Synthesis of aroyl[bis(4-hydroxycoumarin-3-yl)]methane using tungstate sulfuric acid in water

Article abstract of DOI:10.3184/174751914X13997396123260

An efficient synthesis of some new aroyl[bis(4-hydroxycoumarin-3-yl)] methanes (dicoumarols) based on the reaction of 4-hydroxycoumarin with arylglyoxals is described. The reactions were efficiently catalysed by tungstate sulfuric acid to afford the produ

Full text of DOI:10.3184/174751914X13997396123260

356 RESEARCH PAPER
VOL. 38 JUNE, 356–357
JOURNAL OF CHEMICAL RESEARCH 2014
Synthesis of aroyl[bis(4-hydroxycoumarin-3-yl)]methane using tungstate
sulfuric acid in water
Saeed Khodabakhshia* Bahador Karamib and Mojtaba Baghernejada
aYoung Researchers and Elite Club, Gachsaran Branch, Islamic Azad University, Gachsaran, Iran
bDepartment of Chemistry, Yasouj University, Yasouj 75918-74831 PO Box 353, Iran
An efficient synthesis of some new aroyl[bis(4-hydroxycoumarin-3-yl)]methanes (dicoumarols) based on the reaction of
4-hydroxycoumarin with arylglyoxals is described. The reactions were efficiently catalysed by tungstate sulfuric acid to afford
the product in moderate to good yields (up to 65%).
Keywords: dicoumarols, tungstate sulfuric acid, arylglyoxal, 4‑hydroxycoumarin
Recently, coumarin derivatives have received attention
because of their biological activities.1–3 Dicoumarol is a
naturally occurring anticoagulant which functions like
vitamin K.4 This compound is an agent for the prevention or
treatment of thrombosis.5 Due to their biological significance,
there has been considerable interest in developing synthetic
strategies for the preparation of dicoumarol derivatives. For
example, a total synthesis starting from salicylaldehyde and
formaldehyde,6 biosynthesis using micro‑organisms such
as Penicillium jenseni,7 and Knoevenagel condensation of
4‑hydroxycoumarins with carbonyls in the presence of several
catalysts have been reported.8–10 We now describe a green
method for the synthesis of some new and known dicoumarols
containing an aroyl group.
It can be concluded that the solvents such as EtOH, MeOH,
and H2O accelerate the condensation reaction. The use of water
is cheaper and safer than using organic solvents.11 Under the
optimised conditions, a variety arylglyoxals 2 were used for
the synthesis of dicoumarol derivatives (Table 3). Arylglyoxals
possessing either electron‑withdrawing or electron‑donating
groups were successfully employed in this reaction.
Recently, organic synthesis in water was reviewed by Fokin
and co‑workers.12 Spectroscopically, the 1H NMR spectrum of
compound 3h shows a sharp singlet at 11.24 ppm as OH protons.
The aromatic protons also appeared at 8.27–7.18 ppm. A sharp
singlet signal at 6.19 ppm corresponds to the methine proton
which has been deshielded because of joining to sp2 carbons
such as C=O and two C=C.
Based on the common mechanistic pathway of the
Knoevenagel and Michael addition reaction, a mechanism for
the acid‑catalysed reaction of 1 with 2 is proposed (Scheme 2).
Results and discussion
In continuation of our previous studies on catalysed organic
reactions, we found that the condensation reaction of
4‑hydroxycoumarin (1) and arylglyoxals 2 in the presence
of catalytic amounts of tungstate sulfuric acid (TSA,
disulfurotungstate acid) leads to dicoumarol derivatives 3
(Scheme 1).
Initially, we used 4‑hydroxycoumarin (1) and phenylglyoxal
as the model reaction system to investigate the reaction
conditions. As can be seen in Table 1, the reaction proceeded
slowly in the absence of catalyst. Increasing the catalyst amount
did not affect the progress of the reaction markedly. It was
observed that the condensation reaction can be successful in
the presence of 5 mol% of the catalyst.
