toward the synthesis of naphthalene-bridged bis-triazole
TRANSCRIPT
University of South FloridaScholar Commons
Graduate Theses and Dissertations Graduate School
June 2017
Toward the Synthesis of Naphthalene-Bridged Bis-Triazole Bimetallic ComplexesSean M. JohnsonUniversity of South Florida, [email protected]
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Scholar Commons CitationJohnson, Sean M., "Toward the Synthesis of Naphthalene-Bridged Bis-Triazole Bimetallic Complexes" (2017). Graduate Theses andDissertations.http://scholarcommons.usf.edu/etd/6872
Toward the Synthesis of Naphthalene-Bridged Bis-Triazole Bimetallic Complexes
by
Sean M. Johnson
A thesis submitted in partial fulfillment of the requirements for the degree of
Master of Science Department of Chemistry
College of Arts and Sciences University of South Florida
Major Professor: Xiaodong Shi, Ph.D. Jianfeng Cai, Ph.D. James Leahy, Ph.D.
Date of Approval: June 14, 2017
Keywords: 1,2,3-Triazole, Coordination, Binuclear, Ligand, Scalable
Copyright © 2017, Sean M. Johnson
DEDICATION
I would like to dedicate this work to my family and friends who have loved and
supported me throughout my graduate studies. My wife, Julie, has been extremely
supportive, both emotionally and intellectually, through this journey. My parents, John and
Kathie, have made this adventure possible through their guidance and encouragement.
My previous lab mates and friends, Xin Cui, Yong Wang, and Xin Wen, I would not have
turned out to be the person I am without your friendship and the wisdom you bestowed
upon me.
ACKNOWLEDGMENTS
I would like to express my appreciation to my current and former research advisors,
Dr. Xiaodong Shi and Dr. Peter Zhang. The training and advising techniques you two
gave me have molded me to appreciate science to the highest level. I appreciate the
opportunity to work with each of you and the groups you each constructed. I would also
like to thank my committee members, Dr. James Leahy and Dr. Jianfeng Cai, for their
comments and suggestions throughout my graduate studies.
I would like to thank my teaching assignment supervisors: Dr. Jon Antilla, Dr. Kirpal
Bisht, Dr. Solomon Weldegirma, Dr. Vasiliki Lykourinou, and Dr. Edwin Rivera. I
appreciate the opportunities you gave me and the knowledge you imparted on me.
I would like to thank my lab mates from Dr. Zhang’s group: Dr. Xin Cui, Dr. Li-mei
Jin, Dr. Peng Sang, Dr. Xue Xu, Dr. Yang Hu, Dr. Chaoqun Li, Dr. Kai Lang, Dr. Joseph
Gill, Dr. Qigan Cheng, Lucas Parvin, Jingyi Wang, Yong Wang, and Xin Wen. I would
also like to thank my lab mates from Dr. Shi’s group: Dr. Haihui Peng, Dr. Shengtao Ding,
Dr. Xiaohan Ye, Dr. Pan Li, Dr. Jin Wang, Dr. Rong Cai, Dr. Seyedmorteza Hosseyni,
Stephen Motika, Boliang Dong, Ying He, Courtney Smith, Abiola Jimoh, Chiyu Wei, Teng
Yuan, and George Pappas. We had many good times and stimulating conversations in
and out of group meetings. You all have helped me to understand the goals I wish to
achieve.
i
TABLE OF CONTENTS
List of Tables .................................................................................................................... ii List of Figures .................................................................................................................. iii List of Abbreviations ........................................................................................................ iv Abstract .......................................................................................................................... vii Chapter 1: Introduction, Background and Highlights of Bimetallic Complexes ................ 1
1.1 Introduction to Bimetallic Complexes .......................................................... 1 1.2 Ligand Design for Bimetallic Complexes .................................................... 1 1.3 Properties of Bimetallic Complexes ............................................................ 3
1.3.1 Redox Potential Based on Metal-Metal Interaction .......................... 3 1.3.2 Catalytic Activity in Organic Transformations .................................. 3
1.4 Conclusion .................................................................................................. 3 1.5 References ................................................................................................. 4
Chapter 2: Large Scale Synthesis of Bis-4-Phenyl-Triazole 1,8-Naphthalene and
Metal Complexation Trials .......................................................................................... 6 2.1 Introduction and Background ...................................................................... 6 2.2 Experimental Methods and Procedures ...................................................... 7
2.2.1 General Information ......................................................................... 7 2.2.2 Representative Procedure for the Preparation of 1,8-Diiodonaphthalene 9 ....................................................................... 8 2.2.3 Representative Procedure for the Preparation of (E)-(2-nitrovinyl)benzene ....................................................................... 9 2.2.4 Representative Procedure for the Preparation of 4-Phenyl-1H-1,2,3-triazole 10 ............................................................... 9 2.2.5 Representative Procedure for the Preparation of 1,8-Bis(4-phenyl-2H-1,2,3-triazol-2-yl)naphthalene 12 ....................... 10 2.2.6 Representative Procedure for Metal Complexation Trials ............. 11
