One-Pot wittig and knoevenagel reactions in ionic liquid as convenient methods for the synthesis of coumarin derivatives

Article abstract of DOI:10.1080/00397910802573163

Efficient synthesis of a variety of 3-substituted coumarins via NaOMe-catalyzed Knoevenagel condensation and one-pot preparation of 3,4-unsubstituted coumarins in the presence of NaOMe via Wittig reaction in room-temperature ionic liquids are described. Knoevenagel condensation of 2-hydroxybenzaldehyde with dimethyl- and diethylmalonate was performed with excellent yields in room-temperature ionic liquids. Although diethyl- and dimethylchloromalonates were mostly recovered unchanged in Knoevenagel condensation, higher conversions were observed via Wittig reaction of these compounds with 2-hydroxybenzaldehyde derivatives and triphenylphosphine. Other 2-hydroxybenzaldehyde derivatives, methyl- and ethylchloroacetates, were reacted in ionic liquids to afford simple coumarins in good yields. These reactions widen the applicability of ionic liquid in organic synthesis. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802573163

This article was downloaded by: [University of Toronto Libraries]
On: 19 February 2013, At: 07:47
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
One-Pot Wittig and
Knoevenagel Reactions in Ionic
Liquid as Convenient Methods
for the Synthesis of Coumarin
Derivatives
Hassan Valizadeh a & Sevil Vaghefi a
a Faculty of Science, Department of Chemistry,
Azerbaijan University of Tarbiat-Moallem, Tabriz,
Iran
Version of record first published: 02 Apr 2009.
To cite this article: Hassan Valizadeh & Sevil Vaghefi (2009): One-Pot Wittig and
Knoevenagel Reactions in Ionic Liquid as Convenient Methods for the Synthesis of
Coumarin Derivatives, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 39:9, 1666-1678
To link to this article: http://dx.doi.org/10.1080/00397910802573163
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,

sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden.
The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be
independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages
whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

Synthetic Communications1, 39: 1666–1678, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802573163
One-Pot Wittig and Knoevenagel Reactions in
Ionic Liquid as Convenient Methods for the
Synthesis of Coumarin Derivatives
Hassan Valizadeh and Sevil Vaghefi
Faculty of Science, Department of Chemistry,
Azerbaijan University of Tarbiat-Moallem, Tabriz, Iran
Abstract: Efficient synthesis of
a variety of 3-substituted coumarins via
NaOMe-catalyzed Knoevenagel condensation and one-pot preparation of
3,4-unsubstituted coumarins in the presence of NaOMe via Wittig reaction
in room-temperature ionic liquids are described. Knoevenagel condensation of
2-hydroxybenzaldehyde with dimethyl- and diethylmalonate was performed with
excellent yields in room-temperature ionic liquids. Although diethyl- and
dimethylchloromalonates were mostly recovered unchanged in Knoevenagel
condensation, higher conversions were observed via Wittig reaction of these
compounds with 2-hydroxybenzaldehyde derivatives and triphenylphosphine.
Other 2-hydroxybenzaldehyde derivatives, methyl- and ethylchloroacetates, were
reacted in ionic liquids to afford simple coumarins in good yields. These reac-
tions widen the applicability of ionic liquid in organic synthesis.
Keywords: Coumarins, ionic liquid, Knoevenagel reaction, Wittig reaction
Currently, there has been an increasing demand for efficient synthetic
processes and solvent-free reactions as a result of environmental con-
cerns. Some old and new methodologies are being used to diminish
and prevent pollution caused by chemical activities. The environmental
acceptability of the process is improved if a multicomponent strategy
is applied. Indeed, it is well known that one-pot treatment of
Received October 11, 2008.
Address correspondence to Hassan Valizadeh, Faculty of Science, Department
of Chemistry, Azerbaijan University of Tarbiat-Moallem, P. O. Box 53714-161,
Tabriz, Iran. E-mail: h-valizadeh@azaruniv.edu
1666

