[Link] et al, /J. Pharm. Sci. & Res. Vol.
2 (8), 2010, 450-458
Synthesis and Characterization of 2,6-Dihydroxy Substituted Chalcones
Using PEG-400 as a Recyclable Solvent
[Link]*, [Link] Prasad, and [Link]
Department of Chemistry, Sri Venkateswara University, Tirupati – 517 502, A.P. India.
Abstract:
A novel method for the synthesis of 2,6-dihydroxy substituted chalcones via Claisen-Schmidt is introduced
using recyclable PEG-400 as an alternative reaction solvent. The reaction is clean with excellent yield, shorter
reaction time and reduces the use of volatile organic compounds (VOCs). The structures of the synthesized
compounds were confirmed by IR, mass spectroscopy and elemental analysis.
Keywords: Chalcone, Claisen-Schmdit condensation, PEG-400, IR, Mass and Elemental spectral analysis
Introduction: carbon bond have been reported. Among
In recent years, Chalcones have found a them the direct Aldol condensation and
wide range of applications in the Claisen-Schmidt condensation still occupy
pharmacological activities such as, prominent positions. The main method for
potential cytotoxic agents, antiviral, the synthesis of chalcones is the classical
anesthetics, mydriatics, antimicrobial, Claisen-Schmidt condensation in the
antimitoitic, antitumor, cytotoxicity, and presence of aqueous alkaline bases,[14]
antipyretic properties[1-9] The presence of Ba(OH)2[15] LiOH, microwave irradiation
a reactive ,-unsaturated ketone function and ultrasound irradiation [16]. They are
in chalcones is found to be responsible for also obtained via Suzuki reaction,[17]
their antimicrobial activity which may be Witting reaction, Friedel-Crafts acylation
altered depending on the type and position with cinnamoyl chloride, or Photo-Fries
of substituent aromatic rings. They also act rearrangement of phenyl cinnamates. In
as potential antiulcer, antifungal, aldol condensation the preparation of
anticancer [10] and antimalerial agents chalcones requires at least two-steps aldol
[11] Chalcones are a group of compounds formation and dehydration. Since aldol
with various substitution patterns on the addition is reversible, mukaiyama or
two aromatic rings of 1,3-diphenyl-2- Claisen-Schmidt condensation approach of
propene-1-one, that are considered as the using enol ether has emerged as an
precursor of flavonoids and isoflavoniods alternative pathway.
are abundant in edible plants. Chalcones The aldol reaction is also performed under
have been prepared by condensing aryl acidic medium,[18] using HCl, BF3, B2O3,
ketones with aromatic aldehydes in p-toluenesulfonic acid etc. Recently
presence of suitable condensing agents. various modified methods for the synthesis
They undergo a variety of chemical of chalcones has been reported, such as by
reactions and are found to be useful in the using SOCl2,[19] natural phosphate,
synthesis of variety of heterocyclic lithium nitrate,[20] amino grafted
compounds[12] like isoxazoles, zeolites,[21] zinc oxide, water,[22]
quinolinones, thiadiazines, Na2CO3,[23], PEG400,[24] silicasulfuric
benzofuranones,benzodiazepine, acid,[25, 26] ZrCl4 and ionic liquid [27]
tetrahydro-2-chromens [13] flavones etc., etc. Jhala et al. synthesized chalcone using
Moreover, these are important basic alumina under micro wave
intermediates in many addition reactions irradiation. However, many of these
of nucleophiles due to inductive methods suffered from harsh reaction
polarization of carbonyl group at the - condition, toxic reagents, strong acidic or
position. These findings explain the basic conditions, prolonged reaction-times,
significant interest of scientist in this poor yields and low selectivity. Although,
particular group of compounds. several modifications have been made to
Several strategies for the synthesis of these counter these problems. There is still a
system, based on the formation of carbon- need for the development of selective and
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[Link] et al, /J. Pharm. Sci. & Res. Vol.2 (8), 2010, 450-458
Fig. 1: IR data of 1-(2,6- dihydroxyphenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one
Fig. 2: Mass spectral data of 1-(2,6- dihydroxyphenyl)-3-(4-hydroxyphenyl) prop-2-en-1-one
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[Link] et al, /J. Pharm. Sci. & Res. Vol.2 (8), 2010, 450-458
Fig. 3: Elemental analysis data of 1-(2,6- dihydroxyphenyl)-3-(4-hydroxy phenyl)prop-2-en-
1-one
better strategies for the synthesis of , - strategies for the synthesis of , -
unsaturated carbonyl compounds. unsaturated carbonyl compounds.