2.3 Results and Discussion ............................................................................ 11 2.3.1 Large Scale Synthesis of Naphthalene-Bridged Bis-Triazole ........ 11 2.3.2 Metal Complexation Trials of 12 .................................................... 13
2.4 Conclusions and Recommendations ........................................................ 14 2.5 References ............................................................................................... 19
Appendix ........................................................................................................................ 21
ii
LIST OF TABLES
Table 1 Metal complexation trials on 12 without the use of base .......................... 16 Table 2 Metal complexation trials on 12 using base .............................................. 17 Table 3 Metal complexation trials on 12 using ligated metal salts ......................... 18
iii
LIST OF FIGURES
Figure 1 Examples of bimetallic complexes using ligand-bridged metals ................. 2 Figure 2 Examples of bimetallic complexes with metal-metal interaction ................. 2 Figure 3 X-ray crystallographic structure of 12 and distances between nitrogens ..................................................................................................... 6
Figure 4 Proposed synthesis of bimetallic naphthalene-bridged bis-triazole ............ 7 Figure 5 Proposed ligand modifications for future complexation experiments ........ 15
iv
LIST OF ABBREVIATIONS
(CH2OH)2 ethylene glycol
(CH3OCH2)2 ethylene glycol dimethyl ether
[Hbpy][Ir(bpy)Cl4] [2,2'-bipyridin]-1-ium iridium (IV) chloride 2,2’-bipyridine
°C degrees Celsius
AuCl gold (I) chloride
bpy 2,2’-bipyridine
CDCl3 chloroform-d
CH3CN acetonitrile
CH3NO2 nitromethane
CO carbon monoxide
CoCl2 cobalt (II) chloride
Cu(bpy)Cl2 copper (II) chloride 2,2’-bipyridine
Cu(ClO4)2 copper (II) chlorate
CuBr copper (I) bromide
CuCl copper (I) chloride
CuCl2 copper (II) chloride
d doublet (in NMR)
d6-DMSO dimehylsulfoxide-d6
DCM dichloromethane
DMF dimethylformamide
v
DMSO dimethylsulfoxide
EGEE 2-ethoxyethanol
EtOH ethanol
Fe(bpy)Cl2 iron (II) chloride 2,2’-bipyridine
FeCl2 iron (II) chloride
g gram(s)
H2O water
HCl hydrochloric acid
Hz hertz
i-Pr isopropyl
IrCl3 irridium (III) chloride
K2CO3 potassium carbonate
KI potassium iodide
L-Pro L-proline
m milli, multiplet (in NMR)
M moles per liter
MeOH methanol
MHz megahertz
mmol millimole(s)
Na2S2O3 sodium thiosulfate
NaHCO3 sodium bicarbonate
NaN3 sodium azide
NaNO2 sodium nitrite
vi
NaOH sodium hydroxide
NBT naphthalene-bridged bis-triazole
NH4Cl ammonium chloride
Ni(bpy)Cl2 nickel (II) chloride 2,2’-bipyridine
NiCl2 nickel (II) chloride
NMR nuclear magnetic resonance
p-TsOH p-toluenesulfonic acid
Pd(bpy)Cl2 palladium (II) chloride 2,2’-bipyridine
Pd(OAc)2 palladium (II) acetate
PdCl2 palladium (II) chloride
PEG400 polyethylene glycol 400
PtCl2 platinum (II) chloride
Py pyridine
Rh2(OAc)4 rhodium (II) acetate dimer
RuCl3 ruthenium (III) chloride
s singlet (in NMR)
t triplet (in NMR)
vii
ABSTRACT
Bimetallic complexes are known to have unique electronic properties and are used
in a variety of organic transformations as catalysts. The use of naphthalene-bridged bis-
triazoles (NBT) for bimetallic complexes is unknown. NBTs have the unique property of
being fluorescent stemming from a twisted intramolecular charge transfer. With the non-
coplanar geometry and the distance between the 1,2,3-triazole rings, we hypothesized
that 1,8-bis(4-phenyl-2H-1,2,3-triazol-2-yl)naphthalene (12) would be a suitable ligand to
synthesize a bimetallic complex. The synthesis of 12 was optimized for large scale
synthesis and was synthesized on a 78 mmol scale in 15% total yield. Metal complexation
trials were conducted on 12 and several insoluble solids were observed.
1
CHAPTER 1:
INTRODUCTION, BACKGROUND AND HIGHLIGHTS OF BIMETALLIC COMPLEXES
1.1 Introduction to Bimetallic Complexes
Many organisms use bimetallic enzymes and cofactors to sustain biological
processes.1 These enzymes and cofactors include: Mo-Fe/V-Fe nitrogenases, Ni-Fe/Fe-
Fe hydrogenases, purple acid phosphatases, Ni-[3Fe-4S] CO dehydrogenases, and class
I ribonucleotide reductases.2-6 The combination of metals in these catalytic cycles allow
for lower energy barriers through redox cycles between the substrates and metals. Over
the past decade, many groups have explored the synthesis of bimetallic complexes and
clusters to study the effects of ligand-metal and metal-metal interactions on the properties
of these complexes and the reactivity toward catalytic transformations.
Bimetallic species exhibit many unique properties, but most interesting is auto-
redox in complexes where the metals are close enough for metal-metal interaction or
share exchangeable ligands which decreases the redox potential.7 This property can be
altered based on the metal-metal distance, the metal species, and the connecting ligand
design. Several groups have explored these manipulations and have discovered a
number of applications to their unique structures.
1.2 Ligand Design for Bimetallic Complexes
There are generally two types of bimetallic complexes: discrete metal centered and
close-proximity metal centered. Discrete metal centered complexes generally act as a
combination of two complexes where the metals do not influence one another in a
2
significant manner.8 For the purposes of this review on bimetallic complexes, we will focus
on close-proximity metal centered complexes for the properties the metals induce on one
another.
