A facile method for the synthesis of thiocoumestan derivatives

Article abstract of DOI:10.1002/jhet.146

(Chemical Equation Presented) An efficient synthesis of thiocoumestan derivatives, starting from catechols and 4-mercaptocoumarin in the presence of potassium ferricyanide as an oxidizing agent (Decker oxidation) was developed. The results indicate that t

Full text of DOI:10.1002/jhet.146

1000
A Facile Method for the Synthesis of Thiocoumestan Derivatives
Davood Nematollahi,a* Javad Azizian,b Mohsen Sargordan-Arani,c
Vol 46
Mahdi Hesari,d and Behrooz Mirzae
aDepartment of Analytic Chemistry, Faculty of Chemistry, Bu-Ali Sina University,
Hamadan 65174, Iran
bDepartment of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran
cFaculty of Chemistry, Islamic Azad University, Shahre Rey Branch, Tehran, Iran
dDepartment of Soil Science, Faculty of Agriculture, Bu-Ali Sina University, Hamadan 65174, Iran
eFaculty of Chemistry, Islamic Azad University, South Tehran Branch, Tehran, Iran
*E-mail: nemat@basu.ac.ir
Received August 21, 2008
DOI 10.1002/jhet.146
Published online 2 September 2009 in Wiley InterScience (www.interscience.wiley.com).
An efficient synthesis of thiocoumestan derivatives, starting from catechols and 4-mercaptocoumarin
in the presence of potassium ferricyanide as an oxidizing agent (Decker oxidation) was developed. The
results indicate that the 4-mercaptocoumarin participates in Michael addition reactions with in situ gen-
erated o-benzoquinones. The present work has led to the development of a one-pot oxidative method
for the synthesis of the 6H-benzothieno[3,2-c][1]benzopyron-6-one derivatives.
J. Heterocyclic Chem., 46, 1000 (2009).
INTRODUCTION
RESULTS AND DISCUSSION
Coumestans, [1] which are derivatives of 6H-benzo-
furo[3,2-c][1]benzopyran-6-one (Fig. 1) have the basic
structure of many natural products such as wedelolactone,
medicagol, psoralidin, isopsoralidin, erosnin, and estro-
genic cumestrol, with interesting physiological activities
[2,3]. The importance of these compounds has led us and
many workers to synthesize a number of these com-
pounds by chemical [4–10] and electrochemical [11–14]
routes. Following our experiences in oxidation of cate-
chols in the presence of nucleophiles [15–23], we envis-
aged that synthesis of thiocoumestans (6H-benzo-
thieno[3,2-c][l]benzopyran-6-one) (Fig. 1) might cause
an enhancement of physiological activities.
In our earlier work, comparison of the values of half
wave potential (E1/2), evaluated from the midpoint
potential between anodic and cathodic peaks for cate-
chol (0.165 V vs. SCE) and potassium ferricyanide
(0.195 V vs. SCE), using cyclic voltammetry, revealed
that potassium ferricyanide was a suitable agent (Decker
agent) for mild oxidation of catechols to their corre-
sponding o-benzoquinones without any effect on the
nucleophile [8]. Therefore, in this work we used
potassium ferricyanide as a stable, easily handled, and
commercially available oxidizing agent. This agent has
also been used in Decker oxidation. During Decker
oxidation, 1,3-disubstituted pyridinium salts converts to
isomeric pyridones [26].
In this direction, some workers synthesize a number
of thiocoumestan derivatives [10,24,25]. But, to the best
of our knowledge, no reaction of in situ generated o-
benzoquinones (2) with 4-mercaptocoumarin (3) has
been previously reported. Therefore, we now discover a
facile and one-pot synthetic route to thiocoumestans
involving oxidation of catechols (1) in the presence of
4-mercapto-coumarin (3), using potassium ferricyanide
as an oxidizing agent (Decker oxidation), in high yield
and purity.
The reaction for oxidation of (1a-c) in the presence of 3
is presented in Scheme 1. As can be seen, when catechols
(1a-c) (1 mmol) was treated with potassium ferricyanide
(4 mmol) in water/acetonitrile mixture (70/30 v/v) contain-
ing 4-mercaptocoumarin (3) (1 mmol) and sodium acetate
(0.2 M), thiocoumestans (4a-c) were obtained in good
yields (Scheme I). In more basic solutions, the formation
of anionic forms of catechols formed by an acid dissocia-
tion reaction was enhanced and the coupling of anionic
C
V
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September 2009
A Facile Method for the Synthesis of Thiocoumestan Derivatives
1001
Scheme 2
Figure 1. Structures of 6H-benzofuro[3,2-c][1]benzopyran-6-one (A)
and 6H-benzothieno[3,2-c][l]benzo pyran-6-one (B).
forms with o-benzoquinones interfered in the Michael
reaction of 4-mercaptocoumarin (3) with o-benzoquinones
(Scheme 2) [23,27,28]. In other words, in an aqueous solu-
tion containing 0.2 M sodium acetate, any dimerization
[27,28] or hydroxylation [29–31] reactions are too slow to
interfere in the synthesis of 4a-c.
