Reaction of coumarin derivatives with nucleophiles in aqueous medium

Article abstract of DOI:10.1515/znb-2008-0110

A series of heterocycles was synthesized by the reaction of α, β-unsaturated ketones of benzopyrans or coumarins with various nucleophiles in aqueous medium bearing two points of diversity. Compared to an identical library generated by conventional parall

Full text of DOI:10.1515/znb-2008-0110

Reaction of Coumarin Derivatives with Nucleophiles in
Aqueous Medium
Mazaahir Kidwai, Priya, and Shweta Rastogi
Green Chemistry Research Laboratory, Department of Chemistry, University of Delhi, Delhi-110007,
India
Reprint requests to Prof. M. Kidwai. Fax: (+91-11) 27666235. E-mail: kidwai.chemistry@gmail.com
Z. Naturforsch. 2008, 63b, 71 – 76; received July 29, 2007
A series of heterocycles was synthesized by the reaction of α,β-unsaturated ketones of benzo-
pyrans or coumarins with various nucleophiles in aqueous medium bearing two points of diver-
sity. Compared to an identical library generated by conventional parallel synthesis, a microwave-
assisted procedure dramatically decreased reaction times from hours to minutes, and yields of
products and intermediates were improved remarkably. This synthetic approach is ecofriendly in
nature which features water as solvent, microwave irradiation, and usage of a “green” catalyst
(K2CO3).
Key words: Aqueous Medium, Potassium Carbonate, Microwave Irradiation (MWI), Nucleophiles,
4-Hydroxycoumarin
Introduction
ates for dyes, pesticides as well as in perfume formu-
lations and in enzymoloy as biological probes [8 – 11].
Fusion of coumarin to pyrimidine/isoxazole/pyrazole
rings to form polycyclic fused compounds may re-
sult in enhanced pharmaceutical efficiency. Isoxazoles,
for example, are important intermediates in the syn-
thesis of natural products, and pyrazoles are impor-
tant ligands in organometallic chemistry, and some of
these compounds are used as components of drugs,
herbicides and fungicides [12– 15]. Some of the ma-
jor advances in chemistry, especially industrial chem-
istry, over the past generation have been in the area of
catalysis. Through the use of catalysts, chemists have
found ways of removing the need for large quantities
of reagent that would otherwise have been required for
chemical transformations and would ultimately have
contributed to the waste stream. The use of K2CO3 as
a catalyst [16] obviates the use of an organic base and
also easily gets washed away with water which con-
tributes to the purity of the product.
In recent years the combination of two prominent
green chemistry principles, “microwaves” and “water”,
has become very popular and received substantial in-
terest due to work of Leadbeater [1] and others [2]
who demonstrated that a great variety of synthetic or-
ganic transformations, in particular transition metal-
catalyzed processes can be carried out very efficiently
and rapidly under these environmentally benign condi-
tions. The use of water as a solvent for organic trans-
formations offers several environmental benefits, and
significant rate enhancements are observed in water
compared to organic solvents [3 – 5]. This acceleration
has been attributed to many factors, including the hy-
drophobic effect, enhanced hydrogen bonding in the
transition state and the cohesive energy and the den-
sity of water [6 – 7]. The product isolation may also be
facilitated by simple phase separation rather than en-
ergy intensive and organic-emitting processes involv-
ing distillation of organic solvents. Thus, the devel-
opment of an efficient synthetic methodology to form
carbon-heteroatom bonds in aqueous media appears to
be attractive.
Motivated by the aforementioned advantages of
water-mediated reactions and in continuation of our
enduring studies on versatile therapeutically impor-
tant heterocycles [17], 1-benzopyran-2-one was em-
ployed as an addendum in Aldol condensation reac-
tions for investigating the synthesis of pyrazole, isoxa-
zole and pyrimidine derivatives of arylidenechromane-
diones.
