Synthesis and characterization of new 4,5-dihydropyrazol-1-yl derivatives

Article abstract of DOI:10.1080/00397911.2019.1627457

In this study, first, a series of chalcone compounds S1–S6 were synthesized from various acetophenone derivatives (acetophenone, p-methyl acetophenone, and p-methoxy acetophenone) and aromatic aldehyde derivatives (benzaldehyde, p-methyl benzaldehyde, and p-methoxy benzaldehyde) by the Claisen–Schmidt condensation reaction. These S1–S6 compounds were then used in the preparation of 4,5-dihydropyrazol-1-yl derivatives S7–S15. Finally, four new compounds S16–S19 were synthesized from compound (S7, S8, S9, and S12) and 2,4-dinitrophenylhydrazine. Therefore, three known and ten new heterocyclic compounds were synthesized and completely characterized using ¹H NMR, ¹³C NMR, IR, and elemental analysis.

Full text of DOI:10.1080/00397911.2019.1627457

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Synthesis and characterization of new 4,5-
dihydropyrazol-1-yl derivatives
Funda Özdemir Güney, İlhan Özer İlhan & Senem Akkoç
To cite this article: Funda Özdemir Güney, İlhan Özer İlhan & Senem Akkoç (2019): Synthesis
and characterization of new 4,5-dihydropyrazol-1-yl derivatives, Synthetic Communications, DOI:
10.1080/00397911.2019.1627457
To link to this article: https://doi.org/10.1080/00397911.2019.1627457
Published online: 18 Jun 2019.
Submit your article to this journal
View Crossmark data
Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=lsyc20

R
SYNTHETIC COMMUNICATIONSV
https://doi.org/10.1080/00397911.2019.1627457
Synthesis and characterization of new 4,5-dihydropyrazol-
1-yl derivatives
a
a
b
€
_
€
_
€
Funda Ozdemir Guney , Ilhan Ozer Ilhan , and Senem Akkoc¸
b
aDepartment of Chemistry, Faculty of Science, Erciyes University, Kayseri, Turkey; Department of Basic
Pharmaceutical Sciences, Faculty of Pharmacy, Suleyman Demirel University, Isparta, Turkey
ABSTRACT
ARTICLE HISTORY
Received 8 April 2019
In this study, first, a series of chalcone compounds S1–S6 were syn-
thesized from various acetophenone derivatives (acetophenone,
p-methyl acetophenone, and p-methoxy acetophenone) and aro-
matic aldehyde derivatives (benzaldehyde, p-methyl benzaldehyde,
and p-methoxy benzaldehyde) by the Claisen–Schmidt condensation
reaction. These S1–S6 compounds were then used in the prepar-
ation of 4,5-dihydropyrazol-1-yl derivatives S7–S15. Finally, four new
compounds S16–S19 were synthesized from compound (S7, S8, S9,
and S12) and 2,4-dinitrophenylhydrazine. Therefore, three known
and ten new heterocyclic compounds were synthesized and com-
KEYWORDS
Chalcone; heterocyclic
compounds; pyrazoline
derivatives
1
pletely characterized using H NMR, 13C NMR, IR, and elemental ana-
lysis.
GRAPHICAL ABSTRACT
CONTACT Senem Akkoc¸
senemakkoc@sdu.edu.tr, senemakkoc44@gmail.com
Department of Basic
Pharmaceutical Sciences, Faculty of Pharmacy, Suleyman Demirel University, Isparta 32260, Turkey.
Supplemental data for this article can be accessed on the publisher’s website.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
ß 2019 Taylor & Francis Group, LLC

€
€
F. OZDEMIR GUNEY ET AL.
2
Introduction
Chalcones, which are compounds with 1,3-diphenyl-2-propen-1-one nucleus in their
structural framework, are one of the major classes of natural products and are considered
as precursors of isoflavonoids and flavonoids.[1] These type of compounds have a wide
spectrum of biological activity such as anticancer,[2] antiviral,[3] antibacterial,[4] antifun-
gal,[5] antiulcer,[6] antimalarial,[7] anti-inflammatory,[8] anti-diabetes,[9] as potential treat-
ment agents of Alzheimer’s disease,[10] leishmanicidal,[11] trypanocidal effects,[11] etc.
