HYDROXYL RADICAL ADDITIONS TO ARENES
A DISSERTATION
SUBMITTED TO THE GRADUATE SCHOOL
IN PARTIAL FULFILLMENT OF THE REQUIREMENTS
FOR THE DEGREE
DOCTOR OF PHILOSOPHY
BY
LEE COURTLAND MOORES
DR. JAMES S. POOLE - ADVISOR
BALL STATE UNIVERSITY MUNCIE, INDIANA JULY 2015
HYDROXYL RADICAL ADDITIONS TO ARENES
A DISSERTATION SUBMITTED TO THE GRADUATE SCHOOL IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE DOCTOR OF PHILOSOPHY
BY
LEE COURTLAND MOORES
DISSERTATION ADIVISOR: DR. JAMES S. POOLE
APPROVED BY:
______Committee Chairperson Date ______Committee Member Date ______Committee Member Date ______Committee Member Date ______Committee Member Date ______Dean of Graduate School Date
BALL STATE UNIVERSITY MUNCIE, INDIANA JULY 2015
ABSTRACT
DISSERTATION: Hydroxyl Radical Addition to Arenes
STUDENT: Lee Courtland Moores
DEGREE: Doctor of Philosophy
COLLEGE: Sciences and Humanities
DATE: July 2015
PAGES: 201
Anthropogenic input of organic compounds into aqueous environments and the effects of these contaminants on ecosystems, as well as human health are of great concern. Many contaminants are found in concentrations in excess of the accepted daily intake (ADI) values.
The fate of these contaminants as they degrade by chemical processes, specifically via reactions with hydroxyl radicals (·OH), and the rate of that degradation, is of interest. Hydroxyl radicals are a major contributor to the breakdown of many contaminants in natural systems.
The present study focused on measuring the product distributions from the reactions of selected substrates with ·OH, and the determination of rates of reactions relative to benzene
(PhH). From the data collected, models for predicting degradation pathways and rates of larger, more complex molecules can be developed.
In this study ·OH was generated by thermolysis, and reacted with two competing substrates. The products of the reaction were trapped with TEMPO, a nitroxyl radical, then derivatized to allow for analysis and characterization by GC/MS. The ratios of ·OH addition products yield relative rate coefficients that may be subjected to Arrhenius analysis to probe the effect of structure on reactivity.
TABLE OF CONTENTS
CHAPTER 1 - INTRODUCTION ...... 1
1.1 Organic Pollutants: Some Representative Classes ...... 2
1.1.1 Polycyclic Aromatic Hydrocarbons (PAHs) ...... 3
1.1.2 Polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs) ...... 4
1.1.3 Agrochemicals ...... 6
1.1.4 Pharmaceuticals and Illicit Drugs ...... 7
1.1.5 Structural Features of Contaminants ...... 10
1.2 Sources, Transport, Fates and Treatment of Environmental Contaminants ...... 13
1.2.1 Sources, Transport and Fates of Contaminants ...... 13
1.2.2 Treatment of Contaminants in Wastewater ...... 15
1.3 Hydroxyl Radical Chemistry ...... 18
1.3.1 Natural Sources of Hydroxyl Radicals ...... 19
1.3.2 Reactions of Hydroxyl Radicals with Organic Compounds ...... 21
1.3.3 Measuring Hydroxyl Radical Reactivity and Selectivity in Solution ...... 31
1.4 A Method for the Study of Hydroxyl Radical Chemistry ...... 34
CHAPTER 2 – EXPERIMENTAL METHODOLOGY ...... 41
2.1 Materials and Instrumentation ...... 41
2.2 Experimental Methods ...... 48
2.2.1 Kinetic Studies in Benzene ...... 48
2.2.2 Degradation of Peroxide Initiator in Acetonitrile ...... 50
i
2.2.3 Kinetic Studies in Acetonitrile ...... 51
2.2.4 Gas Chromatography Mass Spectrometry (GC/MS) ...... 52
CHAPTER 3 – THE REACTIVITY AND SELECTIVITY OF HYDROXYL RADICAL
REACTIONS IN HYDROCARBON SOLVENTS ...... 57
3.1 Introductory Remarks ...... 57
3.2 Selectivity of Hydroxyl Radical Addition to Toluene (Methylbenzene) ...... 59
3.3 Selectivity of Hydroxyl Radical Addition to other Aromatic Substrates ...... 65
3.3.1 o-Xylene (1,2-Dimethylbenzene) ...... 65
3.3.2 m-Xylene (1,3-Dimethylbenzene) ...... 67
3.3.3 p-Xylene (1,4-Dimethylbenzene) ...... 70
3.3.4 Anisole (Methoxybenzene) ...... 70
3.3.5 Trifluorotoluene (α,α,α-Trifluoromethylbenzene) ...... 75
3.4 Reactivity of Hydroxyl Radical Addition to Toluene ...... 78
3.5 Reactivity of Hydroxyl Radical Addition to Other Aromatics ...... 84
3.5.1 o-Xylene (1,2-Dimethylbenzene) ...... 84
3.5.2 m-Xylene (1,3-Dimethylbenzene) ...... 85
3.5.3 p-Xylene (1,4-Dimethylbenzene) ...... 87
3.5.4 Anisole (Methoxybenzene) ...... 89
3.5.5 Chlorobenzene ...... 91
3.5.6 Trifluorotoluene (α,α,α-trifluoromethylbenzene) ...... 93
CHAPTER 4 –HYDROXYL RADICAL REACTIONS IN ACETONITRILE: THE EFFECT OF
SOLVENT ON RADICAL REACTIONS ...... 102
ii
4.1 Introductory Remarks ...... 102
4.2 Hydroxyl Radical Addition to Toluene (Methylbenzene) ...... 103
4.3 Hydroxyl Radical Addition to other Aromatic Substrates ...... 112
4.3.1 o-Xylene (1,2-Dimethylbenzene) ...... 112
4.3.2 m-Xylene (1,3-Dimethylbenzene) ...... 115
4.3.3 p-Xylene (1,4-Dimethylbenzene) ...... 119
4.3.4 Chlorobenzene ...... 120
4.3.5 Trifluorotoluene (α,α,α-Trifluoromethylbenzene) ...... 124
4.4 Structure-Reactivity Relationships ...... 127
4.5 Preferential Addition of ·OH to ortho-Positions ...... 131
CHAPTER 5 – CONCLUSIONS AND FUTURE EXPERIMENTATION ...... 137
5.1 Introductory Remarks ...... 137
5.2 Future Exploration of ·OH Reactivity ...... 140
5.2.1 Continued Investigation of Arene Reactivity ...... 140
5.2.2 Secondary Oxidation Products ...... 143
5.2.3 Expansion of Solvent Effects ...... 146
APPENDIX I – CALIBRATION CURVES OF STANDARDS...... 150
APPENDIX II – THERMAL DECOMPOSITION OF AZOHYDROPEROXIDE INITIATOR IN
ACETONITRILE ...... 155
APPENDIX III – ADDITIONAL DATA FOR HYDROXYL RADICAL ADDITIONS TO ARENES
...... 158
BIBLIOGRAPHY ...... 182
iii
List of Figures
Figure 1. Representative PAHs...... 3
Figure 2. PCBs and PDBEs...... 4
Figure 3. Representative agrochemicals...... 6
Figure 4.Representative pharmaceuticals, illicit drugs, and chlorination products...... 7
Figure 5. Sulfmethoxazole decomposition during chlorination...... 10
Figure 6. Modes of reactivity for OH...... 21
Figure 7. Potential energy profile of the reaction of A + B → C → D + E...... 23
Figure 8. Reaction energy profiles...... 27
Figure 9. Resonance contributors of cyclohexadienyl radical...... 28
Figure 10. Resonance contributors potentially significant to ·OH reactions...... 29
Figure 11. ΔG of hydrogen abstraction reactions of α-D-glucopyranose and OH...... 34
Figure 12. Distribution of hydroxylation on toluene...... 60
Figure 13. Relative Arrhenius plot of 2-methylphenol/3-methylphenol...... 62
Figure 14. Relative Arrhenius plot of 3-methylphenol/4-methylphenol...... 63
Figure 15. Relative Arrhenius plot of 4-methylphenol/2-methylphenol...... 63
Figure 16. Distribution of hydroxylation of o-xylene...... 66
Figure 17. Distribution of hydroxylation of m-xylene...... 68
Figure 18. Distribution of hydroxylation of anisole...... 71
Figure 19. Distribution of hydroxylation of chlorobenzene...... 74
Figure 20. Distribution of hydroxylation of trifluorotoluene...... 76
Figure 21. Arrhenius plot of the competitive reaction between toluene and benzene...... 79
Figure 22. Arrhenius plot of the competitive reaction between toluene, accounting for only the
ortho- product, and benzene and OH...... 80
iv
Figure 23. Arrhenius plot of the competitive reaction between toluene, accounting for only the
meta- product, and benzene and OH...... 81
Figure 24. Arrhenius plot of the competitive reaction between toluene, accounting for only the
para- product, and benzene and OH...... 82
Figure 25. Arrhenius plot of the competitive reaction between p-xylene and benzene...... 88
Figure 26. Hammett correlations of monosubstituted arenes...... 95
Figure 27. Activation energy Hammett correlation...... 97
Figure 28. Reactivity of substituted arenes relative to benzene correlated to ionization potential.
...... 99
Figure 29. Distribution of hydroxylation on toluene...... 104
Figure 30. Arrhenius plot of 2-methylphenol/3-methylphenol...... 106
Figure 31. Arrhenius plot of 4-methylphenol/2-methylphenol...... 106
Figure 32. Arrhenius plot of 3-methylphenol/4-methylphenol...... 107
Figure 33. Arrhenius plot of the competitive reaction between toluene, accounting for only the
ortho- product, and benzene with OH...... 109
Figure 34. Arrhenius plot of the competitive reaction between toluene, accounting for only the
meta- product, and benzene with OH...... 110
Figure 35. Arrhenius plot of the competitive reaction between toluene, accounting for only the
para product, and benzene with OH...... 110
Figure 36. Distribution of hydroxylation on o-xylene...... 113
Figure 37. Distribution of hydroxylation on m-xylene...... 116
Figure 38. Distribution of hydroxylation on chlorobenzene...... 121
Figure 39. Distribution of hydroxylation on trifluorotoluene...... 125
Figure 40. Hammett correlations of monosubstituted arenes...... 128
Figure 41. Activation energy Hammett correlation...... 129
v
Figure 42. Reactivity of substituted arenes relative to benzene correlated to ionization potential.
...... 130
Figure 43. Expected OH addition products to heterocyclic and polycyclic arenes...... 142
Figure 44. Calibration curve for phenol ...... 150
Figure 45. Calibration curves for methylphenols...... 151
Figure 46. Calibration curves for o-dimethylphenols...... 151
Figure 47. Calibration curves for m-dimethylphenols...... 152
Figure 48. Calibration curve for p-dimethylphenol...... 152
Figure 49. Calibration curve for methoxyphenols...... 153
Figure 50. Calibration curves for chlorophenols...... 153
Figure 51. Calibration curves for trifluoromethylphenols...... 154
Figure 52. Decomposition kinetics for trial 1...... 156
Figure 53. Decomposition kinetics for trial 2...... 156
Figure 54. Decomposition kinetics for trial 3...... 157
Figure 55. Competitive Arrhenius plot of isomeric products from addition of OH to o-xylene. .. 159
Figure 56. Competitive Arrhenius plot of OH addition to o-xylene and benzene, accounting for
only the 2,3-dimethylphenol product...... 160
Figure 57. Competitive Arrhenius plot of OH addition to o-xylene and benzene, accounting for
only the 3,4-dimethylphenol product...... 161
Figure 58. Competitive Arrhenius plot of 2,4-dimethylphenol and 3,5-dimethylphenol...... 163
Figure 59. Competitive Arrhenius plot of 2,6-dimethylphenol and 2,4-dimethylphenol...... 163
Figure 60. Competitive Arrhenius plot of 3,5-dimethylphenol and 2,6-dimethylphenol...... 164
Figure 61. Competitive Arrhenius plot of OH addition to m-xylene and benzene, accounting for
only the 2,4-dimethylphenol product...... 166
Figure 62. Competitive Arrhenius plot of OH addition to m-xylene and benzene, accounting for
only the 3,5-dimethylphenol product...... 166
vi
Figure 63. Competitive Arrhenius plot of OH addition to m-xylene and benzene, accounting for
only the 2,6-dimethylphenol product...... 167
Figure 64. Competitive Arrhenius plot of 3-methoxyphenol and 2-methoxyphenol...... 169
Figure 65. Competitive Arrhenius plot of 4-methoxyphenol and 2-methoxyphenol...... 169
Figure 66. Competitive Arrhenius plot of 3-methoxyphenol and 4-methoxyphenol...... 170
Figure 67. Competitive Arrhenius plot of OH addition to anisole and benzene, accounting for only
the 2-methoxyphenol product...... 170
Figure 68. Competitive Arrhenius plot of OH addition to anisole and benzene, accounting for only
the 3-methoxyphenol product...... 171
Figure 69. Competitive Arrhenius plot of OH addition to anisole and benzene, accounting for only
the 4-methoxyphenol product...... 171
Figure 70. Competitive Arrhenius plot of 2-chlorophenol and 3-chlorophenol...... 173
Figure 71. Competitive Arrhenius plot of 4-chlorophenol and 2-chlorophenol...... 173
Figure 72. Competitive Arrhenius plot of 4-chlorophenol and 3-chlorophenol...... 174
Figure 73. Competitive Arrhenius plot of OH addition to chlorobenzene and benzene, accounting
for only the 3-chlorophenol product...... 175
Figure 74. Competitive Arrhenius plot of OH addition to chlorobenzene and benzene, accounting
for only the 4-chlorophenol product...... 176
Figure 75. Competitive Arrhenius plot of OH addition to chlorobenzene and benzene, accounting
for only the 2-chlorophenol product...... 176
Figure 76. Competitive Arrhenius plot of 3-trifluoromethylphenol and 4-trifluoromethylphenol. 178
Figure 77. Competitive Arrhenius plot of 3-trifluoromethylphenol and 2-trifluoromethylphenol. 178
Figure 78. Competitive Arrhenius plot of 2-trifluoromethylphenol and 4-trifluoromethylphenol. 179
Figure 79. Competitive Arrhenius plot of trifluorotoluene and benzene, accounting only for the 3-
trifluoromethylphenol product...... 180
vii
Figure 80. Competitive Arrhenius plot of trifluorotoluene and benzene, accounting only for the 4-
trifluoromethylphenol product...... 181
Figure 81. Competitive Arrhenius plot of trifluorotoluene and benzene, accounting only for the 2-
trifluoromethylphenol product...... 181
List of Tables
Table 1. Rate coefficients and reaction times of OH initiator decomposition, and reaction times for
7 half-lives in benzene, based on published values in cyclohexane ...... 49
Table 2. Calculated rate coefficients for the decomposition of peroxide, and reaction times in
acetonitrile...... 50
Table 3. GC separation method parameters ...... 53
Table 4. GC/MS parameters used to analyze sample composition...... 55
Table 5. Concentration ratios, and natural log transformed ratios of products from OH addition to
toluene...... 61
Table 6. Arrhenius parameters calculated for OH addition to toluene...... 64
Table 7. Arrhenius parameters calculated for the addition of OH to o-xylene...... 66
Table 8. Arrhenius parameters calculated for the addition of OH to m-xylene...... 69
Table 9. Arrhenius parameters calculated for the addition of OH to anisole...... 72
Table 10. Arrhenius parameters calculated for the addition of OH to chlorobenzene...... 74
Table 11. Arrhenius parameters calculated for the addition of OH to trifluorotoluene...... 77
Table 12. Arrhenius parameters for the competitive addition of OH to toluene and benzene. ....83
Table 13. Arrhenius parameters for the competitive addition of OH to o-xylene and benzene. ..85
Table 14. Arrhenius parameters for the competitive addition of OH to m-xylene and benzene. .86
Table 15. Arrhenius parameters for the competitive addition of OH to p-xylene and benzene. ..88
Table 16. Arrhenius parameters for the competitive addition of OH to anisole and benzene. ....89
viii
Table 17. Arrhenius parameters for the competitive addition of OH to chlorobezene and benzene.
...... 91
Table 18. Arrhenius parameters for the competitive addition of OH to trifluorotoluene and
benzene...... 94
Table 19. Hammett constants for mono-substituted substrates ...... 96
Table 20. Ionization potentials and relative rate constant...... 100
Table 21. Concentration ratios, and natural log transformed ratios of products from OH addition
to toluene...... 105
Table 22. Arrhenius parameters calculated for OH addition to toluene...... 108
Table 23. Arrhenius parameters for the competitive addition of OH to toluene and benzene in
acetonitrile and hydrocarbon solvents...... 111
Table 24. Arrhenius parameters calculated for the addition of OH to o-xylene...... 114
Table 25. Arrhenius parameters calculated for the addition of OH to m-xylene...... 118
Table 26. Arrhenius parameters calculated for the addition of OH to p-xylene...... 120
Table 27. Arrhenius parameters calculated for the addition of OH to chlorobenzene...... 123
Table 28. Arrhenius parameters calculated for the addition of OH to trifluorotoluene...... 126
Table 30. Comparison of SAR correlations...... 130
Table 31. Concentration ratios of isomeric products from addition of OH to o-xylene in benzene
and acetonitrile...... 159
Table 32. Concentration ratios of addition products of OH and o-xylene relative to phenol in
benzene and acetonitrile...... 160
Table 33. Concentration ratios of isomeric products from addition of OH to m-xylene in benzene.
...... 162
Table 34. Concentration ratios of isomeric products from addition of OH to m-xylene in acetonitrile.
...... 162
ix
Table 35. Concentration ratios of addition products of OH and m-xylene relative to phenol in
benzene and acetonitrile ...... 165
Table 36. Concentration ratios of isomeric products from addition of OH to anisole in benzene.
...... 168
Table 37. Concentration ratios of isomeric products from addition of OH to chlorobenzene
inhydrocarbon and acetonitrile...... 172
Table 38. Concentration ratios of addition products of OH and chlorobenzene relative to phenol
in benzene...... 174
Table 39.Concentration ratios of addition products of OH and chlorobenzene relative to phenol in
acetonitrile...... 175
Table 40. Concentration ratios of isomeric products from addition of OH to trifluorotoluene in
hydrocarbons and acetonitrile...... 177
Table 41. Concentration ratios of addition products of OH and trifluorotoluene relative to phenol
in benzene...... 179
Table 42. Concentration ratios of addition products of OH and trifluorotoluene relative to phenol
in acetonitrile...... 180
List of Schemes
Scheme 1. Photolytic generation of hydroxyl radical from N-hydroxypyridine-2-thione...... 31
Scheme 2. Degradation pathway of nitrobenzene upon reaction with •OH...... 33
Scheme 3. A competitive rate study of PhCH3 v. PhH with ·OH in the presence of N-oxyl radical
trap...... 35
Scheme 4. Generation of ·OH by thermal decomposition...... 36
Scheme 5. Induced decomposition of ·OH initiator, and retardation using N-oxyl trap...... 37
Scheme 6. Synthesis of TMS phenyl ether standards...... 43
x
Scheme 7.Synthesis of TEMPO ...... 46
Scheme 8. Synthesis of 2-Propanone, 2-(1,1-dimethylethyl)hydrazone ...... 47
Scheme 9. Synthesis of 2-tert-butyl-2-hydroperoxypropan-2-yl-2-diazene...... 48
Scheme 10. Reaction of toluene with OH...... 59
Scheme 11. Reaction of o-xylene with OH...... 65
Scheme 12. Reaction of m-xylene with OH...... 67
Scheme 13. Reaction of anisole with OH...... 70
Scheme 14. Reaction of chlorobenzene with OH...... 73
Scheme 15. Reaction of trifluorotoluene with OH...... 76
Scheme 16. Competitive reaction of toluene and benzene...... 79
Scheme 17. Competitive reaction of o-xylene and benzene ...... 84
Scheme 18. Competitive reaction of m-xylene and benzene...... 85
Scheme 19. Competitive reaction of p-xylene and benzene...... 87
Scheme 20. Competitive reaction of anisole and benzene ...... 89
Scheme 21. Competitive reaction of chlorobenzene and benzene...... 91
Scheme 22. Competitive reaction of trifluorotoluene and benzene...... 93
Scheme 23. Reaction of toluene with OH in acetonitrile...... 103
Scheme 24. Reaction of o-xylene with OH in acetonitrile...... 112
Scheme 25. Reaction of m-xylene with OH in acetonitrile...... 115
Scheme 26. Competitive reaction of p-xylene and benzene in acetonitrile...... 119
Scheme 27. Reaction of chlorobenzene with OH in acetonitrile...... 121
Scheme 28. Reaction of trifluorotoluene with OH in acetonitrile...... 124
Scheme 29. Steric interaction between methylated arenes and TEMPO during possible adduct
formation...... 132
Scheme 30. Oxygen trapping of cyclohexadienyl radical, and re-aromatization...... 133
Scheme 31. Intermediates of OH addition to naphthalene...... 134
xi
Scheme 32. Isomerization of ipso addition product...... 135
Scheme 33. Approach of OH during hydrogen abstraction reactions...... 136
Scheme 34. Delocalization of unpaired electron in m-cresol OH addition...... 143
Scheme 35. Dakin oxidation...... 144
Scheme 36. ortho- formylation of phenol...... 145
Scheme 37. Oxidation of cyclohexanediones...... 145
Scheme 38. Reduction of benzoquinone to hydroquinone...... 145
xii
CHAPTER 1 - INTRODUCTION
It is generally accepted that in a modern, industrialized society, we have the ability to synthesize and utilize chemicals with a vast array of useful and beneficial properties. When these chemicals escape into the environment they may have unanticipated deleterious effects. Similarly, many chemical processes central to our society (such as energy production), generate byproducts which may be potentially harmful. Sometimes, these products may by processed harmlessly by biological and geochemical means; in other cases they are not, and their persistence and/or toxicity in the environment may cause long-term harm to ecosystems and human health. In such cases, it is incumbent upon us, as a society, to intervene to prevent such harm – by limiting the output of pollutants, by treatment of waste streams, by remediation of affected sites, or by other means. The preservation and maintenance of natural air and water resources in the United States are guiding principles behind the Clean Air Act (1970),1 and the Clean Water Act (1972).2
If we are to minimize the impact of pollutants in the environment, we must be able to understand and model the fundamental chemistry of these pollutants, particularly with highly reactive species that are generated in the environment, such as the hydroxyl radical (·OH). In this study, the reactivity and selectivity of hydroxyl radical reactions with model compounds structurally similar to environmental pollutants is described. The data obtained are one method to understand these processes at a molecular level, to provide accurate data useful to those who model such chemistry in the environment.
Chapter 1. Introduction
1.1 Organic Pollutants: Some Representative Classes
In recent decades, organic pollutants have been detected with increasing frequency in trace concentrations in the environment.3 These contaminants cover a wide range of chemical classes, broadly classified as emerging contaminants (ECs) or persistent organic pollutants (POPs). There is no clear definition of ECs.4 Often the definition is dependent on the timing of the analyses, as the reappearance of some contaminants thought to have been eradicated from the environment, or newly discovered ecotoxicological effects of existing contaminants, have recently given rise to the term re-emerging contaminants.4 ECs cover a wide range of compounds, including pharmaceuticals and personal care products (PPCPs), agrochemicals, industrial chemicals, and natural products of biological origin, such as domoic and kainic acids found in harmful algal blooms.4-5 Persistent organic pollutants (POPs), sometimes referred to as legacy contaminants, include the more extensively studied species such as polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). Many ECs and POPs are known to exhibit deleterious effects upon human and/or ecological health.4, 6
Exposure risk to humans is calculated based on the acceptable daily intake (ADI) value, from studies marking the lowest observed adverse effect level in acute toxicity studies.3 In water supplies, for example, contaminants of greatest concern occur in concentrations greater than the
ADI for a person consuming 2 L of water per day, the lower end of recommended daily consumption.3 Many studies have been undertaken to show the toxicity a given contaminant has on individuals; however, it is difficult to extrapolate these studies to the complex mixture of contaminants found in the environment.7
A comprehensive review of the chemistry of all detected contaminant classes lies outside the scope of this work. Instead, certain classes of contaminants are briefly considered to provide
2
Chapter 1. Introduction
illustrative examples of structural motifs common to many environmental contaminants of potential concern.
1.1.1 Polycyclic Aromatic Hydrocarbons (PAHs)
PAHs have been found in many environments as they are typically widely dispersed, and have noted carcinogenic and genotoxic properties, which increase with UV exposure due to their ability to absorb radiation and generate reactive oxygen species (ROS).8 Some commonly occurring PAHs are shown in Figure 1.
Figure 1. Representative PAHs.
PAHs are introduced to the atmosphere and aquatic environment as incomplete combustion byproducts found in the exhaust of many combustion engines, from oil drilling sites and spills, as well as from coking processes in which carbon-containing materials are heated to high temperatures in the absence of oxygen.8a, 9 These modes of introduction lead to easy dispersal of the contaminants in the atmosphere.8a Models have been found to underestimate the concentrations of PAHs in the environment, leading to the discovery of the importance of secondary emission sources, particularly near oil shale fields.10 PAHs are typically sparingly soluble in water with solubilities ranging between 34,800 to only 1.82 μg/L, and exhibit large octanol-water partition coefficients (logKow) with values of 3.26 and 6.24 measured for naphthalene and benzopyrene, respectively,11 indicative of their low solubility in water. Addition of alkyl groups to the rings leads to increased toxicity and further reduces their solubility. Due to these properties, PAHs can accumulate in sediments, and are correlated to the amount and quality, or degree of oxidation due to diagenesis, of organic carbon present.12 There is a
3
Chapter 1. Introduction
correlation between the age of sediments and their binding affinity, as younger, less heavily oxygenated humic soils adsorb PAHs more strongly.12 During their transport PAHs are subjected to photolytic oxygenation which increases their toxicity.13 Elevated levels of PAHs are found in soils surrounding coking plants, often associated with heavier organic matter.12 The ratios of different PAHs can be used, with noted uncertainties, to determine the source of their introduction to the environment.10 Biodegradation of these compounds has been shown to be effective in remediation of soils.8b
1.1.2 Polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs)
PCBs (Figure 2) were historically used as insulating fluids in capacitors and transformers, hydraulic fluids, and to a lesser extent in adhesives, plastics, pesticide extenders, lubricants, and heat transfer systems.14 Although production of PCBs has been banned since 1977, it is still common to find them in mammalian blood samples and throughout the environment.15 The continued observation of PCBs under these circumstances is credited to its cycling in the environment through vaporization into the atmosphere, and subsequent re-deposition to the terrestrial environment during precipitation events. In addition, leaching of material from waste disposal sites contributes to PCB concentrations.14
Figure 2. PCBs and PDBEs.
In general, increasing the degree of chlorination tends to increase the recalcitrance of the contaminant.14 In acute toxicity studies, PCBs were found to cause acne-like outbreaks, auditory and visual impairment, and spasms.14 Chronic exposure to PCBs leads to the same symptoms 4
Chapter 1. Introduction
as the acute toxicity studies, but are accompanied by irritation of throat and nose, as well as changes in liver function. There is some evidence to suggest a lifetime exposure to PCBs has a carcinogenic effect as well.14
Polybrominated dipehnylethers (PBDEs) are typically used as flame retardants in petroleum-derived products such as foams, fabrics, electronics, and building materials.16
Legislation has been passed in the last 15 years prohibiting the use of PBDEs in many products, and in some cases their production has been banned. The recalcitrance, bioaccumulation and magnification, vapor pressure, and toxicity of these molecules all increase with fewer bromine substituents.16 Decomposition of these species is typically believed to proceed via photolytic debromination, but it is unclear if this is the mechanism by which degradation occurs in the environment.16 PBDEs are characterized by their low solubility in water and high lipophilicity, causing them to strongly adsorb to soils, sediments, and sludge.17 PDBEs are maintained in the bloodstream due to their close resemblance to naturally occurring thyroid hormones and their high lipophilicity. PDBEs are known to behave as endocrine disruptors.16 Exposure studies in mice and rats have shown PDBEs delay puberty, and exhibit neurotoxicity in neonates with long lasting behavioral effects.16
Concentrations of PCBs are tending to decrease in human and ecological samples.
However, PDBE concentrations are increasing at an exponential rate except in nations and states that have banned their production or use.16 The concentrations of these two contaminant classes are not correlated well with one another, and are indicative of a difference in exposure rates and/or sources. Research is still needed on the effects of their metabolites, since only the commercially available mixtures, which differ from those found in the environment or animal tissues, have been studied.16
5
Chapter 1. Introduction
1.1.3 Agrochemicals
Chloroacetanilide herbicides, one of the most commonly used class of herbicides in the
US, are typically applied to corn and soybean crops to control grasses and broadleaf weeds.18
They are highly mobile in the environment through waterways and do not adsorb well to soil.19
They do, however, associate with organic carbon in soil.18 The primary metabolites, i.e., dechlorinated sulfonic and oxanilic acids, accumulate in soils but are difficult to analyze, as are many polar ionic compounds.18-19 The toxicity of metolachlor (Figure 3) is still a matter of debate, as its presence increases liver nodules and mental deficiencies in rats, but not rabbits.20 Their metabolites not mutagenic nor bioaccumulative at concentrations typically found in the environment, but may persist for years.18
Figure 3. Representative agrochemicals.
Organophosphorus pesticide (OP) residues have been found throughout the environment in ground and surface waters, as well as in food designated for human consumption.21 OPs disrupt the nervous system of insects as well as many non-target organisms such as bees, aquatic invertebrates, and birds.22 This occurs via binding and phosphorylation of acetylcholinesterase, which causes acetylcholine, a neurotransmitter, to accumulate and continually stimulate receptors throughout the central and peripheral nervous systems.23 OPs are transformed in the liver into oxons, in which the sulfur bound to phosphorus is converted to an oxygen, which become more 6
Chapter 1. Introduction
potent toxins.23 OPs are transferred via runoff of treated fields or drifting in the wind during application.22 The primary degradation pathway of OPs in an aqueous environment is hydrolysis to yield nitrophenol.24 However, this may not always be a homogeneous hydrolysis reaction in the environment as adsorption onto clays, such as bentonite, bearing amine substituents shows formation of an intermediate, which is particularly important at near-neutral pH.24 Natural organic matter (NOM) has been found to reduce the nitro group of OPs in anoxic environments when suitable electron donors are present, as is often the case in sediments.22 The EPA has determined that there is little risk of human exposure through drinking water from ground water wells, and only during high rates of precipitation and run-off immediately after application.23
1.1.4 Pharmaceuticals and Illicit Drugs
Of the myriad drugs, both prescribed and illicit, only a few classes are discussed, and their representative structures shown in Figure 4. All these drugs have been detected in wastewater, but typically their metabolites are detected in larger concentrations.25
Figure 4.Representative pharmaceuticals, illicit drugs, and chlorination products.
7
Chapter 1. Introduction
The extensively studied pharmacokinetics of prescribed medications cannot be used when predicting degradation and transformation in the environment as other reaction pathways predominate in these instances.26 Unaltered drugs can be introduced through excrement or during disposal of unwanted or expired medications, as the FDA often suggests disposal in garbage or in certain cases flushing the drugs down a toilet.27 It is, in fact, illegal to possess some of these drugs without a doctor’s prescription, and they cannot be taken to a pharmacy or law enforcement agencies for disposal.28 It is difficult to elucidate the effects exhibited by these contaminants on aquatic biota as they are introduced with many other contaminants, and an apparent synergistic effect is observed.29
Morphine is the prototypical, and arguably the first, analgesic from which all others are ranked; the ranking of analgesics is typically based on rodent tests.30 Morphine is excreted to a small extent as the parent drug when administered to patients, but is the major metabolite of heroin.25 Wastewater treatment plants (WWTPs) in Europe were shown to remove the drug below the limit of quantification (LOQ), but not below the limit of detection.31
Benzodiazepines (BZDs), shown in Figure 4, represent an extensively studied class of compounds with more than 3000 structural analogs synthesized.30 There are 35 different BZDs in use throughout the world, all of which contain an electron withdrawing group at position 7 (R1 in Figure 4).30 Of these, diazepam (Valium ®) is the most widely prescribed and clonazepam
(Klonopin ®) is the longest acting.30 They are typically used as anxiolytics, hypnotics, and soporifics depending on their duration of action.30 Diazepam is insufficiently degraded in WWTPs, adsorbs onto sediments, and is rather persistent in the environment.26, 32 When treated by ozonolysis, degradation is very slow, and possibly only occurs by reactions with ·OH.32 The drug is also resistant to degradation by microbial methods, but what degradation occurs proceeds via demethylation; the demethylated molecule is also the major human metabolite.33 Diazepam has been detected in both receiving and finished (see below) waters of a drinking water treatment 8
Chapter 1. Introduction
plant at median concentrations of 0.43 and 0.33 ng/L, respectively.34 Exposure studies in fish have shown significant alterations in gene expression at ppt concentrations, particularly those governing circadian rhythm.35
Synthetic estrogens shown in Figure 4 have been found in surface waters at concentrations that may disrupt normal hormonal activity in aquatic communities.3 Mestranol is demethylated to ethinyl estradiol in the liver.36 Ethinyl estradiol has been shown to be degraded
37 by nitrifying bacteria in concert with the transformation of NH3 to NO3 in a co-metabolic process.
Algae have also been shown to degrade ethinyl estradiol by brominating the aromatic ring, which may pose an increased risk to biota as many brominated organics have heightened lipophilicities which increase the chance of bioconcentration.38 Ethinyl estradiol is more potent, by a factor of
100, than the endogenous hormone, and feminization effects have been observed in young fish communities, sometimes complete.39 The synthetic and endogenous hormones exhibit additive effects, and total estrogenic loads should be used when correlating data from the environment, particularly when the concentrations are below the lowest observed effect concentrations of the individual molecules.39b
Sulfamethoxazole (
Figure 5, below) is an antibiotic medication that is detected in many wastewater streams.
It degrades in surface waters by photolysis, but ground waters are susceptible to accumulation of the drug since photolysis cannot take place.40 The antimicrobial is found in surface waters at
9
Chapter 1. Introduction
median concentrations of 0.015 μg L-1, and has been shown to inhibit microbial nitrate reduction rates at these concentrations.3, 40
Figure 5. Sulfmethoxazole decomposition during chlorination.
Degradation of the molecule occurs quite rapidly during chlorination in WWTPs, with substantial oxidation of the drug in the range of 5-30 minutes by chlorination of the aniline moiety, which can lead to the minor ortho- chlorinated product or, upon a second chlorination, the major product, N-chloro-p-benzoquinoneimine.41 These, and other oxidation products may be more toxic to aquatic biota than the parent compound.41-42 The antimicrobial activity of some of the transformation products was analyzed, and those which retained the sulfonamide moiety, although less potent, were still found to exhibit antimicrobial properties.42
1.1.5 Structural Features of Contaminants
The diverse contaminants presented herein contain a structural feature in common - an aromatic ring or rings. Aromatic systems may consist of substituted or fused benzene rings, but may also incorporate atoms such as N, O or S in heterocyclic systems. Aromatic rings are a very common moiety in many biologically active compounds and POPs, as well as a common moiety in pollutants in general – the properties of aromatic rings that make them desirable in new product syntheses may also contribute to persistence and toxicity in the environment.
A working definition of an aromatic compound is that it consists of a continuous, cyclic array of p-orbitals that may overlap to generate a set of extended (delocalized) -orbitals. In a 10
Chapter 1. Introduction
single ring compound, there is an additional stipulation that the delocalized -system contain (4n
+ 2) electrons (n = 0,1,2…) – the “Huckel rule”.43 This delocalization results in these compounds exhibiting remarkable stability relative to their conjugated, open chain counterparts.43 In benzene, the stabilization afforded by aromaticity is approximately 152 kJ/mol. This stabilization makes the formation of aromatic compounds thermochemically favorable, and reduces their reactivity - aromatic rings are unreactive towards most reagents, and are difficult to oxidize or reduce (even in the laboratory setting, forcing conditions must be applied to observe such reactions). When reactivity is observed, the intermediates formed are high in energy, and will quickly decompose, often re-establishing the aromaticity of the system – substitution on the ring is far more commonplace than addition to the -system.
The reactivity of aromatic rings, and groups attached to aromatic rings, are known to be dependent on ring substituents - the aromatic ring system is very efficient at transmitting substituent effects, even from relatively remote positions. The effects are well-known, and correlations between the reactivity of a ring and its substituents have been constructed using the
Hammett equation.44 The Hammett equation is to a large degree, the archetype of the structure- reactivity relationship, from which many others are derived. To a large extent, the reactivity of an aromatic ring can be controlled by the judicious selection of substituents. One can construct similar relationships that correlate parameters such as toxicity and bioavailability with substitution in a similar manner.45 Finally, it should be possible to determine if, how, and where on a molecule substitution of a reactive species (such as ·OH) might occur, based on the functional groups present on the ring. This, in turn, would indicate where on the molecule environmental decomposition might occur, and what the primary breakdown products would be. In addition, one could also obtain a sense of the reactivity of the molecule, and the timeframe involved with the decomposition process.
11
Chapter 1. Introduction
The planarity of aromatic rings is useful in principle, as it provides a conformationally rigid framework that in principle allows the design of molecules with groups in specific spatial relationships. This is useful, for example, when designing pharmaceuticals. However, planarity also can cause toxicological problems: planar structures are able to insert into the double helix of
DNA in a process known as intercalation. This toxicity has been manipulated to target specific base pair sequences, and many anti-cancer drugs have been developed utilizing this approach.46
While this may be beneficial in a clinical setting, broad environmental dispersion of such compounds is undesirable. Planarity, although a common constraint to determine aromaticity, is not always necessary. Some molecules, such as carbon nanotubes or fullerenes, exhibit properties typical of aromatic systems, but do not conform to the planarity “rule”. Such compounds are also being detected in increasing amounts in the environment, and their impact is currently being assessed.47
Understanding the reactions aromatic moieties undergo is particularly useful in developing models for the degradation of molecules containing aromatic rings. To effectively model these biological, geological, and chemical transformations simple aromatic systems provide a good starting point. Once effective models can be constructed with simple aromatic systems, it will become possible to model more complex and unstudied systems.