Coumarin or [1]benzopyran-2[H]-one is an impor-
tant heterocyclic scaffold in the field of medicinal
chemistry and the molecular skeleton is used in laser
materials, photosensitizers, brighteners as intermedi-
0932–0776 / 08 / 0100–0071 $ 06.00 © 2008 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com
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72
M. Kidwai et al. · Reaction of Coumarin Derivatives with Nucleophiles in Aqueous Medium
Table 1. Comparison of reaction times and yields for 5, 7, 10,
11a – d.
Results and Discussion
In the present study, we disclose a simple and
effective synthetic route that produces high yields
of a series of potentially active coumarin-fused
pyrazoles, isoxazoles and pyrimidine derivatives.
Various methods reported for their synthesis so far
employed the use of hazardous solvents like diphenyl-
nitrilimine [18], acetic acid [19], pyridine [20],
xylene [21] and harmful catalysts like hydrochloric
acid [22], triethylamine [23], etc. These procedures
were “greenified” for the desired organic functional
group transformation by conducting the reaction in
water. Firstly, 4-hydroxy-2H[1]benzopyran-2-one (4-
hydroxycoumarin) (1) was condensed with aromatic
or heteroaromatic aldehydes 2a–d in water under
microwave irradiation to yield 3-arylidenechromane-
2,4-diones 3a–d (Scheme 1). The use of base required
in such reactions was obviated by performing the re-
action in water which not only avoided the use of base
but also gave good yields (75 – 90 %) within 4.0 – 6.0
minutes of microwave irradiation (MWI). Products
3a–d were easily isolated from the reaction medium
Method B
time (h) /
yielda (%)
6.0/48
7.5/50
7.0/52
6.5/45
7.5/45
7.0/52
8.0/53
6.5/40
7.5/40
5.5/45
6.5/45
7.0/53
6.0/45
8.0/56
7.5/55
6.5/50
Method C
time (h) /
yielda (%)
5.0/62
6.5/65
5.5/67
5.5/68
6.5/70
5.5/72
6.5/75
5.0/66
6.0/68
4.5/72
4.5/72
5.5/74
4.5/74
6.5/76
6.5/72
4.5/75
Method D
time (min) /
yielda (%)
2.5/80
2.5/85
2.0/84
2.0/82
3.0/88
2.5/85
3.0/88
2.0/86
2.5/86
1.5/84
1.5/84
2.0/90
2.0/88
3.0/90
3.0/85
Com-
pound
5a
5b
5c
5d
7a
7b
7c
R
4-OCH3C6H4
4-ClC6H4
thiophen-2-yl
C6H5
4-OCH3C6H4
4-ClC6H4
thiophen-2-yl
C6H5
OCH3C6H4
4-ClC6H4
thiophen-2-yl
C6H5
4-OCH3C6H4
4-ClC6H4
thiophen-2-yl
C6H5
7d
10a
10b
10c
10d
11a
11b
11c
11d
1.5/90
a
Isolated and unoptimized yields.
as they precipitated as insoluble solids from water, and
the structures of the known α,β-unsaturated carbonyl
compounds were found to be in consistency with the
spectroscopic data [24]. The reaction conditions of the
second step (Scheme 1) were optimized for the cy-
clocondensation of 3a–d with the nitrogen containing
nucleophiles (NH2-G) hydroxylamine hydrochloride,
hydrazine, urea and thiourea to afford 3-(substituted
aryl)-3,3a-dihydrochromeno[4,3-c]isoxazol-4-ones
5a–d, and pyrazol-4-ones 7a–d, 4-substituted-1,2,3,4-
tetrahydro-benzopyrano[4,3-d]pyrimidine-2,5-diones
10a–d and 4-substituted-1,2,3,4-tetrahydrobenzopyr-
ano[4,3-d]pyrimidine-2-thioxo-5-ones 11a–d.
