i

The Synthesis of Substituted Pentadentate Ligand Scaffolds and their Future Application

in Ruthenium-Catalyzed Water Oxidation

By

Manpreet Singh

A thesis submitted to the faculty of the University of Mississippi in partial fulfillment of

the requirements of the Sally McDonnell Barksdale Honors College

Oxford

May 2016

Approved by

__________________________________

Advisor: Doctor Jonah Jurss

__________________________________

Reader: Doctor Jared Delcamp

__________________________________

Reader: Doctor Gregory Tschumper

ii

© 2016

Manpreet Singh

ALL RIGHTS RESERVED

iii

ABSTRACT

Rising global energy demands coupled with depleting natural resources have led to a strong

emphasis on finding new sources of energy that are renewable and which limit the negative

impact on the environment. One of the strongest candidates is utilizing solar energy to drive

water oxidation to produce hydrogen as a fuel source. In order to do this, a better

understanding of the mechanism involved in this process must be revealed. Homogenous

molecular catalysts allow mechanistic studies and can be also used in Photoelectrochemical

Cells (PECs) and other systems to produce chemical fuels. In this work, the new syntheses

of 2,6-bis(1,1-bis(2-pyrazyl)ethyl)pyrazine (PZ5Me2) and 2,6-bis(1,1-di(pyridin-2-

yl)ethyl)pyrimidine (PY4PMMe2) are described, in addition several previously reported

pentadentate polypyridine derivatives have been prepared, all of which will be ligated to

ruthenium to form new catalysts for water oxidation.

iv

ACKNOWLEDGEMENTS

I would like to thank Dr. Jurss for his tremendous support throughout my undergraduate

career. His constant guidance and encouragement is greatly appreciated and I can truly

say I have learned a great deal since working under his direction. I would like to also

thank all of the graduate students in the Jurss group, especially Amir Khadivi, Lizhu

Chen, and Sayontani Sinha Roy, for their help in the lab and answering my questions. My

deepest gratitude goes to my friends and family who provide me with great support. I

would like to acknowledge my mom Kamlesh Kaur, my sister Harpreet Kaur, and my

best friends Kajol Champaneri and Hetal Champaneri. These women inspire and motivate

me to work hard every day and become the best person I can be. Finally, I would like to

thank the Sally McDonnell Barksdale Honors College for funding my project and making

my time at the University of Mississippi a unique experience.

v

TABLE OF CONTENTS

Introduction…………………………………………………..………….……………...1

Energy Crisis……………………………………………………………………1

Water Oxidation………………………………………………………………...6

Natural Photosynthesis and Water Splitting in the OEC……………………….7

Historical Water Oxidation Catalysts…………………………………………..11

Results and Discussion…………………………………………………….….........…..15

Conclusion………………………………………………………………….…………..20

Experimental Procedure……………………………..…………………………...…….21

References……………………………………………………….…………..…………24

1H NMR Data…………………………………….……………………..……………...30

13C NMR Data…………………………………….……………………..….......……...35

1

Introduction.

Energy Crisis

One of the biggest challenges facing modern civilization is mitigating the effects of

fossil fuel consumption and creating a sustainable energy future. With the ever decreasing

amount of nonrenewable fossil fuels paired with an increasing demand for these resources,

this energy crisis paints a bleak image of the future if “business as usual” continues. In the

United States alone, 81% of the energy consumed in 2014 was from nonrenewable sources

(petroleum, natural gas, and coal), whereas nuclear power and renewable sources only

provided 8% and 10%, respectively.[1] The category of renewable sources includes all

energy generated from solar, geothermal, wind, biomass, hydroelectric as shown in (Figure

1), which shows how little these sources have been utilized as means of energy production.

