Preheated fly-ash catalyzed aldol condensation: Efficient synthesis of chalcones and antimicrobial activities of some 3-thienyl chalcones

Article abstract of DOI:10.4067/S0717-97072013000200008

In the present study we have prepared a series of some chalcones using solvent - free Aldol - condensation by microwave irradiation. The yields of the ketones are more than 60%. The synthesised chalcones were characterized by their analytical, physical and spectral data. The antimicrobial activities of substituted styryl 3-thienyl ketones have been studied using Bauer-Kirby method.

Full text of DOI:10.4067/S0717-97072013000200008

J. Chil. Chem. Soc., 58, Nº 2 (2013)
PREHEATED FLY-ASH CATALYZED ALDOL CONDENSATION: EFFICIENT SYNTHESIS OF CHALCONES
AND ANTIMICROBIAL ACTIVITIES OF SOME 3-THIENYL CHALCONES
RANGANATHAN ARULKUMARAN1, SAMBANDHAMOORTHY VIJAYAKUMAR1, S PAZHANIVEL
SAKTHINATHAN1, DAKSHNAMOORTHY KAMALAKKANNAN1, KALIYAPERUMAL RANGANATHAN1,
RAMAMOORTHY SURESH1, RAJASEKARAN SUNDARARAJAN1 GANESAN VANANGAMUDI1 AND
GANESAMOORTHY THIRUNARAYANAN2*
1 Postgraduate and Research Department of Chemistry, Government Arts College, C-Mutlur, Chidambaram-608102, India.
2 Department of Chemistry, Annamalai University, Annamalainagar-608002, India.
(Received: June 28, 2012 - Accepted: January 22, 2013)
ABSTRACT
In the present study we have prepared a series of some chalcones using solvent - free Aldol - condensation by microwave irradiation. The yields of the ketones
are more than 60%. The synthesised chalcones were characterized by their analytical, physical and spectral data. The antimicrobial activities of substituted styryl
3-thienyl ketones have been studied using Bauer-Kirby method.
Key words: Styryl 3-thienyl ketones, Preheated fly-ash, Crossed-aldol reaction, Solvent free synthesis, Antimicrobial activities
formation during the reaction.
INTRODUCTION
General procedure for synthesis of chalcones
There are numerous greener and solvent-free1,2 synthetic methods available
for synthesis of organic compounds. The reactions involving the formation of
carbon-carbon bond and carbon-heteroatom bond are important and interesting
in green synthesis. Based on this the Aldol3, Crossed–aldol4, Knoevenagel5,
Mannich6, Michael7 and Wittig8 reactions have been applied for synthesising
isomeric biologically active compounds such as chalcones and alkenes. Thermal
condensation reactions have been found to be sluggish and time-consuming
with poor yields. However in the microwave conditions, the reaction is faster,
giving appreciable yield involving easier process of isolation of the products.
Scientists and specially chemists have used microwave irradiation technique
for solid phase green synthesis8,9. Numerous green catalysts such as fly-ash:
sulphuric acid1, silica-sulphuric acid10,11anhydrous zinc chloride12, ground
chemistry catalysts-grinding the reactants with sodium hydroxide13, aqueous
alkali in lower temperature14, solid sulphonic acid from bamboo15, barium
hydroxide16 anhydrous sodium bicarbonate17, microwave assisted synthesis18,
Fly-ash:water2,19, triphenylphosphite20, alkali earth metals21, KF/Al2O322 and
sulfated titania23 and silicotungstic acid24 have been reported for the synthesis of
many number of organic compounds. Chalcones possess various multipronged
activities such as antimicrobial25, antidepressants26, antiplasmodial27, anti-aids28
and insect antifeedant activities3, 29. In the present investigation, the authors
wish to report a new green catalyst preheated fly-ash for efficient synthesizing
chalcones by Crossed-Aldol condensation reaction. The yields of chalcones are
more than 60%. The synthesized chalcones are characterized by their physical
constants, Mass, IR and NMR spectral data as they are unknown compounds
so far. The purities of the known synthesized chalcones have been checked by
their physical constants and their spectral data earlier published in literature.
