Common NMR Method for Structure Elucidation of Organic Molecule
ELUCIDATION OF REACTIONS IN ORGANIC …...ELUCIDATION OF REACTIONS IN ORGANIC PHOTOCHEMISTRY BY...
Transcript of ELUCIDATION OF REACTIONS IN ORGANIC …...ELUCIDATION OF REACTIONS IN ORGANIC PHOTOCHEMISTRY BY...
ELUCIDATION OF REACTIONS IN ORGANIC PHOTOCHEMISTRY
BY
JASON MARK PIFER
A Dissertation Submitted to the Graduate Faculty of
WAKE FOREST UNIVERSITY GRADUATE SCHOOL OF ARTS AND SCIENCES
in Partial Fulfillment of the Requirements
for the Degree of
DOCTOR OF PHILOSOPHY
Chemistry
May, 2015
Winston-Salem, North Carolina
Approved By:
Paul B. Jones, Ph.D., Advisor
Richard T. Williams, Ph.D., Chair
S. Bruce King, Ph.D.
Akbar Salam, Ph.D.
Mark E. Welker, Ph.D.
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ACKNOWLEDGEMENTS
I have a hard time taking credit for my accomplishments due to the numerous
positive influences surrounding me in my personal life and their involvement in making
me who I am today. Their contributions are invisible to the uninformed observer but words
cannot fully describe how appreciative I am of all of my friends and family and how
instrumental they are in my success and happiness.
First and foremost I want to thank my fiancé Linda, who opened my mind to the
world. She has given me an immeasurable amount of support over the past five years, and
her unwavering commitment to my education and well-being continue to provide me with
the stability and inspiration to achieve great things.
I also need to thank my family for their continued support in my pursuit of
knowledge. My mother, Linda Danieley, deserves the most of this credit for her sacrifices
towards my well-being throughout my life. My step-father, Ned Danieley, and my brother,
Sean Pifer, also deserve an immense amount of recognition for their encouragement and
for serving as my role models.
I want to express my gratitude to Hunter, John, Jesse, Jake, Patrick, Clay, Alex,
Edward, Nathan, Josh, and Nate. Some of these gentlemen have been around since the very
beginning, and some more recently befriended me, but my time spent with all of them is
irreplaceable. I need to specifically thank John King for the contribution he made towards
my intellectual development. Without the two years I lived with John I likely would have
missed out on learning some of the most deeply philosophical lessons that are so dear to
my heart. I will carry the conversations and debates we had with me for the rest of my life.
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If and when I go on to achieve more in my life it will be in no small part due to the
individuals mentioned above and their contribution to my intellectual prosperity. There are
countless other friends and family members who, while for the sake of brevity I will not
list by name, have been a source of inspiration and support. To all of these people, I thank
you for everything.
I would also like to thank my advisor, Dr. Paul B. Jones, for the chemistry
knowledge imparted to me and his support in my research. I must also thank the Jones
group members of past and present, most notably Gina Hilton and Alec Christian, for
providing valuable insight and creating a pleasant atmosphere in the lab. I extend my
gratitude to my fellow graduate student colleagues Amanda Pickard and Kathryn Riley
who, through our camaraderie, were all able to complete our doctorates and have some fun
along the way. Additionally I want to thank Dr. Marcus Wright for his help with NMR and
other instrumentation, alongside the conversations we shared towards a better
understanding of human nature. I also extend my thanks to Dr. Julie Reisz Haines for her
help with GC-MS and HRMS (especially in the unfortunately timed instrument
malfunctions) and Dr. Cynthia Day for her expert crystallography. Lastly I would like to
thank Wake Forest University and the WFU Translational Sciences Institute for financial
support.
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TABLE OF CONTENTS
Page
List of Schemes X
List of Tables XIV
List of Figures XIV
List of Abbreviations XVI
Abstract XXII
Chapter 1 Introduction 1
1.1 Photochemistry 1
1.1.1 Photochemical Pathways 2
1.1.2 Electronic Transitions 3
1.1.3 Intersystem Crossing and Triplet Processes 4
1.1.4 Photosensitization and Other Phenomena 6
1.1.5 Carbonyl Photochemistry 7
1.1.6 Pericyclic Photochemical Reactions 9
1.2 Anthraquinone Photochemistry 10
1.2.1 Benzyloxy and Alkoxy Substituted Anthraquinones 11
1.2.2 1,2-Dialkoxy Anthraquinones 15
1.3 Aquatolide Formation in Asteriscus Aquaticus 16
1.4 Research Objectives 17
Chapter 2 Synthesis of Proposed Intermediates of the Dimerization of 1,2- 19
Dialkoxy-9,10-anthraquinones
2.1 Targeted Intermediates 19
2.2 Attempted Synthesis via Diels-Alder Reaction 20
VI
2.3 Attempted Synthesis via Various Palladium Catalyzed Coupling 21
Reactions
2.3.1 Attempts at Hydration of 1-(1-Decenyl)-2-Methoxy-9,10- 23
anthraquinone
2.3.2 Dihydroxylation attempts of 1-(1-Decenyl)-2-Methoxy-9,10- 24
anthraquinone
2.3.3 Reduction of 1-(1-Decenyl)-2-Methoxy-9,10-anthraquinone 24
2.3.4 Irradiation of 1-Decyl-2-Methoxy-9,10-anthraquinone 25
2.4 Other Attempted Reactions with 2-Methoxy-9,10-anthraquinon-1-yl 26
trifluoromethanesulfonate
2.4.1 Nucleophilic Aromatic Substitution of 1-Triflate and 2- 26
Triflate Anthraquinones
2.4.2 β-Hydride Elimination of Alkyl Boronic Acids 27
2.5 Attempted ortho-Lithiations of 9,10-dimethoxy-2- 27
(methoxymethoxy)anthracene
2.6 Conclusions 29
2.7 Experimental Procedures 30
2.7.1 General Methods 30
2.7.2 Synthetic Methods 31
2.7.3 Photochemistry Methods 37
Chapter 3 Synthesis and Photochemistry of Various 1,2-Disubstituted 39
Anthraquinones
3.1 Introduction 39
3.2 Via 1-Hexadecyloxy-2-iodo-9,10-anthraquinone 40
3.2.1 1-Hexadecyloxy-2-cyano-9,10-anthraquinone 42
3.2.2 1-Hexadecyloxy-2-phenyl-9,10-anthraquinone 44
VII
3.2.3 Other Attempts at Synthesis with 1-Hexadecyloxy-2-iodo- 45
9,10-anthraquinone
3.3 Via 1-Allyloxy-9,10-anthraquinone and Related Attempts 45
3.3.1 1-Hexadecyloxy-2-(1-propenyl)-9,10-anthraquinone 46
3.3.2 1-Hexadecyloxy-2-n-propyl-9,10-anthraquinone 47
3.4 Via Alizarin 47
3.4.1 1-((3,7-dimethyloct-6-en-1-yl)oxy)-2-methoxyanthraquinone 48
3.4.2 1-Phenethyloxy-2-hexadecyloxy-9,10-anthraquinone 49
3.4.3 1-Hexadecyloxy-2-methoxymethyl-9,10-anthraquinone 49
3.4.4 1-Hexadecyloxy-2-hydroxy-9,10-anthraquinone 50
3.4.5 1-Hexadecyloxy-9,10-anthraquinon-2-yl 51
trifluoromethanesulfonate
3.4.6 1-n-Propyloxy-2-hexadecyloxy-9,10-anthraquinone 52
3.4.7 1-Hexadecyloxy-9,10-anthraquinon-2-yl acetate 52
3.4.8 Attempt to Synthesize 1-Hexadecyloxy-9,10-anthraquinon- 53
2-yl pivalate
3.5 Conclusions 54
3.6 Experimental Procedures 55
3.6.1 General Methods 55
3.6.2 Synthetic Methods 55
3.6.3 Photochemistry Methods 64
Chapter 4 Investigation of the Dimerization Mechanism of 1,2-dialkoxy- 73
9,10-anthraquinones
4.1 Introduction 73
4.2 J. Young Tube Experiments 74
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4.2.1 1,2-Dihexadecyloxy-9,10-anthraquinone 75
4.2.2 1-Dodecyloxy-9,10-anthraquinone 81
4.3 Reactions of 2-Hexadecyloxy Dimer 85
4.3.1 Reaction with Dimethylamine 85
4.3.2 Reaction with Triflic Anhydride 86
4.4 Irradiation of 1-Dodecyloxy-9,10-anthraquinone with 1,2- 87
Didodecyloxy-9,10-anthraquinone
4.5 Irradiation of 1-Dodecyloxy-9,10-anthraquinone at Alternate 88
Wavelengths
4.6 Synthesis and Irradiation of 2-Methoxy-1-palmitoyl-9,10- 88
anthraquinone
4.7 Irradiation of 1-((3,7-dimethyloct-6-en-1-yl)oxy)-2- 93
methoxyanthraquinone
4.7.1 Approximation of the Rate of Hydrogen Abstraction in 93
the Proposed Mechanism
4.7.2 Calculation of the Rate Constant for Cyclization of 112 94
4.8 Conclusions 96
4.9 Experimental Procedures 98
4.9.1 General Methods 98
4.9.2 Synthetic Methods 98
4.9.3 Photochemistry Methods 100
Chapter 5 Summary of Anthraquinone Projects 103
Chapter 6 Validation of the Formation of Aquatolide via a [2+2] 107
Photocycloaddition from Asteriscunolide C
6.1 Introduction 107
6.2 Irradiation of Asteriscunolides in Dichloromethane 107
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6.3 Irradiation of Asteriscunolides in Acetonitrile and the Discovery of 116
a New Photoproduct
6.4 Summary 120
6.5 Experimental Procedures 120
6.5.1 Photochemistry Methods 120
6.5.2 Analytical Methods 120
Chapter 7 Summary 123
References 127
Appendix A 135
Appendix B 149
Appendix C 161
Curriculum Vitae 169
X
LIST OF SCHEMES
Page
Scheme 1. Absorption of a photon and potential reaction pathways. 1
Scheme 2. Intermolecular hydrogen abstraction occurs between a triplet 8
excited ketone and an alcohol.
Scheme 3. Example of Norrish Type I (top) and Norrish Type II (bottom) 9
reactions.
Scheme 4. The molecular orbital arrangement of photochemically excited 10
2,4-hexadiene makes the disrotatory ring closure allowed.
Scheme 5. Irradiation of 1-methyl anthraquinone leads to hydrogen 11
abstraction and a resonance stabilized biradical.
Scheme 6. Irradiation of 1-alkoxy-9,10-anthraquinones in polar solvents 12
releases an aldehyde from the anthraquinone moiety.
Scheme 7. Irradiation of 1-(3,3,-dimethyl-2-propenyloxy)-9,10-anthraquinone 13
(8) in a 1:1 acetic acid/water mixture yields three different
anthraquinone derivatives and aldehyde 9.
Scheme 8. Selectivity and isolated yields of irradiation products of benzyloxy 14
substituted anthraquinones in various solvents.
Scheme 9. Proposed mechanism for the observed photorearrangement of 1- 15
benzyloxy-9,10-anthraquinone (12, R = Ph) and 1-dodecyloxy-
9,10-anthraquinone (R = C11H23) in nonpolar solvents.
Scheme 10. Proposed mechanism for the observed photochemical 16
rearrangement upon irradiation of 1,2-dialkoxy-9,10-anthraquinones
in nonpolar solvents.
Scheme 11. Potential mechanism for formation of aquatolide (47) from 17
asteriscunolide C (50).
Scheme 12. Proposed synthesis of 61, an analog of 39. 20
Scheme 13. Synthesis of 67 from alizarin (62). 21
Scheme 14. Preparation of vinyl stannane 68 in one step from cyclohexanone 23
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Scheme 15. Attempts at hydration of alkene 67 were unsuccessful. 23
Scheme 16. Dihydroxylation of 67 with AD-mix β, as well as epoxidation 24
with m-CPBA and subsequent ring opening were unsuccessful.
Scheme 17. Catalytic hydrogenation of 67 resulted in decomposition without 25
poisoning of the catalyst. Poisoning the catalyst with Ph2S results
in selective reduction of the alkene.
Scheme 18. Aerobic irradiation of anthraquinone 75 in benzene returned 26
starting material.
Scheme 19. Β-Hydride elimination to form 80 is the main reaction product 27
in the attempted Suzuki coupling of triflate 64 with an sp3
boronic acid.
Scheme 20. Methoxymethyl (MOM) protection of phenol 81 followed by 28
reduction and methylation of the quinone carbonyls forms
anthracene 83.
Scheme 21. Lithiation attempts of 83 were unsuccessful for the desired 29
regioselectivity.
Scheme 22. Irradiation of 1,2-dialkoxy anthraquinones forms dimer 45, 40
while 1-alkoxy anthraquinones form ketone 15.
Scheme 23. Synthesis of 1-hexadecyloxy-2-iodo anthraquinone (87). 40
Scheme 24. Irradiation of 87 yields 1-hydroxy anthraquinone (85) and 41
hexadecanal.
Scheme 25. Proposed mechanism for the formation of 1-hydroxy-9,10- 41
anthraquinone (85) and hexadecanal from the irradiation
of 87.
Scheme 26. Synthesis of 1-hexadecyloxy-2-cyano anthraquinone in one 42
step followed by anaerobic irradiation in benzene.
Scheme 27. Synthesis of 1-hexadecyloxy-2-phenyl anthraquinone in one 44
Step followed by anaerobic irradiation in benzene.
Scheme 28. Sonogashira couplings with 1-hexadecyloxy-2-iodo-9,10- 45
anthraquinone (86) were unsuccessful.
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Scheme 29. Synthesis of 1-hydroxy-2-n-propyl-9,10-anthraquinone (97) 46
via Claisen rearrangement and subsequent catalytic
hydrogenation.
Scheme 30. Alkylation of 1-hydroxy-2-allyl anthraquinone (96) formed 46
1-hexadecyloxy-2-prop-1-enyl anthraquinone (97). Irradiation
of 98 yields an unexpected photoproduct 99 as a mixture of
stereoisomers.
Scheme 31. Proposed mechanism for the rearrangement observed after 47
irradiation of 98.
Scheme 32. Alkylation of 1-hydroxy-2-n-propyl anthraquinone (97) 47
formed 1-hexadecyloxy-2-n-propyl anthraquinone (105).
Irradiation of 105 yields dimer 106 and pentadecane.
Scheme 33. Synthesis of 1-hydroxy-2-methoxy-9,10-anthraquinone (63) 48
and 1-hydroxy-2-hexadecyloxy-9,10-anthraquinone (107)
from alizarin (62) was achieved.
Scheme 34. Mitsunobu reaction of citronellol with 1-hydroxy-2-methoxy- 49
9,10-anthraquinone yielded 108. Irradiation of 108 yields
dimer 109 and a mixture of alkyl groups 110 and 111.
Scheme 35. Alkylation of 1-hydroxy-2-hexadecyloxy anthraquinone (107). 49
Scheme 36. Alkylation of 1-hydroxy-2-methoxymethyloxy anthraquinone 50
(119) formed 1-hexadecyloxy-2-methoxymetyhloxy
anthraquinone (120). Irradiation of 120 yields dimer 121 and
pentadecane.
Scheme 37. Deprotection of 1-hexadecyloxy-2-methoxymethyl-9,10- 51
anthraquinone (115).
Scheme 38. Triflation of 1-hexadecyloxy-2-hydroxy anthraquinone (122). 51
Scheme 39. Alkylation of 1-hydroxy-2-hexadecyloxy anthraquinone (107) 52
formed 1-n-propyloxy-2-hexadecyloxy anthraquinone (125).
Irradiation of 125 yields dimer 113.
Scheme 40. Acylation of 1-hexadecyloxy-2-hydroxy-9,10-anthraquinone. 52
Scheme 41. Acylation of alizarin (62) formed 1-hydroxy-9,10- 53
anthraquinon-2-yl pivalate (127). Attempted alkylation
with bromohexadecane led to migration of the pivaloyl
group prior to alkylation.
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Scheme 42. Proposed mechanism for the observed photorearrangement 74
of 1-dodecyloxy-9,10-anthraquinone in nonpolar solvents.
Scheme 43. Irradiation of 1,2-dialkoxy-9,10-anthraquinones in nonpolar 75
solvents.
Scheme 44. Anaerobic irradiation of 36 in a sealed J. Young tube. 76
Scheme 45. Anaerobic irradiation of 12 in a sealed J. Young tube. 81
Scheme 46. The addition of a nucleophile or an electrophile to the reaction 85
mixture after irradiation but prior to air exposure.
Scheme 47. Addition of dimethylamine to a solution of dimer 45 forms 86
dimethylamide 136.
Scheme 48. Proposed mechanism for addition of dimethylamine to a 86
solution of dimer 45.
Scheme 49. Addition of triflic anhydride to a solution of dimer 45. 87
Scheme 50. Irradiation of an equimolar solution of 142 and 131. 87
Scheme 51. Irradiation of 1-dodecyloxy-9,10-anthraquinone at both 366 88
nm and 300 nm yielded the expected ketone 15.
Scheme 52. Irradiation of 1-hexadecyloxy-2-hydroxy-9,10-anthraquinone 89
Scheme 53. Irradiation of 2-methoxy-1-palmitoyl-9,10-anthraquinone 89
Scheme 54. Irradiation of 108 releases alkyl radical 112. 94
Scheme 55. Synthesis of Barton ester 116 in one step followed by 96
irradiation to release alkyl radical 112.
Scheme 56. Revised mechanism for the formation of dimer 45. 97
Scheme 57. Revised mechanism for the formation of ketone 36. 85
Scheme 58. Irradiation of asteriscunolides A-D. 108
Scheme 59. Stepwise cyclization of asteriscunolide C (149) to form 109
aquatolide (150).
Scheme 60. All possible ring closures of asteriscunolides A-D. 119
XIV
LIST OF TABLES
Page
Table 1. Attempted Stille couplings of triflate 69 with stannane 68. 22
Table 2. Irradiation of 36 yields dimer 130, ketone 129, or other 54
products not shown.
LIST OF FIGURES
Page
Figure 1. A Jablonski diagram illustrates the possible pathways an electron 3
can follow after photon absorption
Figure 2. A spin flip is “spin-allowed” via p-orbital rotation as a means of 5
angular momentum compensation
Figure 3. Triplet sensitization (top), triplet quenching (middle), and triplet- 7
triplet annihilation (bottom).
Figure 4. 1,4-Benzoquinone (left) is the most common isomer of 11
benzoquinone. 9,10-Anthraquinone (right) is the most common
anthraquinone isomer, with the numbering scheme for substituents
indicated.
Figure 5. Structures of natural products found in the plant Asteriscus aquaticus 17
including the originally proposed structure of aquatolide, which has
since been proven to be incorrect.
Figure 6. Irradiation of 1-hexadecyloxy-2-cyano-9,10-anthraquinone (91) 43
formed aryl alkyl ketone 92.
Figure 7. 1H NMR of 1,2-Dihexadecyloxy-9,10-anthraquinone (36) in 77
d6-benzene.
Figure 8. 1H NMR of the product of 1,2-dihexadecyloxy-9,10- 78
anthraquinone irradiation in d6-benzene as a mixture of
diastereomers.
XV
Figure 9. 1H NMR of dimer 45 in d6-benzene. 79
Figure 10. 1H NMR of dimer 45 after irradiation of the dimer solution shown 80
in Figure 9 in d6-benzene.
Figure 11. 1H NMR of 1-dodecyloxy-9,10-anthraquinone (12) prior to 82
irradiation.
Figure 12. 1H NMR of 1-dodecyloxy-9,10-anthraquinone (12) after irradiation. 83
Figure 13. 1H NMR of purified ketone 15. 84
Figure 14. GC-MS trace of the irradiation product of 2-methoxy-1-palmitoyl- 90
9,10-anthraquinone (138) showing the formation of 1-
chloropentadecane (139).
Figure 15. 1H NMR of the irradiation product of 2-methoxy-1-palmitoyl- 91
9,10- anthraquinone (138) showing the formation of 1-
chloropentadecane (139).
Figure 16. Irradiation of 2-methoxy-1-palmitoyl-9,10-anthraquinone 92
compared to purified 2-methoxy dimer.
Figure 17. Integration of the peaks shown for 110 and 111 in the GC trace 95
were used in Equation 8.
Figure 18. Overlaid GC traces of pure asteriscunolides and aquatolide. 110
Figure 19. GC-MS data after irradiation of asteriscunolide B for 32 hours. 111
Figure 20. The four graphs below show the rate of formation and 112
disappearance of each asteriscunolide and aquatolide upon
irradiation.
Figure 21. The four graphs below show the formation of aquatolide upon 114
irradiation of each asteriscunolide.
Figure 22. GC-MS data for irradiation (32 hours) of asteriscunolide B in 117
acetonitrile.
Figure 23. NMR data for the newly created compound from asteriscunolide 118
irradiation in acetonitrile.
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LIST OF ABBREVIATIONS
1* singlet excited state
3* triplet excited state
Ac acetyl
AcOH acetic Acid
anthraquinone 9,10-anthraquinone
ast asteriscunolide
BHT butylhydroxytoluene
Bn benzyl
13C{1H} proton decoupled carbon-13 NMR
c speed of light
CN cyano
COSY correlation spectroscopy
d doublet
dba dibenzylideneacetone
dd doublet of doublets
Δ heat
DIAD diisopropyl azodicarboxylate
DCC N,N’-dicylohexylcarbodiimide
DCM dichloromethane
DIPEA diisopropylethylamine
DMAP 4-dimethylaminopyridine
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DMF N,N-dimethylformamide
DMSO dimethylsulfoxide
equiv equivalent
E energy
Et ethyl
Et3N triethylamine
Et2O diethyl ether
EtOAc ethyl acetate
EtOH ethanol
F fluorescence
FPT freeze-pump-thaw
g gram
GC gas chromatography
GC-MS gas chromatography-mass spectrometry
1H proton NMR
h Planck’s constant
H-abstraction hydrogen abstraction
HCl hydrochloric acid
HMBC heteronuclear multiple bond correlation
HMQC heteronuclear multiple quantum coherence
HO highest occupied molecular orbital
hν irradiation
hr hour
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HRMS high resolution mass spectrometry
Hz hertz
ic internal conversion
ISC intersystem crossing
k rate constant
λ wavelength
LU lowest unoccupied molecular orbital
M molar
m multiplet
m-CPBA meta-chloroperoxybenzoic acid
Me methyl
MeCN acetonitrile
MeI iodomethane
MeOH methanol
Me2NH dimethylamine
mg milligram
MHz megahertz
mL milliliter
μL microliter
mm millimeter
μm micrometer
mM millimolar
μM micromolar
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mmol millimole
μmol micromole
MO molecular orbital
MOM methoxymethyl
MS mass spectrum
n nonbonding orbital
n-BuLi n-butyl lithium
n-Pr n-propyl
nm nanometer
NMR nuclear magnetic resonance
NR no reaction
ν frequency
[O] oxidation
OMe methoxy
o-furyl 2-furyl
o-tol ortho-tolyl
p pentet
P product
P phosphorescence
Pd palladium
Pd/C palladium on carbon
Ph phenyl
PhH benzene
XX
PhMe toluene
π pi bonding orbital
π* pi antibonding orbital
Φ quantum efficiency
PPh3 triphenylphosphine
ppm parts per million
q quartet
Q quencher
Φ quantum yield
R relaxation
RIP radical ion pair
RP radical pair
RT room temperature
s singlet
s second
S singlet state
S substrate
S* excited state substrate
SET single electron transfer
σ sigma bonding orbital
σ* sigma antibonding orbital
t triplet
T triplet state
XXI
TBAF tetra-n-butylammonium fluoride
t-BuLi tert-butyl lithium
OTf trifluoromethylsulfonate
THF tetrahydrofuran
TLC thin layer chromatography
TMEDA tetramethylethylenediamine
triflate trifluoromethylsulfonate
UV ultraviolet
VIS visible
W watt
XXII
ABSTRACT
Jason Mark Pifer
ELUCIDATION OF REACTIONS IN ORGANIC PHOTOCHEMISTRY
Dissertation under the direction of
Dr. Paul B. Jones, Associate Professor of Chemistry
Organic photochemistry is a unique discipline which allows for reactivity that is
unavailable in the ground state. 1,2-Dialkoxy anthraquinones exhibit photochemistry
which releases an alkane functional group from the 1-position and forms a dimer from the
anthraquinone moiety. This reactivity is observed for a plethora of 1,2-dialkoxy-9,10-
anthraquinones; however different products are observed for 1-ethoxy and 1-benzyloxy
substituted anthraquinones which instead produce a 1-keto derivative.
Prior to my arrival in the Jones group, the mechanism for the observed
photodimerization of 1,2-dialkoxy-9,10-anthraquinones was investigated in limited detail.
A mechanism for this rearrangement was proposed, involving three separate photon
absorptions, multiple H-abstractions, and a Norrish Type I cleavage prior to dimerization.
This proposed mechanism was thoroughly tested and was found to be incorrect based on
the formation of dimer in anaerobic conditions.
The functional groups on both the 1 and 2- positions play key roles in the ability
for this dimerization to occur. A variety of 1,2-disubstituted anthraquinones were
XXIII
synthesized and irradiated at 419 nm in order to investigate the functional group tolerance
of alkane release.
