Reaction of dimethyl sulfoxide-acetic anhydride with 4-hydroxy-coumarin, its derivatives under microwave conditions

Article abstract of DOI:10.14233/ajchem.2013.13483

4-Hydroxycoumarin and various biscoumarins synthesized under microwave conditions were treated with the DMSO-Ac2O reagent under the same conditions to yield different products. A comparative account of the reactions with conventional procedure, as reporte

Full text of DOI:10.14233/ajchem.2013.13483

Asian Journal of Chemistry; Vol. 25, No. 6 (2013), 3019-3022
http://dx.doi.org/10.14233/ajchem.2013.13483
Reaction of Dimethyl Sulfoxide-Acetic Anhydride with
4-Hydroxy-coumarin and Its Derivatives Under Microwave Conditions
1,*
1
2
SAIMA QADIR , KHALIQUZ ZAMAN KHAN and ARIF JAN
1Department of Chemistry, University of Kashmir, Hazratbal, Srinagar-190 006, India
2Biotechnology Division, Indian Institute of Integrative Medicine, Sanatnagar, Srinagar-190 005, India
*Corresponding author: E-mail: saimaqadir@rediffmail.com
(Received: 20 January 2012;
Accepted: 10 December 2012)
AJC-12510
4-Hydroxycoumarin and various biscoumarins synthesized under microwave conditions were treated with the DMSO-Ac2O reagent
under the same conditions to yield different products. A comparative account of the reactions with conventional procedure, as reported in
literature, has been drawn and improved yields have been obtained in minimum time under microwave conditions for the first time.
Key Words: Biscoumarins, Dimethyl sulfoxide, Acetic anhydride, Microwave irradiation.
measured in chloroform (spectral grade) on a Shimadzu UV-
1650PC UV/Visible spectrophotometer. 1H NMR spectra were
recorded on a 200 MHz instrument using CDCl3 as the solvent
and TMS as the internal standard.All the solvents and chemicals
used were of AR grade and 4-hydroxycoumarin, in particular,
was spectrochemical grade. All the reactions were irradiated
in a multimode Sharp CarouselTM microwave oven at medium-
hi power. The products formed have been identified by a
comparison of their spectra with those reported in literature
wherever possible. Physical properties also agree well in
accordance with the data reported in literature6.
INTRODUCTION
Dimethyl sulfoxide initially used as a dipolar aprotic
solvent especially in kinetic studies has found extensive use
in synthetic organic chemistry over the years. Kornblum et al.1
first used it to bring about the oxidation of allylic halides and
alcohols1. Subsequent use of sulfoxonium yield as a source of
methylene in the preparation of oxiranes and cyclopropanes
by Corey and co-workers2,3 opened a new area of DMSO
chemistry4.
Dimethyl sulfoxide has been used as an oxidizing agent
as such in combination with electrophillic activators like
acetic anhydride, a variety of reactions have been reported4,5.
4-Hydroxycoumarin (1a) and derivatives have been reported
to react with DMSO/Ac2O under varying conditions of tempe-
rature to yield a range of products (Scheme-I)6. Prior heating
of the reagent has been reported to modify the property of the
reagent to yield different products with 4-hydroxycoumarin
derivatives. In some cases, either an oxidative rearrangement
takes place or the formation of sulfonium yields6.
Dimethyl sulfoxide was dried according to the standard
procedure. In all the reactions, a 2:1 v/v ratio of DMSO-Ac2O
OH
OAc
O
O
O
DMSO-Ac2
O
DMSO-Ac2
O
_
room temp.
Reflux temp
+
O
O
O
O
SMe2
3k
1a
3j
DMSO-Ac2
O
DMSO-Ac2
Preheated
O
However, the reaction conditions are time consuming and
tedious either requiring days at room temperature or hours of
reflux at higher temperatures6. It was worth doing them under
microwave conditions.
Reflux 24hrs
OH
O
OH
O
O
OH
O
DMSO-Ac2
Reflux
O
EXPERIMENTAL
O
O
O
Melting points were taken in open capillaries using the
electrothermal method on a Labotech/Perfit instrument and
are uncorrected. Infrared spectra were recorded on a Perkin
Elmer 2000-FT spectrometer. Ultraviolet spectra were
O
2a
3a
Scheme-I: Reaction of 4-hydroxycoumarin with DMSO/Ac2O to yield
different products