12
Chapter 1. Introduction
1.2 Sources, Transport, Fates and Treatment of Environmental Contaminants
1.2.1 Sources, Transport and Fates of Contaminants
There are many routes of contaminant introduction to the environment, differentiated as point and non-point sources. Point sources of contamination are a pollutant comes from a known, discrete source, such as WWTP effluent or industrial factories.48 Many PPCPs are introduced through the sewage system, or through direct dumping of product into drains.49 Industrial contaminants are often sent to separate WWTPs than are domestic wastes.49 Many studies show that treatment through WWTPs, both municipal and industrial, do not fully remove the myriad contaminants before discharge into receiving surface waters.49
Non-point sources of contamination occur over a relatively larger area where the origination of the contaminant is difficult to ascertain, whether from agrochemical runoff from fields or via cleaning of dispersion equipment, or atmospheric deposition28, 50 Herbicides and pesticides are introduced by runoff from fields that have been treated, and via cleaning of the dispersion equipment.49 Veterinary medicines are introduced through runoff from livestock pastures, or fields fertilized with manure from medicated animals.49 There is a large influx of pesticides in suburban areas, which is accredited to over-usage.51 Contaminants are also introduced into the environment through incomplete hydrocarbon combustion.8a
Contaminants are transported throughout the environment by surface waters, and typically to a much slower extent by groundwater.49 During transport through riparian environments, contaminants can undergo a multitude of changes including hydrolysis and oxidation with highly
- reactive oxygen species (ROS) such as ·OH, or the hydroperoxyl radical (·OOH), superoxide (O2
1 52 53 ), and singlet oxygen ( O2). These reactions add polar hydroxyl groups to the molecules, which enhance their solubility in water.24 The contaminants can be taken up by organisms, which can release metabolites to the environment, or lead to bio-concentration of contaminants that are
13
Chapter 1. Introduction
lipophilic.54 Bio-concentration can lead to bio-magnification, where contaminants are spread throughout the food web, and concentrate in higher trophic levels via predation.54b Persistent contaminants are believed to end up in the ocean; however, detection is difficult due to dilution and the difficulties of extracting contaminants from highly saline waters.55
Solubility of contaminants in water is an important factor, as hydrophobic contaminants will form aggregates and hamper their movement to the oceans, either by precipitation or chelation to soil minerals.22, 56 Contaminants become sequestered in the soil and become unavailable to local biota. Since bioavailability is not often analyzed in site remediation studies of soils, this can lead to a “do nothing” approach to decontamination of soils.56 However, such an approach can be used to lessen the costs of remediation by identifying pools of contaminants that will no longer affect the environment.56
Many contaminants can be transported through the atmosphere if they are sufficiently volatile, or have a high vapor pressure.57 Volatile organic contaminants can be dissolved into water droplets formed in clouds, and return to the surface in precipitation.57 For example, pesticides have been found in national parks throughout the Western U.S., carried through the atmosphere to later be deposited.57-58 Many of these compounds are soluble in water, and the partition coefficient, (Henry’s constant), must be incorporated to estimate concentrations in both solution and vapor phases.59
Contaminants are exposed to high-energy radiation in the upper atmosphere and can undergo photolysis reactions.60 Contaminants will also be exposed to ozone, and ozonolysis reactions are observed.61 Contaminants will also encounter the hydroxyl radical ·OH in the upper atmosphere.61-62 ·OH will readily react with organic compounds leading to their oxidation, and eventual mineralization to mineral acids or other inorganic molecules. Complexation between
14
Chapter 1. Introduction
organic molecules and mineral acids in the atmosphere decreases their hydrophobicity, and can lead to particulates around which clouds can form.61
1.2.2 Treatment of Contaminants in Wastewater
Availability of fresh, clean water is of utmost importance to human health. Publicly owned treatment works (POTWs), or wastewater treatment plants (WWTPs have all but eliminated the risks of water-borne illnesses such as cholera in industrialized nations.28 However, there are some anthropogenic contaminants that are not effectively removed during typical water treatment processes, particularly contaminants which exhibit hydrophilic properties.63 Continual release of contaminated water through WWTPs increases the risk to organisms that live in aquatic environments, such as behavioral effects or antibiotic resistance.5, 25, 64 Acute toxicity studies of individual contaminants on different biotic compartments have noted that rarely can these studies be extrapolated to understand chronic effects.65 Furthermore, it is difficult to pinpoint which contaminant is exhibiting the observed effects on aquatic biota near WWTPs, as there are apparent synergistic effects when exposed to the myriad contaminants that are discharged to the environment through effluent.65
Typical treatments applied in wastewater and drinking water treatment plants may include the following:66
Screen filtration, the removal of large debris with stationary and moving screens;
Adsorption of organic compounds onto activated carbon, to eliminate taste, color and odor.
This process preferentially removes hydrophobic compounds;66
Preliminary hypochlorite (bleach) addition for removal of microbes and pathogens;
Flocculation via the addition of chelating/coagulating salts, such as iron, calcium,
aluminum, and other multivalent cations. These positive charges will interact with the
15
Chapter 1. Introduction
negatively charged contaminants leading to the formation of aggregates. This is
enhanced by a slow churning of the water. The aggregates, or floc, will float to the top of
the tank where it can be removed by skimming.
Sedimentation: the portion of aggregates not removed by skimming the flocculation tanks
can be removed by sedimentation in a large pond. This technique can also be applied in
earlier stages of water treatments to remove colloids and large particulates.
Filtration: particulates that have not been removed by flocculation or sedimentation
techniques can be removed by passing the water through a porous medium such as
activated carbon or ground walnuts.66
These methods have proved only partially effective at the removal of many environmental contaminants.66 Other techniques which have shown better efficacy include:
Ultraviolet (UV) irradiation: UV radiation will initiate photoreactions as the radiation is of
the correct energy to excite electrons in molecules. It can also be used to eliminate
microbes and pathogens. UV radiation must be applied to particulate-free water to avoid
the so-called “shadow effect”. UV irradiation of contaminated waters has been growing in
implementation, but nitrate levels must be closely monitored. Irradiation of nitrate, a very
common contaminant, produces nitrite, which is toxic.67
Microfiltration (MF) and reverse osmosis (RO): These are broadly similar techniques in
that transport across a microporous medium is used to remove contaminants. Both
techniques have better removal efficiencies of contaminants than filtration, but the residue
and retentate in MF and RO respectively, are considered toxic waste. In RO the retentate
is often recycled through the system multiple times before disposal. Disposal of these
wastes presents problems and adds to costs.
The use of permeable reactive barriers (PRB) as a remediation technique is currently
being explored.68 The barrier consists of either zerovalent iron (ZVI) or, less commonly, 16
Chapter 1. Introduction
activated carbon. The ZVI is susceptible to oxidation in the presence of oxygen, ultimately
leading to the reactivity being compromised.
Activated sludge: Many contaminants can be taken up by microbes and removed from
water. Often this will result in excretion of metabolites, but at much lower concentrations.
Microbial degradation in activated sludge is effective at removing many contaminants
found in wastewater; however, certain compounds remain resistant to these processes.66
It is hypothesized in such cases that either the molecule cannot be utilized for respiration,
or that it is energetically unfavorable to develop the appropriate enzyme to digest the
contaminant at such small concentrations.28, 37
While these methodologies have been shown to be effective at removing contaminants, these technologies suffer from high startup or maintenance costs.66 Alternative advanced oxidative processes (AOPs) are currently being investigated as an option for alternative or additional water treatment.69 AOPs are dependent on the generation of reactive oxygen species (ROS), a class of diverse, highly reactive chemicals, whose commonality is an oxygen atom at the reactive
- center. ROS include, but are not limited to, species such as superoxide (O2 ), hydrogen peroxide
- • (H2O2), organic peroxides (ROOR’), peroxynitrite (ONOO ), hydroperoxyl radicals (HOO ), and hydroxyl radicals (·OH).52 Typically, AOPs are treatment processes that predominantly generate the most reactive of the ROS, ·OH, which can be utilized to degrade contaminants.5 Two common reaction pathways for ·OH are abstraction of hydrogens from alkyl groups, and addition to aromatic rings in an electrophilic fashion.52, 70 Addition of hydroxyl groups to persistent contaminants potentially increases the rate of biodegradation via enzymatic reactions with catechol dioxygenase.64c
Development of kinetic models will improve the treatment process, as dwell times in specific compartments of a WWTP need to be known. Reasonably robust models have been developed for the degradation of environmental contaminants, but they have some limitations. 17
Chapter 1. Introduction
Rate data is required, and these must be either modeled or experimentally measured.71 Both methods of obtaining rate data have disadvantages – Experimentally-measured rates are very time-consuming, and predictive models have only been developed for individual reaction or reagent classes.71 Models have also been developed that assume complete mineralization, i.e., conversion of an organic compound to CO2 and mineral acids. There are many pathways for such mineralization reactions, and all must be accounted for.72 Complete mineralization is not always necessary in the field, as other, less expensive, techniques can be applied once the recalcitrant contaminant has been hydroxylated.
Kinetic data can also be used to investigate persistence of contaminants in the environment.5 Models are hampered by the complexity of the chain reactions initiated by ·OH with electron-rich sites of the myriad contaminants present in aqueous solutions.73 The United
States Environmental Protection Agency (USEPA) utilizes a predictive method for gaseous ·OH reactions with various contaminants.73 The model takes into account various substituents of contaminants, and has good predictive capabilities when compared to experimental numbers.73
However, applying this group contribution method is much more complicated in aqueous systems due to changes in reactivates because of cage effects and the strong hydrogen bonding of ·OH to carbonyl moieties.73-74 Group contribution methods are also hampered when sufficient experimental data is not available.75
1.3 Hydroxyl Radical Chemistry
Many of the reactions which generate ·OH in the environment have also been utilized in laboratory settings. Environmental chemists have utilized these reactions under controlled conditions in an attempt to better understand the natural processes of remediation.76 In particular, Fenton
18
Chapter 1. Introduction
chemistry and TiO2 photoexcitation have been extensively studied as these reactions provide a means of large-scale production of hydroxyl radicals.77
1.3.1 Natural Sources of Hydroxyl Radicals
In the gas phase, ·OH plays an important role in the destruction of many components of the atmosphere, and is a key component of combustion processes.76, 78 In the atmosphere ·OH is generated from solar radiation interacting with moisture directly, dissolved components of cloud and fog waters, or through ozone and subsequent reactions with water.76 Data for the reaction rates of ·OH has been extensively researched and tabulated.79 The rates of formation, and disappearance are strongly correlated, and are used to calculate the steady-state concentration of ·OH.80
In the aquatic environment there is a multitude of reactions which can generate ·OH. Fe(II) is commonly found in groundwater. Iron is leached from many minerals, commonly abbreviated
FeOX.81 Iron salts participate in a process called the Fenton reaction with hydrogen peroxide, to form ·OH.77b Fenton chemistry is dependent on oxygen concentrations, which reduces the produced radical from the ·OH reaction; and pH, as Fe(III) will precipitate under basic conditions.82
Fe(II) and H2O2 are both formed in natural waters by reactions with sunlight. H2O2 is
·- produced by disproportionation of superoxide (O2 ), catalyzed by photoexcited natural organic matter (NOM). NOM is the largest carbon-containing component of most waters, and is known to aid in the transfer of many metals (including iron) as carboxyl groups, a prevalent moiety in
NOM, form strong complexes with metals improving their solubility.82-83,83b Fe(II) is produced by photoexcitation of various carboxyl chelated complexes.83b It has also been discovered that other metals, copper, cobalt, and silver, undergo similar catalytic cycles to generate hydroxyl radicals in Fenton-like reactions. The efficiency of the other metals is lower than that of iron, and often
19
Chapter 1. Introduction
require higher concentrations of the more toxic metals.84 Photolysis of nitrate is another manner in which hydroxyl radicals can be generated. In an excited state the nitrate will disproportionate to give an oxygen radical anion. This radical anion will abstract a hydrogen from water to produce a hydroxyl radical and a hydroxide anion.85
It has recently been discovered chelated metals in NOM can also transport long-lived radicals, called environmentally persistent free radicals (EPFRs).86 The EPFRs are generated in one-electron redox reactions, and then participate in redox cycles similar to semiquinones to generate ·OH.86 It is unclear at present whether complexed iron can degrade contaminants other than the NOM to which it is bound in natural waters. This is due to the high reactivity of ·OH, and the fact that NOM is a major sink. Some 88%, of generated ·OH react with NOM with typical rate coefficients of 2-14 x 108 L (mol C)-1 s-1.80, 86 NOM has also been shown to produce a number of other reactive species that degrade environmental contaminants or add hydroxyl moieties, and it is difficult to distinguish which ROS is responsible.87
With respect to implementation of AOPs, the ability of NOM to act as a dominant ROS sink will hamper the removal process of contaminants through competing reactions.88 It is necessary to remove the NOM from water prior to treatment by AOPs to attain measurable efficiency of contaminant oxidation. Thus, AOPs are often applied as a tertiary water remediation technique, sometimes called a polishing step, once a majority of contaminants have been removed through filtration and biological techniques.87-88 Similarly, salt concentrations may play a role since some ionic compounds, particularly nitrite and bromide, can effectively quench ·OH.
80,89 The products of these reactions will react, in some cases slowly, with organic molecules to generate halogenated compounds.89 The toxicity of many compounds is increased upon addition of halogens, in particular chlorine, and may lead to greater bioaccumulation of the product.16, 54b
- 90 Bromide will react to form toxic bromate, BrO3 , during ozonlysis treatments. Bromide is found in increased concentrations in groundwater near coastal areas due to infiltration of seawater.90 20
Chapter 1. Introduction
1.3.2 Reactions of Hydroxyl Radicals with Organic Compounds
·OH will participate in hydrogen abstraction, addition, and electron transfer reactions
(Figure 6).52, 91
Figure 6. Modes of reactivity for OH.
Hydrogen abstraction (HA) is typically the pathway of reactions between ·OH and alkyl groups. This involves the simultaneous cleavage of a C-H bond to generate a carbon-centered radical, and the formation of the highly stable O-H bond of water.52 As a general principle, the greater the reactivity of the radical the lower the selectivity of its reactions:43 ·OH has been shown to be highly reactive and reacts with little discrimination with respect to hydrocarbon substitution
21
Chapter 1. Introduction
at a diffusion-controlled rate.52, 77a, 92 Abstraction can be directed by favorable, product-stabilizing resonance effects, such as those arising from a lone pair of electrons on an adjacent atom, as in
N- and O-containing molecules.5 The product radical may subsequently undergo a multitude of possible reactions to relieve the spin density; for example, a second abstraction may occur with molecular oxygen to generate ·OOH and an unsaturated molecule (typically an alkene).
Addition typically involves the formation of a new O-C bond arising from hydroxyl radical attack on a -system, such as an alkene. The formed carbon-centered radical is itself reactive towards alkenes, leading to long chain polymer formation. Fenton chemistry has been used to generate hydroxyl radical as an initiating species for free radical homo- and co-polymerization of alkenes and dienes.93 Alkynes tend to be considerably less reactive as radical attack leads to the formation of unstable vinylic radicals.93 Finally, hydroxyl radical may react with -electrons in aromatic ring systems to yield addition products that are resonance-stabilized cyclohexadienyl radicals (Figure 6). These species will typically react to re-establish the aromaticity of the system via reactions such as hydrogen abstraction.
Electron transfer reactions may generate carbocations (oxidation) and carbanions after an addition reaction.91b For a given electron transfer reaction to occur between a donor and acceptor, the vertical ionization energy VIE, of the donor must be less than the vertical electron affinity VEA of the acceptor, i.e., the generated cation must have a reduction potential less than that of ·OH.52
Theoretical calculations and experimentation have shown that ·OH (E0 = 1.9 V relative to NHE), reacts as an electrophile, and that direct electron transfer to carbon centers will typically not be dominant.52, 70 Oxidized metals can form hydro-complexes with ·OH, which leads to EPFRs.86
Reduced metals, or less heavily oxidized metals, may participate in a redox reaction to generate hydroxide anions, raising the pH of the solution.91a
22
Chapter 1. Introduction
Reactions are often visualized in reaction energy profiles, or Gibbs free energy diagrams, which aid in elucidating potential pathways as shown in Figure 7. The free energy of reaction,
G (or Gr) indicates the position of the equilibrium of a reversible reaction, which may also be expressed as an equilibrium constant K,
[퐷]푑[퐸]푒 ∆퐺 = −푅푇푙푛퐾, 퐾 = [퐴]푎[퐵]푏
Where a, b, d and e are the stoichiometric coefficients for the reactants and products respectively.
ǂ
ΔG C Energy
A + B
ΔG
D + E Reaction Progress
Figure 7. Potential energy profile of the reaction of A + B → C → D + E. The species C is an example of a reactive
intermediate, and is not observed in the product mixture.
23
Chapter 1. Introduction
The free energy of reaction is typically expressed in terms in enthalpic (a measure of the thermodynamic stability of a compound) and entropic (a change in the degree of order or probability) terms:
∆퐺 = ∆퐻 − 푇∆푆
ΔH is often calculated from the relative enthalpies of formation (ΔHf) of reactants and products, and can be estimated based on the homolytic bond dissociation energies (BDE) of a compound. C-H and to a lesser extent C-X (C-C and C-Cl) BDEs have been widely used as a measure of the relative stabilization afforded by various functional groups attached to the carbons of alkyl free radicals, and of free radical stability in general.
The rate of reaction for Figure 7 may be given by:
1 푑[퐸] 1 푑[퐷] 1 푑[퐵] 1 푑[퐴] = = − = − = 푘[퐴]푛[퐵]푚 푒 푑푡 푑 푑푡 푏 푑푡 푎 푑푡 where m and n correspond to the order of reaction with respect to each of the reactants. The rate coefficient k is found to exhibit a dependence on temperature that may be described empirically by the Arrhenius equation:
−퐸푎 푘 = 퐴푒 푅푇
where A is denoted the Arrhenius pre-exponential, and Ea the activation energy. R is the ideal gas constant, and T the temperature in K. The latter describes a reaction barrier that is characterized by a critical molecular geometry (the transition state, corresponding to the peaks in the free energy diagram, Figure 7) the reacting system must attain in order for reaction to occur.
Transition State Theory (TST) provides an expression
∆퐺ǂ ∆퐻ǂ ∆푆ǂ 휅푘 푇 −( ) 휅푘 푇 −( ) ( ) 푘 = ( 퐵 ) 푒 푅푇 = ( 퐵 ) 푒 푅푇 푒 푅 ℎ ℎ
24
Chapter 1. Introduction
in terms of the free energy, enthalpy and entropy of activation (G‡, H‡ and S‡). is the transmission coefficient (usually approximately equal to 1), kB the Boltzmann constant, h is
Planck’s constant.52 The two equations can be related by:
‡ ∆퐻 = 퐸푎 − 푅푇 and
ℎ ∆푆ǂ = 푅 [푙푛 ( ) + 푙푛퐴 − 1] 푘퐵푇
Ultimately, it is the magnitude of ΔGǂ that determines the magnitude of the rate coefficient and the rate of a reaction. However, the transition state, by its very definition, is not an experimentally accessible entity. If we are to be able to predict the value of a rate coefficient for a given reaction, it would be useful to derive a relationship that can exhibit correlations between rates and entities we can access experimentally – reactants, products, and to a lesser extent, intermediates. One such theory, the Bell-Evans-Polanyi Theory, posits a linear relationship between the activation energy and the enthalpy of reaction (ΔH). Alternatively, a relationship may be constructed between ΔGǂ and the overall energy change of a reaction ΔG (the Marcus equation).43.
∆퐺0 ∆퐺ǂ = 퐺̃[1 + ( )]2 4퐺̃ where 퐺̃ is the energy related with the activation process, also called the intrinsic barrier, and ΔG0 is the change in free energy for the considered reaction.
Energies of ground state molecules, transition states, and intermediates have been routinely calculated with the advent of modern computing. This data can be used to find the lowest energy pathway, which is most likely to occur in the process of converting reactants to products. Similarly, one may calculate ΔHf for ranges of molecules to show the stabilizing/destabilizing effects substituents, such as aromatic rings and other unsaturated 25
Chapter 1. Introduction
moieties, can have on bond dissociation energies for complicated molecules. The implementation of Frontier Molecular Orbital (FMO) Theory is also utilized by physical chemists. This theory correlates reactivity to the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO). The closer these two are in energy, the more favorable the reaction.43
Utilizing an enthalpic approach leaves many questions as to the reactivity of a molecule.
Reactions, by and large, are carried out in the solution phase which strongly affects bond dissociation, but calculations by DFT and MO methods are normally carried out in the gas phase.
The Hammond postulate is a commonly used tool in physical organic chemistry, and attempts to relate the energies of transition states (ΔGǂ) with those of observable species. The
Hammond postulate states that the TS will be structurally similar to the species (reactant, product or intermediates) that are closer in energy, and that the structural features (such as functional groups) that stabilize these species will also stabilize the transition state. The Hammond postulate is a starting point for the formulation of structure-reactivity relationships. It should be noted that like the Bell-Evans-Polanyi and Marcus relationships, the Hammond postulate is not necessarily universally applicable.
There are three broad cases of transition state characteristics, which are depicted in
Figure 8. Transition states are often described as early or late, as in a) and c), respectively. This designation is more simply stated as, the TS is more similar to the reactants (R) or more similar to the intermediate or product (I or P). Given the high reactivity of hydroxyl radicals, it is reasonable to assume that the transition states for many, if not most, ·OH reactions may be considered early.
26
Chapter 1. Introduction
a) b) c) TS TS TS I or P R
Energy R
I or P
I or P R
Reaction Progress
Figure 8. Reaction energy profiles of a) an early reactant-like TS, b) an intermediate TS, and c) a late,
intermediate/product-like TS.
In reactions where multiple sites of reaction are possible, there is the possibility that certain sites may react in preference to others – such reactions are denoted regioselective, or in cases where only a single site is reacted upon, regiospecific. In such cases, it is important to consider the relative energies of the different TSs (or according to the Hammond postulate, the observable species nearest in energy) which will lead to products. If the process is kinetically controlled, the magnitude of ΔGǂ for each TS will govern the distribution of products—the pathway with the lowest energy will lead to the preferred product.
As an illustrative example, consider the case of electrophilic aromatic substitution (EAS) reactions, a well-known reaction of aromatic systems, and a reaction with possible parallels to the reaction of interest in this study. The rate limiting step is the attack of an electrophile (typically shown as a cationic species E) on the aromatic ring: the disruption of the aromaticity typically makes this step endothermic, and the transition state would be considered late: G‡ is strongly influenced by the factors that stabilize the potential intermediates (Figure 9). The resonance 27
Chapter 1. Introduction
contributors for attack at the ortho- and para- positions allow for delocalization of the positive charge onto the carbon bearing the substituent (R). If the substituent can donate electrons into the ring via resonance or induction the stability of the intermediate is greatly enhanced. The product resulting from attack at the meta- position has no resonance contributors which can be stabilized by the substituent, and is disfavored. It must be noted that there are three resonance contributors for addition to the meta- position which are not shown; only those which have a greater stabilizing effect are shown.
R
p - - + - o E
+ E m + E R R H E R
H E E H
R R R R H H E E
* * H H E E
Figure 9. Resonance contributors of cyclohexadienyl radical.
Groups which donate electrons (electron donating groups or EDG), either through resonance (through conjugated -bond systems) or induction (through the σ-bond frameworks), will lead to a product distribution which greatly favors ortho- and para- substitution, whereas electron withdrawing groups (EWG) lead to meta- dominated substituted products. For a reaction that proceeds via an early TS (such as hydroxyl radical addition to the ring), the Hammond
28
Chapter 1. Introduction
postulate suggests that the nature of the reactant is critical. The resonance contributors for reactant molecules bearing EDG and EWG are shown in Figure 10.
EDG EDG EDG
EWG EWG EWG
Figure 10. Resonance contributors potentially significant to ·OH reactions.
Once again, the presence of EDG activate rings toward electrophiles (such as ·OH, according to previous work)70 by increasing the electron density of the ring, and the ortho- and para- sites show the most enhanced reactivity.
It was noted nearly a century ago that the dissociation constants of benzoic acid and various substituted benzoic acids could be characterized by a substituent constant, σ, which was found to exhibit linear correlations with many observable reaction rates.43 Thus, a structure- reactivity relationship could be constructed - the Hammett Equation:
푘 푙표𝑔 = 𝜎𝜌 푘0
where k is the rate constant for a substituted arene, and k0 is the rate constant of the un- substituted analog, is the substituent constant, and ρ is the reaction constant. This is one of the most commonly applied SAR for describing the reactions of aromatic rings. The substituent
29
Chapter 1. Introduction
constant σ is found from the measurement of the acid dissociation constant, and incorporates both resonance and inductive effects. σ is differentiated into effects observed at the para- position,
σp, and meta- position, σm. The meta- position is dominated by inductive effects, and the para- by resonance and inductive effects to a lesser degree.
When the log of the ratio of rate constants is plotted with the corresponding σ the slope of the line is taken as ρ. The value of ρ is indicative of the amount of negative charge build-up that is generated on the ring during a reaction, and the sensitivity of the reaction to the substituents.
In cases where ρ > 1, the reaction is more sensitive to substituent interactions than the benzoic acid dissociation. For 0 < ρ < 1 the reaction is less sensitive to substitution. In cases where ρ = 0 there is no sensitivity of the reaction to substitution. Finally, the case of ρ < 0 is indicative of a build-up of positive charge (or conversely a loss of electron density) in the ring during the reaction.
Hammett plots are a very useful tool in probing the electronic effects which different substituents impose onto a system. Data for ortho- and ipso- substituents is typically excluded as there is a steric component that also influences reactivity.94 In the case of hydroxyl radical chemistry, there is the additional possibility that unusual stabilization of the ortho- product may be observed due to favorable intramolecular hydrogen bonding interactions. The plot of such data will give insight into the stabilizing/destabilizing effects of substituents through electronic interactions. The electronic interactions are strongest for those substituents able to stabilize radicals through resonance delocalization of electrons, than for inductive effects, which are based on electronegativity.
30
Chapter 1. Introduction
1.3.3 Measuring Hydroxyl Radical Reactivity and Selectivity in Solution
There are a number of experimental studies of hydroxyl radical kinetics and selectivities.
Kinetic data may be measured by direct or indirect methods. The first involves direct measurement of an absolute rate of reaction, typically via spectroscopic means; the second usually involves utilization of relative rate data for a pair of competing reactions where the absolute rate coefficient for one is known.
Generation of ·OH is accomplished by irradiation of a precursor, N-hydroxypyridine-2- thione with pulsed radiation from a laser (Scheme 1).70 ·OH does not have a useful spectroscopic signature in condensed phases, but the strong transient absorbance that trans-stilbene exhibits at 390 nm upon addition of ·OH to either the o- or p- position of the aromatic rings provides a spectroscopic “reporter” that can be used in competitive kinetic experiments.95 In the presence of a competing substrate the absorbance of trans-stilbene will decrease, with the magnitude of the decrease correlated to the reaction rate of the competing substrate and ·OH.95
Scheme 1. Photolytic generation of hydroxyl radical from N-hydroxypyridine-2-thione.
A large number of studies have been published utilizing ·OH generation by a pulse of - radiation with water (pulse radiolysis), with direct detection of the products (or in competition with a reporter species).96 -irradiation generates ·OH in dilute aqueous solutions, as well as hydrated 31
Chapter 1. Introduction
electrons, molecular and atomic hydrogen, and hydrogen peroxide.92 Radiolysis techniques are dependent on how much of the incident radiation is absorbed by the reactants. The efficiencies are given as G values, which represent the number of reactive species generated per 100 eV.92
Solvated electrons can generate ·OH in the presence of N2O-saturated aqueous solutions. This is a very efficient manner of generating ·OH while minimizing the amount of hydrogen atoms found in the solution as hydroxide anions are also formed.88, 92
The limitations of these methods are that although they provide useful kinetic data, they provide relatively little information regarding the selectivity of reaction. Many reactions that generate ·OH also alter the pH of the solution, and ·OH behaves quite differently. Under basic conditions (pH > 7), for example, the presence of hydroxide will remove the hydroxyl radical generating an oxygen radical anion and a molecule of water.92
Selectivity data is often obtained from the classical product distribution study. As an illustrative example, Fenton-like chemistry has been utilized to investigate the degradation of nitrobenzene and the relative abundance of the products found from differing pathways of degradation.14, 97 The study showed that the electrophilic nature of the hydroxyl radical was consistent with previous studies, in that the meta-isomer and its subsequent products were favored.70 Under certain conditions attack at the ipso position was observed followed by elimination of the nitro group to re-aromatize the product. The products of ·OH aromatic addition can be seen in Scheme 2.
Utilizing this approach made the kinetics much more complex, as the concentration of all components of the mixture were in constant flux.97 In addition, it is difficult to study a single elementary step in the reaction, since the products obtained react with additional hydroxyl radicals to generate secondary products that lead to complex mixtures, and initial regioselective preferences may be distorted or even hidden by the selectivities in subsequent steps. In principle,
32
Chapter 1. Introduction
it would be desirable to design an experiment whereby the primary products may be “trapped” to prevent further reaction.
Scheme 2. Degradation pathway of nitrobenzene upon reaction with •OH.
In a similar vein, an electro-Fenton process was used to degrade multiple members of the chloroacetanilide class of herbicides.6a The product distributions were derivatized and analyzed by GC/MS. The herbicides were mostly degraded within the first 5 minutes of the reaction process; however, the treatment was carried out for 20 minutes to observe the biological oxygen demand (BOD) and chemical oxygen demand (COD). The ratio BOD/COD must reach 0.3 before the contaminants can be biodegraded.6a 33
Chapter 1. Introduction
Computational studies of reactivity have become more readily available due to the advent of supercomputing facilities: as an illustrative example, Density functional theory (DFT) was employed to investigate the reactions of ·OH with various sugars and sweeteners.52 Hydrogen abstraction from the carbon atoms was found to be more favorable than from the oxygen atoms in all cases except when comparing C1 to O1.52 The individual activation energies are shown in
Figure 11.
Figure 11. ΔG (kcal/mol) of hydrogen abstraction reactions of α-D-glucopyranose and OH.52
While instructive, one must always recall that calculations by DFT and other MO methods are normally carried out in the gas phase and that in the solution phase (and particularly in water), both hydroxyl radical and any putative substrate are susceptible to stabilizing solvent-solute interactions that will change the energetics of reaction. A large amount of study, and considerable progress, has been made in attempting the model reactions in solution using such methods.
1.4 A Method for the Study of Hydroxyl Radical Chemistry
This research describes the development and implementation of a method that combines the ability to obtain selectivity information from a product study, coupled with the ability to obtain
34
Chapter 1. Introduction
relative rate coefficient data from a competitive kinetic experiment. The primary reaction products are isolated and prevented from further reaction.
The prominent features of the experimental procedure may be illustrated by considering the competing reactions of hydroxyl radical with benzene (PhH) and toluene (PhCH3) are shown in Scheme 3.
Scheme 3. A competitive rate study of PhCH3 v. PhH with ·OH in the presence of N-oxyl radical trap.
The central feature of Scheme 3 is the nitroxide radical (also known as nitroxyl or aminoxyl) trap,
2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO), which is used to terminate the radical reaction by abstracting a hydrogen from the formed cyclohexadienyl radicals.98
Nitroxide radicals are stabilized species, where the spin may be delocalized on both nitrogen and oxygen atoms in a “three-electron bond”.93 The primary mode of decomposition of such radicals involves disproportionation via hydrogen transfer from the position adjacent to the nitrogen.99 Emplacement of alkyl groups at these positions (as in TEMPO) blocks this pathway, allowing these radicals to exhibit long-term persistency: TEMPO is isolable as an orange, crystalline solid. Nitroxide radicals will react with carbon-centered radicals but are unreactive toward oxygen-centered radicals.100 The primary mode of reaction for these species is via radical- radical coupling to generate stable alkoxylamines. The coupling reactions are typically reversible
35
Chapter 1. Introduction
at high temperatures, but alkoxylamines derived from relatively stable free radicals (such as 3 alkyl radicals and allyl radicals – structurally analogous to the radicals generated in this study) will exhibit reversible coupling even at moderate temperatures.101 These species have been extensively used to investigate polymerization reactions,102 and the reversibility of radical coupling formed the starting basis for the process known as RAFT polymerization.103
The abstraction of hydrogen from the cyclohexadienyl radical, which is favorable as it returns aromaticity to the ring, greatly simplifies the reaction allowing for the observation of each addition product. Such reactions have been observed in polymerizing systems involving ·OH reacting with styrene.100 Cyclohexadienyl radicals would continue to react in the absence of nitroxide radical trap to generate a much more complex product mixture.
The generation of ·OH shown Scheme 4 utilizes thermal decomposition of an azohydroperoxide. The decomposition is greatly favored by the generation of dinitrogen, one of the best leaving groups known.43 The stability of t-butyl radicals, due to the multiple opportunities for hyperconjugation with neighboring methyl groups, also favors this decomposition reaction.43
In the absence of a radical trap the reaction will generate t-butyl alcohol via solvent cage recombination, and addition to an arene will not be favored.104
Scheme 4. Generation of ·OH by thermal decomposition.
Decomposition of the azahydroperoxide in the presence of TEMPO greatly retards induced decomposition of the initiator by trapping the generated t-butyl radical shown in Scheme
5.100
36
Chapter 1. Introduction
Scheme 5. Induced decomposition of ·OH initiator, and retardation using N-oxyl trap.
In retarding the induced decomposition, generation of ·OH will follow first order kinetics.104 The peroxide has a weak UV absorbance at 368 nm, making it possible to determine the kinetics of decomposition in various solvents at various temperatures. The half-life, t1/2 of the initiator over a range of temperatures may be determined by:104
0.693 푡 = 1/2 푘
The rate of reaction of hydroxyl radical with a given substrate would be expected to follow second order kinetics:
푑[퐻푂•] − = 푘[퐻푂•][substrate] 푑푡
However, the reaction is carried out under pseudo-first order conditions, whereby the concentration of the reactants is in great excess, and remains effectively constant throughout the course of the reaction. The large excess of competing aromatic substrates also reduces the chance that a second addition of ·OH will occur to generate dihydroxyarenes. This is quite important as the hydroxylated product (containing a resonance-donating –OH group on the ring) might be expected to be more reactive to the electrophilic ·OH.43 Termination by the trap lessens the occurrence of a chain reaction where hydrogen abstraction occurs between the radical and a
37
Chapter 1. Introduction
molecule of the starting material, as well as the coupling of cyclohexadienyl radicals which would generate substituted biphenyls.
The rate equation of this simplified competing reaction in Scheme 3 can now be written as:
푑[· 푂퐻] − = (푘 [· OH][PhH] + 푘 [· OH][PhCH ] + 푘 [· OH][PhCH ] + 푘 [· OH][PhCH ]) 푑푡 푃ℎ퐻 표− 3 푚− 3 푝− 3
where kPhH is the rate coefficient for addition to benzene, ko- the rate coefficient for addition to toluene in the ortho- position, and so on. It should be noted that this expression is for addition reactions only, and hydrogen abstraction from the benzylic position is not considered. Assuming that the abstraction of hydrogen and coupling reactions by TEMPO are irreversible, the rate of formation of phenol from benzene is given by:
푑[푃ℎ푂퐻] = 푘 [PhH][· OH] 푑푡 푃ℎ퐻 and the rates of formation of the three isomers of cresol (methylphenol) from toluene may be given by:
푑[퐶퐻 푃ℎ푂퐻] 3 = (푘 + 푘 + 푘 )[푃ℎ퐶퐻 ][· OH] 푑푡 표− 푚− 푝− 3
Under pseudo-first order conditions the ratio of the products is given by:
푑[퐶퐻 푃ℎ푂퐻] [퐶퐻 푃ℎ푂퐻] 푘표− + 푘푚− + 푘푝− [푃ℎ퐶퐻 ] 3 = 3 = ( ) ( 3 ) 푑[푃ℎ푂퐻] [푃ℎ푂퐻] 푘푃ℎ퐻 [푃ℎ퐻]
By trapping the cyclohexadienyl intermediates all of the addition products may be observed. Due to the paramagnetic broadening exhibited by solutions containing persistent radicals nuclear magnetic resonance (NMR) cannot be used to analyze the product distribution.
However, methods for separation and identification and quantitation of such compounds by
38
Chapter 1. Introduction
GC/MS are known.105 With appropriate calibration of the analytical GC/MS method, the concentrations of each addition product in the mixture may be determined, and the relative rate coefficients calculated. Relative Arrhenius plots can be generated to determine the pre-
exponential factor ratio (APhCH3/APhH) and the difference in activation energy (ΔEa = EaPhH –
EaPhCH3). Due to the exponential nature of Ea, very small differences in activation energy will lead to large differences in reactivity. It is germane to note the differences in Ea observed in this study are likely to be small, and will consequently be susceptible to significant experimental uncertainty.
Similarly, the differences in A factor are typically expected to be quite similar to one another.
The data can be further mined to look at the ratios of different substitution products of a given reactant (i.e. ortho- v. para- and ortho- v. meta- substitutions). This approach will allow for the determination of the selectivity of ·OH of a given substrate. From this data Hammett plots can be generated to show how substitution governs the reactivity of a given aromatic system. The ortho- substituted products cannot be included in this analysis due to steric interactions; however, the relative percentages of each constitutional isomer will be discussed in terms of reactivity.
Knowledge of how reactivity is correlated to structure will help to bolster existing models utilized in remediation studies. As more kinetic data is made available it will become possible to simply look at a contaminants structure and measure or calculate some of its properties, to obtain insight into its reactivity towards the hydroxyl radical (and potentially other ROS), and predict the likely degradation products. This will greatly enhance remediation efforts by allowing for the degradation of previously unstudied molecules to be predicted without requiring additional experimentation.
The overall aims of this study may be summarized as follows:
To develop an experimental methodology, based on the known chemistry of nitroxide
radicals and carbon-centered radicals, that is capable of trapping the intermediates formed 39
Chapter 1. Introduction
from hydroxyl radical attack on aromatic rings. The trapped products must be stable
enough to allow derivatization and analysis.
To develop an analytical methodology capable of selectively detecting and quantifying the
products resulting from hydroxyl radical to arene rings.
To investigate the reactivity of benzene, and substituted benzenes, toward the hydroxyl
radical. Previous experimental studies indicate that the hydroxyl radical may be
considered electrophilic, and that arene reactivity is derived from the nucleophilicity of the
substrate. These studies have used unsubstituted rings, or rings substituted with non-
polar methyl groups – it would be useful to determine whether such behavior holds for
more complex and more polar groups.
To investigate the selectivity of hydroxyl radical with arenes, to determine whether (a)
selectivity is in fact observed for such reactions, and (b) whether the observed selectivity
is consistent with the hypothesis that hydroxyl radical is electrophilic. In particular, it would
be useful to determine, at least on a qualitative, if not quantitative basis, whether the
observed selectivity mirrors that of traditional (non-radical) electrophilic aromatic
substitution.
To determine whether the observed reactivity and selectivity for these reactions is
amenable to quantitative structure-reactivity analysis in the form of linear relationships
such as the Hammett equation.
The development of the experimental methodology and the nature of the obtained kinetic data are described herein.
40
CHAPTER 2 – EXPERIMENTAL METHODOLOGY
2.1 Materials and Instrumentation
All chemicals were purchased from commercial sources, and used without further purification unless specified.
Substrates: Benzene (99.9%), m-xylene (1,3-dimethylbenzene), p-xylene, anisole, and trifluoromethylbenzene were purchased from Sigma Aldrich, toluene from Fisher Scientific, o- xylene from Fluka, and chlorobenzene from Spectrum Chemicals.
Monosubstituted phenols: 2-, 3- and 4-methylphenols (cresols); 2-, 3- and 4-chlorophenols; 2-, 3- and 4-methoxyphenols; and 2-, 3- and 4-trifluoromethylphenols (α,α,α-trifluorocresols) were purchased from Sigma Aldrich.
Disubstituted phenols: 2,3-, 2,4- 2,5-, 2,6-, 3,4- and 3,5-dimethylphenols were purchased from
Sigma Aldrich.
