Physical organic chemistrySecond edition
Neil S. Isaacs
Foreword to first edition
vi i
Foreword to second edition
ix
Symbols and abbreviations
xxvi iMechanistic designations
xxvii
r Models of chemical bonding
1
1 .1 Covalency and molecular structure
11 .1 .1 The valence bond (VB) model
21 .1 .2 The molecular orbital (MO) model
31 .2 Approximate molecular orbital theory
31 .2.1 The Hückel molecular orbital (HMO) method
41 .2 .2 Properties of Hückel molecular orbitals
1 31 .2 .3 The relationship between MO and VB models
261 .2 .4 Advanced MO methods
271 .3 Properties of covalent bonds
3 11 .3 .1 Bond lengths
3 11 .3 .2 Interbond angles
341 .3 .3 Force constants
351 .3 .4 Bond and molecular dipole moments
361 .3 .5 Molecular and bond polarizabilities
391 .3 .6 Bond dissociation enthalpies (BDE)
4 31 .3.7 Group additivities to bond enthalpies
4 51 .4 Intermolecular forces
541 .4.1 Electrostatic forces
541 .4.2 Ion-pairs
5 81 .4.3 Short-range intermolecular forces
6 31 .4.4 The hydrogen bond
6 71 .4.5 Charge-transfer complexes
741 .4.6 Crowns, cryptates, calixarenes and cyclodextrins
76Problem sReferences
s Kinetics and thermodynamics
8 7
2.1 Enthalpy
8 82.1 .1 Endothermic reactions
902.2 Entropy
902.3 The Gibbs function, G
922.4 Factors that contribute to entropy
942.5 Chemical equilibrium
962 .6 Some useful thermodynamic relationships
982 .6 .1 Temperature dependence
992 .7 The application of thermodynamics to rate processes
1002 .7 .1 Activation
1002 .7 .2 The potential energy surface
10 12 .7 .3 The transition state model
1042.8 Properties of the transition state
1052 .8 .1 Activation parameters
1052 .8 .2 Heat capacity of activation
1062 .8 .3 Variation of rate with pressure
1072 .9 The uses of activation parameters
10 82 .9 .1 The empirical treatment of rates of simpl e
irreversible reactions
10 82 .9 .2 The rate-determining step
11 12 .9 .3 Relative rates
11 22 .9 .4 Entropies and volumes of reaction
11 32.9.5 The isokinetic relationship
11 62.10 The location of the transition state
11 82.10 .1 The Hammond Postulate
11 82.10 .2 Reactivity and selectivity
12 12.10 .3 Kinetic and thermodynamic control of products 12 22 .10.4 The principle of least motion
12 32 .10.5 The principle of microscopic reversibility
1242 .10.6 Limitations of the transition-state theory
12 5Problem sReference s
3 Reagents and reaction mechanisms
12 9
3 .1 Polar and radical pathways
1293 .1 .1 Polar reactions
1303 .1 .2 Nucleophiles
13 13 .1 .3 Electrophiles
1323 .1 .4 Radicals
1323 .1 .5 Reactivity
1333 .2 A classification of fundamental reaction types
1333 .2 .1 Bond formation and bond breaking
1343 .2 .2 Transfer reactions
1343 .2 .3 Elimination (E) and addition (Ad)
136
3.2.4 Pericyclic reactions
1363.2 .5 Oxidations and reductions
1373.3 Reaction mechanism
1383 .3 .1 The advantages of synchronous reactions
1383.4 Electron supply and demand
139. 3.5 Transition-state properties and structural change
140Problem sReferences
4 Correlation of structure pith reactivity
146
4.1 Electronic demands
1464.2 The Hammett equation
1494.3 Substituent constants a
15 14.4 Theories of substituent effects
15 14.4.1 The resonance effect
15 34.4.2 The inductive effect
15 54.5 Interpretation of a-values
1564.5 .1 Unshared-pair (n) substituents, -7C
15 74 .5 .2 Alkyl groups
15 84.5 .3 Electron-withdrawing groups, -2
1604 .5 .4 Cationic centres