A revised mechanism for the photodimerization of 1,2-dialkoxy-9,10-
anthraquinones has been proposed to incorporate these discoveries. The revised
mechanism proposes that oxidation of an intermediate occurs via reduction of the starting
anthraquinone to the hydroquinone. This mechanism has also been supported by the
synthesis and irradiation of a proposed intermediate to form the expected alkoxy dimer.
In a separate project, the photochemistry of a series of natural products was
investigated. Asteriscunolides A-D, found in the plant Asteriscus aquaticus, were
suspected to be direct precursors to another natural product, aquatolide, which can also be
found in the plant. The irradiation of asteriscunolides A-D found that natural product
aquatolide is formed photochemically via [2+2] photocycloaddition from asteriscunolide
C. This suggests that aquatolide is made photochemically from asteriscunolide C in
Asteriscus aquaticus.
1
CHAPTER 1
INTRODUCTION
1.1 Photochemistry
Photochemistry is the study of reactions that result from the excitation of atoms or
molecules by the absorption of light. Scheme 1 is a simplified paradigm for photochemical
reactions; when a chemical species (S) absorbs a photon, an electron is promoted from the
ground state to an excited state (S*). There are several different pathways by which the
excited state species can get back to a stable ground state: by release of a photon or of heat,
forming intermediate I or reforming S in the case of a back reaction. Intermediate I can
then go on to form various products, or can reform starting material S. Both S* and I can
also undergo chemical reactions, the route of focus for most photochemical studies
including the ones covered in this dissertation.1a
Overall yield, quantum yield (Φ) and quantum efficiency (ϕ) can be measured for
these types of reactions. Percent yield is calculated as represented in Equation 1. The
2
equations for quantum yield and quantum efficiency are represented in Equations 2 and 3,
respectively.1b All three yields are lowered when undesired products P1 or P2 are formed,
while only Φ and ϕ are lowered when a back reaction occurs from S* or I.
Yield = actual yield P
theoretical yield P Equation 1
Φ = moles P
moles of photons absorbed by S Equation 2
ϕ = moles I
moles S∗ Equation 3
1.1.1 Photochemical Pathways
A chemical species that absorbs a photon promotes an electron from the highest
occupied molecular orbital (HO) to a higher energy unoccupied orbital, most commonly
the lowest unoccupied molecular orbital (LU). For the sake of this dissertation we will only
consider the lowest energy excited states S1 and T1; while higher energy excited states
exist, relaxation to S1 and T1 occurs faster than nearly all other processes per Kasha’s rule.2
All processes that result from absorption of a photon are considered photochemical
processes. Processes through which photon emission occurs (fluorescence,
phosphorescence) are known as radiative transitions. Processes which do not release a
photon are described as radiationless transitions.
From the singlet excited state the molecule may undergo internal conversion (which
involves the release of heat), fluorescence (which involves the release of a photon), or
3
intersystem crossing (ISC). ISC involves a spin flip, where the excited electron becomes
unpaired from the remaining electron in the HO. Any process, including ISC, in which an
electron changes spin is a “spin forbidden” process. The triplet state is inherently lower in
energy than its respective singlet excited state, as the energy increase from paired electrons
is relieved. From the triplet state, the molecule can release a photon in the form of
phosphorescence or relax via a radiationless transition back to the ground state, both of
which are a form of ISC and therefore are spin forbidden processes. This information is
summarized in a Jablonski diagram (Figure 1).3 It is worth noting that in both the singlet
and triplet excited states a chemical reaction(s) may also occur as the process by which the
electron reaches ground state.
1.1.2 Electronic Transitions
The energy of a photon is directly related to the wavelength as shown in Equation
4, where h is Planck’s constant, c is the speed of light, λ is the wavelength, and ν is the
frequency.
4
E = hc
λ= hν Equation 4
While the electromagnetic spectrum spans a huge magnitude of wavelengths (λ =
0.0001 nm to λ = 1 x 1010 nm), organic photochemistry only occurs within the ultraviolet
(UV, λ = 200-400 nm), visible (λ = 400-700 nm), and near infrared (near IR, λ = 700-1000
nm). A chromophore, defined as a molecule which absorbs a photon of light, will exhibit
an energy transition equal to the energy of the absorbed photon.4 The nature of the HO of
a chromophore varies depending on the functional groups involved. Molecules which
contain π bonds can promote an electron from a π bonding orbital to a π* antibonding
orbital (π→π*). Molecules which contain atoms with lone pairs can promote an electron
from a nonbonding orbital to a π* antibonding orbital (n→π*). It is very uncommon for an
electron to be promoted to σ* orbitals, as σ→σ*, π→σ*, and n→σ* transitions are
extremely high in energy relative to n→π* and π→π* transitions and will not be considered
for the sake of this dissertation. Both n→π* and π→π* transitions are lowered in energy
with the addition of conjugation, allowing molecules with aromatic rings or other forms of
extended conjugation to absorb photons that can extend into or past the visible spectrum.5
1.1.3 Intersystem Crossing and Triplet Processes
Energy and momentum must be conserved for both radiative and radiationless
transitions.6c This implies that for any transition the net energy change and net angular
momentum change must be zero. Conservation of momentum is specific to transitions
which result in a spin change, as these changes by themselves would result in a net angular
5
momentum change, making them unallowed. Therefore an electronic transition which
involves a spin flip requires a compensatory interaction with another source of angular
momentum change, making the net change zero.6 The two most common means in organic
molecules of compensating for this change in angular momentum are spin-spin coupling
and spin-orbit coupling.
Spin-spin coupling involves a change in nuclear spin angular momentum which is
exactly opposite from the electron spin angular momentum. For example a proton with spin
½ may undergo hyperfine coupling with an electron of spin -½ in a neighboring atom,
allowing for ISC of the electron to spin ½ and inversion of the proton spin to -½.6
Spin-orbit coupling relies on a change in orientation of an orbital which is coupled
to the electron undergoing angular momentum change. A good example is of an electron
in a py orbital with a partially vacant px orbital (Figure 2). Rotation of the py orbital about
the z-axis (which is visually the same effect as the electron jumping from the py to the px
orbital) compensates for one unit of orbital angular momentum, allowing for ISC to occur
along with the accompanying change in electron angular momentum.6
6
1.1.4 Photosensitization and Other Phenomena
Due to the nature of organic molecules, some triplet excited states are more
accessible than others. As the behavior of a molecule in the triplet excited state may be of
interest, photosensitization allows for conversion of a molecule to the triplet excited state.
This phenomenon occurs via energy transfer from a triplet excited state “sensitizer”,
promoting a “sensitized” molecule directly to the triplet excited state while the sensitizer
relaxes to the singlet ground state (Figure 3, top). Photosensitizers must have a triplet
energy higher than the molecule being sensitized, and typically exhibit high rates of ISC.7
Triplet quenching is a conceptually similar but experimentally opposite
phenomenon that occurs when a triplet state molecule relaxes to the ground state via energy
transfer to a ground state single “quencher”. The quencher is promoted to the triplet state
and undergoes ISC back to the singlet ground state (Figure 3, middle). Commonly this is
achieved by using conjugated dienes as quenchers, which rapidly undergo E/Z-
isomerization as a method of relaxation to the ground state. Triplet quenchers are useful
for determining whether or not a photochemical reaction proceeds from the triplet state.8
Another similar process known as triplet-triplet annihilation involves the collision
of two triplet state molecules and results in one singlet excited molecule and one singlet
ground state molecule (Figure 3, bottom). As is true for any process which relies on
molecular collisions, the rate of triplet-triplet annihilation increases with concentration.9
7
1.1.5 Carbonyl Photochemistry
Carbonyls are common functional groups in photochemical reactions, and their
photochemistry is particularly relevant to this dissertation. The photochemistry exhibited
is highly dependent on the excited state type (n, π* or π, π*), which can be predicted based
on the functional groups attached to the carbonyl. It is worth noting that most carbonyl
photochemistry occurs exclusively in ketones and aldehydes.
The excited state of a carbonyl is dependent on the nature of the reactive excited
state (S1 or T1). The reactive excited state can be predicted based on the rate of ISC. For
example ISC occurs quickly for aryl-alkyl and aryl ketones (~1011 – 1012 s
-1), while alkyl
ketones undergo ISC much slower (~107 – 108 s-1). Few photochemical processes have
8
rates faster than 1011 s-1 and therefore rarely outcompete ISC in aryl-alkyl and di-aryl
ketones.10
One common photochemical reaction pathway for carbonyls is intermolecular
hydrogen abstraction (Scheme 2). Excitation followed by intersystem crossing (in most
cases) in the presence of an alcohol such as isopropanol allows for H-abstraction to occur
from the α-CH of the alcohol. The resulting radical pair goes on to form homo-dimers of
the carbonyl while the isopropanol goes on to form acetone.11a H-abstraction occurs based
on bond dissociation energies (BDEs) rather than acidity, and will occur readily with
molecules such as Bu3SnH (Sn-H BDE = 267 kJ/mol, C-H BDE = 337 kJ/mol).11b
Carbonyls can also undergo intermolecular photochemical pathways, the most
common of which are Norrish Type I and II reactions. Both Type I and II reactions occur
primarily from the triplet excited state but can still occur from the singlet excited state,
albeit slower. Norrish Type I (Scheme 3, top) reactions involve α-cleavage from the
carbonyl to yield an acyl and alkyl radical pair (RP). Type I reactions can have a variety of
disproportionation and RP combination products. Norrish Type II reactions (Scheme 3,
bottom) involve intramolecular H-abstraction to form a 1,n-biradical. Most commonly
Norrish Type II reactions involve γ-hydrogen abstraction, yielding a 1,5-biradical. The 1,5-
9
biradical can then cyclize to form a cyclobutanol, break the 2-3 bond to form the
appropriate alkene and enol (which tautomerizes to the ketone), or undergo back-
abstraction to reform the starting material.12 For both cases there are many other possible
outcomes which will be explored in further detail later in this dissertation.
1.1.6 Pericyclic Photochemical Reactions
Pericyclic reactions can occur both photochemically and thermally. The governing
principles of pericylic reactions, known as the Woodward-Hoffman rules,13 can be used to
predict the possible reaction pathways. Thermal pericyclic reactions are allowed with either
4n+2 π electrons and disrotatory orbital rotation or 4n π electrons and conrotatory orbital
rotation. Conrotatory and disrotatory rotations are defined as two orbitals rotating in the
same or opposite directions, respectively. Photochemical pericyclic reactions proceed
exactly opposite from thermal reactions, with either 4n+2 π electrons and conrotatory
10
rotation or 4n π electrons and disrotatory orbital rotation. Using the [2+2] ring closure of
2,4-hexadiene as an example, Scheme 4 demonstrates these rules and shows the MO
analysis which these rules are based on. The nature of the rotation affects the resulting
stereochemistry if a stereocenter is generated in the reaction.13
1.2 Anthraquinone Photochemistry
Quinones are aromatic diones, and can have many possible structures. The simplest
quinone is benzoquinone, most commonly in the form of 1,4-benzoquinone (Figure 4, left)
Anthraquinones are quinone derivatives of anthracene; the most common anthraquinone
isomer is 9,10-anthraquinone (Figure 4, right), and the remainder of this dissertation will
refer to 9,10-anthraquinone simply as “anthraquinone”. Due to the aromatic rings and their
conjugation with the carbonyl groups, anthraquinone absorbs nearly into the visible
11
spectrum and the addition of electron donating substituents allow for the molecules to
absorb visible light. The carbonyl groups readily abstract hydrogen as the resulting acyl
radical is stabilized via resonance with both aromatic rings and the second ketone (Scheme
5).
1.2.1 Benzyloxy and Alkoxy Substituted Anthraquinones
Irradiation of 1-alkoxy anthraquinones in protic solvents such as methanol was
found to release the 1-alkoxy group as an aldehyde while also producing 1-hydroxy
anthraquinone. The accepted mechanism (Scheme 6) involves photon absorption and ISC
followed by δ H-abstraction to form a 1,5-biradical. Single Electron Transfer (SET) from
the alkyl radical to the anthracene moiety forms zwitterion 4 (a resonance structure of 3),
12
which is susceptible to nucleophilic attack by the solvent to form an acetal (5). Hydrolysis
of the acetal and air oxidation of the anthracenediol (5) form the observed aldehyde 6 and
1-hydroxy anthraquinone (7).14-16 This reaction was utilized by Brinson and Jones as a
method to release biologically active aldehydes.17
An unusual reaction was discovered when 1-(3,3-dimethyl-2-propenyloxy)-9,10-
anthraquinone (8, Scheme 7) was irradiated in oxygenated methanol. The expected 1-
hydroxy anthraquinone (7) was formed alongside a previously unobserved photoproduct,
which was determined to be 10 via X-ray crystallography. When the same compound was
irradiated in a deoxygenated acetic acid/water mixture 10 was isolated in 50% yield and
another side product 11 was isolated in 11% yield.18
13
The photochemistry of closely related 1-benzyloxy anthraquinone was initially
investigated by Brinson and Jones18 and further investigated by Sarma and Jones.19 The
results show that when 1-benzyloxy anthraquinone (12) is irradiated in methanol, the same
1-hydroxy anthraquinone (7) is the major product (Scheme 8). However new products 13
and 14 are observed; 13 is attributed to a photo-Claisen rearrangement and 14 attributed to
a reductive rearrangement. Upon further exploration it was discovered that when the same
1-benzyloxy anthraquinone is irradiated in nonpolar solvents, such as hexane or benzene,
ketone 15 is observed as the major product.
Additional 1,n-dibenzyloxy anthraquinones were synthesized and displayed
surprisingly different photoproducts. 1,2-Dibenzyloxy (16, Scheme 8) anthraquinone
yields similar photoproducts to 1-benzyloxy anthraquinone (12). 1,4-Dibenzyloxy
anthraquinone (20) yields some similar photoproducts but notably does not produce the
keto derivative in any of the tested solvents. 1,5-Dibenzyloxy anthraquinone (24) gave a
variety of photoproducts, including keto derivative 27. Interestingly only the mono-ketone
is observed; 1,5-dibenzoyl anthraquinone is not observed. 1,8-Dibenzyloxy anthraquinone
(30) was insoluble in both methanol and hexane, and upon irradiation in benzene gave one
single novel photoproduct (31) in 70% yield.19
14
The formation of the new keto product 15 from 12 was attributed to hydrogen
abstraction followed by ipso cyclization of biradical 32 and immediate ring opening to
form alcohol 34, followed by intramolecular redox to form 35 (Scheme 9). Exposure to air
15
oxidizes anthracenediol 35 to reform the quinone (15) similar to the final step in Scheme
6.19 The same reactivity was observed for 1-dodecyloxy-9,10-anthraquinone (R = C11H23).
1.2.2 1,2-Dialkoxy Anthraquinones
When irradiated in polar solvents 1,2-dialkoxy anthraquinones behave similar to 1-
alkoxy anthraquinones, releasing an aldehyde and the expected 1-hydroxy anthraquinone.
When irradiated in nonpolar solvents the ketone analogous to 15 was not observed but
another new product, dimer 45, was isolated (Scheme 10). This was attributed to a
mechanism with steps identical to the first five of ketone 15 formation. It was proposed
that dihydroxyanthracene 40 undergoes further photochemical rearrangement by Norrish
Type I cleavage to release an alkyl radical, with H-abstraction by the alkyl radical to form
16
RH and cyclization of the anthraquinone moiety (42) to form lactone 43. Oxidation of the
center ring forms a bis-benzylic radical which then dimerizes to form 45.
1.3 Aquatolide Formation in Asteriscus Aquaticus
Aquatolide, a natural product formed in the plant Asteriscus aquaticus,20 is an
interesting molecule with a history of skepticism in its structural assignment. The initially
proposed structure (46, Figure 5) was recently disproven via quantum-chemical NMR
calculations, experimental NMR analysis, and X-ray crystallography.21 The correct
structure was identified as 47, hypothesized to form from a [2+2] photocycloaddition from
asteriscunolide C (50), one of four isomers also found in Asteriscus aquaticus. The
proposed [2+2] photocycloaddition would likely form the C2‒C9/C3‒C10 bonds from
asteriscunolide C as shown in Scheme 11.
17
1.4 Research Objectives
There are multiple research projects discussed in this dissertation. The first research
project was to further understand the observed photochemical rearrangement of 36 to form
45. This was conducted by two methods. First, structural analogs of 36 were synthesized
to test the functional group tolerance of the observed photochemical rearrangement.
Second, irradiation of 36 and NMR analysis of the photoproduct prior to air exposure was
accomplished to test the proposed mechanism. A revised mechanism was proposed for the
18
formation of dimer 45 from 1,2-dialkoxy-9,10-anthraquinones. Furthermore, this revised
mechanism is supported by the synthesis and irradiation of a proposed intermediate in the
revised mechanism.
The goal of the second research project was to identify natural product aquatolide
as a photoproduct of asteriscunolides A-D, along with other products of asteriscunolide
irradiation. This was achieved by irradiation of all four pure asteriscunolides and analysis
of the reaction products.
19
CHAPTER 2
SYNTHESIS OF PROPOSED INTERMEDIATES OF THE
DIMERIZATION OF 1,2-DIALKOXY-9,10-ANTHRAQUINONES
2.1 Targeted Intermediates
Based on the mechanism shown in Scheme 10, intermediates 39 and 40 were
identified as the most stable and most likely isolable intermediates. If the mechanism is
correct, irradiation of either proposed intermediate will yield dimer formation and release
of RH. If the mechanism is incorrect then the synthesized proposed intermediate should
not yield dimer and release of alkane RH.
20
2.2 Attempted Synthesis via Diels-Alder Reaction
Synthesis of 39 was first attempted via Diels-Alder reaction. The proposed
synthetic route (Scheme 12) involved synthesis of the Weinreb amide of stearic acid (54)
from stearoyl chloride (53) followed by nucleophilic addition of vinyl Grignard to form an
α,β-unsaturated ketone (55). Silylation of the ketone would yield silyl-enol-ether 57 which
would then undergo a Diels-Alder reaction with 2-bromo-1,4-naphthoquinone (56) and
subsequent elimination to form anthraquinone 59. Desilylation and alkylation would yield
60. The final step would involve photochemical benzylic hydroxylation of the alkyl chain
via irradiation in the presence of oxygen.22 However isolation of silyl-enol-ether 57 proved
to be difficult as the reaction either decomposed (most likely due to polymerization of 55)
or would return starting material. A one-pot silylation and Diels-Alder attempt with 2-
bromo-1,4-napthaquinone (56) was also fruitless and returned both 55 and 56.
21
2.3 Attempted Synthesis via Various Palladium Catalyzed Coupling Reactions
Triflate 64 was synthesized from alizarin (62) in two steps via alkylation of the 2-
position and triflation of the remaining phenolic oxygen with triflic anhydride. Sonogashira
coupling of 64 was attempted with 1-decyne but was unsuccessful under a variety of
conditions. Suzuki coupling of 64 with boronic acid 66 was successful under the conditions
shown in Scheme 13, although the reaction was unreliable and many times returned
starting material or decomposed. Boronic acid 66 was synthesized via borylation of 1-
decyne with catecholborane in one step.
Stille coupling of triflate 69 (Table 1, synthesized under identical conditions to 64)
was also attempted but was never successful in excess of 10% yield. Optimization of the
reaction was also unsuccessful, with the ligands and palladium being varied extensively.
22
Table 1 summarizes the attempted conditions. The stannane (68) was prepared in one step
from cyclohexanone (Scheme 14).
Entry Pd (0) source Ligand Solvent Additives Temp Yield
1 Pd(PPh3)4 PPh3* Dioxane
LiCl (3 equiv.)
BHT (cat.)
H2O (50 μL)
Reflux 0%
2 Pd(PPh3)4 PPh3* DMF BHT (cat.)
H2O (50 μL) 80 °C 0%
3 Pd(PPh3)4 PPh3* Dioxane
CuI (cat.)
BHT (cat.)
H2O (50 μL)
Reflux 0%
4 PdCl2(PPh3)4 PPh3 DMF
LiCl (8 equiv.)
CuI (cat.)
BHT (cat.)
110 °C < 5%
5 PdCl2(PPh3)4 PPh3 PhMe
LiCl (8 equiv.)
CuI (cat.)
BHT (cat.)
Reflux 0%
6 Pd2(dba)3 PPh3 DMF LiCl (1.2 equiv.) 80 °C 0%
7 Pd2(dba)3●
[HP(tBu)3]BF4
P(tBu)3* DMF KF (1.3 equiv.) 80 °C 0%
8 Pd2(dba)3 P(o-tol)3 DMF LiCl (1.2 equiv) 80 °C < 10%
9 Pd2(dba)3 P(o-furyl)3 DMF LiCl (1.2 equiv) 100 °C 0%
23
2.3.1 Attempts at Hydration of 1-(1-Decenyl)-2-Methoxy-9,10-anthraquinone (67)
Hydration was first attempted by stirring anthraquinone 67 with perchloric acid in
acetonitrile (Scheme 15, top), which was unsuccessful and gave back starting material.
Oxymercuration/demercuration was then attempted, but was very low yielding and
appeared to give a mixture of products (Scheme 15, bottom).
24
2.3.2 Dihydroxylation attempts of 1-(1-Decenyl)-2-Methoxy-9,10-anthraquinone (67)
Anthraquinone 67 was treated with AD-mix β and refluxed in an acetone/water
mixture overnight, but returned starting material (Scheme 16, top). Epoxidation and
subsequent ring opening was attempted with m-CPBA followed by the addition of water.
90% of the anthraquinone was returned as starting material with the remaining 10%
identified as a possible mixture of dihydroxylated stereoisomers (74, Scheme 16, bottom).
2.3.3 Reduction of 1-(1-Decenyl)-2-Methoxy-9,10-anthraquinone
Unsuccessful attempts to hydroxylate 67 led to a new proposed synthetic route
involving benzylic hydroxylation of a 1-alkyl group on the anthraquinone.22 Catalytic
hydrogenation of 67 was attempted with Pd/C, but gave a mixture of decomposed products
25
presumably resulting from reduction of the quinone carbonyls and partial reduction of the
aromatic rings. Poisoning the catalyst with Ph2S prior to hydrogenation23 was successful in
the synthesis of 75 (Scheme 17).
2.3.4 Irradiation of 1-Decenyl-2-Methoxy-9,10-anthraquinone
Irradiation of 75 at 313 and 419 nm in the presence of oxygen was unsuccessful in
synthesizing the corresponding benzylic alcohol; in fact, no change in the starting material
was observed after several hours of irradiation (Scheme 18). A control irradiation of 1-
methyl anthraquinone (76) at 419 nm followed by a reductive workup yielded the predicted
alcohol (77) in 30 minutes.22 This confirmed that the predicted benzylic hydroxylation of
75 was due to the molecule’s poor reactivity as opposed to errors in reaction setup or faulty
equipment.
26
2.4 Other Attempted Reactions with 2-Methoxy-9,10-anthraquinone-1-yl-
trifluoromethanesulfonate
2.4.1 Nucleophilic Aromatic Substitution of 1-Triflate and 2-Triflate Anthraquinones
The first attempt at a Sonogashira coupling of 64 with 1-decyne in the presence of
n-butylamine gave near quantitative yields of nucleophilic addition of the primary amine
to the 1-position. However, the ability to displace the triflate group was limited to amines
and thiols; attempts at nucleophilic addition of iodide and chloride (via KI and LiCl,
respectively) were unsuccessful.
27
2.4.2 β-Hydride Elimination of Alkyl Boronic Acids
Suzuki type coupling of 64 with sp3 boronic acids was attempted in an effort to
directly synthesize the 1-alkyl substituted anthraquinone. The primary reaction product
was 2-methoxy anthraquinone (80), presumably from β-hydride elimination of the
anthraquinone-palladium complex (Scheme 19).
2.5 Attempted ortho-Lithiations of 9,10-dimethoxy-2-(methoxymethoxy)anthracene
The phenol in 2-hydroxy-9,10-anthraquinone (81, Scheme 20) was protected with
a methoxy methyl (MOM) group prior to protection of the carbonyl groups as methyl
ethers. The resulting compound (83) was designed to selectively lithiate in the 1-position,
due to the combined directing properties of the methyl ether and MOM groups.24
28
Initial lithiation attempts with n-butyl lithium (n-BuLi) in THF followed by
addition of an aldehyde were unsuccessful and gave back starting material (Scheme 21).
Tetramethyl ethylenediamine (TMEDA), which activates the n-BuLi by breaking up the
BuLi tetramers and hexamers,25 was added alongside n-BuLi in THF prior to addition of
an aldehyde but also gave back starting material. t-BuLi in THF followed by aldehyde
addition was then attempted, but crude product analysis showed a slew of products due to
lack of lithiation selectivity. Selectivity was finally achieved with the addition of t-BuLi to
83 (Scheme 21) in hexane at -78 oC followed by quenching with D2O; however, the
lithiation occurred selectively at the 3- position to form 84, as opposed to lithiating the
desired 1- position. The same selectivity was then observed with n-BuLi in hexane.
29
2.6 Conclusions
The failure to synthesize a proposed intermediate in the photochemical
rearrangement of 36 led to the development of other methods to test the proposed
mechanism. These methods are discussed in further detail in chapters 3 and 4, including
the synthesis and irradiation of a newly proposed intermediate in section 4.6.