The antimicrobial activities of these chalcones have been studied using Bauer-
Kirby method.
Appropriate mixture of aryl methyl ketone (2 mmol) substituted
benzaldehydes (2 mmol) and preheated fly-ash(0.5g) taken in 50ml corning
glass tube and tightly capped. The reaction mixture was subjected to microwave
irradiation for 8-10 minutes at 460W, 2450Hz, in a microwave oven (Scheme
1) (LG Grill, Intellowave, Microwave Oven, 160-800W) and then cooled to
room temperature. Added 10 ml of dichloromethane, the organic layer has
been separated which on evaporation yields the solid product. The solid, on
recrystallization with benzene-hexane mixture gives glittering pale yellow
solid.
Scheme 1: Synthesis of chalcones using preheated fly-ash catalyzed aldol
condensation between aryl methyl ketones and aryl aldehydes.
RESULTS AND DISCUSSION
1, 2, 20, 31
Fly ash is a waste air-pollutant and it has many chemical species
SiO2, Fe2O3, Al2O3, CaO, MgO and insoluble residues. The waste Fly-ash is
converted into preheated fly-ash by heating this in an hot air oven for 2h at
110°C and it is used as useful catalyst as preheated fly-ash. The above said
chemical residues such as SiO2, Fe2O3, Al2O , CaO, MgO species present in the
fly-ash have enhanced the catalytic activity.3During the course of the reactions
these species are responsible for the promoting effects on condensation
between the aryl ketone and aryl aldehydic groups leading to the formation
of unsaturated ketone. The proposed general reaction mechanism is shown in
Figure. 1. For this condensation, generally a base is a preferred catalyst. In the
case of base catalyzed aldol condensation, generally the mechanism involves
the formation of anion of ketone. While in our case preheated fly-ash acts as
a solid catalyst, it assists for condensation between enol form of ketone and
aldehyde. This catalyst also assists the dehydration of the aldol condensed
product then to form chalcones. A similar mechanism has been proposed
for this condensation with other catalyst 24. Further we have investigated this
reaction with 2 mmol(0.25g) of 3-acetylthiophene and benzaldehyde(0.21g)
with in the same condition, the observed yield is 67%. The effect of catalyst
loading was studied with this reaction (32, Scheme 2) by varying the catalyst
quantity from 0.1 to 1 g. As the catalyst quantity is increased from 0.2 to 0.5
g, the percentage of yield of product is increased from 64 to 67%. Further
increase the catalyst amount there is no significant increasing of the percentage
of product. This catalytic effect is shown in Figure 2. The optimum quantity of
EXPERIMENTAL
Materials and Methods
All chemicals used were purchased from Sigma-Aldrich and E-Merck
chemical companies. Fly-ash was collected from the Thermal Power Plant II,
Neyveli Lignite Corporation, Tamilnadu, India. Melting points of all chalcones
were determined in open glass capillaries on Mettler FP51 melting point
apparatus and are uncorrected. Infrared spectra (KBr, 4000-400cm-1) were
recorded on AVATAR-300 Fourier transform spectrophotometer. The NMR
spectra of chalcones have been recorded in INSTRUM AV300 spectrometer,
operating at 500MHz for 1H and 125.46MHz for 13C spectra in DMSO solvent
using TMS as internal standard. Mass spectra were recorded on a SIMADZU
GC-MS2010 Spectrometer using Electron Impact (EI) techniques.
Preparation of preheated fly-ash
`The fly-ash was heated on hot air oven at 110°C for 2h. During the heating
demoisturising takes place. This preheating helps for avoiding colloidal
e-mail:drgtnarayanan@gmail.com
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J. Chil. Chem. Soc., 58, Nº 2 (2013)
catalyst loading was found to be 0.4 g. We have carried out this reaction with
various substituted ketones and benzaldehydes. The results, analytical and mass
spectral data are summarized in Table 1. The Uv, IR and NMR spectroscopic
data of the chalcones (entries 32-40) are presented in Table 2 and 3. There is
no significant effect observed for the effects of substituents on the condensation
reaction. The reusability of this catalyst was studied the reaction of 3-thienyl
ketone and benzaldehyde. The reusability of catalyst on crossed-aldol reaction
of 3-thienyl ketone and benzaldehydes was not observed. Because the second
run of this reaction did not give more than 60% of yield and the observed yield
is 25-27% only. There was appreciable loss in its effect of catalytic activity
was observed in the second run. In this protocol the reaction gave good yields
of the chalcones during the condensation without any environmental discharge.