1604.6 Reaction constants, p
16 14 .7 Deviations from the Hammett equation
16 14 .7 .1 Random deviations
16 34 .7 .2 Mechanistic change
'1634 .7 .3 Enhanced resonance
1644 .7 .4 Variable resonance interactions
16 84.8 Dual-parameter correlations : the flowering of LFER
1704 .8 .1 Inductive substituent constants
17 14 .8 .2 The Taft model
17 14 .8 .3 Other chemical model systems : modern o and
QR scales
17 54.9 Molecular orbital considerations
1834.10 Cross-interaction terms
1864 .10 .1 The sign of p;;
187Problem sReferences
f Solvent effects
193
5 .1 The structure of liquids
1945.2 Solutions
1955 .3 Solvation
19 85 .3 .1 Polarity
-
19 95 .3.2 Polarizability
199
5 .3 .3 Hydrogen bonding
19 95 .3 .4 Donor-acceptor interactions
19 95 .4 Thermodynamic measures of solvation
20 05 .4.1 Free energies of solution and transfer functions
20 25 .4.2 Activities of solutes
20 25 .4 .3 `Solvation' in the gas phase
20 45 .5' The effects of solvation on reaction rates and equilibria
20 55 .5 .1 Solvent effects on rates
20 75 .6 Empirical indexes of solvation
2085 .6 .1 Scales based on physical properties
2085 .6 .2 Scales based on solvent-sensitive reaction rates
2145 .6 .3 Scales based on spectroscopic properties
21 65 .6 .4 Scales for specific solvation
2205 .7 Relationships between empirical solvation scales
22 35 .8 The use of solvation scales in mechanistic studies
22 35 .8 .1 Multiparameter solvation analysis
226Problem sReferences
6 Acids and bases, electrophiles and nucleophiles
23 5
6 .1 Acid-base dissociation
23 56 .2 The strengths of oxygen and nitrogen acids
23 76 .2.1 The effect of pressure on acid-base dissociation 24 06 .2 .2 The interpretation of KA
24 06.3 Linear free-energy relationships
24 26.4 Rates of proton transfers
24 36.5 Structural effects on amine protonation
24 36 .5 .1 Linear free-energy relationships
24 56.6 Acidities of carbon acids
24 66 .6 .1 The measurement of weak acidity
24 86 .7 Factors that influence carbon acidity
24 96 .7 .1 Electronic effects of adjacent - R and - I groups
24 96 .7 .2 Stabilization by d-orbitals
2506 .7 .3 s-Character of carbon hybridization
2506.7.4 Aromaticity
25 16 .8 Rates of ionization of carbon acids
2526.9 Gas-phase acidity and basicity
25 56 .10 Theories of proton transfer
2576 .11 Highly acidic and highly basic solutions
25 96 .11 .1 Highly acidic solutions
2606 .11 .2 Highly basic media
2656 .12 Nucleophilicity and electrophilicity
2656 .12 .1 Measurement of nucleophilicity : nucleophilicit y
and basicity
266
6 .12 .2 Hard and soft acids and bases : frontier orbita linteractions
2676 .12 .3 Nucleophilicity scales
2706 .12 .4 The relationship between nucleophilicity an d
nucleofugacity
2746 .12 .5 The `a-effect'
27 66 .12 .6 Ambident nucleophiles
27 76.13 The measurement of electrophilicity
28 06 .14 Brr nsted relationships in nucleophilic reactions
28 06.15 The Leffler index
28 2Problem sReferences
Kinetic isotope effects
28 7
7.1 Isotopic substitution
28 77.2 Theory of isotope effects : the primary effect
28 87.3 Transition-state geometry
29 57.4 Secondary kinetic isotope effects
29 67 .4 .1 `Inductive' and `steric ' isotope effects
30 17.5 Heavy atom isotope effects
30 27.6 The tunnel effect
30 47.7 Solvent isotope effects
30 77.7.1 Fractionation factors
30 87 .7 .2 Solvent isotope effects in mixed isotopic solvents :
the proton inventory technique
