A facile and general synthesis of tropolonyl-substituted chalcone derivatives

Article abstract of DOI:10.3184/030823410X12740293863464

A facile and general synthesis of a series of new troplonyl-substituted chalcone derivatives by Claisen-Schmidt condensation reaction from 3-acetyltropolone and substituted benzaldehydes as well as pyridine aldehydes is described. The method using 5% aq. KOH as catalyst and 50% aq. methanol as solvent is attractive since it specifically generates (E )-isomers with high yields under mild reaction conditions.

Full text of DOI:10.3184/030823410X12740293863464

JOURNAL OF CHEMICAL RESEARCH 2010
RESEARCH PAPER 269
MAY, 269–273
A facile and general synthesis of tropolonyl-substituted chalcone
derivatives
Mingqin Changa, Yang Lib, Hong Zhanga and Wentao Gaob*
aCollege of Chemistry & Chemical Engineering, Bohai University, Jinzhou 121000, P. R. China
bInstitute of Superfine Chemicals, Bohai University, Jinzhou 121 000, P. R. China
A facile and general synthesis of a series of new troplonyl-substituted chalcone derivatives by Claisen–Schmidt con-
densation reaction from 3-acetyltropolone and substituted benzaldehydes as well as pyridine aldehydes is described.
The method using 5% aq. KOH as catalyst and 50% aq. methanol as solvent is attractive since it specifically generates
(E)-isomers with high yields under mild reaction conditions.
Keywords: tropolone, chalcone, Claisen–Schmidt condensation, aldehydes
In 1945, Dewar1 predicted correctly the structure of tropolone
(2-hydroxycyclohepta-2,4,6-trienone) based on the known
natural products, colchicines and stipitatic acid.2 In identify-
ing the unique molecular structure (depicted in Fig. 1) of tro-
polone and its derivatives, i.e. a non-benzenoid “aromatic”
compound, a new field in chemistry was launched. Since his
discovery, tropolone natural products and synthetic tropolone
derivatives have attracted considerable interest due to the
unique structure and properties of the tropolone ring. Numer-
ous tropolone natural products and several synthetic tropolone
compounds have shown a range of potent biological activi-
ties.3–10 For example, some tropolones extracted from Goupia
glabra exhibit significant toxicity towards a panel of DNA
damage checkpoint defective yeast mutants, and behave as
genotoxins, which highlights their potential to be used as anti-
cancer drugs.11 The tropolone moiety plays an important role
in molecular assemblies for a fast and efficient lead generation
in the new drug discovery. Despite featuring only seven-ring
carbon atoms and no stereocentres, the synthesis of substituted
tropolones continues to be a considerable synthetic challenge.
Tropolone derivatives are scarce in nature,12 occurring only in
lower plants and fungi,13 and limited information is available
on these compounds.
Fig. 2
biosynthesis of flavonoids, which are common components of
the human diet.41–47 The complex pharmacological activities
together with the easy synthetic reproduction and derivatisa-
tion of the core structure (depicted in Fig. 2) have caused
considerable interest in the exploitation of the unique chalcone
template for the discovery of prospective lead compounds.
In light of these findings and in view of the rapid assembly
of molecular diversity being an important goal of synthetic
organic chemistry as well as one of the key paradigms of
modern drug discovery, a general and broad synthesis of tro-
polonyl-substituted chalcone compounds would be very attrac-
tive. Moreover, this kind of tropolonyl-substituted chalcone
derivatives can be useful precursors for the synthesis of several
unusually heterocycle-fused troponoid compounds as well as
more complex systems. But as far as we know, only few reports
exist for the synthesis of tropolonyl-substituted chalcones.48–50
However, all these reports are of individual syntheses and
are just limited to the synthesis of several methoxy- or
heterocycle-substituted derivatives. No efforts have been made
to develop a general synthetic approach. Therefore it is
of interest to find a general synthesis of a wide variety of
tropolonyl-substituted chalcone derivatives and the results of
our investigations in this field are reported herein.
