Novel pyrazoline monomers were synthesized via an aldol condensation and Michael addition reaction. Computational studies showed that increasing substituent size on the pyrazoline ring increases molecular energy. Partial charge calculations indicated substituents contribute equally to guest complexation. A model dendrimer was prepared using pyrazoline monomer 2g to demonstrate dendrimer synthesis.

1. Facile Synthesis and Computational Studies of Novel Pyrazoline Based Monomers and Dendrimers
for Potential Use as Encapsulating Agents
John Caruso III and Dr. Amy M. Balija
Fordham University, Department of Chemistry, 441 E. Fordham Road, Bronx, NY 10458
Abstract: The inability to effectively remove organic pollutants in water poses a serious threat to
the environment. Dendrimers, with their interior voids, are a possible solution to remove these
organic pollutants. In this research, novel pyrazoline based dendrimers are being synthesized and
their physical properties examined to determine the impact of dendritic functionality on small
molecule entrapment. The dendritic monomers are prepared via an aldol condensation followed by
a Michael addition/cyclization cascade to produce trisubstituted pyrazolines. The pyrazolines are
then coupled to a core, affording a model dendrimer. Computational studies of the pyrazoline
systems have been completed to examine how functional groups on the ring influence overall
molecular energy and partial charge.
Conclusions: Novel pyrazoline monomers were prepared and the resulting products were
isolated with minimal purification. Among the pyrazoline products synthesized, percent yield
increases as more electron withdrawing R-groups are placed on the molecule. Through
computational studies, it was shown that steric factors associated with different substituents
influence the overall molecular energy. However, the electronic factors such as partial charge are
also likely to impact the ability of a dendrimer to complex small molecules, including environmental
pollutants.
Acknowledgments: FCRH Dean’s Office (Summer Science Internship), Fordham University for
financial assistance, Dr. Balija for her guidance in teaching various lab techniques and Cara
McDavitt, Daniel Brauer, and Jeremie Keller for their experimental data.
References:
1. Newkome, G. R.; Moorefield, C. N.; Vögtle, F. Dendrimers and Dendrons: Concepts, Synthesis,
and Applications; Wiley-VCH Verlag GmbH: Weinheim, Germany, 2001.
2. Voit, B.; Komber, H.; Lederer, A. Hyperbranched Polymers: Synthesis and Characterization
Aspects. In Synthesis of Polymers: New Structures and Methods; Schlueter, D. A.; Hawker, C. J.;
Sakamoto, J. Eds.; Wiley-VCH Verlag GmbH & Co: Weinheim, Germany, 2012; pp 701-740.
3. Monaco, O. N.; Tomas, S. C.; Kirrane, M. K.; Balija, A. M. Beilstein J. Org. Chem. 2013, 9, 2320-
2327.
4. a. Levai, A.; Jeko, J. J. Heterocyclic Chem. 2006, 43, 111-115. b. Levai, A.; Jeko, J. J.
Heterocyclic Chem. 2006, 43, 1303-1309.
5. ChemWebMO, Fordham University
Introduction: Highly branched macromolecular structures such as dendrimers1 and
hyperbranched polymers2 provide an attractive vehicle to remove pollutants due to their interior
cavities. While promising approaches have been developed, these systems utilize a patching
method in which the periphery of known architectures are modified with specific functionalities.
Alternatively, dendrimers provide the branched architecture while maintaining the ability to
incorporate functional groups at precise locations which may be ideal for removing specific
pollutants.
Research Goals: The goal of this research is to prepare novel pyrazoline based monomers
efficiently using commercially available starting materials. The physical properties of these
pyrazoline rings will be analyzed using standard experimental and theoretical methods. Novel
dendrimers containing the pyrazoline rings will be synthesized and analyzed.
As the atomic radius of the
substituent ‘R’ increased, the overall
energy of the structure increased. In
comparison, the molecular energy
was computed for dendrimer 3 and
was approximately 2 times higher in
energy than 2g. Thus, steric
congestion appears to destabilize the
low energy conformation of the
trisubstituted pyrazoline system.
Partial charges on the pyrazoline were calculated since the physical properties of the corresponding
dendrimer can be impacted. A linear correlation was observed between the partial charges of the A
and B substituents. This result suggests that within a dendrimer, both branches of the pyrazoline
monomer would contribute equally to complexation of a small molecule guest.
Compound R % Yield
1a H 81
1b OCH3 62
1c OBn 49
1d N(CH3)2 39
1e CH3 53
1f Br 22
1g Cl 59
1h F 39
1i 1-napthaldehyde 39
Computational Studies: Previous research in the Balija lab indicated that functional group
composition impacts the ability for dendrimers to remove organic pollutants from water.3 Therefore,
computational studies were performed to determine how small changes in the pyrazoline
composition impact the molecular energy and partial charges of the pyrazoline system. Semi-
empirical calculations were performed using Hartree-Fock (HF) theory and the basis set 3-21G.5
Previous work in the Balija lab group has shown that novel bis-benzylamine based dendrimers can
remove pyrene, a polycyclic aromatic hydrocarbon (PAH) pollutant, from an aqueous environment.3
Building upon this success, new monomers are being explored for incorporation into dendrimers
and other highly branched macromolecules. Trisubstituted pyrazolines,4 which can be effectively
prepared via a two step process with no column chromatography, are hypothesized to be a novel
monomer for the construction of dendrimers. The unique structure of the pyrazoline system could
impart favorable properties for the formation and evaluation of host-guest complexes between a
dendrimer and a small molecule guest, particularly compounds which are found as contaminants in
the environment.
Synthesis of Pyrazoline Monomers: Benzaldehyde derivatives and acetone were reacted with
sodium hydroxide in 95% ethanol. The resulting di(benzylidine)acetones 1 underwent a Michael
addition and cyclization cascade with 4-hydrazinylbenzoic acid to provide 1,3,5-trisubstituted
pyrazoline ring systems 2.
Pyrazoline Based Dendrimer Families
1H NMR Spectral Data
Compound R % Yield
2a H 18
2e CH3 81a
2f Br 88
2g Cl 33
2h F 80
Size Exclusion Chromatography
Results and Discussion:
A
B
0.00E+00
1.00E+03
2.00E+03
3.00E+03
4.00E+03
5.00E+03
6.00E+03
7.00E+03
8.00E+03
2a 2b 2c 2d 2e 2f 2g 2h 2i 3
KiloHartree
Calculated Pyrazoline Molecular Energies
Calculated Properties of Pyrazolines and Dendrimers
2g
2g
-CH3
-N(CH3)2
-OCH3
-H
-F
-Cl
-Br
y = 0.9752x - 0.0021
R² = 0.988
-0.45
-0.3
-0.15
0
0.15
-0.45 -0.3 -0.15 0 0.15
AccuratePartialChargeB
Accurate Partial Charge A
Synthesis of a Novel Pyrazoline Dendrimer: As a proof of concept, compound 2g was employed
in the synthesis of a two-armed model dendrimer.
1 2
3
ppm13 12 11 10 9 8 7 6 5 4 3 2 1 0
ppm7.5 7
15 16 17 18 19 20
3
2g
2g
aThe reaction performed using microwave irradiation.