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Green synthesis of chalcones derivatives
Conference Paper in AIP Conference Proceedings · April 2021
DOI: 10.1063/5.0042002
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Green synthesis of chalcones derivatives
Cite as: AIP Conference Proceedings 2331, 040020 (2021); https://doi.org/10.1063/5.0042002
Published Online: 02 April 2021
Dewi Septianingtyas, Nahda Zafira, Zulhipri, et al.
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© 2021 Author(s).
2331, 040020
Green Synthesis of Chalcones Derivatives
Dewi Septianingtyas, Nahda Zafira, Zulhipri, Fera Kurniadewi, and Hanhan
Dianhar a)
Chemistry Study Program, Faculty of Mathematics and Natural Sciences
Universitas Negeri Jakarta, Jalan Rawamangun Muka, Kel. Rawamangun
East Jakarta 13220, Indonesia
a)
Corresponding author: hanhan@unj.ac.id
Abstract. Chalcone is a common natural pigment and one of the important intermediates in flavonoid biosynthesis.
It has broad bioactivities such as anti-inflammatory, anti-cancer, and anti-fungal properties. In this research,
chalcone derivatives were synthesized as a precursor of hydrogenation transfer reaction to afford dihydrochalcones.
This study aimed to synthesize chalcone derivatives and determine the effect of hydroxyl substituents qualitatively.
Our experiment was carried out to synthesis some chalcone derivatives at room temperature just by stirring process.
In this study the synthesis of chalcone derivatives was started from 5 mmol various benzaldehyde and acetophenone
in the presence of a 60% KOH catalyst solution then the mixture was stirred for 1.5 hours and allowed to stand for
16 hours. The solution of 10% HCl was added and the formed crystal was then purified by recrystallization. The
purity of chalcones yielded was investigated by Thin Layer Chromatography (TLC) and melting point test while the
structure was then characterized by UV-vis and NMR spectroscopy. It was found that the optimal stirring time was
1.5 hours, the yield of hydroxyl substituted chalcone was higher than the compound which was not substituted. It can
be concluded that the synthesis results in hydroxyl substituted chalcone derivatives have higher yields compared to
chalcone derivatives without hydroxyl substitution.
INTRODUCTION
Chalcone (C15H12O), 1,3-diphenyl-1-propen-1-one is a very important compound in nature. Chalcones
contain two aromatic rings (A and B) and one carbon atom α, β-unsaturated. Chalcone, as a precursor of
flavonoids and isoflavonoids that are widely found in Indonesian plants. Chemically, chalcone consists of open
chain flavonoids in which two aromatic rings join with three carbons in the α, β-unsaturated carbonyl system
[1]. Chalcone is synthesized by Claisen-Schmidt condensation, which involves the cross-aldol condensation of
aldehydes and ketones with a base or acid catalyst followed by a dehydration reaction. Chalcone is a common
natural pigment and one of the important intermediaries in flavonoid biosynthesis [2].
In laboratory synthesis chalcone can be made using the Claisen-Schmidt reaction by reacting acetophenone
compounds or their derivatives with benzaldehyde or their derivatives using strong bases such as NaOH, KOH,
Ba(OH)2, LiOH.2H2O or NaH as catalysts in polar solvents. Other catalysts that can also be used are sodium
phosphate and aluminum-magnesium hydroxide hydrate. Whereas acid catalysts are usually used such as HCl,
AlCl3, BF3-Et2O, TiCl4, RuCl3 [3]. Recently, there have been many synthetic studies involving chalcone
compounds. From previous research conducted by [4] chalcone synthesis was carried out without the use of
solvents, this method produced very high product yields. In the study [4] benzaldehyde and acetophenone were
used in the presence of solid NaOH in mortars, with large crude product yields ranging from 81-94%. In 2014
[5] reported that chalcone compound (1,3-diphenyl-2-propen-1-one) and its derivative 4-methoxychalcone could
be synthesized by microwave irradiation (400 watt power for 9 minutes) with a catalyst acid
(bentonite/montmorillonite) and yield percentage of 1.72% and 5.21%.
Several years later [6] reported the synthesis of several chalcone derivatives using two methods, namely the
conventional method and the microwave irradiation method. In the research [6] 2-acetyl-5-methyl-furan and
aldehyde compounds and alcohol solvents were used. From his research [6] states that most chalcone derivatives
have the potential to have cytotoxic and antioxidant activities. The most recent research was in 2019 [7] in
which 3,4,4 'trimethoxychalcone was synthesized from 4-methoxy acetophenone and 3,4-dimethoxy
benzaldehyde with variations in the amount of NaOH catalyst and time variation. [7] reported that the optimum
amount of NaOH catalyst was obtained which was 8 mmol and the optimum reaction time was 3 hours. In this
The 2nd Science and Mathematics International Conference (SMIC 2020)
AIP Conf. Proc. 2331, 040020-1–040020-4; https://doi.org/10.1063/5.0042002
Published by AIP Publishing. 978-0-7354-4075-3/$30.00
040020-1
research, synthesis of chalcone which can be used as a precursor in the reaction of hydrogenation transfer
between chalcone compound and Hantzsch ester will produce dihydrochalcone compound. In this study,
benzaldehyde compounds will be reacted with acetophenone compounds in an alkaline atmosphere and chalcone
compounds will be produced. In this study, a conventional method was used in which the synthesized compound
was purified through the recrystallization process and its purity tested by TLC.