30
2.7 Experimental Procedures
2.7.1 General Methods
Unless otherwise indicated, all reagents were commercially purchased from Sigma-
Aldrich and used without further purification, or prepared as described below. Solvents
were purified by passing over an alumina column. TLC was performed on fluorescein
doped aluminum backed silica gel plates, 200 μm thick. Preparative TLC was performed
using fluorescein doped glass backed silica gel plates, 500 μm thick. All TLC was
visualized with 254 nm or 366 nm light unless otherwise indicated. Column
chromatography was performed using silica gel, 60 Å pore size 40-63 μm particle size, or
by basic alumina when indicated, 60-325 mesh, Brockman activity I. 1H NMR spectra were
recorded using a 300 MHz Bruker DPX spectrometer with a qnp 5mm probe operating
TopSpin 1.3, and a 500 MHz Bruker DRX spectrometer using either a bbo 5mm or tbi
5mm probe operating TopSpin 1.3. 13C NMR spectra were also recorded on the
aforementioned spectrometers at 75.48 and 125.77 MHz, respectively. Chemical shifts are
reported in parts per million (δ) relative to residual deuterated solvents (CDCl3 or C6D6).
Coupling constants (J values) are reported in hertz (Hz).
31
2.7.2 Synthetic Methods
Synthesis of Stearoyl Chloride (53). Stearic acid (5 g, 17.6 mmol) was added to thionyl
chloride (3.0 mL, 25 mmol) and refluxed for 12 hrs under an argon atmosphere. Residual
thionyl chloride was removed via rotary evaporation to give 5.06 g of 53 (95%).26 1H NMR
(300 MHz, CDCl3): δ 8.32 – 8.20 ppm (m, 3H), 1.63 (p, 2H, J = 7.29 Hz), 1.40-1.18 (m,
28H), 0.88 (t, 3H, J = 7.00 Hz). 13C{1H} NMR (75 MHz, CDCl3) δ 178.97 ppm, 33.85,
31.92, 29.68, 29.64, 29.63, 29.58, 29.42, 29.35, 29.23, 29.05, 24.68, 22.68, 14.10.
Synthesis of N-methoxy-N-methylstearamide (54). Stearoyl chloride (4.70 g, 15.5
mmol) was added to a mixture of N,O-dimethylhydroxylamine hydrochloride (1.18 g, 12.1
mmol) in dichloromethane (25 mL). The reaction was cooled to 0 °C and pyridine (3.12
mL, 38.7 mmol) was added dropwise. The reaction was stirred for 8 hours and allowed to
warm to room temperature before diluting the reaction with dichloromethane. The resulting
solution was washed three times with 10% HCl and once with brine. The organic layer was
dried with MgSO4, filtered, and the filtrate was concentrated via rotary evaporation to yield
54 (71%). The 1H NMR data matched that which is previously reported in the literature.26
32
1H NMR (300 MHz, CDCl3) δ 3.68 ppm (s, 3H), 3.18 (s, 3H), 2.41 (t, 2H, J = 7.6 Hz), 1.63
(p, 2H, J = 7.8 Hz), 1.40-1.18 (m, 28H), 0.88 (t, 3H, J = 7.0 Hz).
Synthesis of 1-eicosen-3-one (55). Vinyl magnesium bromide (16 mL of 1M solution in
THF, 17.6 mmol) was added to a solution of N-methoxy-N-methylstearamide (5.77 g, 17.6
mmol) in THF (160 mL) under an argon atmosphere. The resulting solution was stirred at
room temperature for 14 hours before being diluted with ether (150 mL) and quenched
with 10% HCl (100 mL). The organic layer was then washed twice with 10% HCl, washed
once with NaHCO3, and washed once with brine before drying with MgSO4 and being
concentrated via rotary evaporation.27 55 was afforded in 34% yield. 1H NMR (300 MHz,
CDCl3) δ 6.36 ppm (dd, 1H, J = 17.7, 10.3 Hz), 6.21 (dd, 1H, J = 17.7, 1.5 Hz), 5.81 (dd,
1H, J = 10.3, 1.5 Hz), 2.57 (t, 2H, J = 7.4 Hz), 1.60 (p, 2H, J = 7.9 Hz), 1.40-1.18 (m,
28H), 0.88 (t, 3H, J = 7.0 Hz).
Synthesis of 1-hydroxy-2-methoxy-9,10-anthraquinone (63). Iodomethane (1.56 mL,
25.1 mmol) was added to a solution of alizarin (2.4 g, 10 mmol, purchase from TCI
America) and lithium carbonate (1.85 g, 25.0 mmol) in DMF (25 mL). The reaction was
33
stirred at room temperature for 14 hours, after which it was quenched with 10% HCl (250
mL) and the resulting precipitate was collected. The orange precipitate was recrystallized
out of hot ethanol (84%). 1H NMR data matched data previously reported in the literature.28
1H NMR (300 MHz, CDCl3) δ 13.06 ppm (s, 1H), 8.38 – 8.27 (m, 2H), 7.90 (d, 1H, J = 8.4
Hz), 7.87 – 7.75 (m, 2H), 7.19 (d, 1H, J = 8.4 Hz), 4.03 (s, 3H).
Synthesis of 2-methoxy-9,10-anthraquinon-1-yl trifluoromethanesulfonate (64).
Trifluoromethane sulfonic anhydride was added to a solution of 1-hydroxy-2-methoxy-
9,10-anthraquinone (2 g, 7.87 mmol) in a mixture of pyridine (9.24 mL, 115 mmol) and
dichloromethane (500 mL) at 0 °C. The reaction was allowed to warm to room temperature
and was stirred for 48 hours before being quenched with water. The aqueous layer was
extracted three times with dichloromethane (100 mL) and the resulting organic layer was
washed with 10% HCl (100 mL), dried with MgSO4 and concentrated by rotary
evaporation (90%).29 1H NMR (300 MHz, CDCl3) δ 8.41 ppm (d, 1H, J = 8.8 Hz), 8.37 –
8.20 (m, 2H), 7.87 – 7.75 (m, 2H), 7.43 (d, 1H, J = 8.8 Hz), 4.05 (s, 3H).
Synthesis of 1-decen-1-ylboronic acid (66). Catecholborane (5 mL, 47 mmol) was added
to a solution of 1-decyne (7.5 mL, 40 mmol) in THF (50 mL) and refluxed under argon
atmosphere for 2.5 hours. Water was added to quench the reaction and stirred for 12 hours
34
and the white precipitate was collected and dried en vacuo before being recrystallized out
of hexane (93%).30 The white solid was identified as a mixture of E/Z isomers and was
used without further purification.
Synthesis of 1-(1-decenyl)-2-methoxy-9,10-anthraquinone (67). Tetrakis
(triphenylphosphine)palladium(0) (92 mg, 5 mol %) was added to a solution of 2-methoxy-
9,10-anthraquinon-1-yl trifluoromethanesulfonate (620 mg, 1.6 mmol), K3PO4 (509.5 mg,
2.4 mmol), 1-decen-1-ylboronic acid (323.5 mg, 1.76 mmol) and catalytic KBr in dioxane
(20 mL). The reaction was stirred under an argon atmosphere for 24 hours before being
quenched with water. The aqueous layer was extracted with dichloromethane (250 mL),
and the organic layer was subsequently washed with brine (100 mL) and dried with MgSO4
before being concentrated via rotary evaporation (83%).31 1H NMR (300 MHz, CDCl3) δ
8.36 ppm (d, 1H, J = 8.7 Hz), 8.32 – 8.13 (m, 2H), 7.87 – 7.63 (m, 2H), 7.27 (d, 1H, J =
8.6 Hz), 6.66 (dt, 1H, J = 11.5, 1.5 Hz), 5.88 (dt, 1H, J = 11.4, 7.3 Hz), 3.95 (s, 3H), 1.79
(qd, 2H, J = 7.3, 1.6 Hz), 1.37 – 1.23 (m, 2H), 1.23 – 1.08 (m, 10H), 0.80 (t, 3H, J = 7.1
Hz).
35
Synthesis of 1-decyl-2-methoxy-9,10-anthraquinone (75). 10 wt % Palladium on
activated carbon (376.5 mg) was added to a solution of 1-decyl-2-methoxy-9,10-
anthraquinone (376.5 mg, 1 mmol) and phenyl sulfide (6.3 μL) in methanol (1.6 L). The
resulting solution was sparged with H2 while stirring for 1 hr. The solution was then
sparged with argon and run through a plug of celite and concentrated via rotary
evaporation.23 The solid was further purified via silica flash column with the mobile phase
run as a gradient from 100% hexane to 100% DCM (72%). 1H NMR (300 MHz, CDCl3):
δ 8.36 – 8.17 ppm (m, 3H), 7.79 – 7.66 (m, 2H), 7.19 (d, 1H, J = 8.6 Hz), 3.96 (s, 3H), 3.25
(t, 2H, J = 7.4 Hz), 1.64 – 1.43 (m, 2H), 1.44 – 1.10 (m, 14H), 0.88 (t, J = 6.3 Hz, 3H).
Synthesis of 2-methoxymethyl-9,10-anthraquinone (82). Chloromethyl methyl ether
(0.74 mL, 9.81 mmol) was added dropwise to a solution of 2-hydroxy-9,10-anthraquinone
(2 g, 8.92 mmol) and diisopropylethylamine (1.70 mL, 9.81 mmol) in dichloromethane
(400 mL) under an argon atmosphere. The reaction was stirred for 10 hours at room
temperature before adding saturated NaHCO3 (100 mL). The organic layer was separated,
dried with MgSO4, and concentrated via rotary evaporation before being recrystallized out
36
of hot ethanol (85%).32 1H NMR (300 MHz, CDCl3) δ 8.35 – 8.23 ppm (m, 3H), 7.88 (d,
1H, J = 2.6 Hz), 7.85 – 7.67 (m, 2H), 7.39 (dd, 1H, J = 8.7, 2.6 Hz), 5.34 (s, 2H), 3.52 (s,
3H).
Synthesis of 2-methoxymethyl-9,10-dimethoxyanthaquinone (83). A solution of
sodium dithionite (5 g, 28.7 mmol) in water (10 mL) was added to a solution of 2-
methoxymethyl-9,10-anthraquinone (1 g, 3.7 mmol) and catalytic tetrabutylammonium
iodide in a mixture of THF (150 mL) and water (50 mL) under an argon atmosphere. After
stirring for 2 hours, an aqueous solution of sodium hydroxide (0.56 M) was added and
stirred for 5 minutes. Iodomethane (1.15 mL, 18.5 mmol) was then added and the resulting
solution was stirred at room temperature for 24 hours. The crude reaction product was
extracted with DCM and concentrated via rotary evaporation before being run through a
plug of basic alumina eluting toluene. Concentration via rotary evaporation and
recrystallization out of hot ethanol afforded 81 (85%).24 1H NMR (300 MHz, CDCl3) δ
8.31 – 8.19 ppm (m, 3H), 7.72 (d, 1H, J = 2.5 Hz), 7.47 (dqd, 1H, J = 9.8, 6.5, 1.5 Hz),
7.26 (dd, 1H, J = 9.4, 2.5 Hz), 5.38 (s, 2H), 4.11 (s, 3H), 4.09 (s, 3H), 3.57 (s, 3H).
37
2.7.3 Photochemistry Methods
300 nm irradiation was performed with a 16 lamp rayonet reactor (peak emission
300 nm). 313 and 366 nm irradiation was performed using a 450W medium pressure
mercury lamp, or irradiated at 366 nm using the same lamp encased in a UO2-doped filter.
Samples were irradiated in pyrex glassware.
38
39
CHAPTER 3
SYNTHESIS AND PHOTOCHEMISTRY OF VARIOUS
1,2-DISUBSTITUTED ANTHRAQUINONES
3.1 Introduction
Work in the Jones group immediately prior to my arrival found that 1,2-dialkoxy
anthraquinones undergo a specific dimerization (45, Scheme 22) pathway upon irradiation,
while 1-alkoxy anthraquinones (unsubstituted at the 2- position) display different reactivity
upon irradiation to form an aryl alkyl ketone (15, Scheme 22). The outcome of these
anthraquinone photoreactions was found to be dictated by the presence of a 2- substituent.
However if R is methyl or phenyl (36, Scheme 22), then the presence of a 2- substituent
has no effect on the reaction and 15 is observed, indicating the nature of the 1- substituent
also affects the photochemical outcome. This also supports the proposed assertion that a
Norrish Type I cleavage occurs, as release of methyl and phenyl radicals is unfavorable.
In an effort to further understand this photochemical rearrangement, various
substituted anthraquinones were synthesized and irradiated. A majority of these
anthraquinones were designed to test the effect of electronic and steric variance of the 2-
substituent on the result of anthraquinone irradiation. Other 1,2-disubstituted
anthraquinones were synthesized to measure reaction rates or to test the effect of variance
in the 1-substituent.
40
3.2 Via 1-Hexadecyloxy-2-iodo-9,10-anthraquinone
1-Hexadecyloxy-2-iodo-9,10-anthraquinone (87, Scheme 23, top) was synthesized
in two steps from 1-hydroxy anthraquinone. Iodination was achieved via electrophilic
aromatic substitution with I2,32 followed by alkylation of the phenol with 1-
bromohexadecane. Iodination was attempted from 1-dodecyloxy-9,10-anthraquinone (88)
but was unsuccessful (Scheme 23, bottom).
41
When 87 was anaerobically irradiated under 419 nm light, 1-hydroxy
anthraquinone (85) was the major product (Scheme 24). The proposed mechanism
(Scheme 25) for this rearrangement involves δ H-abstraction to form the 1,5-diradical (89)
followed by homolytic C-I bond cleavage and hydrogen atom transfter to form 90.
Hydrolysis and oxidation of 90 forms 1-hydroxy anthraquinone (85) and hexadecanal upon
exposure to air, similar to the reactivity observed by Blakespoor albeit with a different
mechanism.15
42
3.2.1 1-Hexadecyloxy-2-cyano-9,10-anthraquinone
Nitrile coupling of cuprous cyanide into 87 afforded 1-hexadecyloxy-2-cyano
anthraquinone (91, Scheme 26) in one step. Further chemistry was attempted to hydrolyze
the nitrile to its respective amide and/or carboxylic acid. Irradiation of 91 did not yield the
expected dimer but formed aryl alkyl ketone 92. The crude NMR for this reaction was
strikingly clean (Figure 6) for a photoreaction. The broad singlet at 3.08 ppm was
attributed to the presence of hydrogen peroxide from the reduction of oxygen.
Hydrolysis of the nitrile in 91 via sulfuric acid and BF3•Et2O were both
unsuccessful and gave back starting material. When hydrolysis of the nitrile was attempted
under basic conditions, the 1-alkoxy group was hydrolyzed to the phenol while the nitrile
was left untouched. Hydrolysis of ketone 92 formed a mixture of products which were
attributed to decomposition of the starting material.
43
Figure 6. Irradiation of 1-hexadecyloxy-2-cyano-9,10-anthraquinone (91) formed aryl
alkyl ketone 92. The broad singlet at 3.08 ppm was attributed to the presence of hydrogen
peroxide from the reduction of oxygen.
44
3.2.2 1-Hexadecyloxy-2-phenyl-9,10-anthraquinone
Suzuki coupling of 86 with phenyl boronic acid gave 93 in 24% yield (Scheme 27,
Top). Suzuki coupling of triflate 94 with the same boronic acid was unsuccessful in
synthesizing 93 under the same conditions (Scheme 27, Bottom). Irradiation of coupled
product 93 formed a non-ketone and non-dimer product that was not structurally identified
due to product complexity; however based on crude NMR data it is speculated that radical
reactions with the aryl π-bonds led to an unexpected set of products similar to the
photochemistry of 98 (Schemes 30 & 31).
45
3.2.3 Other Attempts at Synthesis with 1-Hexadecyloxy-2-iodo-9,10-anthraquinone
Sonogashira coupling of 1-hexadecyloxy-2-iodo-9,10-anthraquinone (86) with two
different alkynes, propargyl trimethylsilane and 2-methylbut-3-yn-2-ol were unsuccessful,
returning starting anthraquinone (Scheme 28). Nucleophilic aromatic substitution of the
iodide with butylamine and potassium hydroxide were also unsuccessful and returned
starting material.
3.3 Via 1-Allyloxy-9,10-anthraquinone and Related Attempts
Claisen rearrangement of 1-allyloxy-9,10-anthraquinone (95) afforded 1-hydroxy-
2-allyl-9,10-anthraquinone (96, Scheme 29). The anthraquinone was reduced with sodium
dithionite to accelerate the Claisen by transforming the electron withdrawing carbonyls to
electron donating alcohols. 96 was reduced via catalytic hydrogenation to form 1-hydroxy-
2-n-propyl-9,10-anthraquinone (97).
46
3.3.1 1-Hexadecyloxy-2-(1-propenyl)-9,10-anthraquinone
Alkylation of 96 in one step with 1-bromohexadecane was achieved (Scheme 30).
During alkylation π-bond migration led to 1-hexadecyloxy-2-prop-1-enyl-9,10-
anthraquinone (98) as the major product instead of the allyl isomer. Irradiation of 98
formed a mixture of stereoisomers (99, Scheme 30). The diastereomers were inseparable
via chromatography. The proposed mechanism (Scheme 31) involves H-abstraction by the
alkene followed by ipso cyclization of the propyl radical and subsequent ring opening to
form the isopropyl group in 102. Biradical coupling followed by homolysis of the C-O
bond and H● transfer forms the observed product 99 as a mixture of stereoisomers.
47
3.3.2 1-Hexadecyloxy-2-n-propyl-9,10-anthraquinone
Alkylation of 1-hydroxy-2-n-propyl-9,10-anthraquinone (97, Scheme 32) with 1-
bromohexadecane yielded 1-hexadecyloxy-2-n-propyl-9,10-anthraquinone (105).
Irradiation of 105 in benzene formed the respective dimer (106).
3.4 Via Alizarin
Alizarin (IUPAC name 1,2-dihydroxy-9,10-anthraquinone) is a natural red dye
found in the plant Rubia cordifolia, and has been used for centuries as a dye for textiles.33
48
The 2-hydroxy group can be selectively alkylated due to its slightly higher acidity
compared to the H-bonded 1-hydroxy phenol (62, Scheme 33). 1-Hydroxy-2-methoxy-
9,10-anthraquinone (63) and 1-hydroxy-2-hexadecyloxy-9,10-anthraquinone (64) were
synthesized from alizarin as shown in Scheme 33, followed by either Williamson ether
synthesis34 or a Mitsunobu reaction35 to alkylate the 1-position as demonstrated later in this
chapter.
3.4.1 1-((3,7-dimethyloct-6-en-1-yl)oxy)-2-methoxy-9,10-anthraquinone
Synthesis of 1-((3,7-dimethyloct-6-en-1-yl)oxy)-2-methoxy-9,10-anthraquinone
(108, Scheme 34) was achieved in one step via Mitsunobu reaction34 of β-citronellol with
1-hydroxy-2-methoxy-9,10-anthraquinone (63). Anaerobic irradiation of 108 in benzene
yielded the expected dimer 109 along with the released alkanes 110 and 111.
49
3.4.2 1-Phenethyloxy-2-hexadecyloxy-9,10-anthraquinone
Synthesis of 1-phenethyloxy-2-hexadecyloxy-9,10-anthraquinone (112, Scheme
35) was achieved in one step via substitution reaction of phenethyl bromide with 1-
hydroxy-2-hexadecyloxy-9,10-anthraquinone (107). Anaerobic irradiation of 112 in
benzene yielded the expected dimer 113 and toluene.
3.4.3 1-Hexadecyloxy-2-methoxymethyl-9,10-anthraquinone
Synthesis of 1-hexadecyloxy-2-methoxymethyl-9,10-anthraquinone (115, Scheme
36) was achieved in one step via substitution reaction of 1-bromohexadecane with 1-
50
hydroxy-2-methoxymethyl-9,10-anthraquinone (114). 114 was synthesized in one step
from alizarin and methoxymethyl chloride. Anaerobic irradiation of 115 in benzene yielded
the expected dimer 116 and pentadecane.
3.4.4 1-Hexadecyloxy-2-hydroxy-9,10-anthraquinone
1-Hexadecyloxy-2-hydroxy-9,10-anthraquinone (117) was synthesized from 1-
hexadecyloxy-2-methoxymethyl-9,10-anthraquinone (115) via acid hydrolysis of the
MOM group (Scheme 37, top). Anaerobic irradiation of 117 in benzene yielded 2-
hydroxy-1-palmitoyl-9,10-anthraquinone (118). The formation of 118 can potentially be
explained by reversible abstraction by the aryl-alkyl ketone formed (119, Scheme 37,
bottom).
51
3.4.5 1-Hexadecyloxy-9,10-anthraquinon-2-yl trifluoromethanesulfonate
Synthesis of 1-hexadecyloxy-9,10-anthraquinon-2-yl trifluoromethanesulfonate
(94, Scheme 38) was achieved via triflation of the phenolic oxygen of 1-hexadecyloxy-2-
hydroxy-9,10-anthraquinone (117). Anaerobic irradiation of 94 yielded 1-hexadecyloxy-
2-hydroxy-9,10-anthraquinone (117), presumably via homolysis of the S-O bond.
52
3.4.6 1-n-Propyloxy-2-hexadecyloxy-9,10-anthraquinone
Synthesis of 1-n-propyloxy-2-hexadecyloxy-9,10-anthraquinone (120, Scheme 39)
was achieved in one step via substitution reaction of 1-bromopropane with 1-hydroxy-2-
hexadecyloxy-9,10-anthraquinone (107). Anaerobic irradiation of 120 in benzene yielded
the expected dimer 113.
3.4.7 1-Hexadecyloxy-9,10-anthraquinon-2-yl acetate
Synthesis of 1-hexadecyloxy-9,10-anthraquinon-2-yl acetate (121, Scheme 40)
was achieved in one step via acylation of 1-hexadecyloxy-2-hydroxy-9,10-anthraquinone
(117) with acetyl chloride. Anaerobic irradiation of 121 in benzene yielded a complex
mixture of products which were not further investigated.
53
3.4.8 Attempts to Synthesize 1-Hexadecyloxy-9,10-anthraquinon-2-yl pivalate
Synthesis of 1-(hexadecyloxy)-9,10-anthraquinon-2-yl pivalate (Scheme 41) was
attempted via acylation of alizarin (62) with pivaloyl chloride followed by alkylation of
122 with bromohexadecane. However, the alkylation resulted in migration of the pivalate
group to the 1- position and alkylation of the 2- position, forming 2-hexadecyloxy-9,10-
anthraquinon-1-yl pivalate (123). This was determined via hydrolysis of the ester in 123 to
form the corresponding 1-hydroxy-2-hexadecyloxy-9,10-anthraquinone. Anaerobic
irradiation of 123 in benzene resulted in no reaction.
3.5 Conclusions
The results of all the anthraquinone irradiations are summarized in Table 2. The
results suggest that the dominant reaction pathway (formation of ketone 124 or dimer 125)
is influenced by both the sterics and electronics of the 2- substituent. Electron donating
alkoxy groups and alkyl groups on the 2- position allow for formation of dimer 125 upon
anaerobic irradiation in benzene, while the electron withdrawing nitrile group yielded
54
ketone 124 as the major product. With no substituent on the 2- position (R’ = H) the major
irradiation product is consistently ketone 124, and there are several examples of direct
analogs forming dimer when a 2-alkoxy group is present (i.e. 126 vs 129). Further, if the
1-alkyl substituent is methyl or phenyl (127 - 130, Table 2), then the presence of a 2-
substituent has no effect on the reaction and ketone 124 is always observed. This suggests
that the ability of the 1- position R group to homolyze heavily influences the reaction fate.
Table 2. Irradiation of 36 yields dimer 125, ketone 124, or other products
not shown.
Entry Compound R= R’= Irradiation
Product
1 120 Et OC16H33 125 + RH
2 126 C15H31 OC16H33 125 + RH
3 115 C15H31 OMOM 125 + RH
4 105 C15H31 n-Pr 125 + RH
5 112 Bn OC16H33 125 + RH
6 108
OMe 125 + RH
7 127 Me OC16H33 124
8 128 Ph OC16H33 124
9 129 C15H31 H 124
10 130 Bn H 124
11 91 C15H31 CN 124
12 117 C15H31 OH 124
13 121 C15H31 OAc Other
14 98 C15H31 Other
15 93 C15H31 Ph Other
16 94 C15H31 OTf Other
17 87 C15H31 I Other
55
3.6 Experimental Procedures
3.6.1 General Methods
Unless otherwise indicated, all reagents were commercially purchased from Sigma-
Aldrich and used without further purification, or prepared as described below. Solvents
were purified by passing over an alumina column. TLC was performed on fluorescein
doped aluminum backed silica gel plates, 200 μm thick. Preparative TLC was performed
using fluorescein doped glass backed silica gel plates, 500 μm thick. All TLC was
visualized with 254 nm or 366 nm light unless otherwise indicated. Column
chromatography was performed using silica gel, 60 Å pore size 40-63 μm particle size, or
by basic alumina when indicated, 60-325 mesh, Brockman activity I. 1H NMR spectra were
recorded using a 300 MHz Bruker DPX spectrometer with a qnp 5mm probe operating
TopSpin 1.3, and a 500 MHz Bruker DRX spectrometer using either a bbo 5mm or tbi
5mm probe operating TopSpin 1.3. 13C NMR spectra were also recorded on the
aforementioned spectrometers at 75.48 and 125.77 MHz, respectively. Chemical shifts are
reported in parts per million (δ) relative to residual deuterated solvents (CDCl3 or C6D6).