Dichloromethane, 2,2,6,6-tetramethylpiperidine, sodium tungstate decahydrate (99%), acetonitrile, methanol, tert-butylhydrazine hydrochloride, chlorotrimethylsilane, and N,O- bis(trimethylsilyl)trifluoroacetamide (BSTFA) were purchased from Sigma Aldrich. Triethylamine and ethyl ether were purchased from Fluka. Hydrogen peroxide (30% wt), sodium bicarbonate,
H2SO4, acetone, MgSO4, NaCl, glacial acetic acid, NaOH were purchased from Fisher Scientific
Chapter 2. Experimental Methodology
or VWR. All gases were purchased from Praxair: oxygen and argon were industrial grade, and helium at ultra-high purity. All gases were used directly from the cylinders.
1H and 13C NMR spectra were obtained on a 300MHz or 400 MHz JEOL Multinuclear FT-
NMR spectrometer in chloroform-d with no internal standard. Chemical shifts were determined relative to the protonated solvent.
Ultraviolet-visible spectroscopy was carried out on an Agilent 8453 spectrometer with a resolution of 1 nm, an acquisition range for 190-1100 nm, at an acquisition rate of 0.5 s. Heated decomposition trials were placed in an Agilent 89090A thermal sample well.
Quantitative GC/MS data were obtained on an Agilient Technologies 7890A gas chromatograph coupled with an Agilent 5975C Mass Spectrometer (Wilmington, DE, USA). The
MS was operated in positive EI mode using a 70 eV electron beam, and calibrated against perfluorotributylamine (PFTBA).
Samples were introduced to the GC with a split/splitless injector set to 250 °C, and a split ratio of between 50 and 200:1. The GC was equipped with a Zebron ZB-5 5% phenyl – 95% dimethylpolysiloxane column (30m L x 0.25 mm ID, 0.25 μm df). Helium was used as a carrier gas with a flow rate of 1 mL min-1.
Mass spectra were collected using continuous acquisition at a rate of 2.71 scans/sec with a range of m/z 10-550 and resolving power of 0.1 Da on a Triple Axis Detector. Samples were identified by a database search using NIST08, and authentic samples generated to confirm retention time. Authentic standards of silylated phenols were generated by known methods, confirmed by 1H NMR, and injected through the GC/MS to obtain retention times.
42
Chapter 2. Experimental Methodology
Synthesis of Silylated Phenols (TMS Phenyl Ethers).106
Scheme 6. Synthesis of TMS phenyl ether standards.
One equivalent of phenol was dissolved in methylene chloride (dried over CaCl2) to make a 0.16M solution. Three equivalents of triethylamine were added, and the flask purged with argon.
The mixture was capped and stirred for 10 minutes. A total of 2.4 equivalents of chlorotrimethylsilane were added, and the reaction mixture stirred overnight at room temperature.
The solvent was removed from the red reaction mixture by rotary evaporation. The residue was washed with ethyl ether, and filtered through a cotton plug to remove solids. The filtrate was concentrated by rotary evaporation, and the product purified by vacuum distillation on a Kügelrohr and the structure confirmed by 1H NMR.
1 Trimethylsilyloxybenzene (TMS derivative of phenol): H NMR (CDCl3, 400 MHz) δ = 7.24 (dd,
J = 8.8, 6.6 Hz, 2H); 6.96 (t, J = 7.3 Hz, 1H); 6.84 (d, J = 6.6 Hz, 2H); 0.26 (s, 9H) ppm: consistent with previously published spectrum.107
1-methyl-2-trimethylsilyloxybenzene (TMS derivative of o-cresol or 2-methylphenol) 1H NMR
(CDCl3, 300 MHz) δ = 7.15 (d, J = 7.1 Hz, 1H); 7.08 (t, J = 7.4, 6.0, Hz, 1H); 6.89 (t, J = 7.4, 7.1
Hz, 1H); 6.79 (d, J = 8.5 Hz, 1H); 0.28 (s, 9H) ppm.
1-methyl-3-trimethylsilyloxybenzene (TMS derivative of m-cresol or 3-methylphenol) 1H NMR
(CDCl3, 400 MHz) δ = 7.15 (t, J = 7.7 Hz, 1H); 6.85 (d, J = 6.9 Hz, 1H); 6.65-6.71 (m, 2H); 0.31
(s, 9H) ppm.
43
Chapter 2. Experimental Methodology
1-methyl-4-trimethylsilyloxybenzene (TMS derivative of p-cresol or 4-methylphenol) 1H NMR
(CDCl3, 400 MHz) δ = 7.04 (d, J = 8.0 Hz, 2H); 6.76 (d, J = 8.4 Hz, 2H); 2.30 (s, 3H); 0.27 (s, 9H) ppm: consistent with previously published spectrum (although the pair of doublets are cited in the literature as a multiplet, and the TMS group is cited at 0.03 ppm).107b, 108
1,2-dimethyl-4-trimethylsilyloxybenzene (TMS derivative of 3,4-dimethylphenol) 1H NMR
(CDCl3, 300 MHz) δ = 6.97 (d, J = 8.3 Hz, 1H); 6.65 (d, J = 2.5 Hz, 1H); 6.58 (dd, J = 8.0, 2.5 Hz,
1H); 2.20 (s, 3H); 2.19 (s, 3H); 0.25 (s, 9H) ppm: consistent with previously published spectrum.107b
1,2-dimethyl-3-trimethylsilyloxybenzene (TMS derivative of 2,3-dimethylphenol) 1H NMR
(CDCl3, 300 MHz) δ = 6.95 (dd, J = 8.1, 7.7 Hz, 1H); 6.76 (d, J = 7.7 Hz, 1H); 6.65 (d, J = 8.0 Hz,
1H); 2.26 (s, 3H); 2.11 (s, 3H); 0.26 (s, 9H) ppm.
1,3-dimethyl-4-trimethylsilyloxybenzene (TMS derivative of 2,4-dimethylphenol) 1H NMR
(CDCl3, 400 MHz) δ = 7.02 (s, 1H); 6.92 (d, J = 8.0 Hz, 1H); 6.74 (d, J = 8.0 Hz, 1H); 2.32 (s, 3H);
2.23 (s, 3H); 0.33 (s, 9H) ppm.
1,3-dimethyl-2-trimethylsilyloxybenzene (TMS derivative of 2,6-dimethylphenol) 1H NMR
(CDCl3, 400 MHz) δ = 7.02 (d, J = 7.7 Hz, 2H); 6.85 (t, J = 7.3 Hz, 1H); 2.26 (s, 6H); 0.31 (s, 9H) ppm.
1,3-dimethyl-5-trimethylsilyloxybenzene (TMS derivative of 3,5-dimethylphenol) 1H NMR
(CDCl3, 400 MHz) δ = 6.67 (s, 1H); 6.54 (s, 2H); 2.31 (s, 6H); 0.31 (s, 9H) ppm: consistent with previously published spectrum (The authors used a 500 MHz NMR and obtained a higher degree of spectral resolution).107b
44
Chapter 2. Experimental Methodology
1,4-dimethyl-2-trimethylsilyloxybenzene (TMS derivative of 2,5-dimethylphenol) 1H NMR
(CDCl3, 300 MHz) δ = 7.00 (d, J = 7.4 Hz, 1H); 6.69 (d, J = 7.7 Hz, 1H); 6.59 (s, 1H); 2.27 (s, 3H);
2.14 (s, 3H); 0.27 (s, 9H) ppm: consistent with previously published spectrum.109
1 1-methoxy-4-trimethylsilyloxybenzene (TMS derivative of 4-methoxyphenol). H NMR (CDCl3,
400 MHz) δ = 6.78 (apparent s, 4H) 3.76 (s, 3H); 0.25 (s, 9H) ppm.
1 1-methoxy-3-trimethylsilyloxybenzene (TMS derivative of 3-methoxyphenol). H NMR (CDCl3,
400 MHz) δ = 7.13 (dd, J = 8.4, 8.1 Hz, 1H); 6.53 (dd, J = 8.4, 2.2 Hz, 1H); 6.45 (dd, J = 8.1, 2.2
Hz, 1H); 6.41 (dd, J = 2.2, 2.2 Hz, 1H); 3.77 (s, 3H); 0.27 (s, 9H) ppm.
1 1-methoxy-2-trimethylsilyloxybenzene (TMS derivative of 2-methoxyphenol). H NMR (CDCl3,
400 MHz) δ = 6.94 (ddd J = 7.7, 7.2, 1.8 Hz, 1H); 6.81-6.89 (m, 3H); 3.82 (s, 3H); 0.25 (s, 9H) ppm.
1 1-chloro-2-trimethylsilyloxybenzene (TMS derivative of 2-chlorophenol) H NMR (CDCl3, 400
MHz) δ = 7.35 (d, J = 7.7 Hz, 1H); 7.13 (ddd, J = 7.7, 8.0, 1.5 Hz, 1H); 6.89-6.93 (m, 2H) ppm; δ
= 0.30 (s, 9H) ppm.
1 1-chloro-3-trimethylsilyloxybenzene (TMS derivative of 3-chlorophenol) H NMR (CDCl3, 400
MHz) δ = 7.16 (t, J = 8.4, 8.1 Hz, 1H); 6.85 (ddd, J = 8.0, 2.2, 0.8 Hz, 1H); 6.86 (dd, J = 2.2, 2.2
Hz, 1H); 6.74 (ddd, J = 8.1, 2.2, 0.7 Hz, 1H); 0.28 (s, 9H) ppm.
1 1-chloro-4-trimethylsilyloxybenzene (TMS derivative of 4-chlorophenol) H NMR (CDCl3, 400
MHz) δ = 7.19 (d, J = 8.8 Hz, 2H); 6.77 (d, J = 8.8 Hz, 2H); 0.26 (s, 9H) ppm.
1-trifluoromethylmethyl-2-trimethylsilyloxybenzene (TMS derivative of o-trifluorocresol or 2-
1 trifluoromethylphenol) H NMR (CDCl3, 400 MHz) δ = 7.54 (d, J = 7.7 Hz, 1H); 7.40 (t, J = 7.7, 8.1
Hz, 1H); 7.01 (t, J = 7.7 Hz, 8.0, 1H); 6.90 (d, J = 8.0 Hz, 1H); 0.31 (s, 9H) ppm.
45
Chapter 2. Experimental Methodology
1-trifluoromethylmethyl-3-trimethylsilyloxybenzene (TMS derivative of m-trifluorocresol or 3-
1 trifluoromethylphenol) H NMR (CDCl3, 300 MHz) δ = 7.34 (t, J = 8.0, 8.0 Hz, 1H); 7.22 (d, J = 7.7
Hz, 1H); 7.08 (s, 1H); 7.00 (d, J = 7.9 Hz, 1H); δ = 0.29 (s, 9H) ppm.
1-trifluoromethylmethyl-4-trimethylsilyloxybenzene (TMS derivative of p-trifluorocresol or 4-
1 trifluoromethylphenol) H NMR (CDCl3, 300 MHz) δ = 7.50 (d, J = 8.3 Hz, 2H); 6.91 (d, J = 8.2,
Hz, 2H); 0.29 (s, 9H) ppm.
2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO).110
Scheme 7.Synthesis of TEMPO
1 equivalent of 2,2,6,6-tetramethyl piperidine was dissolved in a 7:1 (v/v) mixture of methanol and acetonitrile. Sodium bicarbonate and sodium tungstate decahydrate were added with vigorous stirring. Hydrogen peroxide was added dropwise to the vigorously stirred mixture, and the solution began to change from colorless to a pale yellow during the addition. The reaction flask was capped and allowed to stir for 11.5 hours at room temperature, by which time the reaction mixture had become dark red. The crude reaction mixture was transferred to a separatory funnel with deionized (DI) H2O, and diluted with DI H2O until complete dissolution of the solids was achieved. The product was extracted with pentane, washed sequentially with 10%
H2SO4 and brine before drying over MgSO4. The organic layer was filtered through a cotton plug to remove solids, and concentrated via rotary evaporation. The red-orange solid product was obtained in a 67% yield.
46
Chapter 2. Experimental Methodology
2-Propananone 1,1-dimethylethylhydrazone (acetone tert-butyl hydrazone).104
H O H O, CH COOH, NaOH NH HCl 2 3 N N 2 N H
Scheme 8. Synthesis of 2-Propanone, 2-(1,1-dimethylethyl)hydrazone
A mixture of 16.5 mL of DI H2O, 47 µL glacial acetic acid and 3.65 mL (50 mmol) acetone was deoxygenated by a thin stream of bubbling argon for 30 min, whereupon 3.43 g (86 mmol) of sodium hydroxide pellets were added with vigorous stirring. 5.125 g (41 mmol) of tert-butyl hydrazine hydrochloride was added, and the reaction stirred for 2 hours at room temperature, during which time a pale yellow organic layer was formed. The crude reaction mixture was transferred to a separatory funnel, and extracted with ethyl ether (3 × 50 mL). The combined organic layers were dried over anhydrous MgSO4, and concentrated via rotary evaporation. The product was purified by vacuum distillation, and its structure confirmed by 1H NMR.
1 H NMR (CDCl3, 400 MHz) = 4.19 (br. s, 1H); 1.91 (s, 3H); 1.70 (s, 3H); 1.16 (s, 9H) ppm; (C6D12, 300 MHz, see below) = 3.95 (br. s, 1H); 1.83 (s, 3H); 1.58 (s, 3H); 1.12 (s, 9H)
111 13 ppm: consistent with previously published spectra. C NMR (CDCl3, 100 MHz) = 144.2, 53.1,
28.7, 25.5, 15.3 ppm: consistent with previously published spectra.
2-tert-butyl-2-hydroperoxypropan-2-yl-2-diazene.
Small volumes of peroxide solution were prepared prior to use. Peroxides are thermally unstable, and may be shock-sensitive. Although the published procedure for preparing this compound does isolate it at low temperatures,100 in this study it was not, in order to minimize unnecessary potential laboratory hazard.112
47
Chapter 2. Experimental Methodology
Scheme 9. Synthesis of 2-tert-butyl-2-hydroperoxypropan-2-yl-2-diazene.
A stock solution of acetone tert-butylhydrazone was prepared in deoxygenated benzene
(0.2 g/25 mL). A quartz cuvette, fitted with a threaded cap and silicone septum was filled with the solution, and oxygen was slowly bubbled through the solution using a fine needle. The UV absorbance of the product, 2-tert-butyl-2-hydroperoxypropan-2-yl-2-diazene, was monitored periodically at 368 nm, where the peroxide exhibits a weak (probably n→*) absorbance.
Oxygenation was halted after absorbance reached a maximum (i.e., no significant change in
100 A368nm over a 10 minute interval). The initiator was used without further purification. A similar reaction was carried out in C6D12 to ascertain that the autoxidation reaction was effective in hydrocarbon solvents.
1 H NMR (C6D12, 300 MHz) = 9.04 (br. s, 1H); 1.34 (s, 6H); 1.19 (s, 9H) ppm: consistent with previously published spectra.100
2.2 Experimental Methods
2.2.1 Kinetic Studies in Benzene
For experiments between 50-60° C: Benzene solutions of prepared peroxide and TEMPO
(2-2.5 equivalents relative to the initiator) were combined with the competing aromatic substrate in a 3 or 5 mL conical reaction vial (Reacti-vial™) with a screw top and silicone rubber/PTFE septum. The solution was deoxygenated with a thin stream of bubbling argon, the vial sealed
(assisted with Teflon tape), and warmed to temperature. The reaction mixture was stirred for a time equivalent to at least 7 half-lives of the initiator, based on the published Arrhenius parameters
48
Chapter 2. Experimental Methodology
for decomposition of the peroxide in cyclohexane.104 The times are shown in Table 1. The reaction vial was cooled to room temperature, and the volatiles removed under a stream of argon.
300 µL of N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) was added to the reaction vial, and the solution deoxygenated by bubbling argon. The reaction vial was warmed to 75 °C for 2 hours to ensure derivatization. The contents of the reaction vial were transferred to a chromatography vial with benzene for analysis.
Rxn time T (°C) 1/T (K-1) k (s-1) dec (hr)
50 0.003096 1.78E-05 75.6
55 0.003049 3.56E-05 37.8
60 0.003003 6.98E-05 19.3
65 0.002959 1.34E-04 10.1
70 0.002915 2.52E-04 5.34
75 0.002874 4.66E-04 2.89
Table 1. Rate coefficients and reaction times of OH initiator decomposition, and reaction times for 7 half-lives in
benzene, based on published values in cyclohexane.104
For experiments between 65-75° C: The TEMPO solution and competing aromatic substrate were combined in a vial, purged with argon, capped and sealed, and warmed to temperature for 10 minutes. Once the sample had thermally equilibrated, the initiator solution was injected through the septum. Work-up, derivitization, and analysis were carried out as described for the lower temperature experiments.
49
Chapter 2. Experimental Methodology
2.2.2 Degradation of Peroxide Initiator in Acetonitrile
The published Arrhenius data for the peroxide was obtained in cyclohexane,104 but it is possible that the rate of decomposition of the peroxide may be different in more polar solvents.
To this end, it was necessary to determine the half-life of the initiator in acetonitrile. The initiator was generated by bubbling oxygen through a solution of hydrazone in cyclohexane using a fine needle, as described in 2.1. The UV-Vis spectrometer was set to the specified temperature, and a cuvette with acetonitrile was thermally equilibrated for 10 minutes. Peroxide solution was added, the cuvette shaken vigorously, and the absorbance at 368 nm monitored over time. The decay traces were fitted to a single exponential curve (first-order decay, see Appendix II). The derived data is shown below in Table 2.
temp. rxn time -1 -1 (°C) kdec (s ) avg kdec (s ) ln(kdec.s) (hr)
30 1.37E-05 -11.20
1.81E-05 35 2.17E-05 2.31E-05 -10.68 55.2 2.94E-05 4.91E-05 40 5.29E-05 6.47E-05 -9.65 30.4 0.000092 4.85E-05 45 8.44E-05 7.56E-05 -9.49 17.1 9.38E-05 0.000114 50 0.000149 1.40E-04 -8.87 9.75 0.000157 0.000198 55 0.000227 2.18E-04 -8.43 5.67 0.000228
60 3.30E-04 -8.02 3.35
Table 2. Calculated rate coefficients for the decomposition of peroxide, and reaction times (7 half-lives) in acetonitrile.
The italicized data was calculated from an extrapolated Arrhenius plot, which excluded the bold data. 50
Chapter 2. Experimental Methodology
It should be noted that induced decomposition of the peroxide has been reported previously,100 so the first order assumption may not be entirely valid. From the collected data an
Arrhenius plot was generated and extrapolated to calculate values for kdec at 30 and 60C (Table
2) from the line of best fit. The absorbance data for the 40 °C data was skewed off the line by a single trial shown in Table 2, and was not used to determine the line of best fit for calculating the
30 and 60 °C data. The reaction times were calculated using the line of best fit for the rate coefficients, rather than the measured values. The reaction times are calculated for 7 half-lives of the initiator to ensure near-complete (99.2%) decomposition.
2.2.3 Kinetic Studies in Acetonitrile
For experiments between 35-45 °C: A benzene solution of prepared peroxide initiator
(benzene approximately 88-100 equivalents relative to the initiator), and an acetonitrile solution of TEMPO (2.5 equivalents relative to the initiator), 100 equivalents (relative to the initiator) of competing aromatic substrate (as a solution in acetonitrile) were combined with acetonitrile for a final volume of 3000 μL acetonitrile in a 3 or 5 mL conical reaction vial (Reacti-vial™) with a screw top and silicone rubber/PTFE septum. The reaction vessel was deoxygenated with a thin stream of bubbling argon, the vial sealed (assisted with Teflon tape), and warmed to temperature. The reaction mixture was heated with stirring for a minimum of 7 half-lives of the initiator (Table 2).
The reaction was cooled to room temperature before removing the volatiles with a stream of argon. 300 μL of BSTFA was added to the reaction vial under a stream of argon. The reaction vial was warmed to 75 °C for 2 hours to ensure derivatization. The contents of the reaction vial were transferred to a chromatography vial with benzene for analysis.
51
Chapter 2. Experimental Methodology
2.2.4 Gas Chromatography Mass Spectrometry (GC/MS)105
GC/MS is a widely used analytical method that employs two distinct instruments in tandem:
Gas chromatography (GC) is utilized to separate individual molecules based largely on their boiling points and their affinity to adsorb to the inside of the column substrate. The column is a long, commonly 30 m, very thin, 0.1 to 0.5 mm, borosilicate tube which is coated with a polymer (often a polysiloxane) on the inside, which is held in a temperature-controlled oven.
Molecules must be sufficiently volatile to enter the gas phase upon injection through a heated injector, and survive the change in phase without alteration of the molecular structure. If a molecule is not sufficiently volatile a chemical derivatization (such as the silylation of alcohols and phenols used in this study) may make separation by GC more amenable.
Once volatilized, the molecules will travel down the column assisted by a carrier gas, sometimes referred to as the mobile phase. At this junction a split ratio may be employed. The split ratio introduces only a portion of the analyte onto the column head, and the remainder is vented. Their differential boiling points and affinities toward the column’s polymeric coating will allow for elution from the column at different retention times. Functionalization of the polymer with polar groups may also assist in separation. The retention time of a given compound can be utilized to identify the compound when one has access to an authentic standard.
The injection port is typically very hot, which will lead to homolysis of any stable alkoxylamines formed by the coupling of TEMPO with carbon centered radicals. Hydrogen abstraction from alkyl side chains is a potential reaction pathway for hydroxyl radicals with arenes, but is one that is undetected by this particular experimental method. Published LFP-based kinetic
52
Chapter 2. Experimental Methodology
isotope effect (KIE) studies for the reaction of hydroxyl with variously deuterated toluenes indicate that hydrogen abstraction is a relatively minor pathway, at least in acetonitrile.70, 95
The relevant parameters for GC analysis of various product mixtures obtained in this study are shown in
Table 3. Note that the oven temperature may be programmed to increase (ramp) at certain rates over the course of an analytical run from an initial temperature (Ti) to a final temperature
(Tf).
T hold ramp T hold split solvent i f acquisition substrate oven time rate(s) (°C oven time ratio delay time (min) (°C) (min) min-1) (°C) (min)
toluene 200 : 1 2 120 4 40 240 0 7
o-xylene 200 : 1 2 120 4 40 240 0 7
1 90 0 m-xylene 200 : 1 2 80 15 33.96 25 314 0
p-xylene 200 : 1 2 120 4 40 240 0 7
anisole 50 : 1 2 120 4 40 240 0 7
chlorobenzene 200 : 1 2 120 4 40 240 0 7
trifluorotoluene 200 : 1 1.5 140 3 50 240 0 5
Table 3. GC separation method parameters, Note that the m-xylene method employs a double ramp.
Mass spectrometry is utilized to in tandem with GC to identify and quantify reaction products. MS relies on generating a charged ion, and multiple methods exist that allow both cations and anions to be analyzed. Pertinent to this discussion is electron impact (EI) ionization:
In EI, a stream of the analyte is bombarded with a beam of electrons. The proximity of the electron
53
Chapter 2. Experimental Methodology
beam to the molecule will eject an electron from the molecule. The electrons from the beam do not collide with electrons in the molecule or the molecule itself. Rather it is the electrostatic repulsion that ejects an electron from the molecule to generate the positively charged cation.
The cation is introduced into a quadrupole mass filter (QMF), which moves the ion through space via electrostatic attractions. At the end of the quadrupole lies the detector. When struck by the cation the detector releases a cascade of electrons. The intensity of the signal is proportional to the m/z ratio of the cation. The detector is very sensitive, and should not be overloaded.
Typically the analyte is dissolved in a solvent, and the solvent delay should be employed to reduce the risk of overloading the detector. A solvent delay allows for the mass spectrometer to not be in use for a given amount of time, and the solvent eluted from the GC column is vented.
The cation that is generated is often of sufficiently high energy that rearrangements and fragmentations to more stable ions are observed. The ion formed in the greatest quantity is termed the base peak. The base peak is normalized, and all other ions will be measured relative to the base peak.
Fragmentation patterns are unique to each individual molecule. The generated mass spectrum can be used to compare against mass spectral databases for identification. This, coupled with a standardized retention time from the GC column, results in readily identifiable spectra. In cases where molecules co-elute from the GC column, a selected ion can be monitored
(SIM) rather than the total ion chromatogram (TIC). This generates an extracted mass chromatogram. The ion selected to generate the extracted mass chromatogram must be chosen with care. It must not be of the same mass as the molecular ion or a fragment of the interfering compound, and is ideally greater in mass. It is also useful to select the base peak or other favorable fragment ion when extracting the chromatogram. The molecular ions, and the base peaks used for SIM extraction in this study are summarized in Table 4.
54
Chapter 2. Experimental Methodology
molecular base method analyte retention time (min) ion peak
2-CH3PhOTMS 190 165 2.93
3-CH3PhOTMS 190 165 3.00 toluene 4-CH3PhOTMS 190 165 3.10 PhOTMS 166 151 2.33
2,3-(CH3)3PhOTMS 194 179 4.41
o-xylene 3,4-(CH3)3PhOTMS 194 179 4.52 PhOTMS 166 151 2.33
2,4-(CH3)3PhOTMS 194 179 21.84
3,5-(CH3)3PhOTMS 194 179 22.05 m-xylene 2,6-(CH3)3PhOTMS 194 179 22.79 PhOTMS 166 151 6.05
2,5-(CH3)3PhOTMS 194 179 4.61 p-xylene PhOTMS 166 151 2.76
2-OCH3PhOTMS 196 166 4.78
3-OCH3PhOTMS 196 181 5.31 anisole 4-OCH3PhOTMS 196 181 5.37 PhOTMS 166 151 2.77 2-ClPhOTMS 200 185 4.58 3-ClPhOTMS 200 185 4.71 chlorobenzene 4-ClPhOTMS 200 185 4.89 PhOTMS 166 151 2.75
3-CF3PhOTMS 234 219 1.79
4-CF3PhOTMS 234 219 1.88 trifluorotoluene 2-CF3PhOTMS 234 219 1.91 PhOTMS 166 151 1.84
Table 4. GC/MS parameters used to analyze sample composition.
When compared to a calibration curve and ideally an internal standard, concentrations can be discerned from the TIC or SIM. The calibration curve is generated by serial dilution of a standard solution, and injection into the GC/MS. The calibration curve must be generated under
55
Chapter 2. Experimental Methodology
the same conditions as the samples are analyzed to ensure consistent fragmentation between the calibration curve and the samples. This includes observing the same ion if using an extracted mass chromatogram for quantization.
Each derivatized product mixture was injected into a GC-MS in triplicate. The base peak for each expected addition product was used to extract individual chromatograms from the TIC.
In most cases this corresponded to the loss of a methyl group (M+-15 Da), as is common in TMS ethers.105 The extracted mass chromatograms were then integrated, and these numbers entered into a spreadsheet.
The integration of phenyl TMS ether was corrected by multiplying by the molar ratio, , to allow for comparison of a 1:1 molar ratio. The integrations were assigned a level of significance based on 3σ (99% confidence) of the triplicate injections. The measured integrations were converted to concentrations with calibration curves (see Appendix I), and the ratios of the products taken. Only integrations that met the limit of quantitation (LOQ) were utilized in the analysis, unless otherwise stated. LOQ was defined as the 95% confidence limit for the intercept obtained from a linear regression analysis of the calibration curves.113 The difference in confidence intervals utilized in the analysis (99% v. 95%) was due to the lack of an internal standard. Percent deviation of the triplicate injections was calculated by taking 3σ/average response. Data for which percent deviation was below a threshold of 10% was averaged to obtain a product ratio for the given reaction. This data was then plotted individually, as well as by average for the given temperature in a relative Arrhenius plots, and the relative Arrhenius parameters determined from linear regression analyses of these plots.
56
CHAPTER 3 – THE REACTIVITY AND SELECTIVITY OF HYDROXYL RADICAL
REACTIONS IN HYDROCARBON SOLVENTS
3.1 Introductory Remarks
Hydrocarbon solvents lie on the opposite end of the “solvent spectrum” from water: they are typically characterized by small or zero dipole moments and limited polarity. They are generally considered to maintain their liquid state via dispersion and weak dipole-dipole interactions, and do not exhibit strong hydrogen bonding interactions. The -system in aromatic rings does impart a certain degree of polarizability, and so dipole–induced dipole interactions may play some role in solvent-solute interactions. These solvents provide a test bed for a proof-of- concept study, such as the one described herein, since the aromatic substrates we wish to consider exhibit a high degree of solubility or miscibility with organic solvents that they do not always exhibit in water. In addition, the peroxide initiator used is likely to degrade rapidly in water, possibly via a non-radical mechanism, and alternative methods of generating ·OH require high energy radiation or an additional work-up step to remove iron salts that would interfere with analysis.
Data presented in this chapter is obtained in mixtures of benzene and the competing substrate. Samples were generated and analyzed by methods outlined in Chapter 2. When a methyl group was present on the compound, as in the cases of toluene, anisole and the three xylene isomers, abstraction of the CH3 hydrogen is a potential reaction pathway for ·OH. In the
Chapter 3. Hydroxyl Radical Reactivity in Benzene
case of the hydrocarbons, trapping of the formed radical would lead to an N-benzyloxypiperidine derivative that would not remain stable in the GC injector.102 In the case of anisole, the trapped radical product would have acetal character, rendering it even more susceptible to decomposition.43, 93
In a number of experiments for the hydrocarbon species, benzaldehyde was observed in the product mixture, and the level observed was found to be dependent on the presence of dissolved oxygen, as there was a decrease in the benzaldehyde product in degassed experiments. This process is known to occur in the gas phase by trapping of the benzyl radical with molecular oxygen. The benzylperoxyl radical is transformed into benzaldehyde upon reaction with a hydroperoxyl radical to re-generate molecular oxygen and water.114 There was not a large change in the amount of benzaldehyde formed relative to the other products in the deoxygenated experiments, which is not surprising due to the low solubility of oxygen in benzene.115 However, benzaldehyde was present even in the degassed experiments, and another mechanism of formation is likely taking place. This could be due to the thermal instability of trapped benzyl radicals101, which could decompose to benzaldehyde and tetramethylpiperidine upon injection through the hot injector port, however, the tetramethylpiperidine was not observed in the TIC. In any case, it is unclear whether conversion of benzyl radical to benzaldehyde would occur in a quantitative manner in these experiments, and so the abstraction pathway cannot be reliably quantified via these methods. Only addition to the ring is considered here.
There is also literature evidence for the elimination of –NO2 groups from nitrobenzene derivatives upon ipso attack of ·OH.97 Experiments were conducted in which the initiator was generated in each of the given competing aromatic substrates, and the experiment conducted in neat solvent. There was no formation of phenol during these experiments, and it can be concluded
• that elimination of NO2 radicals was an isolated case – certainly, NO2 is known to be a stable species. Thus, all phenol observed in the following experiments was due strictly to attack of ·OH
58
Chapter 3. Hydroxyl Radical Reactivity in Benzene
on benzene, and not via elimination of methyl, trifluoromethyl, methoxyl, etc. radicals. In the case of the xylenes, these experiments were not undertaken as the product would be the corresponding cresols, upon elimination of a methyl radical, which were not observed in any of the samples.
In the discussion below, the data for toluene is presented in full, with all associated figures and tables. To assist the reader, data for all other substrates has simply been tablulated. The complete datasets may be found in Appendix III.
3.2 Selectivity of Hydroxyl Radical Addition to Toluene (Methylbenzene)
Selectivity data was generated by comparing the concentrations of each addition site on the competing substrate. In the case of toluene, three addition products are possible (Scheme 10).
Scheme 10. Reaction of toluene with OH.
Figure 12 shows the distribution of cresol isomers generated by the radical hydroxylation of toluene. It is evident that the product distribution remains relatively invariant over the temperature range investigated (50-75C, 323-348K), indicating only relatively small differences in relative activation energies for hydroxyl radical attack at the different sites. The meta- product is clearly disfavored in this substitution when compared to the ortho- and para- products. Although approximately equal amounts of meta- and para- products are formed, it must be recalled that there is only one para- position while there are 2 meta- positions. These observations are in general agreement with the postulated electrophilic nature of ·OH.
59
Chapter 3. Hydroxyl Radical Reactivity in Benzene
distribution of methylphenols 0.7
0.6 avg % 2- MePhOTMS 0.5
0.4 avg % 3- 0.3 MePhOTMS 0.2
0.1 Ratio Ratio isomerofdistribution avg % 4- 0 MePhOTMS 45 55 65 75 Temperature (°C)
Figure 12. Distribution of hydroxylation on toluene. Data points plotted are an average of each injection at the given
temperature and error bars represent the standard deviation of the injections at the given temperature.
Relative Arrhenius parameters for attack of hydroxyl radical at each position of toluene were determined by plotting the natural log of concentration ratios of two isomeric products against the inverse absolute temperature. This manipulated Arrhenius equation gives the y-intercept as the
-1 -1 ratio of A factors, Arel and the negative slope multiplied by R (8.314 J mol K ) gives the differential energy of activation, ΔEa. For products P1 and P2, a plot of ln([P1]/[P2]) against 1/T will give relative
Arrhenius pre-exponential:
Arel = A1/A2
And differential activation energy:
ΔEa = Ea 1– Ea 2
Concentration ratios, and natural log transformed ratios of products from OH addition to toluene are shown in Table 5, and the relative Arrhenius plots in Figure 13, Figure 14, and Figure 15.
Each table and Arrhenius plot has been generated in a manner such that P1 is listed first followed
60
Chapter 3. Hydroxyl Radical Reactivity in Benzene
by P2. That is, in the first comparison of Table 5, Error! Reference source not found.2- methylphenol is P1, and 3-methylphenol is P2.
Concentration Ratios
2-methylphenol v. 4-methylphenol v. 3-methylphenol v. 3-methylphenol 2-methylphenol 4-methylphenol temp. temp-1 ln conc. ln conc. ln conc. conc. ratio conc. ratio conc. ratio (°C) (1/K) ratio ratio ratio
3.68 1.30 0.273 -1.300 0.92 -0.08 75 0.00287 3.70 1.31 0.273 -1.297 0.987 -0.013 3.7 1.3 0.29 -1.24 0.996 -0.004 3.7 1.3 0.265 -1.328 0.982 -0.018 3.77 1.33 0.268 -1.318 0.982 -0.018 70 0.00291 3.78 1.33 0.270 -1.308 0.989 -0.011 3.84 1.35 0.29 -1.24 3.58 1.27 0.27 -1.29 0.94 -0.06 3.7 1.3 0.279 -1.278 0.954 -0.047 65 0.00296 3.76 1.32 0.279 -1.275 0.976 -0.024 3.8 1.3 3.7 1.3 0.26 -1.34 0.91 -0.09 3.8 1.3 0.28 -1.28 0.954 -0.047 60 0.003 3.9 1.4 0.30 -1.22 0.96 -0.04 4.0 1.4 3.8 1.3 0.271 -1.305 0.921 -0.082 3.92 1.37 0.28 -1.29 0.92 -0.08 55 0.00305 0.941 -0.061 3.9 1.4 0.28 -1.26 0.951 -0.050 4 1 0.279 -1.276 0.91 -0.09 50 0.00309 3.8 1.3 0.28 -1.27 0.93 -0.07 3.9 1.4 0.3 -1.3 1 0
Table 5. Concentration ratios, and natural log transformed ratios of products from OH addition to toluene. Significant
figures cited were determined from the degree of experimental error associated with each experiment.
The data presented are internally consistent regardless of the ratio taken. That is, plotting ortho-/meta- returns the same result as a plot of meta-/ ortho-, unless otherwise stated.
61
Chapter 3. Hydroxyl Radical Reactivity in Benzene
2-methylphenol v. 3-methylphenol
1.38 - 1.36
1.34
1.32
MePhOTMS]/[3 -
1.3 MePhOTMS]) y = 166.56x + 0.8352
1.28 R² = 0.2329 ln(avg ln(avg [2
1.26 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315 Temp-1 (1/K)
Figure 13. Relative Arrhenius plot of 2-methylphenol/3-methylphenol.
The data in Figure 13 shows a clear energetic favoritism towards the ortho- isomer as would be expected in electrophilic substitution reactions. Dixon’s Q-test was applied to the datasets to identify outlier data – some points come close to the Q-test cutoffs, and these points may be eliminated with further experimentation. Figure 14 is the Arrhenius plot for the reaction of
·OH to toluene comparing the meta- and para- isomers. As with the ortho-/meta- comparison there is a clear slope associated with the data indicating favoritism towards the para- isomer, as would be expected in electrophilic substitution. The slope is larger in magnitude than the ortho-
/meta- plot, confirming that there is a slight energetic preference towards the para- isomer than the ortho- isomer.
62
Chapter 3. Hydroxyl Radical Reactivity in Benzene
3-methylphenol v. 4-methylphenol 0 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315
-0.01 - -0.02 -0.03 -0.04
-0.05 MePhOTMS]/[4
- -0.06
MePhOTMS]) -0.07 y = -222.71x + 0.6161
-0.08 R² = 0.3419 ln(avg ln(avg [3 -0.09 -0.1 Temp-1 (1/K)
Figure 14. Relative Arrhenius plot of 3-methylphenol/4-methylphenol.
4-methylphenol v. 2-methylphenol -1.2 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315
-1.22 -
-1.24
-1.26
-1.28 MePhOTMS]/[2 - -1.3
MePhOTMS]) y = 53.304x - 1.4418 -1.32 R² = 0.0181
ln(avg ln(avg [4 -1.34
-1.36 Temp-1 (1/K)
Figure 15. Relative Arrhenius plot of 4-methylphenol/2-methylphenol.
Figure 15 is the Arrhenius plot of the para- and ortho- cresol isomers generated from the addition of ·OH to toluene. The reactive sites leading to these products are both activated towards
63
Chapter 3. Hydroxyl Radical Reactivity in Benzene
electrophilic substitution, and by the small slope it is evident that there is very little difference in
2 the Ea of the two transition states. The data are quite scattered, evidenced by the low R value.
The calculated ratio of A factors and ΔEa values calculated from the Arrhenius plots are shown in
Table 6 with their associated range and error. The ratio of the two A factor ratios comparing the ortho- isomer show a larger favoritism towards the ortho- isomer than might be expected on probabilistic terms. For example, if the energy barriers for hydroxyl radical attack at ortho- and para- are effectively the same, one would expect a 2:1 ratio of ortho-:para- products. The values of Arel indicate that the ortho- product is unusually favored, and the favoritism is due to some entropic effect. The A factor ratio for the comparison of meta- and para- products is very near the expected value of 2.
Arrhenius Parameters
competing ΔE error A ratio range a % error products (kJ/mol) (kJ/mol)
2-MePhOH v. 2.3 1.9 2.8 -1.4 0.58 41.6 3-MePhOH
4-MePhOH v. 0.24 0.18 0.31 -0.44 0.79 178.7 2-MePhOH
3-MePhOH v. 1.9 1.5 2.3 1.9 0.62 33.6 4-MePhOH
Table 6. Arrhenius parameters calculated for OH addition to toluene.
The reasons for the very high degree of dominance of the ortho- isomer over the para- isomer is unclear, although it is consistent with previous solution phase studies.116 There is no opportunity for significant hydrogen bonding between the CH3 group and ·OH. Abstraction of the
64
Chapter 3. Hydroxyl Radical Reactivity in Benzene
CH3 hydrogens does occur to some extent, as benzaldehyde was observed in all samples analyzed.