METHOD
In this study, chalcone derivatives were synthesized from benzaldehyde and acetophenone, where the
benzaldehyde compound was varied as benzaldehyde and 4-hydroxy benzaldehyde. This research was
conducted at the Research Laboratory of Chemistry Study Program, Faculty of Mathematics and Natural
Sciences, State University of Jakarta
Synthesis of Chalcone
The experiment was started by adding 5 mmol of acetophenone into 5 ml of ethanol in a round bottom flask,
then 5 mmol of benzaldehyde was added to the flask. Then to the mixture was added 60% KOH solution, the
addition was done by dripping slowly while stirring with a stirrer and then the mixture was stirred with a stirrer
for 1.5 hours. When stirring does not involve heating where stirring is carried out at room temperature. After
mixing, the mixture is allowed to stand for 14 to 16 hours at room temperature. After being allowed to stand for
up to 16 hours the mixture was tested for purity by TLC and melting point test, then the mixture was added with
10% HCl of 1.5 ml. Then the crude product formed is filtered with a Buchner filter and washed with cold
aquadest to neutral. Furthermore, recrystallization with cold ethanol is carried out using a Buchner filter until
the precipitate is separated from the filtrate. Then the filtered filtrate is evaporated and dried at room
temperature.
Synthesis 4-Hydroxy Chalcone
The experiment was started by adding 5 mmol of acetophenone into 5 ml of ethanol in a round bottom flask,
then 5 mmol of 4-hydroxy benzaldehyde was added to the flask. Then to the mixture was added 60% KOH
solution, the addition was done by dripping slowly while stirring with a stirrer and then the mixture was stirred
with a stirrer for 1.5 hours. When stirring does not involve heating where stirring is carried out at room
temperature. After mixing, the mixture is allowed to stand for 14 to 16 hours at room temperature. After being
allowed to stand for up to 16 hours the mixture was tested for purity by TLC and melting point test, then the
mixture was added with 10% HCl of 1.5 ml. Then the crude product formed is filtered with a Buchner filter and
washed with cold aquadest to neutral. Furthermore, recrystallization with cold ethanol is carried out using a
Buchner filter until the precipitate is separated from the filtrate. Then the filtered filtrate is evaporated and dried
at room temperature.
RESULT AND DISCUSSION
In this experiment, the synthesis of chalcone derived from benzaldehyde with acetophenone which involved
the use of KOH as an alkaline atmosphere was given, while the chalcone synthesis reaction was shown in Figure
1. The benzaldehyde compounds used were varied by 2 types, benzaldehyde, and 4-hydroxy benzaldehyde. This
experiment also involved the use of HCl with a concentration of 10%. Before starting the experiment, the first
KOH solution is made with a concentration of 60%. The making of the KOH solution is by dissolving 3 grams
of KOH solid into 5 ml aquadest. KOH solution is used because KOH is a basic catalyst used in synthesis other
than NaOH and KOH tends to work effectively in mild reactions. In KOH solution there is OH- as base
nucleophiles (enolates) that have higher nucleophility than acid nucleophiles [8].
CH3
O
OHC
O
KOH
+
Benzaldehyde
H2O
Chalcone
Acetophenone
FIGURE 1. Chalcone Synthesis Reaction from Benzaldehyde and Acetophenone
040020-2
The first experiment was started by putting 5 mmol of acetophenone into 5 ml of ethanol in a round bottom
flask, then adding 5 mmol of benzaldehyde to the flask. Then to the mixture was added 60% KOH solution, the
addition was done by dripping slowly while stirring with a stirrer and then the mixture was stirred with a stirrer
for 1.5 hours. When stirring does not involve heating where stirring is carried out at room temperature [9]. In
this experiment room temperature was choose because usually, the synthesis was in high-temperature water
(200O to 350OC), so we try the other way with a mild condition (room temperature). After mixing, the mixture
becomes bright yellow which is then allowed to stand for 14 to 16 hours at room temperature. Next, the mixture
was tested for purity by TLC and melting point. In the TLC test, we used N-Hexane and ethyl acetate (19:1) as
an eluent. When plate shined by UV there is one dot, which means the sample was pure and there's no
contaminant, from melting point test show that the melting point from the sample was similar to chalcone
melting point.
