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.

III

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.

IV

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.

V

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


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





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

VIII

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





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

IX

6.3 Irradiation of Asteriscunolides in Acetonitrile and the Discovery of 116

a New Photoproduct

6.4 Summary 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

XI

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.

XII

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.

XIII

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.

XVI

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

XVII

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

XVIII

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

XIX

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-


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.

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


















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).


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):

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.

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.

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


















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.


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.

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


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.

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.

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


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.

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


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.

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.

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






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.


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

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).



162




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.


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.

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