Fig. 1
On the other hand, the 1,3-diarylprop-2-enone (chalcone)
moiety has earned the status of a privileged pharmacophore
as compounds bearing this moiety possess a broad spectrum
of biological activity.14 Recent studies on biological evaluation
of chalcones revealed them to be anti-malarial,15–19 anti-
cancer,20–22 anti-leishmanial,23–25 anti-inflammatory,26,27 antimi-
totic,28 anti-tuberculosis,29,30 cardiovascular,31 cell differentia-
tion inducing,32 nitric oxide regulation modulatory33,34 and
anti-hyperglycemic agents.35 Diarylprop-2-enones inhibit vari-
ous enzymes such as CysLT1,36 COX/5-LOX,37 EGFR tyrosine
kinase38 and tyrosinase39 that play crucial roles in the biochem-
ical pathways of different diseases. Recently, Nishida Jun et al.
reported that some chalcone-bearing hydroxyl groups can
act as potential inhibitors of tyrosinase.40 Chalcones have
also been considered the main biological precursors for the
As shown in Scheme 1, 22 new tropolone-substituted chal-
cones 2a–v were readily prepared by using Claisen–Schmidt
condensation of 3-acetyltropolone (1) with various substituted
aldehydes (1.5 molar equv.) with 5% aqueous KOH as catalyst
at room temperature for 24 h. These conditions were found to
be satisfactory for the synthesis of the derivatives in good to
excellent yields. The experimental procedure was very simple.
In all cases, the products were isolated by simple filtration in
practically pure form. The current method was fairly general,
clean, and efficient, providing an expeditious access to the
preparation of various tropolone-substituted chalcones. It is
noteworthy that if the reagents are added simultaneously to
50% aqueous methanol, or 5% KOH solution is added first,
none of the desired products were obtained. Only when 5%
KOH solution was added dropwise slowly to the 50% metha-
nol solution of aldehyde and 3-acetyltropolone under stirring
did the reaction proceeds as shown. The results summarised
* Correspondent. E-mail: bhuzh@163.com

270 JOURNAL OF CHEMICAL RESEARCH 2010
Table 1 Melting points, yields and MS data of compounds 2a–v
Entry
Compd
R
M.p./°C
Yield/%
MS (ES+) m/z [M+H]+
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
2r
3-Me
4-Me
4-Et
2-OEt
4-OEt
3-OPh
2-Cl
3-Cl
4-Cl
2-Br
3-Br
129–130
180–181
165–167
136–138
170–172
120–122
160–161
182–184
184–186
162–164
176–178
200–201
236–238
205–207
220–222
218–220
220–222
166–167
242–244
254–256
194–196
210–212
84
93
79
83
87
84
91
82
92
85
84
89
83
84
89
92
80
89
78
83
50
48
267.2
267.2
281.1
297.1
297.1
345.1
287.1
287.1
287.1
330.7 (79Br)
331.4 (79Br)
331.1 (79Br)
298.1
4-Br
3-NO2
4-NO2
4-CN
2,3-(Cl)2
2,4-(Cl)2
2,6-(Cl)2
3,4-(Cl)2
3,5-(Cl)2
–
298.1
278.2
321.1 (35Cl)
321.1 (35Cl)
320.7 (35Cl)
321.1 (35Cl)
321.0 (35Cl)
254.1
2s
2t
2u
2v
–
254.1
in Table 1 indicate the scope and generality of the Claisen–
Schmidt reaction of 3-acetyltropolone with the various
substituted aldehydes.
The Claisen–Schmidt condensation reaction of 3-acetyltro-
polone with different aldehydes proved to be efficient furnish-
ing excellent yields of the corresponding tropolone-substituted
chalcones. For example, the tropolone-substituted chalcones
2a–f (entries 1–6) bearing electron-donating substituents such
as methyl, ethyl, ethoxy and phenoxy groups on the benzene
ring, were obtained in 79–93% yields. Similarly, the other
products 2g–t (entries 7–20) bearing electron-withdrawing
groups such as halo-, nitro-, cyano- in –ortho, -meta and -para
positions were obtained in 78–92% yields. Thus we concluded
that the effect of substituent groups is not very strong. How-
ever, in the Claisen–Schmidt condensation reaction using 2-
pyridine aldehyde or 3-pyridine aldehyde, the corresponding

JOURNAL OF CHEMICAL RESEARCH 2010 271
Table 2 Spectroscopic data of compounds 2a–v
Compd.
