Facile polyethylene glycol (PEG-400) promoted synthesis of some new heteryl (E)-styryl sulfones

Article abstract of DOI:10.3184/030823409X430176

An efficient and convenient synthesis of heteryl (E)-styryl sulfones is described. Reaction of an 3-(2-bromoacetyl)coumarin with sodium (E)-styrenesulfinates yields the corresponding styryl sulfones promoted by polyethylene glycol (PEG-400) as an efficien

Full text of DOI:10.3184/030823409X430176

JOURNAL OF CHEMICAL RESEARCH 2009
APRILꢂꢃꢌꢏꢑ±239
RESEARCH PAPER 237
Facile polyethylene glycol (PEG-400) promoted synthesis of some new
heteryl (E)-styryl sulfones
Nalajam Guravaiah and Vedula Rajeswar Rao*
Department of Chemistry, National Institute of Technology, Warangal (AP) -506 004, India
An efficient and convenient synthesis of heteryl (E)-styryl sulfones is described. Reaction of an 3-(2-
bromoacetyl)coumarin with sodium (E)-styrenesulfinates yields the corresponding styryl sulfones promoted by
polyethylene glycol (PEG-400) as an efficient reaction medium at room temperature
Keywords: 3-(2-bromoacetyl)coumarin, sodium (EꢀꢁVW\UHQHVXO¿QDWHꢂꢃ3(*ꢁꢄꢅꢅꢃDQGꢃVW\U\OꢃVXOIRQHV
The styryl sulfone moiety has been found in numerous
biologically interesting compounds. These compounds
include anticancer1-5 and inhibitors for several enzymes such
as cyclooxygenase-2 (COX-2).6 The traditional procedures
for assembling these compounds were reported from the
the same reaction was performed under DMF as solvent, for
ꢈꢃKRXUVꢃDWꢃUHÀX[HGꢃWHPSHUDWXUHꢃWKHꢃUHDFWLRQꢃ\LHOGꢃZDVꢃꢉꢉꢊꢃ
only. The addition of a small amount of water (10:2 mL)
FRXOGꢃLPSURYHꢃWKHꢃUHDFWLRQꢃHI¿FLHQF\ꢂꢃKHQFHꢃWKHꢃUHDFWLRQꢃ\LHOGꢃ
increased to 70%.
When we carried out the reaction in polyethylene glycol
(PEG-400), the formation of product was complete in
12 min in 94% yield. This is due to high polarity of solvent
DQGꢃ SUREDEO\ꢃ DOVRꢃ WKHꢃ VROXELOLW\ꢃ RIꢃ WKHꢃ VXO¿QDWHꢃ VDOWꢃ LQꢃ WKLVꢃ
solvent is high. In addition to this when the same reaction
has been carried out in solid sate with a few drops of DMF
as organic base and one equivalent K2CO3 as inorganic base
the coupling product afforded was 86% and 70% respectively.
Among the solvents tested, PEG-400 gave best result, with
the alternative solvents (entries 1–4) and solid state (entries
5–6) methods failing to improve the yield of products. These
promising results encouraged us to explore the generality of
this reaction. It was found that a variety of D-haloketones and
VXO¿QDWHVꢃZHUHꢃVXLWDEOHꢃIRUꢃWKLVꢃUHDFWLRQꢂꢃJLYLQJꢃWKHꢃGHVLUHGꢃ
products in good yields.In conclusion, we have developed a
PLOGꢂꢃLQH[SHQVLYHꢂꢃIDVWꢃDQGꢃHI¿FLHQWꢃV\QWKHVLVꢃRIꢃVW\U\OꢃVXOIRQHVꢃ
using polyethylene glycol 400 as the reaction medium.
Knoevenagel condensation of arylsulfonylacetic acid with
1, 7-11
araldehydes,
coupling of mercapto compounds with
haloketones or arylhalides followed by sulfonation, reduction
DQGꢃ¿QDOO\ꢃGHK\GUDWLRQꢃWRꢃJHWꢃVW\U\OꢃVXOIRQHVꢆ1, 12
Although the above methods are quite useful, they have
some limitations such as the isolation of intermediates, harsh
reaction conditions, longer reaction times and overall yields
are less. None of these methods are simple, nor can they be
usefully applied for the generation of functionally substituted
styryl sulfones. We need to overcome these drawbacks to
explore an alternative method. Among emerging strategies,
direct coupling of DꢁKDORNHWRQHVꢃ DQGꢃ VXO¿QLFꢃ DFLGꢃ VDOWVꢃ LQꢃ
solvents like absolute ethanol, aqueous ethanol, DMF, aqueous
DMF, phase transfer catalyst conditions were therefore
suitable for the preparation of unsaturated sulfone moiety.