Table 1 The effect of TSA amount in the synthesis of 3a in H2O under reflux
Entry
Catalyst/mol%
Time/min
Yield/%
1
2
3
4
–
3
5
180
180
55
30
65
75
75
10
50
Table 2 The effect of several solvents for the synthesis of 3a using TSA
under reflux
Entry
Solvent
MeOH
EtOH
Time/min
Yield/%
The effects of several solvents on the reaction progress were
investigated as shown in Table 2.
1
2
3
4
5
6
40
35
60
120
55
55
73
75
70
50
75
75
THF
CH2Cl2
EtOH/H2O (1/1)
H2O
OH
Ar
HO
O
OH
2
O
O
Table 3 Synthesis of dicoumarols using TSA (5 mol%) under reflux in H2O
TSA (5 mol%)
H2O, reflux
1
Entry
Ar
Time/min
Yield/%a
M.p. [Lit.]/oC
+
O
O
O
O
3a
3b
3c
3d
3e
3f
C6H5
4-F–C6H4
70
65
70
60
55
75
70
60
80
75
70
75
70
65
68
82
193–1959 [200–202]9
233–235
240–242 [236–238]9
244–246 [240–242]9
261–263
3
O
O
4-Br–C6H4
4-NO2–C6H4
4-MeO–C6H4
3-MeO–C6H4
4-Cl–C6H4
Ar
2
Scheme 1 Synthesis of dicoumarol derivatives catalysed by TSA.
205–207
250–252
255–257
3g
3h
2-Naphthyl
* Correspondent. E‑mail: saeidkhm@yahoo.com
aIsolated yields.
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JOURNAL OF CHEMICAL RESEARCH 2014 357
7.79–7.75 (m, 2H), 7.56–7.50 (m, 2H), 7.33–7.24 (m, 4H), 6.94 (t, 2H,
J=8.6 Hz); 13C NMR (75 MHz, CDCl3): 192.9, 165.4, 152.4, 133.2,
132.0, 130.7, 130.6, 125.0, 124.5, 116.7, 116.3, 115.9, 115.6, 42.8.
O
O
O O
H
O
O
O
OH
S
S
W
S
O
O
O
HO
O
O
O O
O
Ar
O
4-Methoxy-benzoyl[bis(4-hydroxycoumarin-3-yl)]methane (3e):
M.p. 265–267 °C. Anal. calcd for C27H18O8: C, 68.94; H, 3.86; found: C,
69.10; H, 3.69%. IR (KBr, cm–1): 3500–3300, 3076, 2978, 1684, 1650,
W
Ar
+
HO
O
O
O
O
O
S
O
1
1620, 1601, 1571, 1263 cm–1; H NMR (CDCl3, 300 MHz): δꢀ=11.22
OH
O
(s, 2H), 8.00 (dd, 2H, J=8.2, 1.6 Hz), 7.77–7.72 (m, 2H), 7.55–7.49 (m,
2H), 7.32–7.24 (m, 4H), 6.77–6.72 (m, 2H), 6.00 (s, 1H), 3.71 (s, 3H);
13C NMR (CDCl3, 75 MHz): δ 193.1, 165.2, 163.5, 152.4, 133.0, 130.4,
128.3, 124.9, 124.5, 116.6, 116.4, 113.8, 55.4, 42.6.
3-Methoxy-benzoyl[bis(4-hydroxycoumarin-3-yl)]methane (3f):
M.p. 205–207 °C. Anal. calcd for C27H18O8: C, 68.94; H, 3.86; found:
C, 69.06; H, 3.65%. IR (KBr, cm–1): 3500–3300, 1693, 1655, 1619, 1602,
1567, 1273, 1427 cm–1; 1H NMR (CDCl3, 300 MHz): δ 11.16 (s, 1H), 8.00
(dd, 2H, J=8.2, 1.6 Hz), 7.55–7.49 (m, 2H), 7.34–7.24 (m, 6H), 7.12 (t,
1H, J=8.2 Hz), 6.94–6.90 (m, 1H), 6.00 (s, 1H), 3.69 (s, 3H); 13C NMR
(CDCl3, 75 MHz): δ 194.2, 165.2, 159.7, 152.4, 136.9, 133.1, 129.4,
125.0, 124.5, 120.2, 120.1, 116.7, 116.4, 112.4, 42.9.