Following our experiences in oxidation of catechols
in the presence of nucleophiles [15–23], it seems that in
water/acetonitrile mixture (70/30 v/v), the inter and intra
Michael addition reactions of anion of 4-mercapto
coumarin (3) to o-benzoquinone (2a-c) is faster than
other secondary reactions [27–31], leading to the thio-
coumestan derivatives (4a-c) as final products.
The oxidation of 1b and 1c in the presence of 3 pro-
ceeded in a similar fashion to that of 1a (Scheme 2).
The existence of a methyl or methoxy group at the C-3
position of these compounds probably causes relevant
Michael acceptors (2b and 2c) to be attacked by 3 at the
C-4 or C-5 positions to yield two types of product in
each case. As in the o-benzoquinones 2b and 2c C-5
more electropositive, we suggest that o-benzoquinones
2b and 2c are selectively attacked at C-5 position by 3
leading to the formation of the products 4b and 4c,
respectively [15–18].
the catechol derivative (4-(4,5-dihydroxy-2-methylphe-
nylthio)-2H-chromen-2-one) 4d as final product.
The synthesis of 4-phenylthio-2H-chromen-2-ones has
been reported previously by us and several groups using
different approaches [32–36]. However, to the best of
our knowledge, no reaction of o-benzoquinone 2d with
4-mercaptocoumarin (3) has been reported and this
method described an efficient and one-pot method for
the synthesis of 4-(4,5-dihydroxy-2-methylphenylthio)-
2H-chromen-2-one (4d).
EXPERIMENTAL
Reagents. All chemicals were reagent grade materials.
Sodium acetate, solvents, and reagents were of proanalysis.
These chemicals were used without further purification. 4-mer-
captocoumarin was prepared by the procedure reported
previously [37].
General procedure for the synthesis of 4a-d. To a stirred
solution of aqueous sodium acetate 0.2 M/acetonitrile (70/30),
4-mercaptocoumarin (3) (1 mmol) was added potassium ferri-
cyanide (4 mmol in the cases of 1a-c and 2 mmol in the case
of 1d). A solution of catechols (1a-d) (1 mmol) in relevant
solution was prepared and added dropwise to the stirred solu-
tion over a period of 20–30 min. The reaction mixture was
kept at r.t., with occasional stirring (1 h for 1a and 2.5 h for
1b-d). The solution become dark and formed precipitates. At
Interestingly, oxidation of 4-methylcatechol (1d) in
the presence of 3 in aqueous sodium acetate/acetonitrile
(70/30) solution, because of the existence of methyl
group at C-4 position of it that is a reactive site of cycli-
zation, proceeds in a different manner to that of 1a-c
(Scheme 3).
According to Scheme 3, generation of o-benzoqui-
none 2d is followed by an intermolecular Michael
addition of 3 to the o-benzoquinone 2d, producing
Scheme 1
Scheme 3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1002
D. Nematollahi, J. Azizian, M. Sargordan-Arani, M. Hesari, and B. Mirza
Vol 46
REFERENCES AND NOTES
the end of the reaction, a few drops of acetic acid were added
and the mixture was placed in a refrigerator overnight. The
solid formed were collected by filtration and washed several
times with water. The final products were characterized by IR,
1H NMR, 13C NMR, and MS spectroscopy.
8,9-Dihydroxy-6H-benzothieno[3,2-c][1]benzopyran-6-one
(C15H8O4S) (4a). mp 265–268ꢀ (dec); ir (potassium bromide):
3367, 3253, 1703, 1628, 1474, 1352, 1322, 1274, 1224, 1201,
1086, 1032, 989, 867, 836, 810, 752 cmꢁ1 1H nmr: d(300
;
MHz, acetone-d6) 7.29 (s, 1H, aromatic), 7.48 (s, 1H, aro-
matic), 7.52 (t, 2H, aromatic), 7.69 (t, 1H, aromatic), 8.03 (dd,
1H, aromatic), 8.8 (broad, OH, this peak observed in DMSO-
d6); 13C nmr: d (75.4 MHz, DMSO-d6) 99.7, 105.7, 106.0,
112.9, 114.6, 117.8, 122.0, 125.9, 132.3, 145.3, 147.1, 150.2,
153.0, 158.6, 158.9; ms: m/z (relative intensity) 284 [M]þ
(95), 266 (73), 233 (60), 177 (45), 144 (10), 140 (35), 121
(30), 89(100), 43 (25).