2H-1-Benzopyran-2-ones are important molecules that
are well known for their biological activity and therapeutic
activities.13-16 These can also be considered as versatile
building blocks and intermediates for the synthesis of various
interesting heterocyclic systems.17-19 In view of the wide range
of biological activities exhibited by 2H-1-benzopyran-2-ones
and styryl sulfones, we became interested to synthesise these
moieties in one molecule, which are expected to enhance the
biological activity compared to simple styryl sulfones. Based
on the above observations, we now report the synthesis of
some novel heteryl styryl sulfones.
Experimental
All the reagents and solvents were pure, purchased from commercial
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23-24
otherwise stated. 3-(2-Bromoacetyl)coumarins,
styrene-E-
sulfonylchlorides25 and sodium (EꢀꢁVWU\UHQHVXO¿QDWHV26 were prepared
by literature procedure. Melting points were determined in open
capillaries with a “Cintex” melting point apparatus Mumbai, India
and were uncorrected. CHNS analysis was done by Carlo Erba EA
1108 automatic elemental analyser. The purity of the compounds was
checked by TLC plates (E.Merek, Mumbai, India), IR spectra (KBr)
were recorded on a BrukerWM-4(X) spectrometer (577 model).
1H NMR spectra were recorded on a Bruker WM-300 spectrometer
in G ppm using TMS as internal standard. Mass spectra (EI-MS) were
determined on Perkin Elmer (SCIEX API-2000, ESI) at 12.5eV.
Polyethylene glycol promoted reactions20-22 have attracted
the attention of organic chemists due to their ease of work
up, the ability to act as phase transfer catalysts and their
inexpensive and eco-friendly nature. In this connection, we
report a synthesis of some new heteryl styryl sulfones in the
SUHVHQFHꢃ RIꢃ SRO\HWK\OHQHꢃ JO\FROꢃ ꢇ3(*ꢁꢄꢅꢅꢀꢃ DVꢃ DQꢃ HI¿FLHQWꢃ
reaction medium.
General procedure for the synthesis of styryl sulfones (3a–l)
A mixture of the sodium (EꢀꢁVW\UHQHVXO¿QDWHꢃ ꢇꢋꢆꢌꢍꢃ PPROꢀꢃ DQGꢃ
3-(2-bromoacetyl)coumarin (1 mmol) was taken in 10 mL of
polyethyleneglycol, and stirred at room temperture for the appropriate
time. After completion of the reaction, as monitored by TLC, the
reaction mass was poured into water and extracted into ethyl acetate.
The organic layer was removed under reduced pressure, and the crude
product was recrystallised from acetone. The PEG was recovered
from the aqueous layer and reused without loss of activity. All the
other compounds were prepared similarly.
Results and discussion
We chose the coupling of 3-(2-bromoacetyl)coumarin with
sodium (EꢀꢁVWU\UHQHVXO¿QDWHꢃ DVꢃ PRGHOꢃ IRUꢃ H[SORULQJꢃ WKHꢃ
optimised reaction condition. It was found that if absolute
HWKDQROꢃ ZDVꢃ XVHGꢃ DORQHꢂꢃ WKHꢃ UHDFWLRQꢃ UHTXLUHVꢃ UHÀX[ꢃ
temperature for a period of eight hours to get the coupling
product in only 42% yield. This is due to the low solubility
RIꢃVXO¿QDWHꢃVDOWVꢃLQꢃRUJDQLFꢃVROYHQWVꢆꢃ,WꢃLVꢃZRUWKꢃQRWLQJꢃWKDWꢃ
the addition of a small amount of water (10:2 mL) could
LPSURYHꢃWKHꢃUHDFWLRQꢃHI¿FLHQF\ꢃWKLVꢃLVꢃSUHVXPDEO\ꢃGXHꢃWRꢃWKHꢃ
increased water solubility of sodium (EꢀꢁVWU\OVXO¿QDWHꢂꢃKHQFHꢃ
the reaction yield increased to 58%. In addition to this when
Spectral data for styryl sulfones
3-(2-(Styrenesulfonyl)acetyl)-2H-chromen-2-one (3a): Reaction time:
ꢋꢌꢃPLQꢂꢃSDOHꢃ\HOORZꢃVROLGꢂꢃ\LHOGꢃꢎꢄꢊꢂꢃPꢆSꢆꢃꢋꢏꢅ±ꢋꢏꢌ°C. IR (KBr, Jmax
cm-1): 1123, 1316 (SO2), 1606 (C=C), 1691 (C=O), 1733 (C=O of
lactone), 1H NMR (CDCl3, GꢃSSPꢀꢐꢃꢍꢆꢅꢈꢃꢇVꢂꢃꢌ+ꢂꢃ±&+2), 7.08 (d, 1H,
J = 15 Hz, SO2 H& &+ꢀꢂꢃꢑꢆꢏ±ꢑꢆꢉꢃꢇPꢂꢃꢋꢅ+ꢂꢃ$U+ꢃDQGꢃ622HC=CH),
8.58 (s, 1H, C4 of coumarin proton), 13C NMR (CDCl3 G ppm), 64.9,
116.8, 118.0, 123.1, 125.3, 125.4, 128.7, 129.0, 130.6, 131.5, 131.9,
135.4, 145.3, 149.3, 155.4, 159.2, 186.2. EI-MS 355[M + H]+. Anal.