IR, ν /cm−1
1H NMR, δ (J in Hz)
HR-ESI-MS (m/z)
Found (Calcd)
2a
3193 (OH), 1651 (C=O), 2.36 (s, 3H, CH3), 7.12–7.14 (m, 1H, ArH), 7.18 (d, 1H, J = 16.0 Hz, H-α),
289.0836 [M+Na]+
C17H14NaO3+
1612 (C=O), 1557 (Ar)
7.22–7.29 (m, 2H, ArH), 7.37–7.42 (m, 3H, ArH), 7.48 (d, 1H, J = 10 Hz,
ArH), 7.61 (d, 1H, J = 16.0 Hz, H-β), 7.68 (d, 1H, J = 10 Hz, ArH)
3197 (OH), 1650 (C=O), 2.38 (s, 3H, CH3), 7.12–7.26 (m, 5H, ArH and H-α), 7.40–7.52 (m, 3H, ArH),
1617 (C=O), 1560 (Ar) 7.61 (d, 1H, J = 16.0 Hz, H-β), 7.67 (d, 1H, J = 10.0 Hz, ArH)
(289.0835)
2b
2c
2d
289.0830 [M+Na]+
C17H14NaO3+
(289.0835)
3190 (OH), 1665 (C=O), 1.24 (t, 3H, J = 7.6 Hz, CH2CH3), 2.67 (q, 2H, J = 7.6 Hz, CH2CH3), 7.12–7.26 303.0993 [M+Na]+
1607 (C=O), 1542 (Ar)
(m, 4H, ArH and H-α), 7.40–7.51 (m, 4H, ArH), 7.62 (d, 1H, J = 15.6 Hz, H-β),
C18H16NaO3+
(303.0992)
7.68 (d, 1H, J = 9.6 Hz, ArH)
3193 (OH), 1649 (C=O), 1.42 (t, 3H, J = 7.0 Hz, OCH2CH3), 4.08 (q, 2H, J = 7.0 Hz, OCH2CH3),
319.0945 [M+Na]+
C18H16NaO4+
1615 (C=O), 1572 (Ar)
6.95–6.87 (m, 2H, ArH), 7.12 (d, 1H, J = 10.0 Hz, ArH), 7.26–7.37 (m, 3H,
ArH), 7.42 (d, 1H, J = 15.2 Hz, H-α), 7.56 (d, 1H, J = 7.6 Hz, ArH), 7.66
(d, 1H, J = 9.6 Hz, ArH), 7.96 (d, 1H, J = 15.6 Hz, H-β)
(319.0941)
2e
2f
3171 (OH), 1660 (C=O), 1.42 (t, 3H, J = 7.0 Hz, OCH2CH3), 4.06 (q, 2H, J = 7.0 Hz, OCH2CH3), 6.88
319.0948 [M+Na]+
C18H16NaO4+
1600 (C=O), 1552 (Ar)
(d, 2H, J = 8.4 Hz, ArH), 7.10 (d, 1H, J = 15.6 Hz, H-α), 7.38–7.52 (m, 4H,
ArH), 7.58 (d, 1H, J = 15.6 Hz, H-β), 7.65 (d, 2H, J = 10.0 Hz, ArH)
(319.0941)
3198 (OH), 1659 (C=O), 7.00–7.04 (m, 3H, ArH), 7.13–7.15 (m, 3H, ArH), 7.18 (d, 1H, J = 16.0 Hz,
367.0947 [M+Na]+
C22H16NaO4+
1601 (C=O), 1565 (Ar)
H-α), 7.33–7.42 (m, 5H, ArH), 7.48 (d, 1H, J = 10.0 Hz, ArH), 7.57 (d, 1H,
J = 16.0 Hz, H-β), 7.68 (d, 1H, J = 10.0 Hz, ArH)
(367.0941)
2g
2h
2i
3202 (OH), 1660 (C=O), 7.14–7.17 (m, 1H, ArH), 7.21 (d, 1H, J = 15.7 Hz, H-α), 7.26–7.34 (m, 2H,
309.0284 [M+Na]+
C16H1135ClNaO3+
(309.0289)
1610 (C=O), 1551 (Ar)
ArH), 7.42 (d, 2H, J = 10.2 Hz, ArH), 7.49–7.55 (m, 1H, ArH), 7.72–7.77
(m, 2H, ArH), 8.08 (d, 1H, J = 15.7 Hz, H-β)
