Synthesis, spectral studies and anti-inflammatory activity of 2-acetyl thiophene

Article abstract of DOI:10.1155/2010/404715

Some new chalcones have been synthesized by the condensation of 2-acetyl thiophene with various aromatic aldehydes in 40% alkali. The synthesized compounds were identified by spectral data and screened for antiinflammatory activity. Some of these compounds showed moderate to considerable anti-inflammatory activity.

Full text of DOI:10.1155/2010/404715

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2010, 7(2), 433-436
http://www.e-journals.net
Synthesis, Spectral Studies and Anti-Inflammatory
Activity of 2-Acetyl Thiophene
B. RAMESH* and B. SOMESWARA RAO
Department of Pharmaceutical Chemistry, Sree Siddaganga College of Pharmacy,
B.H.Road, Tumkur-572102. Karnataka, India.
rameshbbatta@gmail.com
Received 19 August 2009; Accepted 10 October 2009
Abstract: Some new chalcones have been synthesized by the condensation of
2-acetyl thiophene with various aromatic aldehydes in 40% alkali. The
synthesized compounds were identified by spectral data and screened for anti-
inflammatory activity. Some of these compounds showed moderate to
considerable anti-inflammatory activity.
Keywords: Chalcone, Synthesis, Anti-inflammatory activity.
Introduction
Chalcones display interesting biological activities, including antimalarial1, anti-
inflammatory2, cytotoxic3,4, anticancer5,6 and antimicrobial activities7,8. In the present study,
some new chalcones (1-8) have been synthesized by the reaction of 2-acetyl thiophene with
different aromatic aldehydes. The structures of the various synthesized compounds are
assigned on the basis of elemental analyses, IR and 1H NMR spectral data. These
compounds were also screened for their anti-inflammatory activity.
Experimental
Melting points were determined on a capillary melting point apparatus and are uncorrected.
1H NMR spectra was recorded in the indicated solvent on Bruker WM 400 MHz
spectrometer with TMS as internal standard. Infrared spectra were recorded in KBr on
Perkin-Elmer AC-1 spectrophotometer. Microanalyses were performed on Carlo Erba EA-
1108 element analyzer and were within the 0.5% of the theoretical values. Column
chromatography was performed on silica gel (Merck, 60-120 mesh).
General procedure for the preparation of chalcones (1-8)
A mixture of 2-acetyl thiophene (0.01 mol) and appropriate aldehyde (0.01 mol) was stirred
in ethanol (30 mL) and then an aqueous solution of KOH (40%, 15 mL) was added to it.

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B. RAMESH et al.
The mixture was kept overnight at room temperature and then it was poured in to crushed
ice and acidified with HC1. The solid separated was filtered and crystallized from ethanol
(Scheme 1). The characterizations data of these compounds are described in Tables 1 & 2.
(1-8)
Scheme 1. Synthesis of some new chalcones of 2-acetyl thiophene (1-8).
Table 1. Physical data of compounds (1-8).
Elemental analyses, %
C
H
N
M.P, Yield,
%
M.F.
°C
1
2
3
4
5
6
7
8
C16H16O4S
C13H9SCl
C14H12O2S
C15H15OSN
C13H8OSCl2
C21H16OS
C14H12OS
C13H10OS
135
110
70
95
96
86
83
92
80
89
87
43.00 43.20 43.10 43.20 10.50 10.80
52.24 52.00 35.94 36.00 9.36
48.55 48.20 41.57 41.30 7.12
45.44 45.45 45.68 45.45 3.42
51.62 52.00 32.06 32.00 3.92
54.90 53.84 41.11 41.02 2.59
50.06 50.00 42.76 42.85 3.61
52.09 52.00 40.11 40.00 4.06
9.00
6.83
3.03
4.00
2.56
3.51
4.00
100
95
140
105
90
Anti-inflammatory activity
Synthesized compounds (1−8) were tested for their anti-inflammatory activity. Male albino
rats weighing between 200-250 g were used for the experiment. Carragenan induced paw
oedema method described by Singh and Ghosh9 was followed for the acute anti-
inflammatory model and the results are presented in Table 3.