8,9-Dihydroxy-7-methyl-6H-benzothieno[3,2-c][1]benzo
pyran-6-one (C16H10O4S) (4b). mp 230–232ꢀ (dec); ir (po-
tassium bromide): 3374, 3163, 2929, 1708, 1603, 1546, 1448,
;
1343, 1289, 1124, 1170, 1030, 961, 859, 760, 639 cmꢁ1 1H
[1] Deschamp, V. C.; Mentzer, C. Comp Rend 1960, 251, 736.
[2] Bickoff, E. M.; Livingston, A. L.; Booth, A. N.; Thompson,
C. R.; Hollwell, E. A.; Beinhart, E. G. J Anim Sci 1960, 19, 4.
[3] Darbarwar, M.; Sundaramurthy, V.; Subba Rao, N. V.
Indian J Chem 1973, 11, 115.
[4] Bhalerao, U. T.; Muralikrishna, C.; Pandey, G. Synth
Commun 1989, 19, 1303.
[5] Someswari, N.; Srihari, K.; Sundaramurthy, V. Synthesis 1977, 609.
[6] Kurosawa, K.; Nogami, K. Bull Chem Soc Jpn 1976, 49, 1955.
[7] Shah, R. R.; Trivedi, K. N. J Ind Chem Soc 1979, 56, 995.
[8] Nematollahi, D.; Habibi, D.; Alizadeh, A.; Hesari, M.
J Heterocycl Chem 2005, 42, 289.
[9] Habibi, D.; Nematollahi, D.; Alizadeh, A.; Hesari, M.
Heterocycl Commun 2005, 11, 145.
[10] Yao, T.; Yue, D.; Larock, R. C. J Org Chem 2005, 70, 9985.
[11] Grujic, Z.; Tabakovic, I.; Trkovnik, M. Tetrahedron Lett
1976, 4823.
[12] Tabakovic, I.; Grujic, Z.; Bejtovic, Z. J Heterocycl Chem
1983, 20, 635.
[13] Golabi, S. M.; Nematollahi, D. J Electroanal Chem 1997, 420, 127.
[14] Golabi, S. M.; Nematollahi, D. J Electroanal Chem 1997, 430, 141.
[15] Nematollahi, D.; Shayani-jam, H. J Org Chem 2008, 73, 3428.
[16] Nematollahi, D.; Amani, A.; Tammari, E. J Org Chem
2007, 72, 3646.
nmr: d(300 MHz, DMSO-d6) 2.40 (s, 3H, methyl); 7.19 (s,
1H, aromatic); 7.48 (t, 1H, aromatic); 7.57 (d, 1H, aromatic);
7.66 (t, 1H, aromatic); 8.04 (dd, 1H, aromatic), 8.04 (broad,
OH) 8.7 (broad, OH); 13C nmr: d (75.4 MHz, DMSO-d6) 20.7
(methyl), 104.6, 112.7, 113.0, 122.4, 125.5, 129.2, 129.8,
132.2, 132.8, 136.1, 138.1, 151.0, 152.7, 163.9, 164.3; ms: m/z
(relative intensity) 298 [M]þ (100), 280 (40), 265 (45), 178
(40), 144 (23), 121 (321), 89 (50), 63 (15).
[17] Nematollahi, D.; Tammari, E. J Org Chem 2005, 70, 7769.
[18] Nematollahi, D.; Habibi, D.; Rahmati, M.; Rafiee, M. J Org
Chem 2004, 69, 2637.
[19] Nematollahi, D.; Afkhami, A.; Tammari, E.; Shariatmanesh,
T.; Hesari, M.; Shojaeifard, M. Chem Commun 2007, 162.
[20] Hosseiny Davarani, S. S.; Nematollahi, D.; Mashkouri
Najafi, N.; Masoumi, L.; Ramyar, S. J Org Chem 2006, 71, 2139.
[21] Nematollahi, D.; Rafiee, M. Green Chem 2005, 7, 638.
[22] Nematollahi, D.; Goodarzi, H. J Org Chem 2002, 67, 5036.
[23] Nematollahi, D.; Rafiee, M. J Electroanal Chem 2004, 566, 31.