Scheme 2: Synthesis of substituted styryl 3-thienyl ketones using
preheated fly-ash catalyzed aldol condensation between 3-acetylthiophene and
substituted benzaldehydes.
Figure 2: Effect of catalyst loading.
Figure 1: The proposed mechanism for the preheated fly-ash catalyzed
aldol condensation between aryl methyl ketone and aryl aldehydes.
Table 1. Analytical and mass spectral data of chalcones synthesized by preheated fly-ash catalyzed aryl methyl ketones and substituted benzaldehydes reaction
of the type Ar─CO─CH3 + Ar′─CHO → Ar─CO─CH═CH─Ar′ under microwave irradiation.
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Table 2. Uv-Visible absorption (λmax, nm) and infrared spectral data (ν, cm-1) of substituted styryl 3-thienyl ketones(entries 32-40).
Entry
32
X
H
λmax
310.40
315.20
314.40
315.20
310.60
339.70
322.40
327.80
317.60
CO(s-cis)
1653.00
1658.00
1654.00
1651.00
1655.00
1652.70
1650.77
1654.62
1656.55
CO(s-trans)
1598.00
1599.00
1596.00
1596.00
1599.00
1589.06
1589.06
1571.70
1592.91
CHip
CHop
CH=CHop
1073.00
1071.00
1068.00
1068.00
1073.00
1072.23
1076.08
1081.87
1068.37
C=Cop
564.00
575.00
570.00
571.00
570.00
595.89
574.68
576.61
574.68
1154.00
1179.00
1176.00
1176.00
1173.00
1191.79
1180.22
1195.65
1172.51
762.00
782.00
753.00
759.00
729.00
767.53
798.38
742.46
752.10
33
3-Br
34
4-Br
35
4-Cl
36
4-F
37
2-OCH3
4-CH3
3-NO2
4-NO2
38
39
40
Table 3. The 1H and 13C NMR spectral data (δ, ppm) of substituted styryl 3-thienyl ketones(entries 32-40)
Microbial activities
40 are effective against Klebsiella with 20-24 mm zone of inhibition while the
other ketones showed a moderate activity. The chalcones 32, 36 and 39 were
active when it is screened against P. vulgaris and the other compounds are less
effective. The ketones 32, 34 and 37 showed activities against E-faecalis when
they are screened with 20-24 mm zone of inhibition.
Chalcones possess
a wide range of biological activities such as
29
antibacterial32, antifungal32, antiviral33, antifeedant3,
,
anticancer34,
antimalarial35, antituberclosis28, antiAIDS36 and antioxidant37 activities. These
multipronged activities present in different chalcones are examined against
respective microbes-bacteria’s and fungi.
Antibacterial sensitivity assay
Antifungal sensitivity assay
Antibacterial sensitivity assay was performed using Kirby-Bauer38 disc
diffusion technique. In each Petri plate about 0.5 ml of the test bacterial sample
was spread uniformly over the solidified Mueller Hinton agar using sterile
glass spreader. Then the discs with 5mm diameter made up of Whatmann No.1
filter paper, impregnated with the solution of the compound were placed on the
medium using sterile forceps. The plates were incubated for 24 hours at 37oC
by keeping the plates upside down to prevent the collection of water droplets
over the medium. After 24 hours, the plates were visually examined and the
diameter values of the zone of inhibition were measured. Triplicate results
were recorded by repeating the same procedure.