Coupling constants (J values) are reported in hertz (Hz).
3.6.2 Synthetic Methods
Synthesis of 1-Hydroxy-2-iodo-9,10-anthraquinone (87).32 A solution of iodine (1.12 g,
4.4 mmol) and iodic acid (1.76 g, 10 mmol) in water (20 mL) was added to a solution of
56
1-hydroxy-9,10-anthraquinone (2.24 g, 10 mmol) in dioxane (60 mL) at 80 °C. The
reaction was refluxed for 2.5 hours, after which it was cooled to room temperature and
poured into 300 mL of water. The resulting precipitate was filtered off and recrystallized
out of a dioxane/water mixture (89%). 1H NMR (300 MHz, CDCl3): δ 13.52 ppm (s, 1H),
8.38 – 8.27 (m, 2H), 8.20 (d, 1H, J = 8.05 Hz), 7.90 – 7.80 (m, 2H), 7.58 (d, 1H, J = 8.05
Hz). 13C{1H} NMR (125 MHz, CDCl3): δ 188.44 ppm, 181.97, 161.21, 146.30, 135.08,
134.42, 133.48, 133.38, 132.55, 127.48, 127.21, 120.56. HRMS (APCI) calc’d for
C14H7IO3H+: 350.9518. Found: 350.9511.
Synthesis of 1-Hexadecyloxy-2-cyano-9,10-anthraquinone (91).36 Cuprous cyanide
(234 mg, 2.61 mmol) was added to a solution of 1-hexadecyloxy-2-iodo-9,10-
anthraquinone (500 mg, 0.87 mmol) in DMF (25 mL). The reaction was stirred under an
argon atmosphere at 110 °C for 14 hours. The reaction was poured into a flask containing
diethyl ether and washed with water (x3). The organic layer was separated, dried with
MgSO4, and concentrated via rotary evaporation (91%). 1H NMR (300 MHz, CDCl3): δ
8.34 – 8.24 ppm (m, 2H), 8.18 (d, 1H, J = 8.0 Hz), 7.97 (d, 1H, J = 8.1 Hz), 7.89 – 7.76
(m, 2H), 4.26 (t, 2H, J = 6.7 Hz), 2.02 (p, 2H, J = 6.6 Hz), 1.66 – 1.50 (d, 2H, J = 13.4 Hz,
1H), 1.49 – 1.12 (m, 24H), 0.88 (t, 3H, J = 6.9 Hz). 13C{1H} NMR (125 MHz, CDCl3): δ
181.99 ppm, 180.95, 162.61, 138.33, 138.16, 134.91, 134.34, 134.13, 132.23, 127.50,
127.07, 126.54, 123.01, 115.28, 115.22, 31.93, 30.22, 29.72, 29.70, 29.68, 29.67, 29.64,
29.58, 29.45, 29.37, 25.72, 22.70, 14.13. HRMS (ESI) calc’d for C31H39NO3H+: 474.3008.
Found: 474.3001.
57
Synthesis of 1-Hexadecyloxy-2-phenyl-9,10-anthraquinone (93).37 Catalytic tetrakis
(triphenylphosphine)palladium(0) was added to a degassed solution of 1-hexadecyloxy-2-
iodo-9,10-anthraquinone (121 mg, 0.21 mmol), tribasic potassium phosphate (65 mg,
0.31 mmol), and phenylboronic acid (30 mg, 0.25 mmol) in dioxane (150 mL). The
reaction was stirred at 80 °C for 14 hours before being quenched with 3 M sodium
hydroxide and 30% hydrogen peroxide. The reaction was extracted with dichloromethane
(50 mL x3) and the organic layer was dried with MgSO4 before being concentrated via
rotary evaporation. The resulting compound was then purified via flash chromatography
eluting a gradient from 100% hexane to 50% dichloromethane/hexane (24%). 1H NMR
(300 MHz, CDCl3): δ 8.35 – 8.24 ppm (m, 2H), 8.20 (d, 1H, J = 8.0 Hz), 7.84 – 7.71 (m,
3H), 7.66 – 7.56 (m, 2H), 7.51 – 7.37 (m, 3H), 3.67 (t, 2H, J = 6.6 Hz), 1.66 – 1.50 (m,
2H), 1.36 – 1.05 (m, 26H), 0.93 – 0.82 (m, 3H). 13C NMR (125 MHz, CDCl3): δ 182.96
ppm, 182.49, 157.69, 143.90, 137.18, 136.03, 135.24, 134.76, 134.03, 133.30, 132.84,
129.43, 128.17, 128.10, 127.25, 126.80, 126.59, 123.32, 74.80, 31.87, 29.92, 29.64,
29.63, 29.60, 29.59, 29.51, 29.45, 29.27, 29.24, 25.70, 22.60, 13.95. HRMS (APCI)
calc’d for C36H44O3: 525.3369. Found: 525.3361.
General Procedure for the Synthesis of 1-Hydroxy-2-alkoxy-9,10-anthraquinones.38
K2CO3 (1.2 equiv) was added to a solution of alizarin (1 equiv) in dimethylformamide (10
mg anthraquinone/mL solvent). The mixture was stirred at room temperature for 5 minutes
before the alkyl halide (1.2 equiv) was added and stirred for 6 hours at room temperature.
The reaction was then quenched with 10% HCl and the precipitate was recrystallized out
of ethanol.
58
1-Hydroxy-2-methoxy-9,10-anthraquinone (63). 84%. 1H NMR (300 MHz, CDCl3): δ
13.04 ppm (s, 1H), 8.37 – 8.27 (m, 2H), 7.89 (d, 1H, J = 8.4 Hz), 7.83 – 7.77 (m, 2H), 7.19
(d, 1H, J = 8.4 Hz), 4.03 (s, 3H).
1-Hydroxy-2-hexadecyloxy-9,10-anthraquinone (107). 31%. 1H NMR (300 MHz,
CDCl3): δ 13.04 ppm (s, 1H), 8.39 – 8.26 (m, 2H), 7.86 (d, 1H, J = 8.4 Hz), 7.82 – 7.76
(m, 2H), 7.16 (d, 1H, J = 8.5 Hz), 4.15 (t, 2H, J = 6.7 Hz), 1.92 (p, 2H, J = 6.8 Hz), 1.50
(2H, p, J = 7.1 Hz), 1.26 (s, 24H), 0.95 – 0.82 (m, 3H). 13C{1H} NMR (125 MHz, CDCl3):
δ 189.17 ppm, 181.46, 153.71, 153.02, 134.69, 134.15, 133.70, 133.41, 127.34, 126.87,
125.06, 121.06, 116.71, 116.11, 69.46, 31.93, 29.71, 29.68, 29.66, 29.59, 29.53, 29.37,
29.36, 28.92, 25.93, 22.70, 14.13. HRMS (APCI) calc’d for C30H40O4H+: 465.2999.
Found: 465.2999.
Synthesis of 1-Hydroxy-2-methoxymethyl-9,10-anthraquinone (114).39 Chloromethyl
methyl ether (0.74 mL, 1.1 equiv) was added to a solution of alizarin (2g, 1 equiv) and
diisopropylethylamine (1.70 mL, 1.1 equiv) in dichloromethane (500 mL). The reaction
was stirred at room temperature for 22 hours before being quenched with saturated sodium
bicarbonate (100 mL). The organic layer was dried with MgSO4 and concentrated via
rotary evaporation and finally recrystallized out of ethanol (85%). 1H NMR (300 MHz,
CDCl3): δ 13.00 ppm (s, 1H), 8.36 – 8.27 (m, 2H), 7.85 (d, 1H, J = 8.4 Hz), 7.83 – 7.76
(m, 2H), 7.48 (d, 1H, J = 8.5 Hz), 5.38 (s, 2H), 3.56 (s, 3H).
59
General Procedure for Williamson Ether Synthesis.17 A solution of tetrabutyl
ammonium fluoride (3 equiv, 1M in THF) was added to a solution of 1-hydroxy-2-iodo-
9,10-anthraquinone (1 equiv), 1-bromohexadecane (2 equiv), and catalytic sodium iodide
in DMF (10 mg anthraquinone/mL solvent). The resulting solution was gently heated and
stirred for 48 hours, allowed to cool before pouring the reaction into water and extracting
with diethyl ether. The organic layer was then poured through a plug of basic alumina
eluting diethyl ether and the filtrate was concentrated via rotary evaporation. The resulting
solid was recrystallized out of ethanol.
1,2-Dihexadecyloxy-9,10-anthraquinone (126). 1H NMR (CDCl3, 300 MHz): δ 8.31 –
8.20 ppm (m, 2H), 8.12 (d, 1H, J = 8.6 Hz), 7.83 – 7.69 (m, 2H), 7.22 (d, 1H, J = 8.7 Hz),
4.09 (m, 4H), 2.03 – 1.79 (m, 4H), 1.64 – 1.46 (m, 4H), 1.44 – 1.18 (m, 44H), 0.88 (t, 6H,
J=6.2 Hz) ppm. 13C NMR (125 MHz, CDCl3): δ 182.53 ppm, 182.40, 158.94, 149.40,
135.37, 133.57, 133.18, 133.12, 127.32, 127.25, 127.09, 126.52, 124.76, 116.90, 74.17,
69.30, 31.87, 30.30, 29.67, 29.64, 29.60, 29.57, 29.55, 29.31, 29.28, 29.18, 26.05, 26.02,
22.59, 13.95. HRMS (APCI) calc’d for C46H72O4H+: 689.5503. Found: 689.5504.
1-Hexadecyloxy-2-iodo-9,10-anthraquinone (87). 44%. 1H NMR (300 MHz, CDCl3): δ
8.32 – 8.20 ppm (m, 3H), 7.84 (d, 1H, J = 8.20 Hz), 7.82 – 7.73 (m, 2H), 4.04 (t, 2H, J =
6.74 Hz), 2.04 (p, 2H, J = 6.83 Hz), 1.60 (p, 2H, J = 7.01 Hz), 1.50 – 1.15 (m, 18H), 0.88
(t, 3H, 6.8 Hz). 13C{1H} NMR (125 MHz, CDCl3): δ 182.77 ppm, 181.61, 159.09, 144.80,
135.80, 134.45, 134.32, 133.74, 132.45, 127.40, 126.74, 125.96, 124.68, 104.72, 75.14,
31.94, 30.23, 29.72, 29.71, 29.68, 29.64, 29.60, 29.37, 26.00, 22.70, 14.13.
60
1-Hexadecyloxy-2-n-propyl-9,10-anthraquinone (105). 1H NMR (300 MHz, CDCl3): δ
8.33 – 8.20 ppm (m, 3H), 8.07 (d, 1H, J = 7.9 Hz), 7.79 – 7.71 (m, 2H), 7.60 (d, 1H, J =
7.9 Hz), 3.96 (t, 2H, J = 6.6 Hz), 2.87 – 2.68 (m, 2H), 1.96 (p, 2H, J = 6.8 Hz), 1.78 – 1.63
(m, 2H), 1.48 – 1.17 (m, 26H), 1.00 (t, J = 7.3 Hz, 3H), 0.88 (t, J = 6.0 Hz, 3H).
1-Phenethyloxy-2-hexadecyloxy-9,10-anthraquinone (112). 14%. 1H NMR (300 MHz,
CDCl3): δ 8.29 – 8.21 ppm (m, 2H), 8.12 (d, 1H, J = 8.6 Hz), 7.80 – 7.72 (m, 2H), 7.42 –
7.15 (m, 6H), 4.32 (t, 2H, J = 7.5 Hz), 4.07 (t, 2H, J = 6.5 Hz), 3.31 (t, 2H, J = 7.5 Hz),
1.84 (p, 2H, J = 6.6 Hz), 1.57 – 1.40 (m, 2H), 1.41 – 1.17 (m, 24H), 0.88 (t, 3H, J = 7.0
Hz).
1-Hexadecyloxy-2-methoxymethyl-9,10-anthraquinone (115). 70%. (1H NMR (CDCl3,
300 MHz): δ 8.30 – 8.20 ppm (m, 2H), 8.11 (d, 1H, J = 8.7 Hz), 7.78 – 7.71 (m, 2H),
7.49 (d, 1H, J = 8.7 Hz), 5.32 (s, 2H), 4.10 (t, 2H, J = 6.8 Hz), 3.54 (s, 3H), 1.95 (p, 2H, J
= 6.9 Hz), 1.62 – 1.47 (m, 2H), 1.47 – 1.17 (m, 18H), 0.88 (t, 3H, J = 6.9 Hz) ppm. 13C
NMR (125 MHz, CDCl3): δ 182.33 ppm, 156.90, 149.91, 135.23, 133.68, 133.24, 132.96,
128.79, 127.48, 127.09, 126.55, 124.50, 120.42, 95.13, 74.50, 56.48, 30.23, 29.63, 29.62,
29.58, 29.47, 25.90, 22.59, 13.95. HRMS (ESI) calc’d for C32H44O5H+: 509.3262.
Found: 509.3260.
2-Hexadecyloxy-9,10-anthraquinon-1-yl Pivalate (123). 1H NMR (300 MHz, CDCl3): δ
8.29 – 8.20 ppm (m, 3H), 7.82 – 7.69 (m, 2H), 7.27 (d, 1H, J = 8.8 Hz), 4.07 (t, 2H, J = 6.4
61
Hz), 1.82 (p, 2H, J = 6.6 Hz), 1.50 (s, 9H), 1.50 – 1.40 (m, 2H) (s, 24H), 0.94 – 0.83 (t,
3H, J = 6.9 Hz).
Synthesis of 1-Hydroxy-9,10-anthraquinon-2-yl Pivalate (122).40 Pivaloyl chloride
(6.44 mL, 1.2 equiv) was added dropwise to a solution of alizarin (10.55g, 1 equiv),
triethylamine (7.32 mL, 1.2 equiv), and DMAP (536 mg, 0.1 equiv) in dichloromethane
(250 mL). The reaction was stirred at room temperature for 40 hours, after which it was
quenched with a solution of NaHSO4 (100 mL, 0.5 M). The aqueous layer was extracted
with DCM (250 mL x3) and the organic layer was dried with magnesium sulfate and
concentrated via rotary evaporation. The resulting yellow solid was purified via flash
chromatography eluting a gradient of 20% DCM in hexane to 100% DCM (35%). 1H NMR
(300 MHz, CDCl3): δ 12.71 ppm (s, 1H), 8.38 – 8.27 (m, 2H), 7.87 (d, J = 8.2 Hz, 1H),
7.84 – 7.79 (m, 2H), 7.44 (d, J = 8.2 Hz, 1H), 1.43 (s, 9H).
General Procedure for Mitsunobu Reactions.35 The appropriate alcohol (1 equiv) was
added to a reaction solution of the appropriate anthraquinone (1 equiv) and
triphenylphosphine (1.3 equiv) in 50/50 THF/toluene (10 mg anthraquinone/mL solvent).
Diisopropylazadicarboxylate (DIAD, 1.3 equiv) was added at 0 °C before being allowed
to warm to room temperature and stir for 24 hours. The solution was then concentrated via
rotary evaporation and purified via flash chromatography using a solvent gradient from
100% hexane to 100% DCM.
62
1-((3,7-dimethyloct-6-en-1-yl)oxy)-2-methoxy-9,10-anthraquinone (108). 53%. 1H
NMR (300 MHz, CDCl3): δ 8.32 – 8.19 ppm (m, 2H), 8.14 (d, 1H, J = 8.6 Hz), 7.81 –
7.67 (m, 2H), 7.24 (d, 1H, J = 8.9 Hz), 5.14 (ddq, 1H, J = 8.6, 5.7, 1.4 Hz), 4.12 (d, 2H, J
= 7.2 Hz), 3.97 (s, 3H), 2.15 – 1.93 (m, 3H), 1.88 – 1.72 (m, 2H), 1.68 (d, 3H, J = 1.4
Hz), 1.62 (d, 3H, J = 1.4 Hz), 1.56 – 1.39 (m, 1H), 1.33 – 1.16 (m, 1H), 1.01 (d, 3H, J =
6.3 Hz). 13C NMR (125 MHz, CDCl3) δ 182.62 ppm, 182.49, 159.32, 149.12, 135.20,
133.79, 133.40, 132.97, 131.09, 127.36, 127.17, 127.12, 126.60, 125.04, 124.93, 115.95,
72.60, 56.23, 37.26, 37.14, 29.49, 25.75, 25.56, 19.53, 17.66. HRMS (ESI) calc’d for
C25H28O4Na+: 415.1885. Found: 415.1880.
Synthesis of 1-hexadecyloxy-2-hydroxy-9,10-anthraquinone (117).41 A solution of
50% HCl/H2O (250 mL) was added to a solution of 1-hexadecyloxy-2-methoxymethyl-
9,10-anthraquinone (7g, 13.7 mmol) in THF (750 mL). The reaction was stirred at room
temperature for 5 days before being quenched with saturated sodium bicarbonate. The
aqueous layer was extracted with ethyl acetate and the organic layer washed with water,
dried with MgSO4 and concentrated via rotary evaporation (75%). 1H NMR (CDCl3, 300
MHz): δ 8.33 – 8.21 ppm (m, 2H), 8.13 (d, 1H, J = 8.5 Hz), 7.87 – 7.69 (m, 2H), 7.35 (d,
1H, J = 8.5 Hz), 6.66 (s, 1H), 4.12 (t, 2H, J = 6.9 Hz), 1.93 (p, 2H, J = 7.0 Hz), 1.57 –
1.44 (m, 2H), 1.43 – 1.17 (m, 20H), 0.88 (t, 3H, J = 6.6 Hz) ppm. 13C NMR (125 MHz,
CDCl3): δ 182.48 ppm, 181.99, 155.74, 145.86, 134.60, 133.60, 133.57, 133.02, 127.58,
126.98, 126.72, 125.75, 125.43, 119.85, 75.72, 30.39, 29.63, 29.62, 29.60, 29.57, 29.51,
29.47, 29.38, 29.27, 25.84, 22.59, 13.95. HRMS (APCI) calc’d for C30H40O4H+:
465.2999. Found: 465.2996.
63
Synthesis of 1-Hexadecyloxy-9,10-anthraquinon-2-yl trifluoromethanesulfonate
(94).29 Trifluoromethanesulfonic anhydride (0.05 mL, 1.1 equiv) was added to a solution
of 1-hexadecyloxy-2-hydroxy-9,10-anthraquinone (130 mg, 1 equiv), pydridine (1.1
equiv), and catalytic DMAP (5 mg) in dichloromethane (50 mL). The reaction was stirred
at room temperature for 20 hours, after which it was quenched with 10% HCl (25 mL).
The organic layer was washed with water and dried with magnesium sulfate before being
concentrated via rotary evaporation. The resulting yellow solid was the recrystallized out
of hot ethanol (29%). 1H NMR(CDCl3, 300 MHz): δ 8.33 – 8.23 ppm (m, 2H), 8.21 (d,
1H, J = 8.6 Hz), 7.88 – 7.74 (m, 2H), 7.65 (d, 1H, J = 8.6 Hz), 4.14 (t, 2H, J = 7.0 Hz),
2.00 (p, 2H, J = 7.1 Hz), 1.64 – 1.44 (m, 2H), 1.44 – 1.16 (m, 24H), 0.88 (t, 3H, J = 6.9,
6.3 Hz) ppm.
Synthesis of 1-Hexadecyloxy-9,10-anthraquinon-2-yl acetate (121).42 Acetyl chloride
(0.45 mL, 6.09 mmol) was added to a solution of 1-hexadecyloxy-2-hydroxy-9,10-
anthraquinone (538 mg, 1.16 mmol) and triethylamine (1.7 mL, 12.18 mmol) in DMF (50
mL). The addition of the acid chloride cause the solution to change from a deep red to
orange). The reaction was gently heated for 4 hours before being quenched with 10% HCl
and extracted with Et2O. The organic layer was washed with water and dried with
magnesium sulfate followed by concentration via rotary evaporation. The resulting solid
was recrystallized out of acetone (67%). 1H NMR (300 MHz, CDCl3): δ 8.32 – 8.23 ppm
(m, 2H), 8.16 (d, 1H, J = 8.4 Hz), 7.82 – 7.74 (m, 2H), 7.49 (d, 1H, J = 8.4 Hz), 4.05 (t,
64
2H, J = 6.7 Hz), 2.38 (s, 3H), 1.89 (p, 2H, J = 6.9 Hz), 1.58 – 1.44 (m, 2H), 1.43 – 1.15
(m, 24H), 0.88 (t, 3H, J = 6.6 Hz).
3.6.3 Photochemistry Methods
Unless otherwise indicated, anthraquinones (1.74 mM in benzene) were irradiated
with a 16 lamp rayonet reactor (peak emission 419 nm) for 16 hours in a roundbottom flask
charged with a magnetic stirbar. Anthraquinones were left on high vacuum for 30 minutes
followed pump/backfilling with argon three times before the addition of benzene.
Glassware and stirbars were oven dried prior to use. Benzene was distilled and left over
sieves (3Å) for 48 hours under an argon atmosphere. The reaction mixture (anthraquinone
and benzene) was sparged with argon for 30 minutes prior to irradiation.
65
Hexadecyloxy dimer (113). HRMS (APCI) calc’d for C62H78O8H+: 951.5769. Found:
951.5736. 1H NMR data shown below (300 MHz, CDCl3):
66
Methoxymethyl dimer (116). 1H NMR data shown below (300 MHz, CDCl3):
67
Methoxy dimer (109). HRMS (ESI) calc’d for C32H40O4Na+: 553.0899. Found: 553.0894.
1H NMR data shown below (500 MHz, CDCl3):
68
2-Hydroxy-1-palmitoyl-9,10-anthraquinone (118). 1H NMR (500 MHz, CDCl3): δ 8.39
– 8.30 ppm (m, 2H), 8.24 (dd, 1H, J = 7.4, 1.7 Hz), 8.15 – 7.97 (m, 1H), 7.90 – 7.79 (m,
2H), 2.72 (t, 2H, J = 7.5 Hz), 1.80 (p, 2H, J = 7.5 Hz), 1.69 – 1.49 (m, 2H), 1.46 – 1.14 (m,
24H), 0.90 (t, 3H, J = 6.9 Hz). 13C{1H} NMR (125 MHz, CDCl3): δ 208.68 ppm, 183.84,
181.58, 158.85, 134.56, 134.03, 133.96, 133.36, 133.01, 131.24, 127.25, 127.21, 125.82,
123.03, 44.48, 31.93, 29.69, 29.66, 29.62, 29.46, 29.36, 29.09, 25.23, 22.69, 14.12. HRMS
(APCI) calc’d for C30H38O4H+: 463.2843. Found: 463.2845.
1-Hydroxy-2-(nonadec-3-en-2-yl)anthraquinone (99). NMR data is shown below.
69
1H NMR (500 MHz, CDCl3):
70
13C {1H} NMR (125 MHz, CDCl3)
71
COSY (500 MHz, CDCl3):
72
73
CHAPTER 4
INVESTIGATION OF THE DIMERIZATION MECHANISM OF 1,2-
DIALKOXY-9,10-ANTHRAQUINONES
4.1 Introduction
The experiments outlined in this chapter were designed to test the proposed
mechanisms for the photochemical rearrangements of 1,2-dialkoxy and 1-alkoxy
anthraquinones, specifically not involving the synthesis of proposed intermediates. J.
Young tube experiments involving the anaerobic irradiation of these anthraquinones tested
the proposed involvement of oxygen in the reaction. Previous experiments involving the
addition of an electrophile or nucleophile to the irradiated mixture, which were proposed
to support the proposed mechanism, were tested via exposure of purified dimer to similar
conditions. Furthermore, crossover experiments investigated the possibility of any redox
potentials unique to either 1-alkoxy or 1,2-dialkoxy anthraquinones. Finally, 1-alkoxy
anthraquinones were irradiated at wavelengths less than 419 nm (the standard for these
reactions) to ensure that the reaction was not limited by the ability of intermediates to
absorb at 419 nm.
74
4.2 J. Young Tube Experiments
Anaerobic irradiation of several anthraquinones in a sealed J. Young tube and
immediate NMR analysis was performed to test the proposed mechanisms for formation of
both 12 (Scheme 42) and 36 (Scheme 43). Specifically these experiments were designed
to investigate the formation of these proposed intermediates via air oxidation (as proposed).
If opening the reaction mixture to air is truly a step in both of the observed rearrangements,
irradiation and immediate NMR analysis via J. Young tube should allow for detection of
35 and 43 in the respective reactions. However, if ketone 15 and dimer 45 are detected in
their respective J. Young irradiations, this indicates the involvement of an oxidant other
than oxygen.