After settling for up to 16 hours the solution mixture was added with 10% HCl as much as 1.5 ml, after
adding HCl it was seen that in the solution began to form precipitates because the addition of HCl would
separate the potassium chalcone salt from the solution [9]. Then the crude product formed is filtered with a
Buchner filter and washed with cold aquadest to neutral. Furthermore, recrystallization with cold ethanol is
carried out using a Buchner filter until the precipitate is separated from the filtrate. Recrystallization was to
purify the product (chalcone) by dissolving in ethanol, so the desired compound or impurities can be removed
from the solution. Then the filtered filtrate is evaporated and dried at room temperature, evaporation is carried
out to separate the remaining deposits in the first filtered filtrate. Evaporation requires heat (air movement above
the sample) that can drive off the solvent from the sample. After that, the sludge was weighed and the resulting
weight was 0.1268 grams and the yield was calculated to be 12.19%.
The second experiment used a variation of benzaldehyde, 4-hydroxy benzaldehyde reacted with
acetophenone. The treatment in this experiment is the same as the previous experiment. In this experiment OH
group when positioned within a structure where it can participate in the delocalization of pi electrons, will
function as a strong electron donor. Hydroxy substituent as an activating substituent increases the rate of
electrophilic substitution and hydroxy can donating an electron to activate the benzene ring toward electrophilic
attack, so the yield would be increased. From this second experiment, we obtained a sediment weight of 1.1228
grams and a yield of 99.8%. From the results of these two experiments that were shown in Table 1, it could be
seen that the second experiment which involved 4-hydroxy benzaldehyde and acetophenone produced a greater
yield. In this case, the addition of hydroxy substituents will increase the yield of the synthesized chalcone
compound [10].
TABLE 1. The result of Chalcone Derivatives Synthesis
O
Acetophenone
Variation
Benzaldehyde
Variation
O
Crude product: Bright Yellow
Weight: 0,1268 gr
Yield: 12.19%
H
O
H
Crude product: Bright Yellow
Weight: 1,1228 gr
Yield: 99,8%
HO
CONCLUSION
In this experiment the results of the synthesis were tested by TLC and melting point test, it was found that
from both tests the synthesized compound was formed. From the yield obtained, the results of the synthesis
040020-3
involving 4-hydroxy benzaldehyde have a higher yield than the results involving only benzaldehyde in the
absence of a hydroxy substituent. From these results, it can be concluded that the addition of hydroxy
substituents to benzaldehyde compounds can increase the yield of chalcone compounds formed.
ACKNOWLEDGMENT
This research was funded by the Dana BLU POK MIPA UNJ 2020 on The Rector’s Letter No.
476/UN39/KU.00.01/2020.
REFERENCES
1.
2.
3.
S. Syam, S. I. Abdelwahab, M. A. Al-Mamary, S. Mohan, Molecules 17(6), pp. 6179–6195 (2012).
A. L. Choudhary, V. Juyal, Int J Pharm Pharm Sci. 3(3), pp. 125–128 (2011).
D. K. Mahapatra, S. K. Bharti, V. Asati, Eur J Med Chem 98, pp. 69–114 (2015). [Online]. Available
from: http://dx.doi.org/10.1016/j.ejmech.2015.05.004
4. G. Chemistry, J Chem Educ. 81(9), pp. 1345–1347 (2004).
5. Suzana, K. Amalia, M. I. S, M. Rudyanto, H. Poerwono, T. Budiati, J Farm dan Ilmu Kefarmasian
Indones. 1(1), pp. 24–27 (2014).
6. M. Rayees Ahmad, V. Girija Sastry, N. Bano, S. Anwar, Arab J Chem 9, pp. S931–S935. [Online].
Available from: http://dx.doi.org/10.1016/j.arabjc.2011.09.002
7. R. Rehana, M. S. Fahreza, M. W. S, ALCHEMY J Penelit Kim. 15(2), p. 228 (2019).
8. D. Dan, V. Dalam, Optimasi Waktu Pengadukan Sintesis Senyawa Kalkon Basa Optimation Stirring
Time of Chalcone Synthesis From. :pp. 83–89.
9. SM, .HPS, .SDG, .NSHNM. Trends Appl Sci Res. 2(1), 52–56 (2007).
10. S. S. Shafi and T. Nadu, Synthesis, Characterisation And Antimicrobial Activity Of Some New
Chalcones M. Elavarasan, M. Thamizh Thendral and S. Syed Shafi * Department of Chemistry,
Thiruvalluvar University, Serkkadu, Vellore - 632115, Tamil Nadu, India. 9(5), pp. 1969–1973 (2018).
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