Different solvents such as ethanol, water or benzene
with different combinations of temperature and reac-
tion time were studied in order to achieve atom econ-
omy within shorter reaction time. In the first experi-
mental trial, the reaction was attempted with ethanol
under conventional reflux conditions. In the next at-
tempt, the cyclization of 4-hydroxycoumarin chal-
cones 3a–d and the nitrogen nucleophile (4, 6, 8, 9)
was performed conventionally in water using a cat-
alytic amount of K2CO3. 4.0– 7.0 hours were taken to
complete the reaction whereas the same reaction was
complete within 3.0 minutes when irradiated under mi-
crowaves with good to excellent yields (80– 90 %),
indicating that higher temperature facilitated efficient
heterocyclization (Table 1). However, the same reac-
tion attempt was unsuccessful when a non-polar sol-
vent like benzene was used with MWI. Hence, the po-
larity of the solvent also had some effect on the cycliza-
Scheme 1.
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M. Kidwai et al. · Reaction of Coumarin Derivatives with Nucleophiles in Aqueous Medium
73
Fig. 1. Structures of compounds 7a and 7c.
tion. When water is heated, dissociation to form acid and any noticeable decomposition. We have developed
and base, catalyzing the reaction, becomes more sig- a method which is not only more environmentally be-
nificant. Also, the use of near critical water instead of nign but also has economic advantages in producing
traditional acid-base processes eliminates the need of a better products less expensively in a short period of
neutralization step and avoids the resulting production time.
of waste salts. Thus, water behaves as a tunable solvent
with the changes of temperature and microwave power
Experimental Section
conditions. In the next step water along with K2CO3
was used for the synthesis of 5, 7, 10 and 11a–d. Here,
the use of K2CO3 served as a mild inorganic water-
soluble base that gets easily washed off with water.
Moreover, the use of K2CO3 was found to be essen-
tial to solubilize 3a – d and to realize the nitrogen nu-
cleophile so that it can react further. The product was
obtained after cooling for 10– 15 minutes.
MW irradiation was carried out in a Kenstar-OM
9925E MW oven (800 W, 2450 MHz). The temperature of
the reaction mixture was measured with a non-contact mini-
gun type IR thermometer (model 8868). IR spectra were
recorded with a Perkin-Elmer FTIR-1710 spectrometer us-
ing KBr pellets. 1H NMR spectra were obtained with a
Bruker Avance Spectrospin 300 spectrometer (300 MHz) us-
ing TMS as internal standard. Elemental analyses were per-
formed with a Heraeus CHN-Rapid analyzer. The melting
points (uncorrected) were determined with a Thomas Hoover
melting point apparatus. 13C NMR spectra were recorded
with a Bruker Topspin Spectrometer at 75.6 MHz. Mass
spectra were recorded with a TOF MS instrument. All re-
actants were purchased from Sigma-Aldrich and Lanchester
and used without further purification. Solvents used for the
reactions were double distilled in a vacuum.
The structures of the synthesized compounds 5, 7,
10 and 11 were confirmed spectroscopically. The in-
frared spectra of the products showed a strong peak
at 1720 cm−1, a value typical of the coumarin car-
boxyl group. The 1H NMR spectra showed a doublet at
δ ∼ 5.5 for 5a – d and at 4.7 ppm for 7a – d, whereas a
singlet at ∼ 6.1 ppm for 10 and 11a – d is a characteris-
tic signal in favor of the proposed product. Apart from
1
IR and H NMR data, mass and 13C NMR spectra as
General procedure for the synthesis of 3-arylidenechromane-
2,4-diones 3a – d
well as elemental analyses also support the structures
of the final products.
Method A
The structures of 7a and 7c (Fig. 1) were further
confirmed with NOESY NMR spectra. Cross corre-
lation peaks due to coupling of 5-H protons (NH,
δ > 11.0) with 6-H (δ > 4.8) and the protons of the
methoxyphenyl group (δ < 7.0) in the case of 7a
(Fig. 1) and between 5-H (NH, δ > 11.0) and 6-H
(δ > 4.8) and the thienyl protons (δ > 7.0) in the case
of 7c have been found.
In conclusion, a synthetic route to various fused het-
erocycles adhering to the green chemistry principles
was followed in aqueous solution without using any
harsh acids or bases thereby eliminating the need of
toxic compounds and solvents. Additionally, the use
of MWI resulted in complete conversion of reactants
To the mixture of 4-hydroxycoumarin (1) (0.01 mol) and
aromatic/heteroaromatic aldehydes 2a – d (0.01 mol), 3 –
4 mL of water was added. The reaction mixture was ex-
posed to microwave irradiation for the appropriate time. The
progress of the reaction was monitored by TLC examination
(Merck TLC: mean particle size 10 – 12 µm; particle size
distribution 5 – 20 µm; layer thickness 250 µm; plate height
30 mm). The solid obtained was filtered, washed with water
and recrystallized from EtOH.
