Documente Academic
Documente Profesional
Documente Cultură
APRIL 2009
APRIL 2009
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ACKNOWLEDGEMENTS
Upon completion of this project, I would like to express my gratitude to many parties.
My heartfelt thanks go to my supervisor, Assoc. Prof. Yazan Zakaria because she gave
me a lot of help, advice and support during the completion of this project. I also want to
thank my partner, Norizan binti Tajudin who always help me and right here beside me
whenever I need helps. Other than that, thank you to all my lecturers and friends who had
involved directly and indirectly in accomplishing this project.
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TABLE OF CONTENTS
Page
ACKNOWLEDGEMENT
TABLE OF CONTENTS
LIST OF TABLES
LIST OF FIGURES
LIST OF ABBREVIATIONS
ABSTRACT
ABSTRAK
iii
iv
vi
viii
x
xi
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CHAPTER 1 INTRODUCTION
1.1
Background of study
1.1.1 Mechanism of aldol condensation
1.2
Problem statement
1.3
Significance of study
1.4
Objectives of study
1
4
6
7
7
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8
8
9
12
13
14
15
18
CHAPTER 3 METHODOLOGY
3.1
Materials
21
3.2
Methods
3.2.1 Procedure to synthesize chalcone using solid sodium hydroxide
22
(NaOH)
3.2.2 Procedure to synthesize chalcone using aqueous sodium hydroxide 22
(NaOH)
CHAPTER 4 RESULTS AND DISCUSSION
4.1
Aldol syntheses of chalcones catalyzed by strong base NaOH
4.2
IR spectral analysis of the chalcones
1
4.3
H NMR spectral analysis of the chalcones
4.3.1 Synthesis of 3-nitro-4-methoxychalcone using solid NaOH
4.3.2 Synthesis of 3-nitro-4-methoxychalcone using aqueous NaOH
4.3.3 Synthesis of 4,4-dimethoxychalcone using solid NaOH
4.3.4 Synthesis of 4,4-dimethoxychalcone using aqueous NaOH
4.3.5 Synthesis of 4-chloro-4-methoxychalcone using solid NaOH
4.4.6 Synthesis of 4-chloro-4-methoxychalcone using aqueous NaOH
13
4.4
C NMR spectral analysis of the chalcones
33
38
40
45
47
50
52
55
CITED REFERENCES
APPENDICES
56
57
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24
27
LIST OF TABLES
Table
Caption
Page
2.1
2.2
11
2.3
13
2.4
17
2.5
18
2.6
3.1
4.1
4.2
28
4.3
30
4.4.
32
4.5
36
4.6
39
4.7
42
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21
4.8
45
4.9
48
4.10
50
4.11
53
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LIST OF FIGURES
Figure
Caption
Page
1.1
1.2
2.1
12
4.1
24
4.2
27
4.3
27
4.4
29
4.5
29
4.6
31
4.7
4.8
33
4.9
34
4.10
35
4.11
39
4.12
40
4.13
41
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4.14
42
4.15
43
4.16
46
4.17
46
4.18
47
4.19
48
4.20
49
4.21
51
4.22
51
4.23
Structure of 3-nitro-4-methoxychalcone
52
4.24
54
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LIST OF ABBREVIATIONS
GCMS
IR
Infrared
NLO
Non-linear optical
NMR
TLC
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ABSTRACT
SOLVENT-FREE SYNTHESIS OF CHALCONE BY ALDOL CONDENSATION
CATALYZED BY SOLID SODIUM HYDROXIDE (NaOH)
Chalcones represent a group of compounds with interesting biological activities that are
formed from an aldol condensation between a benzaldehyde and an acetophenone in the
presence of NaOH as a catalyst. Although traditionally synthesized using aqueous sodium
hydroxide in organic solvents, in this study three different chalcones were synthesized
using a solventless procedure. The solvent-free synthesis of three chalcones was carried
out by grinding the benzaldehyde
(3-nitro, 4-methoxy, 4-chloro) and 4methoxyacetophenone in the presence of solid sodium hydroxide with a mortar and
pestle. Chalcones were obtained in high yields (76-86%), high purity, and shorter
reaction time (within five minutes). The results seemed to indicate the success of the
solvent-free aldol synthesis which is simple, highly efficient and eco-friendly. For
comparison, the three chalcones were also synthesized by the traditional aldol
condensation catalyzed by aqueous sodium hydroxide in ethanol afforded lower yield
(62-72%) and required longer reaction time (62-75 min).
