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Synthesis of Chalcone Derivatives and Evaluation Their Biological Activities

Article · January 2016

DOI: 10.24271/garmian.3

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‫مجلة جامعة كرميان‬ Journal of Garmian University ‫طؤظاري زانكؤي طةرميان‬
https://doi.org/10.24271/garmian.3

Synthesis of Chalcone Derivatives and Evaluation Their

Biological Activities
Aso H. Hasan
University of Garmian, Department of Chemistry, College of Education, Kurdistan- Iraq.
Corresponding author, E-mail: aso.hameed@garmian.edu.krd

Abstract
In this study, some chalcone derivatives (A1, A2, A3 and A4) were synthesized from various aryl ketones
and aryl aldehydes in alkaline medium. The synthesized compounds have been characterized by melting
point, FT-IR, 1H NMR and 13C NMR Spectroscopic techniques. All the synthesized compounds were
screened for their biological activities (antibacterial and antioxidant activities).
Key words: Chalcone, IR, NMR Spectroscopy, antibacterial, antioxidant activities.

Introduction
The chemistry of chalcones (Figure 1) has generated intensive scientific studies throughout the
world. Especially interest has been focused on the synthesis and biodynamic activities of chal-
cones. The CH=CH–C=O chain allows for electronic delocalization of a free-radical position via
extensive mesomeric effects and free-radical stabilization through the so-called capto-dative ef-
fect, a concept introduced by Viehe et al, 1980 [1]. The capto-dative effect is based on the fol-
lowing concept: while carbocations are stabilized by electron-donating substituents and carbani-
ons are stabilized by electron-withdrawing substituents, radicals gain stability when flanked by a
push–pull system [2]. The name “Chalcones” was given by Kostanecki and Tambor. These com-
pounds are also known as benzalacetophenone or benzylidene acetophenone [3].

O
Figure 1: The Chalcone structure

Many chalcone compounds were synthesized have been reported that exhibits a wide range of
biological activities including antioxidative [4], antiplatelet [5], antimicrobial [6], anti-
inflammatory [7] and antitumor [8] properties. The presence of a reactive α,β- unsaturated keto
function in chalcones is found to be responsible for their biological activities [9]. These findings
motivated us to synthesize chalcones.

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‫مجلة جامعة كرميان‬ Journal of Garmian University ‫طؤظاري زانكؤي طةرميان‬
Different methods are available for the preparation of chalcones [10-12]. The most convenient
method is the Claisen-Schimdt condensation of equimolar quantities of arylmethylketone with
aryl aldehyde in the presence of alcoholic alkali [13].

Experiment
Melting points were recorded on Stuart apparatus. IR spectra were recorded using Shimadzu FT-
IR spectrophotometer. NMR spectrum was recorded using CDCl3 on Bruker Avance (400 MHz)
and their chemical shifts are recorded in δ (ppm) units with respect to (TMS) as internal standard.
UV spectra were recorded on a Shimadzu (UV 1800). All the chemicals used were of analytical
grade.

Synthesis of Chalcone derivatives (A1-A4)

A well stirred solution of substituted acetophenone (0.01 mol) and substituted benzaldehyde
(0.01 mol) in 96 % ethanol (15 mL) was added with 5 % KOH (12.5 mL) and left with stirring
for 3-4 hours at room temperature. After that, the mixture was poured into iced water (30 mL)
and acidified with HCl (10%). Then the mixture evaporated to give chalcones (Figure 2).

Synthesis of 1-(3,4-Dimethoxyphenyl)-3-[2-(3-nitrobenzyloxy)-phenyl]-propenone (A1):

