Synthesis and characterization of some novel 3-bromo-2-acetylthiophene chalcones and biological evaluation of their ethyl-4-(3-bromothien-2-yl)-2-oxo- 6-(aryl)cyclohex-3-ene-1-carboxylate derivatives

Article abstract of DOI:10.1080/10426500802414189

Novel chalcones 1-(3-bromothien-2-yl)-3-(aryl)prop-2-en-1-ones derived from 3-bromo-2-acetylthiophene and their cyclization product with ethylacetoacetate such as 4-(3-bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-3-ene-1-carboxylate derivatives were synthesize

Full text of DOI:10.1080/10426500802414189

This article was downloaded by: [Laurentian University]
On: 03 June 2013, At: 09:30
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Phosphorus, Sulfur, and Silicon
and the Related Elements
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Synthesis and Characterization
of Some Novel 3-Bromo-2-
acetylthiophene Chalcones and
Biological Evaluation of Their
Ethyl-4-(3-bromothien-2-yl)-2-
oxo-6-(aryl)cyclohex-3-ene-1-
carboxylate Derivatives
B. V. Ashalatha a , B. Narayana a & K. K. Vijaya Raj a
a Department of Post-Graduate Studies and Research
in Chemistry, Mangalore University, Mangalagangotri,
India
Published online: 22 Jun 2009.
To cite this article: B. V. Ashalatha , B. Narayana & K. K. Vijaya Raj (2009): Synthesis
and Characterization of Some Novel 3-Bromo-2-acetylthiophene Chalcones and
Biological Evaluation of Their Ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-3-
ene-1-carboxylate Derivatives, Phosphorus, Sulfur, and Silicon and the Related
Elements, 184:7, 1904-1919
To link to this article: http://dx.doi.org/10.1080/10426500802414189
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,

sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden.
The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be
independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages
whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

Phosphorus, Sulfur, and Silicon, 184:1904–1919, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802414189
Synthesis and Characterization of Some Novel
3-Bromo-2-acetylthiophene Chalcones and Biological
Evaluation of Their Ethyl-4-(3-bromothien-2-yl)-2-oxo-6-
(aryl)cyclohex-3-ene-1-carboxylate Derivatives
B. V. Ashalatha, B. Narayana, and K. K. Vijaya Raj
Department of Post-Graduate Studies and Research in Chemistry,
Mangalore University, Mangalagangotri, India
Novel chalcones 1-(3-bromothien-2-yl)-3-(aryl)prop-2-en-1-ones derived from 3-
bromo-2-acetylthiophene and their cyclization product with ethylacetoacetate
such as 4-(3-bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-3-ene-1-carboxylate deriva-
tives were synthesized and studied by X-ray, analytical, and spectral methods. Com-
pounds were screened for their anti-inflammatory, analgesic, and antimicrobial
activities. The compound ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(4-propoxyphenyl)
cyclohex-3-ene-1-carboxylate5c exhibited promising anti-inflammatory, analgesic
and antibacterial activities.
Keywords Biological evaluation; 3-bromo-2-acetylthiophene chalcones; characteriza-
tion; cyclohex-3-ene-1-carboxylate; synthesis
Chalcone and the corresponding heterocyclic analogs are valuable in-
termediates in organic synthesis1and exhibit a wide range of biological
activities.2,3 An important feature of chalcones is their ability to act
as activated unsaturated systems in conjugated additions of carban-
ions in the presence of suitable basic catalysts.4,5 For example, the
Michael addition of ethylacetoacetate to chalcone yields 4,6-diaryl-2-
oxo-cyclohex-3-ene-1-carboxylate derivatives, which are efficient syn-
thons for building spiranic compounds.6 Cyclohexenone derivatives are
well known lead molecules for the treatment of inflammation and
autoimmune diseases.7–9 In the present work, synthesis and char-
acterization of some novel 3-bromo-2-acetylthiophene chalcones and
Received 17 November 2007; accepted 4 August 2008.
The authors are thankful to The Head, SAIF, CDRI, Lucknow, India, for FABMass
and NMR analysis and to Prof. N. Suchetha Kumari, Department of Biochemistry, K. S.
Hegde Medical Academy, Deralakatte, 574 162, India, for biological studies.
Address correspondence to B. Narayana, Department of Post-Graduate Studies and
Research in Chemistry, Mangalore University, Mangalagangotri, 574 199, India. E-mail:
nbadiadka@yahoo.co.uk
1904

Ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-3-ene-1-carboxylates
1905
biological evaluation of their Michael addition products such as ethyl-4-
(3-bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-3-ene-1-carboxylate deriva-
tives are discussed.
RESULTS AND DISCUSSION
Chemistry
The reaction of chalcones with ethylacetoacetate is known to lead to
three structurally diverse types of compounds, depending on the ex-
perimental conditions employed. The catalyst plays a major role in
directing the reaction to different end products.10–12 A strong Lewis
acid such as BF3.etherate generates pyrylium cations from the reac-
tion of chalcones and acetoacetic esters, but a basic catalyst would
turn the intermediate Michael addition product into cyclohexenones
through the intramolecular cyclocondensation of the methyl group orig-
inating from acetoacetic acid ester and the ketone function of the ini-
tial chalcone. Thus in the presence of a base, bromothienyl-containing
chalcones 3a–o and ethyl acetoacetate 4 produce cyclohexenones
5a–h by means of an intermediate Michael adduct, as given Scheme
1. 3-Bromo-2-acetylthiophene was synthesized from 3-bromothiophene
O
O
Br
Br
O
H
Base
Ar
CH3
Ar
MeOH
+
S
S
( 1)
( 2a-o)
( 3a-o)
H3C
Base
COOC2H5
O
( 4)
O
O
COOC2H5
H3C
*
*
COOC2H5
Br
O
Br
Ar
Ar
S
S
( 5a-h)
SCHEME 1 The reaction pathway.

1906
B. V. Ashalatha et al.
by the acetylation of 3-bromothiophene with acetyl chloride in the
presence of SnCl4 in benzene as per the reported procedure.13 (3-
Bromothien-2-yl)-3-(aryl)prop-2-en-1-ones were prepared by the re-
action of 2-acetyl-3-bromothiophene with aromatic aldehydes in the
presence of sodium hydroxide and methanol as solvent. The newly
synthesized chalcones were characterized by elemental and X-ray anal-
ysis. The resulting (3-bromothien-2-yl)-3-(aryl)prop-2-en-1-ones upon
treatment with ethyl acetoacetate in the presence of sodium hydrox-
ide in ethanol proceeded the reaction through Michael addition prod-
uct intermediate yielded 4-(3-bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-
3-ene-1-carboxylate by intramolecular cyclocondensation of the methyl
group originating from acetoacetic acid ester and the ketone func-
tion of initial chalcone. The target ethyl-4-(3-bromothien-2-yl)-2-oxo-
6-(aryl)cyclohex-3-ene-1-carboxylates were characterized by elemen-
tal, single crystal X-ray, and spectral data. The characterization data
of each compound are presented in Tables I and II. The spectral
data are given in the Experimental section. The structures of chal-
cones and ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-3-ene-1-
carboxylates were confirmed by single crystal X-ray study.14–19
The structure of ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(1,3-benzo-
dioxol-5-yl)cyclohex-3-ene-1-carboxylate 5b was confirmed by 1H-NMR,
13C-NMR, and FAB mass spectral analysis. The 1H-NMR spectrum
displayed a triplet that appeared at δ 1.10 integrated for three pro-
tons of CH3 and a quartet at 4.08 integrated for two protons of the
CH2 of the ethyl ester side chain. A multiplet appeared at δ 2.95–
3.14, which are due to two single CH protons and another multiplet
at δ 3.66–3.73 are for CH2 protons of the of the cyclohexenone ring.
A singlet seen at δ 5.95 is due to methylene dioxide protons, and an-
other singlet seen at δ 6.76 is due to H-3 of cyclohexenone ring. The
benzene ring protons appeared as a singlet at δ 6.80 and a doublet
at δ 6.82 (J = 2.4Hz). The thiophene protons appeared as two dou-
blets at δ 7.07 (J = 5.4Hz) and 7.38 (J = 5.4Hz). The 13C-NMR spec-
trum displayed peaks at δ 14.01 (CH3), 38.06 (CH2), 43.76 (CH), 38.10
(CH2), 59.78 (CH), 61.04 (CH2), 101.13 (-OCH2O-), 107.55 (CH), 108.55
(CH), 125.63 (=CH), 127.81 (CH), 133.44 (CH), 134.41, 135.33, 135.41,
146.88, 147.87, 150.68, 168.99 (C=O ester), and 193.40 (C=O ring) ac-
counts for 20 carbon atoms in the molecule. The FAB mass spectrum
gave molecular ion peak at m/z 449 (100%) and an isotopic peak at 451
(90%). The other prominent peaks are m/z 403 (48%, M- CH3CH2OH),
405 (46%, (M-(CH3CH2OH+2), 375 (55%, M-OCHOEt), and 377 (58%,
(M-OCHOEt)+2) respectively. The fragmentation pattern of 5b is given
in Scheme 2.