General procedure for the synthesis 5a – d, 7a – d, 10a – d
and 11a – d
Method B (conventional method)
To the mixture of 3-arylidenechromane-2,4-diones 3a – d
into products without the formation of side products (0.01 mol), a nucleophile [hydroxylamine hydrochloride (4)
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M. Kidwai et al. · Reaction of Coumarin Derivatives with Nucleophiles in Aqueous Medium
/ hydrazine hydrate (6) / urea (8) / thiourea (9), (0.015 mol)] S 11.83. – IR (nujol): ν = 1610, 1670 cm−1. – 1H NMR
and K2CO3 (1.0 – 1.5 mg) (not in case of urea and thiourea), (300 MHz, CDCl3, TMS): δ = 2.28 (d, 1 H, J = 9.8 Hz),
10 mL of EtOH was added. The reaction mixture was re- 5.52 (d, 1 H, CH-O, J = 8.0 Hz), 6.75 – 7.40 (m, 7 H, Ar-H +
fluxed for the appropriate time with constant stirring. The thienyl). – MS: m/z (%) = 270.8 (100) [M]+.
reaction was monitored by TLC examination. Upon com-
pletion of the reaction, the solid obtained was filtered, and
washed with water. Then the product was purified by column
chromatography [silica gel, elution with n-hexane : EtOAc
8 : 2 (v/v)] followed by recrystallization from EtOH.
3-Phenyl-3,3a-dihydrochromeno[4,3-c]isoxazol-4-one (5d)
M. p. 166 – 168 ◦C. – C16H11O3N: calcd. C 72.45, H 4.15,
N 5.28; found C 72.35, H 4.18, N 5.30. – IR (nujol): ν =
1615, 1670 cm−1. – 1H NMR (300 MHz, CDCl3, TMS): δ =
2.26 (d, 1 H, J = 9.8 Hz), 5.50 (d, 1 H, CH-O, J = 8.0 Hz),
6.81 – 7.66 (m, 9 H, Ar-H). – MS: m/z (%) = 264.7 (100)
[M]+.
Method C (conventional method)
This method is the same as method B except that water
was used as solvent.
3-(4-Methoxyphenyl)-3,3a-dihydro-2H-chromeno[4,3-c]-
Method D (microwave-assisted synthesis)
pyrazol-4-one (7a)
In an Erlenmeyer flask were placed 3-arylidenechrom-
ane-2,4-diones 3a – d (0.01 mol), a nucleophile [hydroxy-
lamine hydrochloride (4) / hydrazine hydrate (6) / urea (8)
/ thiourea (9) (0.015 mol)] and K2CO3 (not in case of urea
and thiourea), and 2 – 3 mL of water. The reaction mixture
was subjected to microwave irradiation (MWI) for a specific
time (Table 1) at low power (560 W). The progress of the
M. p. 175 – 177 ◦C. – C17H14O3N2: calcd. C 69.38,
H 4.76, N 9.52; found C 69.36, H 4.78, N 9.50. – IR (nujol):
ν = 1615, 1665, 3450 cm−1. – 1H NMR (300 MHz, CDCl3,
TMS): δ = 2.47 (d, 1 H, J = 9.6 Hz), 3.83 (s, 3 H, OCH3),
4.81 (d, 1 H, J = 8.2 Hz), 6.80 – 7.55 (m, 8 H, Ar-H), 11.21
(s, 1 H, NH). – NOE correlations: 1-H/2-H, 3-H/2-,4-H,
reaction was monitored by TLC examination at intervals of 5-H/6-,7-H, 7-H/8-H, -OCH3/9-,8-H, 10-H/6-,9-H. – MS:
m/z (%) = 293.5 (100) [M]+.