Figure 1: Energy consumption by energy source in the year 2014.[1]

2

By 2050, the Energy Information Agency (EIA) projects a 56% increase in energy

consumption.[2] In addition to the increasing energy demand, because the main sources of

energy are not renewable, there is a limit to what we can extract from the earth. Some

forecasters have predicted the peak of oil production to occur within the decade, while

others have projected it to be much later.[3] If preventative measures are not taken,

dwindling supply could have an especially disastrous effect on the United States, which

alone consumes 21% of the total oil produced in the world.[4]

While the consumption and the production are big problems, another problem is the

negative consequences of burning fossil fuels on the environment. Using nonrenewable

carbon-based fuels like coal releases greenhouse gasses into the atmosphere that are

attributed as the main source of global warming. In the last 150 years, there has been an

increase in atmospheric CO2 levels from 280 parts per million to over 400 parts per million

due in part to industrial activity.[5] In addition, CO2 from the atmosphere has been diffusing

into the oceans at a higher rate to form carbonic acid (H2CO3) and has directly caused an

increase in oceanic acidity by 30%.[6] These statistics show the significant impact that

human activity has had on the environment.

In light of these challenges, there are clear motives for pursing sustainable energy

technologies in order to minimize the negative impacts of fossil fuel combustion. With

strong efforts from the scientific community, there has been a global campaign to switch

to alternative sources of energy. One of the main results of this campaign has been a keen

interest in harnessing the free energy provided by the sun. Annually, the earth’s atmosphere

receives 342 watts (W) of solar energy/m2, of which 144 W/m2 is absorbed by the Earth’s

surface.[6] Based on these values, the theoretical potential of the sun’s extractable energy

3

is calculated to be 89,300 TW, which means more energy strikes the earth’s surface in 1.5

hours than worldwide energy consumption in 2001 from all sources combined.[7]

While these numbers validate the sun’s potential to serve as the ultimate power source,

there are many problems currently associated with solar energy. First, solar energy is

intermittent and only available when the sun is visible to solar panels. Second, the energy

obtained from the sun must be stored in an effective manner in order to use when needed

and for mobile applications, primarily transportation. To solve these problems of energy

storage and transportation, photocatalytic water splitting to produce H2 has received

significant interest as a way to store solar energy in the form of chemical bonds. The

splitting of H2O is of particular interest because it a carbon neutral process in which the

only byproduct is O2. In addition, the combustion of H2 would yield water as the only

byproduct. This splitting of water occurs in two different steps, proton reduction and water

oxidation depicted in Equation 1 and 2, respectively.

2H2O O2 + 4H+ + 4e- (1)

4H+ + 4e- H2 (2)

Photoelelectrochemical Cells (PECs) incorporate these two half-reactions into one

system by employing separate catalysts for water oxidation and proton reduction.

Producing H2 as a fuel using this artificial photosynthetic process requires the integration

of multiple steps. The first step is light absorption, then excited-state electron transfer,

followed by directional long-range electron transfer driven by free energy gradients, which

4

allows for single-electron transfer activation of multi-electron catalysis.[8] Figure 2 depicts

a generic PEC design based on a “dye-sensitized solar cell” configuration in which an

excited state chromophore (C) transfers electrons into the conduction band of a

semiconductor (S), which is aided by the absence of energy levels between the conduction

and valence bands. This property inhibits back electron transfer once redox equivalents are

delivered to the cathode and is required for multi-electron reactions where multiple redox

equivalents must be concentrated at a single site in order for water oxidation to occur. [8]

Figure 2: A generic photoelectrochemical cell (PEC) for water splitting.[8]

While the PEC device shows a simple and straightforward mechanism for

production of H2 from sunlight, this technology is still at its initial stages before it may be

able to provide an efficient solution. Often times, heterogeneous materials are used in

catalyzing water oxidation and proton reduction. These have their limitations in that they

often have restricted active sites for catalysis, while the remainder of the structure primarily

serves as a scaffold for stability purposes.[9] With the use of molecular catalysts, which

have a compact and tunable active site, a higher volumetric activity can be retained with

S

5

comparably small stabilizing scaffolds. Mechanistic studies of these molecules can be

performed using electrochemical techniques which can provide further insight into the

design of future motifs capable of hydrogen production and also serve as models for

complex biological metalloenzyme active sites and advanced materials.[10] In lieu of these

advantages, molecular catalysts also face limitations in their applicability due to their high

overpotentials (amount of energy needed versus the thermodynamic value of a given

reaction), limited catalytic activity in water, and short lifetimes.