Figure 1. Examples of bimetallic complexes using ligand-bridged metals9,11
There are a few ligand designs that allow for metal-metal interaction. One of the
designs involves the use of bridging ligands between the metals. This design allows the
metals to interact by exchanging the ligand and thus decreasing the redox potential of
the metal pair. Several examples include halogen bridging ligands or organic bis-
chelating ligands (Figure 1).9-14 Another ligand design involves constructing coordinating
groups in close proximity to allow the metals to interact directly (Figure 2).1
Figure 2. Examples of bimetallic complexes with metal-metal interaction1
P PPd Pd
Cl ClCl Cl
i-Pri-Pr i-Pr
i-Pr
1
Co Co
N
N
2
N Co
Cl
CoN
N
N
N
N
NN Fe
Cl
CoN
N
N
N
N
NN Mn
Cl
CoN
N
N
N
N
NN Fe
Cl
FeN
N
N
N
N
NN Mn
Cl
FeN
N
N
N
N
N
3 4 5 6 7
3
1.3 Properties of Bimetallic Complexes
1.3.1 Redox Potential Based on Metal-Metal Interaction
Bimetallic complexes possessing a metal-metal interaction are susceptible to
autoredox or decreased oxidative or reductive potential. Lu et al. prepared Co-Co, Co-
Fe, Co-Mn, Fe-Fe, and Fe-Mn complexes that exhibit quasi-reversible/irreversible
oxidation and quasi-reversible/reversible reduction at low redox potentials.1 Qu et al..
prepared Co-Co and Co-Fe complexes that also exhibit reversible reduction at low redox
potentials.12
1.3.2 Catalytic Activity in Organic Transformations
Bimetallic complexes have shown useful in many organic transformations. One of
the oldest and most used bimetallic catalysts is Rh2(OAc)4. Rh2(OAc)4 has been used to
demonstrate C-H functionalization and cyclopropanation.13-14 Uyeda et al.. showed Ni-Ni
complexes were efficient for hydrosilyation reactions and alkyne cycloadditions.15-16
Iwasawa et al.. showed Pd-Al, Pd-Ga, and Pd-In complexes were efficient for
hydrosilyation reactions of carbon dioxide.17 Ritter et al.. showed Pd-Pd complexes were
efficient for hydroxylation reactions on ketones.18 Ding et al. showed cyanation of
aldehydes using Ti-Ti complexes bridged by oxo groups.19 Gong et al. were able to show
efficient oxidative coupling of 2-naphthols using V-V complexes that showed
enantioselectivity.20
1.4 Conclusion
Bimetallic complexes exhibit unique properties that act quite differently than the
monometallic complex of the same metal. These complexes exhibit unique electronic
properties. The electronic properties are the foundation for the unique catalytic reactivity
4
some complexes possess. Further investigations into bimetallic complexes will reveal
patterns with geometry, metal choice, and ligand design toward the electronic properties
they possess.