30 seconds. On completion, the reaction mixture was cooled
and filtered, washed with cold water and dried. The rest was
the same as in method B.
3-(4-Chlorophenyl)-3,3a-dihydrochromeno[4,3-c]pyrazol-
4-one (7b)
3-(4-Methoxyphenyl)-3,3a-dihydro-chromeno[4,3-c]-
isoxazol-4-one (5a)
◦
M. p. 188 C. – C16H11O2N2Cl: calcd. C 64.32, H 3.68,
N 9.38; found C 64.30, H 3.63, N 9.35. – IR (nujol): ν =
M. p. 188 – 190 ◦C. – C17H13O4N: calcd. C 69.15, H 4.40,
1605, 1660, 3450 cm−1. – 1H NMR (300 MHz, CDCl3,
N 4.74; found C 69.13, H 4.38, N 4.72. – IR (nujol): ν = TMS): δ = 2.45 (d, 1 H, J = 9.6 Hz), 4.83 (d, 1 H, J =
1605, 1660 cm−1. – 1H NMR (300 MHz, CDCl3, TMS): δ = 8.2 Hz), 6.82 – 7.58 (m, 8 H, Ar-H), 11.23 (s, 1 H, NH). –
MS: m/z (%) = 299.0 (100) [M]+. – 13C NMR (75.6 MHz,
2.27 (d, 1 H, J = 9.8 Hz), 3.84 (s, 3 H, OCH3), 5.51 (d, 1 H,
CH-O, J = 8.0 Hz), 6.86 – 7.53 (m, 8 H, Ar-H). – 13C NMR CDCl3, TMS): δ = 129.7, 125.5, 131.3, 122.5, 153.7, 171.0,
(75.6 MHz, CDCl3, TMS): δ = 129.6, 125.7, 133.2, 123.5, 56.3, 48.0, 143.5, 129.0, 130.5, 133.8, 131.5, 129.5, 158.6,
154.6, 171.0, 47.2, 66.9, 128.5, 129.7, 134.3, 129.5, 128.6,
139.0, 166.6, 125.1, 61.2. – MS: m/z (%) = 295.2 (100) [M]+.
128.1.
3-(Thiophene-2-yl)-3,3a-dihydrochromeno[4,3-c]pyrazol-4-
3-(4-Chlorophenyl)-3,3a-dihydrochromeno[4,3-c]isoxazol-
one (7c)
4-one (5b)
◦
M. p. 172 C. – C14H10N2O2S: calcd. C 62.22, H 3.70,
M. p. 175 – 177 ◦C. – C16H10O3NCl: calcd. C 64.10, N 10.37, S 11.85; found C 62.12, H 3.73, N 10.40,
H 3.33, N 4.67; found C 64.13, H 3.34, N 4.68. – IR (nu- S 11.84. – IR (nujol): ν = 1615, 1670, 3455 cm−1. –
jol): ν = 1615, 1665 cm−1. – H NMR (300 MHz, CDCl3, 1H NMR (300 MHz, CDCl3, TMS): δ = 2.49 (d, 1 H, J =
1
TMS): δ = 2.25 (d, 1 H, J = 9.8 Hz), 5.59 (d, 1 H, CH-O, J = 9.6 Hz), 4.84 (d, 1 H, J = 8.2 Hz), 6.77 – 7.69 (m, 7 H,
8.0 Hz), 6.80 – 7.55 (m, 8 H, Ar-H). – MS: m/z (%) = 299.3 Ar-H + thienyl), 11.24 (s, 1 H, NH). – MS: m/z (%) =
(100) [M]+.
270.0 (100) [M]+. – NOE correlations: 1-H/2-H, 3-H/2-,4-H,
5-H/6-,7-H, 8-H/7-,9-H.