Calcd for C19H14O5S: C, 64.40; H, 3.98; S, 9.05. Found: C, 64.47; H,
3.96; S, 9.00%.
* Correspondent. E-mail: vrajesw@yahoo.com

238 JOURNAL OF CHEMICAL RESEARCH 2009
6-Bromo-3-(2-(styrenesulfonyl)acetyl)-2H-chromen-2-one (3b):
7LPHꢐꢃꢋꢈꢃPLQꢂꢃSDOHꢃ\HOORZꢃVROLGꢂꢃ\LHOGꢃꢎꢋꢊꢂꢃPꢆSꢆꢃꢋꢑꢌ±ꢑꢄ°C. IR (KBr,
Jmax cm-1): 1137, 1357 (SO2), 1623 (C=C), 1689 (C=O), 1733 (C=O
of lactone), 1H NMR (CDCl3, GꢃSSPꢀꢐꢃꢍꢆꢋꢍꢃꢇVꢂꢃꢌ+ꢂꢃ±&+2), 7.24(d,
1H, SO2 H& &+ꢀꢂꢃꢑꢆꢏꢍ±ꢑꢆꢎꢑꢃꢇPꢂꢃꢎ+ꢂꢃ$U+ꢃDQGꢃ622HC=CH), 8.84 (s,
1H, C4 of coumarin proton), Anal. Calcd for C19H13 BrO5S: C, 52.67;
H, 3.02; S, 7.40. Found: C, 52.61; H, 3.00; S, 7.44%.
6, 8-Dibromo-3-(2-(styrenesulfonyl)acetyl)-2H-chromen-2-one (3c):
Time: 22 min, pale yellow solid, yield 90%, m.p. 180°C. IR (KBr,
Jmax cm-1): 1135, 1351 (SO2), 1601 (C=C), 1692 (C=O), 1740(C=O
of lactone), 1H NMR (CDCl3, GꢃSSPꢀꢐꢃꢄꢆꢎꢈꢃꢇVꢂꢃꢌ+ꢂꢃ±&+2), 6.95(d,
1H, J = 16 Hz SO2 H& &+ꢀꢂꢃꢑꢆꢌ±ꢑꢆꢉꢃꢇPꢂꢃꢈ+ꢂꢃ$U+ꢃDQGꢃ622HC=CH),
8.4 (s, 1H, C4 of coumarin proton), Anal. Calcd for C19H12 Br2O5S:
C, 44.56; H, 2.36; S, 6.26. Found: C, 44.52; H, 2.32; S, 6.30%.