3201 (OH), 1672 (C=O), 7.13–7.17 (m, 1H, ArH), 7.29 (d, 1H, J = 16.4 Hz, H-α), 7.34 (s, 1H, ArH),
309.0285 [M+Na]+
C16H1135ClNaO3+
(309.0289)
1611 (C=O), 1550 (Ar)
7.42–7.58 (m, 5H, ArH and H-β), 7.70 (d, 1H, J = 7.2 Hz, ArH), 7.85 (s, 1H,
ArH)
3198 (OH), 1658 (C=O), 7.17–7.19 (m, 1H, ArH), 7.21 (d, 1H, J = 15.6 Hz, H-α), 7.26–7.32 (m, 2H,
309.0288 [M+Na]+
C16H1135ClNaO3+
(309.0289)
1612 (C=O), 1563 (Ar)
ArH), 7.42 (d, 2H, J = 10.4 Hz, ArH), 7.51 (d, 1H, J = 10.0 Hz, ArH),
7.72–7.77 (m, 2H, ArH), 8.08 (d, 1H, J = 15.0 Hz, H-β)
3210 (OH), 1660 (C=O), 7.13–7.18 (m, 1H, ArH), 7.22 (d, 1H, J = 16.0 Hz, H-α), 7.32 (d, 1H, J =
2j
352.9780 [M+Na]+
C16H1179BrNaO3+
(352.9784)
1609 (C=O), 1541 (Ar)
10.4 Hz, ArH), 7.35–7.44 (m, 2H, ArH), 7.51–7.56 (m, 1H, ArH), 7.60–7.68
(m, 2H, ArH), 7.77 (d, 1H, J = 16.0 Hz, H-β), 7.87–7.91 (m, 1H, ArH).
3205 (OH), 1671 (C=O), 7.14–7.16 (m, 2H, ArH), 7.21 (d, 1H, J = 16.0 Hz, H-α), 7.25–7.30 (m, 1H,
2k
2l
352.9785 [M+Na]+
C16H1179BrNaO3+
(352.9784)
1608 (C=O), 1549 (Ar)
ArH), 7.42 (d, 1H, J = 10.0 Hz, ArH), 7.50–7.55 (m, 3H, ArH), 7.58 (d, 1H,
J = 16.0 Hz, H-β), 7.74 (d, 1H, J = 10.4 Hz, ArH).
3194 (OH), 1650 (C=O), 7.07–7.12 (m, 1H, ArH), 7.21 (d, 1H, J = 16.0 Hz, H-α), 7.26–7.29 (m, 3H,
352.9783 [M+Na]+
C16H1179BrNaO3+
(352.9784)
1611 (C=O), 1562 (Ar)
ArH), 7.45–7.52 (m, 3H, ArH), 7.57 (d, 1H, J = 16.0 Hz, H-β), 7.61–7.64
(m, 1H, ArH)
2m
2n
2o
2p
2q
2r
3210 (OH), 1680 (C=O), 7.00–7.17 (m, 2H, ArH), 7.41–7.47 (m, 2H, ArH and H-α), 7.63 (d, 1H,
296.0565 [M-H]−
C16H10NO5−
1612 (C=O), 1529 (Ar)
J = 10.8 Hz, ArH), 7.81 (d, 1H, J = 8.0 Hz, ArH), 7.86–7.90 (m, 2H, ArH),
8.43 (d, 1H, J = 15.6 Hz, H-β), 8.45 (d, 1H, J = 5.6 Hz, ArH)
3200 (OH), 1677 (C=O), 7.02–7.07 (m, 2H, ArH), 7.13 (d, 1H, J = 15.6 Hz, H-α), 7.35–7.42 (m, 3H,
(296.0564)
320.0522 [M+Na]+
C16H11NNaO5+
(320.0529)
1610 (C=O), 1550 (Ar)
ArH), 7.48 (d, 1H, J = 4.4 Hz, ArH), 7.60 (d, 1H, J = 16.0 Hz, H-β), 8.50
(d, 1H, J = 5.2 Hz, ArH), 8.62 (d, 1H, J = 5.2 Hz, ArH)
3210 (OH), 1674 (C=O), 7.16–7.21 (m, 1H, ArH), 7.38 (d, 1H, J = 16.0 Hz, H-α), 7.44 (d, 1H, J =
300.0632 [M+Na]+