3-(Thiophene-2-yl)-3,3a-dihydrochromeno[4,3-c]isoxazol-
4-one (5c)
3-Phenyl-3,3a-dihydrochromeno[4,3-c]pyrazol-4-one (7d)
M. p. 168 – 170 ◦C. – C14H9O3NS: calcd. C 61.99,
M. p. 164 – 166 ◦C. – C16H12O2N2: calcd. C 72.72,
H 3.32, N 5.16, S 11.80; found C 61.98, H 3.21, N 5.14, H 4.54, N 10.60; found C 72.11, H 4.56, N 10.57. – IR (nu-
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M. Kidwai et al. · Reaction of Coumarin Derivatives with Nucleophiles in Aqueous Medium
75
jol): ν = 1605, 1660, 3440 cm−1. – 1H NMR (300 MHz, 4-(4-Methoxyphenyl)-1,2,3,4-tetrahydrobenzopyrano[4,3-
CDCl3, TMS): δ = 2.47 (d, 1 H, J = 9.6 Hz), 4.81 (d, 1 H, d]pyrimidine-2-thioxo-5-one (11a)
J = 8.2 Hz), 6.80 – 7.65 (m, 9 H, Ar-H), 11.25 (s, 1 H, NH). –
M. p. 234 – 236 ◦C (234 ◦C [25]). – C18H14O3N2S: calcd.
C 63.85, H 4.14, N 8.28, S 9.46; found C 63.89, H 4.12,
N 8.25, S 9.45. – IR (nujol): ν = 1675, 3455 cm−1. –
1H NMR (300 MHz, CDCl3, TMS): δ = 3.84 (s, 3 H,
OCH3), 6.07 (s, 1 H), 6.83 – 7.53 (m, 8 H, Ar-H), 11.50 (brs,
2 H, 2NH). – MS: m/z (%) = 338.6 (100) [M]+.
MS: m/z (%) = 264.0 (100) [M]+.
4-(4-Methoxyphenyl)-1,2,3,4-tetrahydrobenzopyrano[4,3-
d]pyrimidine-2,5-dione (10a)
M. p. 242 ◦C (240 ◦C [25]). – C18H14O4N2: calcd.
C 67.08, H 4.34, N 8.69; found C 67.05, H 4.31, N 8.73. –
IR (nujol): ν = 1660, 3450 cm−1. – 1H NMR (300 MHz,
CDCl3, TMS): δ = 3.86 (s, 3 H, OCH3), 6.12 (s, 1 H), 6.85 –
7.55 (m, 8 H, Ar-H), 11.53 (brs, 2 H, 2NH). – MS: m/z (%) =
321.8 (100) [M]+.
4-(4-Chlorophenyl)-1,2,3,4-tetrahydrobenzopyrano[4,3-d]-
pyrimidine-2-thioxo-5-one (11b)
M. p. 187 – 189 ◦C (188 – 190 ◦C [26]).
–
C17H11O2N2ClS: calcd. C 59.56, H 3.21, N 8.17, S 9.34;
found C 59.54, H 3.20, N 8.1, S 9.35. – IR (nujol): ν = 1680,
3450 cm−1. – 1H NMR (300 MHz, CDCl3, TMS): δ = 6.08
(s, 1 H), 6.86 – 7.82 (m, 8 H, Ar-H), 11.50 (brs, 2 H, 2NH). –
MS: m/z (%) = 342.0 (100) [M]+.
4-(4-Chlorophenyl)-1,2,3,4-tetrahydrobenzopyrano[4,3-d]-
pyrimidine-2,5-dione (10b)
M. p. 161 – 163 ◦C (162 – 164 ◦C [26]). – C17H11O3N2Cl:
calcd. C 62.48, H 3.36, N 8.57; found C 62.49, H 3.36,
N 8.54. – IR (nujol) : ν = 1670, 3450 cm−1. – 1H NMR
(300 MHz, CDCl3, TMS): δ = 6.11 (s, 1 H), 6.89 – 7.65 (m,
8 H, Ar-H), 11.52 (brs, 2 H, 2NH). – MS: m/z (%) = 326.0
(100) [M]+.