1907

1908

1909

1910

1911

1912
B. V. Ashalatha et al.
O
O
O
CH3
S
H
Br
O
m/z 449/ 451
O
-
C2H5OCHO
-CH3CH2OH
O
+
.
O
O
+
.
S
S
Br
O
Br
O
O
O
m/z 375/ 377
m/z 403/ 405
SCHEME 2 Mass fragmentation pattern of 5b.
Biological Activity
Anti-Inflammatory Activity (Carrageenan Induced Acute Paw
Edema Test)
Six of the newly synthesized compounds 5b, 5c, 5d, 5e, 5f,
and 5h were evaluated for their anti-inflammatory activity against
carrageenan-induced acute paw edema in rats weighing 150–200g.20
Albino rats of Wistar strain (150–200 g) and Swiss albino mice (25–
30 g) were used for the experiment. They were housed in standard
polypropylene cages and kept under room temperature (24 2◦C), rel-
ative humidity (60–70%) in a 12 h light–dark cycle. The animals were
given a standard laboratory diet and water ad libitum. Food was with-
drawn 12 h before and during experimental hours. Institutional ethics
committee approved all the experiments.
The results are shown in Table III. The rats were divided in to eight
groups of one each, as group 1 received 10 mL/kg of 2% gum acacia,
group 2 received Indomethacin at a dose of 2 mg/kg. The 3rd, 4th, 5th,
6th, 7th, and 8th group were administered the test compounds 5b,
5c, 5d, 5e, 5f, and 5h, respectively, at a dose of 50 mg/kg suspended in

Ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-3-ene-1-carboxylates
1913
TABLE III Anti-Inflammatory Activity of Ethyl-4-(3-
bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-3-ene-1-carboxylates
5a-h by Carrageenan-Induced Acute Paw Edema Method
Drug/compound
no.
Dose
(mg/kg, p.o)
Increase in paw edema % Inhibition of
volume in mL
paw edema
2% Gum acacia
(Control)
Indomethacin
10 mL/kg
2
0.63
–
0.27
57.14
(Standard drug)
5b
5c
5d
5e
5f
50
50
50
50
50
50
1.8
–185.71
85.71
–142.86
42.85
28.57
42.85
0.09
1.53
0.36
0.45
0.36
5h
10ml/kg of 2% gum acacia orally by gavage feeding. Acute inflammation
was produced by subplantar injection of 0.1 mL of 1% suspension of
carrageenan with gum acacia in normal saline in the left hind paw of the
rats, 1 h after oral administration of the drugs.20 The paw volume was
measured plethysmometrically (Ugo Basile, Italy) at 0 h and 3 h after
carrageenan injection. The difference between the two readings was
taken as the volume of edema, and the percentage anti-inflammatory
activity was calculated using the formula, % Of edema inhibition = 100
– (Vtest/Vcontrol)× 100
Where, Vcontrol = Volume of paw edema in control group
Vtest = Volume of paw edema in drug treated group
The results were expressed as % inhibition of edema over the
untreated control group. Table III shows anti-inflammatory activity
of ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-3-ene-1-carboxy-
lates 5a–h. The percentage of inhibition was compared with that of
standard drug Indomethacin (2.0 mg/kg). The most active compound
was ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(4-propoxyphenyl)cyclohex-3-
ene-1-carboxylate 5c. A dose of 50 mg/kg p.o decreased the carrageenan-
induced edema by 85.71%, while the Indomethacin in a dose 2 mg/kg
p.o used as standard drug decreased carrageenan induced edema by
57.14%. The compounds ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(2,5-di-
methoxyphenyl)cyclohex-3-ene-1-carboxylate 5e and ethyl-4-(3-bromo-
thien-2-yl)-2-oxo-6-(4-(N,N-dimethylamino)phenyl)cyclohex-3-ene-1-
carboxylate 5h decreased the carrageenan induced edema by 42.85%.