In comparing the activation energies of each isomer it is evident that there is some favoritism towards the para- isomer. This is possibly due to the steric hindrance at the ortho- site, which would be similarly activated towards electrophilic substitution. The numbers are in good agreement showing para- favored over ortho- by ~0.4 kJ/mol. This is nearly the same difference, and well within experimental error, when looking at these two isomers compared to the disfavored meta- product. All data, with the exception of the Ea para- v. ortho- comparison, give small errors and ranges.
3.3 Selectivity of Hydroxyl Radical Addition to other Aromatic Substrates
3.3.1 o-Xylene (1,2-Dimethylbenzene)
The possible reaction outcomes depicted in Scheme 11 are discussed throughout this section.
Scheme 11. Reaction of o-xylene with OH.
Figure 16 shows the percent distribution of products of o-xylene by ·OH. It is clear that there is a much greater preference for the 2,3-dimethylphenol. This is similar to the situation described above for toluene. Both reactive sites on the molecule should be relatively equal in energy when considering the TS. This is in terms of electrophilic substitution, as each has a methyl group in the meta- position and is activated by a donating methyl group in the ortho- and para-
65
Chapter 3. Hydroxyl Radical Reactivity in Benzene
position, for 2,3-dimethyl phenol and 3,4-dimethyl phenol, respectively. As previously observed for toluene, there is clear favoritism towards the ortho- substituted product.
Distribution for o-dimethylphenols 0.650
0.600 avg % 2,3- Me2PhOTMS 0.550
0.500
0.450
0.400 avg % 3,4- Me2PhOTMS
0.350 Ratio Ratio isomerofdistribution 0.300 45 55 65 75 Temperature (°C)
Figure 16. Distribution of hydroxylation of o-xylene. Data points plotted are an average of each injection at the given
temperature and error bars represent the standard deviation of the injections at the given temperature.
From the generated Arrhenius plot (see Appendix III) there is a clear negative trend in the line of best fit. However, this is due primarily to a single data point at 50 °C (-0.641), which appears to be outlier data. However, with the limited data set this point cannot be removed via Dixon’s Q- test and meets the requisite instrument variation, and must be accounted for. The data calculated from this plot is shown in
Table 7.
Arrhenius Parameters
competing ΔEa error A ratio range % error products (kJ/mol) (kJ/mol)
3,4-Me2PhOH v. 1.8 3.5 0.89 2.7 1.9 71.0 2,3-Me2PhOH
66
Chapter 3. Hydroxyl Radical Reactivity in Benzene
Table 7. Arrhenius parameters calculated for the addition of OH to o-xylene.
Removal of this point decreases the slope of the line to ~ +30 K, and indicates that there is little difference in Ea between the two products. This would be expected as both products are activated by ortho- and para- methyl groups for the 2,3-dimethylphenol and 3,4-dimethylphenol, respectively.
A reciprocal comparison of these two products returns a very similar slope, but a meaningful interpretation is still difficult. The 3,4-dimethylphenol/2,3-dimethylphenol data that is presented is due to the smaller error and range. Though there is good agreement between the two reciprocal plots, it is not surprising that the analysis returns poor data based on the data point discussed. Further experimentation will be needed to assess the true value of ΔEa, and the A ratio to potentially eliminate the troubling point. However, this may not make for a better interpretation as the uncertainty associated with very small energy differences (i.e., flat lines) is difficult to overcome.
3.3.2 m-Xylene (1,3-Dimethylbenzene)
Scheme 12 depicts the possible addition reaction outcomes for m-xylene with ·OH and
Figure 17 shows the percent distribution of the three products formed.
Scheme 12. Reaction of m-xylene with OH.
Again, there is a clear preponderance towards the positions ortho- to a methyl group. The trend exhibited in toluene and o-xylene is exacerbated in the case of 2,6-dimethyl phenol.
67
Chapter 3. Hydroxyl Radical Reactivity in Benzene
Distribution of m-dimethylphenols 0.6
0.5 avg % % 2,4- Me2PhOTMS 0.4
0.3 avg % % 2,6- Me2PhOTMS 0.2
0.1 avg % % 3,5- Ratio Ratio isomerofdistribution Me2PhOTMS 0 45 55 65 75 Temperature (°C)
Figure 17. Distribution of hydroxylation of m-xylene. Data points plotted are an average of each injection at the given
temperature and error bars represent the standard deviation of the injections at the given temperature.
Although the graph shows a larger percentage of the 2,4-dimethyl phenol, the number of reactive sites must be accounted for. By symmetry there are two positions that would lead to the
2,4- substituted product, but only one for the 2,6- substituted product.
The Arrhenius plots from which ΔEa and the A ratios for the 2,4-dimethylphenol, 3,5- dimethylphenol, and 2,6-dimethylphenol products could be calculated are given in Appendix III. It should be noted that the concentration of 3,5-dimethylphenol in the product distribution is small, and there is a slight overlap with the 2,4-dimethylphenol peak during chromatographic separation.
Due to the small relative amounts and co-eluting peaks, the calculated concentrations are susceptible to significant instrumental uncertainty. Arrhenius plots constructed for isomers relative to the 3,5-dimethylphenol product were characterized by very poor R2 values and considerable uncertainty in the calculated ΔEa. Regression analyses returned values of ΔEa with large errors,
68
Chapter 3. Hydroxyl Radical Reactivity in Benzene
and the value of Arel that in the case of the 2,4-/3,5- comparison associated with a large range.
The calculated values obtained from the Arrhenius plots are shown in
Table 8.
Arrhenius Parameters competing A ΔEa error % range products ratio (kJ/mol) (kJ/mol) error
2,4-Me PhOH v. 2 4.7 14 1.5 -0.94 3.0 321.7 3,5-Me2PhOH
2,6-Me PhOH v. 2 1.68 1.37 2.06 2.4 0.57 24.4 2,4-Me2PhOH
3,5-Me PhOH v. 2 0.16 0.072 0.36 -0.82 2.2 273.5 2,6-Me2PhOH
Table 8. Arrhenius parameters calculated for the addition of OH to m-xylene.
The values associated with the Arrhenius plot for the major 2,6- and 2,4-dimethylphenol regioisomers show much greater R2 values, and this comparison is much more accurate than those involving the 3,5- product: both the A ratio and ΔEa return a smaller range and error, respectively, from the regression analysis. The data shows an energetic preference for the 2,4- dimethylphenol product. On the other hand, the ratio of the A factor ratio is somewhat greater than the expected value of 0.5 (based on a probabilistic analysis of the number of each type of reactive site on the molecule), heavily favoring the 2,6-isomer, in a manner apparently similar to the preference observed for ortho-attack in toluene (recall that the value for Arel in o-xylene cannot be considered reliable due to its large range). The ratio of A factors for 3,5-dimethylphenol and
69
Chapter 3. Hydroxyl Radical Reactivity in Benzene
2,6-dimethylphenol in this case does return a large range, but similarly it is not near the expected value of 1.
We may anticipate significant steric hindrance to attack at the position between (ortho- to) the two methyl groups, as opposed to the position ortho- to one and para- to the other. This may be reflected in a larger activation barrier for attack at this site. However, we still observe favoritism for this site in terms of the Arrhenius pre-exponential. The remaining product, 3,5-dimethyl phenol, is clearly disfavored in the substitution reaction. This is expected as the reactive site is not activated towards electrophiles since it is meta- to both methyl groups, whereas the other two products contain at least one activating group in the proper orientation to stabilize the TS. This supports the hypothesis of the electrophilic nature of the ·OH.
3.3.3 p-Xylene (1,4-Dimethylbenzene)
There is only one product generated in this reaction due to the symmetry of the molecule.
The reactivity of p-xylene with respect to benzene will be considered in the following section.
3.3.4 Anisole (Methoxybenzene)
The possible reaction products of addition of ·OH to anisole are shown in Scheme 13, and the percentage distribution of these products in Figure 18.
Scheme 13. Reaction of anisole with OH.
70
Chapter 3. Hydroxyl Radical Reactivity in Benzene
It is quite evident from the plot that the ortho- product is dominant, and the meta- product is highly disfavored. Since –OCH3 is considered an electron-donating, and radical stabilizing group, one would expect electrophilic ·OH attack to occur at sites where the spin density can access this group; that is, at ortho- and para- sites. The low formation of the meta- product is expected, as the site is not activated towards electrophilic attack.
Distribution of methoxyphenols 0.9 0.8 avg % 2- 0.7 MeOPhOTMS 0.6 0.5 0.4 avg % 4- MeOPhOTMS 0.3 0.2
Ratio Ratio isomerofdistribution 0.1 avg % 3- MeOPhOTMS 0 45 55 65 75 Temperature (°C)
Figure 18. Distribution of hydroxylation of anisole. Data points plotted are an average of each injection at the given
temperature and error bars represent the standard deviation of the injections at the given temperature.
Ultimately, the dataset used to generate relative Arrhenius data for reaction of hydroxyl radical with anisole is quite limited, largely due to the relatively low concentrations of the meta- and para- products generated. The calibration curves for these three products were rather poor compared to the others generated, and for the meta- and para- products often did not encompass the observed integrations from the GC/MS. Given that these calibration curves were used to define the limit of quantitation (LoQ) for the analytical method, a large amount of the obtained data cannot be used in its current form. The limitations of the data eliminated all of the data obtained at 75 °C, and greatly limited comparative data involving the meta- isomer.
71
Chapter 3. Hydroxyl Radical Reactivity in Benzene
Table 9 shows the derived Arrhenius parameters for this substrate; some of which contain large errors or ranges.
Arrhenius Parameters
competing A ΔEa error range % error products ratio (kJ/mol) (kJ/mol)
3-MeOPhOH v. 0.042 0.075 0.024 -1.6 1.6 101.4 2-MeOPhOH
4-MeOPhOH v. 0.076 0.11 0.053 -2.9 1.0 34.4 2-MeOPhOH
3-MeOPhOH v. 0.40 0.54 0.30 0.37 0.79 215.6 4-MeOPhOH
Table 9. Arrhenius parameters calculated for the addition of OH to anisole.
The A factor ratio for ortho-/meta- is much larger than expected, by a factor of 25: even larger than the favoritism observed for methyl-substituted rings. In the case of anisole, one may postulate that this is due to favorable hydrogen bonding interactions between the methoxy group and the incoming ·OH, or possibly between the –OCH3 moiety and the hydroperoxide initiator prior to decomposition. The ΔEa for meta- - ortho- shows an energetic preference for formation of the meta- isomer. The error associated with the value is very large, however.
As in the comparison of 3- v. 2-methoxyphenols the ratio of A factors for the para-/ortho- is much less than anticipated on probabilistic grounds, and may again reflect a favorable hydrogen bonding interaction. The ΔEa calculation shows a lower energy pathway for formation of the para-
72
Chapter 3. Hydroxyl Radical Reactivity in Benzene
product. Both of these values return smaller errors, likely due to the larger concentrations for the para- product in the product mixture.
The A factor ratio for the meta-/para- comparison is again below the expected value, although it is in a narrow range. This is likely due to the low concentrations of meta- product, and the limited number of data points. The ΔEa here shows favoritism towards substitution at the meta- position, but is associated with a large error. This, again, is likely due to the limitations imposed by LoQ and the poor calibration curve.
3.3.5 Chlorobenzene
Figure 19 shows the percent substitution of the different regio-isomers from the reaction of chlorobenzene with ·OH (Scheme 14).
Scheme 14. Reaction of chlorobenzene with OH.
As would be expected by EAS trends the meta- isomer has gained favor, at least relative to the situation observed in anisole. The chloro- group is still radical stabilizing, largely due to resonance effects. However, the resonance effect is lessened due to weaker p-orbital overlap (an orbital
“size mismatch”). As such, the chloro group remains ortho-/para- directing, but the activation of the ring toward electrophiles is weaker.43 It is noteworthy that there is no exceptional preference for the ortho- isomer as in the cases of arenes containing a methyl group or hydrogen bond accepting methoxyl (Table 10).
73
Chapter 3. Hydroxyl Radical Reactivity in Benzene
Distribution of chlorophenols 0.5000 avg % o- ClPhOTMS 0.4500
0.4000 avg % p- 0.3500 ClPhOTMS
0.3000 avg % m-
0.2500 ClPhOTMS Ratio distribution isomerRatio of
0.2000 45 55 65 75 Temperature (°C)
Figure 19. Distribution of hydroxylation of chlorobenzene. Data points plotted are an average of each injection at the
given temperature and error bars represent the standard deviation of the injections at the given temperature.
Arrhenius Parameters
competing A range ΔEa error % products ratio (kJ/mol) (kJ/mol) error
2-ClPhOH v. 0.75 2.2 0.26 -2.1 3.0 142.5 3-ClPhOH
4-ClPhOH v. 0.46 1.4 0.15 -1.4 3.1 228.7 2-ClPhOH
4-ClPhOH v. 0.63 0.77 0.52 -1.8 0.55 30.9 3-ClPhOH
Table 10. Arrhenius parameters calculated for the addition of OH to chlorobenzene.
The concentration ratios used in generating an Arrhenius plot for comparing the ortho- versus meta- (and ortho- v. para-) products are quite scattered over each temperature range, and
74
Chapter 3. Hydroxyl Radical Reactivity in Benzene
smaller errors and ranges were obtained using a plot of the average ratio for each temperature
(see Appendix III). The ratio of the para- and meta- products gave more consistent results. Due to the scattering in the data interpretation is difficult. The data shows that the para- isomer is favored energetically. This may be due to the fact that inductive withdrawal plays a greater role with chloro- groups than with any of the groups discussed thus far. One might expect that the electron density at the ortho- position may be lessened due to the proximity of –Cl, making it less attractive to the electrophilic hydroxyl radical. While it is true that –Cl is also a more bulky 3rd row atom, the longer C-Cl bond length (relative to C-C or C-O) means that it is often considered sterically less demanding than these groups. The ratio of A factors is very near the probabilistic value of 0.5 for para- vs. ortho-, and reasonably close to the value of 1.0 that might be expected for meta- vs. ortho-. The ΔEa shows the expected trend of directing towards the para- position relative to the meta-. The Arrhenius plot for this comparison was the only one with a clear trend, leading to the conclusion that most of the error observed lies in measuring the concentration ratios of the ortho- isomer.
All of the A factor ratios for this substrate, in comparison for the previously discussed substrates, are quite close to the expected values based on reactive sites, although only the para- and meta- ratio is in a small range. The percent distribution and subsequent ΔEa calculations show the expected trend of reactivity towards substitution of electrophilic ·OH.
3.3.5 Trifluorotoluene (α,α,α-Trifluoromethylbenzene)
The trifluoromethyl group is a strongly inductively withdrawing group, with no significant resonance effect. If the EAS model holds true, we would expect the product distribution (Scheme
15 and Figure 20) to exhibit greater favoritism toward meta- substitution.
75
Chapter 3. Hydroxyl Radical Reactivity in Benzene
Scheme 15. Reaction of trifluorotoluene with OH.
Distribution of trifluoromethylphenols 0.55
0.5 avg % 3- 0.45 CF3PhOTMS 0.4
0.35 % 2-CF3PhOTMS 0.3 0.25
0.2 avg % 4-
0.15 CF3PhOTMS Ratio Ratio isomerofdistribution 0.1 45 55 65 75 Temperature (°C)
Figure 20. Distribution of hydroxylation of trifluorotoluene. Data points plotted are an average of each injection at the
given temperature and error bars represent the standard deviation of the injections at the given temperature.
There were very significant restrictions on calculating the concentration of 4- trifluoromethylphenol, as nearly all data points fell below the LoQ. However, the data is presented in full for this substrate without removal of these data points. As the only strongly deactivated arene studied it is unsurprising that there is finally a flip in reactivity at the meta- position, again providing support for the electrophilic nature of ·OH. The preference for addition of ·OH at this position is due to the inductive withdrawal of electrons through the sigma framework in the molecule, leading to this being the position which has the least positive charge.
76
Chapter 3. Hydroxyl Radical Reactivity in Benzene
The data obtained from the Arrhenius plots generated with the above concentration ratios is shown in Table 11. The data for the meta- and para- was all tightly clustered, with only a few outliers which did not fail Dixon’s Q-test. The R2 value of the meta- vs. para- competitive Arrhenius plot confirms the relatively good linear fit and trend of the data. The determination of ΔEa in this analysis is apparently quite accurate, but the ratio of A factors, although close to the expected value of 1, have large ranges associated with the calculation. The energetic preference towards the meta- position is expected as this substrate is deactivated towards electrophilic substitution.
Arrhenius Parameters
competing A ΔEa error % range products ratio (kJ/mol) (kJ/mol) error
3-CF PhOH v. 3 1.1 0.95 1.3 -1.9 0.40 20.8 4-CF3PhOH
3-CF PhOH v. 3 0.92 0.58 1.5 -1.4 1.3 91.4 2-CF3PhOH
2-CF PhOH v. 3 1.4 0.95 2.1 -0.016 1.1 7096 4-CF3PhOH
Table 11. Arrhenius parameters calculated for the addition of OH to trifluorotoluene.
The concentration ratios of the meta- and ortho- contain a number of low lying data points that do not fit within the clustering of the plot, but do not lie far enough away to fail Dixon’s Q-test, and skew the slope of the best fit line. The ΔEa is likely an underestimation of what the true value is, which is further evidenced by the high percent error and associated with the calculation. The given value does show the expected trend of meta- being energetically favored over the ortho- isomer, confirming the electrophilic nature of ·OH. The ratio of A factors is near the expected value, but similar to the calculation of ΔEa has considerable error.
77
Chapter 3. Hydroxyl Radical Reactivity in Benzene
The concentration ratios of the ortho- and para- products has some scattering of the 50 and 55 °C data points; however, the general trend of a flat line is still observed. As in the case of chlorobenzene, there is no unusually high preference for the ortho- substituted product in contrast to the methyl substituted arenes discussed above. The ratio of A factors is lower than the anticipated value of 2, but is contained within the error of the intercept. One would expect little energetic difference between the two deactivated positions, which is supported by the small value of Ea.
3.4 Reactivity of Hydroxyl Radical Addition to Toluene
The general trends of the expected reactivity of ·OH were confirmed in the experiments. The more activated the ring, the higher proportion of ortho- and para- products were observed. Similarly, the more deactivated the ring the greater proportion of the product distribution was for the meta- isomer. The electrophilic nature of ·OH was confirmed in all cases.
The data presented for the selectivity of ·OH is, for the most part associated with small errors and ranges, which demonstrates that this experimental method is an adequate means for analyzing this phenomenon. In many cases there was significant selectivity of ·OH, which is often incorrectly termed indiscriminant. Ultimately, however, it is desirable to understand reactivity patterns not only within substrates, but between substrates as well. Therefore, we determined the relative reactivity of ·OH towards the substrates and a reference compound, benzene.
The data was generated by comparing the concentrations of phenol (the ·OH addition product of benzene) and the regioisomers of a competing substrate by taking their ratios, and the
Arrhenius plots were generated. Only the data for toluene is presented in full.
A conceptual representation of the competitive reaction between toluene and benzene is shown in Scheme 16. It is, in principle, possible to construct an Arrhenius plot for the competitive
78
Chapter 3. Hydroxyl Radical Reactivity in Benzene
reaction between toluene and benzene (Scheme 16). However, the derived data is of limited utility outside of the temperature region shown. Indeed, there is no theoretical requirement for the graph shown in Figure 21 to be linear at all. There is a clear positive trend showing that there is a greater proportion of cresols formed at lower temperatures indicative of generally lower energy transition states.
Scheme 16. Competitive reaction of toluene and benzene.
Toluene v. benzene 1.1
1
0.9
0.8
0.7 y = 548.34x - 0.8032 MePhOTMS]/[PhOTMS]) 0.6
Σ[ R² = 0.1748 0.5
ln(avg ln(avg 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315 Temp-1 (1/K)
Figure 21. Arrhenius plot of the competitive reaction between toluene and benzene.
79
Chapter 3. Hydroxyl Radical Reactivity in Benzene
Individual cresol isomers were also plotted against phenol to ascertain the reactivity of each reactive site compared to that of benzene. Figure 22 shows the reactivity toward the ortho- addition product relative to benzene. The similarity to Figure 21 is consistent with the ortho-cresol being the dominant product.
2-methylphenol v. phenol 0.7 0.6 0.5 0.4 0.3
0.2 MePhOTMS]/[PhOTMS]
- y = 576.17x - 1.3178 0.1 R² = 0.1959 ln([2 0 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315 Temp-1 (1/K)
Figure 22. Arrhenius plot of the competitive reaction between toluene, accounting for only the ortho- product, and
benzene and OH.
Figure 23 is the Arrhenius plot for the competitive reaction of benzene and toluene at the meta- position. The graph has greater scatter in the data points due to the lower concentrations of the meta- product formed, and the difficulties associated with its precise determination by
GC/MS. There is still an evident positive trend, but the slope is much smaller, and the y-intercept is now negative.
The Arrhenius plot for attack at the para- position relative to benzene is shown in Figure
24. The data for the 50 and 65 °C sets could not be subjected to Dixon’s Q-test due to the limited
80
Chapter 3. Hydroxyl Radical Reactivity in Benzene
population size, and the outlier at 70 °C nearly fails the statistical test. This plot gives the best fit based on R2 values of the three isomeric products.
3-methylphenol v. phenol -0.6
-0.7
-0.8 y = 298.8x - 1.8186 R² = 0.0789 -0.9
MePhOTMS]/[PhOTMS]) -1 -
ln([3 -1.1 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315 Temp-1 (1/K)
Figure 23. Arrhenius plot of the competitive reaction between toluene, accounting for only the meta- product, and
benzene and OH.
81
Chapter 3. Hydroxyl Radical Reactivity in Benzene
4-methylphenol v. phenol -0.6
-0.7
-0.8
-0.9
-1
y = 673.54x - 2.8982 MePhOTMS]/[PhOTMS])
- -1.1 R² = 0.2328
ln([4 -1.2 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315 Temp-1 (1/K)
Figure 24. Arrhenius plot of the competitive reaction between toluene, accounting for only the para- product, and benzene and OH.
The information gleaned from the Arrhenius plots is shown in Table 12. The ratio of A factors for the comparison of the ortho- product, although associated with a large range, is quite close to the expected value of 0.33 (two such reactive sites on toluene, six equivalent sites of attack on benzene). This is quite surprising as in the previous section there was found to be a pronounced affinity to addition at the ortho- site. The slope of the best fit line, and the calculated
ΔEa show an ehthalpic favoritism towards formation of the cresol product.
Arrhenius Parameters
competing A ΔEa error % range products ratio (kJ/mol) (kJ/mol) error
2-MePhOH 0.27 0.11 0.68 -4.8 2.6 54.1 v. PhOH
3-MePhOH 0.16 0.074 0.36 -2.5 2.2 88.2 v. PhOH
0.055 0.021 0.14 -5.6 2.6 46.9
82
Chapter 3. Hydroxyl Radical Reactivity in Benzene
4-MePhOH v. PhOH
Table 12. Arrhenius parameters for the competitive addition of OH to toluene and benzene.
The remaining values are consistent with the relative Arrhenius values dealing with the selectivity of addition of hydroxyl radical to toluene, as would be expected. The comparison of the para- product returns smaller errors for both of the Arrhenius parameters.
83
Chapter 3. Hydroxyl Radical Reactivity in Benzene
3.5 Reactivity of Hydroxyl Radical Addition to Other Aromatics
3.5.1 o-Xylene (1,2-Dimethylbenzene)
A conceptual diagram depicting the competitive reaction between o-xylene and benzene with ·OH is illustrated in Scheme 17. The data used in generating relative Arrhenius parameters was rather limited due to instrumental variation, and the data eliminated from this set was subject to a 10% variation in 2σ/average response ratio. Even with the lower level of confidence there is a limited number of data points that could be used. In addition to elimination of data points due to instrumental variation, there were six experiments which generated samples that could not be quantitated as the concentrations of one or more of the addition products fell below the LoQ in the competitive analysis of o-xylene and benzene.
Scheme 17. Competitive reaction of o-xylene and benzene
Analysis of the Arrhenius plots was carried out, and the calculated Arrhenius parameters are presented in Table 13. Comparison of the individual isomeric products to phenol show both o-xylene sites are more reactive than benzene. The individual comparisons return A factor ratios that are very close to the expected values, but with significant error ranges. Although the general trends expected were observed, no conclusive evidence can be drawn from this experimental
84
Chapter 3. Hydroxyl Radical Reactivity in Benzene
data set. Further experimentation is required to confirm these results and return statistically significant values.
Arrhenius Parameters A competing range ΔEa error % rati products (kJ/mol) (kJ/mol) error o
2,3-Me PhOH 2 0.54 3.5 0.082 -3.2 5.3 166.0 v. PhOH
3,4-Me PhOH 2 0.40 2.9 0.056 -2.9 5.6 191.3 v. PhOH
Table 13. Arrhenius parameters for the competitive addition of OH to o-xylene and benzene.
3.5.2 m-Xylene (1,3-Dimethylbenzene)
The competitive reaction between m-xylene and benzene is depicted in Scheme 18.
Scheme 18. Competitive reaction of m-xylene and benzene.
85
Chapter 3. Hydroxyl Radical Reactivity in Benzene
The values calculated from the Arrhenius plot are given in Table 14. There is a significantly greater than expected A factor ratio for the comparison of the 2,4-dimethylphenol product to phenol. This is a reflection of the effect leading to preferential addition of ·OH ortho- to a methyl substituent. The error in the ΔEa is lower than in the comparison of all reactive sites of m-xylene and benzene; however, it is still large. It is also considerably lower than the ortho- site in toluene, which should have similar activation towards electrophilic species like ·OH.
Arrhenius Parameters
competing A ΔEa error % range products ratio (kJ/mol) (kJ/mol) error
2,4-Me PhOH 2 0.85 0.52 1.4 -2.3 1.3 59.5 v. PhOH
3,5-Me PhOH 2 0.14 0.061 0.31 -2.2 2.3 103.1 v. PhOH
2,6-Me PhOH 2 1.2 0.82 1.7 -0.41 1.0 246.1 v. PhOH
Table 14. Arrhenius parameters for the competitive addition of OH to m-xylene and benzene.
The A factor ratio for 3,5-dimethylphenol/phenol is very close to the expected value of
0.17, and has a much smaller range than the other isomeric comparisons. There is considerable scatter in this plot leading to the large error associated with the ΔEa. Due to the low amounts of the 3,5-dimethylphenol formed during the electrophilic addition of ·OH the large error was anticipated.
Analysis of the Arrhenius plot for 2,6-dimethylphenol and phenol returns data with large uncertainties, based on the regression analysis. The ratio of the A factors is greater than anticipated, similar to the value obtained during the 2,4-dimethylphenol comparison. The ΔEa
86
Chapter 3. Hydroxyl Radical Reactivity in Benzene
found for this product is close to what would be expected considering the value shown in Table 8 in the previous section and that given for the reactivity of 2,4-dimethylphenol in Table 14. Both tables give values for the 2,4-dimethylphenol product being favored energetically by 2.4 and 2.3
KJ/mol, respectively. The best fit line comparing 2,6-dimethylphenol and phenol should be relatively flat, which causes there to be considerable error in calculating the ΔEa.
3.5.3 p-Xylene (1,4-Dimethylbenzene)
The competitive reaction of p-xylene and benzene in shown in Scheme 19, and the
Arrhenius plot of the two competing substrates in Figure 25.
Scheme 19. Competitive reaction of p-xylene and benzene.
There is one data point that is a clear outlier at 65 °C. However, due to other data points at this temperature failing the instrumental variation criterion, Dixon’s Q-test could not be performed. Even if the level of significance were lowered to allow for inclusion of the point necessary to remove this data point statistically, other data points would be included that would further skew the data. Removal of this one data point gives a much better fit based on the R2 value, increasing it to 0.27. The Arrhenius parameters for the p-xylene competitive experiments with benzene are shown in Table 15.
87
Chapter 3. Hydroxyl Radical Reactivity in Benzene
ln(avg. [2,5-Me2PhOTMS]/[PhOTMS]) 1.8 1.7 y = 494.61x - 0.1314 R² = 0.0779 1.6 1.5 1.4 1.3
1.2 Me2PhOTMS]/[PhOTMS]) - 1.1 1 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315
Temp-1 (1/K) ln(avg. ln(avg. [2,5
Figure 25. Arrhenius plot of the competitive reaction between p-xylene and benzene.
Arrhenius Parameters competing A ΔEa error % range products ratio (kJ/mol) (kJ/mol) error
2,5-Me PhOH 2 0.88 0.22 3.6 -4.1 3.9 95.4 v. PhOH
Table 15. Arrhenius parameters for the competitive addition of OH to p-xylene and benzene.
Both calculated values have very large errors. Removal of the single data point discussed above results in a ΔEa value of -4.7 kJ/mol. Thus it is likely that the value of ΔEa is slightly greater in magnitude than that presented in the table. The A factor ratio from the above graph is greater than expected, but as the only product generated from addition to p-xylene is going to involve reaction ortho- to a methyl substituent, this is consistent with observations for toluene and other xylenes. Removal of the single data point brings the A factor ratio equal to the 0.66 expected value, but it is still associated with a large error.
88
Chapter 3. Hydroxyl Radical Reactivity in Benzene
3.5.4 Anisole (Methoxybenzene)
The competitive reaction between anisole and benzene is depicted in Scheme 20, and the
Arrhenius parameters for the competitive reactions of anisole and benzene are given in Table 16.
Scheme 20. Competitive reaction of anisole and benzene
Arrhenius Parameters
competing A ΔEa error % range products ratio (kJ/mol) (kJ/mol) error
2-MeOPhOH 1.0 1.6 0.7 -6.9 1.2 18.1 v. PhOH
3-MeOPhOH 0.059 0.089 0.039 -7.7 1.1 14.8 v. PhOH
4-MeOPhOH 0.13 0.21 0.083 -8.3 1.3 15.6 v. PhOH
Table 16. Arrhenius parameters for the competitive addition of OH to anisole and benzene.
89
Chapter 3. Hydroxyl Radical Reactivity in Benzene
The data set is quite limited due to the low concentrations of the meta- and para- products of ·OH addition to anisole which fell below the defined LoQ. The concentration ratios used to generate the competitive Arrhenius plots exclude data for the 75 °C experiments across all data sets with the exception of the ortho- comparison, due to the rather high LoQ associated with the meta- and para- products, and their low concentrations. This could be remedied by generating new calibration curves to accurately determine the concentrations of the meta- and para- products which had smaller integrations. As the ortho- products were found to be dominant, very few of the experiments were eliminated by the LoQ test.
From the Arrhenius parameters, it is again apparent that a significant entropic effect leads to preferential formation of the ortho- ·OH addition product. This may be due to hydrogen bonding of ·OH with the methoxy group, or between the hydroperoxide initiator used. This entropic effect dominates the reaction despite the concentration of anisole being quite small compared to the amount of benzene in the reactions. The ortho- product is also favored energetically, with a very small error.
The Arrhenius parameters for the meta- product, even with the limitations imposed on the data set due to LoQ, are returned with small errors. The A factor ratio is lower than expected, and the range does not encompass the expected value of 0.33. The ΔEa shows that this product is even more favored enthalpically than the ortho- isomer.
The Arrhenius parameters of the 4-methoxyphenol product relative to phenol formation are also associated with small errors, despite the limitations of the data set imposed by LoQ. The
A factor ratio is the closest to the expected probabilistic value of all three isomeric products, and the range encompasses this value of 0.17. ΔEa shows greater favoritism for para- than was observed for the ortho- product, which is consistent with the selectivity data.
90
Chapter 3. Hydroxyl Radical Reactivity in Benzene
3.5.5 Chlorobenzene
The competitive reaction between chlorobenzene and benzene with ·OH is depicted in
Scheme 21.
Scheme 21. Competitive reaction of chlorobenzene and benzene.
The values calculated from the Arrhenius plots (see Appendix III) are shown in Table 17.
Arrhenius Parameters
competing A ΔEa error % range products ratio (kJ/mol) (kJ/mol) error
2-ClPhOH 0.23 0.055 0.96 -0.52 4.0 770.8 v. PhOH
3-ClPhOH 0.14 0.027 0.72 -0.61 4.6 764.4 v. PhOH
4-ClPhOH 0.092 0.017 0.51 -2.2 4.8 214.8 v. PhOH
Table 17. Arrhenius parameters for the competitive addition of OH to chlorobezene and benzene.
91
Chapter 3. Hydroxyl Radical Reactivity in Benzene
The Arrhenius parameters obtained for the ortho- product and phenol gives a very flat best fit line, which is susceptible to significant experimental uncertainty. The A factor ratio of the two products in question is reasonably close to the expected value of 0.33, and within the range of the statistical value. This value is certainly not close to the magnitude exhibited in the ortho- products when a methyl or methoxy group is present. ΔEa of this comparison is difficult to obtain from such a shallow slope, but does show that the ortho- product is favored relative to phenol.
The Arrhenius parameters obtained from the plotting of the meta- and para- concentration ratios contain large errors, likely due to the similar reactivity of both benzene and chlorobenzene substrates. The A factor ratio is smaller than expected, but contains the presumed value in the range. The ΔEa shows that both the meta- and para- isomers are favored, but the uncertainty is significant.
The reactivity of the two substrates used in this comparison are too close to one another to obtain good results. The A factor ratios of the chlorophenols are all smaller than expected, but to a less extent for the ortho- isomer. The preponderance of ·OH towards the ortho- position may not be isolated to the cases in which there is a methyl or methoxyl group present; however, those groups appear to augment the amount of ortho- product observed. Likely better ΔEa data would be obtained if the competing substrate was more reactive than benzene, such as toluene or a xylene isomer.
92
Chapter 3. Hydroxyl Radical Reactivity in Benzene
3.5.6 Trifluorotoluene (α,α,α-trifluoromethylbenzene)
A schematic representation of the competitive reaction between benzene and trifluorotoluene is shown in Scheme 22.
Scheme 22. Competitive reaction of trifluorotoluene and benzene.
The measurements of the concentration of each product allowed for generation of the competitive
Arrhenius plots. However, the determinations of para- isomer concentration were subject to error due to LoQ limitations. The data set is the most complete across all of the different substrates analyzed. There was very little variation in the GC/MS instrument, and only a few data points could be removed by Dixon’s Q-test. There were limitations based on LoQ, but these were not accounted for in the analysis as discussed previously. The derived Arrhenius data are shown in
Table 18. Regression analysis of the Arrhenius plot of the meta- product relative to phenol returns large errors for both Arrhenius parameters. The A factor ratio is very close to the expected value, but covers a wide range. ΔEa from the analysis shows a strong favoritism towards formation of phenol.
The A factor ratios for the ortho- and para- products is much smaller than the probabilistic ratios, yet the value is associated with a narrow range. ΔEa shows a preference for ·OH addition
93
Chapter 3. Hydroxyl Radical Reactivity in Benzene
to benzene. This shows that the preferential addition of ·OH to the ortho- position in the methylated arenes is due to the –CH3 group, rather than placement of an exocyclic carbon.
Arrhenius Parameters
competing A ΔEa error % range products ratio (kJ/mol) (kJ/mol) error
3-CF3PhOH v. PhOH 0.36 0.12 1.1 4.1 3.0 74.6
4-CF PhOH 3 0.068 0.039 0.12 1.5 1.6 103.4 v. PhOH
2-CF PhOH 3 0.080 0.055 0.12 0.98 1.0 106.0 v. PhOH
Table 18. Arrhenius parameters for the competitive addition of OH to trifluorotoluene and benzene.
The reaction was dominated by the meta- product as shown in the section above, but the
ΔEa calculations of each individual isomer were not in good agreement with the ΔEa values from the selectivity section. In fact, the data show almost an opposite trend. This is primarily due to a single experiment – due to the low concentrations of ortho- and para- products, this experiment does not show up in the selectivity studies due to LoQ limitations. However, the ratio of 2- trifluoromethylphenol/phenol does not share such limitations, and falls just within the acceptance limits defined by the Dixon Q-test. Elimination of this single data point generates a value for Ea which is more consistent with the selectivity data. This particular example illustrates the difficulty of determining relative Arrhenius parameters where activation energy differences are small and the dataset is limited. If further experimentation is undertaken, the ratio of reactants should be altered to allow for larger concentrations of the trifluoromethylphenols.
94
Chapter 3. Hydroxyl Radical Reactivity in Benzene
3.6 Summary: Structure-Reactivity Relationships
The mono-substituted substrates were analyzed using the Hammett equation:
푘 푙표𝑔 = 𝜎𝜌 푘0
The substituent constants σ used are shown in
Table 19, and k0 in this case is the rate coefficient for benzene. The plots were generated from the averaged meta- and para- products relative to phenol for the 70 °C experiments (Figure 26).
Hammett correlation 0.5 p-OMe y = -1.7622x - 0.2353 R² = 0.7528 0 H m-OMe
m-CH3 p-CH3 -0.5
m-Cl p-Cl -1
m-CF3
log log ([RPhOTMS]/[PhOTMS]) p-CF3 -1.5 -0.4 -0.2 0 0.2 0.4 0.6 σ
Figure 26. Hammett correlations of monosubstituted arenes.
The Hammett plot shows a reasonable degree of correlation for both meta- and para- substitution: there are no reliable Hammett substituent parameters for ortho-positions, as these positions are prone to complicating factors such as steric demand, or hydrogen bonding interactions. The slope of the line of best fit is correlated to the reaction constant, ρ, and the negative correlation indicates a buildup of positive charge in the addition transition state that is alleviated by electron donating groups (EDGs).
Hammett constants
95
Chapter 3. Hydroxyl Radical Reactivity in Benzene
substituent σm σp
methoxy 0.12 -0.27
methyl -0.07 -0.17
chloro 0.37 0.23
trifluoromethyl 0.43 0.54
Table 19. Hammett constants for mono-substituted substrates44
The negative trend is typical of electrophilic substitution reactions, and is further support for the assertion that the hydroxyl radical is an electrophilic species and exhibits a degree of regioselectivity that reflects this. The magnitude of is sufficiently large to indicate this reaction is more sensitive to substituents than the acidity data from which the Hammett constants were originally developed. This is consistent with the assertion that in this case the positive charge is built up in the ring itself, rather than at a more remote benzylic position.
Recalling the nature of the Arrhenius equation, a similar degree of correlation might be expected for ΔEa as a function of Hammett substituent constant (Figure 27). Figure 27 exhibits a clear positive trend in the data (recall that stabilization of the transition state by EDGs should result in a lowering of the activation energy). The data is a decent fit, with the meta- addition to anisole being an apparent outlier. Recall that m-methoxyphenol is generated in a small proportion of the anisole product mixture, and it is possible that the obtained result may not be accurate.
96
Chapter 3. Hydroxyl Radical Reactivity in Benzene
ΔEa Hammett correlation 8
y = 10.491x - 3.3689 6 R² = 0.4932 4 m-CF3
2 p-CF3
0 a
E m-Cl
m-CH3 -2 p-Cl Δ p-CH3 -4 -6 m-OMe p-OMe -8 -10 -12 -0.4 0.1 0.6 σ
Figure 27. Activation energy Hammett correlation.