3107.7.3 Examples of solvent isotope effects
31 2Problem sReferences
8 Steric and conformational properties
319
8 .1 The origins of steric strain
31 98 .2 Examples of steric effects upon reactions
32 28 .2 .1 Ortho effects
32 28 .2 .2 F-strain effects
32 48 .2.3 Bond-angle strain
32 58 .2 .4 Steric inhibition of resonance
32 68 .2.5 Steric acceleration
32 78 .2.6 Steric enhancement of resonance
32 88.2.7 Calculation of steric effects : the molecula r
mechanics method
32 88 .3 Measurement of steric effects upon rates
33 18 .3.1 The Taft-Ingold hypothesis
332
8 .3 .2 Other steric parameters
33 38 .3 .3 Examples of steric LFER
33 78 .4 Conformational barriers to bond rotation
33 88 .4.1 Spectroscopic detection of individual conformers
34 18 .4.2 Acyclic compounds
34 28 .4.3 Cyclic compounds
34 68 .5 Rotations about partial double bonds
3508 .5 .1 Inversion at Group V elements
35 18 .6 Chemical consequences of conformational isomerism :
the Winstein-Holness-Curtin-Hammett principle
352Problem sReference s
9 Homogeneous catalysis
36 9
9.1 Acid and base catalysis
3699 .1 .1 Specific and general catalysis
37 19 .1 .2 Mechanisms of acid catalysis
3749.1 .3 Methods of distinguishing between Al and A 2
reactions
37 69 .1 .4 Linear free-energy relationships ; the Brenste d
Catalysis Law
37 99 .1 .5 Interpretation of the Brensted coefficients
38 19 .1 .6 Nucleophilic catalysis
38 49 .1 .7 Potential-energy surfaces for proton transfers
38 59 .1 .8 Solvent isotope effects
38 99 .1 .9 Electrophilic catalysis
39 09 .2 The mechanisms of some catalysed reactions
39 29 .2.1 Substitutions a- to a carbonyl group
39 29 .2 .2 Keto-enol equilibria
39 49 .2 .3 Hydrolyses of acetals, ketals, orthoesters and
related compounds
39 79 .2 .4 Dehydration of aldehyde hydrates and related
compounds
39 89 .2 .5 The formation of oximes, semicarbazones and
hydrazones
39 89 .2 .6 Decarboxylation
3999 .2 .7 Acid-catalysed alkene-alcohol interchange
4009 .2 .8 Some acid-catalysed rearrangements
40 19 .2 .9 Rate-limiting proton transfers
4079.3 Catalysis by non-covalent binding
4099 .3 .1 Host-guest interactions
41 1Problem sReferences
to
Substitution reactions at carbon
41 8
10 .1 Substitutions at saturated carbon
41810 .1 .1 Nucleophilic substitution (S N 2)
41810 .1 .2 The bimolecular reaction, S N 2
42210 .1 .3 Solvolytic reactions-the S N 1 spectrum
43310 .1 .4 Measurement of solvent participation
43510 .1 .5 Kinetic isotope effects
43810 .1 .6 The structures of intermediates in S N1 reactions
44010 .1 .7 The phenomenon of `return'
44210 .1 .8 Rearrangement criteria for return
44310 .1 .9 The `special' salt effect : an ion exchange in an
ion-pair
44510 .1 .10 Structural effects upon ionization
44710 .1 .11 Leaving-group effects
44910 .1 .12 Bridgehead systems
45 110.1 .13 Linear free-energy relationships
45 110.1 .14 Intramolecular assistance in ionization
45 510.1 .15 Activation parameters
45 710.1 .16 The S N1 reactions
46010.1 .17 Aliphatic S N 2 reactions in the gas phase
46 110.2 Electrophilic substitutions at saturated carbon
46310.2 .1 The S E1 mechanism
46310.2.2 The S E 2 mechanism
46410.2 .3 Electrophilic substitution via enolization
46810 .3 Nucleophilic displacements at a vinyl carbon
46910 .4 Electrophilic displacements at an aromatic carbon
47310 .4 .1 Timing of bond-breaking and making
47410 .4 .2 The general mechanism for electrophili c