1914
B. V. Ashalatha et al.
Compounds ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(1,3-benzodioxol-5-yl)
cyclohex-3-ene-1-carboxylate 5b and ethyl-4-(3-bromothien-2-yl)-2-
oxo-6-(4-butoxyphenyl)cyclohex-3-ene-1-carboxylate 5d aggravated
the inflammation. The compound 5c can be considered as the most
active amongst the tested compounds.
Analgesic Activity (Hot Plate Test)
Six of the newly synthesized compounds 5b, 5c, 5d, 5e, 5f, and
5h were evaluated for their analgesic activity by the hot plate test.
Male albino mice weighing 18–26 g were used for the experiment. They
were housed in clean polypropylene cages and kept under room tem-
perature (24
2◦C), relative humidity 60–70% in a 12 h light-dark
cycle. The animals were fed a standard laboratory diet and water ad
libitum. Each experimental group consisted of six animals/dose, and all
the animals were used only once. The experiment was conducted after
obtaining approval from the institutional animal ethics committee.
The hot plate test was conducted according to the procedure de-
scribed by Eddy and Leinbatch.21 In this test, reaction of mice to painful
stimulus was measured. Mice were placed on the metal plate heated to
55 0.4◦C and covered with a glass cylinder (25 cm high, 15 cm diam-
eter). The time(s) elapsing the first pain response (licking or jumping)
was determined by a stop watch, and then recorded as response latency,
prior to, and 60 and 180 min following the p.o administration of the in-
vestigated compounds. The results are given in Table IV.
Pethidine was used as standard drug in the present study. Com-
pounds
ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(4-propoxyphenyl)cyclo-
hex-3-ene-1-carboxylate 5c has shown highest activity at a dose of
TABLE IV Analgesic Activity of Eethyl-4-(3-bromothien-2-yl)-2-oxo-
6-(aryl)cyclohex-3-ene-1-carboxylates 5a-h in the Hot Plate Test
Time of reaction to pain stimulus
at time (h) [s] SEM
Drug/compound
no.
Dose
(mg/kg)
0
1
3
Control
Pethidine (Standard drug)
10 mL/kg
8.25
8.5
8.51
7.9
8.6
9.4
8.2
16.4
11.1
14.2
8.9
9.2
10.4
9.1
8.8
14.3
10.2
13.9
9.1
9.9
11.1
9.2
5
50
50
50
50
50
50
5b
5c
5d
5e
5f
8.24
8.3
5h

1915

1916
B. V. Ashalatha et al.
50 mg/kg, which is comparable to that of the standard drug Pethidine,
while compound ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(1,3-benzodioxol-
5-yl)cyclohex-3-ene-1-carboxylate 5b has shown moderate activity. The
rest of the compounds did not show analgesic activity in the model
used. This inference is based on a pilot study in a small number of
animals only. Further studies using larger samples have to be done
to obtain conclusive data. The compound 5c exhibited promising
anti-inflammatory and analgesic activity, which can be recommended
for further studies.
Antibacterial and Antifungal Activities
All the newly synthesized ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(aryl)
cyclohex-3-ene-1-carboxylates 5a–h were screened for their antibacte-
rial activity against Escherichia coli, Staphyllococcus aureus (Smith),
Psuedomonus aeruginosa (Gessard), and Klebsiella pneumoniae (Fried-
lander) bacterial strains by the disc diffusion method.22–24 The com-
pounds were also screened for their antifungal activity against As-
pergilus flavus (NCIM No.524), Aspergilus fumigatus (NCIM No.902),
Penicillium marneffei (recultured), and Trichophyton mentagrophytes
(recultured) in DMSO by the serial plate dilution method.22–24 The
results are given in Table V. Nitrofurazone was used as the standard
antibacterial drug and Itraconozole was used as the standard antifun-
gal drug.
It can be seen from the studies that the compounds ethyl-4-(3-
bromothien-2-yl)-2-oxo-6-(1,3-benzodioxol-5-yl)cyclohex-3-ene-1-carbo-
xylate
5b,
ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(4-propoxyphenyl)
cyclohex-3-ene-1-carboxylate 5c, ethyl-4-(3-bromothien-2-yl)-2-oxo-
6-(phenyl) cyclohex-3-ene-1-carboxylate 5f, and ethyl-4-(3-bromothien-
2-yl)-2-oxo-6-(4-(N,N-dimethylamino)phenyl)cyclohex-3-ene-1-carbox-
ylate 5h exhibited comparable activity with the standard drug Nitro-
furazone. None of the compounds exhibited considerable antifungal
activity.
CONCLUSION
A few novel chalcones such as 1-(3-bromothien-2-yl)-3-(aryl)prop-2-en-
1-ones derived from 3-bromo-2-acetylthiophene and their cyclized
products with ethyl acetoacetate, such as 4-(3-bromothien-2-yl)-2-
oxo-6-(aryl)cyclohex-3-ene-1-carboxylate derivatives, were synthesized
and evaluated for anti-inflammatory, analgesic, and antimicro-
bial activities. The compound ethyl 4-(3-bromothien-2-yl)-2-oxo-6-(4-

Ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-3-ene-1-carboxylates
1917
propoxyphenyl)cyclohex-3-ene-1-carboxylate 5c emerged as a promis-
ing anti-inflammatory, analgesic, and antibacterial agent.
EXPERIMENTAL
Melting points were taken in open capillary tubes and are uncorrected.
The purity of the compounds was confirmed by thin layer chromatogra-
phy using Merck silica gel 60 F254 coated aluminium plates. IR spectra
were recorded on Shimadzu-FTIR Infrared spectrometer in KBr (νmax
in cm−1). 1H NMR spectra were recorded in CDCl3 and in DMSO-d 6 on
a Varian (300 MHz) spectrometer using TMS as internal standard, and
13C NMR spectra were recorded in CDCl3 and in DMSO-d on a Var-
6
ian (75 MHz) spectrometer. FABMS spectra were recorded on a JEOL
SX 102/DA-6000 mass spectrometer using argon/xenon (6kv, 10 mA)
as the FAB gas. The starting material 3-bromo-2-acetylthiophene was
synthesized by the acetylation of 3-bromothiophene with acetylchloride
in presence of SnCl4 in benzene as per the reported procedure.13
1H-NMR (300 MHz): δ 2.69 (s, 3H, COCH3), 7.10 (d (J = 5.1 Hz) 1H,
ArH), 7.52 (d (J = 5.1 Hz) 1H, ArH).
General Procedure for the Synthesis of
(3-Bromothien-2-yl)-3-(aryl)prop-2-en-1-ones 3a–o
2-Acetyl-3-bromothiophene (0.01 mol) and aryl aldehydes (0.01 mol)
were taken in methanol (25 mL), and 5 mL of 10% sodium hydroxide
solution was slowly added to it under stirring at 15–20◦C. Stirring
continued for 2 h at the same temperature. Progress of the reaction
was monitored by TLC. The solid that separated was filtered out and
washed with cold methanol. Recystallization from methanol yielded the
pure compounds in 62–89% yields.
General Procedure for the Synthesis of Ethyl-4-(3-bromo-
thien-2-yl)-2-oxo-6-(aryl)cyclohex-3-ene-1-carboxylates 5a–h
The chalcones (3-bromothien-2-yl)-3-(aryl)prop-2-en-1-ones (0.03 mol)
and ethyl acetoacetate (0.03 mol) were refluxed in 15 mL ethanol for
2 h in the presence of 0.5 mL 10% sodium hydroxide. The reaction
mixture was kept overnight. The solid that separated was filtered out
and recrystallized from ethanol to yield the required material as an
isomeric mixture in 58–78% yield.