(1.31gm, 31.26%) of the compound was obtained as orange solids with m.p. (122-126 °C), from
the reaction of 3,4-dimethoxyacetophenone and 2-(3-Nitrobenzyloxy)-benzaldehyde; IR vmax cm-
1
: 2910(sp3 C-H), 1647 (C=O), 1587 and 1448 (C=C aromatic), 1512 (Ar-NO2); 1H NMR (400
MHz, CDCl3) ppm: δ 7.75 (1H, d, J= 16.0 Hz, H-β), 6.65 (2H, d, H-3 and H-6′′), 7.32 (1H, d, J=
16.0 Hz, H-α), 6.88 (2H, d, H-2 H-2′ and H-6′), 7.52 (2H, d, H-4 and H-6′), 7.60 (3H, s, H-2′, H-
2′′), 7.64 (2H, d, H-4′′), 7.32 (1H, d, H-5′), 7.75 (1H, d, H-5′′), 3.93 (2H, s, OCH2), 3.01 (6H, s,
OCH3) ; 13C NMR (CDCl3, 400 MHz): δ 40.28 (2xOCH3), 56.18 (OCH2), 110.10 (C-3), 111.98
(C-5′), 116.65 (C-2 and C-2′′), 122.69 (C-1 and C-3), 122.99 (C-α, C-5′ and C-4), 130.42 (C-1,
C-5′, C-4 and C-6), 132.27 (C-6′′), 145.11 (C- β and C-1′), 149.23 (C-3′ and C-3′′), 152.01 (C-4′),
152.88 (C-2), 188.92 (C=O).

Synthesis of 1-(3,4-Dimethoxy-phenyl)-3-(4-dimethylaminophenyl)-propenone (A2): (2.17

gm, 69.77 %) of the compound obtained as white solids with m.p. (153-158 °C), from the reac-
tion of 3,4-dimethoxyacetophenone and 4-dimethyaminobenzaldehyde; IR vmax cm-1: 2953 (sp3 C-
H), 1660 (C=O), 1581and 1487 (C=C aromatic), 1161 (-OCH3), 1328 (C-N); 1H NMR (400

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‫مجلة جامعة كرميان‬ Journal of Garmian University ‫طؤظاري زانكؤي طةرميان‬
MHz, CDCl3) ppm: δ 8.08 (1H, d, J= 12.0 Hz, H-β), 6.80 (2H, d, H-3 and H-5), 7.57 (1H, d, J=
12.0 Hz, H-α), 6.95 (1H,d, H-5′), 7.04 (2H, d, H-2 and H-6), 8.31 (1H, s, H-2′), 7.46 (1H, d, H-
6′), 3.93 (3H, s, OCH3) , 5.24 (3H, s, OCH3), 1.22 (6H, s, N(CH3)2) ; 13
C NMR (CDCl3, 400
MHz): δ 56.16 (2xCH3), 69.49 (-OCH3), 109.94 and 110.93 (C-3 and C-5), 112.69 (C-5′), 123.03
(C-1), 121.88.42 (C-2′), 122.54 (C-6′), 123.21 and 124.75 (C-2 and C-6), 130.07 (C-α), 129.95
(C-1′), 138.82 (C-4′), 131.56 (C-β), 131.66 (C-4), 133.65 (C-3′), 189.11 (C=O).

Synthesis of 3-(4-Fluoro-phenyl)-1-p-tolylpropenone (A3): (1.52 gm, 63.33%) of the com-

pound obtained as milky powder with m.p. (131-133 °C), from the reaction of 4-methyl aceto-
phenone and 4-fluorobenzaldehyde; IR vmax cm-1: 2916 (sp3 C-H), 1656 (C=O), 1571 and 1448
(C=C aromatic), 1211 (C-F); 1H NMR (400 MHz, CDCl3) ppm: δ 7.73 (1H, d, J= 16.0 Hz, H-β),
7.27 (2H, d, J= 8.0 Hz, H-2 and H-6), 7.42 (1H, d, J= 16.0 Hz, H-α), 7.09 (2H, d, J= 8.0 Hz, H-3
and H-5),7.90 (2H, d, J= 8.0 Hz, H-2′ and H-6′), 7.59 (2H, d, J= 8.0 Hz, H-3′ and H-5′), 2.42
(3H, s, CH3); 13
C NMR (CDCl3, 400 MHz): δ 21.82 (CH3), 116.13 (C-3), 116.35 (C-5), 128.7
(C-2), 129.50 (C-3), 130.38 (C-2′), 130.48 (C-6′), 121.96 (C-α), 131.41 (C-3′), 131.44 (C-5′),
162.90 (C-β), 135.7 (C-1′), 143.20 (C-4′), 143.86 (C-4), 165.40 (C-1), 189.93 (C=O).