75
4.2.1 1,2-Dihexadecyloxy-9,10-anthraquinone
Anaerobic irradiation (419 nm, 16 hours) of 1,2-dihexadecyloxy-9,10-
anthraquinone (36, Scheme 44, Top) in d6-benzene followed by 1H NMR analysis showed
the formation of dimer 45 as a mixture of diastereomers. 1H NMR of the starting material
is shown in Figure 7, and the irradiation product, a nearly pure mixture of dimer
diastereomers, is shown in Figure 8, with nearly pure dimer shown in Figure 9. It is worth
mentioning that when the nearly pure diastereomer of dimer 36 was irradiated at 419 nm,
a mixture of diastereomers formed at approximately a 50:50 ratio (Figure 10). This is
achieved by homolysis of the elongated C-C dimer bond and recombination of the resulting
diradical (44, Scheme 44, Bottom). It is also significant that the presence of a large amount
of water (0.4 ppm, Figures 7, 8) had no effect on the outcome of the photoreaction.
76
77
Figure 7. 1H NMR of 1,2-Dihexadecyloxy-9,10-anthraquinone (36) in d6-benzene.
78
Figure 8. 1H NMR of the product of 1,2-dihexadecyloxy-9,10-anthraquinone irradiation in
d6-benzene as a mixture of diastereomers. The presence of a large amount of water (0.4
ppm) had no effect on the reaction.
79
Figure 9. 1H NMR of dimer 45 in d6-benzene. The dimer was purified via trituration and
significantly more of one diastereomers is found.
80
Figure 10. 1H NMR of dimer 45 after irradiation of the dimer solution shown in Figure 9
in d6-benzene.
81
4.2.2 1-Dodecyloxy-9,10-anthraquinone
Anaerobic irradiation (419 nm, 16 hours) of 2-dodecyloxy-9,10-anthraquinone (12,
Scheme 45) in d6-benzene followed by 1H NMR analysis showed the formation of ketone
15 prior to air exposure. Figure 11 shows the 1H NMR for the starting material (12), while
Figure 12 shows the 1H NMR of the irradiated product, mostly containing ketone 15.
Figure 13 is the 1H NMR of purified product 15.
82
Figure 11. 1H NMR of 1-dodecyloxy-9,10-anthraquinone (12) prior to irradiation.
83
Figure 12. 1H NMR of 1-dodecyloxy-9,10-anthraquinone (12) after irradiation, containing
mostly ketone 15.
84
Figure 13. 1H NMR of purified ketone 15.
85
4.3 Reactions of 2-Hexadecyloxy Dimer
It was previously thought that either a nucleophile or electrophile, added once
irradiation was complete, reacted with monomer unit 43 to form the respective products
(Scheme 46). The assumption of the presence of monomer 43 was tested by reacting pure
dimer 45 with a nucleophile and an electrophile.
4.3.1 Reaction with Dimethylamine
When dimer 45 was stirred in solution with dimethylamine, amide 131 was
identified as the major product (Scheme 47). The proposed mechanism for this addition
(Scheme 48) involves nucleophilic addition of the amine to the lactone, ring opening, and
dimer bond cleavage.
86
4.3.2 Reaction with Triflic Anhydride
Addition of triflic anhydride to a solution of dimer 45 in benzene did not yield
triflate 133 as expected (Scheme 49), and instead yielded a complex mixture of products
which could not be structurally identified. It is proposed that the observation of 133 as
shown in Scheme 46 arises from hydrolysis of dimer 45 (by wet triethylamine and/or wet
benzene), allowing for 134 to attack the triflic anhydride (Scheme 50). Special care was
taken to dry the solvent and the amine for the reaction shown in Scheme 49, so the triflated
product 133 is not observed.
87
4.4 Irradiation of 1-Dodecyloxy-9,10-anthraquinone with 1,2-Didodecyl-9,10-
anthraquinone
A second crossover experiment was designed to test the possibility of some
intermolecular effect allowing the dimerization reaction to occur. Anaerobic irradiation of
an equimolar solution of 1-dodecyloxy-9,10-anthraquinone (135) and 1,2-dihexadecyl-
9,10-anthraquinone (126) in benzene yielded the expected dimer (136) and ketone (137),
with no crossover products detected (Scheme 50).
88
4.5 Irradiation of 1-Dodecyloxy-9,10-anthraquinone at alternate wavelengths
It was hypothesized that formation of ketone 15 was the result of an intermediate
no longer absorbing the 419 nm light used during irradiation. Irradiation of 1-dodecyloxy-
9,10-anthraquinone (12) at 366 nm and 300 nm yielded the expected ketone 15 as the major
product (Scheme 51).
4.6 Synthesis and Irradiation of 2-Methoxy-1-palmitoyl-9,10-anthraquinone
Irradiation of 117 (as discussed in chapter 3) forms 2-hydroxy-1-palmitoyl-9,10-
anthraquinone (118), which was subsequently alkylated with iodomethane to form 2-
methoxy-1-palmitoyl-9,10-anthraquinone 138 (Scheme 52). Anaerobic irradiation (peak
emission 419 nm) of this anthraquinone in carbon tetrachloride forms dimer 109 and 1-
chloropentane (139), as confirmed by GC-MS and NMR (Figures 14 — 16). This suggests
that 138 is an intermediate in the photochemical dimerization of 1,2-dialkoxy-9,10-
anthraquinones and that the previously proposed 41 does not undergo type I cleavage.
89
90
Figure 14. GC-MS trace of the irradiation product of 2-methoxy-1-palmitoyl-9,10-
anthraquinone (138) showing the formation of 1-chloropentadecane (139).
91
Figure 15. 1H NMR of the irradiation product of 2-methoxy-1-palmitoyl-9,10-
anthraquinone (138) showing the formation of 1-chloropentadecane (139). The chemical
shifts highlighted exactly match literature values.43
92
Figure 16. Irradiation of 2-methoxy-1-palmitoyl-9,10-anthraquinone (138, red) compared
to purified 2-methoxy dimer (109, blue) shows the formation of dimer in the reaction
solution.
93
4.7 Irradiation of 1-((3,7-Dimethyloct-6-en-1-yl)oxy)-2-methoxyanthraquinone
Synthesis of 1-((3,7-Dimethyloct-6-en-1-yl)oxy)-2-methoxyanthraquinone (108)
was discussed in chapter 3. This anthraquinone was used to measure the rate of H-
abstraction by released alkane 141 (Scheme 54). If 140 is the H-atom donor (as predicted
in the previously proposed mechanism from Chapter 1) the H-abstraction rate (rate2,
Scheme 54) is predicted to be fast, as both the released alkane 141 and H-atom donor 140
are assumed to be within the solvent cage and very reactive. However, if the H-atom donor
is outside the solvent cage (i.e. some other intermediate) then the rate of cyclization (rate1,
Scheme 54) would be expected to outcompete abstraction (rate2).
4.7.1 Approximation of the Rate of Hydrogen Abstraction in the Proposed
Mechanism
If both cyclization (formation of 143) and abstraction (formation of 111) are
assumed to be irreversible then the rate laws for cyclization (rate1, Equation 5) and H-
abstraction (rate2, Equation 6) are as shown below. The ratios of products 110 to 111 are
equal to a ratio of the rates (Equation 7), which, once simplified and rearranged, can be
solved for k2[142] (Equation 8).
The ratio of [111] to [110] was calculated via integration of the GC trace for the
respective compounds (Figure 17). When these values and k1 (calculated in 4.7.2,
Equation 12) are inserted into equation 8, k2[142] is found to be 1.8x104 s-1. This number
94
is much smaller than expected, indicating that either k2 or [142] are lower than expected.
k2 is expected to be fast due to the readily abstractable phenolic hydrogen in 142. In the
proposed mechanism the effective concentration of 142 should be high due to the spatial
proximity of the released alkyl radical (141) to the H-atom donor. The lower than expected
value for k2[142] suggests that the proposed mechanism is in need of revision. Specifically,
this suggests that 140 may not be the intermediate which undergoes alkyl radical
homolysis, and as a result 142 is not the H-atom donor.
rate1 = 𝑘1[𝟏𝟒𝟏] (Equation 5)
rate2 = 𝑘2[𝟏𝟒𝟏][𝟏𝟒𝟐] (Equation 6)
[𝟏𝟏𝟎]
[𝟏𝟏𝟏]=
rate1
rate2=
𝑘1[𝟏𝟒𝟏]
𝑘2[𝟏𝟒𝟏][𝟏𝟒𝟐] (Equation 7)
95
𝑘2[𝟏𝟒𝟐] = 𝑘1[𝟏𝟏𝟏]
[𝟏𝟏𝟎] (Equation 8)
𝑘2[𝟏𝟒𝟐] = (3.65 ∗ 106 s−1)3.92 ∗ 105 M
7.83 ∗ 107 M= (3.65 ∗ 106 s−1)(5 ∗ 10−3) = 1.8 ∗ 104 s−1
Figure 17. Integration of the peaks shown for 110 and 111 in the GC trace were used in
Equation 8.
4.7.2 Calculation of the Rate Constant for Cyclization of 141
The rate constant for cyclization of 141 (k1) was found via a similar experiment
with the Barton ester of citronellic acid (Scheme 55). Following the same relative rate
principles, Equations 9 and 10 can be expressed as a ratio (Equation 11), which can be
simplified and solved for k1 = 3.65x106 s-1 (Equation 12). The rate constant (k3) for H-
abstraction from Bu3SnH by a primary radical is known (k3 = 2.4 x 106 M-1 s-1).44
96
rate1 = 𝑘1[𝟏𝟒𝟏] (Equation 9)
rate3 = 𝑘3[𝟏𝟒𝟏][Bu3SnH] (Equation 10)
[𝟏𝟏𝟎]
[𝟏𝟏𝟏]=
rate1
rate3=
𝑘1[𝟏𝟒𝟏]
𝑘3[𝟏𝟒𝟏][Bu3SnH] (Equation 11)
𝑘1 =𝑘3[𝟏𝟏𝟎][Bu3SnH]
[𝟏𝟏𝟏] (Equation 12)
4.8 Conclusions
The results from the experiments discussed in this chapter suggest that the
previously proposed mechanism for the photorearrangements of 1,2-dihexadecyloxy-9,10-
anthraquinone (36) is incorrect and in need of revision. One potential explanation is the
97
oxidation step in both reactions occurs via redox with a quinone intermediate or starting
material. A revised mechanism is shown in Scheme 56. This mechanism is supported by
the formation of a dimer product upon irradiation of 2-methoxy-1-palmitoyl-9,10-
anthraquinone (138), a direct analog of proposed intermediate 146.
98
4.9 Experimental Procedures
4.9.1 General Methods
Unless otherwise indicated, all reagents were commercially purchased from Sigma-
Aldrich and used without further purification, or prepared as described below. Solvents
were purified by passing over an alumina column. TLC was performed on fluorescein
doped aluminum backed silica gel plates, 200 μm thick. Preparative TLC was performed
using fluorescein doped glass backed silica gel plates, 500 μm thick. All TLC was
visualized with 254 nm or 366 nm light unless otherwise indicated. Column
chromatography was performed using silica gel, 60 Å pore size 40-63 μm particle size, or
by basic alumina when indicated, 60-325 mesh, Brockman activity I. 1H NMR spectra were
recorded using a 300 MHz Bruker DPX spectrometer with a qnp 5mm probe operating
TopSpin 1.3, and a 500 MHz Bruker DRX spectrometer using either a bbo 5mm or tbi
5mm probe operating TopSpin 1.3. 13C NMR spectra were also recorded on the
aforementioned spectrometers at 75.48 and 125.77 MHz, respectively. Chemical shifts are
reported in parts per million (δ) relative to residual deuterated solvents (CDCl3 or C6D6).
Coupling constants (J values) are reported in hertz (Hz).
4.9.2 Synthetic Methods
Synthesis of 2-Hexadecyloxy-N,N-dimethyl-9,10-anthraquinon-1-yl-carboxamide
(131). A solution of dimethyl amine (37.5 μL, 33% in EtOH, 0.21 mmol) was added to a
99
degassed solution of 2-hexadecyloxy dimer (45, 10 mg, 0.0105 mmol) in benzene (15 mL).
A drop of acetic acid was added and the reaction was stirred for three hours before being
concentrated via rotary evaporation (41%). The crude NMR is below.
1H NMR data (300 MHz, CDCl):
Synthesis of 2-Methoxy-1-palmitoyl-9,10-anthraquinone (136).45 Iodomethane (5 μL,
1.10 equiv) was added to a solution of 2-hydroxy-1-palmitoyl-9,10-anthraquinone (35
mg, 0.76 mmol, 1 equiv) and cesium carbonate (25.4 mg, 1.05 equiv) in DMF (5 mL).
The reaction mixture was stirred at room temperature for 18 hours, after which additional
iodomethane (2 μL) was added and the reaction was allowed to stir for another 16 hours.
100
The reaction was then poured into water and extracted with diethyl ether. The organic
layer was concentrated via rotary evaporation before eluting through a plug of basic
alumina with Et2O. The resulting solution was concentrated via rotary evaporation and
recrystallized out of hexane (36%). 1H NMR (500 MHz, CDCl3): δ 8.40 (d, 1H, J = 8.6
Hz), 8.32 (dd, 1H, J = 7.3, 1.6 Hz), 8.24 (dd, 1H, J = 7.6, 1.6 Hz), 7.81 (dtd, 2H, J = 17.5,
7.4, 1.6 Hz), 7.33 (d, 1H, J = 8.8 Hz), 3.97 (s, 3H), 3.00 – 2.86 (m, 1H), 2.81 – 2.66 (m,
1H), 1.90 (p, J = 7.6 Hz, 2H), 1.51 – 1.41 (m, 2H), 1.42 – 1.23 (m, 27H), 0.90 (t, J = 6.9
Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 205.30 ppm, 183.18, 181.81, 160.21, 134.43,
133.95, 133.34, 133.26, 132.65, 131.78, 130.42, 127.44, 127.16, 126.81, 115.97, 56.37,
43.54, 31.93, 30.33, 29.71, 29.67, 29.61, 29.57, 29.37, 29.16, 23.38, 22.70, 14.13. HRMS
(APCI) cacl’d for C31H40O4H+: 477.2999. Found: 477.2997.
4.9.3 Photochemistry Methods
Unless otherwise indicated, anthraquinones (1.74 mM in benzene) were irradiated
with a 16 lamp rayonet reactor (peak emission 419 nm) for 16 hours in a roundbottom flask
charged with a magnetic stirbar. Anthraquinones were left on high vacuum for 30 minutes
followed by pump/backfilling with argon three times before the addition of benzene.
Glassware and stirbars were oven dried prior to use. Benzene was distilled and left over
sieves (3Å) for 48 hours under an argon atmosphere. The reaction mixture (anthraquinone
and benzene) was sparged with argon for 30 minutes prior to irradiation.
101
300 nm irradiation was performed with a 16 lamp rayonet reactor (peak emission
300 nm). 313 and 366 nm irradiation was performed using a 450W medium pressure
mercury lamp, or irradiated at 366 nm using the same lamp encased in a UO2-doped filter.
102
103
CHAPTER 5
SUMMARY OF ANTHRAQUINONE PROJECTS
The photochemistry of substituted anthraquinones has been thoroughly investigated
by the Jones group.17-19 It is known that irradiation of 1-alkoxy and 1-benzyloxy
anthraquinones in polar protic solvents releases an aldehyde14,15 and can be used to release
biologically active aldehydes.17 It was discovered that 1-alkoxy and 1-benzyloxy
anthraquinones (2-unsubstituted) form an entirely different product (ketone 15) and no
longer release the aldehyde group when irradiated in nonpolar solvents. A mechanism was
proposed for the observed rearrangement of 1-alkoxy and 1-benzyloxy anthraquinones to
ketone 15 (Scheme 9).
It was also discovered that 1,2-dialkoxy anthraquinones, when irradiated in
nonpolar solvents, undergo a slightly different photochemical rearrangement which
releases an alkane and forms a dimer (45) with an elongated C-C bond from the
anthraquinone moiety. Upon further investigation it was revealed that the alkyl group was
the result of photochemical release of a radical, and a mechanism was proposed for this
photochemical reaction (Scheme 10). The mechanism involved three separate photon
absorptions, multiple H-abstractions, and a Norrish Type I cleavage prior to dimerization.
It was found that both substituents could dictate the pathway of the photochemical
rearrangement. With a 2-alkoxy group, if the 1- alkoxy group was longer than ethyl the
dimerization pathway was observed. However, with 1-benzyloxy and 1-ethyloxy
substituents the ketone (15) forming pathway was observed regardless of the 2- substituent.
104
A set of experiments were designed to gain a better understanding of this photochemical
rearrangement.
First and foremost, the proposed mechanism for formation of dimer 45 from 1,2-
didodecyloxy-9,10-anthraquinone (36) has been proven incorrect. The detection of dimer
45 upon anaerobic irradiation of 36 rules out the proposed involvement of air to oxidize
43. The formation of dimethyl amide 131 upon addition of dimethyl amine to dimer 45
further supports the anaerobic formation of dimer 45 from irradiation of 1,2-dialkoxy
anthraquinones.
Additionally, the rate of H-abstraction by the released alkyl radical in the
photodimerization of 1,2-dialkoxy-9,10-anthraquinones was found to be significantly
slower than expected. (k2[142] = 1.8x104, k2 = rate constant of hydrogen abstraction). This
indicates that either k2 or [142] (or both) are lower than expected based on the previously
proposed mechanism and, as a result, the proposed mechanism is in need of revision.
Specifically, this suggests that 140 may not be an intermediate, and similarly 142 is not the
H-atom donor.
A new mechanism has been proposed for the photochemical rearrangement of 1,2-
dialkoxy anthraquinones. While much of the mechanism remains unchanged, it is proposed
that dihydroxyanthracene 40 is oxidized to anthraquinone 144 before undergoing Norrish
Type I cleavage. Immediate cyclization to form 44 and subsequent dimerization forms 45,
while the alkyl radical escapes the solvent cage and abstracts a hydrogen from the reduced
oxidant involved in the formation of 146 (Scheme 56). The involvement of intermediate
146 is supported by the formation of the corresponding dimer product upon irradiation of
105
2-methoxy-1-palmitoyl-9,10-anthraquinone (138), a direct analog of proposed
intermediate 146.
Lastly, the functional group tolerance for the dimerization of 1,2-dialkoxy
anthraquinones and release of RH was examined. Electron donating 2- substituents almost
always allowed the dimerization to occur, while withdrawing groups never led to dimer
formation and either formed ketone 36 or underwent a unique reaction pathway.
Additionally, many different 1-alkoxy (2-unsubstituted) anthraquinones and a variety of
irradiation conditions were tested. No 1-alkoxy anthraquinones were found to undergo the
dimerization pathway upon irradiation.
106
107
CHAPTER 6
VALIDATION OF THE FORMATION OF AQUATOLIDE VIA [2+2]
PHOTOCYCLOADDITION FROM ASTERISCUNOLIDE C
6.1 Introduction
The natural product aquatolide, found in the plant Asteriscus aquaticus, is thought
to be formed by an intramolecular [2+2] photoreaction of Asteriscunolide C.
Asteriscunolides A-D, also found in Asteriscus aquaticus, were isolated and irradiated to
test this hypothesis. Reactions were followed by GC-MS.
6.2 Irradiation of Asteriscunolides in Dicholoromethane
Pure solutions of asteriscunolides A-D (148-151), obtained from the Tantillo lab,
UC-Davis) in dichloromethane were irradiated at 366 nm. Irradiation of each
asteriscunolide formed aquatolide (152) while also undergoing E/Z isomerization to
eventually form all four asteriscunolides with the exception of asteriscunolide D (Scheme
58). The lack of asteriscunolide D was attributed to its high strain relative to the other
isomers. Prolonged irradiation of all asteriscunolides (> 32 hours) led to decomposition of
the asteriscunolides. Aquatolide is assumed to form via [2+2] photocycloaddition from
asteriscunolide C, with C2-C9 and C3-C10 bonds forming. For a concerted 4π
photocyclization to be allowed it must undergo a disrotatory motion. However, the
108
cyclization is likely stepwise and therefore the stereochemistry observed is likely due to
the product, aquatolide (152), being the less strained possibility. Full arrow pushing is
shown in Scheme 59. GC data for each asteriscunolides pure and after irradiation is shown
in Figures 18 and 19. Figures 20 and 21 show the rate of formation and disappearance of
each asteriscunolide and aquatolide upon irradiation of each pure asteriscunolide.
109
110
Figure 18. Overlaid GC traces of pure asteriscunolides and aquatolide.
111
Figure 19. GC-MS data after irradiation of asteriscunolide B for 32 hours in dichloromethane. The
MS shown is that of aquatolide, demonstrating the formation of aquatolide upon irradiation of the
asteriscunolides. Isomerization to other asteriscunolides is seen by the presence of each
asteriscunolide in the GC trace, with the exception of asteriscunolide D.
112
Figure 20. The four graphs below show the rate of formation and disappearance of each
asteriscunolide and aquatolide upon irradiation. The title of each graph indicates which
isomer was irradiated.
0
100
200
300
400
500
600
700
800
0 10 20 30 40
% S
tan
dar
d
Time (h)
Asteriscunolide A
Aquat
C
B
A sum
0
200
400
600
800
1000
1200
1400
0 10 20 30 40
% S
tan
dar
d
Time (h)
Asteriscunolide B
Aquat
C
B
A Sum
113
Figure 20 (Continued).
0
200
400
600
800
1000
1200
0 10 20 30 40
% S
tan
dar
d
Time (h)
Asteriscunolide C
Aquat
C
B
A Sum
0
500
1000
1500
2000
2500
0 10 20 30 40
% S
tan
dar
d
Time (h)
Astersicunolide D
Aquat
C
B
D
A Sum
114
Figure 21. The four graphs below show the formation of aquatolide upon irradiation of
each asteriscunolide. The title of each graph indicates which isomer was irradiated.
0
5
10
15
20
25
30
35
40
0 10 20 30 40
% S
tan
dar
d
Time (h)
Asteriscunolide A
Aquat
0
2
4
6
8
10
12
14
16
18
20
0 10 20 30 40
% S
tan
dar
d
Time (h)
Asteriscunolide B
Aquat
115
Figure 21 (continued).
0
5
10
15
20
25
30
35
40
0 10 20 30 40
% S
tan
dar
d
Time (h)
Asteriscunolide C
Aquat
0
10
20
30
40
50
60
0 10 20 30 40
% S
tan
dar
d
Time (h)
Astersicunolide D
Aquat
116
6.3 Irradiation of Asteriscunolides in Acetonitrile and the Discovery of a New
Photoproduct
When pure solutions of asteriscunolides A-D in acetonitrile were irradiated at the
same wavelength similar reactivity was observed in the formation of aquatolide (152) and
isomerization to form all four asteriscunolides (148-151). However, a previously
unobserved isomer was detected in the GC trace (Figure 22). Purification of the mystery
product via preparatory TLC was attempted but due to the extremely small amount of
material used during irradiation (< 50 mg) and the low product yield (< 5%) it was never
isolated. It is hypothesized based on a crude NMR (Figure 21) that the unknown product
was the result of a C2-C7/C3-C6 or C2-C6/C3-C7 closure due to the presence of two sets
of alkene peaks (Scheme 60).
117
Figure 22. GC-MS data for irradiation (32 hours) of asteriscunolide B in acetonitrile. The
new peak comes in at 21.116 minutes, and the mass spec for the molecule is shown.
118
Figure 23. NMR data for the newly created compound from asteriscunolide irradiation in
acetonitrile. The two alkene peaks suggest one of the structures highlighted in Scheme 60.
119
Scheme 60. All possible ring closures of asteriscunolides A-D, with the relevant C7/C3-C6 or C2-
C6/C3-C7 closures highlighted.
120
6.4 Summary
The formation of aquatolide (152) from irradiation of asteriscunolide C (151) was
demonstrated. This suggests that aquatolide is made photochemically from asteriscunolide
C in the plant Asteriscus aquaticus.
6.5 Experimental details
6.5.1 Photochemistry Methods
Asteriscunolides were set up as 2 mg/mL solutions in the indicated solvent (DCM,
Hexane, MeCN). Solvent was bubble degassed with Argon for 20 minutes prior to its
addition to a 4 mL vial containing the appropriate asteriscunolide and a magnetic stir bar.
Samples were either irradiated at 313 and 366 nm using a 450W medium pressure mercury
lamp, or irradiated at 366 nm using the same lamp encased in a UO2-doped filter.
Irradiation was stopped after the indicated time period and samples removed while 100 μL
aliquots were taken with disposable syringes for later GC-MS analysis.
6.5.2 Analytical Methods
Once irradiation was completed and prior to GC-MS analysis, a naphthalene
standard in HPLC acetone was prepared and used to dilute the asteriscunolide samples to
the appropriate concentration.
121
All samples were analyzed via gas chromatography/mass spectrometry on an
Agilent 7890A spectrometer with an Agilent 19091S column, 30 m x 250 μm x 0.25 μm.
The inlet was kept at 250 °C during a 50:1 split injection, while the oven was held at 100
°C for 3 minutes before being increased to 230 °C at 5 °C/min. He was used as the carrier
gas at a flow rate of 1.2 mL/min. The MS source and quadrupole were set at 230 °C and
150 °C, respectively.