Therefore, many studies have been done on chalcones by researchers.[12–17]
Heterocyclic compounds containing nitrogen elements have an important place in
chemistry due to their medical and pharmaceutical properties.[18] For example, there is
great research interest in benzimidazole,[19] imidazole,[20] pyrrole,[21] pyridine,[22] pyra-
zine[23] and indole,[24] which are known significant classes of heterocyclic compounds
due to their varying biological activities. Pyrazolines, which are a five-membered ring
including two nitrogen atoms and a double bond, are biologically active mole-
cules.[25–28] In this study, due to the immense bioactive significance of heterocyclic
compounds, we decided to synthesis and characterize thirteen compounds based on 4,5-
dihydropyrazol-1-yl.
Results and discussion
Spectral characterization of compounds
In this study, three known and ten new heterocyclic compounds were synthesized in
considerable good yields, which ranged from 57% to 84% (Schemes 1–3). Synthesis of
the chalcone derivatives S1–S6 was conducted in one step. Using the prepared S1–S6
compounds, the pyrazoline derivatives S7–S15 and S16–S19 were synthesized in two
and three steps, respectively. The confirmation of molecular structures of S7–S19 was
1
vindicated by H NMR, 13C NMR, IR, and elemental analysis. Yields, melting points,
and elemental analysis results of compounds S7–S19 are given in Table 1.
The aromatic protons of compounds S7–S19 were obtained within the range of d
1
6.80 and 8.83 ppm in H NMR spectra. In 13C NMR spectra, the carbon signal belong-
ing to the carbonyl group (C¼O) was obtained in a lower area, compared to other
Table 1. Selected properties of synthesized compounds.
Melting
Entry Compounds Yield (%) point (oC)
IR(C¼N)
1595.14
1511.75
1594.82
1605.92
1507.7
1512.57
1604.61
1511.9
Elemental analysis found (calc.)
1
S7
S8
79
72
84
78
77
81
67
77
75
64
63
57
63
101–103
97–100
C: 73.01 (73.45); H: 6.73 (6.16); N: 9.82 (9.52).
C: 77.15 (77.67); H: 6.83 (6.52); N: 10.15 (10.06).
C: 74.15 (74.00); H: 6.89 (6.54); N: 9.14 (9.08).
C: 74.31 (74.00); H: 6.12 (6.54); N: 9.19 (9.08).
C: 78.41 (78.10); H: 6.67 (6.29); N: 7.18 (7.29).
C: 81.73 (81.49); H: 6.23 (6.57); N: 7.38 (7.60).
C: 78.53 (78.10); H: 6.78 (6.29); N: 7.15 (7.29).
C: 81.75 (81.33); H: 6.63 (6.26); N: 7.49 (7.90).
C: 81.69 (81.33); H: 6.95 (6.26); N: 7.61 (7.90).
C: 60.23 (60.75); H: 4.19 (4.67); N: 17.69 (17.71).
2
3
4
5
6
7
8
9
10
11
12
13
S9
101–103
105–107
110–112
105–108
106–109
108–110
106–109
107–109
114–117
112–113
110–111
S10
S11
S12
S13
S14
S15
S16
S17
S18
S19
1493.5
1595.9 and 1644.9
1511.65 and 1643.52 C: 62.35 (62.87); H: 4.44 (4.84); N: 18.51 (18.33).
1510.6 and 1644.9
1510.9 and 1650.7
C: 61.83 (61.47); H: 4.35 (4.95); N: 17.05 (17.20).
C: 67.03 (67.87); H: 5.62 (5.14); N: 15.75 (15.32).

R
SYNTHETIC COMMUNICATIONSV
3
signals, at d 172.53, 167.78, 168.71, 168.61, 168.92, 168.90, 168.77, 169.00, and
169.00 ppm for S7–S15, respectively. The formation of the desired compounds was also
confirmed by IR, which showed the presence of stretching bands for the C¼N vibra-
tions at 1595.14, 1511.75, 1594.82, 1605.92, 1507.70, 1512.57, 1604.61, 1511.90, 1493.50,
1595.90, 1511.65, 1510.60, and 1510.90 cmꢀ1 for compounds S7–S19, respectively.
However, in the IR spectra, the C¼O vibrations were 1642.56, 1643.31, 1643.59,
1654.83, 1636.40, 1654.84, 1649.65, 1654.80, and 1652.30 cmꢀ1 for S7–S15, respectively.