C17H11NNaO3+
(300.0631)
1617 (C=O), 1550 (Ar)
10.0 Hz, ArH), 7.52–7.57 (m, 5H, ArH), 7.67 (d, 1H, J = 15.6 Hz, H-β), 7.82
(d, 1H, J = 9.6 Hz, ArH)
3200 (OH), 1675 (C=O), 7.15–7.21 (m, 2H, ArH), 7.23–7.26 (m, 2H, ArH), 7.35–7.39 (m, 2H, ArH),
342.9891 [M+Na]+
C16H1035Cl2NaO3+
(342.9899)
1610 (C=O), 1564 (Ar)
7.43 (d, 1H, J = 16.4 Hz, H-α), 7.49–7.54 (m, 1H, ArH), 7.80 (d, 1H, J =
16.4 Hz, H-β)
3200 (OH), 1670 (C=O), 7.14–7.19 (m, 1H, ArH), 7.34 (d, 1H, J = 15.8 Hz, H-α), 7.36 (s, 1H, ArH),
342.9898 [M+Na]+
C16H1035Cl2NaO3+
(342.9899)
1613 (C=O), 1557 (Ar)
7.50 (d, 1H, J = 12.0 Hz, ArH), 7.57 (d, 1H, J = 12.0 Hz, ArH), 7.63–7.66
(m, 2H, ArH), 7.74 (d, 1H, J = 15.8 Hz, H-β), 7.97 (d, 1H, J = 8.0 Hz, ArH)
3201 (OH), 1665 (C=O), 7.15–7.20 (m, 1H, ArH), 7.32–7.36 (m, 2H, ArH), 7.43 (d, 1H, J = 15.9 Hz,
342.9890 [M+Na]+
C16H1035Cl2NaO3+
(342.9899)
1612 (C=O), 1550 (Ar)
H-α), 7.54 (d, 1H, J = 10.2 Hz, ArH), 7.66 (d, 1H, J = 9.4 Hz, ArH), 7.72
(d, 1H, J = 7.8 Hz, ArH), 7.82 (d, 1H, J = 15.9 Hz, H-β), 7.91 (d, 1H, J =
7.8 Hz, ArH)
2s
2t
3218 (OH), 1670 (C=O), 7.13–7.18 (m, 1H, ArH), 7.32 (d, 1H, J = 16.0 Hz, H-α), 7.49–7.58 (m, 4H,
342.9891 [M+Na]+
C16H1035Cl2NaO3+
(342.9899)
1609 (C=O), 1548 (Ar)
ArH and H-β), 7.68 (d, 1H, J = 8.0 Hz, ArH), 7.75 (d, 1H, J = 8.4 Hz, ArH),
8.08 (s, 1H, ArH)
210 (OH), 1675 (C=O),
1611 (C=O), 1557 (Ar)
7.13–7.17 (m, 1H, ArH), 7.32 (d, 1H, J = 10.3 Hz, ArH), 7.38 (d, 1H, J = 16.1 318.9931 [M-H]−
Hz, H-α), 7.48–7.58 (m, 3H, ArH and H-β), 7.66 (s, 1H, ArH), 7.87 (s, 2H,
C16H9Cl2O3−
(318.9934)
ArH)
2u
2v
3105 (OH), 1660 (C=O), 6.99–7.06 (m, 2H, ArH), 7.20 (d, 1H, J = 15.8 Hz, H-α), 7.38–7.44 (m, 2H,
254.0814 [M+H]+
C15H12O3+
1594 (C=O), 1551 (Ar)
ArH), 7.51–7.55 (m, 2H, ArH), 7.73 (d, 1H, J = 15.8 Hz, H-β), 8.52–8.57
(m, 1H, ArH), 8.62–8.65 (m, 1H, ArH)
3200 (OH), 1670 (C=O), 7.07–7.16 (m, 2H, ArH), 7.28 (d, 1H, J = 15.8 Hz, H-α), 7.44–7.51 (m, 1H,
(254.0812)
254.0816 [M+H]+
C15H12O3+
1609 (C=O), 1542 (Ar)
ArH), 7.56–7.62 (m, 1H, ArH), 7.77 (d, 1H, J = 8.0 Hz, ArH), 7.83–7.91
(m, 2H, ArH), 7.99 (d, 1H, J = 15.8 Hz, H-β), 8.17–8.20 (m, 1H, ArH)
(254.0812)

