1. DIRECT SYNTHESIS OF TETRAZINE-BASED
COVALENT ORGANIC NETWORKS
• Songyang Han
Biological and Chemical Sciences
• Illinois Institute of Technology
• April 14th 2015
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2. Outlines
Motivation and Objectives
Background Information
Design: polymerization via Inverse Electron-Demand Diels-
Alder Reactions
Design: polymerization via Coupling Reactions
Design: polymerization via Modified Pinner Reaction/
Ni(OTf)2 CatalyzedReaction
Future Directions
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3. Hock et al., ACS Catal. 2013, 3, 826−830
Motivation and Objectives
Metal catalysts suffer stability and recycling issues
Immobilize metals onto heterogeneous supports
Hydrosilylation of ketones and aldehydes
Low catalyst loading
Mild and fast
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4. • Porous
• Support metal
• Catalytic active
Ultimate Goal
PSM
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5. How?
Why not directly synthesize what we want?
Not possible!
http://www.ezorchards.com/farm-market/pears/
http://www.tech-food.com/kndata/1045/0090482.htmhttp://www.foodnewsie.com/articles/pearapple-cross-breed-or-mutant
A pear with apple shape?
Monomer1 Monomer2 Polymers
A
B
E
C
D A D
A B
E
A
A
5

6. Smarter Strategy
We plant apple tree, graft pear branches
A X A X
B
C
D
E
A
A
A
A
Polymerization PSM
Monomer1 Monomer X PolymersPolymer X
Result: pear looks like apple and share apple scent
 Introduce functionalities by post-synthetic modification
Happy End achieved by changing strategy
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7. Introduction
 Inorganic materials: activated carbon and zeolites
 Inorganic-organic hybrid polymers: metal-organic
frameworks, coordination polymers
 Organic polymers
Porous Materials
http://www.moftechnologies.com/
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8.  Sodium aluminium silicate minerals
 oxygen, silicon and aluminum atoms forming
tetrahedral single units(Al is negative charged)
 Microporous(<2nm) with regular pore sizes
 Functionalized by doping certain counter-ions
instead of Sodium
 Robust, dirt cheap
Porous Materials
Zeolites
http://en.wikipedia.org/wiki/Zeolite#/media/File:Zeolite-ZSM-5-3D-vdW.png
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9.  Metal-organic frameworks
 Metal containing cores, ligands and organic bridges
reversible linkage
 Micro- and mesoporous (2 nm - 50 nm) uniform
pore sizes, large surface areas
 Post-synthetic modification however, limited
 Air/moisture-sensitive
Porous Materials
MOFs
Xamena et al., Journal of Catalysis 250 (2007) 294–298
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10.  Porous Organic Polymers(POP), conjugated
microporous polymers(CMP), porous aromatic
frameworks(PAF))
 Highly cross-linked, amorphous, high internal
surface area, not uniform pore sizes
 Stable than MOF
 More Choices for post-synthetic modification
Porous Materials
Covalent Organic Networks
https://communities.acs.org/docs/DOC-3866
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11. Porosity of Covalent Organic Networks
Ultra high Porosity
Left: Ben et al., Angew. Chem. Int. Ed. 2009, 48, 9457 –9460.
Right: Yaghi et al., Science 2007, 316, 268 – 272.
BET surface are:5600 m2/g BET surface are:4210 m2/g
Activated Carbon: 500 m2/g
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12. Han et al., ACS Appl. Mater. Interfaces 2013, 5, 4166−4172.
Synthesize of Covalent Organic Networks
Click Chemistry
Condensation (ketal formation)
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13. J.-X. Jiang, et al Chem. Commun., pp. 486-488, 2008.
P. M. Budd, et alChemical Communications, pp. 230-231, 2004 .
 Cyclization
(trimerization)
 Coupling
Synthesize of Covalent Organic Networks
Click Chemistry (Continue)
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14. What are attractive features of such materials?
Several Routes towards the same goal
Feature of Covalent Organic Networks
Nguyen et al., ACS Catal. 2011, 1, 819–835.