Synthesis of 3-(4-Dimethylaminophenyl)-1-(4-methoxyphenyl)-propenone (A4): (1.39 gm,

49.37%) of the compound obtained as yellow solids with m.p. (124-126 °C), from the reaction of
4-methoxyacetophenone and 4-dimethylaminobenzaldehyde; IR vmax cm-1: 2999 (sp3 C-H), 1598
(C=O), 1570 and 1550 (C=C aromatic), 1165 (-OCH3), 1332 (C-N); 1H NMR (400 MHz,
CDCl3) ppm: δ 7.74 (1H, d, J= 16.0 Hz, H-β), 7.50 (2H, d, J= 8.0 Hz, H-2 and H-6), 7.31 (1H, d,
J= 16.0 Hz, H-α), 6.66 (2H, d, J= 8.0 Hz, H-3 and H-5), 8.0 (2H, d, J= 8.0 Hz, H-2′ and H-6′),
6.93 (2H, d, J= 8.0 Hz, H-3′ and H-5′), 3.85 (3H, s, OCH3), 3.18 (6H, s, N(CH3)2); 13
C NMR
(CDCl3, 400 MHz): δ 40.30 (2xCH3), 55.60 (-OCH3), 111.98 (C-3 and C-5), 113.81 (C-3′ and C-
5′), 122.98 (C-1), 130.42 (C-2′ and C-6′), 130.69 (C-2 and C-6), 116.81 (C-α), 132.62 (C-1),
152.05 (C-4′), 145.10 (C-β), 163.11 (C-4), 189.65 (C=O).

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‫مجلة جامعة كرميان‬ Journal of Garmian University ‫طؤظاري زانكؤي طةرميان‬
4''
5''
NO2
3''
6'' 2''
1'' 5'
5' H2CO H3CO
H3CO 6' 3
6' 6 5
4' CH3
4' 2
3' 1' 3' 1' 1 4 N
1 4 H3CO
H3CO 2' CH3
2' O 2 3
O 6 5

A1 A2

5' 5'
H3C 6 5
H3CO 6' 6 5
6' 4' CH3
4'
1' 1' 1 4 N
1 4 F 3'
3' CH3
2' 2'
2 3 O 2 3
O

A3 A4

Figure 2: Structures of Synthesized Compounds.

Biological activities Procedures

DPPH Radical scavenging activity
The free radical scavenging activity of synthesized compounds was evaluated using 1,1-diphenyl-
2-picrylhydrazyl (DPPH) method proposed by Blois [14] with some modification. 200 μL of
each sample (stock solution (1mg/mL) was diluted to final concentration of 1000, 500, 250, 125,
62.5, 31.25 μg/ml) was added to 3.8 mL of metahnolic DPPH solution (5mg in 250 ml). After 30
minutes at room temperature in a dark place, the absorbance was measured at 517 nm. MeOH
was used for the baseline correction. Vitamin C was used as standard with same concentration as
compounds. The IC50 value, defined as the amount of antioxidant necessary to decrease the initial
DPPH concentration by 50% was calculated from the results. All tests were carried out in dupli-
cate. The results were reported in mean values expressed as the percentage of DPPH which was
scavenged (% DPPH) calculated using the following equation. The graph pad Prism program was
used to calculate the IC50 value.

% DPPH = X 100
Where Abs. C is the absorbance of the control reaction and Abs. S is absorbance of the sample.

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‫مجلة جامعة كرميان‬ Journal of Garmian University ‫طؤظاري زانكؤي طةرميان‬
Antibacterial activity
The antibacterial assay was conducted (Gram-positive bacteria (Staphylococcus aureus and
Streptococcus agalactiae) and Gram-negative bacteria (Klebsiella pneumoniae and Escherichia
coli) by using disc diffusion method (DDM) as described by Mbaveng et al. [15]. The Mueller-
Hinton agar solution was poured into petri dishes. Then, the agar plates were kept in refrigerator
overnight. 6 mm diameter disc was impregnated with 60 μL of the solution of each compound (1
mg/mL) dissolved in MeOH. MeOH was used as the negative control. The petri dishes were in-
cubated for 24 hours at 37°C.