[24] Conley, R. A.; Heindel, N. D. J Org Chem 1975, 40, 3169.
[25] Conley, R. A.; Heindel, N. D. J Chem Soc Chem Commun
1974, 733b
8,9-Dihydroxy-7-methoxy-6H-benzothieno[3,2-c][1]enzo
pyran-6-one (C16H10O5S) (4c). mp 245–248ꢀ (dec); ir (po-
tassium bromide): 3641, 3521, 3359, 2923, 2852, 1704, 1628,
1605, 1596, 1466, 1442, 1418, 1396, 1345, 1265, 1204, 1081,
1
955, 932, 890, 857, 797, 757,746 cmꢁ1; H nmr: d(300 MHz,
acetone-d6) 4.23 (s, 3H, OMe); 7.21 (s, 1H, aromatic); 7.53
(m, 2H, aromatic); 7.70 (t, 1H, aromatic); 8.11 (dd, 1H, aro-
matic); 8.80 (broad, OH, this peak observed in DMSO-d6); 13C
nmr: d (75.4 MHz, acetone-d6) 60.7 (methoxy), 100.1, 106.4,
113.2, 115.8, 117.4, 121.7, 125.1, 131.7, 137.9, 142.4, 142.5,
145.7, 153.5, 157.8, 159.0; ms: m/z (relative intensity) 314
[M]þ (100), 298(15), 281(60), 271(30), 253 (9), 189 (6), 178
(80), 138 (20), 121 (61), 63 (30), 43 (7).
4-(4,5-Dihydroxy-2-methylphenylthio)-2H-chromen-2-one
(C16H12O4S) (4d). mp 273–275ꢀ (dec); ir (potassium bro-
mide): 3344, 1686, 1600, 1546, 1519, 1445, 1414, 1344, 1320,
1270, 1187, 1158, 950, 869, 841, 824, 767, 743 cmꢁ1 1H
;
[26] Katritzky, A. R. Advances in Heterocyclic Chemistry,
Vol. 41; Academic Press: New York, 1987; p. 276.
[27] Nematollahi, D.; Rafiee, M.; Samadi-Maybodi, A. Electro-
chim Acta 2004, 49, 2495.
[28] Ryan, M. D.; Yueh, A.; Wen-Yu, C. J Electrochem Soc
1980, 127, 1489.
[29] Papouchado, L.; Petrie, G.; Adams, R. N. J Electroanal
Chem 1972, 38, 389.
[30] Papouchado, L.; Petrie, G.; Sharp, J. H.; Adams, R. N.
J Am Chem Soc 1968, 90, 5620.
nmr: d(300 MHz, DMSO-d6) 2.29 (s, 3H, methyl), 5.41 (s, 1H,
aromatic), 7.01 (s, 1H, aromatic), 7.10 (s, 1H, aromatic), 7.44
(m, 2H, aromatic), 7.69 (d, 1H, aromatic), 7.94 (d, 1H, aro-
matic), 8.5 (broad, 2H,OH); 13C nmr: d (75.4 MHz, acetone-
d6) 19.2, 107.3, 113.4, 117.2, 118.1, 118.7, 123.5, 124.2,
124.6, 132.9, 135.6, 145.0, 148.9, 152.9, 157.5, 158.5; ms: m/z
(relative intensity) 300 [M]þ (38), 272 (8), 267 (16), 178 (24),
145 (30), 121 (44), 89 (100), 77 (40), 63 (78), 39 (50).
[31] Young, T. E.; Griswold, J. R.; Hulbert, M. H. J Org Chem
1974, 39, 1980.
[32] Hsihmat, M. A.; Zayed, O. H.; Nawar, S. M. A. D.; Ahmed
A. Tetrahedron 1963, 9, 1831.
[33] Peinhardt, G.; Reppel, L. Pharmazie 1970, 25, 68.
[34] Andres, D. F.; Dietrich, U.; Laurent, E. G.; Marquet, B. S.
Tetrahedron 1997, 53, 647.
[35] Grigg, R.; Vipong, D. Tetrahedron 1989, 45, 7587.
[36] Namatollahi, D.; Azizian, J.; Sargordan-Arani, M.; Hesari,
M.; Jameh-Bozorgi, S.; Alizadeh, A.; Fotouhi, L.; Mirza, B. Chem
Pharm Bull 2008, 56, 1562.
Acknowledgments. Financial support for this work by the Iran
National Science Foundation (INSF), Tehran, Iran, is gratefully
acknowledged.
[37] Majumdar, K. C.; Ghosh S. K. Tetrahedron Lett 2002, 43, 2115.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet