Reaction of dimethyl sulfoxide with 4-acyloxycoumarins

Article abstract of DOI:10.1080/00397910902906560

Dimethyl sulfoxide converts 4-acetoxycoumarin (1) exclusively to 2-(2-hydroxybenzoyl)-2-[(methylthio)methyl]-2,3-dihydro-4H-furo[3,2-c] chromen-4-one (3) at 180°C under a nitrogen atmosphere, but in the absence of nitrogen, the products obtained are dicou

Full text of DOI:10.1080/00397910902906560

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Reaction of Dimethyl Sulfoxide
with 4-Acyloxycoumarins
Tabassum Ara a , Khaliquz Zaman Khan b & Khalida
Tasneem c
a Department of Chemistry, National Institute of
Technology, Srinagar, India
b Department of Chemistry, University of Kashmir,
Srinagar, India
c Department of Chemistry, Northeastern Regional
Institute of Science and Technology, Nirjuli, India
Version of record first published: 12 Nov 2009.
To cite this article: Tabassum Ara, Khaliquz Zaman Khan & Khalida Tasneem (2009):
Reaction of Dimethyl Sulfoxide with 4-Acyloxycoumarins, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry,
39:24, 4416-4422
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Synthetic Communications1, 39: 4416–4422, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902906560
Reaction of Dimethyl Sulfoxide with
4-Acyloxycoumarins
Tabassum Ara,1 Khaliquz Zaman Khan,2 and Khalida Tasneem3
1Department of Chemistry, National Institute of Technology,
Srinagar, India
2Department of Chemistry, University of Kashmir, Srinagar, India
3Department of Chemistry, Northeastern Regional Institute of Science and
Technology, Nirjuli, India
Abstract: Dimethyl sulfoxide converts 4-acetoxycoumarin (1) exclusively to 2-(2-
hydroxybenzoyl)-2-[(methylthio)methyl]-2,3-dihydro-4 H-furo[3,2-c]chromen-4-
one (3) at 180ꢀC under a nitrogen atmosphere, but in the absence of nitrogen,
the products obtained are dicoumarol and its dehydrative cyclization products
7 H-bis[1]benzopyrano[4,3-b: 30,40-c]pyran-6,8-dione (9) and (3). Under similar
conditions, 4-benzoyloxycoumarin (1a) affords benzoic acid, 4-hydroxy-
3-({2-[(methylthio)methyl]-3-oxo-2,3-dihydro-1-benzofuran-2-yl}methyl)-2H-
chromen-2-one (7), and 3-(2-hydroxybenzoyl)-3,4-dihydro-2H,5H-pyrano[2,3-b]
chromen-5-one (8).
Keywords: 4-Acetoxycoumarin, 4-benzoyloxycoumarin, DMSO
INTRODUCTION
Dimethyl sulfoxide (DMSO) activated by acetic anhydride brings about a
range of transformations in 4-hydroxycoumarins and dicoumarols under
varying conditions, whereas DMSO alone has been found to convert
4-acetoxycoumarin (1) into sulphur ylide (2) almost quantitatively at
120ꢀC.[1,2] Because these reactions are temperature dependent, it was
Received December 6, 2008.
Address correspondence to Tabassum Ara, Department of Chemistry,
National Institute of Technology, Srinagar 190006, J&K, India. E-mail:
saithfb7@rediffmail.com
4416

Dimethyl Sulfoxide with 4-Acyloxycoumarins
4417
worth investigating the interaction of 4-acyloxycoumarins with DMSO
at elevated temperatures.
RESULTS AND DISCUSSION
4-Acetoxycoumarin was prepared easily by the method of Korte and
coworkers.[3] When it was treated with dry DMSO at about 180ꢀC under
nitrogen atmosphere, it did not undergo the expected Fries rearrange-
ment to give 3-acetyl-4-hydroxycoumarin or the ylide (2). However, it
exclusively afforded a new compound, which was structurally evaluated
and whose molecular formula was found to be C20H16O5S. The PMR
spectrum of the compound shows the presence of a methylthiomethoxy
group (methylene-S protons at d3.05 and S-methyl protons at d2.05).
The rest of the protons showed chemical shift values compatible with
structure (3). The infrared (IR) spectrum showed absorption for carbonyl
groups at 1720 and 1670 cmꢁ1, and the mass spectrum (MS) exhibited a
peak at the greatest m=z value, 320, which could arise through facile loss
of the MeSH group from the molecular ion, apart from expected
fragments at m=z 307 arising through loss of –CH2SMe group. These
are in conformity with the structure (3) assigned for the compound.
The formation of (3) must have occurred through intermediacy of dicou-
marol, formation of which 4-acyloxycoumarin can be accounted for as
per the reaction sequence depicted in Scheme 1. One of the coumarin
rings of the dicoumarol then gets destabilized by undergoing methylthio-
methylation at C-3, and the resulting intermediate (4) suffers hydrolysis
and decarboxylation under the reaction conditions to give a ketone (5).
The ketone then undergoes oxidative phenolic coupling to give com-
pound (3) (route A, Scheme 2). As evident from the sequence of reactions
taking place and mentioned in Schemes 1 and 2, the only available species
reacting with 4-hydroxycoumarins and dicoumarol is CH2 ¼ Sþ ꢁ Me,
and therefore formation of (3) and (6), from this reaction only, can be
easily justified.
When carried out at 140ꢀC and without nitrogen atmosphere, the
same reaction proved destructive, but chromatography of the reaction
mixture afforded compound 3, dicoumarol, and dehydrative cyclization
product of the latter (9). This confirms initial formation of dicoumarol
in this reaction, which in the presence of traces of (CH3)2þSOAc
undergoes dehydrative cylization to give (9) (Scheme 2).
The course of the reaction slightly changed when 4-benzoyloxycou-
marin (1a) was treated with DMSO at 150ꢀC. Chromatography of the
reaction mixture afforded the expected benzoic acid as the major com-
pound. The oxosulfonium species (6) in this case underwent cylization