1.5 References
1. Tereniak, S.; Carlson, R.; Clouston, L.; Young Jr., V.; Bill, E.; Maurice, R.; Chen,
Y.; Kim, H.; Gagliardi, L; Lu, C. J. Am. Chem. Soc., 2014, 136, 1842–1855
2. Lee, C.; Hu, Y.; Ribbe, M. PNAS, 2009, 106, 9209-9214
3. Fontecilla-Camps, J.; Volbeda, A.; Cavazza, C.; Nicolet, Y. Chem. Rev., 2007,
107, 4273
4. Schenk, G.; Mitić, N.; Hanson, G.; Comba, P. Coordination Chemistry Reviews,
2013, 257, 473-482
5. Dobbek, H.; Svetlitchnyi, V.; Gremer, L.; Huber, R.; Meyer, O. Science, 2001, 293,
1281-1285
6. Cotruvo, J.; Stubbe, J. Annu Rev Biochem., 2011, 80, 733-767
7. Liddle, S. T. Molecular Metal-Metal Bonds: Compounds, Synthesis, Properties;
Wiley-VCH: Weinheim, 2015
8. Sabater, S.; Mata, J.; Peris, E. Eur. J. Inorg. Chem., 2013, 4764–4769
9. Azerraf, C.; Cohen, S.; Gelman, D. Inorg. Chem., 2006, 45, 7010−7017
10. Powers, D.; Ritter, T. Nature Chem., 2009, 1, 302-309
11. Mokhtarzadeh, C.; Carpenter, A.; Spence, D.; Melaimi, M.; Agnew, D.;
Weidemann, N.; Moore, C.; Rheingold, A.; Figueroa, J. Organometallics, 2017, 36,
2126–2140
5
12. Tong, P.; Xie, W.; Yang, D.; Wang, B.; Ji, X.; Lia, J.; Qu, J. Dalton Trans., 2016,
45, 18559-18565
13. Doyle, M.; Duffy, R.; Ratnikov, M.; Zhou, L. Chem. Rev., 2010, 110, 704–724
14. Davies, H.; Manning, J. Nature, 2008, 451, 417-424
15. Steiman, T.; Uyeda, C. J. Am. Chem. Soc., 2015, 137, 6104–6110
16. Pal, S; Uyeda, C. J. Am. Chem. Soc., 2015, 137, 8042–8045
17. Takaya, J.; Iwasawa, N. J. Am. Chem. Soc., 2017, 139, 6074–6077
18. Chuang, G.; Wang, W.; Lee, E.; Ritter, T. J. Am. Chem. Soc., 2011, 133, 1760–
1762
19. Zhang, Z.; Wang, Z.; Zhang, R.; Ding, K. Angew. Chem. Int. Ed., 2010, 49, 6746
–6750
20. Guo, Q.; Wu, Z.; Luo, Z.; Liu, Q.; Ye, J.; Luo, S.; Cun, L.; Gong, L. J. Am. Chem.
Soc., 2007, 129, 13927–13938
6
CHAPTER 2:
LARGE-SCALE SYNTHESIS OF BIS-4-PHENYL-TRIAZOLE 1,8-NAPHTHALENE AND METAL COMPLEXATION TRIALS
2.1 Introduction and Background
Bimetallic complexes possess unique properties and applications. They are used
for catalysis, electronics, and magnetic applications.1-3 Qu et al. synthesized Co-Co and
Co-Cu bimetallic complexes using dithiolate as the bis-chelating ligand which exhibited
the potential to reduce protons for hydrogen evolution.4 Carmona et al. produced a Mo-
Mo quadruple bonded bimetallic complex exhibiting reactivity toward hydrogen
activation.5
Figure 3. X-ray crystallographic structure of 12 and distances between nitrogens6
7
In 2014, Shi et al. synthesized the first naphthalene-bridged bis-triazole (NBT).6
These NBTs exhibited a unique non-planarity and distances comparable to metal-metal
bond distances (Figure 1). Thus, we explored the large-scale synthesis and metal
complexation of 12 (Figure 2). Through optimization of the reaction conditions and
synthetic pathway, we could synthesize enough 12 to explore metal complexation.
Figure 4. Proposed synthesis of bimetallic naphthalene-bridged bis-triazole
2.2 Experimental Methods and Procedures
2.2.1 General Information
All reactions dealing with air and/or moisture-sensitive reactions were carried out
under an atmosphere of argon using oven-dried glassware and standard syringe/septa
techniques. Unless otherwise noted, all commercial reagents and solvents were obtained
from commercial providers and used without further purification. The following
compounds were prepared by literature methods: Cu(bpy)Cl2, Fe(bpy)Cl2,
II
NHNN
NINN
NN NN NN
NH2 NH2 1. HCl, NaNO2
2. KI CuBr, L-Pro, K2CO3
CuBr, L-Pro, K2CO3
MLn, Base
N
N
N
MLn MLn
N
N
N
8 9
10
11
10
12 13
8
[Hbpy][Ir(bpy)Cl4], Ni(bpy)Cl2, and Pd(bpy)Cl2.7-11 Chemical shifts were reported relative
to internal tetramethylsilane (d 0.00 ppm), d6-DMSO (d 2.50 ppm), or CDCl3 (d 7.26 ppm)
and d6-DMSO (d 39.5 ppm) or CDCl3 (d 77.0 ppm) for 13C NMR on an INOVA-400
magnet.
2.2.2 Representative Procedure for the Preparation of 1,8-Diiodonaphthalene 9
Procedure modified from Göbel et al.12 8 (50 g, 300 mmol) was pulverized to a fine
powder using a mortar and pestle. The powder was added to 12 M HCl (500 mL) in a 4 L
Erlenmeyer flask equipped with an overhead mechanical stirrer. The mixture was stirred
as ice-water (500 mL) was added slowly. The reaction vessel was cooled in a salt-ice
bath. To the vigorously stirred reaction vessel, NaNO2 (65 g, 900 mmol) dissolved in water
(500 mL) was added over 30 minutes making sure the reaction did not exceed 5 °C. After
adding the NaNO2 solution, KI (315 g,1.8 mol) dissolved in water (500 mL) was added
over 30 minutes. After addition of the KI solution, the reaction flask was heated on a
hotplate until iodine fumed above the solution. Once cool, the reaction mixture was slowly
neutralized with solid NaOH (240 g). The mixture was then filtered through a cotton plug.
The collected solid was subjected to Soxhlet extraction with diethyl ether (500 mL). The
extract was then diluted with diethyl ether until completely dissolved. The ethereal solution
was transferred to a separatory funnel and washed with saturated Na2S2O3 solution until
no more iodine remained in the organic layer. The ethereal solution was washed with
brine and then passed through a silica gel plug. The ether was evaporated and the
product was recrystallized from hot hexanes to yield yellow needles (34.197 g, 30% yield).
1H NMR (400 MHz, CDCl3): d 8.41 (dd, J = 7.6, 1.2 Hz, 2H), 7.82 (dd, J = 8.0, 1.2 Hz,
9
2H), 7.05 (dd, J = 8.0, 7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3): d 172.5, 144.0, 131.0,
126.9, 110.0, 96.0.
2.2.3 Representative Procedure for the Preparation of (E)-(2-nitrovinyl)benzene
Procedure modified from Johnson et al.13 To an Erlenmeyer flask of methanol (400
mL), NaOH (20 g, 500 mmol) was added Once the methanolic solution cooled, it was
added dropwise to a stirred solution of freshly distilled benzaldehyde (40 mL, 394 mmol)
and CH3NO2 (60 mL, 1.118 mol) in a round-bottom flask cooled to 0 °C. The reaction was
allowed to stir for an additional 30 minutes, then was poured into ice cold 1 M HCl (500
mL). The mixture was vacuum filtered onto a filter paper lined Buchner funnel and the
precipitate was washed with ice-cold water and ice-cold ethanol. The product was
recrystallized from DCM and hexanes to afford yellow needles (48.39 g, 82% yield). 1H
NMR (400 MHz, CDCl3): d 7.96 (d, J = 13.6 Hz, 1H), 7.56 (d, J = 13.6 Hz, 1H), 7.52-7.47
(m, 5H). 13C NMR (100 MHz, CDCl3): d 172.8, 137.4, 132.5, 130.4, 129.7, 129.5.