Conclusion
In the present study, three known and 10 new heterocyclic compounds based on 4,5-
dihydropyrazol-1-yl including electron-withdrawing or electron-donating substituents
on the positions of the C3 or C5 aryl groups were synthesized and fully characterized
by spectroscopic and analytic methods.
Experimental section
Chemical materials used in experimental studies
All the chemicals used in the synthesis were purchased from the companies Merck,
Carlo Erba, Aldrich, and Fluka. These chemicals are benzaldehyde, 4-methyl benzalde-
hyde, 4-methoxy benzaldehyde, 4-methyl acetophenone, 4-methoxy acetophenone, 2,4-
dinitrophenylhydrazine, sodium hydroxide, acetic acid, ethanol, hexane, and methanol.
Instrumentations
With a Shimadzu FT-IR 8400 spectrophotometer, the FT-IR spectra were recorded from
1
4000 to 400 cmꢀ1. H and 13C NMR spectra were recorded on a Bruker 400 MHz Ultra
Shield NMR. Elemental analysis was determined using a CHNS-932 LECO apparatus.
Synthesis of benzalacetophenone derivatives
The synthesis of chalcone compounds S1–S6 were conducted as illustrated below
(Scheme 1). Sodium hydroxide (NaOH) (22 g) was added to a 1 L three-necked flask.
200 mL of water and 140 mL of ethyl alcohol (EtOH) were mixed in the flask and the
O
O
O
O
OH
H
CH3
NaOH
C2H5OH
+
-H2O
R1
R2
R1
R2
R1
R2
Yield
83%
88%
75%
81%
77%
85%
S1 R1: H
S2 R1: H
S3 R1: CH3
S4 R1: CH3
S5 R1: OCH3
S6 R1: CH3
R2: OCH3
R2: CH3
R2: OCH3
R2: H
R2: CH3
R2: CH3
Scheme 1. Synthesis of chalcone derivatives.

€
€
F. OZDEMIR GUNEY ET AL.
4
contents were dissolved by mixing in ice with a magnetic stirrer. Then, an acetophenone
derivative (acetophenone for S1 and S2, p-methyl acetophenone for S3, S4, and S6, p-
methoxy acetophenone for S5) were slowly added drop wise into this mixture with the
aid of the dropping funnel. After this process was completed, a benzaldehyde derivative
(p-methoxy benzaldehyde for S1 and S3, p-methyl benzaldehyde for S2, S5, and S6,
benzaldehyde for S4) was added to the three-necked flask. The reaction was stirred in
the salt-ice mixture for 5–6 h. The temperature was kept around (ꢀ10 ꢁC). The product
was precipitated with the addition of EtOH. The precipitated solid was left in the
refrigerator overnight. After filtration of the product in vacuum, the product was
washed several times with 200 mL of water þ 140 mL of EtOH mixtures. The product
was placed in a Petri dish and dried on P2O5 in vacuum desiccators for two nights.
3-(4-Methoxyphenyl)-1-phenylprop-2-en-1-one (S1), 1-phenyl-3-p-tolylprop-2-en-1-
one (S2), 3-(4-methoxyphenyl)-1-p-tolylprop-2-en-1-one (S3), 3-phenyl-1-p-tolylprop-2-
en-1-one (S4), 1-(4-methoxyphenyl)-3-p-tolylprop-2-en-1-one (S5), and 1,3-di-p-tolyl-
prop-2-en-1-one (S6) were prepared in one step. The colors of the obtained compounds
were orange, yellow, yellow, yellow, yellow, yellow for S1–S6, respectively. The melting
points of the compounds were measured at 72–75 ꢁC, 90–94 ꢁC, 95–98 ꢁC, 72–75 ꢁC,
96–99 ꢁC, and 96–99 ꢁC for S1–S6, respectively.
Reactions of chalcones with different hydrazide derivatives
The synthesis of pyrazoline compounds was carried out according to literature proce-
dures.[27,29–31] Chalcone derivatives (S1–S6) weighed at the stoichiometric ratio, acetic
hydrazide, and KOH were added to a reaction flask and ethyl alcohol was added to the
reaction medium as solvent (Scheme 2). It was refluxed for 5 h on a magnetic stirrer.
The presence of the new product was checked using TLC, and ice was added to the
reaction mixture after 5 h. After the reaction flask was left in the refrigerator for 1 day,
the product precipitated, was filtered off, and was crystallized in ethanol. The final
product was dried in vacuum desiccators over P2O5.
The synthesis of compounds S7–S15 were completed according to the above men-
tioned general synthetic procedure. The characterization data of S7–S15 are
given below.