4418
T. Ara, K. Z. Khan, and K. Tasneem
Scheme 1. Mechanism of formation of dicoumarol from (1) and (1a).

Dimethyl Sulfoxide with 4-Acyloxycoumarins
4419
Scheme 2. Mechanism for the formation of (3) and (9) from (1), (7), and (8)
from (1a).
involving phenolic hydroxyl, apparently because of the presence of
PhCOOꢁ, to yield a coumaranone derivative (7), an isomer of (3), as
the second major product of the reaction. The difference between (3)
and (7) lies in the PMR spectrum. The methylene protons in (3) as AB
doublets at d3.28 are being replaced by a singlet at d3.23 in (7) in which

4420
T. Ara, K. Z. Khan, and K. Tasneem
they are nonequivalent. The IR spectrum, showing coumaranone and lac-
tone carbonyls at 1720 and 1700 cmꢁ1, respectively, is devoid of the –OH
stretching band. The third compound from this reaction, a minor one,
was identified as 2-hydroxybenzoyl-pyranobenzopyran (8), formation
of which can be accounted for from the cyclization involving the hydro-
xyl group at C-2 of lactone ring and methylene of methylthiomethyl
group at elevated temperatures in DMSO accompanied by elimination
of thiomethanol (Scheme 2). Such a cyclization has been achieved very
successfully during conversion of 3-phenyl-4-hydroxycoumarin to isofla-
vonone.[2] The structure for the compound is well supported by its IR,
NMR, and mass spectra. Though the fine aliphatic protons in the
PMR spectrum in the region of 2.86–4.60 are not well resolved, the IR
spectrum showing broad carbonyl bands at 1685 cmꢁ1 and mass
spectrum showing Mþ at 322 and fairly stronger peaks at m=z 174 and
147 are in full agreement with this structure.
EXPERIMENTAL
Reaction of 4-Acetoxycoumarin with DMSO
At 180ꢀC Under Nitrogen
4-Acetoxycoumarin (750 mg) in DMSO (10 ml) was refluxed under a nitro-
gen atmosphere for 3 h, cooled, and poured into cold water. The oily and
turbid material that separated out was extracted with ether. The ethereal
layer was washed thoroughly with water and dried over anhydrous sodium
sulfate, and the solvent was removed. The solid mass thus obtained
afforded pale yellow crystalline material upon crystallization from
benzene–petroleum ether and was characterized as 2-(2-hydroxybenzoyl)-
2-[(methylthio)methyl]-2,3-dihydro-4 H-furo[3,2-c]chromen-4-one (3).
At 140ꢀC
4-Acetoxycoumarin (2 g) was heated with DMSO (18 ml) at 140ꢀC for
10 h. The reaction mixture was cooled, poured over cold water, and then
extracted with ethyl acetate. The organic layer was separated with water
and dried over sodium sulfate, and the solvent was removed. Chromato-
graphy of the residue over silica gel afforded three pure compounds,
which were characterized as 2-(2-hydroxybenzoyl)-2-[(methylthio)
methyl]-2,3-dihydro-4H-furo[3,2-c]chromen-4-one (3) (yield 84 mg),