4-(Thiophen-2-yl)-1,2,3,4-tetrahydrobenzopyrano[4,3-d]-
pyrimidine-2-thioxo-5-one (11c)
M. p. 245 – 247 ◦C. – C15H10N2O2S: calcd. C 57.32,
H 3.18, N 8.91, S 20.38; found C 57.31, H 3.15, N 8.71,
S 20.34. – IR (nujol): ν = 1680, 3455 cm−1. – 1H NMR
(300 MHz, CDCl3, TMS): δ = 6.08 (s, 1 H), 6.77 – 7.65 (m,
7 H, Ar-H + thienyl), 11.40 (brs, 2 H, 2NH). – MS: m/z (%) =
314.7 (100) [M]+.
4-(Thiophen-2-yl)-1,2,3,4-tetrahydrobenzopyrano[4,3-d]-
pyrimidine-2,5-dione (10c)
M. p. 168 – 170 ◦C. – C15H10N2O3S: calcd. C 60.40,
H 3.35, N 9.39, S 10.73; found C 60.4, H 3.37, N 9.36,
S 10.75. – IR (nujol): ν = 1675, 3440 cm−1. – 1H NMR
(300 MHz, CDCl3, TMS): δ = 6.14 (s, 1 H), 6.79 – 7.65 (m,
7 H, Ar-H + thienyl), 11.55 (brs, 2 H, 2NH). – 13C NMR
(75.6 Hz, CDCl3, TMS): δ = 127.6, 126.3, 129.5, 122.3,
153.8, 171.0, 104.5, 54.8, 127.5, 129.5, 126.4, 143.5, 162.0,
149.2, 140.8. – MS: m/z (%) = 297.8 (100) [M]+.
4-Phenyl-1,2,3,4-tetrahydrobenzopyrano[4,3-d]pyrimidine-
2-thioxo-5-one (11d)
M. p. 188 – 189 ◦C (188 ◦C [25]). – C17H12O2N2S: calcd.
C 62.23, H 3.89, N 9.09, S 10.38; found C 62.21, H 3.87,
N 9.07, S 10.39. – IR (nujol): ν = 1670, 3445 cm−1. –
1H NMR (300 MHz, CDCl3, TMS): δ = 6.05 (s, 1 H), 6.79 –
7.68 (m, 9 H, Ar-H), 11.48 (brs, 2 H, 2NH). – 13C NMR
(75.6 MHz, CDCl3, TMS): δ = 128.6, 125.0, 130.1, 122.3,
152.8, 171.0, 101.9, 58.2, 129.1, 130.3, 128.5, 130.1, 128.9,
144.4, 184.2, 163.2, 129.8. – MS: m/z (%) = 308.0 (100)
[M]+.
4-Phenyl-1,2,3,4-tetrahydrobenzopyrano[4,3-d]pyrimidine-
2,5-dione (10d)
◦
M. p. 162 – 163 ◦C (162 C [25]). – C17H12O3N2: calcd.
C 69.86, H 4.10, N 9.58; found C 69.85, H 4.14, N 9.56. –
IR (nujol): ν = 1680, 3445 cm−1. – 1H NMR (300 MHz,
CDCl3, TMS): δ = 6.12 (s, 1 H), 6.79 – 7.65 (m, 9 H, Ar-H),
11.53 (brs, 2 H, 2NH). – MS: m/z (%) = 292.0 (100) [M]+.
Acknowledgement
The authors are thankful to CSIR, New Delhi, for their
financial assistance.
[1] N. E. Leadbeater, Chem. Commun. 2005, 23, 2881 –
2902.
[3] C. O. Kappe, Angew. Chem. Int. Ed. 2004, 43, 6250 –
6284.
[2] a) M. Kidwai, S. Saxena, R. Mohan, R. Venkatara-
manan, J. Chem. Soc., Perkin Trans. I 2002, 1845 –
1846; b) M. Kidwai, Pure Appl. Chem. 2001, 73, 147 –
151; c) M. Kidwai, S. Rastogi, R. Thakur, S. Saxena,
Z. Naturforsch. 2004, 59b, 606 – 608.
[4] a) L. Perreux, A. Loupy, Tetrahedron 2001, 57, 9199 –
9223; b) M. Kidwai, K. Singhal, S. Kukreja, Z. Natur-
forsch. 2006, 62b, 732 – 736.