6-Chloro-3-(2-(styrenesulfonyl)acetyl)-2H-chromen-2-one (3d):
Time: 19 min, pale yellow solid, yield 93%, m.p. 152°C. IR (KBr,
Jmax cm-1): 1128, 1322 (SO2), 1607 (C=C), 1692 (C=O), 1734 (C=O
of lactone), 1H NMR (CDCl3, Gꢃ SSPꢀꢐꢃ ꢄꢆꢈꢎꢃ ꢇVꢂꢃ ꢌ+ꢂꢃ ±&+2ꢀꢂꢃ ꢑꢆꢄꢎ±
7.56 (m, 6H, ArH and SO2H& &+ꢀꢂꢃ ꢑꢆꢑꢎ±ꢑꢆꢈꢏꢃ ꢇPꢂꢃ ꢌ+ꢂꢃ$U+ꢃ DQGꢃ
SO2HC=CHꢀꢂꢃꢈꢆꢅꢑ±ꢈꢆꢋꢌꢃꢇPꢂꢃꢌ+ꢂꢃ$U+ꢀꢃꢈꢆꢑꢈꢃꢇVꢂꢃꢋ+ꢂꢃ&4 of coumarin
proton.) Anal. Calcd for C19H13 ClO5S: C, 58.69; H, 3.37; S, 8.25.
Found: C, 58.64; H, 3.31; S, 8.20%.
6, 8-Dichloro-3-(2-(styrenesulfonyl)acetyl)-2H-chromen-2-one (3e):
7LPHꢐꢃ ꢌꢋꢃ PLQꢂꢃ SDOHꢃ \HOORZꢃ VROLGꢂꢃ \LHOGꢃ ꢎꢅꢊꢂꢃ PꢆSꢆꢃ ꢋꢉꢈ±ꢋꢑꢅ°C.
IR (KBr, Jmax cm-1): 1135, 1325 (SO2), 1623 (C=C), 1608 (C=O),
1734 (C=O of alctone), 1H NMR (CDCl3, G ppm): 4.69 (s, 2H,
±&+2ꢀꢂꢃꢑꢆꢄꢎ±ꢑꢆꢍꢏꢃꢇPꢂꢃꢍ+ꢂꢃ$U+ꢃDQGꢃ622H& &+ꢀꢂꢃꢑꢆꢑꢍ±ꢑꢆꢑꢎꢃꢇPꢂꢃꢌ+ꢂꢃ
ArH and SO2HC=CHꢀꢂꢃꢈꢆꢅꢈ±ꢈꢆꢋꢌꢃꢇPꢂꢃꢌ+ꢂꢃ$U+ꢀꢂꢃꢈꢆꢉꢋꢃꢇVꢂꢃꢋ+ꢂꢃ&4 of
coumarin proton). Anal. Calcd for C19H12Cl2O5S: C, 53.91; H, 2.86;
S, 7.58. Found: C, 53.86; H, 2.81; S, 7.54%.
3-(2-(Styrenesulfonyl)acetyl)-2H-benzo[h]chromen-2-one (3f): Time:
ꢌꢄꢃPLQꢂꢃ<HOORZꢃVROLGꢂꢃ\LHOGꢃꢈꢎꢊꢂꢃPꢆSꢆꢃꢌꢅꢉ±ꢌꢅꢈ°C. IR (KBr, Jmax cm-1):
1127, 1343 (SO2), 1609 (C=C), 1623 (C=O), 1716 (C=O of lactone)
1H NMR (CDCl3, GꢃSSPꢀꢐꢃꢄꢆꢑꢉꢃꢇVꢂꢃꢌ+ꢂꢃ±&+2ꢀꢂꢃꢑꢆꢉꢌ±ꢑꢆꢉꢈꢃꢇPꢂꢃꢉ+ꢂꢃ$U+ꢃ
and SO2HC=CH), 8.07 (d, 1H, J = 15 Hz, SO2HC=CHꢀꢂꢃꢈꢆꢏꢅ±ꢈꢆꢏꢏꢃꢇPꢂꢃ
6H, ArH), 8.6 (s, 1H, C4 coumarin proton). Anal. Calcd for C23H16O5S:
C, 68.30; H, 3.99; S, 7.93. Found: C, 68.24; H, 3.91; S, 7.89%.