1918
B. V. Ashalatha et al.
Spectral Data
Ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(1,3-benzodioxol-5-
yl)cyclohex-3-ene-1-carboxylate
IR (KBr, cm−1): 1650 (νc=o Ketone), 1742 (νc=o Ester); 1H-NMR (300 MHz):
δ 1.10 (t, 3H, CH3), 2.95–3.14 (m, 2H, -CH-CH-Ar), 3.66–3.73 (m, 2H,
CH2CHAr), 4.08 (q, 2H, -OCH2), 5.95 (s, 2H, -OCH2O), 6.76 (s, 1H,
=CH), 6.80 (s, 1H, ArH), 6.82 (d (J = 2.4 Hz) 1H, ArH), 7.07 (d (J =
5.4Hz) 2H, ArH), 7.38 (d (J = 5.4Hz) 1H, ArH); 13C-NMR (75 MHz):
δ 14.01(CH3), 38.06 (CH2), 43.76 (CH), 38.10 (CH2), 59.78 (CH), 61.04
(CH2), 101.13 (-OCH2O-), 107.55 (CH), 108.55 (CH), 125.63 (=CH),
127.81 (CH), 133.44 (CH), 134.41, 135.33, 135.41, 146.88, 147.87,
150.68, 168.99 (C=O), 193.40 (C=O); FABMS: 443 (100%, M+), 451
(90%, M+2), 403 (48%, M- CH3CH2OH), 405 (46%, (M-(CH3CH2OH+2),
375 (55%, M-OCHOEt), 377 (58%, (M-OCHOEt)+2).
Ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(4-
propoxyphenyl)cyclohex-3-ene-1-carboxylate
IR (KBr, cm−1): 1643 (νc=o Ketone), 1727 (νc=o Ester); 1H-NMR (300 MHz):
δ 1.03 (t, 3H, CH3), 1.06 (t, 3H, CH3), 1.80 (sextet, 2H, CH2), 3.05–
3.09(m, 2H, -CH-CH-Ar), 3.72–3.75 (m, 2H, CH2CHAr), 3.90 (t, 2H,
-OCH2), 4.05 (q, 2H, -OCH2), 6.837( s, 1H, =CH), 6.87 (d (J = 9.0 Hz)
2H, ArH), 7.07 ( d(J = 5.4 Hz) 1H, ArH), 7.22 ( d (J = 9.0 Hz) 2H,
ArH),7.38 (d (J = 5.4Hz) 1H, ArH); 13C-NMR (75 MHz): δ 10.46 (CH3),
13.95 (CH3), 22.52 (CH2), 38.10 (CH2), 43.29 (CH), 59.84 (CH), 60.93
(OCH2), 69.47 (OCH2), 111.08, 114.69 (CH), 125.63 (=CH), 127.71(CH),
128.29 (CH), 132.37, 133.39 (CH), 135.41, 150.76, 158.43, 169.09 (C=O),
193.61(C=O); FABMS: 463 (100%, M+), 465 (100%, M+2), 389 (48%,
M-OCHOEt), 417 (30%, M-CH3 CH2OH).
Ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(2,5-
dimethoxyphenyl)cyclohex-3-ene-1-carboxylate
IR (KBr, cm−1): 1660 (νc=o Ketone), 1726 (νc=o Ester); 1H-NMR (300 MHz):
δ 1.08 (t, 3H, CH3), 3.04–3.26 (m, 2H, -CH-CH-Ar), 3.75 (s, 3H, -OCH3)
3.82 (s, 3H, -OCH3), 3.96-4.03 (m, 2H, CH2CHAr), 4.06 (q, 2H, -OCH2),
5.95 (s, 2H, -OCH2O), 6.78 (s, 1H, =CH), 6.83 (d (J = 3.6 Hz), 1H, ArH),
6.84 (d (J = 3.6 Hz), 2H, ArH), 7.06 (d (J = 5.1 Hz) 2H, ArH), 7.38 (d (J =
5.4 Hz) 1H, ArH); 13C-NMR (75 MHz): δ 13.92 (CH3), 35.50 (CH2), 40.12
(CH), 55.68 (OCH3), 55.91 (OCH3), 57.33 (CH), 60.75 (CH2), 110.87,
112.19, 112.65, 115.11, 125.38 (=CH), 127.57 (CH), 129.26, 133.32,
135.56, 151.32, 151.65, 153.47, 169.23 (C=O), 194.17 (C=O); FABMS:
m/z 485 (98%, M+), 466 (100%, M+1), 467 (98%, M+2), 419 (40%, M-
CH3CH2OH), 421 (38%, (M-(CH3CH2OH+2).