H
O
O
O
-2 H2O
OH
H
H
O
O
Ar
O
H
O
O
Ar
O
O
4
OH
O
5
4-Chloro-benzoyl[bis(4-hydroxycoumarin-3-yl)]methane
(3g):
O
M.p. 250–252 °C. Anal. calcd for C26H15ClO7: C, 65.76; H, 3.18; found:
C, 65.91; H, 3.03%. IR (KBr, cm–1): 3500–3300, 3080, 2884, 1713,
O
O O
O
OH
S
W
S
+
3
1
1665, 1650, 1614, 1564, 1266, 1090, 767 cm–1; H NMR (DMSO‑d6,
HO
O
O O
O
400 MHz): δ 11.10 (s, 2H), 7.85 (d, 2H, J=6.0 Hz), 7.72 (d, 2H,
J=5.2 Hz), 7.62–7.52 (m, 4H), 7.31–7.25 (m, 4H), 6.28 (s, 1H); 13C NMR
(DMSO‑d6, 100 MHz): δ 196.1, 165.9, 163.3, 152.2, 135.9, 131.6, 131.2,
129.3, 125.9, 123.8, 123.4, 118.0, 115.8, 101.6, 42.9.
Scheme 2 Plausible mechanism for the TSA-catalysed reaction of
4-hydroxycoumarin with arylglyoxal.
2-Naphthoyl[bis(4-hydroxycoumarin-3-yl)]methane (3h): M.p.
255–257 °C. Anal. calcd for C30H18O7: C, 73.47; H, 3.70; found: C,
73.68; H, 3.75%. IR (KBr, cm–1): 3550–3300, 1694, 1653, 1617, 1565,
1454, 1280 cm–1; 1H NMR (CDCl3, 300 MHz): δ 11.24 (s, 2H), 8.27 (s,
1H), 8.01 (dd, 2H, J1 =8.2, J2 =1.6 Hz), 7.83–7.72 (m, 4H), 7.54–7.43 (m,
4H), 7.33–7.23 (m, 4H), 6.19 (s, 1H). 13C NMR (DMSO‑d6, 75 MHz): δ
177.3, 166.6, 163.6, 152.3, 134.4, 134.3, 131.8, 131.5, 129.1, 127.9, 127.5,
126.7, 124.1, 123.9, 123.3, 118.5, 115.7, 101.6, 43.1.
Conclusions
In summary,
a highly efficient coupling reaction of
4‑hydroxycoumarin and arylglyoxals has been developed.
The method is simple and generates a diverse range of new
and known dicoumarols in good yields. Note that the presence
of transformable functionalities in the products makes them
potentially valuable for further synthetic manipulations.
The authors are grateful to Young Researchers and Elite Club
(Iran) for partial support.
Experimental
All chemicals were purchased from Merck Aldrich. Arylglyoxals and
TSA were prepared as described previously.13,14 The reactions were
monitored by TLC (silica‑gel 60 F254, hexane: ethyl acetate). IR spectra
were recorded on a FT‑IR JASCO‑680 and the 1H NMR spectra were
obtained on a Bruker DPX‑400 or 300 MHz Avance 2 instrument.
The vario El CHNS was used for elemental analysis. The structure of
new compounds was completely deduced from their spectral data and
elemental analysis. The known compounds 3a, 3c and 3d have been
characterised by FT‑IR, melting points and comparison with previous
reports.9
Received 13 February 2014; accepted 11 April 2014
Paper 1402466 doi: 10.3184/174751914X13997396123260
Published online: 10 June 2014
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