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