Dimethyl Sulfoxide with 4-Acyloxycoumarins
4421
dicoumarol[yield 28 mg, mp 284–85ꢀC (decomposition)] and 7 H-bis[1]
benzopyrano[4,3-b:30,40-c]pyran-6,8-dione (9). Identity of the dicoumarol
was established through direct comparison with an authentic sample.
Data
2-(2-Hydroxybenzoyl)-2-[(methylthio)methyl]-2,3-dihydro-4H-
furo[3,2-c]chromen-4-one (3)
Yield 500 mg, mp 204ꢀC. k max (MeOH) 245 and 315 nm. IR (KBr):
1
1720, 1670, 1635, 1615 cmꢁ1. H NMR (CDCl3, 90 MHz): d 8.80 (1 H,
s, OH), 7.1–7.9 (8H, m, ArH), 3.28 (2 H, q, CꢁCH2ꢁC), 3.05 (2 H, s,
ꢁCH2Sꢁ), 2.05 (3H, s, ꢁSCH3). m=z: 368 (Mþ missing), 320 (base peak,
307, 346, 187, 174, 147, 146, 121, and 120. Found C, 64.82; H, 4.45.
C20H16O5S requires C, 65.21; H, 4.34%.
7H-Bis[1]benzopyrano[4,3-b:30,40-c]pyran-6,8-dione (9)
Yield 17 mg, mp 285–310ꢀC (decomp). IR (KBr): 1390, 1675, 1725, and
3420 cmꢁ1 1H NMR (CDCl3–DMSO-d6, 400 MHz): d7.4–8.1 (ArH),
.
3.6 (2 H, s, ꢁCH2ꢁ). m=z: 18 (Mþ), 289, 62, 149, 121, and 83.
Reaction of 4-Benzoyloxycoumarin with DMSO
4-Benzoyloxycoumarin (3.2 g) was heated in DMSO at 150ꢀC for 10 h.
The reaction mixture was cooled and diluted with water. The resulting
turbid solution was extracted with ethyl acetate, the organic layer was
washed with water and dried over anhydrous sodium sulfate, and
the solvent was removed. The oily residue obtained was subjected to
chromatography over silica gel. Elution with benzene–ethyl acetate
afforded three products. The first was benzoic acid (mp 116–117ꢀC,
yield 1.08 g), the identity of which was confirmed through direct compar-
ison with an authentic sample. The second compound, crystallized
from benzene, was identified as 4-hydroxy-3-({2-[(methylthio)methyl]-
3-oxo-2,3-dihydro-1-benzofuran-2-yl}methyl)-2 H-chromen-2-one
(7).
The third compound also crystallized from benzene was identified as
3-(2-hydroxybenzoyl)-3,4-dihydro-2 H,5 H-pyrano[2,3-b]chromen-5-
one (8).

4422
T. Ara, K. Z. Khan, and K. Tasneem
Data
4-Hydroxy-3-({2-[(methylthio)methyl]-3-oxo-2,3-dihydro-1-
benzofuran-2-yl}methyl)-2H-chromen-2-one (7)
Yield 0.2 g, mp 195–196ꢀC. IR (KBr): 735, 1610–1620, 1670, 1700–1720,
1
2320 and 3150 cmꢁ1. H NMR (DMSO-d6, CFT-20) d 7.1–8 (8 H, m,
ArH and OH), 3.23 (2 H, s, ꢁCH2ꢁ), 3.15 (2 H, s, ꢁCH2Sꢁ), 2.02
(3 H, s, ꢁSCH3ꢁ). m=z: 321 (Mþ), 178, 159, 147, 121, 105, 91, and 78.
3-(2-Hydroxybenzoyl)-3,4-dihydro-2H,5 H-pyrano[2,3-b]
chromen-5-one (8)
Yield 0.18 g, mp 152ꢀC, IR (KBr): 740, 1610, 1680 (broad), and 3400
1
cmꢁ1. H NMR (CDCl3, CFT-20): d 6.8–8.28 (8 H, m, ArH), 2.86–4.60
(5 aliphatic protons). m=z: 322 (Mþ), 321, 174, 169, 147, 121, 105, 92,
77, and 61.
REFERENCES
1. Khan, K. Z.; Minhaj, N.; Tasneem, K.; Zaman, A.; Dean, F. M. The reaction
of DMSO and acetic anhydride with 4-hydroxycoumarin and dicoumarol.
J. Chem. Soc., Perkin Trans. 1 1983, 4, 841.
2. Khan, K. Z.; Tasneem, K.; Rehman, M.; Prakash, S: Zaman, A. Reaction of
DMSO and acetic anhydride with 3-substituted 4-hydroxycoumarin. Indian J.
Chem. Sect. B 1985, 24B, 42–46.
3. Matzat, N.; Wamhoff, H.; Korte, F. Acyl-lactone rearrangement: Mechanism
of acyl rearrangement in 4-acetoxycoumarin. Chem. Ber. 1969, 102, 3122.