Results and Discussion

Having successfully synthesized Chalcones (A1, A2, A3 and A4) by condensation of substituted
acetophenones with substituted benzaldehydes using alcoholic KOH as a catalyst (Scheme 1).
The synthesized compounds were found to be in poor to good yields (31-69%). Compared with
standard Vitamin C the compounds (A2 and A3) showed excellent antioxidant activity (IC50
>50%). Presumably due to the presence of more methoxy together with nitrogen and floro
groups. Table 1 displayed IC50 for different synthesized chalcones. The graph shown in Figure 1
visualizing the pattern of each compound compared with the positive control used. The com-
pounds were no active against the bacterial strain used.

O
R H alc. KOH R
+
O 3-4 hrs, r.t. R'
R' O
Scheme 1: Synthetic route for the preparation of compounds.

Table 1: Antioxidant Activity of the Chalcones.

No. Compounds IC50 (mg/mL)

1 A1 ---
2 A2 0.1095
3 A3 0.1936
4 A4 ---
5 Vitamin C. (std) 0.6365

--- indicates no activity

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‫مجلة جامعة كرميان‬ Journal of Garmian University ‫طؤظاري زانكؤي طةرميان‬

Figure 3: Free radical scavenging activities of compounds A2, A3 and Vitamin C.

Conclusion
In present study four derivatives of chalcone were synthesized via Claisen-Schmidt condensation
under the influence of strong base. The structures of synthesized compounds were elucidated by
its 1H NMR, 13C NMR and FT-IR spectra. Two types of bioassays namely antioxidant and anti-
bacterial test were carried out. According to the results obtained, it can be concluded that (A2 and
A3) were had antioxidant activity, while none of the synthesized compound has antibacterial ac-
tivity. Further study, the antibacterial activity of the synthesized compounds could be deeply in-
vestigated by broadening spectrum of the bacterial strain and modification of the method.

Acknowledgments
I would like to thanks Dr. Ayad Faiq, Mr. Hasan Muhamad, Mr. Ramal ahamd and Mss. Rezan
Husen for their providing research facilities to carry out research work.

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References
1- Stella, L., Janousek, Z., Merényi, R., & Viehe, H. G. (1978). Stabilization of Radicals by
“Capto‐Dative” Substitution - C- C Addition to Radicophilic Olefins. Angewandte Chemie In-
ternational Edition in English, 17(9), 691-692.
2- Aichaoui, H., Guenadil, F., Kapanda, C. N., Lambert, D. M., McCurdy, C. R., and Poupaert,
J. H. (2009). Synthesis and pharmacological evaluation of antioxidant chalcone derivatives of
2 (3H)-benzoxazolones. Medicinal chemistry research, 18(6), 467-476.
3- S. V. Kostanecki and Tambor, J. (1899). Ueber die sechs isomeren monooxybenzalacetophe-
none (monooxychalkone). Berichte der deutschen chemischen Gesellschaft,32(2), 1921-1926.
4- Manmohan, S., Arindam, P., & Pratap, S. H.(2011) Synthesis and Characterization of Some
Novel Chalcone Derivatives: An Intermediate for Various Heterocyclics Compounds. 1(1):1-
7.
5- Zhao, L. M., Jin, H. S., Sun, L. P., Piao, H. R., & Quan, Z. S. (2005). Synthesis and evaluation
of antiplatelet activity of trihydroxychalcone derivatives. Bioorganic & medicinal chemistry
letters, 15(22), 5027-5029.
6- Sivakumar, P. M., Ganesan, S., Veluchamy, P., & Doble, M. (2010). Novel chalcones and 1,
3, 5‐triphenyl‐2‐pyrazoline derivatives as antibacterial agents. Chemical biology & drug de-
sign, 76(5), 407-411.
7- Nowakowska, Z. (2007). A review of anti-infective and anti-inflammatory chalcon-
es. European Journal of Medicinal Chemistry, 42(2), 125-137.
8- Sakai, T., Eskander, R. N., Guo, Y., Kim, K. J., Mefford, J., Hopkins, J. and Hoang, B. H.
(2012). Flavokawain B, a kava chalcone, induces apoptosis in synovial sarcoma cell
lines. Journal of Orthopaedic Research, 30(7), 1045-1050.
9- Prasad, Y. R., Rao, A. L. and Rambabu, R. (2008). Synthesis and antimicrobial activity of
some chalcone derivatives. Journal of Chemistry, 5(3), 461-466.
10- Rupe, H. and Wasserzug, D. (1901). Notizen über chromophore Gruppirungen. Berichte der
deutschen chemischen Gesellschaft, 34(3), 3527-3531.
11- Hermes, S.A. (1969) Chemische Berichte, 70, Article ID: 96422h.
12- Breslow, D. S. and Hauser, C. R. (1940). Condensations. 1 XI. Condensations of Certain Ac-
tive Hydrogen Compounds Effected by Boron Trifluoride and Aluminum Chloride2. Journal
of the American Chemical Society, 62(9), 2385-2388.
13- K. Kazauki, K. Hitayama, S. Yokomor and T. Soki. (1976). Chemical Abstract, 85, 591.