1H NMR spectra were recorded using a 300 MHz Bruker DPX spectrometer with a
qnp 5mm probe operating TopSpin 1.3, and a 500 MHz Bruker DRX spectrometer using
either a bbo 5mm or tbi 5mm probe operating TopSpin 1.3.
122
123
CHAPTER 7
SUMMARY
The photochemistry of substituted anthraquinones has been thoroughly investigated
by the Jones group.17-19 It is known that irradiation of 1-alkoxy and 1-benzyloxy
anthraquinones in polar protic solvents releases an aldehyde14,15 and can be used to release
biologically active aldehydes.17 It was discovered that 1-alkoxy and 1-benzyloxy
anthraquinones (2-unsubstituted) form an entirely different product (ketone 15) and no
longer release the aldehyde group when irradiated in nonpolar solvents. A mechanism was
proposed for the observed rearrangement of 1-alkoxy and 1-benzyloxy anthraquinones to
ketone 15 (Scheme 9).
It was also discovered that 1,2-dialkoxy anthraquinones, when irradiated in
nonpolar solvents, undergo a slightly different photochemical rearrangement which
releases an alkane and forms a dimer (45) with an elongated C-C bond from the
anthraquinone moiety. Upon further investigation it was revealed that the alkyl group was
the result of photochemical release of a radical, and a mechanism was proposed for this
photochemical reaction (Scheme 10). The mechanism involved three separate photon
absorptions, multiple H-abstractions, and a Norrish Type I cleavage prior to dimerization.
It was found that both substituents could dictate the pathway of the photochemical
rearrangement. With a 2-alkoxy group, if the 1- alkoxy group was longer than ethyl the
dimerization pathway was observed. However with 1-benzyloxy and 1-ethyloxy
substituents the ketone (15) forming pathway was observed regardless of the 2- substituent.
124
A set of experiments were designed to gain a better understanding of this photochemical
rearrangement.
First and foremost, the proposed mechanism for formation of dimer 45 from 1,2-
didodecyloxy-9,10-anthraquinone (36) has been proven incorrect. The detection of dimer
45 upon anaerobic irradiation of 36 rules out the proposed involvement of air to oxidize
43. The formation of dimethyl amide 131 upon addition of dimethyl amine to dimer 45
further supports the anaerobic formation of dimer 45 from irradiation of 1,2-dialkoxy
anthraquinones.
Additionally, the rate of H-abstraction by the released alkyl radical in the
photodimerization of 1,2-dialkoxy-9,10-anthraquinones was found to be significantly
slower than expected. (k2[142] = 1.8x104, k2 = rate constant of hydrogen abstraction). This
indicates that either k2 or [142] (or both) are lower than expected based on the previously
proposed mechanism and, as a result, the proposed mechanism is in need of revision.
Specifically, this suggests that 140 may not be an intermediate, and similarly 142 is not the
H-atom donor.
A new mechanism has been proposed for the photochemical rearrangement of 1,2-
dialkoxy anthraquinones. While much of the mechanism remains unchanged, it is proposed
that dihydroxyanthracene 40 is oxidized to anthraquinone 144 before undergoing Norrish
Type I cleavage. Immediate cyclization to form 44 and subsequent dimerization forms 45,
while the alkyl radical escapes the solvent cage and abstracts a hydrogen from the reduced
oxidant involved in the formation of 146 (Scheme 56). The involvement of intermediate
146 is supported by the formation of the corresponding dimer product upon irradiation of
125
2-methoxy-1-palmitoyl-9,10-anthraquinone (138), a direct analog of proposed
intermediate 146.
Lastly, the functional group tolerance for the dimerization of 1,2-dialkoxy
anthraquinones and release of RH. Electron donating 2- substituents almost always allowed
the dimerization to occur, while withdrawing groups never led to dimer formation and
either formed ketone 36 or underwent a unique reaction pathway. Additionally, many
different 1-alkoxy anthraquinones and a variety of irradiation conditions were tested. No
1-alkoxy anthraquinones were found to undergo the dimerization pathway upon irradiation.
Chapter 6, involving the irradiation of asteriscunolides A-D, found that natural
product aquatolide (150) can be formed photochemically via [2+2] photocycloaddition
from asteriscunolide C (149). This suggests that aquatolide is made photochemically from
asteriscunolide C in the plant Asteriscus aquaticus.
126
127
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135
APPENDIX A
Figure A1. Crystal Structure of 93 (C36H44O3).
Experimental.
A clear pale yellow plate-like specimen of C36H44O3, approximate dimensions
0.030 mm x 0.290 mm x 0.320 mm, was used for the X-ray crystallographic analysis. The
X-ray intensity data were measured on a Bruker APEX CCD system equipped with a
graphite monochromator and a MoKα sealed x-ray tube (λ = 0.71073 Å).
The total exposure time was 18.57 hours. The frames were integrated with the
Bruker SAINT software package using a narrow-frame algorithm. The integration of the
data using a triclinic unit cell yielded a total of 28563 reflections to a maximum θ angle
of 30.21° (0.71 Å resolution), of which 8665 were independent (average redundancy
136
3.296, completeness = 98.6%, Rint = 3.61%, Rsig = 3.49%) and 5840 (67.40%) were
greater than 2σ(F2 ). The final cell constants of a = 5.7551(5)Å, b = 9.2812(8)Å, c =
28.039(2)Å, α = 91.0170(10)°, β = 92.3080(10)°, γ = 98.8010(10)°, volume = 1478.4(2)
Å3 , are based upon the refinement of the XYZ-centroids of 6157 reflections above 20
σ(I) with 7.171° < 2θ < 60.09°. The ratio of minimum to maximum apparent transmission
was 0.981. The calculated minimum and maximum transmission coefficients (based on
crystal size) are 0.9770 and 0.9980.
The structure was solved and refined using the Bruker SHELXTL Software
Package, using the space group P -1, with Z = 2 for the formula unit, C36H44O3. The final
anisotropic full-matrix least-squares refinement on F2 with 353 variables converged at R1
= 5.81%, for the observed data and wR2 = 17.31% for all data. The goodness-of-fit was
1.016. The largest peak in the final difference electron density synthesis was 0.397 e- /Å3
and the largest hole was -0.173 e- /Å3 with an RMS deviation of 0.053 e- /Å3. On the
basis of the final model, the calculated density was 1.179 g/cm3 and F(000), 568 e-.
Crystal data, data collection and structure refinement details are summarized in tables
below.
(a72vFinal)
Crystal data
C36H44O3 Z = 2
Mr = 524.71 F(000) = 568
Triclinic, P¯1 Dx = 1.179 Mg m-3
a = 5.7551 (5) Å Mo Kα radiation, λ = 0.71073 Å
b = 9.2812 (8) Å Cell parameters from 5511 reflections
c = 28.039 (2) Å θ = 3.6–30.0°
137
α = 91.017 (1)° μ = 0.07 mm-1
β = 92.308 (1)° T = 193 K
γ = 98.801 (1)° Plate, yellow
V = 1478.4 (2) Å3 0.32 × 0.29 × 0.03 mm
Data collection
Bruker APEX CCD
diffractometer
5840 reflections with I > 2σ(I)
Radiation source: sealed tube Rint = 0.036
Graphite monochromator θmax = 30.2°, θmin = 3.6°
ϕ and ω scans h = -8→8
28563 measured reflections k = -13→13
8665 independent reflections l = -39→39
Refinement
Refinement on F2 Primary atom site location: structure-
invariant direct methods
Least-squares matrix: full Hydrogen site location: inferred from
neighbouring sites
R[F2 > 2σ(F2)] = 0.058 H-atom parameters constrained
wR(F2) = 0.173 w = 1/[σ2(Fo2) + (0.090P)2 + 0.1552P]
where P = (Fo2 + 2Fc
2)/3
S = 1.02 (Δ/σ)max = 0.001
8665 reflections Δmax = 0.40 e Å-3
353 parameters Δmin = -0.17 e Å-3
0 restraints
Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes)
are estimated using the full covariance matrix. The cell esds are taken into
account individually in the estimation of esds in distances, angles and torsion
angles; correlations between esds in cell parameters are only used when they are
defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is
used for estimating esds involving l.s. planes.
138
Fractional atomic coordinates and isotropic or equivalent isotropic displacement
parameters (Å2)
x y z Uiso*/Ueq
O1 0.52389 (15) 0.68203 (9) 0.19376 (3) 0.0354 (2)
O2 0.80548 (18) 0.48414 (11) 0.16881 (4) 0.0501 (3)
O3 0.28149 (18) 0.35508 (12) 0.00635 (4) 0.0504 (3)
C1 0.4263 (2) 0.65073 (12) 0.14902 (4) 0.0304 (2)
C2 0.2720 (2) 0.74339 (13) 0.13201 (4) 0.0327 (3)
C3 0.1544 (2) 0.71105 (15) 0.08798 (5) 0.0408 (3)
H3 0.0461 0.7714 0.0765 0.049*
C4 0.1924 (2) 0.59256 (15) 0.06061 (5) 0.0394 (3)
H4 0.1051 0.5697 0.0313 0.047*
C5 0.6233 (3) 0.17902 (16) 0.03010 (5) 0.0473 (3)
H5 0.5318 0.1544 0.0013 0.057*
C6 0.7980 (3) 0.09902 (16) 0.04357 (6) 0.0534 (4)
H6 0.8249 0.0186 0.0242 0.064*
C7 0.9335 (3) 0.13553 (16) 0.08502 (6) 0.0499 (4)
H7 1.0541 0.0806 0.0939 0.060*
C8 0.8946 (2) 0.25157 (15) 0.11367 (5) 0.0429 (3)
H8 0.9891 0.2766 0.1420 0.051*
C9 0.6761 (2) 0.45394 (13) 0.13340 (4) 0.0340 (3)
C10 0.3968 (2) 0.38323 (14) 0.04374 (4) 0.0367 (3)
C11 0.5814 (2) 0.29625 (13) 0.05884 (5) 0.0364 (3)
C12 0.7167 (2) 0.33175 (13) 0.10090 (4) 0.0344 (3)
C13 0.4805 (2) 0.53571 (12) 0.12008 (4) 0.0302 (2)
C14 0.3571 (2) 0.50654 (13) 0.07562 (4) 0.0328 (3)
C15 0.2374 (2) 0.87298 (13) 0.16137 (4) 0.0334 (3)
C16 0.4138 (2) 0.99340 (14) 0.16572 (5) 0.0409 (3)
H16 0.5556 0.9933 0.1495 0.049*
C17 0.3842 (3) 1.11377 (15) 0.19360 (5) 0.0466 (3)
H17 0.5058 1.1956 0.1964 0.056*
139
C18 0.1793 (3) 1.11503 (16) 0.21721 (5) 0.0469 (3)
H18 0.1594 1.1972 0.2364 0.056*
C19 0.0028 (3) 0.99593 (17) 0.21276 (5) 0.0477 (3)
H19 -0.1389 0.9967 0.2290 0.057*
C20 0.0305 (2) 0.87564 (15) 0.18493 (5) 0.0413 (3)
H20 -0.0924 0.7947 0.1819 0.050*
C21 0.4707 (3) 0.57262 (14) 0.22920 (5) 0.0404 (3)
H21A 0.6128 0.5688 0.2500 0.048*
H21B 0.4251 0.4759 0.2132 0.048*
C22 0.2732 (2) 0.60590 (14) 0.25931 (5) 0.0406 (3)
H22A 0.2338 0.5250 0.2816 0.049*
H22B 0.1324 0.6094 0.2381 0.049*
C23 0.3276 (2) 0.74852 (14) 0.28818 (5) 0.0383 (3)
H23A 0.3585 0.8305 0.2661 0.046*
H23B 0.4720 0.7475 0.3085 0.046*
C24 0.1269 (2) 0.77314 (15) 0.31962 (5) 0.0416 (3)
H24A -0.0168 0.7741 0.2990 0.050*
H24B 0.0953 0.6901 0.3413 0.050*
C25 0.1741 (2) 0.91376 (15) 0.34941 (5) 0.0419 (3)
H25A 0.1976 0.9974 0.3278 0.050*
H25B 0.3215 0.9151 0.3690 0.050*
C26 -0.0243 (2) 0.93232 (16) 0.38219 (5) 0.0437 (3)
H26A -0.1702 0.9343 0.3624 0.052*
H26B -0.0518 0.8465 0.4028 0.052*
C27 0.0228 (2) 1.06965 (15) 0.41370 (5) 0.0416 (3)
H27A 0.1716 1.0696 0.4327 0.050*
H27B 0.0442 1.1558 0.3931 0.050*
C28 -0.1727 (2) 1.08422 (15) 0.44752 (5) 0.0423 (3)
H28A -0.1897 1.0000 0.4690 0.051*
H28B -0.3226 1.0803 0.4286 0.051*
C29 -0.1306 (2) 1.22418 (15) 0.47775 (5) 0.0423 (3)
H29A -0.1129 1.3084 0.4563 0.051*
H29B 0.0191 1.2279 0.4968 0.051*
140
C30 -0.3268 (2) 1.23908 (15) 0.51151 (5) 0.0426 (3)
H30A -0.4769 1.2340 0.4926 0.051*
H30B -0.3429 1.1558 0.5333 0.051*
C31 -0.2849 (2) 1.38010 (15) 0.54102 (5) 0.0432 (3)
H31A -0.2671 1.4632 0.5191 0.052*
H31B -0.1351 1.3846 0.5600 0.052*
C32 -0.4802 (2) 1.39737 (15) 0.57470 (5) 0.0414 (3)
H32A -0.6304 1.3924 0.5558 0.050*
H32B -0.4973 1.3149 0.5969 0.050*
C33 -0.4361 (2) 1.53927 (15) 0.60360 (5) 0.0435 (3)
H33A -0.4161 1.6214 0.5813 0.052*
H33B -0.2867 1.5433 0.6227 0.052*
C34 -0.6304 (2) 1.56034 (15) 0.63705 (5) 0.0413 (3)
H34A -0.7804 1.5559 0.6181 0.050*
H34B -0.6494 1.4792 0.6597 0.050*
C35 -0.5820 (3) 1.70396 (17) 0.66508 (6) 0.0505 (4)
H35A -0.5612 1.7848 0.6423 0.061*
H35B -0.4325 1.7078 0.6841 0.061*
C36 -0.7752 (3) 1.7274 (2) 0.69836 (6) 0.0599 (4)
H36A -0.9244 1.7232 0.6799 0.090*
H36B -0.7351 1.8231 0.7145 0.090*
H36C -0.7910 1.6511 0.7222 0.090*
Atomic displacement parameters (Å2)
U11 U22 U33 U12 U13 U23
O1 0.0456 (5) 0.0319 (4) 0.0275 (4) 0.0039 (4) -0.0043 (4) -0.0032 (3)
O2 0.0512 (6) 0.0541 (6) 0.0466 (6) 0.0192 (5) -0.0163 (5) -0.0132 (5)
O3 0.0558 (6) 0.0585 (6) 0.0364 (5) 0.0114 (5) -0.0080 (4) -0.0156 (4)
C1 0.0324 (5) 0.0314 (6) 0.0259 (5) 0.0010 (4) 0.0004 (4) -0.0016 (4)
C2 0.0336 (6) 0.0334 (6) 0.0312 (6) 0.0049 (5) 0.0024 (5) -0.0015 (5)
C3 0.0428 (7) 0.0449 (7) 0.0365 (7) 0.0150 (6) -0.0057 (5) -0.0011 (5)
C4 0.0429 (7) 0.0458 (7) 0.0295 (6) 0.0095 (5) -0.0071 (5) -0.0043 (5)
141
C5 0.0547 (8) 0.0430 (7) 0.0437 (8) 0.0063 (6) 0.0069 (6) -0.0111 (6)
C6 0.0605 (9) 0.0407 (8) 0.0610 (10) 0.0120 (7) 0.0162 (8) -0.0096 (7)
C7 0.0507 (8) 0.0394 (7) 0.0625 (10) 0.0139 (6) 0.0123 (7) 0.0020 (7)
C8 0.0461 (7) 0.0375 (7) 0.0458 (8) 0.0078 (5) 0.0044 (6) 0.0027 (6)
C9 0.0371 (6) 0.0321 (6) 0.0325 (6) 0.0047 (5) -0.0003 (5) -0.0010 (5)
C10 0.0411 (6) 0.0380 (6) 0.0295 (6) 0.0017 (5) 0.0024 (5) -0.0056 (5)
C11 0.0418 (6) 0.0328 (6) 0.0340 (6) 0.0033 (5) 0.0059 (5) -0.0026 (5)
C12 0.0389 (6) 0.0300 (6) 0.0340 (6) 0.0037 (5) 0.0044 (5) 0.0012 (5)
C13 0.0332 (6) 0.0288 (5) 0.0277 (6) 0.0025 (4) 0.0005 (4) -0.0005 (4)
C14 0.0363 (6) 0.0346 (6) 0.0267 (6) 0.0034 (5) 0.0003 (5) -0.0024 (5)
C15 0.0357 (6) 0.0348 (6) 0.0307 (6) 0.0097 (5) -0.0009 (5) -0.0011 (5)
C16 0.0381 (6) 0.0395 (7) 0.0454 (7) 0.0055 (5) 0.0072 (5) -0.0016 (6)
C17 0.0522 (8) 0.0362 (7) 0.0501 (8) 0.0043 (6) 0.0006 (6) -0.0055 (6)
C18 0.0594 (9) 0.0431 (7) 0.0417 (8) 0.0203 (6) -0.0009 (6) -0.0077 (6)
C19 0.0456 (7) 0.0568 (9) 0.0447 (8) 0.0200 (6) 0.0085 (6) -0.0054 (7)
C20 0.0346 (6) 0.0463 (7) 0.0431 (7) 0.0066 (5) 0.0028 (5) -0.0016 (6)
C21 0.0568 (8) 0.0364 (6) 0.0288 (6) 0.0110 (6) -0.0013 (5) 0.0004 (5)
C22 0.0488 (7) 0.0398 (7) 0.0306 (6) 0.0003 (6) -0.0003 (5) -0.0034 (5)
C23 0.0403 (7) 0.0410 (7) 0.0314 (6) 0.0009 (5) 0.0008 (5) -0.0051 (5)
C24 0.0432 (7) 0.0437 (7) 0.0352 (7) -0.0019 (5) 0.0053 (5) -0.0061 (5)
C25 0.0438 (7) 0.0429 (7) 0.0366 (7) -0.0009 (5) 0.0063 (5) -0.0060 (5)
C26 0.0427 (7) 0.0467 (8) 0.0393 (7) -0.0008 (6) 0.0067 (6) -0.0082 (6)
C27 0.0426 (7) 0.0431 (7) 0.0374 (7) 0.0011 (5) 0.0070 (5) -0.0051 (6)
C28 0.0418 (7) 0.0450 (7) 0.0381 (7) 0.0006 (6) 0.0047 (5) -0.0060 (6)
C29 0.0438 (7) 0.0419 (7) 0.0400 (7) 0.0018 (6) 0.0064 (6) -0.0039 (6)
C30 0.0440 (7) 0.0434 (7) 0.0388 (7) 0.0016 (6) 0.0059 (6) -0.0057 (6)
C31 0.0433 (7) 0.0428 (7) 0.0419 (7) 0.0010 (6) 0.0075 (6) -0.0046 (6)
C32 0.0420 (7) 0.0427 (7) 0.0383 (7) 0.0024 (5) 0.0044 (5) -0.0039 (6)
C33 0.0438 (7) 0.0417 (7) 0.0437 (8) 0.0020 (6) 0.0066 (6) -0.0044 (6)
C34 0.0412 (7) 0.0431 (7) 0.0392 (7) 0.0057 (5) 0.0024 (5) -0.0029 (6)
C35 0.0512 (8) 0.0475 (8) 0.0526 (9) 0.0076 (6) 0.0055 (7) -0.0094 (7)
C36 0.0652 (10) 0.0638 (10) 0.0549 (10) 0.0240 (8) 0.0060 (8) -0.0117 (8)
142
Geometric parameters (Å, º) for (a72vFinal)
O1—C1 1.3614 (13) C22—H22B 0.9900
O1—C21 1.4414 (16) C23—C24 1.5232 (18)
O2—C9 1.2187 (14) C23—H23A 0.9900
O3—C10 1.2204 (15) C23—H23B 0.9900
C1—C2 1.4036 (17) C24—C25 1.5197 (18)
C1—C13 1.4095 (16) C24—H24A 0.9900
C2—C3 1.3893 (17) C24—H24B 0.9900
C2—C15 1.4885 (16) C25—C26 1.5223 (18)
C3—C4 1.3796 (18) C25—H25A 0.9900
C3—H3 0.9500 C25—H25B 0.9900
C4—C14 1.3873 (18) C26—C27 1.5211 (18)
C4—H4 0.9500 C26—H26A 0.9900
C5—C6 1.383 (2) C26—H26B 0.9900
C5—C11 1.3987 (18) C27—C28 1.5204 (18)
C5—H5 0.9500 C27—H27A 0.9900
C6—C7 1.380 (2) C27—H27B 0.9900
C6—H6 0.9500 C28—C29 1.5207 (18)
C7—C8 1.383 (2) C28—H28A 0.9900
C7—H7 0.9500 C28—H28B 0.9900
C8—C12 1.3942 (19) C29—C30 1.5229 (19)
C8—H8 0.9500 C29—H29A 0.9900
C9—C13 1.4904 (17) C29—H29B 0.9900
C9—C12 1.4939 (17) C30—C31 1.5182 (18)
C10—C11 1.4826 (19) C30—H30A 0.9900
C10—C14 1.4903 (17) C30—H30B 0.9900
C11—C12 1.3923 (17) C31—C32 1.5222 (18)
C13—C14 1.4104 (16) C31—H31A 0.9900
C15—C20 1.3879 (18) C31—H31B 0.9900
C15—C16 1.3902 (17) C32—C33 1.5161 (18)
C16—C17 1.3878 (19) C32—H32A 0.9900
C16—H16 0.9500 C32—H32B 0.9900
143
C17—C18 1.377 (2) C33—C34 1.5211 (19)
C17—H17 0.9500 C33—H33A 0.9900
C18—C19 1.382 (2) C33—H33B 0.9900
C18—H18 0.9500 C34—C35 1.5177 (19)
C19—C20 1.3836 (19) C34—H34A 0.9900
C19—H19 0.9500 C34—H34B 0.9900
C20—H20 0.9500 C35—C36 1.518 (2)
C21—C22 1.5086 (19) C35—H35A 0.9900
C21—H21A 0.9900 C35—H35B 0.9900
C21—H21B 0.9900 C36—H36A 0.9800
C22—C23 1.5231 (17) C36—H36B 0.9800
C22—H22A 0.9900 C36—H36C 0.9800
C1—O1—C21 117.00 (9) C25—C24—C23 114.16 (11)
O1—C1—C2 116.16 (10) C25—C24—H24A 108.7
O1—C1—C13 122.99 (10) C23—C24—H24A 108.7
C2—C1—C13 120.81 (10) C25—C24—H24B 108.7
C3—C2—C1 118.81 (11) C23—C24—H24B 108.7
C3—C2—C15 121.60 (11) H24A—C24—H24B 107.6
C1—C2—C15 119.59 (10) C24—C25—C26 113.10 (11)
C4—C3—C2 121.00 (12) C24—C25—H25A 109.0
C4—C3—H3 119.5 C26—C25—H25A 109.0
C2—C3—H3 119.5 C24—C25—H25B 109.0
C3—C4—C14 120.51 (11) C26—C25—H25B 109.0
C3—C4—H4 119.7 H25A—C25—H25B 107.8
C14—C4—H4 119.7 C27—C26—C25 114.07 (11)
C6—C5—C11 119.98 (14) C27—C26—H26A 108.7
C6—C5—H5 120.0 C25—C26—H26A 108.7
C11—C5—H5 120.0 C27—C26—H26B 108.7
C7—C6—C5 120.25 (13) C25—C26—H26B 108.7
C7—C6—H6 119.9 H26A—C26—H26B 107.6
C5—C6—H6 119.9 C28—C27—C26 113.57 (11)
C6—C7—C8 120.38 (14) C28—C27—H27A 108.9
144
C6—C7—H7 119.8 C26—C27—H27A 108.9
C8—C7—H7 119.8 C28—C27—H27B 108.9
C7—C8—C12 119.97 (14) C26—C27—H27B 108.9
C7—C8—H8 120.0 H27A—C27—H27B 107.7
C12—C8—H8 120.0 C27—C28—C29 113.75 (11)
O2—C9—C13 123.01 (11) C27—C28—H28A 108.8
O2—C9—C12 119.17 (11) C29—C28—H28A 108.8
C13—C9—C12 117.80 (10) C27—C28—H28B 108.8
O3—C10—C11 121.10 (11) C29—C28—H28B 108.8
O3—C10—C14 121.04 (12) H28A—C28—H28B 107.7
C11—C10—C14 117.86 (11) C28—C29—C30 113.77 (11)
C12—C11—C5 119.62 (12) C28—C29—H29A 108.8
C12—C11—C10 120.68 (11) C30—C29—H29A 108.8
C5—C11—C10 119.69 (12) C28—C29—H29B 108.8
C11—C12—C8 119.80 (12) C30—C29—H29B 108.8
C11—C12—C9 121.82 (11) H29A—C29—H29B 107.7
C8—C12—C9 118.38 (12) C31—C30—C29 113.37 (11)
C1—C13—C14 118.26 (11) C31—C30—H30A 108.9
C1—C13—C9 121.78 (10) C29—C30—H30A 108.9
C14—C13—C9 119.75 (10) C31—C30—H30B 108.9
C4—C14—C13 120.22 (11) C29—C30—H30B 108.9
C4—C14—C10 118.11 (11) H30A—C30—H30B 107.7
C13—C14—C10 121.66 (11) C30—C31—C32 114.09 (11)
C20—C15—C16 118.99 (12) C30—C31—H31A 108.7
C20—C15—C2 120.91 (11) C32—C31—H31A 108.7
C16—C15—C2 120.10 (11) C30—C31—H31B 108.7
C17—C16—C15 120.45 (12) C32—C31—H31B 108.7
C17—C16—H16 119.8 H31A—C31—H31B 107.6
C15—C16—H16 119.8 C33—C32—C31 113.32 (11)
C18—C17—C16 120.20 (13) C33—C32—H32A 108.9
C18—C17—H17 119.9 C31—C32—H32A 108.9
C16—C17—H17 119.9 C33—C32—H32B 108.9
C17—C18—C19 119.57 (13) C31—C32—H32B 108.9
145
C17—C18—H18 120.2 H32A—C32—H32B 107.7
C19—C18—H18 120.2 C32—C33—C34 114.42 (11)
C18—C19—C20 120.61 (13) C32—C33—H33A 108.7
C18—C19—H19 119.7 C34—C33—H33A 108.7
C20—C19—H19 119.7 C32—C33—H33B 108.7
C19—C20—C15 120.18 (13) C34—C33—H33B 108.7
C19—C20—H20 119.9 H33A—C33—H33B 107.6
C15—C20—H20 119.9 C35—C34—C33 113.11 (12)
O1—C21—C22 110.93 (11) C35—C34—H34A 109.0
O1—C21—H21A 109.5 C33—C34—H34A 109.0
C22—C21—H21A 109.5 C35—C34—H34B 109.0
O1—C21—H21B 109.5 C33—C34—H34B 109.0
C22—C21—H21B 109.5 H34A—C34—H34B 107.8
H21A—C21—H21B 108.0 C34—C35—C36 113.83 (13)
C21—C22—C23 114.52 (11) C34—C35—H35A 108.8
C21—C22—H22A 108.6 C36—C35—H35A 108.8
C23—C22—H22A 108.6 C34—C35—H35B 108.8
C21—C22—H22B 108.6 C36—C35—H35B 108.8
C23—C22—H22B 108.6 H35A—C35—H35B 107.7
H22A—C22—H22B 107.6 C35—C36—H36A 109.5
C22—C23—C24 112.28 (11) C35—C36—H36B 109.5
C22—C23—H23A 109.1 H36A—C36—H36B 109.5
C24—C23—H23A 109.1 C35—C36—H36C 109.5
C22—C23—H23B 109.1 H36A—C36—H36C 109.5
C24—C23—H23B 109.1 H36B—C36—H36C 109.5
H23A—C23—H23B 107.9
C21—O1—C1—C2 118.12 (12) C3—C4—C14—C10 -177.82 (12)
C21—O1—C1—C13 -64.04 (15) C1—C13—C14—C4 1.92 (17)
O1—C1—C2—C3 -175.56 (11) C9—C13—C14—C4 -172.96 (11)
C13—C1—C2—C3 6.55 (18) C1—C13—C14—C10 -177.53 (10)
O1—C1—C2—C15 4.20 (16) C9—C13—C14—C10 7.59 (17)
C13—C1—C2—C15 -173.69 (11) O3—C10—C14—C4 -2.78 (19)
146
C1—C2—C3—C4 -1.8 (2) C11—C10—C14—C4 177.02 (11)
C15—C2—C3—C4 178.43 (12) O3—C10—C14—C13 176.68 (12)
C2—C3—C4—C14 -2.8 (2) C11—C10—C14—C13 -3.53 (17)
C11—C5—C6—C7 -0.8 (2) C3—C2—C15—C20 72.95 (17)
C5—C6—C7—C8 0.5 (2) C1—C2—C15—C20 -106.80 (14)
C6—C7—C8—C12 0.5 (2) C3—C2—C15—C16 -107.36 (15)
C6—C5—C11—C12 0.1 (2) C1—C2—C15—C16 72.89 (16)
C6—C5—C11—C10 178.88 (13) C20—C15—C16—C17 0.6 (2)
O3—C10—C11—C12 178.17 (12) C2—C15—C16—C17 -179.05 (12)
C14—C10—C11—C12 -1.63 (17) C15—C16—C17—C18 -0.1 (2)
O3—C10—C11—C5 -0.59 (19) C16—C17—C18—C19 -0.3 (2)
C14—C10—C11—C5 179.61 (12) C17—C18—C19—C20 0.2 (2)
C5—C11—C12—C8 0.88 (19) C18—C19—C20—C15 0.4 (2)
C10—C11—C12—C8 -177.88 (12) C16—C15—C20—C19 -0.8 (2)
C5—C11—C12—C9 -178.75 (12) C2—C15—C20—C19 178.86 (13)
C10—C11—C12—C9 2.48 (18) C1—O1—C21—C22 -97.68 (12)
C7—C8—C12—C11 -1.2 (2) O1—C21—C22—C23 -62.48 (14)
C7—C8—C12—C9 178.48 (12) C21—C22—C23—C24 -177.34 (11)
O2—C9—C12—C11 -177.14 (12) C22—C23—C24—C25 179.55 (12)
C13—C9—C12—C11 1.53 (17) C23—C24—C25—C26 -177.33 (12)
O2—C9—C12—C8 3.22 (18) C24—C25—C26—C27 177.88 (12)
C13—C9—C12—C8 -178.11 (11) C25—C26—C27—C28 -177.93 (13)
O1—C1—C13—C14 175.69 (10) C26—C27—C28—C29 -177.78 (12)
C2—C1—C13—C14 -6.57 (17) C27—C28—C29—C30 179.80 (12)
O1—C1—C13—C9 -9.54 (18) C28—C29—C30—C31 -179.18 (12)
C2—C1—C13—C9 168.20 (11) C29—C30—C31—C32 179.55 (12)
O2—C9—C13—C1 -2.64 (19) C30—C31—C32—C33 -179.59 (12)
C12—C9—C13—C1 178.76 (10) C31—C32—C33—C34 179.16 (12)
O2—C9—C13—C14 172.06 (12) C32—C33—C34—C35 -179.44 (12)
C12—C9—C13—C14 -6.55 (17) C33—C34—C35—C36 179.51 (13)
C3—C4—C14—C13 2.7 (2)
147
Computing details.