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15. • Present condition of Covalent Organic Networks
• Employ synthetic strategies that will result in new functionality in
polymers that can then be post-synthetic modified
• Broaden the classes of ligands that can be generated
Why We Care about Covalent Organic Networks
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16. Synthesis of Covalent Organic Network Catalysts
Nguyen et al., ACS Catal. 2011, 1, 819–835.
 Centers Linkers
Covalent Organic Network
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17. Implementation of 1,2,4,5-Tetrazines as Key Functionality
High nitrogen containing aromatic
compounds, electron deficient
Early studies on explosives
Recent studies on Inverse Electron
Demand Diels-Alder Reaction
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18. 1,2,4,5-Tetrazines Applied in Polymer Science
Anseth et al., Biomacromolecules, 2013, 14 (4), pp 949–953
 Inverse electron-demand Diels-Alder reaction
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19. • Initial Strategy: Double Diels-Alder Reaction
• Formation of Triazene from Tetrazine
• Triazene could undergo
Second D-A Reaction to
Pyridazine
• Requirement: Reactivity of tetrazines must be guaranteed
Clean reaction without side-reactions
Design: Polymerization via Inverse Electron Demand Diels-
Alder Reaction
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20. Reactivity on Tetrazines and Dienophiles
Inverse electron-demand Diels-Alder reaction
D. L. Boger et al Journal of the American Chemical Society, vol. 107, pp. 5745-5754, 1985.
Electron-deficient dienes
Electron-rich dienophiles
D. L. Boger et al The Journal of organic chemistry, vol. 68, pp. 3593-3598, 2003.
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21. Reactivity Test of Tetrazines and Dienophiles
R.T. dioxane
N2 bubbling, color faded,
product isolated
Tetrazines Reaction with weak dienophile
R.T dioxane
overnight No reaction
Reflux dioxane sealed
overnight
Red color disappeared
Product isolated
R.T. DMF/Phenol
3h
No Reaction
70-100°C
DMF/Phenol(note 1)
30minutes
Color faded
Product isolated
70-100°C
overnight
Almost No reaction
80% Starting Tetrazine
Recovered
R.T. dioxane No Reaction
70°C overnight
No Reaction, Starting
Tetrazine Quantatively
Recovered
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22. Reactivity Test of Tetrazines and Dienophiles
Tetrazines Reaction with strong dienophile
R.T. dioxane
N2 bubbling, color faded
Multiple spots on TLC
R.T in DMF 1h
Red precipitate formed
detected
R.T in ACN 3h No Reaction
70°C overnight
Starting Tetrazine
Quantitively Recovered
R.T. dioxane 3h No Reaction
70°C overnight
No Reaction Starting
Tetrazine Recovered
R.T. dioxane Simutaneously precipitaton
detected
70°C overnight Color faded
Several Spot on TLC
Electron rich substituted pyrazole
tetrazine is not reactive
SnAr Reaction happened on dipyrazole
tetrazine
60°C
30minutes
N2 generated
Color faded
Product isolated
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23.  Multiple Reactions of amidine with
tetrazines and triazene rearrangement
 The bad solubility of amidine as well as
hard to make
 Failed to push second Diels-Alder
reaction through desired pathway
Issues in Double Diels-Alder Reaction
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24. Solubility is the eternal problem
The special requirement for amidine
synthesis
Tetrazine and amidine reactions are hard
to control, methylthioimidate can be
alternative, however make procedure
even complicate
Conclusions
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25. Design: Polymerization via Coupling Reactions
Tetrazine containing polymers
Ding et al., J. Am. Chem. Soc. 2010, 132, 13160–13161
 Used for solar cells
 Good thermal stability
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26. • Build up a polymer that contains tetrazine
• More post synthetic modifications can be
done on the tetrazine
Things to concern
• Can other coupling reaction be used
• Higher reactivity, the better?
Why polymerization via coupling
Benefit
• Which monomer is easier to
synthesize and can improve the
overall reactivity
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27. • Benefit sometimes have drawbacks
A. Kotschy et al. Tetrahedron, vol. 60, pp. 1991-1996, 2004.
Screening the Coupling Method
• Coupling Reaction limited to Suzuki Reaction
and Stille Reaction
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28. • Can we make boronic acid
containing tetrazines?