6

Water Oxidation

The water oxidation step in water splitting is the most challenging step because it

is thermodynamically and kinetically demanding. This step requires the removal of four

electrons and four protons from two water molecules and the concomitant formation of an

O-O bond, which is a key step in evolving O2.[8] The water oxidation step in Equation 1

has an standard electrode potential (E°) of -1.23 V vs NHE at pH 0 and an Eo of -0.815 V

at pH 7, calculated using Equation 3, in which n = number electrons, F is Faraday’s constant

(96485 C mol-1), and Eo is the standard cell potential.

∆Go = −n F Eo (3)

Due to this being a four-electron reaction, it has a relatively high free-energy

change of 359 kJ mol-1.[10] To obtain four protons and four electrons during the oxidation

of water, and achieve oxygen-oxygen bond formation, multiple intermediates at the catalyst

site are required. Such a mechanism avoids inefficient one-electron transfer intermediates

like ∙OH due to their slow formation or high overpotential, E° of the OH/H2O is -2.31 V.[11]

By avoiding single electron transfer in favor of accumulating multiple redox equivalents at

the single catalytic site, multi-electron catalysis can be carried out at more modest

potentials.[11] Proton coupled electron transfer occurs throughout this process as a natural

consequence of the decreasing electron density on the metal; charge build up is avoided as

protons (H+) are lost as electrons are removed.[11]

7

Natural Photosynthesis and Water Splitting in the OEC

While water oxidation is very difficult and may appear to be a daunting endeavor,

Nature has provided a blueprint for this reaction, which is a key step in photosynthesis.

Photosynthesis is the process in which biological molecules use energy from the sun to

generate an electrochemical potential, which is coupled to the synthesis of adenine

triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH). ATP is

the molecular unit of currency in intracellular energy transfer which is fundamentally used

to power all anabolic processes in biological systems.[12] The NADPH produced is a

cofactor and also used in anabolic processes like lipid synthesis, but primarily serves as a

reducing agent or electron donor in photosynthesis. The splitting of water evolves O2 gas

and produces electrons, which are ultimately funneled to NADP+ via many enzymes and

electron shuttles to produce NADPH. Water oxidation (equation 1) in natural

photosynthesis ultimately enables carbon dioxide reduction to carbohydrates in the Calvin

cycle. The overall reaction is given in equation 4.

6H2O + 6CO2 + 24h → C6H12O6 + 6O2 (4)

Equation 4 is a simple representation of an overall reaction that involves a very intricate

and complex process as summarized partially (excluding the Calvin cycle) in the so-called

Z scheme of photosynthesis, Figure 3[12]. In Photosystem II, photons absorbed by the

antenna chlorophyll units of the plant chloroplast excite pigment 680 (P680) to P680* which

8

then donates an electron to pheophytin to form P680+. The pheophytin donates an electron

to plastoquinone and goes through the Q cycle and then finally transfers an electron to the

cytochrome b6f complex, which utilizes a proton gradient for ATP synthesis and supplies

an electron to the plastocyanin. This sequence of steps is repeated with each photon

absorbed.

Figure 3: Z-scheme for photosynthesis showing Photosystem I and II in chloroplast.[12]

The oxidation of water to O2 and the accompanying release of four protons and four

electrons is one of the most energetically demanding processes found in Nature, as evident

from its standard potential, Eo of -1.23 V vs NHE. Nature has developed a way of

overcoming this high energy demand through the use of an enzyme called the Oxygen-

9

Evolving Complex (OEC) located in the lumen of the thylakoid. The oxidation of water is

conducted through a heteronuclear Mn4CaO5 cluster.[15] This cluster catalyzes the water

oxidation reaction in a stepwise process called the Kok cycle, which is shown in Figure

4.[14]

Figure 4: The Kok cycle in the Oxygen Evolving Complex (OEC) in natural photosynthesis.[34]