Data collection: Bruker SMART; cell refinement: Bruker SAINT; data reduction: Bruker
SAINT; program(s) used to solve structure: SHELXL2014 (Sheldrick 2014); program(s)
used to refine structure: SHELXL2014 (Sheldrick 2014); molecular graphics: Bruker
SHELXTL; software used to prepare material for publication: Bruker SHELXTL.
Acknowledgements.
The WFU X-ray Facility thanks the National Science Foundation(grant CHE-0234489)
for funds to purchase the X-ray instrument and computers.
References.
Bruker (2014). APEX2 (Version 2014.7-1). Bruker AXS Inc., Madison, Wisconsin, USA.
Sheldrick (2014). SHELXL (Version 2014/3). Bruker AXS Inc., Madison, Wisconsin,
USA.
Bruker (2002). SMART version 5.628. Bruker AXS Inc., Madison, Wisconsin, USA.
Bruker (2014). SAINT version 8.34a. Bruker AXS Inc., Madison, Wisconsin, USA.
Sheldrick, G. M. (2014). SADABS, Version 2014/3. University of Göttingen, Germany.
148
149
APPENDIX B
Figure B1. Crystal Structure of 1-Decyl-2-benzyloxy-9,10-anthraquinone (75a,
C31H34O3).
Experimental.
A clear yellow plate-like specimen of C31H34O3, approximate dimensions 0.040
mm x 0.200 mm x 0.280 mm, was used for the X-ray crystallographic analysis. The X-
ray intensity data were measured on a Bruker APEX CCD system equipped with a
graphite monochromator and a Mo Kα sealed x-ray tube (λ = 0.71073 Å).
150
The total exposure time was 21.19 hours. The frames were integrated with the
Bruker SAINT software package using a narrow-frame algorithm. The integration of the
data using a triclinic unit cell yielded a total of 18690 reflections to a maximum θ angle
of 30.10° (0.71 Å resolution), of which 7324 were independent (average redundancy
2.552, completeness = 98.1%, Rint = 2.54%, Rsig = 3.16%) and 5176 (70.67%) were
greater than 2σ(F2). The final cell constants of a = 7.846(3) Å, b = 8.751(3) Å, c =
19.550(6) Å, α = 78.719(4)°, β = 86.065(4)°, γ = 74.284(4)°, volume = 1267.0(7) Å3, are
based upon the refinement of the XYZ-centroids of 4637 reflections above 20 σ(I) with
7.302° < 2θ < 60.11°. Data were corrected for absorption effects using the multi-scan
method (SADABS). The ratio of minimum to maximum apparent transmission was
0.906. The calculated minimum and maximum transmission coefficients (based on crystal
size) are 0.9793 and 0.9970.
The structure was solved and refined using the Bruker SHELXTL Software
Package, using the space group P -1, with Z = 2 for the formula unit, C31H34O3. The final
anisotropic full-matrix least-squares refinement on F2 with 308 variables converged at R1
= 5.19%, for the observed data and wR2 = 15.08% for all data. The goodness-of-fit was
1.025. The largest peak in the final difference electron density synthesis was 0.397 e-/Å3
and the largest hole was -0.178 e-/Å3 with an RMS deviation of 0.045 e-/Å3. On the basis
of the final model, the calculated density was 1.192 g/cm3 and F(000), 488 e-.
151
(a84sFinal)
Crystal data
Identification code a84s
Chemical formula C31H34O3
Formula weight 454.58
Temperature 193(2) K
Wavelength 0.71073 Å
Crystal size 0.040 x 0.200 x 0.280 mm
Crystal habit clear yellow plate
Crystal system triclinic
Space group P -1
Unit cell dimensions a = 7.846(3) Å α = 78.719(4)°
b = 8.751(3) Å β = 86.065(4)°
c = 19.550(6) Å γ = 74.284(4)°
Volume 1267.0(7) Å3
Z 2
Density (calculated) 1.192 g/cm3
Absorption coefficient 0.075 mm-1
F(000) 488
Data collection
Diffractometer Bruker APEX CCD
Radiation source sealed x-ray tube, Mo Kα
Theta range for data collection 3.54 to 30.10°
Index ranges -11<=h<=11, -12<=k<=12, -27<=l<=27
Reflections collected 18690
Independent reflections 7324 [R(int) = 0.0254]
Coverage of independent reflections 98.1%
Absorption correction multi-scan
Max. and min. transmission 0.9970 and 0.9793
Structure solution technique direct methods
Structure solution program Bruker SHELXTL
152
Refinement method Full-matrix least-squares on F2
Refinement program Bruker SHELXTL
Function minimized Σ w(Fo2 - Fc
2)2
Data / restraints / parameters 7324 / 0 / 308
Goodness-of-fit on F2 1.025
Final R indices 5176 data; I>2σ(I) R1 = 0.0519, wR2 = 0.1340
all data R1 = 0.0753, wR2 = 0.1508
Weighting scheme w=1/[σ2(Fo
2)+(0.0784P)2+0.1176P]
where P=(Fo2+2Fc
2)/3
Largest diff. peak and hole 0.397 and -0.178 eÅ-3
R.M.S. deviation from mean 0.045 eÅ-3
Atomic coordinates and equivalent isotropic atomic displacement parameters (Å2) for
a84s. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.
x/a y/b z/c U(eq)
O1 0.12375(13) 0.81682(10) 0.91821(5) 0.0448(2)
O2 0.42336(14) 0.27515(11) 0.09636(5) 0.0491(3)
O3 0.04772(11) 0.34540(10) 0.81331(5) 0.0374(2)
C1 0.17574(15) 0.69090(13) 0.95986(6) 0.0306(2)
C2 0.18239(14) 0.52896(12) 0.94388(6) 0.0280(2)
C3 0.10821(14) 0.51130(13) 0.88359(6) 0.0287(2)
C4 0.12704(15) 0.35373(14) 0.87172(6) 0.0314(2)
C5 0.21874(16) 0.21793(14) 0.91739(7) 0.0354(3)
C6 0.28874(16) 0.23799(13) 0.97658(6) 0.0344(3)
C7 0.27033(15) 0.38981(13) 0.99116(6) 0.0298(2)
C8 0.34726(15) 0.39826(14) 0.05698(6) 0.0330(3)
C9 0.32715(15) 0.55843(13) 0.07439(6) 0.0306(2)
C10 0.39465(16) 0.57125(15) 0.13657(6) 0.0360(3)
C11 0.37646(17) 0.72031(16) 0.15329(7) 0.0397(3)
C12 0.28823(18) 0.85931(16) 0.10872(7) 0.0397(3)
C13 0.22125(16) 0.84788(14) 0.04675(7) 0.0357(3)
C14 0.24127(15) 0.69820(13) 0.02860(6) 0.0303(2)
C15 0.08498(17) 0.19338(15) 0.78987(7) 0.0388(3)
C16 0.26371(16) 0.15556(14) 0.75462(6) 0.0345(3)
153
C17 0.39581(18) 0.01865(14) 0.78018(7) 0.0389(3)
C18 0.55926(19) 0.98661(17) 0.74679(8) 0.0471(3)
C19 0.59185(19) 0.08954(19) 0.68789(8) 0.0507(4)
C20 0.4611(2) 0.22596(18) 0.66175(8) 0.0496(3)
C21 0.29789(18) 0.25905(15) 0.69496(7) 0.0418(3)
C22 0.01521(15) 0.64908(13) 0.82805(6) 0.0314(2)
C23 0.14496(16) 0.69047(14) 0.76986(6) 0.0337(3)
C24 0.05656(16) 0.82890(14) 0.71285(6) 0.0355(3)
C25 0.17985(18) 0.86585(15) 0.65211(6) 0.0388(3)
C26 0.09884(18) 0.01937(15) 0.60076(6) 0.0406(3)
C27 0.22217(19) 0.05940(16) 0.54080(7) 0.0425(3)
C28 0.1485(2) 0.22255(17) 0.49458(7) 0.0472(3)
C29 0.2672(2) 0.26130(17) 0.43301(7) 0.0477(3)
C30 0.1939(3) 0.42192(19) 0.38607(9) 0.0627(5)
C31 0.3080(3) 0.4525(2) 0.32228(9) 0.0720(5)
Bond lengths (Å) for a84s.
O1-C1 1.2225(13) O2-C8 1.2248(13)
O3-C4 1.3606(15) O3-C15 1.4405(15)
C1-C14 1.4902(17) C1-C2 1.4966(16)
C2-C3 1.4021(17) C2-C7 1.4161(14)
C3-C4 1.4097(16) C3-C22 1.5116(15)
C4-C5 1.3917(16) C5-C6 1.3750(18)
C5-H5 0.95 C6-C7 1.3804(17)
C6-H6 0.95 C7-C8 1.4810(17)
C8-C9 1.4715(17) C9-C10 1.3945(17)
C9-C14 1.3998(15) C10-C11 1.3741(19)
C10-H10 0.95 C11-C12 1.3893(18)
C11-H11 0.95 C12-C13 1.3847(18)
C12-H12 0.95 C13-C14 1.3888(17)
C13-H13 0.95 C15-C16 1.5020(18)
C15-H15A 0.99 C15-H15B 0.99
C16-C17 1.3869(17) C16-C21 1.3884(18)
154
C17-C18 1.3824(19) C17-H17 0.95
C18-C19 1.372(2) C18-H18 0.95
C19-C20 1.381(2) C19-H19 0.95
C20-C21 1.380(2) C20-H20 0.95
C21-H21 0.95 C22-C23 1.5302(17)
C22-H22A 0.99 C22-H22B 0.99
C23-C24 1.5210(15) C23-H23A 0.99
C23-H23B 0.99 C24-C25 1.5204(18)
C24-H24A 0.99 C24-H24B 0.99
C25-C26 1.5212(16) C25-H25A 0.99
C25-H25B 0.99 C26-C27 1.5166(18)
C26-H26A 0.99 C26-H26B 0.99
C27-C28 1.5195(18) C27-H27A 0.99
C27-H27B 0.99 C28-C29 1.5128(19)
C28-H28A 0.99 C28-H28B 0.99
C29-C30 1.510(2) C29-H29A 0.99
C29-H29B 0.99 C30-C31 1.508(2)
C30-H30A 0.99 C30-H30B 0.99
C31-H31A 0.98 C31-H31B 0.98
C31-H31C 0.98
Bond angles (°) for a84s.
C4-O3-C15 119.24(9) O1-C1-C14 118.67(10)
O1-C1-C2 122.84(11) C14-C1-C2 118.46(9)
C3-C2-C7 119.56(10) C3-C2-C1 122.34(9)
C7-C2-C1 118.08(10) C2-C3-C4 118.20(10)
C2-C3-C22 125.00(10) C4-C3-C22 116.75(10)
O3-C4-C5 123.18(11) O3-C4-C3 115.07(10)
C5-C4-C3 121.75(11) C6-C5-C4 119.06(11)
C6-C5-H5 120.5 C4-C5-H5 120.5
C5-C6-C7 121.23(10) C5-C6-H6 119.4
C7-C6-H6 119.4 C6-C7-C2 120.14(11)
C6-C7-C8 117.05(10) C2-C7-C8 122.81(10)
O2-C8-C9 120.86(12) O2-C8-C7 120.91(11)
155
C9-C8-C7 118.22(10) C10-C9-C14 119.81(11)
C10-C9-C8 119.93(10) C14-C9-C8 120.25(11)
C11-C10-C9 120.35(11) C11-C10-H10 119.8
C9-C10-H10 119.8 C10-C11-C12 120.10(12)
C10-C11-H11 119.9 C12-C11-H11 119.9
C13-C12-C11 119.97(12) C13-C12-H12 120.0
C11-C12-H12 120.0 C12-C13-C14 120.56(11)
C12-C13-H13 119.7 C14-C13-H13 119.7
C13-C14-C9 119.18(11) C13-C14-C1 119.09(10)
C9-C14-C1 121.70(10) O3-C15-C16 111.29(10)
O3-C15-H15A 109.4 C16-C15-H15A 109.4
O3-C15-H15B 109.4 C16-C15-H15B 109.4
H15A-C15-H15B 108.0 C17-C16-C21 119.04(12)
C17-C16-C15 121.41(12) C21-C16-C15 119.55(11)
C18-C17-C16 120.28(12) C18-C17-H17 119.9
C16-C17-H17 119.9 C19-C18-C17 120.27(13)
C19-C18-H18 119.9 C17-C18-H18 119.9
C18-C19-C20 119.99(14) C18-C19-H19 120.0
C20-C19-H19 120.0 C21-C20-C19 120.05(13)
C21-C20-H20 120.0 C19-C20-H20 120.0
C20-C21-C16 120.35(12) C20-C21-H21 119.8
C16-C21-H21 119.8 C3-C22-C23 110.92(9)
C3-C22-H22A 109.5 C23-C22-H22A 109.5
C3-C22-H22B 109.5 C23-C22-H22B 109.5
H22A-C22-H22B 108.0 C24-C23-C22 112.60(10)
C24-C23-H23A 109.1 C22-C23-H23A 109.1
C24-C23-H23B 109.1 C22-C23-H23B 109.1
H23A-C23-H23B 107.8 C25-C24-C23 113.76(10)
C25-C24-H24A 108.8 C23-C24-H24A 108.8
C25-C24-H24B 108.8 C23-C24-H24B 108.8
H24A-C24-H24B 107.7 C24-C25-C26 113.38(11)
C24-C25-H25A 108.9 C26-C25-H25A 108.9
C24-C25-H25B 108.9 C26-C25-H25B 108.9
H25A-C25-H25B 107.7 C27-C26-C25 113.82(11)
C27-C26-H26A 108.8 C25-C26-H26A 108.8
156
C27-C26-H26B 108.8 C25-C26-H26B 108.8
H26A-C26-H26B 107.7 C26-C27-C28 113.44(12)
C26-C27-H27A 108.9 C28-C27-H27A 108.9
C26-C27-H27B 108.9 C28-C27-H27B 108.9
H27A-C27-H27B 107.7 C29-C28-C27 113.99(12)
C29-C28-H28A 108.8 C27-C28-H28A 108.8
C29-C28-H28B 108.8 C27-C28-H28B 108.8
H28A-C28-H28B 107.7 C30-C29-C28 114.42(13)
C30-C29-H29A 108.7 C28-C29-H29A 108.7
C30-C29-H29B 108.7 C28-C29-H29B 108.7
H29A-C29-H29B 107.6 C31-C30-C29 113.46(14)
C31-C30-H30A 108.9 C29-C30-H30A 108.9
C31-C30-H30B 108.9 C29-C30-H30B 108.9
H30A-C30-H30B 107.7 C30-C31-H31A 109.5
C30-C31-H31B 109.5 H31A-C31-H31B 109.5
C30-C31-H31C 109.5 H31A-C31-H31C 109.5
H31B-C31-H31C 109.5
Torsion angles (°) for a84s.
O1-C1-C2-C3 -8.48(18) C14-C1-C2-C3 173.71(10)
O1-C1-C2-C7 170.22(11) C14-C1-C2-C7 -7.59(15)
C7-C2-C3-C4 -1.07(16) C1-C2-C3-C4 177.61(10)
C7-C2-C3-C22 -178.34(10) C1-C2-C3-C22 0.34(17)
C15-O3-C4-C5 -11.61(16) C15-O3-C4-C3 169.11(10)
C2-C3-C4-O3 178.26(9) C22-C3-C4-O3 -4.25(14)
C2-C3-C4-C5 -1.03(16) C22-C3-C4-C5 176.46(10)
O3-C4-C5-C6 -177.48(10) C3-C4-C5-C6 1.75(17)
C4-C5-C6-C7 -0.31(18) C5-C6-C7-C2 -1.79(17)
C5-C6-C7-C8 178.74(11) C3-C2-C7-C6 2.48(16)
C1-C2-C7-C6 -176.26(10) C3-C2-C7-C8 -178.08(10)
C1-C2-C7-C8 3.18(16) C6-C7-C8-O2 -0.09(17)
C2-C7-C8-O2 -179.54(11) C6-C7-C8-C9 -179.05(10)
C2-C7-C8-C9 1.49(16) O2-C8-C9-C10 -0.25(17)
C7-C8-C9-C10 178.72(10) O2-C8-C9-C14 179.42(11)
157
C7-C8-C9-C14 -1.61(16) C14-C9-C10-C11 0.35(17)
C8-C9-C10-C11 -179.98(11) C9-C10-C11-C12 0.95(18)
C10-C11-C12-C13 -1.16(19) C11-C12-C13-C14 0.06(19)
C12-C13-C14-C9 1.22(18) C12-C13-C14-C1 -176.88(11)
C10-C9-C14-C13 -1.42(16) C8-C9-C14-C13 178.91(10)
C10-C9-C14-C1 176.63(10) C8-C9-C14-C1 -3.05(16)
O1-C1-C14-C13 7.87(17) C2-C1-C14-C13 -174.23(10)
O1-C1-C14-C9 -170.18(11) C2-C1-C14-C9 7.72(16)
C4-O3-C15-C16 -76.34(13) O3-C15-C16-C17 119.25(13)
O3-C15-C16-C21 -61.06(15) C21-C16-C17-C18 0.34(19)
C15-C16-C17-C18 -179.97(12) C16-C17-C18-C19 -0.3(2)
C17-C18-C19-C20 0.1(2) C18-C19-C20-C21 0.2(2)
C19-C20-C21-C16 -0.2(2) C17-C16-C21-C20 -0.08(19)
C15-C16-C21-C20 -179.78(12) C2-C3-C22-C23 92.36(13)
C4-C3-C22-C23 -84.94(12) C3-C22-C23-C24 -179.94(10)
C22-C23-C24-C25 -176.42(10) C23-C24-C25-C26 -171.40(11)
C24-C25-C26-C27 178.72(11) C25-C26-C27-C28 -173.23(11)
C26-C27-C28-C29 -177.85(12) C27-C28-C29-C30 179.03(13)
C28-C29-C30-C31 -175.75(15)
Anisotropic atomic displacement parameters (Å2) for a84s. The anisotropic atomic
displacement factor exponent takes the form: -2π2[ h2 a*2 U11 + ... + 2 h k a* b* U12 ]
U11 U22 U33 U23 U13 U12
O1 0.0615(6) 0.0261(4) 0.0416(5) 0.0038(3) -0.0136(4) -0.0065(4)
O2 0.0633(6) 0.0330(5) 0.0387(5) 0.0050(4) -0.0106(4) 0.0024(4)
O3 0.0358(5) 0.0319(4) 0.0430(5) -0.0093(4) -0.0035(4) -0.0041(3)
C1 0.0289(5) 0.0259(5) 0.0332(6) 0.0000(4) 0.0005(4) -0.0052(4)
C2 0.0257(5) 0.0250(5) 0.0288(5) 0.0009(4) 0.0036(4) -0.0043(4)
C3 0.0237(5) 0.0262(5) 0.0320(5) -0.0001(4) 0.0036(4) -0.0041(4)
C4 0.0274(5) 0.0303(5) 0.0343(6) -0.0029(4) 0.0038(4) -0.0068(4)
C5 0.0386(6) 0.0249(5) 0.0393(6) -0.0023(4) 0.0046(5) -0.0066(5)
C6 0.0359(6) 0.0254(5) 0.0355(6) 0.0028(4) 0.0040(5) -0.0042(4)
C7 0.0296(5) 0.0254(5) 0.0293(5) 0.0021(4) 0.0047(4) -0.0048(4)
C8 0.0321(6) 0.0306(5) 0.0299(6) 0.0027(4) 0.0036(4) -0.0041(4)
158
C9 0.0267(5) 0.0315(5) 0.0290(5) 0.0015(4) 0.0043(4) -0.0062(4)
C10 0.0331(6) 0.0404(6) 0.0296(6) 0.0024(5) 0.0009(5) -0.0081(5)
C11 0.0419(7) 0.0480(7) 0.0311(6) -0.0036(5) 0.0005(5) -0.0175(6)
C12 0.0439(7) 0.0381(6) 0.0391(7) -0.0061(5) 0.0023(5) -0.0155(5)
C13 0.0362(6) 0.0309(6) 0.0379(6) -0.0007(5) 0.0003(5) -0.0094(5)
C14 0.0277(5) 0.0299(5) 0.0302(5) 0.0004(4) 0.0026(4) -0.0072(4)
C15 0.0368(7) 0.0333(6) 0.0478(7) -0.0105(5) -0.0019(5) -0.0093(5)
C16 0.0365(6) 0.0293(5) 0.0381(6) -0.0089(5) -0.0042(5) -0.0063(5)
C17 0.0440(7) 0.0302(6) 0.0403(7) -0.0064(5) -0.0066(5) -0.0048(5)
C18 0.0419(7) 0.0412(7) 0.0531(8) -0.0155(6) -0.0070(6) 0.0039(6)
C19 0.0393(7) 0.0591(9) 0.0529(8) -0.0216(7) 0.0041(6) -0.0049(6)
C20 0.0552(9) 0.0513(8) 0.0407(7) -0.0055(6) 0.0041(6) -0.0144(7)
C21 0.0440(7) 0.0356(6) 0.0409(7) -0.0040(5) -0.0052(6) -0.0033(5)
C22 0.0283(5) 0.0280(5) 0.0332(6) -0.0008(4) -0.0026(4) -0.0026(4)
C23 0.0336(6) 0.0303(5) 0.0326(6) 0.0010(4) -0.0021(5) -0.0050(5)
C24 0.0372(6) 0.0321(6) 0.0334(6) 0.0016(5) -0.0056(5) -0.0068(5)
C25 0.0424(7) 0.0384(6) 0.0321(6) 0.0008(5) -0.0042(5) -0.0090(5)
C26 0.0458(7) 0.0396(7) 0.0324(6) 0.0025(5) -0.0047(5) -0.0103(6)
C27 0.0489(8) 0.0426(7) 0.0326(6) 0.0009(5) -0.0036(5) -0.0109(6)
C28 0.0575(9) 0.0408(7) 0.0368(7) 0.0015(5) 0.0015(6) -0.0087(6)
C29 0.0589(9) 0.0432(7) 0.0362(7) 0.0004(5) 0.0019(6) -0.0115(6)
C30 0.0757(11) 0.0461(8) 0.0525(9) 0.0083(7) 0.0077(8) -0.0073(8)
C31 0.0940(14) 0.0602(10) 0.0520(10) 0.0119(8) 0.0076(9) -0.0215(10)
Hydrogen atomic coordinates and isotropic atomic displacement parameters (Å2) for
a84s.