272 JOURNAL OF CHEMICAL RESEARCH 2010
3
4
M. Yamato, J. Ando, J. Sakai, K. Hashigaki, Y. Wataya, S. Tsukagoshi,
T. Tashiro and T. Tsuruo, J. Med. Chem., 1992, 35, 267.
G.H. Harris, K. Hoogsteen, K.C. Silverman, S.L. Raghoobar, G.F. Bills,
R.B. Lingham, J.L. Smith, H.W. Dougherty, C. Cascales and F. Paláez,
Tetrahedron, 1993, 49, 2139.
F. Mayerl, Q. Gao, S. Huang, S.E. Klohr, J.A. Matson, D.R. Gustavson,
D.M. Pirnik, R.L. Berry, C. Fairchild and W.C. Rose, J. Antibiot., 1993, 46,
1082.
D. Miyamoto, Y. Kusagaya, N. Endo, A. Sometani, S. Takeo, T. Suzuki,
Y. Arima, K. Nakajima and Y. Suzuki, Antiviral Res., 1998, 39, 89.
P. Cai, D. Smith, B. Cunningham, S. Brown-Shimer, B. Katz, C. Pearce,
D. Venables and D. Houck, J. Nat. Prod., 1998, 61, 791.
U. Lange, C. Schumann and K.L. Schmidt, Eur. J. Med. Res., 2001, 6,
150.
products 2u and 2v (entries 21 and 22) were obtained in
only moderate yields of 50% and 48%, respectively. We also
attempted to increase to three- to five-fold the excess of KOH
(15–25%) but this was found to decrease the yields of the
two products due to the occurrence of some side reactions
like 1,4-Michael additions. All the synthesised compounds
have not been reported previously and their structures were
confirmed by spectroscopic data, which are listed in Table 2.
All spectroscopic data are in accordance with the described
structures. The molecular formulae were usually established
from the quasi-molecular ion [M+Na]+ peak of, indicating
the presence of the positive-mode HR-ESI-MS 11 degrees of
unsaturation. Different procedures were used for 2m, 2t, 2u
and 2v. In the IR spectra of compounds 2a–v, the absorptions
relating to an α,β-unsaturated carbonyl moiety stretch were
observed at 1594–1615 cm−1 and tropolone carbonyl moiety
stretching frequency in 1649–1680 cm−1. The 1H NMR spectra
for all the synthesised compounds show the signals of aromatic
hydrogens between 6.88 and 8.62 ppm. The main features of
5
6
7
8
9
E. Matsumura, Y. Morita, T. Date, H. Tsujibo, M. Yasuda, T. Okabe,
N. Ishida and Y. Inamori, Biol. Pharm. Bull., 2001, 24, 299.
10 J.E. Baldwin, A.V.W. Mayweg, G.J. Pritchard and R.M. Adlington,
Tetrahedron Lett., 2003, 44, 4543.
11 D. Mesa-Siverio, A. Estévez-Braun, Á.G. Ravelo, J.R. Murguia and
A. Rodríguez-Afonso, Eur. J. Org. Chem., 2003, 4243.
12 E. Ellington, J. Bastida, F. Viladomat, V. Simanek and C. Codina, Biochem.
Syst. Ecol., 2003, 31, 715.
13 R.F. Angawi, D.C. Swenson, J.B. Gloer and D.T. Wicklow, Tetrahedron
Lett., 2003, 44, 7593.
1
the H NMR data are the resonances of the vinylic protons
14 J.R. Dimmock, D.W. Elias, M.A. Beazely and N.M. Kandepu, Curr. Med.
Chem., 1999, 6, 1125.
15 M. Liu, P. Wilairat and M.L. Go, J. Med. Chem., 2001, 44, 4443.
16 J.N. Domínguez, J.E. Charris, G. Lobo, N.G. de Domínguez, M.M.
Moreno, F. Riggione, E. Sanchez, J. Olson and P.J. Rosenthal, Eur. J. Med.
Chem., 2001, 36, 555.
appearing as doublets at δHα 7.10–7.43 ppm and δHβ 7.57–
7.99 ppm. The coupling constants 3JHα-Hβ, in the range of 15.6–
16.4 Hz indicate the E-configuration of these vinylic systems.
As reported in the chalcone literature51, the Claisen–Schmidt
condensation reaction yields only E-stereoisomers.