Ethyl-4-(3-bromothien-2-yl)-2-oxo-6-(aryl)cyclohex-3-ene-1-carboxylates
1919
REFERENCES
[1] D. N. Dhar, The Chemistry of Chalcones and Related Compounds (Wiley-
Interscience, New York, 1981).
[2] J. R. Dimmock, D. W. Elias, M. A. Beazely, and N. M. Kandepu, Curr. Med. Chem.,
6, 1125 (1999).
[3] V. Opletalova and D. Sedivy, Ceska Slov. Farm., 48, 252 (1999).
[4] H. O. House, Modern Synthetic Reactions, 2nd ed. (W. A. Benjamin, Menlo Park,
CA, 1972), p. 595.
[5] M. E. Jung, In Comprehensive Organic Synthesis, B. M. Trost and I. Fleming, Eds.
(Pergamon Press, Oxford, UK, 1991), Vol. 4, p. 1.
[6] V. Padmavathi, K. Sharmila, A. S. Reddy, and D. B. Reddy, Indian J. Chem., 40B,
11 (2001).
[7] (a) M. Tanaka, F. Nara, K. Suzuki, T. Hosoya, and T. Ogita, J. Am. Chem. Soc.,
119, 7871 (1997); (b) F. Nara, M. Tanaka, T. Hosoya, K. Suzuki-Konagai, and T.
Ogita, J. Antibiot., 52, 525 (1999); (c) F. Nara, M. Tanaka, S. Masuda-Inoue, Y.
Yamamoto, H. Doi-Yoshioka, K. Suzuki-Konagai, S. Umakura, and T. Ogita, J. An-
tibiot., 52, 531 (1999); (d) T. R. Hoye and M. A. Tennakoon, Org. Lett., 2, 1481
(2000).
[8] R. Kolesnick and D. W. Golde, Cell, 77, 325 (1994).
[9] F. Hiromichi, K. Naoyuki, S. Yoshinari, N. Yasushi, and K. Yasuyuki, Tetrahedron
Lett. 43, 4825 (2002).
[10] W. Davey and J. R. Gwilt, J. Chem. Soc., 1015 (1957).
[11] J. A. VanAllan and G. A. Reynolds, J. Org. Chem., 33, 1102 (1968)
[12] A. Sammour, M. T. Elzimaity, and A. Abdel-Maksoud, J. Chem. U. A. R., 12, 481
(1969).
[13] Ya. L. Go’ldfarb and Yu. B. Va’kenshtien, Doklady Akademii. Nauk SSSR, 128, 536
(1959).
[14] W. T. Harrison, H. S. Yathirajan, B. V. Ashalatha, S. Bindya, and B. Narayana, Acta
Cryst., E62, o4164 (2006).
[15] H. S. Yathirajan, B. Ashalatha, B. Narayana S. Bindya, and M. Bolte, Acta Cryst.,
E62, o4551 (2006).
[16] H. S. Yathirajan, B. K. Sarojini, B. Narayana, B. V. Ashalatha, and M. Bolte, Acta
Cryst., E62, o3964 (2006).
[17] H. S. Yathirajan, B. K. Sarojini, B. Narayana, S. Bindya, and M. Bolte, Acta Cryst.,
E62, o4048 (2006).
[18] H. S. Yathirajan, B. Narayana, B. V. Ashalatha, B. K. Sarojini, and M. Bolte, Acta
Cryst., E62, o5010 (2006).
[19] A. Fischer, H. S. Yathirajan, B. V. Ashalatha, B. Narayana, and B.K. Sarojini, Acta
Cryst., E63, o254 (2007).
[20] C. A. Winter, E. A. Risley, and G. W. Nuss, Proc. Soc. Exp. Biol. Med., 111, 544
(1962).
[21] N. B. Eddy and D. Leinbatch, J. Pharmacol. Exp. Ther., 107, 385 (1953).
[22] R. Cruickshank, J. P. Duguid, B. P. Marmion, and R. H. A. Swain, Medicinal Micro-
biology, 12th Ed. (Churchil Livingstone, London, 1975), Vol. II, p. 196.
[23] A. H. Collins, Microbiological Methods, 2nd ed.(Butterworth, London, 1976).
[24] B. A. Arthington, M. Motley, D. W. Warnock, and C. J. Morrison., J. Clin. Microbiol-
ogy, 38, 2254 (2000).