3-(2-(p-Methylstyrenesulfonyl)acetyl)-2H-chromen-2-one
(3g):
7LPHꢐꢃꢋꢄꢃPLQꢂꢃSDOHꢃ\HOORZꢃVROLGꢂꢃ\LHOGꢃꢎꢏꢊꢂꢃPꢆSꢆꢃꢋꢏꢌ±ꢋꢄꢄ°C. IR (KBr,
Jmax cm-1): 1119, 1307 (SO2), 1606 (C=C), 1692 (C=O), 1725 (C=O
of lactone), 1H NMR (CDCl3, G ppm): 2.38 (s, 3H, CH3), 5.07 (s, 2H,
±&+2), 7.01 3 (d, 1H, J = 15 Hz, SO2 HC=CH), 7.54 (d, 1H, J = 15 Hz,
SO2HC=CHꢀꢂꢃꢑꢆꢋꢈ±ꢑꢆꢉꢈꢃꢇPꢂꢃꢈ+ꢂꢃ$U+ꢀꢂꢃꢈꢆꢍꢑꢃꢇVꢂꢃꢋ+ꢂꢃ&4 of coumarin
proton), 13C NMR (CDCl3 G ppm), 21.5, 65.0, 116.8, 118.0, 123.3,
124.3, 125.3, 128.7, 129.2, 129.8, 130.6, 135.2, 142.2, 145.3, 149.2,
155.4, 159.2, 186.2, EI-MS 367 [M-H]-.Anal. Calcd for C20H16O5S: C,
65.20; H, 4.38; S, 8.70. Found: C, 65.10; H, 4.30; S, 8.64%.
6-Bromo-3-(2-(p-methylstyrenesulfonyl)acetyl)-2H-chromen-2-
one (3h):ꢃ 7LPHꢐꢃ ꢋꢈꢃ PLQꢂꢃ SDOHꢃ \HOORZꢃ VROLGꢂꢃ \LHOGꢃ ꢎꢌꢊꢂꢃ PꢆSꢆꢃ ꢋꢑꢉ±
178°C. IR (KBr, Jmax cm-1): 1137, 1357 (SO2), 1606 (C=C), 1683
(C=O), 1736 (C=O of lactone), 1H NMR (CDCl3, G ppm): 2.9(s, 3H,
CH3ꢀꢂꢃꢍꢆꢋꢍꢃꢇVꢂꢃꢌ+ꢂꢃ±&+2), 7.25 (d, 1H, J = 15 Hz, SO2 HC=CH),
ꢑꢆꢏꢅ±ꢑꢆꢈꢅꢃꢇPꢂꢃꢈ+ꢂꢃ$U+ꢃDQGꢃ622HC=CH), 8.79 (s, 1H, C4 of coumarin
proton), Anal. Calcd for C20H15BrO5S: C, 53.70; H, 3.38; S, 7.17.
Found: C, 53.78; H, 3.32; S, 7.10%.
6, 8-Dibromo 3-(2-(p-methylstyrenesulfonyl)acetyl)-2H-chromen-
2-one (3i):ꢃ7LPHꢐꢃꢌꢄꢃPLQꢂꢃSDOHꢃ\HOORZꢃVROLGꢂꢃ\LHOGꢃꢎꢅꢊꢂꢃPꢆSꢆꢃꢋꢉꢈ±
170°C. IR (KBr, Jmax cm-1): 1127, 1317 (SO2), 1603 (C=C), 1691
(C=O), 1740 (C=O of lactone), 1H NMR (CDCl3, G ppm): 2.4 (s,
3H, CH3ꢀꢂꢃꢄꢆꢎꢃꢇVꢂꢃꢌ+ꢂꢃ±&+2), 7.15 (d, 1H, J = 15 Hz, SO2 HC=CH),
ꢑꢆꢏ±ꢑꢆꢍꢇPꢂꢃꢑ+ꢂꢃ$U+ꢃDQGꢃ622HC=CH), 8.4 (s, 1H, C4 of coumarin
proton), Anal. Calcd for C20H14Br2O5S: C, 45.65; H, 2.68; S, 6.09.
Found: C, 45.60; H, 2.72; S, 6.12%.
6-Chloro-3-(2-(p-methylstyrenesulfonyl)acetyl)-2H-chromen-
2-one (3j):ꢃ7LPHꢐꢃꢋꢑꢃPLQꢂꢃSDOHꢃ\HOORZꢃVROLGꢂꢃ\LHOGꢃꢎꢌꢊꢂꢃPꢆSꢆꢃꢋꢍꢉ±
157°C. IR (KBr, Jmax cm-1): 1128, 1315 (SO2), 1609 (C=C), 1690
(C=O), 1735 (C=O of lactone), 1H NMR (CDCl3, G ppm): 2.4 (s, 3H,
CH3ꢀꢂꢃꢍꢆꢅꢃꢇVꢂꢃꢌ+ꢂꢃ±&+2), 6.95(d, 1H, J = 15 Hz, SO2 H& &+ꢀꢃꢑꢆꢌ±ꢑꢆꢑꢃ
(m, 8H, ArH and SO2HC=CH), 8.4 (s, 1H, C4 of coumarin proton),
Anal. Calcd for C20H15ClO5S: C, 59.63; H, 3.75; S, 7.96. Found: C,
59.72; H, 3.79; S, 7.93%.