The OEC cycles through five intermediates going stepwise from S0 to S4 which are

each involved in the successive removal of electrons from the Mn centers. Photosystem II

is a dimer composed of two subunits called D1 and D2.[13] As mentioned above, the initial

excitation of P680 in Photosystem II to P680* and its subsequent transfer of an electron to

pheophytin forms the P680•+ cation. The P680•+ is then reduced by a redox-active tyrosine,

Tyrz, which generates a tyrosine radical cation Tyrz•+.[29] The TyrZ•+ radical oxidizes (not

shown in Figure 4) the resting S0 state to the S1 state of the Mn4CaO5 cluster, shown in

Figure 4. Additional oxidation with the TyrZ•+ radical of the cluster lead to the transition

from the S1 state to the S2 state, and then again from the S2 to S3. The S3 is again oxidized

to the final S4 state. In S4, O2 evolution takes place where this highly reactive S4 state

10

spontaneously reverts to the S0 state by oxidizing water and resumes the catalytic cycle.

Each transition in this cycle is done through the removal of one electron.

Figure 5: Proposed mechanisms involved of the Mn4CaO5 for oxygen evolution.[33]

While the exact mechanism for water oxidation by the Mn4CaO5 cluster is yet to be

elucidated, an important step is the formation of an oxygen-oxygen bond either via a

Mn(IV) oxyl radical or a Mn(V)oxo shown in Figure 5.[13,17] Figure 5 only shows a portion

of this catalyst for simplicity. Calcium is a vital cofactor in this system as it is suggested to

be involved in the modulation of the reduction potentials of the manganese centers,

localizing the charge and thus facilitating access to the higher oxidation states necessary

for efficient O2 production.[31] In addition, calcium serves as a Lewis acid to activate a

substrate water molecule to create a better nucleophile.[30]

11

Historical Water Oxidation Catalysts

Figure 6: Structure of the Blue Dimer, the first catalyst molecular catalyst capable of water oxidation.

The first ever molecular catalyst for water oxidation was the blue Ru dimer, cis,cis-

[(byp)2(H2O)RuIIIORuIII(OH2)(byp)2]4+, shown in Figure 6.[8] This blue dimer has

undergone extensive studies to elucidate its mechanism and the key steps required for water

oxidation catalysis. Several studies have suggested the mechanism for blue dimer catalyzed

water oxidation to be the one shown in Figure 6.[18] An important sequence in this

mechanism is the stepwise oxidation of [(byp)2(H2O)RuIIIORuIII(OH2)(byp)2]4+ to the

intermediate [(bpy)2(O)RuVORV(O)(bpy)2]. The (O)RuVORuV(O)4+ exists as a short-lived

intermediate and goes through fast water oxidation to form the (HOO)RuIVORuIV(O)4+

species.[17] Additional oxidation coupled with proton loss initiates O2 release with the

complex returning to its reduced state. A problem faced by this catalyst is that the release

12

of O2 causes anion binding or anation, which blocks the catalytic activity of this complex

until the anion is displaced by another water molecule.

Figure 7: The mechanism employed by the Ru dimer for water oxidation.[17]

While the blue dimer was a trailer blazer for water oxidation, an important question

was whether two metal centers (or potentially more through bimolecular pathways

involving two blue dimer molecules) were required for water oxidation.[19] From the

mechanism of the blue dimer, it was revealed that the key O-O bond forming step occurred

at only one metal site. This opened the door for monomeric metal catalysts with only one

metal site, in which several were found to be proficient catalysts for water oxidation.

Three catalysts were designed in which two were capable of water oxidation with

Ce(IV) as the oxidant, while the third one only showed appreciable reactivity for oxidation

of organic substances. The two analogs capable of water oxidation were

13

[Ru(tpy)(bpm)(OH2)]2+ and [Ru(tpy)(bpz)(OH2)]

2+ where tpy is 2,2′:6′,2′′-terpyridine, bpm

is 2,2’-bipyrimidne, and bpz is 2,2’-bipyrazine. The third catalyst for organic substrate

oxidation was [Ru(typ)(bpy)(OH2)]2+ where bpy is 2,2'-bipyridine. The general structure

of the tpy series is shown in Figure 8.