2.2.4 Representative Procedure for the Preparation of 4-Phenyl-1H-1,2,3-triazole 10
Procedure modified from Guan et al.14 NaN3 (31.64 g, 810 mmol) and DMSO (300
mL) were added to a round bottom flask equipped with a magnetic stir bar. The mixture
was heated to 90 °C and a solution of (E)-(2-nitrovinyl)benzene (48.39 g, 324 mmol) and
p-TsOH•H2O (18.53 g, 324 mmol) in DMSO (300 mL) was added dropwise over 30
minutes. The reaction mixture was allowed to stir for an additional 10 minutes and then
transferred to a separatory funnel. The mixture was diluted with ethyl acetate and
saturated NH4Cl solution was added. The mixture was extracted with saturated NH4Cl
three times. The organic layer was washed with saturated NaHCO3 solution and brine,
then dried with anhydrous sodium sulfate. The organic solution was concentrated and
10
recrystallized with hot toluene to afford white needles (27.90 g, 60% yield). 1H NMR (400
MHz, d6-DMSO): d 8.34 (s, 1H), 7.87 (dt, J = 8.0, 1.6 Hz, 2H), 7.44 (tt, J = 8.0, 1.6 Hz,
2H), 7.33 (tt, J = 8.0, 1.6 Hz, 1H). 13C NMR (100 MHz, d6-DMSO): d 152.5, 129.3, 126.0,
115.2, 114.7, 110.0.
2.2.5 Representative Procedure for the Preparation of 1,8-Bis(4-phenyl-2H-1,2,3-triazol-
2-yl)naphthalene 12
Procedure modified from Shi et al.6 9 (30 g, 79 mmol), 10 (12.61 g, 86.9 mmol),
CuBr (1.13 g, 7.9 mmol), L-proline (1.82 g, 15.8 mmol), and K2CO3 (21.82 g, 158 mmol)
were added to a round bottom flask equipped with a magnetic stir bar. The flask was
sealed with a septum and the atmosphere was replaced with argon. Dry DMSO (200 mL)
was added to the flask via syringe and the flask was heated to 80 °C for 6 hours. The
contents were filtered through a pad of Celite and transferred to a separatory funnel. The
mixture was diluted with ethyl acetate and water was added. The mixture was extracted
with brine three times. The organic layer was passed through a pad of silica gel and
evaporated. The intermediate product 11 was confirmed by crude NMR and then
transferred to a round bottom flask equipped with a magnetic stir bar. 11 (28.66 g, 23.7
mmol), CuBr (1.13 g, 7.9 mmol), L-proline (1.82 g, 15.8 mmol), and K2CO3 (27.28 g, 23.7
mmol) were added and sealed with a septum. The atmosphere was replaced with argon
and DMSO (400 mL) was added via a syringe. The flask was heat to 120 °C for 12 hours,
then the contents were filtered through a pad of Celite and transferred to a separatory
funnel. The mixture was diluted with ethyl acetate and water was added. The mixture was
extracted with brine three times. The organic layer was passed through a pad of silica gel
and evaporated. The residue was dissolved in ethyl acetate and triturated with hexanes,
11
filtered and recrystallized from DCM and hexanes to afford yellow crystals (16.36 g, 50%
yield). 1H NMR (400 MHz, CDCl3): d 8.09 (dd, J = 8.4, 1.2 Hz, 2H), 7.95 (dd, J = 7.4, 1.2
Hz, 2H), 7.68 (dd, J = 8.2, 7.4 Hz, 2H), 7.57 (s, 2H), 7.52−7.47 (m, 4H), 7.28−7.21 (m,
6H). 13C NMR (100 MHz, CDCl3): d 172.3, 148.1, 148.0, 135.4, 135.3, 129.9, 129.2, 128.3,
126.8, 125.7, 123.7, 109.8.
2.2.6 Representative Procedure for Metal Complexation Trials
12 (41 mg, 0.1 mmol), metal salt (1-4 equiv.), base (2-10 equiv.), and solvent (0.1-
0.5 M) were added to a 5 mL vial equipped with a magnetic stirbar. The vial was fitted
with a septum and the atmosphere replaced with argon. The vial was heated up to the
specified temperature. The reaction was allowed to run for 8 hours. The reaction progress
was checked by thin layer chromatography. Once complete the mixture was filtered by
vacuum filtration and NMR was conducted on the filtrate using matching deuterated
solvent. The filtered solid was collected and weighed, but proved insoluble for NMR
characterization.
2.3 Results and Discussion
2.3.1 Large Scale Synthesis of Naphthalene-Bridged Bis-triazole
The scalability of the ligand hinges on three substrates: 9, 10, and 12. The
challenge associated with synthesizing 9 is the low yields and the purification of the
starting material 8. The challenge associated with synthesizing 10 was the purification
involving column chromatography. The challenge associated with synthesizing 12 was
the purification involving column chromatography.