6, 8-Dichloro-3-(2-(p-methylstyrenesulfonyl)acetyl)-2H-chromen-
2-one (3k):ꢃ7LPHꢐꢃꢌꢌꢃPLQꢂꢃSDOHꢃ\HOORZꢃVROLGꢂꢃ\LHOGꢃꢎꢅꢊꢂꢃPꢆSꢆꢃꢋꢉꢌ±
164°C. IR (KBr, Jmax cm-1): 1127, 1317 (SO2), 1609 (C=C), 1685
(C=O), 1738 (C=O of lactone) 1H NMR (CDCl3, G ppm): 2.38 (s,
3H, CH3ꢀꢂꢃꢄꢆꢈꢍꢃꢇVꢂꢃꢌ+ꢂꢃ±&+2ꢀꢂꢃꢑꢆꢌꢅ±ꢑꢆꢄꢃꢇPꢂꢃꢈ+ꢂꢃ$U+ꢃDQGꢃHWK\OHQHꢃ
protons), 8.2 (s, 1H, C4 of coumarin proton), Anal. Calcd for
C20H14Cl2O5S: C, 54.93; H, 3.23; S, 7.33. Found: C, 54.90; H, 3.29;
S, 7.38%.
Table 1 Optimisation of reaction for the formation of 3a under
a range of condition
Entry Solvent
Time/h
Isolated
yield/%a
3-(2-(p-Methylstyrenesulfonyl)acetyl)-2H-benzo[h]chromen-2-one
(3l): Time: 27 min, yellow solid, yield 88%, m.p. 214°C. IR (KBr,
Jmax cm-1): 1130, 1313 (SO2), 1620 (C=C), 1673 (C=O), 1721 (C=O
of lactone), 1H NMR (CDCl3, G ppm): 2.40 (s, 3H, CH3), 4.9 (s, 2H,
±&+2), 7.17 (d, 1H, J = 15 Hz, SO2 H& &+ꢀꢂꢃ ꢑꢆꢌꢍ±ꢑꢆꢑꢃ ꢇPꢂꢃ ꢋꢋ+ꢂꢃ$U+ꢃ
and SO2HC=CH), 8.4 (s, 1H, C4 of coumarin proton), Anal. Calcd for
C24H18O5S: C, 68.88; H, 4.34; S, 7.66. Found: C, 68.82; H, 4.30; S, 7.61%.
1
2
3
4
5
6
7
Absolute ethanol
8
42
58
Aqueous ethanol
DMF
8
8
8
0.15
0.15
0.12
66
Aqueous DMF
70
Solid state (few drops of DMF)
Solid state (1 equiv of K2CO3)
PEG-400
86b
70b
94c
This work was supported by grants from CSIR, New Delhi
for the sanction of the project (No.01 (2062) 06/EMR-II) is
gratefully acknowledged.
aReagents and conditions: D-halo ketone (1 mmol) sodium
E-styrenesulfinate (1.25 mmol), reflux temperature in given
solvent.
Received 7 December 2008; accepted 2 February 2009
Paper 08/0325 doi: 10.3184/030823409X430176
Published online: 21 April 2009
bReaction was carried out at solid state.
cReaction was carried out at room temperture.
R1
R1
R2
O
O
O
O
O
O
R2
PEG-400
rt
O
S
O
+
R
Br
R
SO2Na
1
2
3
(g) R= R1=H, R2=CH3
(h) R=Br, R 1=H,R2=CH3
(i) R=R 1=Br, R2=CH3
(j) R=Cl, R 1=R2=CH3
(k) R=R 1=Cl, R2=CH3
(l) 7,8 benzo, R 2=CH3
(a) R= R 1= R2= H
(b) R=Br, R 1
=R2=H
(c) R=R 1=Br, R2=H
(d) R=Cl, R 1
=R2=H
(e) R=R 1=Cl, R2=H
(f) 7,8 benzo, R 2=H
Scheme 1

JOURNAL OF CHEMICAL RESEARCH 2009 239
13 R. O' Kennedy and R.D. Thomas, Coumarins: biology, application, and
mode of action; Wiley, Chichester, U K, 1997.
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