However, many of these methods suffered Herein for the first time we describe a
from harsh reaction condition, toxic simple and convenient method for the
reagents, strong acidic or basic conditions, synthesis of chalcones using poly ethylene
prolonged reaction times, poor yields and glycol (PEG) has been found to be an
low selectivity. Although, several interesting solvent system. In continuation
modifications had been made to counter of own work on chalcones as
these problems. There is still a need for the perrecursorsin the synthesis of various
development of selective and better heterocycles [28], we have planned to
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[Link] et al, /J. Pharm. Sci. & Res. Vol.2 (8), 2010, 450-458
synthesize a series of novel hetero chalcones by applying the principles of
Fig.4: IR data of 1-(2,6- dihydroxyphenyl)-3-(3-hydroxyphenyl)prop-2-en-1-one
Fig. 5: Mass spectral data of 1-(2,6- dihydroxyphenyl)-3-(3-hydroxyphenyl) prop-2-en-1-one
453
[Link] et al, /J. Pharm. Sci. & Res. Vol.2 (8), 2010, 450-458
Fig. 6: Elemental analysis data of 1-(2,6- dihydroxyphenyl)-3-(3-hydroxy phenyl)prop-2-en-
1-one
Table.1: Physicochemical characterization data for synthesized compounds
Compound Molecular Molecular Yield M.P Elemental analysis
Number formula weight (%) °C
C H N
1 C15 H11 ClO3 274 71 198 66.54 4.06
(66.75) (4.04) -
2 C15 H12 O4 256 75 140 70.41 4.68
(70.37) (4.72) -
3 C15 H12 O4 256 81 190 70.18 4.58
(70.37) (4.72) -
4 C15 H11 NO5 285 64 192 63.24 4.72 4.96
(63.21) (3.89) (4.91)
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[Link] et al, /J. Pharm. Sci. & Res. Vol.2 (8), 2010, 450-458
Table.2: Interpreted IR spectral data of synthesized compounds
Compound Compound IR. Spectral data
number
1 3-(4-chlorophenyl)-1- IR (KBr) v cm-1, (-OH) 3212 cm-1,
(2,6-dihydroxyphenyl) (C=0) 1682 cm-1, (C=C) 1591 cm-1
prop-2-en-1-one
2 1-(2,6-dihydroxyphenyl)-3- IR (KBr) v cm-1, (-OH) 3234 cm-1,
(4-hydroxyphenyl) (C=0) 1626 cm-1, (C=C) 1527 cm-1
prop-2-en-1-one
3 1-(2,6-dihydroxyphenyl)-3- IR (KBr) v cm-1, (-OH) 3369 cm-1,
(3-hydroxyphenyl) (C=0) 1684 cm-1, (C=C)1599 cm-1
prop-2-en-1-one
4 1-(2,6-dihydroxyphenyl)-3- IR (KBr) v cm-1, (-OH) 3200 cm-1 ,
(4-nitrophenyl) (C=0) 1672 cm-1, (C=C)1591 cm-1
2 1
Table.3: Mass spectral data of synthesized compounds
Compound Compound Molecular Mass
Number weight spectral
data
1 3-(4-chlorophenyl)-1-(2,6-dihydroxyphenyl) prop-2-en-1-one 274 274 M+2
2 1-(2,6-dihydroxyphenyl)-3-(4-hydroxyphenyl) prop-2-en-1-one 256 256 M+H
3 1-(2,6-dihydroxyphenyl)-3-(3-hydroxyphenyl) prop-2-en-1-one 256 256 M-H
4 1-(2,6-dihydroxyphenyl)-3-(4-nitrophenyl) prop-2en-1-one 285 285 M+
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green chemistry, using PEG400 as an
alternative reaction medium [29]. PEG is an OH
