturation 1225
Structure of proteins 1226
Peptide chain 1226
Side chains. Isoelectric point. Electrophoresis 1227
Conjugated proteins. Prosthetic groups. Coenzymes 1228
Secondary structure of proteins 1229
Biochemistry, molecular biology, and organic chemistry 1235
Mechanism of enzyme action. Chymotrypsin 1236
Nucleoproteins and nucleic acids 1241
Chemistry and heredity. The genetic code 1246
Suggested Readings
1251
Answers to Problems 1263
Index
1279