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‫مجلة جامعة كرميان‬ ‫‪Journal of Garmian University‬‬ ‫طؤظاري زانكؤي طةرميان‬
‫‪14- Blois, M.S., 1958. Antioxidation determination by the use of a stable free radical. Nature, 26,‬‬
‫‪1199-1200.‬‬
‫‪15- Mbaveng, A.T., Ngameni, B., Kuete, V., Simo, I.K., Ambassa, P., Roy, R., Bezabih, M.,‬‬
‫‪Etoa, F., Ngadjui, B.T., Abegaz, B.M., Meyer, J.J.M., Lall, N. and Beng, P. (2008). Antimi-‬‬
‫‪crobial Activity of the Crude Extracts and Five Flavonids from the Twigs of Dorstenia barteri‬‬
‫‪(Moraceae). J. Etho. 116: 483-489.‬‬

‫تحضير مركبات الجالكوني (‪ )Chalcone‬وقياس فعالياتها البايولوجية‬

‫اسو حميد حسن‬
‫جامعة كرميان‪ -‬كلية التربية‪ -‬قسم الكيمياء‬

‫في هذه الدراسة تم تحضير عدة مشتقات من مركبات الجالكوني (‪ )Chalcone‬من مركبات اريل‬
‫كيتون واريل الديهايد مختلفة في وسط قاعدي‪.‬وتم تشخيص المركبات المحضرة عن طريق‬
‫والرنين النووي‬ ‫قياس درجة االنصهار وتقنيات مطيافية االشعة تحت الحمراء‪FT-IR‬‬
‫المغناطيسي بنوعيه ‪ 1H NMR‬و ‪ . 13C NMR‬وتم تقدير الفعاليات البايولوجية لهذه المركبات‬
‫كمضادات بكتيرية ومضادات اكسدة‪.‬‬

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‫مجلة جامعة كرميان‬ Journal of Garmian University ‫طؤظاري زانكؤي طةرميان‬

Figure 4: 1H NMR spectrum of compound A1

Figure 5: 1H NMR spectrum of compound A1

Figure 6: FT-IR spectrum of compound A1

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‫مجلة جامعة كرميان‬ Journal of Garmian University ‫طؤظاري زانكؤي طةرميان‬

Figure 7: 1H NMR spectrum of compound A2

Figure 8: 13C NMR spectrum of compound A2

Figure 9: FT-IR spectrum of compound A2

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‫مجلة جامعة كرميان‬ Journal of Garmian University ‫طؤظاري زانكؤي طةرميان‬

Figure 10: 1H NMR spectrum of compound A3

Figure 11: 13C NMR spectrum of compound A3

Figure 12: FT-IR spectrum of compound A3

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 ‫مجلة جامعة كرميان‬ Journal of Garmian University ‫طؤظاري زانكؤي طةرميان‬

Figure 13: 1H NMR spectrum of compound A4

Figure 14: 13C NMR spectrum of compound A4

Figure 15: FT-IR spectrum of compound A4

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