Investigation of Organic Reactions and Their Mechanisms

The Investigation of Organic Reactions and Their Mechanisms......Page 2
Contents......Page 8
Contributors......Page 18
Foreword......Page 20
Preface......Page 24
1.2 The nature of mechanism and reactivity in organic chemistry......Page 26
1.3.1 Product analysis, reaction intermediates and isotopic labelling......Page 27
1.3.1.1 Example: the acid-catalysed decomposition of nitrosohydroxylamines......Page 28
1.3.2 Mechanisms and rate laws......Page 29
1.3.3.1 Example: the acid- and base-catalysed decomposition of nitramide......Page 31
1.3.4 Kinetics in homogeneous solution......Page 32
1.3.4.1 Example: the kinetics of the capture of pyridyl ketenes by n -butylamine......Page 33
1.3.5 Kinetics in multiphase systems......Page 34
1.3.6 Electrochemical and calorimetric methods......Page 35
1.3.7 Reactions involving radical intermediates......Page 37
1.3.8 Catalysed reactions......Page 38
References......Page 41
2.1 Introduction and overview– why study organic reaction mechanisms?......Page 43
2.2.1 Quantitative determination of product yields......Page 46
2.2.2 Product stabilities, and kinetic and thermodynamic control of product formation......Page 48
2.3.1 Stereochemical considerations......Page 50
2.3.2 Use of isotopic labelling......Page 51
2.4 Mechanistic evidence from variations in reaction conditions......Page 52
2.6 Kinetic evidence from monitoring reactions......Page 57
2.6.1 Sampling and analysis for kinetics......Page 58
2.7.1 Product-determining steps in SN1 reactions......Page 59
2.7.2 Selectivities......Page 61
2.7.3 Rate– product correlations......Page 63
Bibliography......Page 68
References......Page 69
3.2.1 Reaction rate, rate law and rate constant......Page 71
3.2.3 Reaction mechanism, elementary step and rate-limiting step......Page 73
3.3 How to obtain the rate equation and rate constant from experimental data......Page 75
3.3.1 Differential method......Page 76
3.3.1.1 Example:reaction between RBr and HO-......Page 77
3.3.2 Method of integration......Page 78
3.3.2.2 Example: decomposition of N2O5 in CCl4......Page 79
3.3.3 Isolation method......Page 81
3.3.3.1 Example: oxidation of methionine by HOCl......Page 82
3.4.1 Rate constants for forward and reverse directions, and equilibrium constants......Page 83
3.5.1 Preliminary studies......Page 84
3.5.2.2 Temperature......Page 85
3.5.2.3 pH......Page 86
3.5.2.4 Solvent......Page 87
3.5.2.5 Ionic strength......Page 88
3.5.2.6 Other experimental aspects......Page 89
3.6.3 Continuous static monitoring......Page 90
3.7.1 Spectrometric methods......Page 91
3.7.1.1 Conventional and slow reactions......Page 92
3.7.1.2 Fast reactions......Page 94
3.7.1.3 Very fast and ultrafast reactions......Page 95
3.7.2 Conductimetry......Page 96
3.7.4 Potentiometry......Page 98
3.7.5 Dilatometry......Page 99
3.7.7 Chromatographic methods......Page 100
References......Page 101
4.1 Introduction......Page 104
4.2.1 Single-step unidirectional reactions......Page 105
4.2.2.1 Consecutive unimolecular (first-order) reactions......Page 106
4.2.2.3 Parallel (competitive) unimolecular (first-order) reactions......Page 108
4.2.3 Complex reaction schemes and approximations......Page 111
4.2.3.1 The steady-state approximation (SSA)......Page 113
4.2.3.3 The rate-determining step approximation......Page 114
4.2.3.4 The steady-state approximation,and solvolysis of alkyl halides and arenesulfonates......Page 115
4.3.1 Chlorination of amino compounds......Page 116
4.3.2 The Aldol reaction......Page 120
4.3.2.1 At low concentrations of aldehyde......Page 121
4.3.2.2 At high concentrations of aldehyde......Page 122
4.3.3 Hydrogen atom transfer from phenols to radicals......Page 123
4.3.4 Oxidation of phenols by Cr(VI)......Page 125
References......Page 128
5.1 Introduction......Page 129
5.2.1 Mass transfer coupled to chemical reaction......Page 130
5.2.1.1 Reaction too slow to occur within the diffusion film......Page 131