aromatic substitution
47510 .4 .3 The nature of the electrophilic reagents
47710 .4 .4 Kinetic isotope effects
48 110 .4 .5 Kinetics of S E2-Ar reactions
48 110 .4 .6 Structural effects on rates
48510 .4 .7 The ortho-para selectivity ratio, so, n = (2fo/fp)
49 110 .4 .8 The nature of the intermediate
49310 .4 .9 Ipso attack
49510 .4 .10 The MO interpretation of aromatic reactivity
49510 .5 Nucleophilic substitution at an aromatic centre
49810.5 .1 The addition-elimination pathwa y
(S N Ar-Ad, E)
49810 .5 .2 The unimolecular mechanism
50310.5.3 The aryne mechanism (E-Ad)
50410.5.4 Nucleophilic substitution via ring opening : the
S N(ANRORC) route
50610.6 Nucleophilic substitutions at carbonyl carbon
50710.6.1 Basic hydrolysis of carboxylic esters
511
10 .6 .2 Acidic hydrolysis of esters
51 910 .6 .3 Stereoelectronic factors in the decomposition of
the tetrahedral intermediate
52 110 .6 .4 Other mechanisms for ester hydrolysis
52 210 .6 .5 Hydrolysis of amides, acyl halides and
anhydrides
52 910 .6 .6 Properties of tetrahedral intermediates
53 310 .6.7 Nucleophilic catalysis in carbonyl substitutions
53 6ProblemsReferences
it Elimination reactions
55 1
11 .1 Base-promoted eliminations in solution
55 111 .1 .1 Kinetic criteria of mechanisms
55 511 .1 .2 Structural effects on rates of elimination
55 611 .1 .3 Kinetic isotope effects
56 211 .1 .4 Variation of the base-solvent system
56 611 .1 .5 Competition between elimination an d
substitution
56 811 .1 .6 Orientation in product formation
57211 .1 .7 Stereochemistry of E2 reactions
57411 .1 .8 Frontier orbital considerations
57911 .1 .9 Elcb reactions
-57911 .1 .10 Ester hydrolysis by the Elcb mechanism
58 111 .2 Intramolecular pyrolytic eliminations (the E ; reactions)
58 111 .2.1 Ester pyrolysis
58211 .2 .2 The Chugaev reaction
58 511 .2 .3 Amine oxide, sulphoxide and selenoxid e
pyrolyses
58611 .2 .4 Pyrolysis of alkyl halides
58 711 .3 a-Eliminations
58 811 .4 Oxidative eliminations
58 911 .4 .1 Oxidations of alcohols by chromium (VI)
59011 .4 .2 The Moffatt oxidation
59 2Problem sReference s
12 Polar addition reactions
599
12.1 Electrophilic additions to alkenes
60012 .1 .1 Kinetics
60012 .1 .2 Effect of structure
60212 .1 .3 Isotope effects
607
12 .1 .4 Orientation and stereochemistry
60 812 .1 .5 The nature of the intermediates in Ad E reactions 610
12.2 Miscellaneous additions
61 312 .2 .1 Hydroboration
61 312 .2 .2 Addition with ring closure ; halolactonization
61 712 .2 .3 Addition of carbocations
61 712 .2 .4 Additions to dienes, alkynes and allenes
61 812 .3 Nucleophilic additions to multiple bonds
62 012 .3 .1 Michael addition
62 112 .3 .2 Carbonyl additions
62 212 .3 .3 Additions to heterocumulenes
62912 .4 Frontier orbital considerations
63 112 .5 Vinyl substitution via addition/elimination
63212 .5 .1 Examples
63 412 .5 .2 Stereochemistry
636ProblemsReference s
13 Intramolecular reactions
643
13 .1 Neighbouring-group participation
64313 .1 .1 The scope of neighbouring-group effects
64613 .1 .2 Methods for recognizing neighbouring-group
participation
64613 .1 .3 The kinetic criterion
64613.1 .4 Linear free-energy relationships
65013 .1 .5 Kinetic isotope effects
65413 .1 .6 Solvent effects
65413 .1 .7 Participation in carbonyl reactions
65613 .1 .8 The stereochemical criterion
65813 .1 .9 The rearrangement criterion