Entry Tetrazine Condition Result
1 -78°C, n-BuLi
Then B(OEt)3
Purple color faded fast. No
desired product was detected
2 -78°C, t-BuLi
Then B(OEt)3
Color faded during lithium
halogen exchange period,
although slower
3 -78°C, B(Oi-Pr)3
Then n-BuLi
No desired product detected
4 -78°C, B(Oi-Pr)3
Then n-BuLi
No bronic acid product
Study of Suzuki Coupling
• Why we want to make
boronic acid containing
tetrazines
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29. • The only choice left is to make
boronic acid on tetraphenyl
methane
Entry Tetrazine Result
1 Around 10% pink precipitate
Not starting material
2 All brownish mud
No sign of product
3 Around 10% dark red product
Not starting material
Test of Suzuki Reaction with Benzene Boronic Acid
Study of Suzuki Coupling
• Tetrazines found destroyed
during test reaction in DMF
with Na2CO3
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30. • Successfully made the
trimethyltin on tetrazine this
time, 30% yield,
Study of Stille Reaction
• No reaction due to
dihydrotetrazine chelation
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31. Successful coupling reaction through Stille Coupling
(in collaborationwith LiliKang)
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32. ATR-IR
 1400 cm-1 C=N
stretches in tetrazines
 Disappearance of
saturated C-H
stretches at 2900-
3000 cm-1
 Peak at 2365 cm-1
might be CO2
Characterizations
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33. Characterizations
Energy dispersive X-ray analysis (EDX)
Spot analysis
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34. BET analysis
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35. Post-Synthetic Modification
In situ generation of enamine
86%
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36. • What is modified pinner
Synthesis?
• How it is applied in tetrazine-
based polymer synthesis?
X.-H. Bu et al., RSC Advances, vol. 2, pp. 408-410, 2012.
• What is the benefit? • No metal
• Only one monomer is needed
for each polymer
Polymerization via Modified Pinner synthesis
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37. • Reference comparison:
Can we make the polymer with the same SSA?
• Will solvent polarity affect the surface area?
POP Hydrazine/ml Sulphur/g Reaction
Time
Temperature Solvent
Tz-1 16 0.6 3 days 90°C None
Tz-2 18 0.6 overnight 90°C Ethylene Glycol
Tz-3 18 0.6 overnight 90°C Benzyl Alcohol
Tz-4 18 0.6 overnight 90°C Glycerol
• Tz-1 and Tz-2 analysis is still going
• Tz-3 BET analysis showed only around 170m2g-1
• Swelling in solvent guaranteed its application as catalyst
Experimental Section
37

38. • Prospective 1-amino-1,3,4-triazole
formation during chronic heating
• Same issue on another reaction
• Color unchanged after oxidization
Issues During Modified Pinner Synthesis
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39. • Solid State C13 NMR
Carbon Shift is different
How to prove existence of 1-amino-1,3,4-triazole?
How to solve the problem?
Reduce reaction time
Prevent high temperature
Any other problems?
Formation of dihydrotetrazine but can not be oxidized
Reaction does not complete properly
Problem Shooting
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40. • Benefit of Lewis Acid Catalyzed
Tetrazine Formation
J. Yang et al., Angewandte Chemie, vol. 124, pp. 5312-5315, 2012.
• Oil-like compound after formation.
Formed plastic-like material after
heating
Ni(OTf)2 Catalyzed Polymer Formation
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41. • Optimize Modified Pinner Tetrazine Formation
• make polymer reactive or with chelation site
• Infinite possibilities using Ni(OTf)2 catalyzed method
Future Direction
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42. Acknowledgement
• Thank Dr. Unni for his guidance during research
• Thank Dr. Rogachev attending the defence
• Special thank for Lili Kang, Ph.D. student in collaboration
• Thank undergraduate student Nicholas Politis, Dan Yi for their help
• Thank my parents, friends and all those who care about me
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