5.2.1.2 Reaction fast relative to the film diffusion time......Page 132
5.2.1.3 Interfacial reactions......Page 134
5.2.2 Phase-transfer catalysis (PTC)......Page 135
5.2.3 System complexity and information requirements......Page 137
5.3.1.1 Gas–liquid reactions......Page 138
5.3.1.2 Dispersed liquid–liquid systems......Page 139
5.3.1.3 Liquid–solid reactions in a stirred reactor......Page 140
5.3.2.1 Techniques based on the Lewis cell......Page 141
5.3.2.2 The rotated disc reactor......Page 142
5.3.2.3 Rotated diffusion cell......Page 143
5.3.2.4 Channel flow techniques......Page 144
5.3.2.5 The jet reactor......Page 145
5.3.2.6 Expanding drop methods......Page 146
5.3.2.8 Microelectrode techniques......Page 147
5.4 Information requirements and experimental design......Page 148
5.5 Summary......Page 149
References......Page 150
6.1 What is organic electrochemistry?......Page 152
6.2 The relationship between organic electrochemistry and the chemistry of radical ions and neutral radicals......Page 155
6.3 The use of electrochemical methods for investigating kinetics and mechanisms......Page 156
6.4.1 Two-electrode and three-electrode electrochemical cells......Page 157
6.4.2 Cells for electroanalytical studies......Page 158
6.4.3.1 The working electrode (W)......Page 159
6.4.5 The electronic instrumentation......Page 160
6.5 Some basics......Page 161
6.5.1 Potential and current......Page 162
6.5.2 The electrochemical double layer and the charging current......Page 163
6.5.3 Mass transport and current......Page 164
6.6.2 Mechanisms and rate laws......Page 166
6.7 The response curves for common electroanalytical methods......Page 167
6.7.1 Potential step experiments (chronoamperometry and double potential step chronoamperometry)......Page 168
6.7.2 Potential sweep experiments (linear sweep voltammetry and cyclic voltammetry)......Page 172
6.7.2.1 CV conditions......Page 176
6.7.2.3 Fitting simulated voltammograms to experimental voltammograms......Page 179
6.7.3 Potential sweep experiments with ultramicroelectrodes......Page 180
A.1 The preliminary experiments......Page 184
A.2 Preliminary studies by cyclic voltammetry......Page 185
A.3 Determination of the number of electrons, n (coulometry)......Page 187
A.4 Preparative or semi-preparative electrolysis, identification of products......Page 189
References......Page 190
7.1.1 General remarks......Page 192
7.1.2 Potential energy surfaces, reaction coordinates and transition structures......Page 193
7.1.3 Absolute and relative energies; isodesmic and homodesmotic equations......Page 195
7.2.1 Molecular mechanics......Page 197
7.2.3 Semiempirical methods......Page 198
7.2.4 Hartree–Fock theory......Page 200
7.2.5 Electron-correlation methods......Page 201
7.2.6 Density functional theory......Page 204
7.2.8 Basis sets......Page 206
7.3.1 The ethane rotational barrier and wave function analysis......Page 207
7.3.2 The nonclassical carbocation problem and the inclusion of solvent effects......Page 212
7.4 Matching computed and experimental data......Page 217
7.5 Conclusions and outlook......Page 218
References......Page 219
8.1 Introduction......Page 223
8.2 Investigation of reaction kinetics and mechanisms using calorimetry and infrared spectroscopy......Page 224
8.2.2 Types of reaction calorimeters......Page 225
8.2.2.2 Power-compensation calorimeters......Page 226
8.2.3 Steady-state isothermal heat-flow balance of a general type of reaction calorimeter......Page 227
8.2.4 Infrared and IR-ATR spectroscopy......Page 230
8.2.5.1 Experimental methods for isothermal calorimetric reaction data......Page 231
8.2.5.2 Experimental methods for isothermal infrared reaction data......Page 234
8.3.1 Calorimetric device used in combination with IR-ATR spectroscopy......Page 236
8.3.2.2 Results and discussion......Page 238
8.3.3 Example 2: sequential epoxidation of 2,5-di-tert-butyl- 1,4-benzoquinone......Page 241
8.3.3.2 Results and discussion......Page 242
8.3.4.1 Materials and methods......Page 247