An alternative approach is based on the results of frontier molecular orbital (FMO) theory, which is constructed on the idea that the reactivity of one compound with another is based on the energies and symmetries of their frontier molecular orbitals, i.e., the highest occupied molecular orbitals (HOMOs) and lowest unoccupied molecular orbitals (LUMOs). The following expression may be derived from FMO theory for a reacting pair A and B:43
표푐푐 푢푛표푐푐 푢푛표푐푐 표푐푐 1 1 ∆퐸 = 퐶 {∑ ∑ + ∑ ∑ } (퐸퐴 − 퐸퐵) (퐸퐴 − 퐸퐵) 퐴 퐵 퐴 퐵
E is the so-called interaction energy between the two molecules, and as a general principle, the greater the interaction the lower the overall energy of the system (i.e., the transition state as A and B approach one another). Note that only interactions between occupied (occ) and unoccupied (unocc) orbitals will generate a stabilizing interaction. The term C refers to the degree of orbital overlap between molecules A and B, and is assumed to be constant for similar reactions.
This expression will be dominated for orbitals with the smallest energy gaps between them: the two possible HOMO-LUMO interactions. Thus;
97
Chapter 3. Hydroxyl Radical Reactivity in Benzene
1 1 ∆퐸 ≈ 퐶 { − } 퐸퐻푂푀푂,퐴 − 퐸퐿푈푀푂,퐵 퐸퐻푂푀푂,퐵 − 퐸퐿푈푀푂,퐴 and one of the terms in this equation will be greater than the other. For an electrophilic (electron accepting) species such as hydroxyl attacking a nucleophilic species such as an aromatic ring, the interaction energy expression is dominated by the term
1 퐶 { } 퐸퐻푂푀푂,퐴푟표푚푎푡𝑖푐 − 퐸퐿푈푀푂,푂퐻
The value for ELUMO,OH is common to all systems studied here, but the value of EHOMO,Aromatic will change. The values for EHOMO may be estimated by the ionization potential (IP), the energy required to remove an electron from the HOMO of a molecule (Koopmans theorem).117 Molecules with higher EHOMO should have smaller energy gaps, larger interaction energies, and faster rates.
We should be able to correlate total reactivity of different arenes relative to benzene with their measured gas phase IPs. Such correlations have been constructed previously for LFP-derived data in acetonitrile at 298K.95
In this case, we use the total relative reactivity of a given substrate; in other words, the ratio of the sum of concentrations of all possible regioisomers, relative to benzene. The data for the 70 °C experiments along with the substrate ionization potential are summarized in Table 20, and the correlation in Figure 28.
98
Chapter 3. Hydroxyl Radical Reactivity in Benzene
kPhR/kPhH 1.5
PhOCH3 m-Ph(CH3)2 y = -1.1425x + 10.346
1.0 R² = 0.9297 )
o-Ph(CH3)2 PhH
k 0.5 p-Ph(CH ) / 3 2
PhCH3 PhH PhR
k 0.0 log log ( -0.5 PhCl PhCF3
-1.0 8 8.5 9 9.5 10 ionization potential (eV)
Figure 28. Reactivity of substituted arenes relative to benzene correlated to ionization potential.
The correlation of the plot is very good, especially due to IPs being determined for the gas phase. The plot shows that the SOMO of ·OH reacts faster with molecules which have a higher energy HOMO, and confirms the electrophilic nature of the species.
Reactivity consistent with such behavior has been previously observed in other experiments where the hydroxyl radical is generated in the presence of arenes.116 These experiments are characterized by low yields of hydroxylated product, possibly due to the absence of a trap species such as TEMPO to isolate the first step. Nonetheless, the authors found that o:m:p ratios for anisole, toluene, and chlorobenzene were 76:0:24, 71:9:20, and 38:23:39, respectively.116 These numbers are in reasonable agreement with the numbers found in the present study. Their experimentation did not elucidate Arrhenius parameters, though, and only a comparison between the percent distribution can be made. Similarly, this behavior does not seem to be characteristic of TEMPO, as other radical traps have also shown this preference.116, 120
Further discussion of this phenomenon is left for later chapters.
99
Chapter 3. Hydroxyl Radical Reactivity in Benzene
avg. log (avg. IP [ΣRPhOTMS] standard substrate [ΣRPhOTMS] [ΣRPhOTMS]/[ (eV) [PhOTMS] deviation [PhOTMS] PhOTMS])
15 PhOMea 8.2 15.2 0.174 15 1.2 15 0.61 PhCla 9.07 0.62 0.022 0.63 -0.2 0.65 3.5 a m-Ph(CH3)2 8.55 3.6 0.071 3.6 0.6 3.6 2.5
a 2.5 o-Ph(CH3)2 8.56 0.393 2.8 0.4 2.9 3.3 3.54 a p-Ph(CH3)2 8.44 3.6 0.074 3.6 0.6 3.69 1.86 2.22 a PhCH3 8.83 0.203 2.2 0.3 2.2 2.3 0.19 b PhCF3 9.68 0.19 0.002 0.19 -0.7 0.19 PhHa 9.24 1.00 (defined) 1.00 0.00
Table 20. Ionization potentials and relative rate constant. a reference 118 b reference 119.
In this chapter, it has been demonstrated that it is possible to generate structure-reactivity relationships for the addition of hydroxyl radical to arenes in hydrocarbon solvents, and that these relationships are consistent with the assertion of the hydroxyl radical as an electrophilic species.
However, the relationships imply a degree of charge separation in the transition state for this reaction, consistent with previous computational studies.70 In such cases, the role of solvent may be significant, which begs the question of whether one would observe similar reactivity relationships in more polar solvents, and ultimately in the more environmentally relevant solvent,
100
Chapter 3. Hydroxyl Radical Reactivity in Benzene
water. Water poses some technical difficulties with the present methodology, and so we must limit ourselves to polar organic molecules, such as acetonitrile. A complementary study of hydroxyl radical reactivity in acetonitrile, and a comparison of the observed reactivity in acetonitrile and hydrocarbon solvents, is described in the next chapter.
101
CHAPTER 4 –HYDROXYL RADICAL REACTIONS IN ACETONITRILE: THE EFFECT OF
SOLVENT ON RADICAL REACTIONS
4.1 Introductory Remarks
Acetonitrile (CH3CN) is a useful solvent to study hydroxyl radical reactivity. It is a polar solvent
(dielectric constant = 36.6 at 20C; water has = 80.2 at the same temperature)121 which may in principle act as a hydrogen bond acceptor. It is known to solvate ionic species to a relatively limited extent (particularly if the ions involved are large, “soft” ions). Furthermore, LFP-based studies have shown that this compound is relatively resistant to hydrogen abstraction by hydroxyl radical, and the relative reactivity of hydroxyl radical reactions with various substrates have been determined in this solvent.95 Acetonitrile lies further along the “solvent spectrum” towards water, but lacks the strong hydrogen-bond donor/acceptor capabilities of water. It is also both a relatively weak acid (pKa (DMSO) = 31.3)122 and a weak base, meaning that reaction mixtures are less susceptible to complexity due to competing acid-base equilibria.
Therefore, reactions similar to those described in the previous chapter to determine the reactivity and selectivity of hydroxyl radical reactions with competing aromatic substrates in acetonitrile may be performed, with a view to comparing both reactivity and selectivity data in both solvents. Because the peroxide initiator decomposes more rapidly in acetonitrile (see Chapter
2), a different temperature range to extract relative Arrhenius data is used, which does have a limited overlap (in temperature) with the experiments carried out in aromatic solvents. The data presented in this chapter is both combined and compared with data obtained in Chapter 3. As
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
with the previous chapter, only the data pertaining to toluene reactivity is presented in full, with summary tabulation of derived data for the remaining substrates.
4.2 Hydroxyl Radical Addition to Toluene (Methylbenzene)
Recall that the addition reaction between toluene and ·OH may generate the three isomeric methylphenols, or cresols, as shown in Scheme 23. As with the previous study, the possibility of hydrogen abstraction from the methyl group is not considered. A previously published LFP study indicates that the overall rate of toluene reaction with hydroxyl radical is effectively unchanged for toluene-d3, relative to toluene-h8. If abstraction were an important process, one should observe a primary kinetic isotope effect (KIE) in considerable excess of 1.
Scheme 23. Reaction of toluene with OH in acetonitrile.
The selectivity data is perhaps most readily visualized in terms of a percentage distribution of the three cresol products. Figure 29 shows the distribution of isomers in both acetonitrile and hydrocarbon solvent. The plots for the two solvents show a high degree of similarity: The amount of the meta- isomer formed is indistinguishable between the two solvents. There is more of the para- product formed in the acetonitrile trials than in the benzene experiments. This increased formation comes at the expense of the ortho- isomer.
103
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
Distribution of methylphenols 0.700 avg % 2-MePhOTMS 0.600 (PhH) 0.500 avg % 2-MePhOTMS (MeCN) 0.400 avg %4-MePhOTMS 0.300 (MeCN) avg % 4-MePhOTMS 0.200 (PhH) 0.100 avg % 3-MePhOTMS Ratio Ratio isomerofdistribution (MeCN) 0.000 30 40 50 60 70 80 avg % 3-MePhOTMS (PhH) Temperature (˚C)
Figure 29. Distribution of hydroxylation on toluene. Data points plotted are an average of each injection at the given
temperature. Circles represent the data obtained from reactions carried out in hydrocarbon solvent (PhH), and
triangles represent the data obtained from reactions carried out in acetonitrile (MeCN).
The plots indicate that the para- isomer has either become more energetically favorable, or that the apparently entropic favoritism for the ortho- isomer (characterized by a larger Arel than would be expected statistically) observed in hydrocarbons has been reduced in acetonitrile.
Arrhenius plots were generated from relative concentration data (Table 21), and the data are plotted alongside data obtained in hydrocarbon solvents. There was very little instrumental variation in these experiments, and only one point was eliminated by failing Dixon’s Q-test for statistical outliers.
Figure 30 shows the Arrhenius plot generated for the ortho- and meta- cresol comparison.
There is a good fit, with the most significant scattering of data points occurring for the 45 °C experiments. The positive correlation is the expected trend based on the electrophilic nature of
·OH. There is clear separation of the data points with the exception of one possibly low point from the benzene data at 50 °C.
104
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
Concentration ratios
2-methylphenol v. 4-methylphenol v. 3-methylphenol v. 3-methylphenol 2-methylphenol 4-methylphenol temp. temp-1 ln conc. ln conc. ln conc. conc. ratio conc. ratio conc. ratio (°C) (1/K) ratio ratio ratio 3.4 1.2 0.328 -1.116 0.861 -0.149 60 0.003 3.5 1.2 0.33 -1.10 0.87 -0.14 3.54 1.26 0.34 -1.09 0.87 -0.14 3.5 1.3 0.33 -1.11 0.84 -0.18 55 0.00305 3.6 1.3 0.332 -1.104 0.85 -0.17 3.6 1.3 0.34 -1.09 0.85 -0.17 3.6 1.3 0.33 -1.10 0.82 -0.19 50 0.00309 3.64 1.29 0.33 -1.10 0.83 -0.19 3.7 1.3 0.33 -1.10 0.84 -0.17 3.4 1.2 0.33 -1.10 0.823 -0.195 45 0.00314 3.6 1.3 0.33 -1.09 0.84 -0.18 3.7 1.3 0.34 -1.09 0.89 -0.12 3.7 1.3 0.33 -1.11 0.80 -0.22 40 0.00319 0.334 -1.097 0.814 -0.206 3.7 1.3 0.34 -1.08 0.86 -0.15 3.7 1.3 0.328 -1.114 0.79 -0.23 35 0.00325 3.7 1.3 0.34 -1.08 0.80 -0.23 3.75 1.32 0.34 -1.07 0.813 -0.207
Table 21. Concentration ratios, and natural log transformed ratios of products from OH addition to toluene.
The Arrhenius plot for the para- and ortho- products is shown in Figure 31. As with the results obtained in hydrocarbon solvents, there is significant scatter at all temperatures with the exception of 50 °C. There is a small positive trend, but the slope is still quite small as expected since both products are formed from sites that are similarly activated towards electrophilic substitution and should have similar energies. It is noteworthy that in both of the figures discussed, the values for Arel determined in acetonitrile have become smaller in magnitude than those measured in hydrocarbons. Again there is clear separation of the two sets of data, but in
105
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
this case there is no overlap of the data. It should also be noted that the differential activation energies Ea are effectively the same.
2-methylphenol v. 3-methylphenol 1.4
- y = 166.56x + 0.8352 1.35 R² = 0.2329
1.3
acetonitrile
MePhOTMS]/[3 1.25 -
benzene MePhOTMS]) 1.2 y = 253.31x + 0.4902 ln(avg ln(avg [2 R² = 0.461 1.15 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 1/T (K-1)
Figure 30. Arrhenius plot of 2-methylphenol/3-methylphenol. Benzene data is shown in red, and acetonitrile data is
shown in blue.
4-methyphenol v. 2-methylphenol -1 0.0028 0.0029 0.003 0.0031 0.0032 0.0033
- -1.05
-1.1
-1.15 y = 52.217x - 1.2609 R² = 0.1286
-1.2 acetonitrile MePhOTMS]/[2
- -1.25 benzene MePhOTMS]) -1.3
y = 53.304x - 1.4418 ln(avg ln(avg [4 -1.35 R² = 0.0181 -1.4 1/T (K-1)
Figure 31. Arrhenius plot of 4-methylphenol/2-methylphenol. Benzene data is shown in red, and acetonitrile data is
shown in blue.
106
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
The Arrhenius plot for the meta- and para- comparison is shown in Figure 32.
3-methylphenol v. 4-methylphenol 0.00
0.0028 0.0029 0.003 0.0031 0.0032 0.0033 - -0.05 y = -222.71x + 0.6161 R² = 0.3419
-0.10
acetonitrile MePhOTMS]/[4
- -0.15 benzene MePhOTMS])
-0.20 y = -263.19x + 0.6427 ln(avg ln(avg [3 R² = 0.4867 -0.25 1/T (K-1)
Figure 32. Arrhenius plot of 3-methylphenol/4-methylphenol. Benzene data is shown in red, and acetonitrile data is
shown in blue.
The plot shows a strong negative trend. There are two data points that may be high enough to cause an overlap in the data if the hydrocarbon data set had been expanded to 45 and 40 °C, and similarly one data point (nearly an outlier by Dixon’s Q-test) in the hydrocarbon data is sufficiently low it may have overlapped with acetonitrile data had it been expanded to 75 °C. The negative trend is consistent with the activation patterns exhibited in toluene towards electrophilic substitution, and the trend lines show a clear distinction between solvents.
How then, do the Arrhenius parameters derived for toluene addition in hydrocarbons compare with those obtained in acetonitrile? The derived data for both are shown in Table 22, and show a reasonably high degree of agreement. All of the values obtained in acetonitrile return
107
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
small errors and ranges upon regression analysis, with the exception of the ΔEa for the para and ortho- comparison, due to their close energies of activation.
Arrhenius parameters - acetonitrile
competing A ΔEa error % range products ratio (kJ/mol) (kJ/mol) error
2-MePhOH v. 1.6 1.3 2.0 -2.1 0.588 27.9 3-MePhOH
4-MePhOH v. 0.28 0.25 0.32 -0.43 0.28 65.1 2-MePhOH
3-MePhOH v. 1.9 1.5 2.3 2.2 0.5619 25.7 4-MePhOH
Arrhenius parameters – hydrocarbons
2-MePhOH v. 2.3 1.9 2.8 -1.4 0.58 41.6 3-MePhOH
4-MePhOH v. 0.24 0.18 0.31 -0.44 0.79 178.7 2-MePhOH
3-MePhOH v. 1.9 1.5 2.3 1.9 0.62 33.6 4-MePhOH
Table 22. Arrhenius parameters calculated for OH addition to toluene.
The A factor ratios show a strong entropic preference for addition to the ortho- site, but in the more polar solvent, the entropic effect leading to the addition at the ortho- site relative to meta- is lessened to nearly 70% the effect observed in the hydrocarbon solvent. The values obtained in the different solvents are not within the error ranges of one another, and a similar trend is
108
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
observed in the comparison of the para and ortho- products. On the other hand, the values for the A factor ratios comparing the meta- and para- isomers are effectively the same in both solvents.
With respect to the differential activation energies, ΔEa, the values obtained from the
Arrhenius plots in each solvent are similar within the experimental uncertainity of each measurement. The difficulty in measuring the ΔEa from very shallow slopes (for example, in the comparison of ortho- and para- isomers) was a constant problem in assessing the reactivity and selectivity of ·OH.
Comparison of reactivity of each of the sites of hydroxyl radical attack relative to benzene yielded largely consistent data in both solvents. The Arrhenius plots constructed for each attack at ortho- meta- and para- sites relative to benzene in both acetonitrile and hydrocarbon solvent are shown in Figure 33, Figure 34, and Figure 35, respectively.
2-methylphenol v. phenol 0.75 y = 576.17x - 1.3178 0.65 R² = 0.1959
0.55
0.45 acetonitrile 0.35 benzene y = 577.77x - 1.3737
MePhOTMS]/[PhOTMS]) R² = 0.3145 - 0.25
0.15
0.0028 0.0029 0.003 0.0031 0.0032 0.0033 ln(avg ln(avg [2 1/T (K-1)
Figure 33. Arrhenius plot of the competitive reaction between toluene, accounting for only the ortho- product, and
benzene with OH.
109
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
3-methylphenol v. phenol 0 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 -0.2
-0.4 y = 366.46x - 1.991 y = 298.8x - 1.8186 R² = 0.1076 R² = 0.0789 -0.6 acetonitrile benzene
-0.8
MePhOTMS]/[PhOTMS]) - -1
ln(avg ln(avg [3 -1.2 1/T (K-1)
Figure 34. Arrhenius plot of the competitive reaction between toluene, accounting for only the meta- product, and
benzene with OH.
4-methylphenol v. phenol 0 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 -0.2
y = 629.92x - 2.6345 -0.4 R² = 0.3214
-0.6 acetonitrile benzene
-0.8
MePhOTMS]/[PhOTMS]) -
-1 y = 673.54x - 2.8982 R² = 0.2328
ln(avg ln(avg [4 -1.2 1/T (K-1)
Figure 35. Arrhenius plot of the competitive reaction between toluene, accounting for only the para product, and
benzene with OH.
Based on the relatively small differences observed in the selectivity discussed above, it is unsurprising that comparison of the different solvent systems results in similar but distinct trend lines for the single isomeric products versus phenol. The data obtained in acetonitrile has a very
110
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
similar trend, but a better fit than benzene. The derived Arrhenius parameters for addition at different sites of toluene relative to addition to benzene are shown for both solvent systems in
Table 23. The data is consistent with the selectivity data, and shows the same qualitative behavior.
Arrhenius parameters - acetonitrile
competing ΔEa error % A ratio range products (kJ/mol) (kJ/mol) error
2-MePhOH 0.25 0.13 0.49 -4.8 1.8 36.9 v. PhOH
3-MePhOH 0.14 0.06 0.31 -3.0 2.2 72.0 v. PhOH
4-MePhOH 0.072 0.035 0.15 -5.2 1.9 36.3 v. PhOH
Arrhenius parameters – hydrocarbons
2-MePhOH 0.27 0.11 0.68 -4.8 2.6 54.1 v. PhOH
3-MePhOH 0.16 0.074 0.36 -2.5 2.2 88.2 v. PhOH
4-MePhOH 0.055 0.021 0.14 -5.6 2.6 46.9 v. PhOH
Table 23. Arrhenius parameters for the competitive addition of OH to toluene and benzene in acetonitrile and
hydrocarbon solvents.
111
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
The determination of the ΔEa for the meta- isomer was the most difficult of the three isomeric products, associated with a large error for the comparison to benzene. There was little difference in the reactivity of toluene relative to benzene in the two solvents. Note however, that the data are a reflection of relative, rather than absolute reactivity. Thus, we cannot necessarily conclude that the reaction of hydroxyl radical with benzene is not faster in acetonitrile (although computational studies suggest it may be);70 we can only conclude that the rate of reaction of benzene and toluene are enhanced (or retarded) to a very similar degree in these two different solvent systems.
4.3 Hydroxyl Radical Addition to other Aromatic Substrates
4.3.1 o-Xylene (1,2-Dimethylbenzene)
Scheme 24 depicts the competitive reaction of ·OH with benzene and o-xylene to generate two isomeric dimethylphenols.
Scheme 24. Reaction of o-xylene with OH in acetonitrile.
Figure 36Figure shows the percent distribution of the products from the addition of ·OH to o-xylene in both acetonitrile and hydrocarbon. Rather surprising was the complete flip in
112
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
selectivity. In the benzene trials the ratio of 2,3-:3,4- was 60:40, but in acetonitrile the ratio was
40:60. This is the only substrate under investigation in which this was observed. All others do show differences in percent distribution, but the same pattern is observed. To place this in context, two competing reactions with similar Arrhenius pre-exponentials need only differ in barrier height by approximately 0.75 kJ/mol to achieve a 60:40 preference in regiosiomers. Thus, a flip in reactivity in a different solvent requires a change of less than 2 kJ/mol in relative energy barrier.
The change in the regioisomer distribution for m-xylene (see below) is of a similar magnitude to that observed here.
Distribution of o-dimethylphenols
0.650 avg % 2,3-Me2PhOTMS (PhH) 0.600
0.550 avg % 3,4-Me2PhOTMS 0.500 (MeCN)
0.450 avg % 2,3-Me2PhOTMS 0.400 (MeCN)
0.350 Ratio Ratio isomerofdistribution avg % 3,4-Me2PhOTMS 0.300 (PhH) 30 40 50 60 70 80 Temperature (°C)
Figure 36. Distribution of hydroxylation on o-xylene. Data points plotted are an average of each injection at the given temperature. Circles represent the data obtained from reactions carried out in benzene, and triangles represent the
data obtained from reactions carried out in acetonitrile.
The derived relative Arrhenius parameters for the various addition reactions are shown in
Table 24. It may be seen that the selectivity data yields Arrhenius data where both values contain small errors. The A ratio of the two products is a third of the expected probabilistic value of 1, reflecting the favoritism of substitution ortho- to a methyl group, and the rather large ΔEa, which
113
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
favors formation of the 3,4-dimethyl substituted product. The hydrocarbon data indicate the opposite trend.
Arrhenius parameters - acetonitrile
competing A ΔEa error % range products ratio (kJ/mol) (kJ/mol) error
3,4-Me PhOH v. 2 0.29 0.22 0.39 -4.3 0.78 18.1 2,3-Me2PhOH
2,3-Me PhOH v. 2 7.8 0.49 120 6.0 7.4 123.8 PhOH
3,4-Me PhOH v. 2 2.3 0.15 36 1.7 7.3 439.3 PhOH
Arrhenius parameters – hydrocarbons
3,4-Me PhOH v. 2 1.8 3.5 0.89 2.7 1.9 71.0 2,3-Me2PhOH
2,3-Me PhOH v. 2 0.54 3.5 0.082 -3.2 5.3 166.0 PhOH
3,4-Me PhOH v. 2 0.40 2.9 0.056 -2.9 5.6 191.3 PhOH
Table 24. Arrhenius parameters calculated for the addition of OH to o-xylene.
The relative reactivity returned large errors for both determined values. This is due in large part to the experiments conducted at 40 °C, and one data point in the 35 °C experiments. Removal of these data points results in smaller errors for both Arrhenius parameters of 3,4-dimethylphenol relative to phenol, but not to the same extent for the 2,3- isomer. The analysis gives ΔEa values of 10 ± 3.1 and 6.1 ± 3.6 kJ/mol for 3,4-dimethylphenol, and 2,3-dimethylphenol, respectively. The
114
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
A factor ratios are 0.031 and 0.094, for 3,4-dimethylphenol, and 2,3-dimethylphenol, respectively.
These values are in good agreement with the values determined for the selectivity.
The flip in the product distribution when the hydrocarbon solvent is changed to acetonitrile is due to an enthalpic factor. Addition to the two ortho- sites is favored entropically in the polar solvent, as evidenced by the change in the A factor ratios. No comparison of the relative kinetic data is possible due to the large errors in both solvents. However, the experiments in acetonitrile are heavily skewed by a few data points that are well off the trend, and removal of those data points gives the values closer to the expected results, or at the very least of the same sign.
4.3.2 m-Xylene (1,3-Dimethylbenzene)
A representation of the addition of ·OH to m-xylene is shown in Scheme 25, in which three isomeric products are produced.
Scheme 25. Reaction of m-xylene with OH in acetonitrile.
The data in acetonitrile was quite limited in this reaction set due to instrumental variation, if we eliminated the data points which failed the 3σ/avg. response or even the 1σ/avg. response criteria. Thus, the data presented was only subjected to limitations on LoQ of the individual isomers, and no ratios were eliminated due to instrumental variation.
The percent distribution of ·OH addition products is shown in Figure 37 for both solvent systems. The products in both solvents are clearly dominated by addition of ·OH to generate 2,4- dimethylphenol, and very little of the 3,5-dimethyl substituted product is formed. In acetonitrile the
115
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
2,4-dimethylphenol is a larger proportion of the product mixture. This increase in relative amounts of addition product comes largely at the expense of the sterically hindered 2,6-dimethyphenol product.
Distribution of m-dimethylphenols 0.80 0.70 avg % 2,4-Me2PhOTMS (MeCN) 0.60 avg % % 2,4-Me2PhOTMS 0.50 (PhH) 0.40 avg % % 2,6-Me2PhOTMS (PhH) 0.30 avg % 2,6-Me2PhOTMS 0.20 (MeCN) 0.10 avg % % 3,5-Me2PhOTMS Ratio Ratio isomerofdistribution (PhH) 0.00 0 20 40 60 80 avg % 3,5-Me2PhOTMS (MeCN) Temperature (°C)
Figure 37. Distribution of hydroxylation on m-xylene. Data points plotted are an average of each injection at the given
temperature. Circles represent the data obtained from reactions carried out in hydrocarbon solvent (PhH), and
triangles represent the data obtained in acetonitrile (MeCN).
The Arrhenius parameters obtained from their analyses are summarized in Table 25. The low concentrations of the 3,5-dimethylphenol product made determinations of the competitive
Arrhenius parameters difficult. The regression analyses of the plots returned small errors for all
Arrhenius parameters, but the A factor ratios are all much greater than the expected values based on reactive sites (with respect to the ranges, the intercept of the Arrhenius equation is a logarithmic term). The entropic effect leading to greater than expected A factor ratios when looking at the ortho- position of substrates with a methyl group is again perpetuated, and exacerbated greatly. There is an apparent synergistic effect of having multiple methyl substituents ortho- to a reactive site, causing the A factor ratios containing this product to be abnormally in favor of
116
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
addition to this site. The effect does not appear to be additive, but with the limitations of the data set no clear determination of the effect can be made. The A factor ratio does not overcome the energetic penalties from the presumably steric interactions of having two methyl groups adjacent to the reactive site.
The ΔEa shows that the more sterically hindered site is energetically disfavored, and based on the comparison of their percent distribution shows that this effect is the dominant component leading to preferential addition at the reactive sites leading to the 2,4-dimethylphenol product rather than the 2,6-dimethylphenol. The ΔEa comparisons for the un-activated 3,5-dimethylphenol product are both in favor of addition at this reactive site, but due to the very large competing A factors, even this does not make addition at this site preferred. The Arrhenius parameters associated with this regioisomer should be treated with great caution since the observed concentrations of this compound were very small. More experimentation is needed to obtain greater confidence in these ratios.
Again there were shown to be significant solvent effects associated with the electrophilic addition of ·OH to arenes. The trends observed in the selectivity in benzene were greatly exacerbated in the acetonitrile tests. The data for 3,5-/2,6-, and its reciprocal analysis may come to better agreement of Arrhenius parameters if the experiments are conducted at larger concentrations of m-xylene to increase the total yield of the 3,5- product. Due to the instrumental variation observed in the acetonitrile experiments, further experimentation will be required to confirm the results - the smaller errors are potentially not a good indication of true values.
Arrhenius parameters - acetonitrile
117
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
competing ΔEa error % A ratio range products (kJ/mol) (kJ/mol) error
2,4-Me2PhOH v. 3,5- 123 59 257 6.8 2.0 29.3 Me2PhOH 2,6-Me2PhOH v. 2,4- 15 8 28 10 1.6 15.7 Me2PhOH 3,5-Me2PhOH v. 2,6- 9E-05 1.6E-05 5E-04 -21 4.7 21.8 Me2PhOH 2,4-Me PhOH 2 27 13 58 7.0 2.0 29.2 v. PhOH 3,5-Me PhOH 2 0.038 0.011 0.13 -4.4 3.3 75.1 v. PhOH 2,6-Me PhOH 2 510 150 1739 18 3.3 18.6 v. PhOH
Arrhenius parameters – hydrocarbons
2,4-Me2PhOH v. 3,5- 4.7 1.6 14 -0.94 3.0 321.7 Me2PhOH
2,6-Me2PhOH v. 2,4- 1.7 1.4 2.1 2.4 0.57 24.4 Me2PhOH
3,5-Me2PhOH v. 2,6- 0.16 0.072 0.36 -0.82 2.2 273.5 Me2PhOH
2,4-Me PhOH 2 0.85 0.52 1.4 -2.3 1.3 59.5 v. PhOH
3,5-Me PhOH 2 0.14 0.061 0.31 -2.2 2.3 103.1 v. PhOH
2,6-Me PhOH 2 1.2 0.82 1.7 -0.41 1.0 246.1 v. PhOH
Table 25. Arrhenius parameters calculated for the addition of OH to m-xylene.
118
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
4.3.3 p-Xylene (1,4-Dimethylbenzene)
The competitive addition of ·OH to p-xylene and benzene is represented in Scheme 26 displaying the sole addition product for each substrate of addition due to the symmetry of the reactants. The acetonitrile data set was limited similar to the other xylene isomers studied, but at different temperatures. The instrumental variation eliminated all of the data points for the 50 °C trials.
Scheme 26. Competitive reaction of p-xylene and benzene in acetonitrile.
In the competitive Arrhenius plot (see Appendix III), the data at 40 °C is much lower than expected causing the trend to have a negative slope. The slope was expected to be positive showing an energetic preference for addition to the activated substrate. The Arrhenius parameters derived from these plots is shown in Table 26. The values were associated with large errors upon regression analysis, particularly the determination of the A factor ratio.
The expectation of an energetic favoritism for addition to p-xylene was not observed over the entire range of data, but restricting the data to the 40-60 °C range did give the expected trend with an energetic favoritism of 29 kJ/mol; however, this value is quite large. Restricting the data to the higher temperatures returned a much smaller error.
119
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
Arrhenius parameters - acetonitrile
competing ΔEa error A ratio range % error products (kJ/mol) (kJ/mol)
2,5-Me PhOH 2 150 5.1 4200 11 8.9 78.2 v. PhOH
Arrhenius parameters – hydrocarbons 2,5-Me PhOH 2 0.67 0.30 1.5 -4.8 2.3 47.4 v. PhOH
Table 26. Arrhenius parameters calculated for the addition of OH to p-xylene.
As the Arrhenius plot shows the energetic preference for ·OH addition to benzene, the greater concentration of 2,5-dimethylphenol formed must come from the A factor, which shown in the table is very large, but subject to an error range spanning three orders of magnitude.
Restricting the data as discussed above results in an A factor ratio of 0.00086. This value is much smaller than the anticipated 0.66 based on reactive sites, and not in line with the A factor ratios observed for other ortho- methylated phenols. Due to the limited data, and the error associated with that which is presented, no conclusion can be drawn pertaining to the Arrhenius parameters.
·OH preferentially adds to p-xylene rather than benzene, but the reasoning, whether entropic (A factor ratio) or enthalpic (ΔEa), cannot be determined. More experimentation is required to obtain a more complete data set, from which greater significance can be drawn.
4.3.4 Chlorobenzene
Scheme 27 shows the three addition products from the reaction of ·OH with chlorobenzene. The percent distribution of the three addition products shown above are presented in Figure 38. The reaction is dominated by formation of the ortho- product, but not to the extent that other reactions presented. The meta- isomeric product has increased to a
120
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
significant portion of the product mixture, largely at the expense of formation of the ortho- isomer.
In switching solvent systems from hydrocarbon to acetonitrile the ortho- product gained favor at the expense of both the para- and meta- to a significant degree.
Scheme 27. Reaction of chlorobenzene with OH in acetonitrile.
Distribution of chlorophenols
0.600 avg % o-ClPhOTMS (MeCN) 0.500 avg % o-ClPhOTMS (PhH)
0.400 avg % p-ClPhOTMS (PhH)
0.300 avg % p-ClPhOTMS (MeCN) 0.200 avg % m-ClPhOTMS (PhH) 0.100 avg % m-ClPhOTMS Ratio Ratio isomerofdistribution (MeCN) 0.000 30 40 50 60 70 80 Temperature (°C)
Figure 38. Distribution of hydroxylation on chlorobenzene. Data points plotted are an average of each injection at the given temperature. Circles represent the data obtained from reactions carried out in hydrocarbon solvent (PhH), and
triangles represent the data obtained in acetonitrile (MeCN).
Similar to the data for toluene selectivity in acetonitrile presented above there was little variation in the instrument, allowing for only one data point to be removed from the acetonitrile
121
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
data set. A second data point was removed due to the limitations imposed by the LoQ for the para- isomeric product.
From the concentration ratios three competitive Arrhenius plots were generated to calculate the A factor ratios, and ΔEa for each reactive site relative to one another. The Arrhenius parameters obtained from these plots are given in Table 27. For the Arrhenius plots the acetonitrile data is, again, a much tighter fit than the benzene data, and there are clear differences in the two data sets (see Appendix III). Determination of the A factor ratios for each selectivity comparison in acetonitrile returned small error ranges upon regression analysis of the concentration ratios. The A factor ratio for ortho-/meta- is near the expected value of 1 based on reactive sites, but is slightly in favor of formation of the meta- isomer. Comparison of the para- isomer’s A factor shows that it is slightly over double the expected value in favor of formation of the para- product for both comparisons The reactivity of these two isomers (meta- and para-) may not be very different in the two solvent systems, as there is significant overlap of the data.
The ΔEa values calculated for acetonitrile show much more consistent results, as the error associated with comparisons involving the ortho- isomer are smaller. In both cases the ortho- isomer is favored. The ΔEa found for the para- and meta- products is statistically insignificant, but very near the value that would be found for the isomers if the ΔEa was found by difference of their individual comparisons to the ortho- product. It is likely that this value is near the true value for the ΔEa of the meta- and para- isomers. The ΔEa data for benzene is somewhat inconsistent considering their theoretically transitive relationship, but does match up with the acetonitrile data quite well compared to the differences observed between solvent systems with methylated arenes.
122
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
Arrhenius parameters - acetonitrile competing ΔEa error A ratio range % error products (kJ/mol) (kJ/mol)
2-ClPhOH v. 0.93 0.72 1.2 -2.6 0.70 26.4 3-ClPhOH
4-ClPhOH v. 1.2 0.90 1.7 2.4 0.81 33.8 2-ClPhOH
4-ClPhOH v. 1.1 0.84 1.5 -0.24 0.81 340.6 3-ClPhOH
2-ClPhOH v. 0.11 0.092 0.14 -3.2 0.59 18.2 PhOH
3-ClPhOH v. 0.081 0.042 0.16 -1.8 1.7 98.5 PhOH
4-ClPhOH v. 0.14 0.098 0.20 -0.83 0.97 117.4 PhOH
Arrhenius parameters – hydrocarbons
2-ClPhOH v. 0.75 0.26 2.2 -2.1 3.0 142.5 3-ClPhOH
4-ClPhOH v. 0.46 0.15 1.4 -1.4 3.1 228.7 2-ClPhOH
4-ClPhOH v. 0.63 0.52 0.77 -1.8 0.55 30.9 3-ClPhOH
2-ClPhOH v. 0.23 0.055 0.96 -0.52 4.0 770.8 PhOH
3-ClPhOH v. 0.14 0.027 0.72 -0.61 4.6 764.4 PhOH
4-ClPhOH v. 0.092 0.017 0.51 -2.2 4.8 214.8 PhOH
Table 27. Arrhenius parameters calculated for the addition of OH to chlorobenzene.
123
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
The ortho- product became more favorable in the acetonitrile due in large part to the change in ΔEa between it and the para- product, as well as an increase in the A factor ratio comparing it to the meta- product. The para- product became less energetically favorable than the meta- and ortho- product leading to a decrease in its rate of formation. The meta- isomer became less favorable to both other isomeric products in the A factor ratio, and less energetically favorable when compared to the ortho- product leading to an overall decrease in the final concentration compared to the other two products.
The acetonitrile experiments all had an increase in energetic stability of addition transition states for chlorobenzene, relative to that leading to formation of phenol. This is consistent with a polarized TS leading to the formation of chlorophenols. This is somewhat expected due to both substituents on the intermediate chlorocyclohexadienyl radical being inductively withdrawing.
4.3.5 Trifluorotoluene (α,α,α-Trifluoromethylbenzene)
The reaction between ·OH and trifluorotoluene to generate three addition products is shown in Scheme 28, and their relative percent distribution is shown in Figure 39.
Scheme 28. Reaction of trifluorotoluene with OH in acetonitrile.
In the case of the deactivated ring, the expected trend of dominance of the product mixture by the meta- isomer is observed in both solvents. The ortho- isomer is not nearly as favored over the para- isomer as observed in the other methylated substrates discussed above. There is a
124
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
small gain in the ortho- product when the solvent was changed to acetonitrile, largely at the expense of the para- isomeric product. The meta- products percent composition of the product mixture is very similar, and in some cases indistinguishable between the two solvents studied.
Distribution of trifluoromethylphenols
0.600 % 3-CF3PhOTMS (PhH)
0.500 % 3-CF3PhOTMS (MeCN)
0.400 avg % 2-CF3PhOTMS (MeCN) 0.300 % 2-CF3PhOTMS (PhH)
0.200 % 4-CF3PhOTMS (PhH) 0.100 avg % 4-CF3PhOTMS Ratio Ratio isomerofdistribution (MeCN) 0.000 30 40 50 60 70 80 Temperature (˚C)
Figure 39. Distribution of hydroxylation on trifluorotoluene. Data points plotted are an average of each injection at the given temperature. Circles represent the data obtained from reactions carried out in hydrocarbon solvent (PhH), and triangles represent the data obtained in acetonitrile (MeCN).
The data for the trifluoromethylphenols in acetonitrile is rather limited due to the high LoQ of the para- isomer. The data was further limited due to instrumental variation, particularly in precisely determining the amounts of the ortho- isomer. The concentrations of the ortho- isomer were quite small, and the susceptibility to instrumental variation was exacerbated by this.
The calculated Arrhenius parameters for the selectivity data in the acetonitrile experiments all, with the exception of the meta-/ortho- A factor ratio, contain large errors (Table 28). The A factor ratios for all acetonitrile experiments are below the expected values based on reactive sites.
The comparison of the para- and meta- isomers gave a very shallow best fit line, which was susceptible to the scatter of data points associated with the 35, and 50 °C trials. The slope is likely positive, as the para- position is deactivated due to the inductive withdrawing effects normally
125
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
associated with CF3 groups. The slope of the line for the ortho- to meta- comparison is similarly shallow, and the ΔEa of the two isomers is subject to very large error as well.