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ABSTRAK
SINTESIS CHALKON BEBAS PELARUT DARIPADA KONDENSASI ALDOL
DIMANGKINKAN OLEH PEPEJAL NATRIUM HIDROKSIDA (NaOH)
Chalkon mewakili satu kumpulan sebatian dengan aktiviti biologi yang menarik, hasil
daripada kondensasi aldol di antara benzaldehid dan asetofenon dengan kehadiran
natrium hidroksida (NaOH) sebagai pemangkin. Walaupun disintesis secara tradisional
dengan menggunakan larutan NaOH, dalam kajian ini, tiga jenis chalkon berlainan telah
disintesis melalui prosedur tanpa pelarut. Sintesis tanpa pelarut ketiga-tiga chalkon
dijalankan dengan menumbuk benzaldehyde (3-nitro, 4-metoksi, 4-kloro) dan 4metoksiasetofenon bersama pepejal NaOH dengan menggunakan lesung. Semua chalkon
terbentuk dengan peratusan hasil yang tinggi (76-86%), ketulenan yang tinggi dan masa
tindak balas yang singkat (dalam masa lima minit). Keputusan membuktikan bahawa
sintesis aldol tanpa pelarut adalah mudah, efisyen dan mesra alam. Sebagai perbandingan,
tiga jenis chalkon lain telah disintesis menggunakan kaedah tradisional kondensasi aldol
yang dimangkinkan oleh larutan NaOH dalam etanol. Peratusan hasil adalah rendah (6272%) dan memerlukan masa tindak balas yang lama (62-75 min).
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CHAPTER 1
INTRODUCTION
1.1
Background of study
Chalcone is an aromatic ketone that forms the central core for a variety of
important
biological
compounds.
Other
names
for
chalcone
are
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There are several methods available for the synthesis of chalcones. The most
widely used is the base-catalyzed such as sodium hydroxide (NaOH), potassium
hydroxide (KOH), barium hydroxide Ba(OH)2 and lithium hydroxide
(LiOHH2O). The acid-catalyzed that had been used to synthesize chalcones
includes aluminum trichloride (AlCl3), dry HCl, boron trifluoride-etherate (BF3Et2O), titanium tetrachloride (TiCl4) and ruthenium trichloride (RuCl3) (Bhagat
et al., 2006)
In this project, the catalysts that were used are solid sodium hydroxide (NaOH)
and aqueous NaOH. The first solid NaOH method was introduced by Palleros in
2004.
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MeO
+
O
4-methoxyacetophenone
NaOH
MeO
O
Substituted benzaldehyde
X = -NO2, OCH3, Cl
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O
Trans-chalcone
Step 4: Dehydration
The hydroxide acts as a base and removes an acidic -hydrogen giving the
reactive enolates. The electrons associated with a negative charge of the enolate
are used to form a carbon-carbon double bond (C=C) and displace a leaving
group, regenerating the hydroxide giving the final product, the conjugated
ketone.
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H 3CO
CH2
O
OH
H3CO
CH2
4-methoxyacetophenone
O
Cl
+ H3C
OCH3
4-chlorobenzaldehyde
O
Cl
O
C
CH C
H
OCH3
HO H
O
Cl
CH C
H
O
C
OCH3
Cl
OH H
C
H
C
H
OCH3
Step 4: Dehydration
OH
Cl
OH H
C
H
C
H
OCH3
Cl
C
H
C
H
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OCH3
1.2
Problem statement
Green chemistry is a term coined in the late 1980s to indicate the design and
use of chemical processes that reduce or eliminate the use and generation of
chemicals hazardous to the environment. More simply stated, it means that one
does a reaction on a small scale and uses safer chemicals, thus producing less
hazardous waste. The aldol synthesis of chalcones is considered a green
experiment because it is carried out without solvent. Instead, the benzaldehyde,
acetophenone, and sodium hydroxide are mixed in a mortar and pestle for a few
minutes to produce the chalcone. The product is washed with a little of water,
and if necessary a small amount of it is recrystallized from ethanol. There has
been tremendous interest in the application of solvent free aldol and crossedaldol reactions which are employed for synthesis of carbonyl compounds due to
the operational simplicity, simple work-up, high yields and eco-friendly nature.