In conclusion, the present investigation has demonstrated a
general synthesis of a wide variety of tropolonyl-substituted
chalcone derivatives in good to excellent yields. The numerous
molecules we have synthesised should allow us to investigate
structure–activity relationships over various biotests. In addi-
tion, as chalcone derivatives these molecules can provide a
bifunctional site for 1,3-dinucleophiles affording heterocyclic
ring-systems, and thus will be used as useful synthons in
troponoid chemistry.
17 V.J. Ram, A.S. Saxena, S. Srivastava and S. Chandra, Bioorg. Med. Chem.
Lett., 2000, 10, 2159.
18 J.A. Geyer, S.M. Keenan, C.L. Woodard, P.A. Thompson, L. Gerena, D.A.
Nichols, C.E. Gutteridge and N.C. Waters, Bioorg. Med. Chem. Lett., 2009,
19, 1982.
19 N. Mishra, P. Arora, B. Kumar, L.C. Mishra, A. Bhattacharya, S.K. Awasthi
and V.K. Bhasin, Eur. J. Med. Chem., 2008, 43, 1530.
20 Y. Xia, Z.Y. Yang, P. Xia, K.F. Bastow, Y. Nakanishi and K.H. Lee, Bioorg.
Med. Chem. Lett., 2000, 10, 699.
21 M.V.B. Reddy, C.R. Su, W.F. Chiou, Y.N. Liu, R.Y.H. Chen, K.F. Bastow,
K.H. Lee and T.S. Wua, Bioorg. Med. Chem., 2008, 16, 7358.
22 L. Dalla Via, O. Gia, G. Chiarelotto and M. G. Ferlin, Eur. J. Med. Chem.,
2009, 44, 2854.
23 L. Zhai, M. Chen, J. Blom, T.G. Theander, S.B. Christensen and A.
Kharazmi, J. Antimicrob. Chemother., 1999, 43, 793.
24 E.C. Torres-Santos, J.M. Rodrigues Jr., D.L. Moreira, M.A.C. Kaplan and
B. Rossi-Bergmann, Antimicrob. Agents Chemother., 1999, 43, 1776.
25 J. Quintin, J. Desrivot, S. Thoret, P. Le Menez, T. Cresteil and G. Lewin,
Bioorg. Med. Chem. Lett., 2009, 19, 167.
26 H.K. Hsieh, L.T. Tsao and J.P. Wang, J. Pharm. Pharmacol., 2000, 52,
163.
27 J.H. Cheng, C.F. Hung, S.C. Yang, J.P. Wang, S.J. Won and C.N. Lin,
Experimental
Melting points (uncorrected) were determined using a WRS-1B
melting points apparatus. H NMR spectra were measured with a
1
Bruker BRX 400 instrument at 400 MHz. The reported chemical shifts
are relative to TMS. Mass spectra were recorded on a Micromass
Platform liquid chromatography mass spectrometry-electrospray ioni-
sation. HRMS (ESI) data were acquired on an Bruker Customer
micrOTOF-Q 125 high-resolution mass spectrometer.
Bioorg. Med. Chem., 2008, 16, 7270.
28 M.S. Karthikeyan, B.S. Holla and N.S. Kumari, Eur. J. Med. Chem., 2007,
42, 30.
Tropolone-substituted chalcone derivatives 3-(3-arylacryloyl)
tropolones (2a–t) or 3-(3-pyridinylacryloyl)tropolones (2u–v),
general procedure
29 L.M. Lin, Y. Zhou, M.T. Flavin, L.M. Zhou, W. Nie and F.C. Chen, Bioorg.
Med. Chem., 2002, 10, 2795.
30 P.M. Sivakumar, S.P. Seenivasan, V. Kumar and M. Doble, Bioorg. Med.
Chem. Lett., 2007, 17, 1695.
To a stirred solution of 3-acetyltropolone (1 mmol, 0.164 g) and the
appropriate benzaldehyde or pyridine aldehyde (1.5 mmol), an aque-
ous solution of 5% KOH (5 mL) was added dropwise. The resulting
solution was stirred at room temperature for 24 h. The reaction
mixture was quenched by addition of 5 mL H2O and acidification with
1 M HCl. The precipitate was collected by filtration, washed with
water, dried, and recrystallised from methanol to give products 2a–v
in 48–97% yields.