R2
O
H
CH3CH2OH
KOH
N
R3
+
H2N
R3
N
N
O
R1
R2
O
R1
Yield
79%
72%
84%
78%
77%
81%
67%
77%
75%
S7 R1: H
S8 R1: H
R2: OCH3
R2: CH3
R2: OCH3
R2: CH3
R2: OCH3
R2: CH3
R2: CH3
R2: CH3
R2: H
R3: CH3
R3: CH3
R3: CH3
R3: CH3
R3: CH2C6H5
R3: CH2C6H5
R3: CH2C6H5
R3: CH2C6H5
R3: CH2C6H5
S9 R1: CH3
S10 R1: OCH3
S11 R1: CH3
S12 R1: CH3
S13 R1: OCH3
S14 R1: H
S15 R1: CH3
Scheme 2. Synthesis of S7–S15.

R
SYNTHETIC COMMUNICATIONSV
5
R2
R2
O2N
R3
R3
N
H
N
CH3COOH
CH3CH2OH
+
H2N
N
NO2
N
N
O
N
NH
R1
R1
NO2
S7-S9, S12
NO2
Yield
S16 R1: H
S17 R1: H
S18 R1: CH3
S19 R1: CH3
R2: OCH3
R2: CH3
R2: OCH3
R2: CH3
R3: CH3
R3: CH3
R3: CH3
R3: CH2C6H5
64%
63%
57%
63%
Scheme 3. Schematic diagram of synthesized S16–S19.
Reactions of 4,5-dihydro-1H-pyrazole derivatives with 2,4-dinitrophenylhydrazine
Synthesized compounds (S7, S8, S9, and S12), 2,4-dinitrophenylhydrazine, and 0.25 mL
of acetic acid were put in a reaction flask (Scheme 3). Ethyl alcohol was added to this
reaction mixture as solvent. It was refluxed for 8 h on a magnetic stirrer. The presence
of the new product was checked using TLC with a sample taken from the reaction
medium at intervals of every hour. After 8 h, the reaction mixture was allowed to cool
down. Then, the solvent in the reaction medium was removed with a Rotary
Evaporator. Hexane was added over oily product, and it was mixed on a magnetic stir-
rer. The solidified product was filtered and crystallized in hexane. The final product was
dried over P2O5 in vacuum desiccators.
(E)-1-(1-(3,5-di-p-tolyl-4,5-dihydropyrazol-1-yl)-2-phenylethylidene)-2-(2,4-
dinitrophenyl)hydrazine, S19
New compound S19 (C31H28N6O4: 548 g/mol) was synthesized from 0.10 g of S12,
0.07 g of 2,4-dinitrophenyl hydrazine and 5 drops of acetic acid. The product was crys-
tallized in hexane. Product: 0.07 g, yield: 63%, m.p.: 110–111 ꢁC. FT-IR (cmꢀ1): 3027.1
(N–H), 2920.3 (C–H), 1510.9–1650.7 (–C¼N), 1322.1–1425.3 (C¼C). 1H NMR
(d¼ppm): 7.03–7.68 (m, 16H, Ar-H), 5.50–5.55 (d, J: 8 Hz, 1H), 4.07–4.19 (q, J: 12Hz,
aliphatic 2H), 3.10–3.75 (t, J: 8 Hz, 2H), 2.30 and 2.42 (s, 6H, CH3). 13C NMR
(d¼ppm): 168.90 (pyrazole C¼N), 153.98 (imine C¼N), 140.68, 138.91, 137.25, 135.52,
129.61, 129.48, 128.71, 128.31, 126.59, and 125.54 (Ar-C), 59.84 (CH), 42.33, and 41.22
(–CH2–), 21.54, and 21.09 (–CH3). Elemental analysis for C31H28N6O4 (548.59 g/mol)
%: Found C: 67.03; H: 5.62; N: 15.75. Anal. Calc. C: 67.87; H: 5.14; N: 15.32.
The characterization data of S7–S18 were given in supplementary information.
1H NMR, 13C NMR, IR spectra, and full characterization data of all compounds can
be found via the “Supplementary Content” section of this article’s webpage.’
Acknowledgments
We thank Abdulai Yahuza Nantomah (Pan African University, Institute of Life and Earth
Sciences including Health and Agriculture-University of Ibadan) and editing office of Erciyes
University for critical reviews of the manuscript.