[5] C. R. Strauss, Angew. Chem. Int. Ed. 2002, 41, 3589 –
3591.
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Unauthenticated
Download Date | 3/22/16 10:56 AM

76
M. Kidwai et al. · Reaction of Coumarin Derivatives with Nucleophiles in Aqueous Medium
[6] R. Breslow, Acc. Chem. Res. 1991, 24, 159 – 164.
[7] M. C. Pirrung, Chem. Eur. J. 2006, 12, 1312 – 1317.
[8] K. H. Drexhage, G. A. Reynold, VIII. Int. Quan-
tum Electronics Conf. 1976, IQEC Technical Digest,
pp. 19 – 20 (Chem. Abstr. 1976, 90, 114369n).
[17] a) M. Kidwai, Priya, K. Singhal, S. Rastogi, Heterocy-
cles 2007, 71, 569 – 576; b) M. Kidwai, Priya, K. Sing-
hal, Heterocycles 2007, in press; c) M. Kidwai, S. Sax-
ena, M. K. R. Khan, S. S. Thukral, Eur. J. Med. Chem.
2005, 40, 816 – 819.
[9] a) P. Czerney, H. Hartmann, J. Liebscher, Z. Chem.
1981, 153, 122 (Chem. Abstr. 1982, 97, 57); b) K. H.
Kaidbey, A. M. Kligman, Arch. Dermatol. 1981, 117,
258 (Chem. Abstr. 1981, 95, 19141e).
[18] T. Fathi, N. Dinh An, G. Sclimitt, E. Cerutti, B. Laude,
Tetrahedron 1988, 44, 4527 – 4536.
[19] B. Chantegrel, A. Nadi, S. Gelin, Tetrahedron Lett.
1983, 24, 381 – 384.
[10] a) T. O. Soine, J. Pharm. Sci. 1964, 53, 231 – 264; [20] A. Levai, J. Heterocycl. Chem. 1998, 35, 13 – 16.
b) T. R. Seshadri, S. Vishwapaul, J. Scient. Ind. Res.
India 1973, 32, 227 – 255.
[21] A. S. Shawali, B. E. Elanadouli, H. A. Albar, Tetrahe-
dron 1985, 41, 1877 – 1884.
[11] S. Tondon, R. Rastogi, J. Scient. Ind. Res. India 1979,
38, 428 – 441.
[22] G. Daidone, S. Plescia, J. Fabra, J. Heterocycl. Chem.
1980, 17, 1409 – 1411.
[12] Y. S. Sanghvi, S. B. Larson, R. K. Robinse, G. R. Re-
vukar, J. Med. Chem. 1989, 32, 945 – 951.
[13] M. Paller, R. J. Ponzio, Chem. Abstr. 1983, 99,
158406r.
[14] L. Prakash, R. Sharma, S. Shukla, R. D. Goyal, Phar-
mazie 1993, 48, 221 – 222; (Chem. Abstr. 1993, 119,
954465t).
[23] I. Strakova, M. Petrova, S. Belyakov, A. Strakovs,
Chem. Heterocyclic Compd. 2003, 39, 1608 – 1616.
[24] B. Refouvelet, C. Guyon, Y. Jacquot, C. Girard,
H. Sein, F. Bevalot, J. F. Robert, B. Heyd, G. Mantion,
L. Richert, A. Xicluna, Europ. J. Med. Chem. 2004, 39,
931 – 937.
[25] D. I. Brahmbhatt, G. B. Raolji, S. U. Pandya, U. R.
Pandya, Indian J. Chem. 1999, 38B, 839 – 842.
[15] H. Arai, K. Shinozaki, S. Niwa, T. Aozuka, M. Seiki,
M. Soeda, S. Veki, Jpn. Kokai Tokkyo Koho 1988, 63, [26] M. Kidwai, P. Sapra, Synth. Commun. 2002, 32, 1639 –
286 – 303 (Chem. Abstr. 1989, 110, 23891v).
[16] M. Kidwai, R. Vekataramanan, B. Dave, Green Chem.
2001, 3, 278 – 279.
1645.
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