31 C. Furman, J. Lebeau, J.C. Fruchart, J.L. Bernier, P. Duriez, N. Cotelle and
E. Teissier, J. Biochem. Mol. Toxicol., 2001, 15, 270.
32 E.J. Park, R. Park and J.S. Lee, J. Kim, Planta Med., 1998, 64, 464.
33 J. Rojas, M. Paya, J.N. Domínguez and M. Luisa Ferrandiz, Bioorg. Med.
Chem. Lett., 2002, 12, 1951.
34 F. Herencia, M.L. Ferrandiz, A. Ubeda, I. Guillen, J.N. Domínguez, J.E.
Charris, G.M. Lobo and M.J. Alcaraz, Free Radical Biol. Med., 2001, 30,
43.
35 M. Satyanarayana, P. Tiwari, B.K. Tripathi, A.K. Srivastava and R. Pratap,
We thank the Foundation of Liaoning Province Key Labora-
tory of Applied Chemistry (Grant No. 2008s001) for financial
support.
Bioorg. Med. Chem., 2004, 12, 883.
36 M.E. Zawaagstra, H. Timmerman, M. Tamura, T. Tohma, Y. Wada, K.
Onogi and M.Q. Zhang, J. Med. Chem., 1997, 40, 1075.
37 Y. Jahng, L.X. Zhao, Y.S. Moon, A. Basnet, E.K. Kim, H.W. Chang, H.K.
Ju, T.C. Jeong and E.S. Lee, Bioorg. Med. Chem. Lett., 2004, 14, 2559.
38 E.B. Yang, Y.J. Guo, K. Zhang, Y.Z. Chen and P. Mack, Biochim. Biophys.
Acta, 2001, 144, 1550.
Received 4 November 2009; accepted 10 April 2010
Paper 090861 doi: 10.3184/030823410X12740293863464
Published online: 8 June 2010
39 S. Khatib, O. Nerya, R. Musa, M. Shmuel, S. Tamir and J. Vaya, Bioorg.
Med. Chem., 2005, 13, 433.
40 N. Jun, H. Gao and K. Jun, Bioorg. Med. Chem., 2007, 15, 2396.
41 Z.T. Li, G. Ngojeh, P. DeWitt, Z. Zheng, M. Chen, B. Lainhart, V. Li and
P. Felpo, Tetrahedron Lett., 2008, 49, 7243.
References
42 Y.K. Rao, S.H. Fang and Y.M. Tzeng, Bioorg. Med. Chem., 2005, 13,
6850.
1
2
M.J.S. Dewar, Nature, 1945, 155, 50.
M.J.S. Dewar, Nature, 1945, 155, 141.

JOURNAL OF CHEMICAL RESEARCH 2010 273
43 A.T. Khan and P. Goswami, Tetrahedron Lett., 2005, 46, 4937.
44 T.T. Dao, Y.S. Chi, J. Kim, H.P. Kim, S. Kim and H. Park, Bioorg. Med.
Chem.Lett., 2004, 14, 1165.
45 R. Sheng, X. Lin, J. Zhang, K.S. Chol, W.H. Huang, B. Yang, Q.J. He and
Y.Z. Hua, Bioorg. Med. Chem., 2009, 17, 6692.
46 X.W. Dong, T. Liu, J.Y. Yan, P. Wu, J. Chen and Y.Z. Hu, Bioorg. Med.
Chem., 2009, 17, 716.
47 P.P. Yadav, P. Gupta, A.K. Chaturvedi, P.K. Shukla and R. Maurya, Bioorg.
Med. Chem., 2005, 13, 1497.
48 K. Imafuku and K. Yamaguchi, Bull. Chem. Soc. Jpn., 1981, 54, 2855.
49 M. Honda and K. Imafuku, Bull. Chem. Soc. Jpn., 1985, 58, 508.
50 W.T. Gao and Z. Zheng, Chin. Chem. Lett., 2000, 6, 503.
51 E.I. Gasull, J.J. Silber, S.E. Blanco, F. Tomas and F.H. Feretti, J. Mol.
Struct. (Theochem), 2000, 203, 131.

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