Cl
environmentally benign reaction solvent, is
it non-toxic, inexpensive, potentially OH
C
recyclable and water soluble, which O
facilitates its removal from the reaction An equimolar mixture of 2,6-hydroxy
product. acetophenone(2.2), aromatic aldehydes(2.2)
Materials and Methods: and KOH (5ml) was stirred in PEG-400
All the products were synthesized and (10ml) at 40°C for 1 hour after the
characterized by their spectral analysis. completion of the reaction (monitored by
Chemicals, 2,6-hydroxy acetophenone, 2- TLC), the crude mixture was worked up in
chloro benzaldehyde, 4-chloro ice-cold water (100 ml). The product which
benzaldehyde, 3-nitrobenzaldehyde were separated out was filtered. The filtrate was
purchased from S.D. fine Chemicals (India). evaporated to remove water leaving PEG
Melting points were uncorrected and behind. The same PEG was utilized to
determined in an open capillary tube. IR synthesize further chalcone.
spectra were recorded in KBr on a JASCO 2) Synthesis of 1-(2,6-dihydroxyphenyl)-3-
FT/IR-5300 The mass spectra were recorded (4-hydroxyphenyl) prop-2-en-1-one
on LCMS-2010 DATA REPORT Reaction with 2,6-dihydroxy acetophenone
SHIMADZU Spectrometer Elemental (2 gm) and 4-hydroxy benzal-dehyde
analysis was carried out on a FLASH EA (2.1gm);1-(2,6-dihydroxyphenyl)-3-(4-
1112 SERIES CHN REPORT THERMO hydroxyphenyl) prop-2-en-1-one was
FINNIGAN. Chalcones were synthesized by obtained by the above procedure.
clasion- Schmidt condensation using PEG- OH
OH
400 as reaction. Solvent. The chemicals and
solvent used were of laboratory grade and
C
were purified completion of the reaction was OH
O
monitored by thin layer chromatography on
3) Synthesis of 1-(2, 6-dihydroxyphenyl)-3-
precoated sheets of silica gel-G (Merck,
(3-hydroxyphenyl) prop-2-en-1-one
Germany) using iodine vapour for detection.
A mixture of 2, 6-dihydroxy acetophenone
The synthetic pathway is presented in
(2.2 gm) in PEG-400 (10 ml) and
Scheme 1 and physicochemical data and
3-hydroxy benzaldehyde (2.1 gm); 1-(2,6-
spectral data for the synthesized compounds
dihydroxyphenyl)-3-(3-hydroxyphenyl)
are given Table (1-3).
CHO prop-2-en-1-one was obtained by the above
OH OH procedure.
PEG-400 OH
CH3 R
Stirring 400C
C C OH
R
=
HO O HO O
a. R= 4-Cl
b. R= 4-OH
c. R= 3-OH
d. R= 4 NO2 C
OH
Scheme 1: Synthetic diagram of 2,6, O
dihydroxy substituted chalcones 4) Synthesis of 1-(2, 6-dihydroxyphenyl)-3-
1) Synthesis of 3-(4-chlorophenyl)-1-(2,6- (4-nitrophenyl)prop-2en-1-one
dihydroxyphenyl) prop-2-en-1-one 1-(2,6-dihydroxyphenyl)-3-(4-nitrophenyl)
prop-2 en-1-one was obtained by the above
described procedure except that starting
456
[Link] et al, /J. Pharm. Sci. & Res. Vol.2 (8), 2010, 450-458
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