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Toward the Synthesis of Naphthalene-Bridged Bis-Triazole Bimetallic ComplexesSean M. JohnsonUniversity of South Florida, seanjohnson@mail.usf.edu

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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