3020 Qadir et al.
Asian J. Chem.
was used. The irradiations were carried out at intervals of one
minute irradiation. Reaction mixtures were taken in a 50 mL
Erlenmeyer flasks covered with a cotton plug to avoid moisture.
TLC monitoring of the reactions established the completion
of reaction or the point of no further progress. The products
precipitated out from the reaction mixture were filtered and
washed thoroughly with distilled water to remove any DMSO/
Ac2O, dried and crystallized from appropriate solvent. The
mother liquor was extracted with diethyl ether and chromato-
graphed using the appropriate solvent system (chloroform:
petroleum ether) 50/50 (v/v) to afford further amount of the
products.
1729.9, 1718.0, 1654.0, 1611.1, 1511.9; MS (m/z): 424 (ESI);
m.p. 287-88 ºC.
Spectral data of 3-dimethylsulphuranylidenechroman-
1
2,4-dione-(3j): H NMR (200 MHz, CDCl3): δ 3.2, 6H, s;
S+(CH3); 7.2-8.1, 4H, (Ar-CH). IR (KBr, νmax, cm-1): 1674.8,
1612, 1598.2, 1556.3, 1358.9, 1291.8, 765.8; MS (m/z): 221.8
(ESI); m.p. 190 ºC.
Spectral data of 4-acetoxy-1H-benzopyran-2-one-
(3k): IR (KBr, νmax, cm-1): 1768.1, 1728.3, 1608.6, 1198.2,
1175.5, 1138.6; Mp 110-112 ºC.
RESULTS AND DISCUSSION
Various dicoumarols synthesized under microwave
conditions7 were treated with the DMSO-Ac2O reagent under
the same conditions and improved yields of the products were
obtained in contrast to the classical procedure (Schemes II-
IV). The advantage of the synthesis is that the reaction time
has also considerably shortened from hours to a few minutes
(Table-1a,b). The product in all the cases crystallized out of
the reaction mixture and the residue on ether-aqueous workup
followed by chromatographic purification yielded further of
the product. This synthetic conversion of dicoumarols to various
derivatives under microwave conditions is much more efficient,
time saving and high yielding than the conventional procedure.
The mechanism of product formation has been shown in
SchemesV-VII. Dimethylsulfoxide being a polar solvent may
contradict the increased rate of reaction because of its interaction
with the microwaves8-10. But the same interaction may have
led to a rapid increase in the temperature of reaction mixture
on microwave exposure.Additionally, factors like superheating
effect8, effects according to reaction mechanism9,10, may also
contribute to increase in reaction rates.
Spectral data of compounds 3a-k
Spectral data of 2, 3-dihydro-2-(2-hydroxybenzoyl)-
1
4H-furo[3,2c][1]benzopyran-4-one-(3a): H NMR (200
MHz, CDCl3): δ 6.35, IH, q, (O = C-CH-O-); δ 6.9-7.8, 8H,
m, (8 ×ArCH); δ 3.6, 2H, m, (-CH-CH2-); δ 11.7, 1H, s, (OH).
IR (KBr, νmax, cm-1): 1717.6, 1707.2, 1649.4; MS (m/z): 307.9
(ESI); m.p. 210-212 ºC; λmax, nm(MeOH): 214, 255, 312, 326.
Spectral data of 7-phenyl-7H-bis-[1]benzopyrano[4,3-
b: 3',4'-c]pyran-6,8-dione-(3b): 1H NMR (200 MHz, CDCl3):
δ 5.2, IH, s, (C6H5-CH). IR (KBr, νmax, cm-1): 1718.1, 1666.3,
1608.8, 1364.9; MS (m/z): 394(ESI); m.p. 320 ºC.
Spectral data of 7-(2-chlorophenyl)-7H-bis-[1]benzo-
1
pyrano[4,3-b:3',4'-c]pyran-6,8-dione-(3c): H NMR (200
MHz, CDCl3): δ 5.2, IH, s, (CH); δ 7-8, 12H, m, (12 × CH). IR
(KBr, νmax, cm-1): 1743.6, 1726.8, 1611.3, 1459.8, 753.7; MS
(m/z): 428 (ESI); m.p. 274-277 ºC.
Spectral data of 7-(3-chlorophenyl)-7H-bis-[1]benzo-
1
pyrano[4,3-b:3',4'-c]pyran-6,8-dione-(3d): H NMR (200
MHz, CDCl3): δ 5.2, IH, s, (CH), δ 7.1-8.2, 12H, m, (12 ×
CH). IR (KBr, νmax, cm-1): 1727.6, 1651.8, 1629.1, 1610.3,
1602.0, 1367.1, 1111.6, 756.7; MS (m/z): 428 (ESI); m.p. 245-
48 ºC.
OAc
OH
O
_
S(CH3)2
+
DMSO-Ac2O
MW
Spectral data of 7-(4-chlorophenyl)-7H-bis-[1]benzo-
1
pyrano[4,3-b:3',4'-c]pyran-6,8-dione-(3e): H NMR (200
+
O
O
O
O
O
O
3k
1a
3j
MHz, CDCl3): δ 5.2, IH, s, (CH), δ 7.25-8.2, 12H, m, (12 ×
CH). IR (KBr, νmax, cm-1): 1728.8, 1714.3, 1667.8, 1611.7;
MS (m/z): 427.9 (ESI); m.p. 330 ºC.
Scheme-II: Microwave-assisted reaction of 4-hydroxycoumarin with dimethyl
sulfoxide-acetic anhydride to yield the acetate (3k) and ylide (3j)
O
Spectral data of 7-(2-nitrophenyl)-7H-bis-[1]benzo-
1
pyrano[4,3-b: 3',4'-c]pyran-6,8-dione-(3f): H NMR (200
OH
OH
OH
O
DMSO-Ac2O
MW
MHz, CDCl3): δ 6.1, IH, s, (CH), δ 7.5-8.5, 12H, m, (12 ×
CH). IR (KBr, νmax, cm-1): 1724.0, 1666.1, 1610.4, 1529.8,
1364.8; MS(m/z): 439 (ESI); m.p. 302 ºC.
O
O
O
O
O
O
2a
3a
Scheme-III: Microwave-assisted transformation of dicoumarol into
dihydrofurocoumarin using dimethyl sulfoxide-acetic anhydride
mixture
Spectral data of 7-(3-nitrophenyl)-7H-bis-[1]benzo-
pyrano[4,3-b: 3',4'-c]pyran- 6,8-dione-(3g): 1H NMR (200
MHz, CDCl3): δ 6.3, IH, s, (CH), δ 6.9-8.3, 12H, m, (12 ×
CH). IR (KBr, νmax, cm-1): 1717.4, 1648.6, 1607.9, 1530.8,
1351.4; MS (m/z): 439 (ESI); m.p. 218 ºC.
R
OH
OH
O
O
DMSO-Ac2
MW
O
Spectral data of 7-(4-nitrophenyl)-7H-bis-[1]benzo-
pyrano[4,3-b: 3',4'-c]pyran-6, 8-dione-(3h): 1H NMR (200
MHz, CDCl3): δ 5.3, IH, s, (CH), δ 7.3-8.3, 12H, m, (12 ×
CH). IR (KBr, νmax, cm-1): 1720, 1650.6, 1607.9, 1531.8,
1355.4; MS(m/z): 438.9 (ESI); m.p. 314 ºC.
R
O
O
O
O
O
O
O
1b-i
Spectral data of 7-(4-methoxyphenyl)-7H-bis-
1
[1]benzopyrano[4,3-b:3',4'-c]pyran-6,8-dione-(3i): H
2b-i
Scheme-IV: Microwave-assisted reaction of substituted biscoumarins with
dimethyl sulfoxide-acetic anhydride mixture to give products
arising out of oxidative rearrangement and cyclisation
NMR (200 MHz, CDCl3): δ 7.25, IH, s, (CH); δ 7.5-7.7, 12H,
m, (12 × CH); δ 3.9, 3H, s, (OCH3). IR (KBr, νmax, cm-1):