Arrhenius parameters - acetonitrile
competing ΔEa error A ratio range % error products (kJ/mol) (kJ/mol)
3-CF PhOH v. 3 2.4 1.4 4.4 -0.081 1.6 1926.1 4-CF3PhOH 3-CF PhOH v. 3 1.2 0.54 2.6 -0.46 2.1 459.4 2-CF3PhOH 2-CF PhOH v. 3 7.8 1.4 45 4.0 4.6 115.7 4-CF3PhOH 3-CF PhOH v. 3 0.080 0.048 0.13 -0.66 1.4 204.0 PhOH 4-CF PhOH v. 3 0.17 0.05543 0.50 3.60 2.9 81.1 PhOH 2-CF PhOH v. 3 0.11 0.062 0.19 1.00 1.5 151.0 PhOH Arrhenius parameters – hydrocarbons 3-CF PhOH v. 3 1.1 0.95 1.3 -1.9 0.40 20.8 4-CF3PhOH
3-CF PhOH v. 3 0.92 0.58 1.5 -1.4 1.3 91.4 2-CF3PhOH
2-CF PhOH v. 3 1.4 0.95 2.1 -0.016 1.1 7095.8 4-CF3PhOH 3-CF PhOH v. 3 0.36 0.12 1.1 4.1 3.0 74.6 PhOH 4-CF PhOH v. 3 0.068 0.039 0.12 1.5 1.6 103.4 PhOH 2-CF PhOH v. 3 0.080 0.055 0.12 0.98 1.0 106.0 PhOH
Table 28. Arrhenius parameters calculated for the addition of OH to trifluorotoluene.
The comparison of the two deactivated positions, although the Arrhenius plot had a large slope, was very susceptible to error based on the scattering of data points, particularly the point
126
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
for the 40 °C experiments at 0.09. This point is likely an error, and more experimentation would readily allow for the removal of the data point by Dixon’s Q-test. When this data point is removed the slope becomes much less steep, as would be expected. The para isomer is most likely favored energetically, due to the steric interactions the approaching ·OH encounters at the ortho- position.
The general trend of expected reactivity was observed, but due to the severe limitation of the data set no conclusive evidence for determined Arrhenius parameters was found.
The selectivity data for the addition of ·OH to trifluorotoluene was too noisy for any comparison of the Arrhenius parameters between the two solvents to be made for the selectivity data. There were some apparent, but slight variations in the selectivity of the reaction based on the percent distribution of products shown in Figure 39. The differences came from the changes in the para- and ortho- isomers, which may not be true variations as there was difficulty in calculating the concentration of the para- isomer due to the high LoQ associated with the calibration curve. Regeneration of this calibration curve may allow for better comparisons of reactivity. Alternatively the reactions can be run again, with greater concentrations of trifluorotoluene to obtain greater integration values.
4.4 Structure-Reactivity Relationships
As with reactions in hydrocarbon solvents, the observed selectivities in acetonitrile are consistent with the assertion of ·OH as an electrophile. It was not always clear which Arrhenius parameter was the dominant factor in determining the reactivity of ·OH towards the arenes relative to benzene. This is largely due to the limited number of experiments run in acetonitrile.
A Hammett plot was generated for the acetonitrile data. The σ values used were the same as in Chapter 3 (see Chapter 3, Table 19). Notably there was no determination completed for anisole (methoxybenzene), which leaves only six determined values as well as the reference reaction. The Hammett plot is shown in Figure 40. There is a clear negative trend, indicating build-
127
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
up of a positive charge during the reaction, and electron donating groups enhance the rate of the reaction. There may be a deviation from the trend in the case of toluene (R = CH3), but with no other activating groups undertaken in this study it is difficult to determine.
Hammett correlation 0 -0.4 -0.2 0 H 0.2 0.4 0.6
p-CH3
m-CH 3-0.5
p-Cl m-Cl y = -1.664x - 0.2946 m-CF R² = 0.7962 -1 3
log log ([RPhOTMS]/[PhOTMS]) p-CF3 -1.5 σ
Figure 40. Hammett correlations of monosubstituted arenes.
The ΔEa of each substrate was plotted as a function of the Hammett substituent constants in Figure 41. There is a clear positive trend in the data, with the only potential outlier being the reference, benzene, at the origin. The positive slope shows that the activation energy is indeed lessened due to stabilization of the substituents in the TS. Both outcomes reflect the reactivity observed in hydrocarbon solvents.
128
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
ΔEa Hammett correlation 8
6 y = 6.7646x - 2.117 4 R² = 0.4758 p-CF3 2 H
a 0
E m-CF3 Δ -2 p-Cl m-CH3 -4 m-Cl
p-CH3 -6 -8 -0.3 -0.2 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 σ
Figure 41. Activation energy Hammett correlation.
FMO theory was invoked to analyze the data from the acetonitrile experiments. As in the previous chapter the total relative energy of the substrate to benzene was plotted against its ionization potential in Figure 42. For the acetonitrile data the 55 °C data was used as it had the smallest variation over all substrates. There is a clear negative trend in the data, with the activated rings appearing in the positive quadrant and the deactivated rings in the negative quadrant. This is the expected trend based on electrophilic properties exhibited by ·OH.
Comparison of the structure-reactivity relationships of the two solvents is not presented visually due to the very close and often overlapping data points in both data sets. Note that the data being considered were obtained in different solvents, and at different temperatures. The comparison is summarized in tabular form in Table 29. In every SAR plot the slope of the trend line is decreased in magnitude for the acetonitrile experiments, but of the same sign. This may be due to the stabilization of positive charge build-up in every TS regardless of substitution by the more polar solvent. The R2 values obtained for the lines of best fit are comparable across each comparison.
129
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
kPhR/kPhH 0.8 m-Ph(CH ) 0.6 3 2
0.4 PhCH3 )
PhH 0.2 PhH k / p-Ph(CH3)2 o-Ph(CH )
0.0 3 2
PhR k -0.2
log log ( PhCl -0.4 y = -0.8735x + 7.9004 R² = 0.8936 -0.6 PhCF3 -0.8 8.2 8.4 8.6 8.8 9 9.2 9.4 9.6 9.8 ionization potential (eV)
Figure 42. Reactivity of substituted arenes relative to benzene correlated to ionization potential.
hydrocarbon acetonitrile plot slope R2 slope R2 Hammett -4.1813 0.7543 -3.8306 0.7959 correlation
ΔE a Hammett 10.491 0.4932 6.7646 0.4758 correlation ionization -1.1425 0.9297 -0.8735 0.8936 potential
Table 29. Comparison of SAR correlations.
The absolute rate coefficients for attack of hydroxyl radical on a range of hydrocarbons including benzene has been measured in acetonitrile at 298 K.95 The authors sought to construct a structure-reactivity relationship using the FMO model in the same manner as described above.
The value of the intercept will change, since those authors were plotting absolute, rather than
130
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
relative, rate coefficients, but the gradient of the line of best fit for their data was -1.033 eV-1. This value is clearly consistent with the data obtained in this study.
In this chapter, it has been demonstrated that it is possible to generate structure-reactivity relationships for the addition of hydroxyl radical to arenes in a polar organic solvent, and that these relationships are consistent with the assertion of hydroxyl radical is an electrophilic species.
These relationships, in agreement with the findings in the previous chapter, imply a degree of charge separation in the transition state for this reaction. These are, again, consistent with computational studies.70
4.5 Preferential Addition of ·OH to ortho-Positions
In both solvent systems studied there was a clear preference for addition of hydroxyl radical at positions ortho- to methyl groups. The expected trends in ΔEa were still observed when isolating the ortho- products; that is, EDGs tend to stabilize the transition state of activated reaction sites. The major differences were observed in the A ratios, which implies this is a largely an entropic, not enthalpic, effect. It could be argued that the preferential addition at the ortho- site is observed for the chlorine substituent, but clearly not for the -CF3. The -CF3 and -Cl groups are inductively withdrawing, and result in a large negative charge around the moiety. The electrophilic
·OH would likely be drawn towards these moieties due to electrostatic attraction, which would bring the ·OH into proximity of the ortho- site. However, ·OH would be oriented with the more positively charged hydrogen towards the electron-rich substituent.
As noted previously, reactivity consistent with such behavior has been previously observed in other experiments where hydroxyl radical is generated in the presence of arenes.116,
123 These experiments did not elucidate Arrhenius parameters, though, and only a comparison between the percent distribution can be made. It was found that a number of different isomeric
131
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
distributions were possible, often depending on the oxidant system used.123 In the work presented above, in all cases in which a methyl substituent was present on the ring there was an inordinate amount of ortho- methyl phenolic products formed. This is could be due to a number of causes.
One such reason would be preferential addition of TEMPO to the cyclohexadienyl radical.
It has been assumed for this study TEMPO acts as an oxidant and abstracts a hydrogen directly from the cyclohexadienyl intermediate. However, an alternative pathway involving coupling of radicals exists (Scheme 29). The scheme shows the unfavorable steric interaction, as reversed parentheses [i.e., )( ] that would result from formation of the meta- adduct.
Scheme 29. Steric interaction between methylated arenes and TEMPO during possible adduct formation.
The cyclohexadienyl radicals generated upon addition of ·OH would also favor addition at the ortho- site, as the unpaired electron can be placed in the p-orbital of the methylated carbon.
This has a stabilizing effect due to the hyperconjugation with the C-H -bonds. In addition, there are two structures which steric interactions for formation of the TEMPO adduct in the meta- isomer
132
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
would be problematic, and energetically unfavorable. The single resonance contributor for the ortho- isomer which would generate steric hindrance is also shown, but is the most stable of the resonance contributors. Coupling with TEMPO is likely to be reversible, even at modest temperatures. If hydroxyl radical addition to meta- positions is similarly reversible (or the intermediate can undergo group migration rearrangements), there is the potential for ortho- products to be favored at the expense of meta- products. Alternatively, the TEMPO adducts may quickly decompose to give the corresponding phenolic products. The para- adducts are not shown in Scheme 29, but would have similar resonance structures to the ortho- isomer.
This hypothesis could readily be tested in the laboratory setting by employing different N- oxyl radical traps. The choice of much more sterically bulky traps, such as di-t-butylnitoxyl124, should show a greater preference for the ortho- addition product. Sterically smaller radical traps, such as ABNO124, should allow for a more facile addition to the meta- adduct, and the preference for addition at the ortho- site would be decreased. Some literature precedence exists for this.
When employing no radical trap other than the bromophenyl radical from the ·OH initiator and relying heavily on disproportionation reactions for termination, very similar substitution patterns were observed. When the reactions were saturated with oxygen a different isomeric distribution was found.116 Triplet oxygen is known to add to the cyclohexadienyl radical, and re-aromatization takes place upon elimination of ·OOH.114, 125 This is shown in Scheme 30.
Scheme 30. Oxygen trapping of cyclohexadienyl radical, and re-aromatization.114
The addition of ·OH to naphthalene has been calculated by density functional theory (DFT) methods. The authors considered the formation of 1-naphthol and 2-naphthol, which we may
133
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
consider as proxies for the addition of hydroxyl radical ortho- and meta- to a methyl group respectively. It should be noted that this system does not provide a proxy for para- addition. We should note, however, that these computational studies are gas-phase studies, and may have limitations in applicability to condensed phases.
The authors found that addition reactions proceeded via epoxide-like transition states of hydroxyl and arene ( Scheme 31).
Scheme 31. Intermediates of OH addition to naphthalene (energies in kJ/mol).126
Calculations indicated that both transition states would favor the formation of 1-naphthol: in the case on the left side of Scheme 31, ortho- addition would be favored over ipso- addition, particularly in the case of naphthalene. In fact, the authors did not discuss such a possibility.
Even in our systems, isomerization to the ortho- product would be heavily favored as removal of the substituent by TEMPO would be much less favorable than abstraction of a hydrogen atom. In experiments discussed in this study there was no detectable removal of the functional groups during reactions with ·OH. This was accomplished by generating the ·OH initiator in the neat arene, and having no competing benzene. There was no formation of phenol detected, and led to the conclusion that no removal of the functional group had taken place.
134
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
The findings from the DFT calculations show a significant energetic advantage for ortho- over meta- substitution. Whether the fact that the 1-naphthol is accessible from more transition states, and whether this contributes to an entropic advantage, is unclear.
If this process were taking place, it would be difficult to elucidate through experimentation.
Theoretical calculation of the different TSs and intermediates could be undertaken, where addition to the ipso position could be accounted for. If this addition to the ipso position occurs, but no elimination of the functional group is taking place (as shown by experimentation) then some isomerization must be happening.
The isomerization could occur through a transition state structurally similar to the complexes depicted above (Scheme 31). If addition does occur to generate the ipso product, and there is no removal of the functional group, then the isomerization pathway depicted may be possible. 1,2-halogen atom shifts are known to occur, particularly when a more stable product can be generated.43
Scheme 32. Isomerization of ipso addition product.
Isomerization would likely not occur in the reverse order, as the stability of the tertiary radical on the far right, is greater than the stability of the cyclohexadienyl radical shown in the middle of
Scheme 32. This process may also be occurring for addition across the C2-C3 bond which would generate the meta- cyclohexadienyl radical, which would not be stabilized by inductive or resonance effects. Finally the para- product would not likely isomerize to the meta- product for the same reasons.
135
Chapter 4. Hydroxyl Radical Reactivity in Acetonitrile
The isomerization process would be indicative of thermodynamic control. Discerning this process would be difficult experimentally, particularly if coupling to TEMPO is reversible and hydrogen abstraction by TEMPO to re-aromatize the ring is slow. Using different concentrations of a radical trap could possibly determine if isomerization is taking place, at least between the disfavored meta- isomer. That is, the greater the concentration of radical trap, the less likely the isomerization would take place before abstracting the hydrogen to return aromaticity to the ring.
Similar to the above discussion, theoretical calculations could allow for the calculation of the different energies of the TS and intermediates. The theoretical approach would be more likely to determine if isomerization is at least possible, as the formation of TEMPO-cyclohexadienyl adducts is in question as well.
A complimentary DFT study showed that there is a pre-reactive complex in which the approaching ·OH is stabilized above the plane of aromatic rings, as shown in Scheme 33.127 The ipso-structure, on the left, was shown to be very slightly energetically favored over the ortho- structure, on the right. From the more stable ipso-structure the bond angle C-H-O shows the angle is smaller for the 1 position of naphthalene by ~9°, but a slightly longer bond length of 0.5 Ǻ.127
The calculation was undertaken to observe the energetic differences in hydrogen abstraction reactions, and no mention of how this would affect the addition to arenes was made. This calculation was also for the gas phase reaction, and incorporating solvation would likely change the relative energies of the two pre-reactive intermediates.
Scheme 33. Approach of OH during hydrogen abstraction reactions. Relative energy given in kJ/mol.127
136
CHAPTER 5 – CONCLUSIONS AND FUTURE EXPERIMENTATION
5.1 Introductory Remarks
In the preceding chapters a new experimental design for probing the reactivity and selectivity of hydroxyl radical with aromatic hydrocarbons was described. Unlike previous methodologies used for such studies the use of a nitroxide radical trap, TEMPO, allowed us to investigate the first step of hydroxyl radical-derived degradation of these species without complicating side reactions or secondary oxidation products. Our initial proof-of-concept approach involved the reaction of toluene relative to benzene in hydrocarbon solvents. While these solvents are not necessarily the most accurate model for water (a more environmentally relevant solvent system), they have the advantage of being readily miscible with the substrate, and both the TEMPO and the peroxide initiator are easily dissolved in these solvents. GC/MS analysis of the derivatized isomeric products allowed the selectivity of the reaction to be determined, and the selectivity is consistent with attack on the ring by an electrophilic species.
The experimental regime as formulated in Chapter 3 was quite amenable to a change in the solvent system (Chapter 4). Only new reaction times were required to be calculated based on the decomposition of the ·OH initiator used (Chapter 2 and Appendix II). With this information in hand, the new experiments in a polar organic solvent were undertaken. Many of the same trends were observed between the two solvents, but a clear stabilizing effect across all substrates was found.
Chapter 5. Conclusions & Future Experimentation
A number of hypotheses were outlined in Chapter 1 which could be tested using this methodology. Our results may be summarized as follows:
Based on the distribution of isomeric products for each substrate the ·OH does behave as
an electrophile. The activated rings had larger proportions of the ortho- and para-
products, and the deactivated rings had a larger proportion of the meta-. The selectivity
data for different isomers exhibited (where possible) a clear correlation with their
respective Hammett parameters, and the reactivity constant derived from the Hammett
analysis is consistent with positive charge build up in the aromatic ring in the transition
state, consistent with HO• behaving as an electrophile. A qualitative similarity between
radical electrophilic attack, and ionic electrophilic attack may be observed.
In each case there was considerable selectivity of ·OH addition to the arenes. In the cases
of the methylated arenes this was largely due to the entropic A factor for the ortho-
position. The reasons for the preference remain unclear, and will form part of future
computational studies.
Reactivity of each aromatic substrate was determined relative to benzene. For many of
the determinations this method worked well; however, when the reactivity of the competing
substrates were similar the results were subject to significant error. Desptie this, it was
possible to derive a linear structure-reactivity curve for all of the compounds used in this
study, based on a Frontier Molecular Orbital approach to chemical reactivity. This
correlation was similar in both non-polar and polar solvents, and similar to those observed
previously by very different methods.
The method described in the previous chapters could be described as broadly successful, but does suffer from certain limitations, notably its inability to detect products derived from abstraction reactions. In addition, there are a number of improvements to be made to this approach in order to obtain more reliable data (recall that although the overall structure-reactivity
138
Chapter 5. Conclusions & Future Experimentation
correlations were quite good, a number of the relative Arrhenius parameters were subject to considerable experimental uncertainty, and the values were often found to be not statistically significant):
One of the problems was that for many cases, detected concentrations of products fell
below the established LoQs for the method. The volumes of the reactions were chosen
based on the reaction vessels on hand. There were a mixture of 3 and 5 mL conical vials,
and regardless of the size of the conical vial 3 mL was used. Increasing the volume to 5
mL or more would likely generate more product, and make determinations of many of the
parameters more accurate.
In addition, a larger concentration of the ·OH initiator could be used in the benzene
experiments. In acetonitrile the concentration of ·OH initiator was approaching the 10%
v/v solution that is deemed safe for alkylhydroperoxides.128 Increasing the concentration
would come with a danger of explosion, and is not recommended.
In nearly all cases the experiment yielded better results for the selectivity data than the
relative reactivity data. This is due to experimental error. After introduction of the ·OH
initiator solution there was a potential for loss of benzene solvent via evaporation due to
leaks in septa, or ill-fitting caps, despite the use of Teflon tape on the threads. The
evaporation of solvent alters the composition of the competing substrates which would be
expected to change the kinetic results. This would not change the outcome greatly for the
selectivity data, which is evidenced by the greater level of confidence and statistical
significance of the selectivity data relative to the reactivity data. A less volatile kinetic
standard (for example, mesitylene: 1,3,5-trimethylbenzene) may provide a better
comparator.
The evaporation of solvent could be curtailed by using vacuum sealed reaction tubes,
which are presently on hand. The freeze-pump-thaw cycles would remove any dissolved
139
Chapter 5. Conclusions & Future Experimentation
oxygen, which could alter the outcome of the reactions due to oxygen behaving as a
radical trap.114 Such an approach does have limitations with regards to temperature: if the
decomposition time of the peroxide is comparable to the thermal equilibration time of the
sample, this will cause problems.
Analysis by GC/MS may be hampered by column degradation, and is strongly dependent
on both the type and overall state of the column. Injection of unprotected alcohols and
thiols will rapidly degrade column efficiency. Ideally, a dedicated, rather than general use,
instrument is desirable.
5.2 Future Exploration of ·OH Reactivity
5.2.1 Continued Investigation of Arene Reactivity
A number of the experiments carried out in acetonitrile could be enhanced with further experimentation, and possibly statistically significant results obtained. The trifluorotoluene experiments, in both solvents would benefit from a larger molar fraction of trifluorotoluene than used in these determinations, to provide more confidence in the measurements of the concentrations of the less favored isomeric products. The calibration curves used in many of these determinations (Appendix I), particularly for anisole, could be re-investigated or re-constructed using more appropriate concentration ranges.
It would be useful to consider the reaction of hydroxyl radical with anisole dissolved in acetonitrile. This would allow for a side-by-side comparison as was done for the other six substrates, and broaden the coverage of the structure-reactivity relationships in this solvent. The hydrogen bonding accepting character of the methoxyl substituent would likely be changed by changing the polarity of the solvent.129
140
Chapter 5. Conclusions & Future Experimentation
The methodology utilized for the determination of competitive Arrhenius parameters is amenable to any number of aromatic substrates. Some would pose more difficulty (aniline, nitrobenzene) due to other competing reactions other than addition taking place with those moieties. Heterocyclic aromatics, polycyclic aromatics, and other substituted aromatics could easily be tested by these methods (Figure 43).
Some preliminary results on the substitution of pyridine showed formation of addition products to the 2- and 4-positions, but no 3- isomer was found. The analysis of these species is complicated by the fact that the initially formed pyridinols are readily tautomerized to pyridine species. The products were able to be derivatized via the method outlined in Chapter 2. It was unclear, however, if the TMS group was added to the hydroxyl group, or to the cyclic nitrogen.
Isoxazole, furan, and benzofuran were also subjected to the competitive addition of ·OH.
No addition products were observed for furan or isoxazole, but this may have been due to the solvent delay being used during analysis by GC/MS if the products eluted quickly from the column.
Similarly, the initial furanol products may potentially tautomerize. Some addition products for the benzofuran trial were observed. However, the NIST08 database used could not recognize the isomers. Generating TMS ether standards of the expected addition products would elucidate the products obtained, as well as eliminate those not formed. Many of the requisite alcohols (or their tautomers) are commercially available.
The competitive addition of ·OH to naphthalene was attempted in benzene, but the low solubility of naphthalene in benzene hampered the precise determination of naphthols formed.
Concentration of the reaction mixture was also difficult as the naphthalene precipitated from the solution during the work up. The determination of biphenyl suffered from the same difficulties in work up and derivitization as naphthalene. The expected addition products were observed, but no attempt to discern their concentrations was made. The smaller amounts of competing substrates used in the acetonitrile tests would alleviate this problem.
141
Chapter 5. Conclusions & Future Experimentation
Figure 43. Expected OH addition products to heterocyclic and polycyclic arenes.
A combination of groups may also prove interesting, as well as confirm some of the findings of the present study. Chlorinated toluenes are readily available from commercial sources.
142
Chapter 5. Conclusions & Future Experimentation
These could be used as models for, and in comparison with, various PCBs, which are also commercially available, to study the effects the different substituents have on the outcome of the reactions. Other substrates combining a multitude of the different substituents used in this dissertation are commercially available as well.
5.2.2 Secondary Oxidation Products
As mentioned in the introductory chapter, addition of a second hydroxyl group would allow biological degradation of aromatics to take place.64c It would be beneficial to obtain the kinetics of the secondary addition reactions to further bolster kinetic models. Determining these rates would pose a number of difficulties, however. The secondary oxidation products have previously been measured by pulse radiolysis techniques for cresols, and show greater reaction rates for the m- cresol.125 This is due to the delocalization of the unpaired electron in the cyclohexadienyl radical onto the carbons containing the OH and CH3 groups (Scheme 34).
Scheme 34. Delocalization of unpaired electron in m-cresol OH addition.
The secondary reactions would likely need to be made relative to phenol, rather than benzene. This is due to the enhanced reactivity of activated rings to the electrophilic ·OH (see anisole section). The method would also not be able to be carried out in benzene, as addition
(although unlikely in this case) would generate more phenol, and the concentration of one of the competing substrates would change over the course of reaction, making the kinetics much more
143
Chapter 5. Conclusions & Future Experimentation
complex. Toluene or xylene could be a potential candidate, but it is more probable the reaction would work better in acetonitrile to avoid formation of more phenolic products from reactions with the solvent.
A further difficulty to overcome would be the radical phenolic coupling associated with radical reactions and the substrates. Greater quantities of the competing substrates would be required, but may be hampered due to solubility. Larger reaction vessels could be purchased, however, the time spent during the workup of the reactions would be a deterrent. Experimentation has shown that concentrating the reaction mixture under reduced pressure alters the composition of the product mixture. A further potential source of complication would be the hydrogen abstraction from the –OH group of phenol, to generate a stabilized phenoxyl radical.
The substrates (primary oxidation products) are already on hand as they were used to make the standards for generating calibration curves, or could be readily purchased from commercial suppliers. Commercial availability of the substituted catechols, resorcinols, and hydroquinones is sparse, and those that are available tend to be quite expensive.
Generating the necessary dihydroxy arenes can be accomplished by known synthetic techniques. From benzaldehyde starting materials, a Dakin oxidation can be performed to obtain the required products (Scheme 35).130.
Scheme 35. Dakin oxidation.
Many benzaldehydes are commercially available, but some are still quite expensive. For the catechols which are not available, an ortho- formylation (Scheme 36) could be accomplished, followed by the Dakin oxidation above.130 This process is amenable to many different substituted
144
Chapter 5. Conclusions & Future Experimentation
phenols, and by careful selection of the starting material multiple necessary products could be produced in a “one-pot” synthesis. Separation may prove difficult, and the ortho- substituted phenols may be necessary for obtaining a single product.
Scheme 36. ortho- formylation of phenol.
The necessary resorcinols could be synthesized from 1,3-cyclohexanediones by oxidation with iodine (Scheme 37).131 This process is amenable to substitution around the ring, including the 2 position. Many of the cyclohexanediones are commercially available. The un-substituted dione is readily available, and easily substituted via enolate chemistry.
Scheme 37. Oxidation of cyclohexanediones.
Generating the hydroquinones can also be accomplished by many known techniques.
Reduction by sodium azide (Scheme 38) has been shown to be rather tolerant to various functional groups.132 However, if the methodology is expanded to contain alkyl groups containing
43 electrophilic centers the azide will likely substitute at the position in an SN1 or SN2 reaction.
Scheme 38. Reduction of benzoquinone to hydroquinone.
145
Chapter 5. Conclusions & Future Experimentation
With the required dihydroxybenzenes in hand, TMS protection could be carried out in the same manner as employed in the present study to generate calibration standards.
5.2.3 Expansion of Solvent Effects
At the outset of this project, the intent was to develop and provide “proof-of-concept” for a methodology to investigate the reactivity and selectivity of hydroxyl radical with arenes, and the data obtained (within the limits of experimental uncertainty) demonstrates this. The expansion of the reactions into a much more polar solvent, acetonitrile, was the first step in a movement towards the environmentally relevant study of ·OH kinetics. The further expansion of the solvent effects exhibited in water is of particular interest for future experimentation.
Notable differences in the competitive kinetics of ·OH addition to arenes in different solvents was shown in Chapter 4, and it is likely that this trend would continue by using water as the solvent. Water is more polar than acetonitrile, and, potentially of greater importance, exhibits strong hydrogen bonding acceptor/donor properties. Continuation of the research into competitive kinetics into a new, more environmentally relevant solvent would supplement existing methodology in water remediation technologies. The possible means of generation of ·OH, the trapping of the resultant cyclohexadienyl radicals to generate stable phenolic compounds, and detection of the trapped products will be discussed.
There are a number of means to generate ·OH in water, some of which were outlined in
Chapter 1, that could be potentially amenable to investigations in water systems. In particular, photoexcitation of TiO2 would provide a good means of generating ·OH for these studies. The reaction is not as sensitive to pH changes as Fenton’s reaction, and the catalyst is recoverable, which extends the lifetime and utility of the substance. Depending on the particle size of the
146
Chapter 5. Conclusions & Future Experimentation
nanoparticle new filtrations apparatus may need to be purchased to effectively remove the solid from the solution, possibly in conjunction with centrifugation. Photoexcitation would be conducted in a photoreactor fitted with a mercury lamp, with a cutoff filter to eliminate potential photochemical reactions of the substrates.
Photoexcitation may require the purchase of quartz glassware, as the typical laboratory
(pyrex) glassware absorbs UV radiation below 300 nm, and would hamper the generation of ·OH
(although it may also provide a partial cutoff filter). Maintaining a constant temperature may also prove difficult, but with development of a suitable reaction vessel this should be possible by flowing water through the reaction vessel in a similar fashion to a reflux condenser. This would allow relative kinetic data to be obtained at different, carefully controlled temperatures, and plotting the concentration ratios in Arrhenius plots.
As photogeneration of ·OH from TiO2 has been proposed as a large-scale water remediation technique,133 and the kinetics from laboratory scale experiments employing this technique would be particularly useful in enhancing kinetic models. There is most certainly an interaction between the organic substrates and the surface of the catalyst. The outcome this interaction has on the oxidative reactions is necessary to know.
Fenton chemistry could also be employed. This reaction is run under acidic conditions to prevent precipitation of the iron catalyst. The typical iron salt used in Fenton chemistry is FeSO4, which upon addition of H2O2 is quickly oxidized to Fe(III). This process also generates a large amount of ·OH, and rapid degradation is observed.77a Once the initial burst of ·OH subsides a much more controlled redox cycle dominates where the reduction of Fe(III) to Fe(II) is the rate determining step.77a Due to the precipitation of Fe(III) at elevated pH levels, the reaction will need to be buffered. In some cases a citrate68 or a phosphate buffer6a is used (circumneutral pH) or the reaction is acidified from the onset with mineral acids.134 This also greatly lessens the scavenging of ·OH by hydroxide ions.92 Undertaking the water reaction using both methods of
147
Chapter 5. Conclusions & Future Experimentation
·OH generation outlined above would help to elucidate which method is potentially better at removal of aromatic compounds from the environment.
To elucidate the selectivity of ·OH addition to arenes, as was accomplished in this study, a radical trap must again be employed. TEMPO likely cannot be employed due to its low solubility in water.135 Other stable nitroxide radicals have been employed in water soluble “living” free- radical polymerization reactions, and could be employed here. N-tert-butyl-N-(1- diethylphosphono-2,2-dimethylpropyl) nitroxide (DEPN) could be a potential candidate for such a radical trapping agent.136 DEPN has been used to control the polymerization of styrene at much lower temperatures than TEMPO, and the adducts (if formed as discussed previously) would likely decompose and return aromaticity to the cyclohexadiene much quicker.136 Two TEMPO derivatives, Tempol and Tempamine+, have been employed in aqueous studies.137
If photocatalysis of TiO2 is to be used, the reaction will need to be carried out under basic conditions if an aminoxyl radical is used as the trapping agent. This is due to the quenching of the radical by superoxide in the presence of protons to generate a hydroxyl amine.138 In the case where Fenton chemistry is buffered with citrate, the buffer may act as a radical trap as it has known anti-oxidant properties.
Expansion into water will prove quite difficult due to the very low solubilities of simple aromatic substances. Larger scales would likely need to be employed to generate sufficient concentrations of the ·OH addition products for accurate quantitation. In nearly all cases of water sample analysis a pre-concentration step is required.139 This is due to the very low solubility of many compounds of interest in water, which typically fall below the limit of detection (LoD).139
Solid phase extraction (SPE), and solid phase micro extraction (SPME) are widely used for analysis of polar, non-volatile compounds.139 SPE are readily available, and offer many advantages over traditional liquid-liquid extraction:
148
Chapter 5. Conclusions & Future Experimentation
Higher and more reproducible recovery,
decreased solvent usage,
cleaner extracts, and
tunable selectivity for extracted compounds.
An SPE cartridge is available from Agilent Technologies, AccuBONDII ENV PS-DVB, that has shown effective concentration of phenolic compounds and characterization by GC/MS.140 The procedure outlined does not incorporate a derivatization step used in the work presented in this dissertation, however, the SPE is amenable to the process.141 This would allow for use of the GC column that is currently in use, as well as the methods developed for analysis in this dissertation.
The experimental framework described would be potentially useful in modeling the degradation of aromatics in waste water applications. However, many of these chemicals are found in groundwater supplies as well. Incorporation of “real-world” problems, such as soil type, salinity, NOM, and pH into different experiments would assist with modeling the remediation of aquifers.
149
APPENDIX I – CALIBRATION CURVES OF STANDARDS
The calibration curves were generated by the methods described in Chapter 2. The calibration curves are based on the average of 3 replicate injections used of each standard. The three replicate injections were subjected to Dixon’s Q-test, and those which failed were not used in the determination of the average detector response.
Phenol (Hydroxyl addition to benzene)
phenol 2500000
2000000
1500000 y = 51482x + 1221.4 R² = 0.9999 1000000
500000 avg.detector response 0 0 10 20 30 40 50 concentration (mM)
Figure 44. Calibration curve for phenol
Appendix I - Calibration of Standards in GC/MS Analyses
Toluene (Methylbenzene)
methylphenol calibration curves 300000 y = 53591x - 446.55 250000 R² = 0.9997 4-methylphenol 200000 y = 49685x - 815.49 R² = 0.9998 150000 3-methylphenol
100000
detector detector response y = 26546x - 455.3 50000 R² = 0.9998 2-methylphenol
0 0 1 2 3 4 5 6 concentration (mM)
Figure 45. Calibration curves for methylphenols.
o-Xylene (1,2-Dimethylbenzene)
o-dimethylphenol calibration curves 3500000
3000000 y = 49473x + 13810 R² = 0.9994 2500000
2000000 3,4-dimethylphenol
1500000 2,3-dimethylphenol 1000000 detector detector response y = 29154x + 5886.3 500000 R² = 0.9995
0 0 20 40 60 80 concentration (mM)
Figure 46. Calibration curves for o-dimethylphenols.
151
Appendix I - Calibration of Standards in GC/MS Analyses m-Xylene (1,3-Dimethylbenzene)
m-dimethylphenol calibration curves 350000
300000 y = 54882x - 3580.9 R² = 0.9998 250000
200000 2,4-dimethyphenol 150000 y = 47022x - 2682.8 R² = 0.9999 3,5-dimethylphenol 100000 2,6-dimethylphenol
detector detector response 50000 y = 35333x - 3766.4 R² = 0.9998 0 0 2 4 6 8 10 -50000 concentration (mM)
Figure 47. Calibration curves for m-dimethylphenols.
p-Xylene (1,4-Dimethylbenzene)
p-dimethylphenol calibration curve 350000
300000 y = 32652x - 2628.5 250000 R² = 0.9999 200000
150000
100000
detector detector response 50000
0 0 2 4 6 8 10 12 -50000 concentration (mM)
Figure 48. Calibration curve for p-dimethylphenol.
152
Appendix I - Calibration of Standards in GC/MS Analyses
Anisole (Methoxybenzene)
methoxyphenol calibration curves 100000 90000 y = 32374x - 49315 R² = 0.99 80000 y = 17758x - 3240.4 70000 R² = 0.995 60000 50000 y = 23633x - 19012 2-methoxyphenol R² = 0.988 40000 3-methoxyphenol 30000 4-methoxyphenol detector detector response 20000 10000 0 0 1 2 3 4 5 concentration (mM)
Figure 49. Calibration curve for methoxyphenols.
Chlorobenzene
chlorophenol calibration curves 1400000
1200000 y = 40775x - 1843.2 R² = 0.9998 1000000 y = 40539x - 5769.4 800000 R² = 0.999 2-chlorophenol 600000 3-chlorophenol
400000 4-chlorophenol detector detector response 200000 y = 23345x - 2120.4 R² = 0.9998 0 0 5 10 15 20 25 30 concentration (mM)
Figure 50. Calibration curves for chlorophenols.
153
Appendix I - Calibration of Standards in GC/MS Analyses
Trifluorotoluene (α,α,α-trifluoromethylbenzene)
trifluoromethylphenol calibration curves 1600000 1400000 y = 88686x + 1113.7 1200000 R² = 0.9991 1000000 800000 4-trifluoromethylphenol 600000 y = 69264x - 1400.1 3-trifluoromethylphenol R² = 0.9997
400000 2-trifluoromethylphenol detector detector response y = 32918x - 242.23 200000 R² = 0.9998 0 0 5 10 15 20 concentration (mM)
Figure 51. Calibration curves for trifluoromethylphenols.
154
APPENDIX II – THERMAL DECOMPOSITION OF AZOHYDROPEROXIDE INITIATOR IN
ACETONITRILE
The decomposition of the azohydroperoxide initiator in acetonitrile was carried out as described in Chapter 2. The absorbance of the initiator was monitored throughout its decay, using the relatively weak absorbance maximum around 368 nm. The kinetics of decomposition is complex, as the reaction does not exhibit either first order or second-order decay. The effect is particularly exacerbated at low temperatures and low concentrations of peroxide: at higher temperatures and higher concentration, the decay exhibits first order behavior.
Plots were constructed based on the integrated first-order rate equation, and were found to exhibit a useful degree of linearity at longer times, from which a first-order rate coefficient and first-order half-life were calculated. In fact, the decay may be quicker than indicated by the first- order equation, and so the calculated half-life is in all likelihood an upper bound of the true half- life. Three trials were carried out in the temperature range 35-55C. The following figures show the linear regression analysis for the linear regions of the first-order plots for decomposition of the peroxide.
Appendix II - Decomposition of Peroxide in Acetonitrile
Trial 1 0 0 2000 4000 6000 8000 10000 12000 -0.2 35 C -0.4 y = -2.31E-05x - 8.21E-02 R² = 9.77E-01 -0.6 40 C -0.8 y = -4.91E-05x - 2.43E-01 R² = 9.86E-01
-1 45 C ln ln (A/A0) -1.2 y = -9.38E-05x - 2.62E-01 y = -2.27E-04x - 2.10E-01 R² = 9.96E-01 50 C -1.4 R² = 9.92E-01
-1.6 y = -1.49E-04x - 2.26E-01 55 C -1.8 R² = 9.94E-01
-2 time (s)
Figure 52. Decomposition kinetics for trial 1.
Trial 2 0 0 2000 4000 6000 8000 10000 12000 y = -2.94E-05x - 2.12E-02 -0.2 R² = 9.92E-01
-0.4 y = -5.29E-05x - 1.22E-03 R² = 9.93E-01 -0.6 35 C
-0.8 y = -4.85E-05x - 2.22E-01 40 C
R² = 9.41E-01 ln ln (A/A0) -1 45 C
50 C -1.2 y = -2.28E-04x - 8.82E-02 R² = 9.86E-01 y = -1.57E-04x - 3.40E-01 55 C -1.4 R² = 9.95E-01
-1.6 time (s)
Figure 53. Decomposition kinetics for trial 2.
156
Appendix II - Decomposition of Peroxide in Acetonitrile
0 Trial 3 0 2000 4000 6000 8000 10000 12000
-0.2 y = -1.81E-05x - 2.71E-01 R² = 9.40E-01 35 C -0.4
40 C -0.6 y = -9.20E-05x - 8.32E-02 45 C ln ln (A/A0) R² = 9.95E-01
-0.8 50 C y = -8.44E-05x - 2.42E-01 R² = 9.91E-01 y = -1.98E-04x - 7.61E-02 55 C -1 R² = 9.75E-01
y = -1.14E-04x - 3.61E-01 -1.2 R² = 9.67E-01 time (s)
Figure 54. Decomposition kinetics for trial 3.
157
APPENDIX III – ADDITIONAL DATA FOR HYDROXYL RADICAL ADDITIONS TO ARENES
The data included in this appendix is associated with the substrates other than toluene, for which a complete treatment is given in the text of the dissertation. Tabulated data refer to calculated relative concentrations of isomeric products relative to each other and to benzene at various temperatures.