The Ru(tpy)(bpz)(OH2)2+ showed 2e- oxidation from RuII-OH2

2+ to RuIV=O2+,

where the Ru(III) species is unstable with respect to disproportionation. Studies of these

catalysts have led to the elucidation of the mechanism depicted in Figure 9. These studies

have shown that an additional 1e- oxidation of the RuIV=O2+ intermediate to the RuV=O3+

species occurs to trigger water oxidation and formation of the O-O bond.

Figure 8: Structure of the tpy series.[19]

14

Figure 9: Mechanism of mononuclear tpy series catalyst.[19]

These mononuclear ruthenium catalysts can reach high oxidation state

intermediates due to proton-coupled electron transfer (PCET) and demonstrate that water

oxidation catalysis follows a general mechanism for many ruthenium polypyridyl aqua

complexes with coordinated H2O.[21] These catalysts serve as a foundation for future

development and more research is taking place in order to maximize the rates and minimize

the overpotentials for water oxidation. Inspired by the tpy series, we have synthesized two

(PZ5Me2 and PY4PMMe2) novel pentadentate ligands, shown in Figure 10, for their

application in the synthesis of new mononuclear ruthenium-based water oxidation

catalysts. Additional ligands already reported in the literature (PY4PZMe2 and CF3-

PY5Me2) were also synthesized for the same purpose.

15

Results and Discussion.

Figure 10: Structures of PY5Me2, PY4PZMe2, PY4PMMe2, CF3-PY5Me2, and PZ5Me2

.

New ligands 2,4-bis(1,1-di(pyridin-2-yl)ethyl)pyrimidine (PY4PMMe2) and 2,6-

bis(1,1-bis(2-pyrazyl)ethyl)pyrazine (PZ5Me2) were prepared for application in water

oxidation catalysis. Additional and previously reported ligands, 2,6-bis(1,1-di(pyridin-2-

yl)ethyl)pyrazine (PY4PZMe2) and 2,2',2'',2'''-((4-(trifluoromethyl)pyridine-2,6-

diyl)bis(ethane-1,1,1-triyl))tetrapyridine (CF3-PY5Me2), were synthesized from literature

procedures. These ligands possess a pentadenate structure that provides the ruthenium

metal center with a highly tunable coordination environment and increased stability

through the chelate effect. The high coordination number maximizes the chelate effect,

which prevents ligand dissociation while leaving a labile coordination site for reactivity

16

with coordinated water. In addition, the neutral nature of the ligands allows the complexes

as a whole to be charged and thereby increases their solubility in water.

Figure 11: Structure of the RuPY5Me2 reported in literature.

A ruthenium complex with the ligand 2,6-bis(1,1-di(pyridin-2-yl)ethyl)pyridine

(PY5Me2) has been reported in the literature (Figure 11), but this complex was only found

to oxidize organic substrates during reactivity studies.[22] This results shows a similarity to

the tpy series, where the bpy analogue was not able to effectively oxidize water, but only

organic substrates. Following this trend, we suspect that the corresponding ruthenium

complexes with the PY4PMMe2, PZ5Me2, PY4PZMe2, and CF3-PY5Me2 ligands will

oxidize water like the bpz and bpm analogues in the tpy series, since pyrimidine, pyrazine,

and tirfluoromethyl-substituted pyridine have lower lying * orbitals. This should enhance

the metal-to-ligand backbonding and provide similar electronic effects in relation to the

bpz and bpm catalysts of the tpy series.[23]

17

Figure 12: Schematic of overall synthesis involving PY4PMMe2 and PZ5Me2 ligands.