To alleviate one challenge with 9, it was found that the commercially prepared 8
could be pulverized with a mortar and pestle and mixed with concentrated HCl before
12
affording the product with little diminished yield from the literature.12 When testing the
particle size dependence on the yield, it was found that the unaltered commercial reagent
in concentrated HCl produced the product in 10% yield. When testing the acid
concentration dependence on the yield, it was found that diluted acid produced the
product in 20% yield when the commercial reagent was pulverized into a fine powder.
Thus, combining ground 8 with concentrated HCl produced the product in 30% yield.
The synthesis of 10 can be completed using a variety of routes. Typically, similar
triazoles are synthesized using protected-azide and phenylacetylene with copper sulfate
and sodium ascorbate as demonstrated by Sharpless et al.15 This method generally
produces high yields and requires three steps in synthesis. The drawback of this route is
the need of column chromatography to purify the protected triazole and the deprotected
triazole.
Another route, the one used, was to synthesize (E)-(2-nitrovinyl)benzene through
the Henry reaction and then undergo a cycloaddition reaction with sodium azide. This
route had a few benefits: the (E)-(2-nitrovinyl)benzene was reported with recrystallization
for purification and the yields were high. When conducted, it was found that yields were
dependent on the reverse Henry reaction occurring in the cycloaddition step and the
scalability was dependent on the amount of DMSO used. Guan et al. showed high yields
with p-TsOH, but when repeated the yields were far from reported values.14 Modifications
to the literature procedure showed increasing p-TsOH and the concentration affected the
yield and scalability of the reaction. It was also found that the product could be purified of
the impurities through acid-base extraction and recrystallization in toluene to supply 10 in
60% yield.
13
Shi et al. produced 12 in good yield utilizing a one-step protocol, but purification
required column chromatography.6 When tried, it was found the reaction was not clean
and indeed would require chromatography to purify, but the two step protocol using CuBr
as the catalyst produced cleaner reactions and could be purified by recrystallization with
50% yield.
2.3.2 Metal Complexation Trials of 12
Complexation of 12 began by heating in the presence of metal salts in ethanol
(Table 1, Entries 1-11). Unfortunately, the solubility of the ligand was potentially a
hindrance to the experiments. Next, the method used for generating iridium triazole
complex from Shi et al. was used and produced an insoluble yellow-orange powder (Entry
12).17 This result possibly indicated an inorganic polymer was generated. Next, the use
of solvents that may coordinate with the proposed metal complex were used to increase
the solubility of the generated complex (Entries 13-16). Unfortunately, these trials resulted
in no conversion of the starting material. This may be due to the lack of base in the
reaction.
Next, complexation of 12 using various bases in a variety of solvents was tested
(Table 2). First, Cu(ClO4)2 with 2,6-lutidine was tested using a method similar to Wang et
al. (Entry 1).16 With an insoluble blue-green powder being formed that was unstable to
humidity, CuCl2 was used to try to make a more stable solid (Entry 2). An insoluble purple
powder was formed and was also unstable to humidity. From that bpy was tested as a
base and axial ligand for a variety of metal salts, but no conversion of starting material
was observed (Entries 3-7). From that K2CO3 was tried as a base for a variety of metal
salts (Entries 8-12). An insoluble blue-green powder was observed for Cu and Ni, but
14
both were unstable to humidity (Entries 8-9). When testing other metals using K2CO3, no
conversion of the starting material was observed (Entries 10-12).
These results led to the hypothesis that using pre-ligated metal salts would
produce complexes that were more soluble and stable than previous examples (Table 3).
Trying bpy ligated metal salts using Py as the base resulted in no conversion of the
starting material (Entries 1-5). We hypothesized Py could interfere with the complexation
due to the ease of coordination, so we used 2,6-lutidine as the base to avoid this due to
steric hindrance (Entries 6-10). Unfortunately, 2,6-lutidine as base did not convert the
starting material.
2.4 Conclusions and Recommendations
The large-scale synthesis of 12 was successfully implemented. Several
complexation trials were tested and led to a few insoluble solids that are to be improved
upon. Future complexation experiments could be improved by increasing the solubility of
the ligand and thereby increase the solubility of the metal complex or by modification of
the coordination mode of the ligand. These ligand modifications could include aliphatic
substituents on the aromatic rings 14, 2-pyridyl substitution of the phenyl rings 15, or
carboxylate substitution of the 5’ positon on the triazoles 16 (Figure 5). Another
modification of the ligand could include synthesizing asymmetric NBTs as seen in Shi’s
paper.6 Other complexation experiments could also include using a step-wise
coordination generating mixed metal complexes. Once a complex is generated it could
be tested for catalysis and materials applications.
15
Figure 5. Proposed ligand modifications for future complexation experiments
PhN
N
N
NMLn MLn
N
N
N
N
14
N
N
N
OMLn MLn
O
N
N
N
16
N
N
N
MLn MLn
N
N
N
15
alkyl alkyl
Ph
O O
16
Tabl
e 1.
Met
al c
ompl
exat
ion
trial
s on
5 w
ithou
t the
use
of b
asea
Res
ult
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
Inso
lubl
e ye
llow
-ora
nge
pow
der
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
a Rea
ctio
n C
ondi
tions
: 5 (0
.1 m
mol
), m
etal
sal
t (4
equi
v.),
12 h
. b Rea
ctio
n co
nditi
ons
from
ref 1
7: E
GEE
:H2O
= 3
:1.