The Arrhenius plots not appearing in the main text of this dissertation are supplied following the concentration ratio tables. These plots contain both the data for the benzene experiments (in red), and the acetonitrile experiments (in blue).
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
Data for o-Xylene (1,2-Dimethylphenol)
3,4-dimethylphenol v. 2,3-dimethylphenol
concentration ratio (PhH) concentration ratio (MeCN) temp. temp-1 ln conc. temp. temp.-1 conc. ln conc. conc. ratio (°C) (1/K) ratio (°C) (1/K) ratio ratio 0.643 -0.441 1.4 0.3 75 0.00287 0.67 -0.39 60 0.003 1.4 0.4 0.70 -0.36 1.5 0.4 0.65 -0.43 1.4 0.4 0.66 -0.41 55 0.00305 1.4 0.4 70 0.00291 0.68 -0.38 1.46 0.38 0.73 -0.31 0.66 -0.42 1.4 0.3 65 0.00296 0.69 -0.37 50 0.00309 1 0 0.69 -0.37 1.5 0.4 0.71 -0.34 1.5 0.4 60 0.00300 45 0.00314 0.72 -0.33 1.6 0.5 0.66 -0.42 40 0.00319 1.5 0.4 55 0.00305 0.67 -0.40 0.70 -0.35 0.527 -0.641 2 0 50 0.00309 0.66 -0.41 35 0.00325 1.63 0.49 1.66 0.50
Table 30. Concentration ratios of isomeric products from addition of OH to o-xylene in benzene and acetonitrile.
3,4-dimethylphenol v. 2,3-dimethylphenol
0.6 - 0.4
0.2 y = 520.82x - 1.2235 R² = 0.7036
0 PhOTMS]/[2,3
2 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 acetonitrile
PhOTMS]) -0.2 Me
2 benzene -
Me -0.4
-0.6 y = -325.35x + 0.5674
ln(avg ln(avg [3,4 R² = 0.1169 -0.8 1/T (K-1)
Figure 55. Competitive Arrhenius plot of isomeric products from addition of OH to o-xylene.
159
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
Concentration Ratios (PhH) concentration ratios (MeCN) 2,3- 3,4- 2,3- 3,4- dimethylphenol dimethylphenol dimethylpheno dimethylphenol v. phenol v. phenol l v. phenol v. phenol ln temp temp-1 conc. ln conc. conc. ln conc. temp. temp-1 conc. conc. ln conc. conc. (°C) (1/K) ratio ratio ratio ratio (°C) (1/K) ratio ratio ratio ratio 1.3 0.2 0.86 -0.15 0.7 -0.3 1.1 0.1 0.0028 75 1.6 0.5 1.07 0.07 60 0.003 1 0 1 0 7 1.66 0.51 1.1 0.1 1.0 0.0 1.3 0.3 1.4 0.4 1.0 0.00 0.8 -0.2 1.2 0.2 0.0030 0.0029 1.5 0.4 1.0 0.0 55 0.8 -0.2 1.2 0.2 70 5 1 1.8 0.6 1.16 0.15 1.0 0.0 1.4 0.3 2.0 0.7 1.3 0.3 0.8 -0.3 1.1 0.1 0.0030 0.0029 1.76 0.57 1.2 0.2 50 0.9 -0.1 1 0 65 9 6 2.5 0.9 1.72 0.54 1.2 0.2 1.6 0.5 0.0030 1.6 0.5 0.0031 1 0 1 0 60 1.2 0.1 45 0 1.8 0.6 4 1.1 0.1 1.6 0.5 0.0030 1.4 0.4 0.94 -0.06 0.0031 55 40 0.35 -1.06 0.53 -0.64 5 1.7 0.5 1.2 0.2 9 0.59 -0.54 1.0 0.0 0.0030 0.0032 50 1.79 0.58 1.2 0.2 35 1 0 2 0 9 5 1 0 2 0
Table 31. Concentration ratios of addition products of OH and o-xylene relative to phenol in benzene and acetonitrile.
2,3-dimethylphenol v. phenol 1.5 y = 383.57x - 0.6161 1 R² = 0.0294
0.5
0
0.0028 0.0029 0.003 0.0031 0.0032 0.0033 PhOTMS]/[PhOTMS]) 2 -0.5
y = -719.71x + 2.0537 Me - R² = 0.0478 -1
-1.5 -1 ln(avg ln(avg 2,3 1/T (K )
Figure 56. Competitive Arrhenius plot of OH addition to o-xylene and benzene, accounting for only the 2,3- dimethylphenol product.
160
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
3,4-dimethylphenol v. phenol
0.6 - 0.4
0.2 y = 520.82x - 1.2235 R² = 0.7036
0 PhOTMS]/[2,3
2 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 acetonitrile
PhOTMS]) -0.2 Me
2 benzene -
Me -0.4
-0.6 y = -325.35x + 0.5674
ln(avg ln(avg [3,4 R² = 0.1169 -0.8 1/T (K-1)
Figure 57. Competitive Arrhenius plot of OH addition to o-xylene and benzene, accounting for only the 3,4- dimethylphenol product.
161
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
Data for m-Xylene (1,3-Dimethylbenzene)
2,4-dimethylphenol v. 2,6-dimethylphenol v. 3,5-dimethylphenol v 3,5-dimethylphenol 2,4-dimethylphenol 2,6-dimethylphenol temp. temp-1 ln conc. ln conc. conc. ratio ln conc. ratio conc. ratio conc. ratio (°C) (1/K) ratio ratio 5.92 1.78 0.72 -0.33 0.22 -1.51 75 0.00287 0.76 -0.27 5.9 1.8 0.24 -1.45 0.76 -0.27 6.2 1.8 0.73 -0.32 0.17 -1.74 6.4 1.9 0.73 -0.32 0.21 -1.56 70 0.00291 7.1 2.0 0.73 -0.31 0.21 -1.55 7.9 2.1 0.74 -0.31 0.22 -1.50 6.38 1.85 0.71 -0.35 0.21 -1.55 6.4 1.9 0.71 -0.34 0.22 -1.53 65 0.00296 0.73 -0.32 6.4 1.9 0.22 -1.52 0.74 -0.30 6.4 1.9 0.72 -0.33 0.20 -1.59 6.4 1.9 0.73 -0.32 0.21 -1.56 60 0.00300 6.8 1.9 0.73 -0.31 0.22 -1.53 8.3 2.1 0.75 -0.29 0.69 -0.38 0.2 -1.7 5.9 1.8 0.69 -0.36 0.21 -1.54 55 0.00305 0.695 -0.364 0.23 -1.48 6.4 1.9 0.72 -0.33 0.23 -1.46 6.21 1.83 0.68 -0.39 0.22 -1.50 50 0.00309 0.70 -0.36 6.2 1.8 0.23 -1.47 0.72 -0.32
Table 32. Concentration ratios of isomeric products from addition of OH to m-xylene in benzene.
2,4-dimethylphenol v. 3,5- 2,6-dimethylphenol v. 2,4- 2,6-dimethylphenol v 3,5- dimethylphenol dimethylphenol dimethylphenol temp. ln conc. ln conc. ln conc. temp-1 (1/K) conc. ratio conc. ratio conc. ratio (°C) ratio ratio ratio 11 2 0.39 -0.95 4.1 1.4 60 0.003002 10.6 2.4 0.39 -0.93 4.2 1.4 9.5 2.2 0.36 -1.02 3.4 1.2 55 0.003047 9.5 2.3 0.37 -0.99 3.5 1.3 11 2 0.4 -0.9 4 1 10 2 0.4 -1.0 4 1 50 0.003095 10 2 0.4 -0.9 4 1 11 2 0.4 -0.9 5 2 10 2 0.3 -1.1 3 1 45 0.003143 10 2 0.3 -1.1 4 1 0.31 -1.16 40 0.003193 0.31 -1.16 0.3 -1.1 8 2 0.3 -1.3 2.4 0.9 35 0.003245 8 2 0.3 -1.2 3 1
Table 33. Concentration ratios of isomeric products from addition of OH to m-xylene in acetonitrile.
162
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
2,4-dimethylphenol v. 3,5-dimethylphenol 2.5 - y = -813.5x + 4.8103 2.4 R² = 0.5372 2.3 2.2
2.1 PhOTMS]/[3,5
2 2
acetonitrile PhOTMS])
Me 1.9
2 -
1.8 benzene Me 1.7 y = 113.09x + 1.5485 1.6 R² = 0.006
ln(avg ln(avg [2,4 1.5 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 1/T (K-1)
Figure 58. Competitive Arrhenius plot of 2,4-dimethylphenol and 3,5-dimethylphenol.
2,6-dimethylphenol v. 2,4-dimethylphenol 0
- 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 -0.2
-0.4
-0.6 y = -283.48x + 0.5184
PhOTMS]/[2,4 y = -1206.7x + 2.7239 R² = 0.4571
2 acetonitrile R² = 0.7573
PhOTMS]) -0.8 Me
2 benzene -
Me -1
-1.2 ln(avg ln(avg [2,6 -1.4 1/T (K-1)
Figure 59. Competitive Arrhenius plot of 2,6-dimethylphenol and 2,4-dimethylphenol.
163
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
3,5-dimethylphenol v. 2,6-dimethylphenol -0.5
- 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 -0.7 y = 2583.1x - 9.3167 -0.9 R² = 0.6777
-1.1 PhOTMS]/[2,6
2 -1.3 acetonitrile
PhOTMS]) Me
2 benzene
- -1.5 Me -1.7 y = 98.179x - 1.8348 R² = 0.0083
-1.9 ln(avg ln(avg [3,5 -2.1 1/T (K-1)
Figure 60. Competitive Arrhenius plot of 3,5-dimethylphenol and 2,6-dimethylphenol.
164
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
Hydrocarbon Solvent
2,4-dimethylphenol v. 3,5-dimethylphenol 2,6-dimethylphenol v. phenol v. phenol phenol temp. temp-1 conc. ln conc. conc. ln conc. conc. ln conc. (°C) (1/K) ratio ratio ratio ratio ratio ratio 1.8 0.6 0.32 -1.15 1.4 0.3 75 0.00287 1.9 0.6 1.4 0.3 0.33 -1.12 1.9 0.7 1.4 0.4 1.9 0.6 1.3 0.3 0.28 -1.26 1.86 0.62 1.3 0.3 70 0.00291 1.9 0.7 1.4 0.3 0.3 -1.2 2.0 0.7 1.4 0.3 1.8 0.6 0.29 -1.24 1.4 0.3 65 0.00296 1.87 0.63 0.293 -1.228 1.4 0.3 1.9 0.7 0.30 -1.19 1.4 0.3 1.7 0.6 0.26 -1.35 1.27 0.24 60 0.00300 1.8 0.6 0.27 -1.29 1.3 0.3 1.81 0.59 0.28 -1.26 1.9 0.6 0.29 -1.24 1.3 0.3 55 0.00305 1.9 0.7 0.31 -1.16 1.3 0.3 2.1 0.7 0.32 -1.14 1.4 0.3 1.9 0.6 0.31 -1.18 1.4 0.3 50 0.00309 2.1 0.7 0.34 -1.09 1.4 0.3 2.2 0.8 0.35 -1.04 1.5 0.4 Acetonitrile 2.0 0.7 0.14 -1.94 0.80 -0.23 60 0.003002 2.3 0.8 0.19 -1.65 0.93 -0.07 1.9 0.6 0.20 -1.62 0.68 -0.39 55 0.003047 2.1 0.7 0.21 -1.54 0.76 -0.27 2.3 0.8 0.22 -1.52 0.92 -0.08
50 0.003095 2 1 0.20 -1.63 0.73 -0.32
45 0.003143 2 1 0.18 -1.71 0.60 -0.51 40 0.003193 1.9 0.7 0.61 -0.49 2 1 0.2 -1.6 0.50 -0.69 35 0.003245 2 1 0.21 -1.54 0.54 -0.61
Table 34. Concentration ratios of addition products of OH and m-xylene relative to phenol in benzene and acetonitrile
165
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
2,4-dimethylphenol v. phenol 0.9 0.8 0.7 0.6 0.5 y = 272.66x - 0.1676 y = -836.96x + 3.2931 0.4 R² = 0.1424 acetonitrile
PhOTMS]/[PhOH]) R² = 0.4741
2 0.3 benzene Me - 0.2 0.1 0
0.0028 0.0029 0.003 0.0031 0.0032 0.0033 ln(avg ln(avg [2,4 1/T (K-1)
Figure 61. Competitive Arrhenius plot of OH addition to m-xylene and benzene, accounting for only the 2,4-
dimethylphenol product.
3,5-dimethylphenol v. phenol 0 0.0028 0.0029 0.003 0.0031 0.0032 0.0033
-0.5 y = 262.93x - 1.9851 R² = 0.063 -1 acetonitrile
-1.5 benzene
PhOTMS]/[PhOTMS])
2
Me - -2 y = 534.63x - 3.2805 R² = 0.1505
-2.5 -1
ln(avg ln(avg [3,5 1/T (K )
Figure 62. Competitive Arrhenius plot of OH addition to m-xylene and benzene, accounting for only the 3,5-
dimethylphenol product.
166
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
2,6-dimethylphenol v. phenol 0.6
0.4 y = 49.655x + 0.1705 R² = 0.0102 0.2
0 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 acetonitrile
-0.2 benzene PhOTMS]/[PhOTMS]) 2 y = -2112.5x + 6.2351 -0.4
Me R² = 0.6897 - -0.6
-0.8 -1
ln(avg ln(avg [2,6 1/T (K )
Figure 63. Competitive Arrhenius plot of OH addition to m-xylene and benzene, accounting for only the 2,6-
dimethylphenol product.
Data for p-Xylene (1,4-Dimethylbenzene)
The relevant data for p-xylene competitive experiments may be found in Chapters 3 and
4. Due to the symmetry of this molecule, only one isomer of dimethylphenol may be formed.
167
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
Data for Anisole (Methoxybenzene)
3-methoxyphenol 3-methoxyphenol v. 4-methoxyphenol v. v. 4- 2-methoxyphenol 2-methoxyphenol methoxyphenol temp. temp-1 conc. ln conc. conc. ln conc. conc. ln conc. (°C) (1/K) ratio ratio ratio ratio ratio ratio 0.072 -2.630 0.20 -1.60 0.36 -1.03 70 0.00291 0.074 -2.603 0.21 -1.57 0.36 -1.03 0.075 -2.587 0.21 -1.55 0.36 -1.03 0.071 -2.641 0.20 -1.60 0.35 -1.04 65 0.00296 0.073 -2.621 0.21 -1.58 0.35 -1.04 0.076 -2.581 0.21 -1.56 0.072 -2.634 0.21 -1.56 0.34 -1.08 60 0.00300 0.076 -2.579 0.22 -1.53 0.35 -1.05 0.080 -2.525 0.22 -1.51 0.36 -1.01 0.22 -1.52 55 0.00305 0.077 -2.559 0.22 -1.51 0.35 -1.05 0.22 -1.50 0.21 -1.57 50 0.00309 0.074 -2.601 0.21 -1.55 0.36 -1.03 0.23 -1.47 4-methoxyphenol 2-methoxyphenol v. 3-methoxyphenol v. v. phenol phenol temp. temp-1 conc. ln conc. conc. ln conc. conc. ln conc. (°C) (1/K) ratio ratio ratio ratio ratio ratio 11 2 75 0.00287 11 2 12 2 0.85 -0.17 2.4 0.9 12 2 0.877 -0.131 2.46 0.90 70 0.00291 11.8 2.5 0.89 -0.11 2.51 0.92 12 2 10 2 0.867 -0.142 2.46 0.90 12 2 0.895 -0.111 2.48 0.91 65 0.00296 12 2 0.896 -0.110 2.55 0.93 12 3 12 2 0.901 -0.105 2.57 0.94 60 0.00300 11.9 2.5 0.94 -0.06 2.59 0.95 13 3 0.963 -0.038 2.82 1.04 13 3 0.99 -0.01 2.82 1.04 13 3 2.8 1.0 55 0.00305 13 3 2.9 1.1 13 3 13 3 1.02 0.02 2.69 0.99 13 3 2.87 1.06 50 0.00309 14 3 3.1 1.1 13.8 2.6
Table 35. Concentration ratios of isomeric products from addition of OH to anisole in benzene.
168
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
3-methoxyphenol v. 2-methoxyphenol -2.5 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315
-2.52 - -2.54 y = 188.66x - 3.1585 -2.56 R² = 0.0974
-2.58
-2.6
MeOPhOTMS]/[2
- MeOPhOTMS])
-2.62 ln([3 -2.64
-2.66 1/T (K-1)
Figure 64. Competitive Arrhenius plot of 3-methoxyphenol and 2-methoxyphenol.
4-methoxyphenol v. 2-methoxyphenol -1.46 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315
-1.48 - -1.5 y = 343.28x - 2.5763 R² = 0.3946 -1.52
-1.54
-1.56
MeOPhOTMS]/[2
- MeOPhOTMS])
-1.58 ln([4 -1.6
-1.62 1/T (K-1)
Figure 65. Competitive Arrhenius plot of 4-methoxyphenol and 2-methoxyphenol.
169
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
3-methoxyphenol v. 4-methoxyphenol -1 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315
-1.01 - -1.02
-1.03
-1.04
-1.05
MeOPhOTMS]/[4
- MeOPhOTMS]) -1.06 y = -44.141x - 0.9084 ln([3 R² = 0.0262 -1.07
-1.08 1/T (K-1)
Figure 66. Competitive Arrhenius plot of 3-methoxyphenol and 4-methoxyphenol.
2-methoxyphenol v. phenol 2.65 2.6 2.55 2.5 2.45
2.4 y = 828.39x + 0.0271
2.35 R² = 0.6163
MeOPhOTMS]/[PhOTMS]) -
2.3 ln([2 2.25 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315 1/T (K-1)
Figure 67. Competitive Arrhenius plot of OH addition to anisole and benzene, accounting for only the 2-
methoxyphenol product.
170
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
3-methoxyphenol v. phenol 0.05
0 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315
-0.05
-0.1
y = 920.78x - 2.8303 MeOPhOTMS]/[PhOTMS])
- -0.15 R² = 0.8347 ln([3 -0.2 1/T (K-1)
Figure 68. Competitive Arrhenius plot of OH addition to anisole and benzene, accounting for only the 3-
methoxyphenol product.
4-methoxyphenol v. phenol 1.15 1.1 y = 998.4x - 2.0206 R² = 0.7589 1.05 1 0.95 0.9
0.85
MeOPhOTMS]/[PhOTMS]) - 0.8 ln([4 0.00285 0.0029 0.00295 0.003 0.00305 0.0031 0.00315 1/T (K-1)
Figure 69. Competitive Arrhenius plot of OH addition to anisole and benzene, accounting for only the 4-
methoxyphenol product.
171
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
Data for Chlorobenzene
Hydrocarbon solvent 4-chlorophenol 2-chlorophenol v. v. 2- 4-chlorophenol v. 3-chlorophenol chlorophenol 3-chlorophenol ln temp temp-1 conc. ln conc. conc. conc. ln conc. conc. . (°C) (1/K) ratio ratio ratio ratio ratio ratio 1.3 0.3 0.8 -0.3 1.1 0.1 75 0.00287 1.5 0.4 0.78 -0.25 1 0 2 0 0.84 -0.17 1.2 0.2 1.5 0.4 0.68 -0.39 1.2 0.2 70 0.00291 1.69 0.53 0.70 -0.36 1.2 0.2 1.8 0.6 0.75 -0.29 1.2 0.2 1.4 0.3 0.64 -0.44 1.17 0.16 65 0.00296 1.6 0.5 0.75 -0.29 1.2 0.2 1.8 0.6 0.88 -0.13 1.5 0.4 0.63 -0.46 1.5 0.4 60 0.00300 1.6 0.5 0.72 -0.33 1.6 0.5 1.9 0.6 0.81 -0.21 1.9 0.6 1.30 0.26 0.68 -0.38 1.30 0.26 55 0.00305 1.8 0.6 1.8 0.6 0.905 -0.100 1.9 0.6 1.9 0.6 1.5 0.4 0.79 -0.24 1.5 0.4 50 0.00309 1.5 0.4 1.5 0.4 0.82 -0.20 1.8 0.6 1.8 0.6 Acetonitrile 2.32 0.84 1.89 0.64 1.23 0.20 0.00300 60 2.36 0.86 1.89 0.64 1.25 0.22 2 2.42 0.88 1.90 0.64 1.28 0.25 2.46 0.90 1.93 0.66 1.2 0.2 0.00304 55 2.5 0.9 1.98 0.68 1.3 0.2 7 2.5 0.9 2.1 0.7 1.28 0.24 2.40 0.87 2.0 0.7 1.2 0.2 0.00309 50 2.5 0.9 2.0 0.7 1.18 0.17 5 2.57 0.94 2.17 0.77 1.2 0.2 0.00314 2.55 0.93 2.0 0.7 1.24 0.22 45 3 2.6 0.9 2.1 0.7 1.3 0.2 2.5 0.9 2.00 0.69 1.2 0.2 0.00319 40 2.57 0.94 2.0 0.7 1.26 0.23 3 2.62 0.96 2.08 0.73 1.29 0.25 0.00324 35 2.5 0.9 2.0 0.7 1.2 0.2 5
Table 36. Concentration ratios of isomeric products from addition of OH to chlorobenzene inhydrocarbon and
acetonitrile.
172
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
2-chlorophenol v. 3-chlorophenol 1.2
1
0.8
ClPhOTMS]) y = 316.47x - 0.0715 - 0.6 R² = 0.5242 acetonitrile 0.4 benzene
0.2 y = 251.36x - 0.2811 ClPhOTMS]/[3 - R² = 0.0299 0 0.0028 0.0029 0.003 0.0031 0.0032 0.0033
1/T (K-1) ln(avg ln(avg [2
Figure 70. Competitive Arrhenius plot of 2-chlorophenol and 3-chlorophenol.
4-chlorophenol v. 2-chlorophenol 0 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 -0.1 -0.2 y = 164.34x - 0.7702
-0.3 R² = 0.0135
ClPhOTMS]) - -0.4 acetonitrile -0.5 benzene y = -288.69x + 0.2015 -0.6 R² = 0.3847
-0.7
ClPhOTMS]/[2 - -0.8 -0.9
1/T (K-1) ln(avg ln(avg [4
Figure 71. Competitive Arrhenius plot of 4-chlorophenol and 2-chlorophenol.
173
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
4-chlorophenol v. 3 chlorophenol 0.300
0.250
0.200
ClPhOTMS]) - 0.150 y = 28.745x + 0.127 acetonitrile 0.100 R² = 0.0066 benzene y = 214.38x - 0.4645 R² = 0.4277
0.050
ClPhOTMS]/[3 - 0.000 0.0028 0.0029 0.003 0.0031 0.0032 0.0033
1/T (K-1) ln(avg ln(avg [4
Figure 72. Competitive Arrhenius plot of 4-chlorophenol and 3-chlorophenol.
2-chlorophenol v. 3-chlorophenol v. 4-chlorophenol v. phenol phenol phenol temp temp-1 conc. ln conc. conc. ln conc. conc. ln conc. . (°C) (1/K) ratio ratio ratio ratio ratio ratio 0.24 -1.43 0.16 -1.80 0.19 -1.65 0.0028 75 0.25 -1.39 0.2 -1.8 0.2 -1.6 7 0.3 -1.4 0.18 -1.72 0.20 -1.60 0.26 -1.35 0.15 -1.88 0.18 -1.70 0.0029 70 0.27 -1.31 0.167 -1.787 0.20 -1.63 1 0.284 -1.260 0.17 -1.78 0.20 -1.62 0.26 -1.36 0.15 -1.91 0.18 -1.74 0.0029 0.27 -1.29 0.163 -1.812 0.191 -1.655 65 6 0.36 -1.02 0.27 -1.30 0.34 -1.09 0.38 -0.96 0.24 -1.42 0.17 -1.80 0.19 -1.64 0.0030 60 0.27 -1.31 0.17 -1.80 0.20 -1.63 0 0.33 -1.12 0.17 -1.76 0.21 -1.57 0.0030 0.25 -1.38 0.14 -1.97 0.17 -1.77 55 5 0.290 -1.238 0.223 -1.501 0.263 -1.337 0.0030 0.26 -1.36 0.17 -1.80 0.20 -1.60 50 9 0.26 -1.36 0.17 -1.76 0.21 -1.56
Table 37. Concentration ratios of addition products of OH and chlorobenzene relative to phenol in benzene.
174
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
2-chlorophenol v. 3-chlorophenol v. 4-chlorophenol v. phenol phenol phenol temp. temp-1 conc. ln conc. conc. ln conc. conc. ln conc. (°C) (1/K) ratio ratio ratio ratio ratio ratio 0.359 -1.024 0.151 -1.892 0.190 -1.662 0.00300 60 0.362 -1.017 0.153 -1.876 0.191 -1.657 2 0.365 -1.007 0.155 -1.866 0.193 -1.645 0.38 -0.96 0.15 -1.87 0.19 -1.68 0.00304 55 0.384 -0.958 0.16 -1.86 0.196 -1.632 7 0.387 -0.950 0.156 -1.859 0.199 -1.615 0.369 -0.996 0.148 -1.913 0.175 -1.744 0.00309 50 0.38 -0.97 0.154 -1.873 0.18 -1.71 5 0.379 -0.969 0.154 -1.870 0.19 -1.66 0.40 -0.92 0.155 -1.866 0.192 -1.648 0.00314 45 0.157 -1.849 3 0.401 -0.914 0.20 -1.61 0.20 -1.63 0.40 -0.92 0.153 -1.880 0.192 -1.649 0.00319 40 0.399 -0.918 0.158 -1.843 0.20 -1.62 3 0.407 -0.899 0.159 -1.839 0.204 -1.590 0.00324 0.40 -0.93 0.19 -1.66 35 0.16 -1.85 5 0.40 -0.93 0.19 -1.64
Table 38.Concentration ratios of addition products of OH and chlorobenzene relative to phenol in acetonitrile.
3-chlorophenol v. phenol -1.250 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 -1.350
-1.450 y = 212.47x - 2.5119 -1.550 R² = 0.0686 y = 72.808x - 1.9757 -1.650 R² = 0.0012 acetonitrile
-1.750 benzene ClPhOTMS]/[PhOTMS]) - -1.850
-1.950
ln(avg ln(avg [3 -2.050 1/T (K-1)
Figure 73. Competitive Arrhenius plot of OH addition to chlorobenzene and benzene, accounting for only the 3-
chlorophenol product.
175
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
4-chlorophenol v. phenol -0.9 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 -1 -1.1 -1.2 -1.3 y = 267.52x - 2.3831 -1.4 y = 99.74x - 1.9622 acetonitrile R² = 0.0152 R² = 0.0492
-1.5 benzene ClPhOTMS]/[PhOTMS])
- -1.6 -1.7 -1.8 ln(avg ln(avg [4 -1.9 1/T (K-1)
Figure 74. Competitive Arrhenius plot of OH addition to chlorobenzene and benzene, accounting for only the 4-
chlorophenol product.
2-chlorophenol v. phenol -0.8 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 -0.9
-1
-1.1 y = 388.53x - 2.1639 R² = 0.6837 acetonitrile
-1.2 benzene ClPhOTMS]/[PhOTMS]) - -1.3 y = 62.455x - 1.4752 R² = 0.0011 -1.4
ln(avg ln(avg [2 -1.5 1/T (K-1)
Figure 75. Competitive Arrhenius plot of OH addition to chlorobenzene and benzene, accounting for only the 2-
chlorophenol product.
176
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
Data for Trifluorotoluene (α,α,α-Trifluoromethylbenzene)
Hydrocarbon Solvent 3-CF3phenol v. 3-CF3phenol v. 2-CF3phenol v. 4-CF3phenol 2-CF3phenol 4-CF3phenol temp. temp-1 conc. ln conc. conc. ln conc. conc. ln conc. (°C) (1/K) ratio ratio ratio ratio ratio ratio 2.1 0.8 1.5 0.4 1.4 0.3 2.1 0.8 1.5 0.4 1.40 0.34 75 0.00287 2.2 0.8 1.5 0.4 1.4 0.4 2.2 0.8 1.5 0.4 1.5 0.4 2.1 0.7 1.4 0.3 1.4 0.3 2.1 0.8 1.5 0.4 1.4 0.3 70 0.00291 2.1 0.8 1.6 0.4 1.4 0.3 2.2 0.8 1.60 0.47 1.5 0.4 2.1 0.8 1.4 0.3 1.43 0.36 2.2 0.8 1.5 0.4 1.45 0.37 65 0.00296 2.21 0.79 1.52 0.42 1.47 0.39 2.22 0.80 1.55 0.44 1.5 0.4 2.2 0.8 1.4 0.3 1.35 0.30 2.2 0.8 1.5 0.4 1.4 0.3 60 0.00300 2.2 0.8 1.6 0.4 1.5 0.4 2.2 0.8 1.6 0.5 1.5 0.4 2.2 0.8 1.4 0.3 1.32 0.28 2.23 0.80 1.4 0.3 1.33 0.29 55 0.00305 2.24 0.81 1.62 0.48 1.37 0.32 1.7 0.5 1.5 0.4 2.2 0.8 1.68 0.52 1.60 0.47 1.4 0.4 1.38 0.32 2.23 0.80 1.56 0.45 1.45 0.37 50 0.00309 1.62 0.48 2.27 0.82 1.5 0.4 1.6 0.5 Acetonitrile 0.39 -0.95 60 0.00300 0.39 -0.93 0.62 -0.48 0.40 -0.92 0.41 -0.89 0.71 -0.35 0.572 -0.558 55 0.00305 0.43 -0.85 0.74 -0.30 0.575 -0.554 0.44 -0.83 0.76 -0.27 0.581 -0.542 0.360 -1.022 0.690 -0.371 0.52 -0.65 50 0.00309 0.364 -1.009 0.69 -0.37 0.52 -0.65 0.405 -0.903 0.70 -0.36 0.587 -0.532 0.75 -0.28 0.39 -0.93 45 0.00314 0.76 -0.27 0.52 -0.65 0.40 -0.92 0.78 -0.25 0.51 -0.68 40 0.00319 0.38 -0.98 0.68 -0.39 0.56 -0.59 0.91 -0.09 0.38 -0.98 0.64 -0.44 0.57 -0.55 35 0.00325 0.41 -0.90 0.66 -0.42 0.59 -0.53 0.44 -0.82 0.75 -0.29 0.63 -0.46
Table 39. Concentration ratios of isomeric products from addition of OH to trifluorotoluene in hydrocarbons and
acetonitrile. 177
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
3-trifluoromethylphenol v. 4- trifluoromethylphenol 1 - y = 39.209x + 0.786 0.95 R² = 0.0055 0.9
0.85 PhOTMS]/[4
3 0.8
acetonitrile
PhOTMS]) CF
3 0.75 - y = 232.94x + 0.0893 benzene
CF 0.7 R² = 0.5365 0.65
ln(avg ln(avg [3 0.6 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 1/T (K-1)
Figure 76. Competitive Arrhenius plot of 3-trifluoromethylphenol and 4-trifluoromethylphenol.
3-trifluoromethylphenol v. 2- trifluoromethylphenol
0.6 -
0.5
0.4 PhOTMS]/[2
3 0.3
acetonitrile
PhOTMS])
CF 3 - 0.2 y = 169.76x - 0.0847 y = 74.504x + 0.1093 benzene CF R² = 0.0495 R² = 0.007 0.1
ln(avg ln(avg [3 0 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 1/T (K-1)
Figure 77. Competitive Arrhenius plot of 3-trifluoromethylphenol and 2-trifluoromethylphenol.
178
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
2-trifluoromethylpehnol v. 4- trifluoromethylphenol 0.8 - y = -329.66x + 1.561 0.7 R² = 0.0306 0.6
0.5 PhOTMS]/[4
3 0.4
acetonitrile
PhOTMS]) CF
3 0.3 - benzene
CF 0.2 y = 1.9326x + 0.3525 0.1 R² = 9E-06
ln(avg ln(avg [2 0 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 1/T (K-1)
Figure 78. Competitive Arrhenius plot of 2-trifluoromethylphenol and 4-trifluoromethylphenol.
3-CF3phenol v. 4-CF3phenol v. 2-CF3phenol v. phenol phenol phenol temp. temp-1 conc. ln conc. conc. ln conc. conc. ln conc. (°C) (1/K) ratio ratio ratio ratio ratio ratio 0.078 -2.545 0.037 -3.308 0.054 -2.918 0.0028 0.088 -2.427 0.042 -3.181 0.058 -2.847 75 7 0.090 -2.405 0.0417 -3.1781 0.0584 -2.8400 0.093 -2.379 0.043 -3.151 0.061 -2.793 0.072 -2.625 0.053 -2.942 0.041 -3.193 0.0029 0.088 -2.429 0.0566 -2.8713 70 1 0.090 -2.412 0.042 -3.180 0.0567 -2.8698 0.0909 -2.3985 0.042 -3.172 0.058 -2.840 0.074 -2.605 0.035 -3.356 0.053 -2.940 0.0029 0.082 -2.496 0.0374 -3.2864 0.0550 -2.8999 65 6 0.0863 -2.4499 0.0391 -3.2429 0.0566 -2.8711 0.0878 -2.4325 0.0395 -3.2302 0.0567 -2.8698 0.076 -2.584 0.035 -3.367 0.053 -2.929 0.0030 0.087 -2.446 0.039 -3.246 0.0562 -2.8790 60 0 0.091 -2.398 0.0417 -3.1777 0.058 -2.854 0.092 -2.384 0.0425 -3.1585 0.059 -2.824 0.076 -2.584 0.036 -3.312 0.0517 -2.9624 0.086 -2.459 0.0380 -3.2693 0.054 -2.921 0.0030 55 0.0871 -2.4410 0.0389 -3.2480 0.0569 -2.8673 5 0.0923 -2.3826 0.0415 -3.1832 0.0588 -2.8341 0.098 -2.318 0.0446 -3.1103 0.0609 -2.7986 0.0505 -2.9859 0.0378 -3.2766 0.0547 -2.9058 0.0030 0.080 -2.523 0.038 -3.261 0.0550 -2.9002 50 9 0.0855 -2.4590 0.0398 -3.2229 0.056 -2.883 0.0889 -2.4206
Table 40. Concentration ratios of addition products of OH and trifluorotoluene relative to phenol in benzene.
179
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
3-CF3phenol v. 2-CF3phenol v. 4-CF3phenol v. phenol phenol phenol temp. temp-1 conc. ln conc. conc. ln conc. conc. ln conc. (°C) (1/K) ratio ratio ratio ratio ratio ratio 0.11 -2.25 0.042 -3.182 0.08 -2.57 60 0.003002 0.042 -3.163 0.107 -2.239 0.081 -2.516 0.065 -2.730 0.098 -2.328 0.042 -3.173 0.072 -2.631 55 0.003047 0.10 -2.30 0.0426 -3.1550 0.0745 -2.5971 0.10 -2.28 0.0429 -3.1487 0.0746 -2.5951 50 0.003095 0.104 -2.268 0.0420 -3.1712 0.0715 -2.6387 0.097 -2.334 0.039 -3.257 0.074 -2.604 45 0.003143 0.099 -2.317 0.0389 -3.2457 0.0747 -2.5942 0.099 -2.311 0.039 -3.236 0.077 -2.564 0.0434 -3.1373 0.078 -2.552 40 0.003193 0.12 -2.16 0.079 -2.538 0.044 -3.134 0.0859 -2.4547 0.099 -2.313 0.040 -3.212 0.068 -2.686 35 0.003245 0.11 -2.24 0.0431 -3.1436 0.070 -2.659 0.11 -2.24 0.044 -3.131 0.074 -2.604
Table 41. Concentration ratios of addition products of OH and trifluorotoluene relative to phenol in acetonitrile.
3-trifluoromethylphenol v. phenol -1.8 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 -2
-2.2
-2.4 y = 79.619x - 2.524 acetonitrile R² = 0.0214
-2.6 benzene PhOTMS]/[PhOTMS])
3 y = -489.29x - 1.012 -2.8
CF R² = 0.0837 - -3
ln(avg ln(avg [3 -3.2 1/T (K-1)
Figure 79. Competitive Arrhenius plot of trifluorotoluene and benzene, accounting only for the 3-trifluoromethylphenol
product.
180
Appendix III - Additional Kinetic Data for Hydroxyl Radical Reactions
4-trifluoromethylphenol v. phenol -2.4 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 -2.6
-2.8 y = -183.37x - 2.6841 y = -433.35x - 1.7961 -3.0 R² = 0.0426 R² = 0.1047 acetonitrile
benzene PhOTMS]/[PhOTMS])
3 -3.2
CF - -3.4
ln(avg ln(avg [4 -3.6 1/T (K-1)
Figure 80. Competitive Arrhenius plot of trifluorotoluene and benzene, accounting only for the 4-trifluoromethylphenol
product.
2-trifluoromethylphenol v. phenol -2.30 0.0028 0.0029 0.003 0.0031 0.0032 0.0033 -2.40
-2.50
-2.60 acetonitrile y = -117.36x - 2.5278
-2.70 R² = 0.0389 benzene
PhOTMS]/[PhOTMS]) 3
-2.80 y = -120.59x - 2.2089 CF - R² = 0.0326 -2.90
ln(avg ln(avg [2 -3.00 1/T (K-1)
Figure 81. Competitive Arrhenius plot of trifluorotoluene and benzene, accounting only for the 2-trifluoromethylphenol
product.