Vol. 25, No. 6 (2013)
Reaction of Dimethyl Sulfoxide-Acetic Anhydride with 4-Hydroxy-coumarin and Its Derivatives 3021
TABLE-1a
SYNTHESIS OF DERIVATIVES FROM VARIOUS DICOUMAROLS AND 4-HYDROXYCOUMARIN
UNDER MICROWAVE IRRADIATION (ERROR 2)
Dicoumarol (mmol)
2a - 6.0
DMSO/AC2O v/v ratio (mL)
TimeMW (min)
R
Product
3a
Yield (%)
Lit. data*
20 %-10 h
13 %-6 h
12:6
10:5
6:3
4
2
1
5
1
4
2
6
3
H
66
66
81
65
69
62
64
63
64
C6H5
2b - 7.3
3b
2ClC6H4
3ClC6H4
4ClC6H4
2NO2C6H4
3NO2C6H4
4NO2C6H4
4CH3OC6H4
61 %-11 h
33 %-8 h
2c - 6.7
3c
4:2
2d - 6.7
3d
6:3
58 %-20 min
10 %-5.5 h
42 %-9 h
2e - 6.7
3e
10:5
6:3
2f - 4.4
3f
2g - 4.4
3g
8:4
26 %-1 h
2h - 2.2
3h
4:2
28 %-1.5 h
2i - 6.8
3i
*[6-9]
TABLE-1b
MICROWAVE-ASSISTED REACTION OF 4-HYDROXYCOUMARIN WITH DMSO-Ac2O MIXTURE (ERROR 2)
4-Hydroxycoumarin (mmol) DMSO/Ac2O mixture (mL) 2:1 v/v ratio
1a - 6.2
TimeMW (min)
4
Product
3j
Yield (%)
Lit. data*
63
2
120 ºC, 5 h, 75 %
110 ºC, 15 %, 5 h
3
3k
*[6]
In order to achieve the microwave-assisted synthetic
conversion, 4-hydroxycoumarin and DMSO-Ac2O were
subjected to microwave irradiation in the corresponding
amounts as shown in Table-1b. 4-Hydroxycoumarin yields a
variety of products with the reagent under different tempe-
ratures (Scheme-I). At room temperature, its acetate (3k) is
obtained. The same was obtained when performed under
microwave irradiation at medium power. But when power level
was increased, its ylide (3j) was the major product along with
minor amounts of the acetate. The mechanism of the formation
of these products has been shown in Scheme-IV. The same
products have been obtained when 4-hydoxycoumarin reacts
with DMSO-Ac2O at 120 ºC6.
is converted to oxosulphonium salt (Y) on treatment with
DMSO/Ac2O.At higher temperature, it cyclizes with the elimi-
nation of dimethyl sulfoxide. At room temperature, though,
only the spiran (Z) is reported to be formed (Scheme-VIII)6.
Since the reaction was carried out under microwave conditions,
no spiran was formed in this case.
Me2S+
OH
O
OH
O
O
O
O
Me2S+OAc
-AcOH
O
O
O
O
O-H
2a
It is observed that majority of the products have very high
melting points as compared with the starting biscoumarins.
This may be due to greater magnitude of Vander Waals forces
due to high molecular weights. Moreover, decrease in yield in
spite of the microwave conditions may be attributed to losses
during isolation, chromatography and crystallization.
O
O
O
O
O
O
H2O:
O
O
- CO2
OH
O
O
3a
Scheme-VI: Mechanism of dihydrofurocoumarin formation from the reaction
of dicoumarol with dimethyl sulfoxide-acetic anhydride
OH
O-Ac
Me2S+OAc
Me2S+O-
Me2S+
_
OAc
O
O
R
R
O
OH
O
O
O
O
OH
O
OH
O
1a
Me2S+OAc
3k
O
O
O
O
O
2b-i
O
+SMe2
H
+SMe2
AcO-
-
or
O
O
O
O
O
O
O
Me2S+
3j
O
O
R
O
O
Scheme-V: Mechanism of ylide formation from 4-hydroxycoumarin using
dimethyl sulfoxide-acetic anhydride as the reagent
R
O
- Me2SO
O
O-H
O
Table-1a shows the relative amounts of the biscoumarins
and DMSO/Ac2O mixture taken in each case. The relative
amounts of DMSO/Ac2O vary with the biscoumarin taken
because of different nature of the reactants as well as to their
solubility to some extent in the reagent. The coumarin hydroxyl
3b-i
Y
Scheme-VII: Mechanism of the formation of different benzopyranopyrans
from the microwave-assisted reaction of dimethylsulfoxide-acetic
anhydride mixture with substituted dicoumarols