Tem
pera
ture
(°C
)
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
140
°C
180
°C
180
°C
180
°C
80 °
C
Solv
ent (
M)
EtO
H (0
.1 M
)
EtO
H (0
.1 M
)
EtO
H (0
.1 M
)
EtO
H (0
.1 M
)
EtO
H (0
.1 M
)
EtO
H (0
.1 M
)
EtO
H (0
.1 M
)
EtO
H (0
.1 M
)
EtO
H (0
.1 M
)
EtO
H (0
.1 M
)
EtO
H (0
.1 M
)
EGEE
/H2O
(0.0
25 M
)
(CH
2OH
) 2 (0
.1 M
)
DM
SO (0
.1 M
)
PEG
400 (
0.1
M)
CH
3CN
(0.1
M)
Met
al S
alt (
equi
v.)
FeC
l 2 (4
equ
iv.)
FeC
l 3 (4
equ
iv.)
PdC
l 2 (4
equ
iv.)
NiC
l 2 (4
equ
iv.)
CoC
l 2 (4
equ
iv.)
AuC
l (4
equi
v.)
PtC
l 2 (4
equ
iv.)
RuC
l 3 (4
equ
iv.)
CuC
l (4
equi
v.)
CuC
l 2 (4
equ
iv.)
IrC3 (
4 eq
uiv.
)
IrCl 3
(4 e
quiv
.)
IrCl 3
(4 e
quiv
.)
IrCl 3
(4 e
quiv
.)
IrCl 3
(4 e
quiv
.)
IrCl 3
(4 e
quiv
.)
Entry
1 2 3 4 5 6 7 8 9 10
11
12b
13
14
15
16
17
Tabl
e 2.
Met
al c
ompl
exat
ion
trial
s on
5 u
sing
bas
ea
Res
ult
Inso
lubl
e bl
ue p
owde
r
Inso
lubl
e pu
rple
pow
der
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
Inso
lubl
e gr
een
pow
der
Inso
lubl
e gr
een
pow
der
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
a Rea
ctio
n C
ondi
tions
: 5 (0
.1 m
mol
), 12
h. b R
eact
ion
cond
ition
s fro
m re
f 16:
DC
M:M
eOH
= 8
:2). Te
mpe
ratu
re (°
C)
25 °
C
60 °
C
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
100
°C
100
°C
100
°C
100
°C
100
°C
Base
(equ
iv.)
2,6-
lutid
ine
(10
equi
v.)
2,6-
lutid
ine
(10
equi
v.)
bpy
(12
equi
v.)
bpy
(12
equi
v.)
bpy
(12
equi
v.)
bpy
(12
equi
v.)
bpy
(12
equi
v.)
K 2C
O3 (
4 eq
uiv.
)
K 2C
O3 (
4 eq
uiv.
)
K 2C
O3 (
4 eq
uiv.
)
K 2C
O3 (
4 eq
uiv.
)
K 2C
O3 (
4 eq
uiv.
)
Solv
ent (
M)
DC
M/M
eOH
(0.1
M)
CH
3CN
(0.1
M)
CH
3CN
(0.1
M)
CH
3CN
(0.1
M)
CH
3CN
(0.1
M)
CH
3CN
(0.1
M)
CH
3CN
(0.1
M)
DM
SO (0
.5 M
)
DM
SO (0
.5 M
)
DM
SO (0
.5 M
)
DM
SO (0
.5 M
)
DM
SO (0
.5 M
)
Met
al S
alt (
equi
v.)
Cu(
ClO
4)2•
6(H
2O) (
4 eq
uiv.
)
CuC
l 2 (4
equ
iv.)
CuC
l 2 (4
equ
iv.)
NiC
l 2•(C
H3O
CH
2)2 (
4 eq
uiv.
)
FeC
l 2•4(
H2O
) (4
equi
v.)
Pd(O
Ac) 2
(4 e
quiv
.)
IrCl 3
(4 e
quiv
.)
CuC
l 2 (4
equ
iv.)
NiC
l 2•(C
H3O
CH
2)2 (
4 eq
uiv.
)
FeC
l 2•4(
H2O
) (4
equi
v.)
Pd(O
Ac) 2
(4 e
quiv
.)
IrCl 3
(4 e
quiv
.)
Entry
1b
2 3 4 5 6 7 8 9 10
11
12
18
Tabl
e 3.
Met
al c
ompl
exat
ion
trial
s on
5 u
sing
liga
ted
met
al s
alts
a
Res
ult
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
No
conv
ersi
on
a Rea
ctio
n C
ondi
tions
: 5 (0
.1 m
mol
), m
etal
sal
t (2
equi
v.),
DM
F (0
.1 M
), 80
°C
, 12
h Tem
pera
ture
(°C
)
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
80 °
C
Base
(equ
iv.)
Py (8
equ
iv.)
Py (8
equ
iv.)
Py (8
equ
iv.)
Py (8
equ
iv.)
Py (8
equ
iv.)
2,6-
lutid
ine
(10
equi
v.)
2,6-
lutid
ine
(10
equi
v.)
2,6-
lutid
ine
(10
equi
v.)
2,6-
lutid
ine
(10
equi
v.)
2,6-
lutid
ine
(10
equi
v.)
Solv
ent (
M)
DM
F(0.
1 M
)
DM
F(0.
1 M
)
DM
F(0.
1 M
)
DM
F(0.
1 M
)
DM
F(0.