181
BIBLIOGRAPHY
1. Summary of the Clean Air Act. http://www2.epa.gov/laws-regulations/summary-clean-air-act (accessed 05/26/2015). 2. Summary of the Clean Water Act. http://www2.epa.gov/laws-regulations/summary-clean-water-act (accessed 05/26/2015). 3. Murray, K. E. T., Sheeba M.; Bodour, Adria A., Prioritizing research for trace pollutants and emerging contaminants in the freshwater environment. Environmental Pollution 2010, 158 (12), 3462-3471. 4. Field, J. A.; Johnson, C. A.; Rose, J. B., What is “emerging”? Environmental Science & Technology 2006, 40 (23), 7105-7105. 5. Jones, K. G.; Cooper, W. J.; Mezyk, S. P., Bimolecular Rate Constant Determination for the Reaction of Hydroxyl Radicals with Domoic and Kainic Acid in Aqueous Solution. Environmental Science & Technology 2009, 43 (17), 6764-6768. 6. (a) Friedman, C. L.; Lemley, A. T.; Hay, A., Degradation of Chloroacetanilide Herbicides by Anodic Fenton Treatment. Journal of Agricultural and Food Chemistry 2006, 54 (7), 2640-2651; (b) Richardson, S. D.; Ternes, T. A., Water Analysis: Emerging Contaminants and Current Issues. Analytical Chemistry 2014, 86 (6), 2813- 2848. 7. Reeves, W. R.; Barhoumi, R.; Burghardt, R. C.; Lemke, S. L.; Mayura, K.; McDonald, T. J.; Phillips, T. D.; Donnelly, K. C., Evaluation of Methods for Predicting the Toxicity of Polycyclic Aromatic Hydrocarbon Mixtures. Environmental Science & Technology 2001, 35 (8), 1630-1636. 8. (a) Mastral, A. M.; Callén, M. S., A Review on Polycyclic Aromatic Hydrocarbon (PAH) Emissions from Energy Generation. Environmental Science & Technology 2000, 34 (15), 3051-3057; (b) Haeseler, F.; Blanchet, D.; Druelle, V.; Werner, P.; Vandecasteele, J.-P., Analytical Characterization of Contaminated Soils from Former Manufactured Gas Plants. Environmental Science & Technology 1999, 33 (6), 825-830; (c) Friedman, C. L.; Zhang, Y.; Selin, N. E., Climate Change and Emissions Impacts on Atmospheric PAH Transport to the Arctic. Environmental Science & Technology 2013, 48 (1), 429-437; (d) Technical Factsheet on: POLYCYCLIC AROMATIC HYDROCARBONS (PAHs). http://www.epa.gov/ogwdw/pdfs/factsheets/soc/tech/pahs.pdf (accessed 02/17); (e) Sellin Jeffries, M. K.; Claytor, C.; Stubblefield, W.; Pearson, W. H.; Oris, J. T., Quantitative Risk Model for Polycyclic Aromatic Hydrocarbon Photoinduced Toxicity in Pacific Herring Following the Exxon Valdez Oil Spill. Environmental Science & Technology 2013, 47 (10), 5450-5458. 9. Tidwell, L. G.; Allan, S. E.; O’Connell, S. G.; Hobbie, K. A.; Smith, B. W.; Anderson, K. A., Polycyclic Aromatic Hydrocarbon (PAH) and Oxygenated PAH (OPAH) Air–Water Exchange during the Deepwater Horizon Oil Spill. Environmental Science & Technology 2015, 49 (1), 141-149. 10. Schuster, J. K.; Harner, T.; Su, K.; Mihele, C.; Eng, A., First Results from the Oil Sands Passive Air Monitoring Network for Polycyclic Aromatic Compounds. Environmental Science & Technology 2015, 49 (5), 2991-2998. 11. de Maagd, P. G.-J.; ten Hulscher, D. T. E. M.; van den Heuvel, H.; Opperhuizen, A.; Sijm, D. T. H. M., Physicochemical properties of polycyclic aromatic hydrocarbons: Aqueous solubilities, n-octanol/water partition coefficients, and Henry's law constants. Environmental Toxicology and Chemistry 1998, 17 (2), 251- 257. 12. Kukkonen, J. V. K.; Landrum, P. F.; Mitra, S.; Gossiaux, D. C.; Gunnarsson, J.; Weston, D., Sediment Characteristics Affecting Desorption Kinetics of Select PAH and PCB Congeners for Seven Laboratory Spiked Sediments. Environmental Science & Technology 2003, 37 (20), 4656-4663. 13. Knecht, A. L.; Goodale, B. C.; Truong, L.; Simonich, M. T.; Swanson, A. J.; Matzke, M. M.; Anderson, K. A.; Waters, K. M.; Tanguay, R. L., Comparative developmental toxicity of environmentally relevant oxygenated PAHs. Toxicology and Applied Pharmacology 2013, 271 (2), 266-275. 14. Technical Factsheet on: POLYCHLORINATED BIPHENYLS (PCBs). http://www.epa.gov/ogwdw/pdfs/factsheets/soc/tech/pcbs.pdf (accessed 02/18). 15. Montaño, M.; Gutleb, A. C.; Murk, A. J., Persistent Toxic Burdens of Halogenated Phenolic Compounds in Humans and Wildlife. Environmental Science & Technology 2013, 47 (12), 6071-6081.
Bibliography
16. Birnbaum, L. S.; Staskal, D. F., Brominated flame retardants: cause for concern? Environmental Health Perspectives 2004, 112 (1), 9-17. 17. Technical Fact Sheet - Polybrominated Diphenyl Ethers (PBDEs) and Polybrominated Biphenyls (PBBs). http://www2.epa.gov/sites/production/files/2014- 03/documents/ffrrofactsheet_contaminant_perchlorate_january2014_final_0.pdf (accessed 02/18). 18. Aga, D. S.; Thurman, E. M., Formation and Transport of the Sulfonic Acid Metabolites of Alachlor and Metolachlor in Soil. Environmental Science & Technology 2001, 35 (12), 2455-2460. 19. Phillips, P. J.; Wall, G. R.; Thurman, E. M.; Eckhardt, D. A., Metolachlor and Its Metabolites in Tile Drain and Stream Runoff in the Canajoharie Creek Watershed. Environmental Science & Technology 1999, 33 (20), 3531-3537. 20. R.E.D FACTS Metolachlor; EPA: epa.gov, 1995; p 15. 21. Lambropoulou, D. A.; Albanis, T. A., Headspace Solid Phase Microextraction Applied to the Analysis of Organophosphorus Insecticides in Strawberry and Cherry Juices. Journal of Agricultural and Food Chemistry 2002, 50 (12), 3359-3365. 22. Guo, X.; Jans, U., Kinetics and Mechanism of the Degradation of Methyl Parathion in Aqueous Hydrogen Sulfide Solution: Investigation of Natural Organic Matter Effects. Environmental Science & Technology 2005, 40 (3), 900-906. 23. Organophosphorus Cumulative Risk Assessment 2006 Update. epa.gov, 2006; p. 522. http://www.epa.gov/pesticides/cumulative/pra_op_methods.htm. 24. Rav-Acha, C.; Groisman, L.; Mingelgrin, U.; Kirson, Z.; Sasson, Y.; Gerstl, Z., A Mechanistic Study of Methyl Parathion Hydrolysis by a Bifunctional Organoclay. Environmental Science & Technology 2006, 41 (1), 106- 111. 25. Burgard, D. A.; Banta-Green, C.; Field, J. A., Working Upstream: How Far Can You Go with Sewage-Based Drug Epidemiology? Environmental Science & Technology 2013, 48 (3), 1362-1368. 26. Löffler, D.; Römbke, J.; Meller, M.; Ternes, T. A., Environmental Fate of Pharmaceuticals in Water/Sediment Systems. Environmental Science & Technology 2005, 39 (14), 5209-5218. 27. Disposal of Unused Medicines: What You Should Know. http://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMe dicine/SafeDisposalofMedicines/ucm186187.htm#Flush_List (accessed 06/22/2015). 28. Daughton, C. G., Pharmaceuticals and Personal Care Products in the Environment. American Chemical Society: 2001; Vol. 791, p 420. 29. Al-Salhi, R.; Abdul-Sada, A.; Lange, A.; Tyler, C. R.; Hill, E. M., The Xenometabolome and Novel Contaminant Markers in Fish Exposed to a Wastewater Treatment Works Effluent. Environmental Science & Technology 2012, 46 (16), 9080-9088. 30. Perrine, D. M., The Chemistry of Mind-Altering Drugs History, Pharmacology, and Cultural Context. The American Chemical Society: 1996; p 480. 31. Castiglioni, S.; Zuccato, E.; Crisci, E.; Chiabrando, C.; Fanelli, R.; Bagnati, R., Identification and Measurement of Illicit Drugs and Their Metabolites in Urban Wastewater by Liquid Chromatography−Tandem Mass Spectrometry. Analytical Chemistry 2006, 78 (24), 8421-8429. 32. Huber, M. M.; Canonica, S.; Park, G.-Y.; von Gunten, U., Oxidation of Pharmaceuticals during Ozonation and Advanced Oxidation Processes. Environmental Science & Technology 2003, 37 (5), 1016-1024. 33. Helbling, D. E.; Hollender, J.; Kohler, H.-P. E.; Singer, H.; Fenner, K., High-Throughput Identification of Microbial Transformation Products of Organic Micropollutants. Environmental Science & Technology 2010, 44 (17), 6621-6627. 34. Benotti, M. J.; Trenholm, R. A.; Vanderford, B. J.; Holady, J. C.; Stanford, B. D.; Snyder, S. A., Pharmaceuticals and Endocrine Disrupting Compounds in U.S. Drinking Water. Environmental Science & Technology 2009, 43 (3), 597-603. 35. Oggier, D. M.; Weisbrod, C. J.; Stoller, A. M.; Zenker, A. K.; Fent, K., Effects of Diazepam on Gene Expression and Link to Physiological Effects in Different Life Stages in Zebrafish Danio rerio. Environmental Science & Technology 2010, 44 (19), 7685-7691. 36. Schmider, J.; Greenblatt, D. J.; von Moltke, L. L.; Karsov, D.; Vena, R.; Friedman, H. L.; Shader, R. I., Biotransformation of Mestranol to Ethinyl Estradiol In Vitro: The Role of Cytochrome P-450 2C9 and Metabolic Inhibitors. The Journal of Clinical Pharmacology 1997, 37 (3), 193-200. 37. Yi, T.; Harper, W. F., The Link between Nitrification and Biotransformation of 17α-Ethinylestradiol. Environmental Science & Technology 2007, 41 (12), 4311-4316. 38. Maes, H. M.; Maletz, S. X.; Ratte, H. T.; Hollender, J.; Schaeffer, A., Uptake, Elimination, and Biotransformation of 17α-Ethinylestradiol by the Freshwater Alga Desmodesmus subspicatus. Environmental Science & Technology 2014, 48 (20), 12354-12361. 39. (a) Lange, A.; Paull, G. C.; Coe, T. S.; Katsu, Y.; Urushitani, H.; Iguchi, T.; Tyler, C. R., Sexual Reprogramming and Estrogenic Sensitization in Wild Fish Exposed to Ethinylestradiol. Environmental Science & Technology 2009, 43 (4), 1219-1225; (b) Thorpe, K. L.; Cummings, R. I.; Hutchinson, T. H.; Scholze, M.; Brighty, G.;
183
Bibliography
Sumpter, J. P.; Tyler, C. R., Relative Potencies and Combination Effects of Steroidal Estrogens in Fish. Environmental Science & Technology 2003, 37 (6), 1142-1149. 40. Underwood, J. C.; Harvey, R. W.; Metge, D. W.; Repert, D. A.; Baumgartner, L. K.; Smith, R. L.; Roane, T. M.; Barber, L. B., Effects of the Antimicrobial Sulfamethoxazole on Groundwater Bacterial Enrichment. Environmental Science & Technology 2011, 45 (7), 3096-3101. 41. Dodd, M. C.; Huang, C.-H., Transformation of the Antibacterial Agent Sulfamethoxazole in Reactions with Chlorine: Kinetics, Mechanisms, and Pathways. Environmental Science & Technology 2004, 38 (21), 5607- 5615. 42. Majewsky, M.; Wagner, D.; Delay, M.; Bräse, S.; Yargeau, V.; Horn, H., Antibacterial Activity of Sulfamethoxazole Transformation Products (TPs): General Relevance for Sulfonamide TPs Modified at the para Position. Chemical Research in Toxicology 2014, 27 (10), 1821-1828. 43. Carey, F. A.; Sundberg, R. J., Advanced Organic Chemistry Part A: Structure and Mechanisms. Springer: 2007; p 1199. 44. Hansch, C.; Leo, A.; Taft, R. W., A survey of Hammett substituent constants and resonance and field parameters. Chemical Reviews 1991, 91 (2), 165-195. 45. Heim, K. E.; Tagliaferro, A. R.; Bobilya, D. J., Flavonoid antioxidants: chemistry, metabolism and structure- activity relationships. Journal of Nutritional Biochemistry 13 (10), 572-584. 46. Prinz, H.; Ishii, Y.; Hirano, T.; Stoiber, T.; Camacho Gomez, J. A.; Schmidt, P.; Düssmann, H.; Burger, A. M.; Prehn, J. H. M.; Günther, E. G.; Unger, E.; Umezawa, K., Novel Benzylidene-9(10H)-anthracenones as Highly Active Antimicrotubule Agents. Synthesis, Antiproliferative Activity, and Inhibition of Tubulin Polymerization. Journal of Medicinal Chemistry 2003, 46 (15), 3382-3394. 47. Dhawan, A.; Taurozzi, J. S.; Pandey, A. K.; Shan, W.; Miller, S. M.; Hashsham, S. A.; Tarabara, V. V., Stable Colloidal Dispersions of C60 Fullerenes in Water: Evidence for Genotoxicity†. Environmental Science & Technology 2006, 40 (23), 7394-7401. 48. Point Source Pollution. http://toxics.usgs.gov/definitions/point_source.html (accessed 02/26). 49. Daughton, C. G.; Ruhoy, I. S., Environmental footprint of pharmaceuticals: The significance of factors beyond direct excretion to sewers. Environmental Toxicology and Chemistry 2009, 28 (12), 2495-2521. 50. (a) Peverly, A. A.; Salamova, A.; Hites, R. A., Locating POPs Sources with Tree Bark. Environmental Science & Technology 2015; (b) Non-Point Source Pollution. http://toxics.usgs.gov/definitions/nonpoint_source.html (accessed 02/26). 51. Templeton, S.; Zilberman, D.; Yoo, S. J., Peer Reviewed: An Economic Perspective on Outdoor Residential Pesticide Use. Environmental Science & Technology 1998, 32 (17), 416A-423A. 52. Hernandez-Marin, E.; Martínez, A., Carbohydrates and Their Free Radical Scavenging Capability: A Theoretical Study. The Journal of Physical Chemistry B 2012, 116 (32), 9668-9675. 53. Welhouse, G. J.; Bleam, W. F., Cooperative hydrogen bonding of atrazine. Environmental Science & Technology 1993, 27 (3), 500-505. 54. (a) Zhang, X.; Oakes, K. D.; Cui, S.; Bragg, L.; Servos, M. R.; Pawliszyn, J., Tissue-Specific In Vivo Bioconcentration of Pharmaceuticals in Rainbow Trout (Oncorhynchus mykiss) Using Space-Resolved Solid- Phase Microextraction. Environmental Science & Technology 2010, 44 (9), 3417-3422; (b) Zhang, Y.; Luo, X.- J.; Wu, J.-P.; Liu, J.; Wang, J.; Chen, S.-J.; Mai, B.-X., Contaminant pattern and bioaccumulation of legacy and emerging organhalogen pollutants in the aquatic biota from an e-waste recycling region in South China. Environmental Toxicology and Chemistry 2010, 29 (4), 852-859; (c) Browne, M. A.; Galloway, T.; Thompson, R., Microplastic—an emerging contaminant of potential concern? Integrated Environmental Assessment and Management 2007, 3 (4), 559-561. 55. Mopper, K.; Stubbins, A.; Ritchie, J. D.; Bialk, H. M.; Hatcher, P. G., Advanced Instrumental Approaches for Characterization of Marine Dissolved Organic Matter: Extraction Techniques, Mass Spectrometry, and Nuclear Magnetic Resonance Spectroscopy. Chemical Reviews 2007, 107 (2), 419-442. 56. Ehlers, L. J.; Luthy, R. G., Peer Reviewed: Contaminant Bioavailability in Soil and Sediment. Environmental Science & Technology 2003, 37 (15), 295A-302A. 57. Landers, D. H.; Simonich, S. M.; Jaffe, D.; Geiser, L.; Campbell, D. H.; Schwindt, A.; Schreck, C.; Kent, M.; Hafner, W.; Taylor, H. E.; Hageman, K.; Usenko, S.; Ackerman, L.; Schrlau, J.; Rose, N.; Blett, T.; Erway, M. M., The Western Airborne Contaminant Assessment Project (WACAP): An Interdisciplinary Evaluation of the Impacts of Airborne Contaminants in Western U.S. National Parks. Environmental Science & Technology 2010, 44 (3), 855-859. 58. Feil, V. J.; Huwe, J. K.; Zaylskie, R. G.; Davison, K. L.; Anderson, V. L.; Marchello, M.; Tiernan, T. O., Chlorinated Dibenzo-p-dioxin and Dibenzofuran Concentrations in Beef Animals from a Feeding Study. Journal of Agricultural and Food Chemistry 2000, 48 (12), 6163-6173. 59. Fang, F.; Chu, S.; Hong, C.-S., Air−Water Henry's Law Constants for PCB Congeners: Experimental Determination and Modeling of Structure−Property Relationship. Analytical Chemistry 2006, 78 (15), 5412- 5418.
184
Bibliography
60. Clifford, G. M.; Hadj-Aïssa, A.; Healy, R. M.; Mellouki, A.; Muñoz, A.; Wirtz, K.; Martín Reviejo, M.; Borrás, E.; Wenger, J. C., The Atmospheric Photolysis of o-Tolualdehyde. Environmental Science & Technology 2011, 45 (22), 9649-9657. 61. Baptista, L.; Pfeifer, R.; da Silva, E. C.; Arbilla, G., Kinetics and Thermodynamics of Limonene Ozonolysis. The Journal of Physical Chemistry A 2011, 115 (40), 10911-10919. 62. Sandhiya, L.; Kolandaivel, P.; Senthilkumar, K., Mechanism and Kinetics of the Atmospheric Oxidative Degradation of Dimethylphenol Isomers Initiated by OH Radical. The Journal of Physical Chemistry A 2013, 117 (22), 4611-4626. 63. Huerta-Fontela, M.; Galceran, M. T.; Ventura, F., Stimulatory Drugs of Abuse in Surface Waters and Their Removal in a Conventional Drinking Water Treatment Plant. Environmental Science & Technology 2008, 42 (18), 6809-6816. 64. (a) Schwartz, T.; Kohnen, W.; Jansen, B.; Obst, U., Detection of antibiotic-resistant bacteria and their resistance genes in wastewater, surface water, and drinking water biofilms. FEMS Microbiology Ecology 2003, 43 (3), 325-335; (b) Chen, Y.; Hu, C.; Hu, X.; Qu, J., Indirect Photodegradation of Amine Drugs in Aqueous Solution under Simulated Sunlight. Environmental Science & Technology 2009, 43 (8), 2760-2765; (c) Keen, O. S.; Baik, S.; Linden, K. G.; Aga, D. S.; Love, N. G., Enhanced Biodegradation of Carbamazepine after UV/H2O2 Advanced Oxidation. Environmental Science & Technology 2012, 46 (11), 6222-6227. 65. Cunningham, V. L.; Buzby, M.; Hutchinson, T.; Mastrocco, F.; Parke, N.; Roden, N., Effects of Human Pharmaceuticals on Aquatic Life: Next Steps. Environmental Science & Technology 2006, 40 (11), 3456-3462. 66. Paul E. Stackelberg , E. T. F., Michael T. Meyer , Steven D. Zauggb,; Alden K. Henderson , D. B. R., Persistence of pharmaceutical compounds and other organic wastewater contaminants in a conventional drinking-water-treatment plant. Science of the Total Environment 2004, 329, 99-113. 67. Goldstein, S.; Rabani, J., Mechanism of Nitrite Formation by Nitrate Photolysis in Aqueous Solutions: The Role of Peroxynitrite, Nitrogen Dioxide, and Hydroxyl Radical. Journal of the American Chemical Society 2007, 129 (34), 10597-10601. 68. Katsoyiannis, I. A.; Ruettimann, T.; Hug, S. J., pH Dependence of Fenton Reagent Generation and As(III) Oxidation and Removal by Corrosion of Zero Valent Iron in Aerated Water. Environmental Science & Technology 2008, 42 (19), 7424-7430. 69. Abdelmelek, S. B.; Greaves, J.; Ishida, K. P.; Cooper, W. J.; Song, W., Removal of Pharmaceutical and Personal Care Products from Reverse Osmosis Retentate Using Advanced Oxidation Processes. Environmental Science & Technology 2011, 45 (8), 3665-3671. 70. DeMatteo, M. P.; Poole, J. S.; Shi, X.; Sachdeva, R.; Hatcher, P. G.; Hadad, C. M.; Platz, M. S., On the Electrophilicity of Hydroxyl Radical: A Laser Flash Photolysis and Computational Study. Journal of the American Chemical Society 2005, 127 (19), 7094-7109. 71. Bakken, G. A.; Jurs, P. C., Prediction of Hydroxyl Radical Rate Constants from Molecular Structure. Journal of Chemical Information and Computer Sciences 1999, 39 (6), 1064-1075. 72. Rojas, M. R.; Pérez, F.; Whitley, D.; Arnold, R. G.; Sáez, A. E., Modeling of Advanced Oxidation of Trace Organic Contaminants by Hydrogen Peroxide Photolysis and Fenton’s Reaction. Industrial & Engineering Chemistry Research 2010, 49 (22), 11331-11343. 73. Minakata, D.; Li, K.; Westerhoff, P.; Crittenden, J., Development of a Group Contribution Method To Predict Aqueous Phase Hydroxyl Radical (HO•) Reaction Rate Constants. Environmental Science & Technology 2009, 43 (16), 6220-6227. 74. (a) Aloisio, S.; Francisco, J. S., Complexes of Hydroxyl and Hydroperoxyl Radical with Formaldehyde, Acetaldehyde, and Acetone. The Journal of Physical Chemistry A 2000, 104 (14), 3211-3224; (b) Gergman, R. G. D., Alwyn G.; Fischer, Hanspeter; Garst, John F.; Ingold, Keith U.; Kerr, J. Alistair; Kochi, Jay K.; Koenig, Thomas; Roberts, Brian P.; Russel, Glen A.; Ward, Harold R.; Wilt, James W., Free Radicals. 1 ed.; John Wiley & Sons: New York City, New York, 1973; Vol. 1, p 713. 75. Blotevogel, J.; Mayeno, A. N.; Sale, T. C.; Borch, T., Prediction of Contaminant Persistence in Aqueous Phase: A Quantum Chemical Approach. Environmental Science & Technology 2011, 45 (6), 2236-2242. 76. Faust, B. C.; Allen, J. M., Aqueous-phase photochemical formation of hydroxyl radical in authentic cloudwaters and fogwaters. Environmental Science & Technology 1993, 27 (6), 1221-1224. 77. (a) Pignatello, J. J.; Oliveros, E.; MacKay, A., Advanced Oxidation Processes for Organic Contaminant Destruction Based on the Fenton Reaction and Related Chemistry. Critical Reviews in Environmental Science and Technology 2006, 36 (1), 1-84; (b) Zepp, R. G.; Faust, B. C.; Hoigne, J., Hydroxyl radical formation in aqueous reactions (pH 3-8) of iron(II) with hydrogen peroxide: the photo-Fenton reaction. Environmental Science & Technology 1992, 26 (2), 313-319. 78. Vu, N. D.; Khamaganov, V.; Nguyen, V. S.; Carl, S. A.; Peeters, J., Absolute Rate Coefficient of the Gas- Phase Reaction between Hydroxyl Radical (OH) and Hydroxyacetone: Investigating the Effects of Temperature and Pressure. The Journal of Physical Chemistry A 2013, 117 (47), 12208-12215. 79. Atkinson, R., Kinetics and Mechanisms of the Gas-Phase Reactions of the Hydroxyl Radical with Organic Compounds. The Journal of Physical and Chemical Reference Data: 1989; Vol. 1, p 246.
185
Bibliography
80. Arakaki, T.; Anastasio, C.; Kuroki, Y.; Nakajima, H.; Okada, K.; Kotani, Y.; Handa, D.; Azechi, S.; Kimura, T.; Tsuhako, A.; Miyagi, Y., A General Scavenging Rate Constant for Reaction of Hydroxyl Radical with Organic Carbon in Atmospheric Waters. Environmental Science & Technology 2013, 47 (15), 8196-8203. 81. Liao, P.; Yuan, S.; Chen, M.; Tong, M.; Xie, W.; Zhang, P., Regulation of Electrochemically Generated Ferrous Ions from an Iron Cathode for Pd-Catalytic Transformation of MTBE in Groundwater. Environmental Science & Technology 2013, 47 (14), 7918-7926. 82. Huang, W.; Brigante, M.; Wu, F.; Mousty, C.; Hanna, K.; Mailhot, G., Assessment of the Fe(III)–EDDS Complex in Fenton-Like Processes: From the Radical Formation to the Degradation of Bisphenol A. Environmental Science & Technology 2013, 47 (4), 1952-1959. 83. (a) Schmitt, D. S., F.; Frimmel, F.H.; Schuessler, W., NOM-facilitated transport of metal ions in aquifers: importance of complex-dissociation kinetics and colloid formation. Water Research 2003, 37 (15), 3541-3550; (b) Southworth, B. A.; Voelker, B. M., Hydroxyl Radical Production via the Photo-Fenton Reaction in the Presence of Fulvic Acid. Environmental Science & Technology 2003, 37 (6), 1130-1136. 84. Oturan, N.; Zhou, M.; Oturan, M. A., Metomyl Degradation by Electro-Fenton and Electro-Fenton-Like Processes: A Kinetics Study of the Effect of the Nature and Concentration of Some Transition Metal Ions As Catalyst. The Journal of Physical Chemistry A 2010, 114 (39), 10605-10611. 85. Zepp, R. G.; Hoigne, J.; Bader, H., Nitrate-induced photooxidation of trace organic chemicals in water. Environmental Science & Technology 1987, 21 (5), 443-450. 86. Gehling, W.; Khachatryan, L.; Dellinger, B., Hydroxyl Radical Generation from Environmentally Persistent Free Radicals (EPFRs) in PM2.5. Environmental Science & Technology 2013, 48 (8), 4266-4272. 87. Page, S. E.; Arnold, W. A.; McNeill, K., Assessing the Contribution of Free Hydroxyl Radical in Organic Matter- Sensitized Photohydroxylation Reactions. Environmental Science & Technology 2011, 45 (7), 2818-2825. 88. Toth, J. E.; Rickman, K. A.; Venter, A. R.; Kiddle, J. J.; Mezyk, S. P., Reaction Kinetics and Efficiencies for the Hydroxyl and Sulfate Radical Based Oxidation of Artificial Sweeteners in Water. The Journal of Physical Chemistry A 2012, 116 (40), 9819-9824. 89. Grebel, J. E.; Pignatello, J. J.; Mitch, W. A., Effect of Halide Ions and Carbonates on Organic Contaminant Degradation by Hydroxyl Radical-Based Advanced Oxidation Processes in Saline Waters. Environmental Science & Technology 2010, 44 (17), 6822-6828. 90. von Gunten, U.; Hoigne, J., Bromate Formation during Ozonization of Bromide-Containing Waters: Interaction of Ozone and Hydroxyl Radical Reactions. Environmental Science & Technology 1994, 28 (7), 1234-1242. 91. (a) Dutta, P. K.; Pehkonen, S. O.; Sharma, V. K.; Ray, A. K., Photocatalytic Oxidation of Arsenic(III): Evidence of Hydroxyl Radicals. Environmental Science & Technology 2005, 39 (6), 1827-1834; (b) Jovanovic, S. V.; Simic, M. G., Mechanism of OH radical reactions with thymine and uracil derivatives. Journal of the American Chemical Society 1986, 108 (19), 5968-5972. 92. Xu, T.; Kamat, P. V.; Joshi, S.; Mebel, A. M.; Cai, Y.; O'Shea, K. E., Hydroxyl Radical Mediated Degradation of Phenylarsonic Acid. The Journal of Physical Chemistry A 2007, 111 (32), 7819-7824. 93. Parsons, A. F., An Introduction to Free Radical Chemistry. 1 ed.; Blackwell Science: 2000; p 238. 94. O'Shea, K. E.; Cardona, C., Hammett Study on the TiO2-Catalyzed Photooxidation of Para-Substituted Phenols. A Kinetic and Mechanistic Analysis. The Journal of Organic Chemistry 1994, 59 (17), 5005-5009. 95. Poole, J. S.; Shi, X.; Hadad, C. M.; Platz, M. S., Reaction of Hydroxyl Radical with Aromatic Hydrocarbons in Nonaqueous Solutions: A Laser Flash Photolysis Study in Acetonitrile. The Journal of Physical Chemistry A 2005, 109 (11), 2547-2551. 96. Herrmann, H., Kinetics of Aqueous Phase Reactions Relevant for Atmospheric Chemistry. Chemical Reviews 2003, 103 (12), 4691-4716. 97. Garcia Einschlag, F. S.; Felice, J. I.; Triszcz, J. M., Kinetics of nitrobenzene and 4-nitrophenol degradation by UV irradiation in the presence of nitrate and nitrite ions. Photochemical & Photobiological Sciences 2009, 8 (7), 953-960. 98. Qiu, Z. W.; Grant, D. M.; Pugmire, R. J., Paramagnetic carbon-13 shifts induced by the free radical Tempo. 2. Nitrogen heterocycles. Journal of the American Chemical Society 1984, 106 (3), 557-563. 99. Hoffmann, A. K.; Henderson, A. T., A NEW STABLE FREE RADICAL: DI-t-BUTYLNITROXIDE. Journal of the American Chemical Society 1961, 83 (22), 4671-4672. 100. Grant, R. D.; Rizzardo, E.; Solomon, D. H., Reactions of hydroxyl radicals with polymerizable olefins. Journal of the Chemical Society, Perkin Transactions 2 1985, (3), 379-384. 101. Chong, Y. K.; Ercole, F.; Moad, G.; Rizzardo, E.; Thang, S. H.; Anderson, A. G., Imidazolidinone Nitroxide- Mediated Polymerization. Macromolecules 1999, 32 (21), 6895-6903. 102. Sciannamea, V.; Jérôme, R.; Detrembleur, C., In-Situ Nitroxide-Mediated Radical Polymerization (NMP) Processes: Their Understanding and Optimization. Chemical Reviews 2008, 108 (3), 1104-1126. 103. Moad, G.; Rizzardo, E.; Thang, S. H., Radical addition–fragmentation chemistry in polymer synthesis. Polymer 2008, 49 (5), 1079-1131. 104. Grant, R. D.; Rizzardo, E.; Solomon, D. H., 2-(t-Butylazo)prop-2-yl hydroperoxide: a convenient source of hydroxyl radicals in organic media. Journal of the Chemical Society, Chemical Communications 1984, (13), 867-868.
186
Bibliography
105. Sparkman, O. D. P., Zelda E.; Kitson, Fulton G., Gas Chromatography and Mass Spectrometry. 2 ed.; Academic Press: Elsevier, 2011; p 611. 106. Onishi, Y.; Nishimoto, Y.; Yasuda, M.; Baba, A., InCl3/Me3SiBr-Catalyzed Direct Coupling between Silyl Ethers and Enol Acetates. Organic Letters 2011, 13 (10), 2762-2765. 107. (a) Olah, G. A.; Gupta, B. G. B.; Narang, S. C.; Malhotra, R., Synthesis methods and reactions. 71. Chlorotrimethylsilane and tert-butyl dimethylsilyl chloride/lithium sulfide, mild and efficient silylating reagents. The Journal of Organic Chemistry 1979, 44 (24), 4272-4275; (b) Tajik, H. N., Kjodabakhsh; Karimian, Somayeh, Silylation of alcohols and phenols by HMDS in the presence of ionic liquid and silica-supported ionic liquids. Iranian Journal of Catalysis 2013, 3 (2), 107-113. 108. Iida, A.; Horii, A.; Misaki, T.; Tanabe, Y., Anilinosilanes/TBAF Catalyst: Mild and Powerful Agent for the Silylation of Sterically Hindered Alcohols. Synthesis 2005, 2005 (16), 2677-2682. 109. Heaney, H.; Papageorgiou, G.; Wilkins, R. F., The functionalisation of electron rich aromatic compounds with 1,3-oxazolidines and 1,3-dimethylimidazolidine. Tetrahedron 1997, 53 (42), 14381-14396. 110. Allen, A. D.; Fenwick, M. F.; Henry-Riyad, H.; Tidwell, T. T., Nitroxyl Radical Reactions with 4-Pentenyl- and Cyclopropylketenes: New Routes to 5-Hexenyl- and Cyclopropylmethyl Radicals. The Journal of Organic Chemistry 2001, 66 (17), 5759-5765. 111. Wang, S.-F.; Warkentin, J., Alkylation of tert-butyl lithiohydrazones of aldehydes and ketones. Canadian Journal of Chemistry 1988, 66 (9), 2256-2258. 112. Baumstark, A. L.; Vasquez, P. C., Oxidation of sulfides by acyclic .alpha.-azohydroperoxides. The Journal of Organic Chemistry 1983, 48 (1), 65-69. 113. Hubaux, A.; Vos, G., Decision and detection limits for calibration curves. Analytical Chemistry 1970, 42 (8), 849-855. 114. Baltaretu, C. O.; Lichtman, E. I.; Hadler, A. B.; Elrod, M. J., Primary Atmospheric Oxidation Mechanism for Toluene. The Journal of Physical Chemistry A 2009, 113 (1), 221-230. 115. Fischer, K.; Noll, O.; Gmehling, J., Experimental Determination of the Oxygen Solubility in Benzene. Journal of Chemical & Engineering Data 2001, 46 (6), 1504-1505. 116. Tezuka, T.; Narita, N.; Ando, W.; Oae, S., Isomer distribution ratios of phenols in aromatic hydroxylation with the hydroxyl radical generated from .alpha.-azohydroperoxide in anhydrous organic media. Comparison with Fenton's reagent. Journal of the American Chemical Society 1981, 103 (11), 3045-3049. 117. Koopmans, T., The distribution of wave function and characteristic value among individual electrons of an atom. Physica (The Hague) 1933, 1, 104-13. 118. Search for Species Data by IE Value. http://webbook.nist.gov/chemistry/ie-ser.html (accessed 06/01/2015). 119. HNU Systems, I., Photoionization Characteristics of Selected Compounds. HNU Systems, Inc.: HNU.com, 1997-99. 120. Smith, M. Reaction of hydroxyl radical with aromatic systems. Ball State University, cardinal scholar.bsu.edu, 2008. 121. Gagliardi, L. G.; Castells, C. B.; Ràfols, C.; Rosés, M.; Bosch, E., Static Dielectric Constants of Acetonitrile/Water Mixtures at Different Temperatures and Debye−Hückel A and a0B Parameters for Activity Coefficients. Journal of Chemical & Engineering Data 2007, 52 (3), 1103-1107. 122. Ripin, D. H., Evans, D. A., pKa's of CH bonds at Nitrile, Heteroaromatic, and Sulfur Substituted Carbon. Evans, D. A., Ed. Harvard University: 2005. 123. Kurata, T.; Watanabe, Y.; Katoh, M.; Sawaki, Y., Mechanism of aromatic hydroxylation in the Fenton and related reactions. One-electron oxidation and the NIH shift. Journal of the American Chemical Society 1988, 110 (22), 7472-7478. 124. Bowry, V. W.; Ingold, K. U., Kinetics of nitroxide radical trapping. 2. Structural effects. Journal of the American Chemical Society 1992, 114 (13), 4992-4996. 125. Choure, S. C.; Bamatraf, M. M. M.; Rao, B. S. M.; Das, R.; Mohan, H.; Mittal, J. P., Hydroxylation of Chlorotoluenes and Cresols: A Pulse Radiolysis, Laser Flash Photolysis, and Product Analysis Study. The Journal of Physical Chemistry A 1997, 101 (51), 9837-9845. 126. Shiroudi, A.; Deleuze, M. S.; Canneaux, S., Theoretical Study of the Oxidation Mechanisms of Naphthalene Initiated by Hydroxyl Radicals: The OH-Addition Pathway. The Journal of Physical Chemistry A 2014, 118 (26), 4593-4610. 127. Shiroudi, A.; Deleuze, M. S., Theoretical Study of the Oxidation Mechanisms of Naphthalene Initiated by Hydroxyl Radicals: The H Abstraction Pathway. The Journal of Physical Chemistry A 2014, 118 (20), 3625- 3636. 128. Dussault, P. Organic peroxides (and ozone): Safety-oriented overview. http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1000&context=chemistryperoxides (accessed 06/17/2015). 129. Joris, L.; Mitsky, J.; Taft, R. W., Effects of polar aprotic solvents on linear free-energy relations in hydrogen- bonded complex formation. Journal of the American Chemical Society 1972, 94 (10), 3438-3442. 130. Hansen, T. V.; Skattebøl, L., One-pot synthesis of substituted catechols from the corresponding phenols. Tetrahedron Letters 2005, 46 (19), 3357-3358.
187
Bibliography
131. Kotnis, A. S., A convenient, practical synthesis of substituted resorcinols: synthesis of DB-2073 and olivetol. Tetrahedron Letters 1991, 32 (29), 3441-3444. 132. Algi, F.; Balci, M., Simple, Mild, and Efficient Method for the Reduction of 1,4‐Benzoquinones to Hydroquinones by the Action of NaN3. Synthetic Communications 2006, 36 (16), 2293-2297. 133. Schneider, J.; Matsuoka, M.; Takeuchi, M.; Zhang, J.; Horiuchi, Y.; Anpo, M.; Bahnemann, D. W., Understanding TiO2 Photocatalysis: Mechanisms and Materials. Chemical Reviews 2014, 114 (19), 9919- 9986. 134. Carlos, L.; Fabbri, D.; Capparelli, A. L.; Prevot, A. B.; Pramauro, E.; Einschlag, F. S. G., Intermediate distributions and primary yields of phenolic products in nitrobenzene degradation by Fenton’s reagent. Chemosphere 2008, 72 (6), 952-958. 135. Chien, Y.-Y.; Kim, E.-G.; Bleam, W. F., Paramagnetic Relaxation of Atrazine Solubilized by Humic Micellar Solutions. Environmental Science & Technology 1997, 31 (11), 3204-3208. 136. Farcet, C.; Lansalot, M.; Charleux, B.; Pirri, R.; Vairon, J. P., Mechanistic Aspects of Nitroxide-Mediated Controlled Radical Polymerization of Styrene in Miniemulsion, Using a Water-Soluble Radical Initiator. Macromolecules 2000, 33 (23), 8559-8570. 137. Dumestre, A.; McBride, M.; Baveye, P., Use of EPR To Monitor the Distribution and Availability of Organic Xenobiotics in Model Soil Systems. Environmental Science & Technology 2000, 34 (7), 1259-1264. 138. Nosaka, Y.; Natsui, H.; Sasagawa, M.; Nosaka, A. Y., Electron Spin Resonance Studies on the Oxidation Mechanism of Sterically Hindered Cyclic Amines in TiO2 Photocatalytic Systems. The Journal of Physical Chemistry B 2006, 110 (26), 12993-12999. 139. Lebedev, A. T. B. G. J., J-M; Betowski, D.; Sparkman, O. D.; Artemenko, K. A.; Fialkov, A. B.; Gordin A.; Amirav, A.; Takats, Z.; Sharma, G.; Noll, R. J.; Ouyang, Z.; Cooks, R. G.; Leykin, A.; Nelms, S.Maleknia, S. D.; Richardson, S. D.; Jones0Lepp, R. L.; Hernandez, F. Ibanez, M.; Portoles, T.; Clement, R.; Reiner, E. J.; Hinz, K-P; Tretyakova, N.; Goggin, M.; Lobodin, V. V.; Rodgers, R. P.; Marshall, A. G.; Schmitt-Kopplin, P.; Harir, M.; Tziotis, D.; Gabelica, Z.; Hertkorn, N.; Spengler, B.; Talibova, A.; Tokarev, M.; Hilkert, A., Comprehensive Environmental Mass Spectrometry. ILM Publications: St Albans, Hertfordshire UK, 2012; p 510. 140. The Secrets of Solid Phase Extraction (SPE) for Sample Preparation. Agilent Technologies: www.chem.agilent.com, pp 29-30. 141. Moeder, M.; Schrader, S.; Winkler, M.; Popp, P., Solid-phase microextraction–gas chromatography–mass spectrometry of biologically active substances in water samples. Journal of Chromatography A 2000, 873 (1), 95-106.
188