€
€
F. OZDEMIR GUNEY ET AL.
6
Author’s contribution
€
_ € _
_ €
F. O. Gu€ney conducted all experiments under the supervision of I. O. Ilhan and S. Akkoc¸, I. O.
_
Ilhan designed the study, and S. Akkoc¸ helped analyze data and wrote the manuscript.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
We would like to thank Erciyes University Research Fund [FBA-2016-6492] for their finan-
cial support.
References
[1] Ghosh, R.; Das, A. Synthesis and Biological Activities of Chalcones and Their Heterocyclic
Derivatives: A Review. World J. Pharm. Pharm. Sci. 2014, 3, 578–595.
[2] Khanapure, S.; Jagadale, M.; Bansode, P.; Choudhari, P.; Rashinkar, G. Anticancer Activity
of Ruthenocenyl Chalcones and Their Molecular Docking Studies. J. Mol. Struct. 2018,
1173, 142–147. DOI: 10.1016/j.molstruc.2018.06.091.
[3] Zhou, D.; Xie, D.; He, F.; Song, B.; Hu, D. Antiviral Properties and Interaction of Novel
Chalcone Derivatives Containing a Purine and Benzenesulfonamide Moiety. Bioorg. Med.
Chem. Lett. 2018, 28, 2091–2097. DOI: 10.1016/j.bmcl.2018.04.042.
[4] Ayman, M.; El-Messery, S. M.; Habib, E. E.; Al-Rashood, S. T.; Almehizia, A. A.;
Alkahtani, H. M.; Hassan, G. S. Targeting Microbial Resistance: Synthesis, Antibacterial
Evaluation, DNA Binding and Modeling Study of New Chalcone-Based Dithiocarbamate
Derivatives. Bioorg. Chem. 2019, 85, 282–292. DOI: 10.1016/j.bioorg.2019.01.001.
[5] Wang, Y.-H.; Dong, H.-H.; Zhao, F.; Wang, J.; Yan, F.; Jiang, Y.-Y.; Jin, Y.-S. The
Synthesis and Synergistic Antifungal Effects of Chalcones against Drug Resistant Candida
albicans. Bioorg. Med. Chem. Lett. 2016, 26, 3098–3102. DOI: 10.1016/j.bmcl.2016.05.013.
[6] Sashidhara, K. V.; Avula, S. R.; Mishra, V.; Palnati, G. R.; Singh, L. R.; Singh, N.;
Chhonker, Y. S.; Swami, P.; Bhatta, R. S.; Palit, G. Identification of Quinoline-Chalcone
Hybrids as Potential Antiulcer Agents. Eur. J. Med. Chem. 2015, 89, 638–653. DOI:
10.1016/j.ejmech.2014.10.068.
[7] Arancibia, R.; Biot, C.; Delaney, G.; Roussel, P.; Pascual, A.; Pradines, B.; Klahn, A. H.
Cyrhetrenyl Chalcones: Synthesis, Characterization and Antimalarial Evaluation. J.
Organomet. Chem. 2013, 723, 143–148. DOI: 10.1016/j.jorganchem.2012.08.024.
[8] Ur Rashid, H.; Xu, Y.; Ahmad, N.; Muhammad, Y.; Wang, L. Promising anti-
Inflammatory Effects of Chalcones via Inhibition of Cyclooxygenase, Prostaglandin E2,
Inducible NO Synthase and Nuclear Factor jb Activities. Bioorg. Chem. 2019, 87,
335–365. DOI: 10.1016/j.bioorg.2019.03.033.
[9] Cai, C.-Y.; Rao, L.; Rao, Y.; Guo, J.-X.; Xiao, Z.-Z.; Cao, J.-Y.; Huang, Z.-S.; Wang, B.
Analogues of Xanthones Chalcones and Bis-Chalcones as a-Glucosidase Inhibitors and
anti-Diabetes Candidates. Eur. J. Med. Chem. 2017, 130, 51–59. DOI: 10.1016/
j.ejmech.2017.02.007.
[10] Cong, L.; Dong, X.; Wang, Y.; Deng, Y.; Li, B.; Dai, R. On the Role of Synthesized
Hydroxylated Chalcones as Dual Functional Amyloid-b Aggregation and Ferroptosis
Inhibitors for Potential Treatment of Alzheimer’s Disease. Eur. J. Med. Chem. 2019, 166,
11–21. DOI: 10.1016/j.ejmech.2019.01.039.