Synthesis, Spectral Studies and Anti-Inflammatory Activity
435
Table 2. Spectral data of the compounds (1-8).
Compound.
1
1H NMR (CDCl3, ppm)
IR (KBr, cm−1)
3330 (−OH).
720(−C=O),
7.69(1H, d, J= 16Hz, −CO−CH=),
7.89 (1H, d, J= 16Hz, =CH−Ar),
3.90-3.95 (9H, s, 3X−OCH3),
1650 (−CH=CH),
1175 (−OCH3),
650(C−S).
7.20 (1H, m, C−41−H), 7.28 (2H, d, C−21−H,
C−51−H), 7.78 (2H, s, C−2−H, C−6−H).
7.70 (1H, d, J=16Hz, −CO−CH=),
7.88 (1H, d, J=16Hz, =CH−Ar),
7.80 (1H, d, J=9Hz, C−51−H),
7.58 (2H, d, C−3−H, C−5−H),
7.40 (2H, d, C−2−H, −C−6−H),
7.38 (1H, d, J=16Hz, C−3−H),
7.20 (1H, m, C-41-H).
2
1725 (−C=O),
1640(−CH=CH),
850 (C−CL),
650 (C−S)
3
1720 (−C=O),
1648 (−CH=CH),
1170 (−OCH3),
666 (C−S)
6.94 (1H, d, J = 16Hz, − CO −CH=),
7.61 (1H, d, J = 16Hz = CH − Ar),
7.86 (2H, d, C−31−H, −C−51−H),
7.68 (2H, d, C−3−H, −C−5−H),
7.18 (1H, m, C−41−H),
6.92 (2H, d, −C−2−H, −C−6−H).
4
5
1730 (−C=0),
1638 (−CH=CH),
1180(N(CH3)2),
676 (C−S)
6.70 (1H, d, J = 16Hz , −CO−CH=), 7.55 (1H, d,
J=16Hz, =CH−Ar), 3.05 (1H, s, N(CH3)2), 7.86
(2H, d, C−51−H, C−31−H), 7.82 (2H, d, C−3−H,
C−5−H), 7.63 (2H, d, C−2−H, C−6−H),
7.17 (1H, m, C−41−H).
1735 (−C=O),
1636 (−CH=CH),
855 (C−Cl),
7.31 (1H, d, J=16Hz, −CO−CH=),
7.87 (1H, d, J=16Hz, =CH−Ar) 7.71 (1H, d,
J=8Hz, −C−5−H), 7.69 (1H, d, J=9Hz, −C−31−H),
7.67 (1H, d, −C−6−H), 7.48 (1H, s, −C−3−H),
7.20 (1H, m, −C−41−H).
686 (C−S)
6
1710 (−C=0),
1655 (−CH=CH),
645 (C−S)
7.44 (1H, d, J= 16Hz, −CO−CH=), 7.74 (1H, d,
J= 16Hz, =CH−Ar) 8.83 (1H, d, J=9Hz,
C−51−H), 8.09 (1H, m, C−41−H), 8.06 (1H, d,
J=9Hz, C−31−H), 7.18-7.79 (10H, m, Ar−H).
7.39(1H, d, J=16Hz , −CO−CH=), 7.56 (1H, d,
J=16Hz, =CH−Ar), 7.88 (1H, d, J=9Hz,
−C−51−H), 7.68 (2H, d, −C−2−H, −C−6−H),
7.58 (1H, d, J=8Hz, −C−31−H), 7.23 (2H, d,
−C−3−H, −C−5−H), 7.19 (1H, m, −C−41−H).
7.69 (1H, d, J=16Hz , −CO−CH=), 7.84 (1H, d,
J=16Hz =CH−Ar), 7.19 (1H, m, C−4−H), 7.87
(1H, d, J=9Hz, C−51−H), 7.44 (1H, m, C−41−H),
7.42 (1H, d, J=9Hz, C−31−H,), 7.40(2H, d,
C−3−H, C−5−H), 7.64 (2H, m, C−2−H, C−6−H).
7
1732(−C=O),
1645 (−CH=CH),
652 (C−S)
8
1700 (−C=0),
1650 (−CH=CH),
650 (C−S)

436
B. RAMESH et al.
Table 3. Anti-inflammatory activity of the compounds (1-8).
% increase in paw thickness of various time intervals
Compound
0.5 h
20.26
0.64
01 h
23.95
0.66
2 h
3 h
67.93
1.65
4 h
6 h
98.98
1.98
Standard
58.02
1.54
97.09
1.95
Control
22.69
1.71
56.46
1.28
72.02
1.86
86.43
4.03
23.59
1.35
87.66
1.55
1
2
36.97
0.78
46.54
3.02*
50.60
2.51*
69.62
1.01
56.95
3.54**
59.89
0.96
65.22
1.59
74.74
1.73
87.66
1.55
3
4
5
6
7
8
49.39
2.97*
44.46
2.20
74.90
3.17*
78.66
4.77***
75.15
3.21*
78.19
4.47***
78.91
4.79***
67.63
1.42
82.42
5.72***
85.68
4.31***
88.36
3.31*
82.24
3.38**
85.51
4.41***
76.32
3.89**
94.43
1.02
69.21
2.58*
64.55
3.28*
55.27
1.44
97.05
4.32**
94.61
1.95
36.79
2.54*
36.26
2.48*
43.91
1.80
50.70
3.77**
50.43
1.36
89.23
3.90**
94.55
2.04
60.66
2.92*
41.30
4.07**
66.96
4.39***
41.88
0.09
18.64
2.01
89.23
3.89**
Control: 1% sodium CMC gel, standard : aceclofenac standard and sample solution is 100 mg/ kg
body weight, values are expressed as mean (n = 6)* = 2.28, ** = 3.75, *** = 4.35.
P* < 0.05, P** < 0.01, P*** < 0.001 compared to control student t-test
Results and Discussion
The screening results revealed that the compounds (1-8) exhibited moderate to considerable
activity when compared with reference standard aceclofenac. The synthesized compounds
showed anti-inflammatory activity in the range of 50-80% whereas standard drug showed
80-85% inhibition in paw edema. The results of anti-inflammatory activity indicated that
compound 4 showed maximum anti-inflammatory activity.
Acknowledgment
We are thankful to the Head, Sophisticated Instrumentation Facility, Indian Institute of
Sciences, Bangalore for 1H NMR spectra and to Sipra Laboratories, Hyderabad for IR spectra.
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