x/a y/b z/c U(eq)
H5 0.2328 0.1129 -0.0922 0.042
H6 0.3509 0.1456 0.0080 0.041
H10 0.4535 0.4764 0.1675 0.043
H11 0.4243 0.7283 0.1954 0.048
H12 0.2739 0.9622 0.1208 0.048
H13 0.1611 0.9432 0.0164 0.043
H15A -0.0071 0.1976 -0.2431 0.047
159
H15B 0.0811 0.1063 -0.1697 0.047
H17 0.3739 -0.0534 -0.1792 0.047
H18 0.6494 -0.1071 -0.2353 0.056
H19 0.7043 0.0670 -0.3349 0.061
H20 0.4836 0.2970 -0.3791 0.06
H21 0.2084 0.3531 -0.3231 0.05
H22A -0.0388 0.7453 -0.1507 0.038
H22B -0.0808 0.6186 -0.1919 0.038
H23A 0.2411 0.7200 -0.2099 0.04
H23B 0.1990 0.5937 -0.2510 0.04
H24A -0.0446 0.8020 -0.3051 0.043
H24B 0.0090 0.9271 -0.2666 0.043
H25A 0.2129 0.7739 -0.3730 0.047
H25B 0.2896 0.8764 -0.3294 0.047
H26A -0.0095 1.0077 -0.4185 0.049
H26B 0.0632 1.1108 -0.3738 0.049
H27A 0.2463 0.9744 -0.4881 0.051
H27B 0.3362 1.0582 -0.4400 0.051
H28A 0.0322 1.2251 -0.5230 0.057
H28B 0.1286 1.3077 -0.4768 0.057
H29A 0.3828 1.2604 -0.5493 0.057
H29B 0.2888 1.1750 -0.5950 0.057
H30A 0.0744 1.4263 -0.6290 0.075
H30B 0.1811 1.5092 -0.5870 0.075
H31A 0.4266 1.4486 -0.6633 0.108
H31B 0.2549 1.5592 -0.7053 0.108
H31C 0.3167 1.3695 -0.7059 0.108
160
161
APPENDIX C
Figure C1. Crystal Structure of 64. (C16H9F3O6S).
Experimental.
A clear colourless irregular-like specimen of C16H9F3O6S, approximate
dimensions 0.070 mm x 0.120 mm x 0.200 mm, was used for the X-ray crystallographic
analysis. The X-ray intensity data were measured on a Bruker APEX CCD system
equipped with a graphite monochromator and a Mo Kα sealed x-ray tube (λ = 0.71073
Å).
The total exposure time was 21.19 hours. The frames were integrated with the
Bruker SAINT software package using a narrow-frame algorithm. The integration of the
162
data using a triclinic unit cell yielded a total of 10818 reflections to a maximum θ angle
of 29.35° (0.73 Å resolution), of which 4159 were independent (average redundancy
2.601, completeness = 98.5%, Rint = 2.76%, Rsig = 3.18%) and 3571 (85.86%) were
greater than 2σ(F2). The final cell constants of a = 7.5519(12) Å, b = 8.1728(13) Å, c =
13.756(2) Å, α = 94.515(2)°, β = 91.923(2)°, γ = 114.461(2)°, volume = 768.4(2) Å3, are
based upon the refinement of the XYZ-centroids of 4411 reflections above 20 σ(I) with
7.691° < 2θ < 60.17°. Data were corrected for absorption effects using the multi-scan
method (SADABS). The ratio of minimum to maximum apparent transmission was
0.911. The calculated minimum and maximum transmission coefficients (based on crystal
size) are 0.9463 and 0.9807.
The structure was solved and refined using the Bruker SHELXTL Software
Package, using the space group P -1, with Z = 2 for the formula unit, C16H9F3O6S. The
final anisotropic full-matrix least-squares refinement on F2 with 236 variables converged
at R1 = 4.42%, for the observed data and wR2 = 12.52% for all data. The goodness-of-fit
was 1.038. The largest peak in the final difference electron density synthesis was 0.505 e-
/Å3 and the largest hole was -0.266 e-/Å3 with an RMS deviation of 0.072 e-/Å3. On the
basis of the final model, the calculated density was 1.670 g/cm3 and F(000), 392 e-.
(C16H9O6SF3Final)
Crystal data
Identification code C16H9O6SF3
Chemical formula C16H9F3O6S
Formula weight 386.29
Temperature 193(2) K
163
Wavelength 0.71073 Å
Crystal size 0.070 x 0.120 x 0.200 mm
Crystal habit clear colourless irregular
Crystal system triclinic
Space group P -1
Unit cell dimensions a = 7.5519(12) Å α = 94.515(2)°
b = 8.1728(13) Å β = 91.923(2)°
c = 13.756(2) Å γ = 114.461(2)°
Volume 768.4(2) Å3
Z 2
Density (calculated) 1.670 g/cm3
Absorption coefficient 0.279 mm-1
F(000) 392
Data collection
Diffractometer Bruker APEX CCD
Radiation source sealed x-ray tube, Mo Kα
Theta range for data collection 3.85 to 29.35°
Index ranges -10<=h<=10, -11<=k<=11, -18<=l<=18
Reflections collected 10818
Independent reflections 4159 [R(int) = 0.0276]
Coverage of independent reflections 98.5%
Absorption correction multi-scan
Max. and min. transmission 0.9807 and 0.9463
Structure solution technique direct methods
Structure solution program Bruker SHELXTL
Refinement method Full-matrix least-squares on F2
Refinement program Bruker SHELXTL
Function minimized Σ w(Fo2 - Fc
2)2
Data / restraints / parameters 4159 / 0 / 236
Goodness-of-fit on F2 1.038
Δ/σmax 0.001
Final R indices 3571 data; I>2σ(I) R1 = 0.0442, wR2 = 0.1189
164
all data R1 = 0.0508, wR2 = 0.1252
Weighting scheme w=1/[σ2(Fo
2)+(0.0747P)2+0.1406P]
where P=(Fo2+2Fc
2)/3
Largest diff. peak and hole 0.505 and -0.266 eÅ-3
R.M.S. deviation from mean 0.072 eÅ-3
Atomic coordinates and equivalent isotropic atomic displacement parameters (Å2) for
C16H9O6SF3. U(eq) is defined as one third of the trace of the orthogonalized Uij
tensor.
x/a y/b z/c U(eq)
S1 0.18853(5) 0.25394(4) 0.17009(3) 0.02965(12)
F1 0.09143(19) 0.47781(16) 0.08280(9) 0.0591(3)
F2 0.9925(2) 0.21186(18) 0.00701(9) 0.0766(4)
F3 0.2922(2) 0.40067(19) 0.00628(9) 0.0717(4)
O1 0.37458(15) 0.41597(13) 0.21983(7) 0.0282(2)
O2 0.47551(17) 0.72559(14) 0.15366(8) 0.0365(3)
O3 0.23255(17) 0.79316(14) 0.58504(8) 0.0375(3)
O4 0.29794(18) 0.23448(14) 0.38047(8) 0.0364(3)
O5 0.02173(17) 0.22124(15) 0.22264(8) 0.0378(3)
O6 0.2481(2) 0.11723(16) 0.13953(10) 0.0492(3)
C1 0.35922(19) 0.55355(17) 0.28342(10) 0.0252(3)
C2 0.4150(2) 0.72022(19) 0.24489(11) 0.0283(3)
C3 0.4063(2) 0.86413(18) 0.30227(11) 0.0308(3)
C4 0.3490(2) 0.84096(18) 0.39621(11) 0.0286(3)
C5 0.30267(19) 0.67789(17) 0.43587(10) 0.0248(3)
C6 0.24795(19) 0.66704(18) 0.53890(10) 0.0264(3)
C7 0.21088(19) 0.49635(18) 0.58258(10) 0.0258(3)
C8 0.1649(2) 0.4837(2) 0.67997(11) 0.0324(3)
C9 0.1259(2) 0.3240(2) 0.72113(12) 0.0362(3)
C10 0.1322(2) 0.1765(2) 0.66570(12) 0.0348(3)
C11 0.1805(2) 0.18913(19) 0.57006(11) 0.0295(3)
C12 0.22073(19) 0.34959(17) 0.52724(10) 0.0248(3)
C13 0.27486(19) 0.35868(17) 0.42421(10) 0.0251(3)
C14 0.30882(18) 0.52961(17) 0.37908(10) 0.0235(3)
C15 0.1410(3) 0.3432(3) 0.05922(13) 0.0479(4)
165
C16 0.5366(3) 0.8934(3) 0.11153(15) 0.0518(5)
Bond lengths (Å) for C16H9O6SF3.
S1-O6 1.4080(12) S1-O5 1.4119(12)
S1-O1 1.5646(11) S1-C15 1.8280(18)
F1-C15 1.323(2) F2-C15 1.324(2)
F3-C15 1.311(2) O1-C1 1.4153(15)
O2-C2 1.3478(18) O2-C16 1.4316(19)
O3-C6 1.2166(17) O4-C13 1.2166(16)
C1-C14 1.3882(19) C1-C2 1.4026(19)
C2-C3 1.390(2) C3-C4 1.379(2)
C3-H3 0.95 C4-C5 1.3919(18)
C4-H4 0.95 C5-C14 1.4075(18)
C5-C6 1.4887(19) C6-C7 1.4850(19)
C7-C8 1.396(2) C7-C12 1.3992(18)
C8-C9 1.386(2) C8-H8 0.95
C9-C10 1.393(2) C9-H9 0.95
C10-C11 1.377(2) C10-H10 0.95
C11-C12 1.4010(18) C11-H11 0.95
C12-C13 1.4871(19) C13-C14 1.5011(18)
C16-H16A 0.98 C16-H16B 0.98
C16-H16C 0.98
Bond angles (°) for C16H9O6SF3.
O6-S1-O5 122.87(8) O6-S1-O1 106.30(7)
O5-S1-O1 112.60(6) O6-S1-C15 106.46(9)
O5-S1-C15 104.22(9) O1-S1-C15 102.31(7)
C1-O1-S1 121.10(9) C2-O2-C16 117.68(13)
C14-C1-C2 122.64(12) C14-C1-O1 122.52(12)
C2-C1-O1 114.63(12) O2-C2-C3 125.65(13)
O2-C2-C1 115.51(12) C3-C2-C1 118.83(13)
C4-C3-C2 119.29(13) C4-C3-H3 120.4
C2-C3-H3 120.4 C3-C4-C5 121.72(13)
166
C3-C4-H4 119.1 C5-C4-H4 119.1
C4-C5-C14 120.12(13) C4-C5-C6 117.97(12)
C14-C5-C6 121.92(12) O3-C6-C7 121.44(13)
O3-C6-C5 120.97(13) C7-C6-C5 117.58(11)
C8-C7-C12 120.20(13) C8-C7-C6 119.02(13)
C12-C7-C6 120.78(12) C9-C8-C7 119.67(14)
C9-C8-H8 120.2 C7-C8-H8 120.2
C8-C9-C10 120.26(14) C8-C9-H9 119.9
C10-C9-H9 119.9 C11-C10-C9 120.35(14)
C11-C10-H10 119.8 C9-C10-H10 119.8
C10-C11-C12 120.20(14) C10-C11-H11 119.9
C12-C11-H11 119.9 C7-C12-C11 119.30(13)
C7-C12-C13 122.10(12) C11-C12-C13 118.60(12)
O4-C13-C12 120.63(12) O4-C13-C14 121.99(13)
C12-C13-C14 117.31(11) C1-C14-C5 117.24(12)
C1-C14-C13 122.53(12) C5-C14-C13 120.11(12)
F3-C15-F1 108.98(15) F3-C15-F2 109.19(16)
F1-C15-F2 108.54(17) F3-C15-S1 112.48(14)
F1-C15-S1 109.75(12) F2-C15-S1 107.82(13)
O2-C16-H16A 109.5 O2-C16-H16B 109.5
H16A-C16-H16B 109.5 O2-C16-H16C 109.5
H16A-C16-H16C 109.5 H16B-C16-H16C 109.5
Torsion angles (°) for C16H9O6SF3.
O6-S1-O1-C1 -161.29(11) O5-S1-O1-C1 -24.05(12)
C15-S1-O1-C1 87.25(12) S1-O1-C1-C14 76.95(15)
S1-O1-C1-C2 -108.23(12) C16-O2-C2-C3 0.0(2)
C16-O2-C2-C1 -179.16(14) C14-C1-C2-O2 174.55(12)
O1-C1-C2-O2 -0.26(18) C14-C1-C2-C3 -4.7(2)
O1-C1-C2-C3 -179.52(12) O2-C2-C3-C4 -177.25(13)
C1-C2-C3-C4 1.9(2) C2-C3-C4-C5 1.1(2)
C3-C4-C5-C14 -1.6(2) C3-C4-C5-C6 178.21(12)
C4-C5-C6-O3 4.4(2) C14-C5-C6-O3 -175.74(13)
C4-C5-C6-C7 -176.25(11) C14-C5-C6-C7 3.58(19)
167
O3-C6-C7-C8 -2.5(2) C5-C6-C7-C8 178.13(12)
O3-C6-C7-C12 177.15(13) C5-C6-C7-C12 -2.17(18)
C12-C7-C8-C9 -1.0(2) C6-C7-C8-C9 178.65(13)
C7-C8-C9-C10 -0.1(2) C8-C9-C10-C11 1.1(2)
C9-C10-C11-C12 -1.0(2) C8-C7-C12-C11 1.2(2)
C6-C7-C12-C11 -178.53(12) C8-C7-C12-C13 -178.16(13)
C6-C7-C12-C13 2.15(19) C10-C11-C12-C7 -0.1(2)
C10-C11-C12-C13 179.23(12) C7-C12-C13-O4 173.91(13)
C11-C12-C13-O4 -5.4(2) C7-C12-C13-C14 -3.19(19)
C11-C12-C13-C14 177.48(11) C2-C1-C14-C5 4.2(2)
O1-C1-C14-C5 178.58(11) C2-C1-C14-C13 -171.73(12)
O1-C1-C14-C13 2.7(2) C4-C5-C14-C1 -0.98(19)
C6-C5-C14-C1 179.18(12) C4-C5-C14-C13 175.02(12)
C6-C5-C14-C13 -4.82(19) O4-C13-C14-C1 3.2(2)
C12-C13-C14-C1 -179.74(11) O4-C13-C14-C5 -172.57(13)
C12-C13-C14-C5 4.48(18) O6-S1-C15-F3 -56.05(15)
O5-S1-C15-F3 172.75(12) O1-S1-C15-F3 55.29(14)
O6-S1-C15-F1 -177.55(12) O5-S1-C15-F1 51.25(14)
O1-S1-C15-F1 -66.21(14) O6-S1-C15-F2 64.39(17)
O5-S1-C15-F2 -66.80(16) O1-S1-C15-F2 175.74(14)
Anisotropic atomic displacement parameters (Å2) for C16H9O6SF3. The anisotropic
atomic displacement factor exponent takes the form: -2π2[ h2 a*2 U11 +...+ 2 h k a* b*
U12].
U11 U22 U33 U23 U13 U12
S1 0.0381(2) 0.02359(18) 0.02811(19) -0.00176(12) -0.00171(14) 0.01486(14)
F1 0.0727(8) 0.0507(6) 0.0589(7) 0.0096(5) -0.0218(6) 0.0319(6)
F2 0.0969(10) 0.0575(8) 0.0492(7) -0.0057(6) -0.0367(7) 0.0113(7)
F3 0.0991(11) 0.0721(9) 0.0344(6) 0.0101(6) 0.0168(6) 0.0246(8)
O1 0.0312(5) 0.0263(5) 0.0295(5) -0.0011(4) 0.0020(4) 0.0150(4)
O2 0.0465(6) 0.0324(5) 0.0329(6) 0.0087(4) 0.0097(5) 0.0175(5)
O3 0.0506(7) 0.0289(5) 0.0368(6) -0.0031(4) 0.0042(5) 0.0213(5)
O4 0.0556(7) 0.0268(5) 0.0344(6) 0.0011(4) 0.0027(5) 0.0251(5)
O5 0.0353(6) 0.0330(5) 0.0391(6) 0.0005(4) 0.0009(5) 0.0090(4)
168
O6 0.0641(8) 0.0341(6) 0.0552(8) -0.0129(5) -0.0054(6) 0.0300(6)
C1 0.0262(6) 0.0218(6) 0.0286(6) -0.0017(5) -0.0011(5) 0.0120(5)
C2 0.0283(6) 0.0261(6) 0.0308(7) 0.0041(5) 0.0000(5) 0.0118(5)
C3 0.0343(7) 0.0214(6) 0.0367(7) 0.0036(5) -0.0022(6) 0.0118(5)
C4 0.0315(7) 0.0217(6) 0.0338(7) -0.0019(5) -0.0027(5) 0.0135(5)
C5 0.0244(6) 0.0210(6) 0.0294(6) -0.0016(5) -0.0033(5) 0.0111(5)
C6 0.0253(6) 0.0238(6) 0.0300(7) -0.0023(5) -0.0025(5) 0.0116(5)
C7 0.0228(6) 0.0255(6) 0.0287(6) 0.0002(5) -0.0021(5) 0.0104(5)
C8 0.0315(7) 0.0368(7) 0.0299(7) 0.0003(6) 0.0012(5) 0.0160(6)
C9 0.0364(8) 0.0426(8) 0.0305(7) 0.0085(6) 0.0039(6) 0.0164(7)
C10 0.0336(7) 0.0320(7) 0.0380(8) 0.0113(6) 0.0009(6) 0.0117(6)
C11 0.0284(7) 0.0242(6) 0.0354(7) 0.0035(5) -0.0017(5) 0.0107(5)
C12 0.0221(6) 0.0231(6) 0.0289(6) 0.0014(5) -0.0027(5) 0.0098(5)
C13 0.0261(6) 0.0207(6) 0.0291(6) -0.0007(5) -0.0037(5) 0.0113(5)
C14 0.0231(6) 0.0196(5) 0.0282(6) 0.0006(5) -0.0024(5) 0.0100(5)
C15 0.0630(12) 0.0429(9) 0.0303(8) 0.0001(7) -0.0097(8) 0.0163(8)
C16 0.0715(13) 0.0451(10) 0.0515(11) 0.0245(8) 0.0251(9) 0.0320(9)
Hydrogen atomic coordinates and isotropic atomic displacement parameters (Å2) for
C16H9O6SF3.
x/a y/b z/c U(eq)
H3 0.4395 0.9773 0.2770 0.037
H4 0.3409 0.9389 0.4349 0.034
H8 0.1603 0.5840 0.7178 0.039
H9 0.0948 0.3150 0.7874 0.043
H10 0.1030 0.0667 0.6940 0.042
H11 0.1866 0.0887 0.5330 0.035
H16A 0.4255 0.9250 0.1035 0.078
H16B 0.5859 0.8816 0.0476 0.078
H16C 0.6401 0.9885 0.1547 0.078
169
CURRICULUM VITAE
Jason Mark Pifer
Education Wake Forest University Winston-Salem, NC
Graduate School of Arts and Sciences
Ph.D., Organic Chemistry, 2015
Duke University Durham, NC
Trinity College of Arts and Sciences
B.S., Chemistry, 2010
Research Wake Forest University Winston-Salem, NC
Experience Advisor: Dr. Paul B. Jones
Designed and executed syntheses of small molecules towards
elucidation of the mechanism for a photochemical rearrangement.
January 2011 – May 2015.
Duke University Durham, NC
Advisor: Dr. Stephen Craig
Analyzed thermal properties of polymer gel mixtures upon
introduction of a gelator additive. May 2009 – August 2010.
Teaching Wake Forest University Winston-Salem, NC
Experience Chemistry Center Teaching Assistant
Facilitated learning for individuals and small groups of
undergraduates by recognizing and correcting shortcomings in
conceptual understandings of chemistry.
Spectroscopy Teaching Assistant
Recorded and produced instructional videos demonstrating proper
use of data analysis software for structural identification. Analyzed
lab samples for ~200 students across 8 different lab sections.
Laboratory TA for College Chemistry I and Organic Chemistry I
Supervised and instructed undergraduate teaching labs of ~24
students. Provided students with written and verbal feedback to
further understanding of chemistry concepts.
Publications, Pifer, Jason M.; Jones, Paul B. Investigation of the
Presentations, Photodimerization of 1,2-Dialkoxy-9,10-Anthraquinones.
and Awards Presented at the 24th Winter I-APS Conference Poster Session.
January 1, 2015.
170
Pifer, Jason M.; Sarma, Saurav J.; Jones, Paul B. Alkyl Radical
Generation via Sequential Photoreactions. Manuscript in
preparation.
Pifer, Jason M.; Lodewyk, Michael W.; Soldi, Cristian; Olmstead,
Marilyn M.; Rita, Juan; Shaw, Jared T.; Tantillo, Dean J.; Jones,
Paul B. Formation of Aquatolide via [2+2] Photocyclization of
Asteriscunolide C. Manuscript in preparation.
Inter-American Photochemical Society Travel Award. December
3, 2014.
Outstanding Teaching Assistant Award. Wake Forest University.
September 5, 2014.
Pifer, Jason M. Photochemistry of 1,2-Dialkoxy-9,10-
anthraquinones and their Derivatives. Presented at the Wake Forest
University Chemistry Department Seminar Series. Winston-Salem,
NC. April 16, 2014.
Pifer, Jason M. Photochemically Cleavable Molecular Cages.
Three Minute Thesis Finalist at the Wake Forest University
Graduate School Research Day. Winston-Salem, NC. March 28,
2014.