R
SYNTHETIC COMMUNICATIONSV
7
ꢀ
ꢀ
[11] Espinoza-Hicks, J. C.; Chacon-Vargas, K. F.; Hernandez-Rivera, J. L.; Nogueda-Torres, B.;
ꢀ
ꢀ
Tamariz, J.; Sanchez-Torres, L. E.; Camacho-Davila, A. Novel Prenyloxy Chalcones as
Potential Leishmanicidal and Trypanocidal Agents: Design, Synthesis and Evaluation. Eur.
J. Med. Chem. 2019, 167, 402–413. DOI: 10.1016/j.ejmech.2019.02.028.
[12] Maragatham, G.; Selvarani, S.; Rajakumar, P.; Lakshmi, S. Structure Determination and
Quantum Chemical Analysis of Chalcone Derivatives. J. Mol. Struct. 2019, 1179, 568–575.
DOI: 10.1016/j.molstruc.2018.11.048.
[13] Reeta, Vinoth, R.; Rangarajan, T. M.; Ayushee, Singh, R. P.; Singh, M. Synthesis of Novel
Chalcones through Palladium-Catalyzed CO Cross-Coupling Reaction of Bromo-
Chalcones with Ethyl Acetohydroxamate and Their Antiplasmodial Evaluation against
Plasmodium Falcipuram in Vitro. Bioorg. Chem. 2019, 86, 631–640. DOI: 10.1016/
j.bioorg.2019.02.016.
[14] Kotlyar, V. M.; Kolomoitsev, O. O.; Nikolaievskyi, D. V.; Pedan, P. I.; Chumak, A. Y.;
Orlov, V. D.; Shishkina, S. V.; Doroshenko, A. O. Photoreactive Fused
Aziridinylpiperazines on the Background of 4-Substituted Chalcones and Their
Benzimidazolic Analogs. J. Mol. Struct. 2019, 1180, 741–746. DOI: 10.1016/
j.molstruc.2018.12.015.
[15] Borge, V. V.; Patil, R. M. Syntheses and Characterization of Copper Metal Complexes
Prepared from Chalcone Derivatives. Microchem. J. 2019, 145, 456–459. DOI: 10.1016/
j.microc.2018.11.001.
[16] Tajudeen Bale, A.; Mohammed Khan, K.; Salar, U.; Chigurupati, S.; Fasina, T.; Ali, F.;
Kanwal, Wadood, A.; Taha, M.; Sekhar Nanda, S.; Ghufran, M.; Perveen, S. Chalcones
and Bis-Chalcones: As Potential a-Amylase Inhibitors; Synthesis, in Vitro Screening, and
Molecular Modelling Studies. Bioorg. Chem. 2018, 79, 179–189. DOI: 10.1016/
j.bioorg.2018.05.003.
_
[17] Burmaoglu, S.; Yilmaz, A. O.; Polat, M. F.; Kaya, R.; Gulcin, I.; Algul, O. Synthesis and
Biological Evaluation of Novel Tris-Chalcones as Potent Carbonic Anhydrase,
Acetylcholinesterase, Butyrylcholinesterase and a-Glycosidase Inhibitors. Bioorg. Chem.
2019, 85, 191–197. DOI: 10.1016/j.bioorg.2018.12.035.
[18] Stefanes, N. M.; Toigo, J.; Maioral, M. F.; Jacques, A. V.; Chiaradia-Delatorre, L. D.;
ꢀ
Perondi, D. M.; Ribeiro, A. A. B.; Bigolin, A.; Pirath, I. M. S.; Duarte, B. F.; et al.
Synthesis of Novel Pyrazoline Derivatives and the Evaluation of Death Mechanisms
Involved in Their Antileukemic Activity. Bioorg. Med. Chem. 2019, 27, 375–382. DOI:
10.1016/j.bmc.2018.12.012.
[19] Akkoc¸, S. Derivatives of 1-(2-(Piperidin-1-yl)Ethyl)-1H-Benzo[d]Imidazole: Synthesis,
Characterization, Determining of Electronic Properties and Cytotoxicity Studies.
ChemistrySelect 2019, 4, 4938–4943.