3022 Qadir et al.
Asian J. Chem.
Me2S+
ACKNOWLEDGEMENTS
R
R
OH
O
O
O
OH
O
OH
Me2S+OAc
The authors are grateful to the Head, Department of Chemistry,
University of Kashmir, Srinagar, for providing the necessary
facilities.
O
O
O
O
O
2b-i
or
REFERENCES
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4113 (1959).
Me2S+
O
R
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Gaylord Chemical Corporation P.O. Box 1209 Slidell, LA 70459-1209
(985) 649-5464, 1-110 and references cited therein.
O
O
O
O
O
O
O
O
O-H
O
R
Z
Y
5. Y. Hayashi and R. Oda, J. Org. Chem., 32, 457 (1967).
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Scheme-VIII: Mechanism of formation of spiran derivative from the reaction
of substituted biscoumarin with dimethyl sulfoxide at room
temperature
7. S. Qadir, A.A. Dar and K.Z. Khan, Synth. Commun., 38, 3490 (2008).
8. D.R. Baghurst and D.M.P. Mingos, J. Chem. Soc., Chem. Commun.,
674 (1992).
Conclusion
Dimethyl sulfoxide activated by acetic anhydride reacts
with 4-hydroxycoumarin and various biscoumarins under micro-
wave conditions to yield a variety of products. The synthesis
is achieved in minimum time and the products obtained have
tremendous pharmacological potential.
9. A. Hoz, A.D. Ortiz and A. Moreno, Chem. Soc. Rev., 34, 164 (2005).
10. N. Kuhnert, Angew. Chem. Int. Ed., 41, 1863 (2002).