74%

72%

18

Ligand synthesis and metalation are outlined in Figure 12 for new compounds

PY4PMMe2 and PZ5Me2. In synthetic scheme A, 1,1’-dipyridyl(ethane) is prepared as

previously described.[25] It is then however reacted with lithium diisopropylamide (LDA)

and refluxed in dioxane for 2 days to enable nucleophilic aromatic substitution with 2,4-

dichloropyrimidine to afford PY4PMMe2 in 74% yield. In scheme B, the 1,1’-

dipyrazyl(ethane) precursor is prepared by lithiation of ethylpyrazine and nucleophilic

aromatic substitution with 2-chloropyrazine in refluxing THF, as previously described.[23]

Next, two equivalents of the dipyrazine arm are lithiated at the methine position and reacted

with 2,6-dichloropyrazine to form the pentapyrazine framework, PZ5Me2, in 72% yield as

a white solid. Lithium diisopropylamide (LDA) is required in reactions involving more

electron deficient rings, such as pyrazine and pyrimidine, as butyl addition to pyrazine

rings was observed with n-butyllithium.[24]

Previous application of the PY5Me2, PY4PZMe2, and CF3-PY5Me2 ligands has

been found with cobalt complexes for proton reduction to make hydrogen gas.[23] The

PY4PMMe2 compound is a novel ligand that has not been reported in the literature. The

synthesis of corresponding ruthenium complexes with these ligands is currently in

progress. A reaction involving metalation of PY4PMMe2 with RuCl3∙3H2O in ethanol lead

to single crystals of [Ru(PY4PMMe2)(CH3CN)]2+, which revealed the structure of this

complex (Figure 13) through X-ray diffraction performed by Prof. Jonah Jurss.

Additionally, metalation of PY4PMMe2 with dichloro(p-cymene)ruthenium(II) dimer gave

a very clean 1H NMR of what we believe to be the same complex. Optimization of the

synthesis and purification of this complex and other ruthenium compounds with this family

19

of pentadentate ligands is currently underway. Reactivity studies and mechanistic studies

with these potential catalysts will then be conducted to compare with previous systems.

Figure 13: Crystal structure of the ruthenium ion in [(PY4PMMe2)Ru(CH3CN)]2+; thermal ellipsoids are shown at the

50% probability level.

20

Conclusion.

Syntheses of two new ligands, PY4PMMe2 and PZ5Me2, have been successfully

completed. Two additional ligands, PY4PZMe2 and CF3-PY5Me2, have also been

successfully prepared from literature procedures. Future work involves the metalation of

these ligands with ruthenium to give new complexes that we anticipate will be highly

active catalysts for water oxidation. Electrochemistry and kinetic studies will be done to

study the mechanism for water oxidation and to assess their catalytic activity. Based on

previous studies, the use of pyrazine and pyrimidine in these ligands should enhance the

catalytic activity for water oxidation.

21

Experimental Procedure

Chemical Information: All synthetic procedures were conducted under nitrogen gas using

Schlenk techniques, unless otherwise noted. THF was dried using Pure Process

Technology solvent purification system. The dioxane was dried using Na metal and

benzophenone ketal and then distilled. 2-etyhpyridine was purchased from Alfa Aesar, 2-

fluropyridine from Oakwood Chemicals, and 2,6-dichlororpyrazine and 2,4-

dichloropyrmidine from Chem-Impex Int’L Inc. All other materials were reagent or ACS

grade and purchased from commercial vendors and used without further purification. 1H

NMR were obtained using Bruker spectrometer operating at 500 MHz. Spectra were

calibrated to solvent residual peaks and are reported in ppm.

X-ray Crystallography. The X-ray crystal structure was obtained by Dr. Jurss. A single

crystal was coated with Paratone-N hydrocarbon oil and mounted on a Kapton loop. The

temperature was maintained at 100 K with an Oxford Cryostream during data collection.

Samples were irradiated with Cu-Kα radiation with λ = 1.54178 Å using a MicroSTAR-H

X8 APEX II diffractometer equipped with a microfocus rotating anode and APEX-II

detector. The Bruker APEX2 v. 2009.1 software package was used to integrate raw data

which were corrected for Lorentz and polarization effects.[26] A semi-empirical absorption

correction (SADABS) was applied.[27] Space groups were identified based on systematic

absences, E-statistics, and successive refinement of the structures. The structures were

solved using direct methods and refined by least-squares refinement on F2 and standard

22

difference Fourier techniques using SHELXL.[28] Thermal parameters for all non-hydrogen

atoms were refined anisotropically, and hydrogen atoms were included at ideal positions

and refined isotropically.

2,4-bis(1,1-di(pyridin-2-yl)ethyl)pyrimidine (Py4PmMe2): 2,4-bis(1,1-di(pyridin-2-

yl)ethyl)pyrimidine (PY4PMMe2): First, 1,1’-dipyridyl(ethane) (4.938 g, 0.0268 mol)

was added to 150 mL dry dioxane in a 2-neck round bottom flask with a magnetic stir bar

and stirred. This mixture was cooled in an ice water bath to 0 oC. LDA (0.0268 mol, 13.4

mL) was added dropwise via syringe over 20 minutes to the reaction mixture and then

stirred for 1 hour. 2,4-dichloropyrmidine (0.00671 mol, 1.0 g) was then added dropwise

via syringe. The ice water bath was sequentially removed and the mixture was allowed to

reach room temperature, followed by refluxing 24 hours at 118 oC. Following this, the

reaction was quenched with excess deionized water. The organic and the aqueous layers

were separated by extracting the organic layer with diethyl ether (3 x 30 mL) and the

organic layers were combined and dried with Na2SO4. This was then filtered using a glass

frit and the solvent was removed from the filtrate using rotary evaporation. Silica gel

chromatography was employed and eluted with 1:1 ethyl acetate:hexanes mixture to obtain

a brown powder (2.2 g) in 74% yield. 1H NMR (CDCl3, 500 MHz): = 8.54 (4H, m), 8.30

(2H, s), 7.48 (4H, m), 7.10 (2H, m), 6.94 (4H, d), 2.28 (3H, s), 2.16 (3H, s).

2,6-bis(1,1-di(pyrazin-2-yl)ethyl)pyrazine, (PZ5Me2): Under nitrogen atmosphere, 50

mL of anhydrous tetrahydrofuran was added to 1,1’-dipyrazyl(ethane) (3.8 g, 20.4 mmol)

in an oven-dried 2-neck round bottom flask equipped with stir bar and reflux condenser.

The reaction vessel was then cooled to -78 oC using a dry ice/acetone bath. A 2.0 M solution

of LDA (1 eq, 20.4 mmol, 10.2 mL) was added via syringe to the stirred solution before

23

allowing it to warm slowly to room temperature. Next, 2,6-dichloropyrazine (0.33 eq, 1.01

g, 6.8 mmol) was added to the red reaction mixture and set to reflux at 85 oC for 2 days.

After cooling to room temperature, the unreacted LDA was quenched with ice, and

organics were extracted with diethyl ether (1X), then dichloromethane (2X). The extract

was dried over anhydrous sodium sulfate, and the solvent was subsequently removed by

rotary evaporation. Purification was achieved by silica gel chromatography to give a white

powder (2.06 g) in 68% yield. 1H NMR (CDCl3, 500 MHz): = 8.48 (6H, m), 8.43 (4H,

br), 8.30 (4H, br s), 2.25 (6H, s). 13C NMR (CDCl3, 125 MHz): = 159.43 (s), 157.91 (s),

145.10 (s), 143.45 (s), 142.68 (s), 142.05 (s), 56.30 (s), 25.84 (s). HR-ESI-MS (M+) m/z

calc. [1 + H+], 449.1945, found, 449.194.

24

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1H NMR Data

2,2'-(ethane-1,1-diyl)dipyridine

500 MHz, CDCl

31

2,6-bis(1,1-di(pyridin-2-yl)ethyl)pyrazine (PY4PZMe2)

500 MHz, CDCl3

32

2,4-bis(1,1-di(pyridin-2-yl)ethyl)pyrimidine (PY4PMMe2)

500 MHz, CDCl3

33

2,2',2'',2'''-((4-(trifluoromethyl)pyridine-2,6-diyl)bis(ethane-1,1,1-triyl))tetrapyridine

(CF3-PY5Me2)

500 MHz, CDCl3

34

2,6-bis(1,1-di(pyrazin-2-yl)ethyl)pyrazine, (PZ5Me2)

500 MHz, CDCl3

35

13C NMR Data

2,6-bis(1,1-di(pyrazin-2-yl)ethyl)pyrazine, (PZ5Me2)

125 MHz, CDCl3