Antifungal sensitivity assay was performed using Kirby-Bauer38 disc
diffusion technique. PDA medium was prepared and sterilized as above. It was
poured (ear bearing heating condition) in the Petri-plate which was already
filled with 1 mL of the fungal species. The plate was rotated clockwise and
counter clock-wise for uniform spreading of the species. The discs were
impregnated with the test solution. The test solution was prepared by dissolving
15mg of the chalcone in 1mL of DMSO solvent. The medium was allowed to
solidify and kept for 24 hours. Then the plates were visually examined and the
diameter values of zone of inhibition were measured. Triplicate results were
recorded by repeating the same procedure.
The antibacterial activities of all prepared chalcones have been studied
against two gram positive pathogenic strains Staphylococcus aureus,
Enterococcus faecalis and four gram negavtive strains Escherichia coli,
Klebsiella species, Psuedomonas and Proteus vulgaris. The disc diffusion
technique was followed using the Kirby-Bauer38 method, at a concentration
of 250 μg/mL with Ampicillin and Streptomycin used as the standard drugs.
The measured antibacterial activities of all oxiranes are presented in Table 4.
Compound 38 showed maximum zone of inhibition against Escherichia coli,
with greater than 20 mm compared to the chalcones 34, 36, 39, and 40 and
they are moderatively active in 13-19 mm of zone of inhibition. Ketone 38 was
active with in 8-12 mm of zone of inhibition. The ketones 33, 37 and 40 were
found to be effective against S. aureus within 20-24 mm of zone of inhibition.
Compounds 34, 36, 38 and 39 are moderately active within 13-19 mm of zone
of inhibition. The chalcone 35 was active within 8-12 mm of zone of inhibition.
The chalcone derivatives 34 and 36 were more active against Pseudomonas
a showing greater than 20 mm zone of inhibition and the other derivatives
showed the zone of inhibitions between 12-19 mm. The ketones 33, 34, 37 and
The study of antifungal activities of all chalcones has been done with
Candida albicans as the fungal strain using the disc diffusion technique and
the other two strains Penicillium species and Aspergillus niger, the dilution
method was adopted. The drug dilution was kept as 50 μg/mL. Griseofulvin
has been taken as the standard drug. The observed antifungal activities of
all chalcones are presented in Table 5. The study of antifungal activities of
all chalcones against C. albicans, showed that the three compounds 34, 37
and 39 are effective with 20 mm as the zone of inhibition in 250 μg/ disc
while chalcones 35, 36, 38 and 40 are active with 13-19 mm zone of
inhibition and the compound 32 was the least active with 8-12 mm zone of
inhibitions. Compounds 35 and 39 are visible against Penicillum species, in
the development of the fungal colony and 2-3 colonies are recorded for the
compounds 33, 36 and 40. The inhibition of ketones against A.niger was less
in two compounds 34, and 37 being highly active followed by 32, 33, 35, 39
and 40. Presence of a methoxy, methyl, dimethyl and bromo substituents are
responsible for antimicrobial activities of chalcones.
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Table 4. Antibacterial activities of substituted styryl 3-thienyl ketones(entries 32-40).
Disc size: 6.35 mm; Duration: 24-45 h; Standard: Ampicillin (30-33 mm) and Streptomycin(20-25 mm); Control: Methanol; ---: No activities; ±:
Active(8-12 mm); +: Moderately active(13-19 mm); ++: Active(20-24 mm).
Table 5. Antifungal activities of substituted styryl 3-thienyl ketones(entries 32-40).
Standard: Griseofulvin and Gentamycin; Duration : 72 h; Control: Methanol; Medium: Potato dextrose agar; ++: No fungal colony; +: One fungal colony;
±: Two-three fungal colonies;---: Heavy fungal colony.
CONCLUSION
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We have developed an efficient catalytic method for synthesis of
chalcones by Crossed-Aldol reaction using a solvent free environmentally
greener catalyst preheated fly-ash under microwave irradiation between aryl
ketones and aldehydes. This reaction protocol offers a simple, economical,
environmentally friendly, non-hazards, easier work-up procedure and good
yields. The antimicrobial activities of chalcones have been studied using
Bauer-Kirby method.
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