€
[20] Gok, Y.; Akkoc¸, S.; Akkurt, M.; Tahir, M. N. Imidazole, Pyrimidine and Diazepine
Containing Heteroaryl-Substituted Heterocyclic Salts as Efficient Ligand Precursors for
Mizoroki–Heck Coupling Reaction: synthesis, Structural Characterization and Catalytic
Activities. J. Iran. Chem. Soc. 2014, 11, 1767–1774. DOI: 10.1007/s13738-014-0449-z.
[21] Wan, S.-H.; Liu, S.-T. Functionalized Pyrroles from Vinylaziridines and Alkynes via
Rhodium-Catalyzed Domino Ring-Opening Cyclization Followed by CC Bond Migration.
Tetrahedron 2019, 75, 1166–1170. DOI: 10.1016/j.tet.2019.01.022.
[22] Song, Y.-L.; Tian, C.-P.; Wu, Y.; Jiang, L-h.; Shen, L.-Q. Design, Synthesis and Antitumor
Activity of Steroidal Pyridine Derivatives Based on Molecular Docking. Steroids 2019, 143,
53–61. DOI: 10.1016/j.steroids.2018.12.007.
[23] Kim, J.; Park, M.; Choi, J.; Singh, D. K.; Jeong Kwon, H.; Kim, S. H.; Kim, I. Design,
Synthesis, and Biological Evaluation of Novel Pyrrolo[1,2-a]Pyrazine Derivatives. Bioorg.
Med. Chem. Lett. 2019, 29, 1350–1356. DOI: 10.1016/j.bmcl.2019.03.044.
[24] Demurtas, M.; Baldisserotto, A.; Lampronti, I.; Moi, D.; Balboni, G.; Pacifico, S.; Vertuani,
S.; Manfredini, S.; Onnis, V. Indole Derivatives as Multifunctional Drugs: Synthesis and
Evaluation of Antioxidant, Photoprotective and Antiproliferative Activity of Indole
Hydrazones. Bioorg. Chem. 2019, 85, 568–576. DOI: 10.1016/j.bioorg.2019.02.007.

€
€
F. OZDEMIR GUNEY ET AL.
8
[25] Ozmen Ozgun, D.; Gul, H. I.; Yamali, C.; Sakagami, H.; Gulcin, I.; Sukuroglu, M.;
Supuran, C. T. Synthesis and Bioactivities of Pyrazoline Benzensulfonamides as Carbonic
Anhydrase and Acetylcholinesterase Inhibitors with Low Cytotoxicity. Bioorg. Chem. 2019,
84, 511–517. DOI: 10.1016/j.bioorg.2018.12.028.
[26] Ahmad, A.; Husain, A.; Khan, S. A.; Mujeeb, M.; Bhandari, A. Synthesis, Antimicrobial
and Antitubercular Activities of Some Novel Pyrazoline Derivatives. J. Saudi Chem. Soc.
2016, 20, 577–584. DOI: 10.1016/j.jscs.2014.12.004.
[27] Ilhan, I. O.; Caglayan, A.; Onal, Z.; Akkoc, S.; Cadır, M. Reactions of Some Pyrazole-3-
Carboxylic Acids and Carboxylic Acid Chlorides with Various O- and N- Nucleophiles.
Loc. 2013, 10, 602–610. DOI: 10.2174/15701786113109990025.
[28] Kadi, A. A.; Yin, W.; Rahman, A. F. M. M. In-Vitro Metabolic Profiling Study of
Potential Topoisomerase Inhibitors ‘Pyrazolines’ in RLMs by Mass Spectrometry.
J. Chromatogr. B 2019, 1114–1115, 125–133. DOI: 10.1016/j.jchromb.2019.03.026.
[29] Levai, A.; Jeko, J. Synthesis of Carboxylic Acid Derivatives of 2-Pyrazolines. Arkivoc 2007,
(i), 134–145.
€
_
_
€
[30] Ilhan, IO.; C¸adir, M.; Saracoglu, M.; Kandemirli, F.; Kokbudak, Z.; Akkoc¸, S. The
Reactions and Quantum Chemical Calculations of Some Pyrazole-3- Carboxylic Acid
Chlorides with Various Hydrazides. Chem. Sci. Rev. Lett. 2015, 4, 838–850.
€
[31] Ilhan, I. O.; Demirkol, K.; Onal, Z.; Akkoc¸, S.; C¸adır, M. Functionalization Reactions of
Various Pyrazole-3-Carboxylic Acid Chlorides with Some Ureas. Asian J. Chem. 2014, 26,
2365–2368. DOI: 10.14233/ajchem.2014.16000.