The condensation of ketones with aldehydes is of special interest and the
crossed-aldol condensation is an effective pathway for those compounds
preparations. However the traditional base-catalyzed reactions suffer from the
reverse reaction and self condensation of starting molecules (Palleros, 2004)
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1.3
Significance of study
Chalcones are the main precursor for the biosynthesis of flavonoids, which are
frequent components of the human diet. Licochalcone A isolated from the roots
of Glycyrrhiza inflata (licorice) has in vitro and in vivo antimalarial and
antileishmanial activity. 3-Methoxy-4-hydroxyloncocarpin isolated from the
roots of Lonchocarpus utilis inhibits NADH:ubiquinone oxidoreductase activity
and synthetic chalcones such as 2,4-dimethoxy-4-allyloxychalcone and 2,4dimethoxy-4-butoxychalcone had been reported as antileishmanial agents.
Recent studies on biological evaluation of chalcones revealed some to be anticancer, anti-inflammatory, antimitotic, anti-tubercular, cardiovascular, cell
differentiation inducing, nitric oxide regulation modulatory and antihyperglycemic agents (Narender et al., 2007)
1.4
Objectives of study
1. To synthesize chalcones using two different catalysts; solid NaOH and
aqueous NaOH in ethanol;
2. To explore the feasibility and effectiveness of using solid NaOH as catalyst
in chalcone synthesis, in place of aqueous NaOH;
3. To characterize chalcones using NMR and IR spectrometry.
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CHAPTER 2
LITERATURE REVIEW
2.1
2.1.1 LiOHH2O as a novel dual activation catalyst for highly efficient and easy
synthesis of 1,3-diaryl-2-propenones by Claisen-Schmidt condenation under
mild conditions
According to Bhagat et al. (2006), commercially available LiOHH2O was found
to be a highly efficient dual catalyst for Claisen-Schmidt condensation of
various aryl methyl ketones with aryl/heteroaryl aldehydes by providing an easy
synthesis of 1,3-diaryl-2-propenones under mild conditions. The reactions were
carried out at room temperature and in short times affording high yields.
Excellent chemoselectivity was observed with carbonyl substrate bearing
halogen atom and nitro group without any competitive aromatic nucleophilic
substitution. The resultant chalcones did not undergo Michael addition with the
ketone enolate. The rate of ClaisenSchmidt condensation was found to be
dependent on the steric and electronic factors of the carbonyl substrates. In this
study,
they
carried
out
the
ClaisenSchmidt
condensation
of
4-
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reactions were carried out in short times (2 min4 h) and were monitored by
GCMS, IR and TLC. No competitive side reactions such as product
decomposition, aromatic nucleophilic substitution and Michael addition were
observed (GCMS). In general, the reactions were clean and the isolated products
were obtained in pure form (IR, NMR and GCMS) without further purification.
Table 2.1 LiOHH2O-catalyzed Claisen-Schmidt reaction of Ar1COCH3 with Ar2CHO.
Entry
Ar1
Ar2
Time (min)
Yield (%)
C6H5
C6H5
85
C6H5
4-OMe-C6H4
15
88
C6H5
4-Cl-C6H4
15
90
C6H5
4-NO2-C6H4
80
4-OMe-C6H4
C6H5
15
80
4-OMe-C6H4
4-Cl-C6H4
30
90
4-OMe-C6H4
4-OMe-C6H4
45
96
4-OMe-C6H4
4-NO2-C6H4
95
4-NO2-C6H4
C6H5
82
10
4-NO2-C6H4
4-OMe-C6H4
95
11
4-Cl-C6H4
4-OMe-C6H4
15
73
synthesized
several
chalcones
by
reacting
various
substituted
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obtained exclusively. The reaction mixture was washed with water to remove
BF3 complexes, concentrated and recrystallized to give pure chalcones in high
yields without column chromatography in most cases. In aqueous KOH or
NaOH assisted reactions, reaction times were much longer (2-4 days), with high
probability of side reactions such as the Cannizzaro reaction. By using BF3Et2O, they obtained chalcones exclusively, within 15-150 min and no side
reactions were observed. They concluded that their method has many advantages
over existing methods such as high yields, simple work-up, short reaction times,
no side reactions, no column-chromatography in most cases, a convenient source
of BF3.
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Yield
(%)
Mp (C)
30
87
148150
15
90
5657
150
80
196198
150
93
187189
60
92
192194
150
90
194196
150
75
134136
Entry
Ketone
Aldehyde
Chalcone (product)
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