1 M
)
DM
F(0.
1 M
)
DM
F(0.
1 M
)
DM
F(0.
1 M
)
DM
F(0.
1 M
)
DM
F(0.
1 M
)
Met
al S
alt (
equi
v.)
Fe(b
py)C
l 2 (2
equ
iv.)
Cu(
bpy)
Cl 2
(2 e
quiv
.)
Ni(b
py)C
l 2 (2
equ
iv.)
Pd(b
py)C
l 2 (2
equ
iv.)
[Hbp
y][Ir
(bpy
)Cl 4)
(2 e
quiv
.)
Fe(b
py)C
l 2 (2
equ
iv.)
Cu(
bpy)
Cl 2
(2 e
quiv
.)
Ni(b
py)C
l 2 (2
equ
iv.)
Pd(b
py)C
l 2 (2
equ
iv.)
[Hbp
y][Ir
(bpy
)Cl 4)
(2 e
quiv
.)
Entry
1 2 3 4 5 6 7 8 9 10
19
2.5 References
1. Pyea, D.; Mankad, N. Chem. Sci., 2017, 8, 1705-1718
2. Georgiev, V.; Mohan, P.; DeBrincat, D.; McGrady, J. Coordination Chem. Rev.,
2013, 257, 290–298
3. Gilroy, K.; Ruditskiy, A.; Peng, H.; Qin, D.; Xia, Y. Chem. Rev., 2016, 116, 10414–
10472
4. Tong, P.; Xie, W.; Yang, D.; Wang, B.; Ji, X.; Lia, J.; Qu, J. Dalton Trans., 2016,
45, 18559-18565
5. Curado, N.; Carrasco, M.; Campos, J.; Maya, C.; Rodríguez, A.; Ruiz, E.; Álvarez,
S.; Carmona, E. Chem. Eur. J., 2017, 23, 194 –205
6. Zhang, Y.; Ye, X.; Petersen, J.; Li, M.; Shi, X. J. Org. Chem., 2015, 80, 3664–3669
7. Detoni, C.; Carvalho, N.; de Souza, R.; Aranda, D.; Antunes, O. Catal Lett, 2009,
129, 79–84
8. Khrizanforov, M.; Strekalova, S.; Khrizanforova, V.; Grinenko, V.; Kholin, K.;
Kadirov, M.; Burganov, T.; Gubaidullin, A.; Gryaznova, T.; Sinyashin, O.; Xu, L.;
Vicic, D.; Budnikova, Y. Dalton Trans., 2015, 44, 19674-19681
9. Cipriano, R.; Hanton, L.; Levason, W.; Pletcher, D.; Powell, N.; Webster, M. Dalton
Trans, 1988, 2483–2490
10. Xiao, Y.; Min, Q.; Xu, C.; Wang, R.; Zhang, X. Angew. Chem. Int. Ed., 2016, 55,
5837–5841
11. BaniKhaled, M.; Becker, J.; Koppang, M.; Sun, H. Cryst. Growth Des., 2016, 16,
1869–1878
12. Weimar, M.; Dürner, G.; Bats, J.; Göbel, M. J. Org. Chem., 2010, 75, 2718–2721
20
13. Boyce, G.; Johnson, J. J. Org. Chem., 2016, 81, 1712–1717
14. Quan, X.; Ren, Z.; Wang, Y.; Guan, Z. Org. Lett., 2014, 16, 5728–5731
15. Rostovtsev, V.; Green, L.; Fokin, V.; Sharpless, B. Angew. Chem. Int. Ed., 2002,
41, 2596–2599
16. Zhang, H.; Yao, B.; Zhao, L.; Wang, D.; Xu, B.; Wang, M. J. Am. Chem. Soc.,
2014, 136, 6326–6332
17. Cai, R.; Yan, W.; Bologna, M.; de Silva, K.; Ma, Z.; Finklea, H.; Petersen, J.; Li,
M.; Shi, X. Org. Chem. Front., 2015, 2, 141–144
21
APPENDIX
NMR data for Chapter 2
22
2.1
2.1
2.33
2.33
22
001
1223
3445
5667
7889
9ppm
II
9
23 0
010
1020
2030
3040
4050
5060
6070
7080
8090
9010
010
0110
1101
2012
0130
1301
4014
0150
1501
6016
0170
1701
8018
0190
1902
0020
0ppm
II
9
24
5.26
5.261.14
1.14
11
001
1223
3445
5667
7889
9ppm
NO2
(E)-(2-nitrovinyl)benzene
25 0
010
1020
2030
3040
4050
5060
6070
7080
8090
90100
100110
110120
120130
130140
140150
150160
160170
170180
180190
190200
200ppm
NO2
(E)-(2-nitrovinyl)benzene
26
0.991
0.991 1.99
1.99
22
0.904
0.904
001
1223
3445
5667
7889
9ppm
NH
NN
10
27 0
010
1020
2030
3040
4050
5060
6070
7080
8090
9010
010
0110
1101
2012
0130
1301
4014
0150
1501
6016
0170
1701
8018
0190
1902
0020
0ppm
NH
NN
10
28
6.01
6.01
3.92
3.921.85
1.85 2.02
2.02
1.91
1.91 2
2
001
1223
3445
5667
7889
9ppm
NN
NN
NN 12
29
002
020
4040
6060
8080
100
1001
2012
0140
1401
6016
0180
1802
0020
0ppm
NN
NN
NN 12