66013 .1 .10 Factors influencing neighbouring-group
participation
662
13 .1 .11 Observation and isolation of cycli cintermediates
66713 .1 .12 a- and z-participation : the question of non-
classical ions
67013 .2 Enzymic reactions
67813 .2 .1 The structures of enzymes
67 813 .2.2 A model for enzyme action
68013 .2 .3 Mechanisms of some enzyme-catalysed reactions 68413 .2 .4 Enzymes that use cofactors
69013 .2 .5 Enzyme model systems
69 3Problem sReferences
r¢ Perigclic reactions
70 1
14 .1 Classification of pericyclic reactions
70 114 .2 The theory of pericyclic reactions
70 214 .2 .1 Conservation of orbital symmetry : correlation
diagrams
70 314 .2 .2 The frontier orbital concept
70 514 .2 .3 The aromaticity concept
70 714 .2 .4 Suprafacial and antarafacial geometries
70 714 .3 Thermal cycloadditions : their scope and characteristics 70 9
14 .3.1 The Diels-Alder reaction 71 114 .3 .2 Stereo- and regiospecificity in Diels-Alde r
reactions
71 514 .3 .3 Retro Diels-Alder reactions
72 114 .3 .4 The nature of the Diels-Alder transition state
72 314 .3 .5 Related six-electron cycloadditions
72 514 .4 Thermal (2 + 2) cycloadditions
72 714 .4 .1 Cycloadditions of cumulenes
72 814 .4 .2 Two-step cycloadditions
73 214 .4 .3 (2 + 2) Cycloreversions
73 414 .5 1,3-Dipolar cycloadditions
73 614 .6 Electrocyclic reactions
74014 .7 Cheletropic reactions
74214 .8 Sigmatropic reactions
74814 .8 .1 Concertedness in sigmatropic rearrangements
75 114 .9 Acid catalysis of the Diels-Alder reaction
75 3Problem sReference s
rJ Reactions via free radicals
767
15 .1 The generation of radicals
76715 .1 .1 Primary processes
76 815 .1 .2 Secondary routes
77215 .2 The detection of radicals
77315 .2 .1 Direct observation
77 315,2 .2 Indirect methods
77915 .2 .3 By chemical characteristics
78415 .3 Reactions of radicals
78 815 .3 .1 Radical coupling
78815 .3 .2 Displacement (abstraction, transfer) reactions
79015 .3 .3 Additions to 7c-systems
79 315 .3 .4 Fragmentation of radicals
79 715 .3 .5 Radical rearrangements
79 815 .3 .6 Radical cyclization reactions
80 115 .3 .7 Linear free-energy relationships
80415 .3 .8 Electron transfer reactions
806
15 .4 Factors influencing the reactivities of radicals
81015 .4.1 Radical stability
81 115 .4.2 Polar influences
81 415 .4.3 Solvent effects on radical reactions
81 715 .4.4 Steric effects in radical reactions
81 715 .4.5 Frontier-orbital considerations
82 115 .5 The stereochemistry of radicals
82 4Problem sReference s
r6 Organic photochemistry
83 7
16 .1 Excited electronic states
83 716 .1 .1 Absorption of light by molecules
83 716 .1 .2 Vertical and horizontal excitation
83 816 .1 .3 Spin multiplicity : singlet and triplet states
83 916 .1 .4 Sensitization and quenching
84016.1 .5 Techniques of photochemistry
84416 .2 Photochemistry of the carbon-carbon double bond
84416.2 .1 Geometrical isomerization
84 416.2.2 Photochemical pericyclic reactions
84 616.2 .3 The di-rr-methane rearrangement
85 116.2 .4 Photoadditions to alkenes
85 216.3 Photoreactions of carbonyl compounds
85 316 .3 .1 Carbon-carbon bond cleavage
85416 .3 .2 Cycloadditions
85 616.4 Photochemistry of aromatic compounds
85 716 .4 .1 Photosubstitutions at the aromatic ring
85 816 .4 .2 The photo-Fries rearrangement
85 916 .4 .3 Valence isomerization
85916 .4 .4 Photocycloadditions
86 116 .4 .5 Photo-oxidations with oxygen
864Problem sReference s
Index
871