8.3.4.2 Results and discussion......Page 248
8.4 Conclusions and outlook......Page 249
References......Page 250
9.1.1 Potential energy surfaces and profiles......Page 252
9.1.2 From molecular potential energy to rates of reaction......Page 254
9.2.1 Reaction classification......Page 256
9.2.2 Consequences of uncoupled bonding changes......Page 257
9.2.3 Sequences of basic reactions......Page 258
9.3.1 Direct observation......Page 259
9.3.2 Deductions from kinetic behaviour......Page 263
9.3.3 Trapping of intermediates......Page 267
9.3.4 Exploitation of stereochemistry......Page 271
9.3.5 Isotopic substitution in theory......Page 274
9.3.6 Isotopic substitution in practice......Page 277
9.3.7 Linear free energy relationships......Page 281
References......Page 283
10.1.1 Radical intermediates......Page 286
10.1.2 Some initial considerations of radical mechanisms and chapter overview......Page 287
10.2 Initiation......Page 289
10.3 Radical addition to alkenes......Page 291
10.5 Nitroxides......Page 293
10.5.1 Nitroxide-trapping experiments......Page 294
10.5.2 Alkoxyamine dissociation rate constant, kd......Page 295
10.5.3 The persistent radical effect (PRE)......Page 298
10.5.4 Nitroxide-mediated living/controlled radical polymerisations (NMP)......Page 300
10.6 Radical clock reactions......Page 301
10.7 Homolytic aromatic substitution......Page 305
10.8.1 Reductions with samarium di-iodide,SmI2......Page 309
10.8.2 SRN1 substitution......Page 312
Bibliography......Page 316
References......Page 317
11.1.1 Definitions......Page 318
11.2.1 Experimental demonstration......Page 319
11.2.2 Reaction flux and third-order terms......Page 322
11.2.3 Brønsted equations......Page 323
11.2.4.1 Cross-correlation effects......Page 324
11.2.4.2 The diffusion-controlled limit as a criterion of mechanism......Page 326
11.2.5.1 Stepwise proton transfer (trapping)......Page 327
11.2.5.2 Stabilisation of intermediates by proton transfer......Page 329
11.2.5.3 Preassociation......Page 331
11.2.5.5 Push–pull and bifunctional acid–base catalysis......Page 332
11.3.1 Detection of intermediates......Page 333
11.3.2 Non-linear free energy relationships and transient intermediates......Page 335
11.4 Enzyme Catalysis......Page 336
11.4.2 Enzyme assay......Page 337
11.4.3.1 Active-site titration......Page 338
11.4.3.2 Active-site directed irreversible inhibitors......Page 340
11.4.4 Kinetic analysis......Page 341
11.4.5 Reversible inhibitors......Page 342
11.4.6.1 Direct observation......Page 343
11.4.6.2 Structural variation......Page 344
11.4.6.4 Kinetics......Page 345
11.4.6.5 Trapping......Page 346
References......Page 347
12.1.1 The challenges inherent in the investigation of organic reactions catalysed by organometallics......Page 349
12.1.2 Techniques used for the study of organometallic catalysis......Page 351
12.1.3 Choice of examples......Page 352
12.2.1 Background and introduction......Page 353
12.2.2 The 31P{1H}NMR investigation of the Rh-catalysed asymmetric phenylation of cyclohexenone......Page 355
12.2.3 Summary and key outcomes from the mechanistic investigation......Page 358
12.3.1 Background and introduction......Page 359
12.3.2 Kinetic studies employing classical techniques......Page 360
12.3.3 ‘Atom accounting ’through isotopic labelling......Page 363
12.3.4 Observation of pro-catalyst activation processes by NMR spectroscopy......Page 366
12.3.5 Summary and mechanistic conclusions......Page 367
12.4.1 Background and introduction......Page 368
12.4.2 Early mechanistic proposals for the alkene metathesis reaction......Page 369
12.4.3 Disproving the ‘pairwise ’mechanism for metathesis......Page 370
12.4.4 Mechanistic investigation of contemporary metathesis catalysts......Page 373
12.4.5 NMR studies of degenerate ligand exchange in generation I and generation II ruthenium alkylidene pro-catalysts for alkene metathesis......Page 376
12.4.6 Summary and mechanistic conclusions......Page 377
References......Page 378
Index......Page 379