Synthesis of Coumarin Derivatives
1667
multi-component reactions (MCRs), consisting of two or more synthetic
steps carried out without isolation of any intermediate, are always
resource effective and environmentally acceptable; thus, they are greener
in comparison to multistep reactions.[1,2] With increasing environmental
concerns and regulatory constraints, the development of environmen-
tally benign organic reactions has become mandatory.[3] Ionic liquids
are a new class of solvents that have attracted growing interest over
the past few years because of their unique physical and chemical prop-
erties.[4] They usually consist of poorly coordinating ion pairs, and a
classical example is the readily accessible 1-butyl-3-methylimidazolium
tetrafluoroborate [bmim][BF4], which is a colorless, nonvolatile, and
odorless liquid.[5] Because such solvents easily dissolve metal salts and
transition-metal catalysts, interesting developments have recently
appeared in synthesis using organometallic reagents.[6,7]
Coumarins represent an important class of compounds because of
their importance in biological systems.[8,9] There have been a wide variety
of noncatalytic methods to synthesize coumarins, such as the Pechmann
condensation of b-ketoesters.[10] However, this method generally requires
strong acids and high reaction temperatures. Moreover, there have been
several metal-catalyzed approaches to coumarins, including a palladium-
catalyzed reaction between phenols and alkynoates.[11]
The Knoevenagel condensation reaction is an important C–C bond-
forming reaction commonly used for the production of fine chemical
intermediates and products (e.g., coumarin derivatives[12,13]) as well as
pharmaceuticals (e.g., nifendipine and nitrendipine derivatives for hyper-
tension drugs[14,15]). We reported the synthesis of coumarin derivatives
via Knoevenagel reaction of 2-hydroxybenzaldehyde derivatives with
some active methylene compounds in aqueous media.[16] In continuation
of our recent interest in ionic liquids (ILs), water, or solventless systems
as green reaction media,[17,18] we study herein the Knoevenagel reaction
for the preparation of coumarin derivatives in imidazolium-based ILs
(Scheme 1).
The study investigates the Knoevenagel condensation reaction
between 2-hydroxybenzaldehyde derivatives 1 and dialkylmalonates 1a
or chlorodialkylmalonates 1b in IL.
Scheme 1.

1668
H. Valizadeh and S. Vaghefi
A typical reaction of 2-hydroxybenzaldehyde with diethylmalonate
and NaOMe was carried out in an IL, [bmim] BF4, at ambient conditions
to form 3-carboethoxycoumarin. However, at room temperature, the
reaction did not proceed further to afford the product, it was carried
out at higher temperatures, and the optimum results were obtained at
95 ꢀC (74%). For further optimization, several ILs based on butylmethy-
limidazolium salts, [bmim]X, with varying anions were screened in the
typical reaction at 95 ꢀC for complete conversions as monitored by
thin-layer chromatography (TLC) to afford the product. Evidently,
[bmim] PF6 was found to be superior in terms of yield (85%) and reaction
time (3 h) as compared with other ILs.
Further reactions with other 2-hydroxybenzaldehyde derivatives and
malonate esters were conducted using [bmim]PF4 as the reaction medium
to afford coumarins 2 (Table 1). Then the generality of these conditions
to other substrates was examined. The results are summarized in Table 1.
Chlorodiethyl- and dimethylmalonates 2b did not react even with
prolonging reaction times, adding other base catalysts such as K2CO3,
piperidine, and triethylamine, and under great microwave (MW) potency.
However, when 1.5 equiv of PPh3, 1.2 equiv chlorodiethyl- or dimethyl-
malonates, 1 equiv 2-hydroxybenzaldehyde derivative, and 1.5 equiv
NaOMe were reacted in [bmim]PF6 as the reaction medium, 3-
carbo(ethoxy or methoxy)coumarin derivatives could be obtained
via Wittig reaction in good yields. For comparison, the yields of 3-
substituted coumarins prepared via the Knoevenagel and Wittig reaction
are shown in Table 1. The Wittig reaction is a good alternative for the
synthesis of 3,4-unsubstituted coumarins, which are more difficult to
access via traditional reactions such as the Pechmann or Knoevenagel
reactions.[23] For more investigation, we repeated the one-pot Wittig
reaction of 2-hydroxybenzaldehyde derivatives, methylchloroacetate,
and triphenylphosphine in ILs for the synthesis of 3-unsubstituted
coumarin derivatives 4 (Scheme 2).
Using NaOMe as catalyst, a typical reaction of 2-hydroxybenzal-
dehyde, methylchloroacetate, and triphenylphosphine was carried out
in the IL [bmim] BF4 at ambient conditions to form simple coumarin.
However, at room temperature, the reaction did not proceed further,
and at medium temperatures the E-cinamic ester 5 was the major pro-
duct. Therefore, the reaction was carried out at higher temperatures,
and the optimum results for the synthesis of coumarin were obtained
at 200–215 ꢀC, which makes it possible to obtain isomerizaion of the
E-cinamic ester toward the Z-isomer, cyclizing toward the corresponding
coumarin (62%). For further optimization, several ILs based on butyl-
methylimidazolium salts [bmiꢁm]X with varying anions such as Clꢁ,
BF4ꢁ, PF6ꢁ, Brꢁ, and AlCl4 were screened in this typical reaction

Synthesis of Coumarin Derivatives
1669
Table 1. Synthesis of 3-substituted coumarin derivatives in [bmim] PF6
Yielda (%) [time (h)]
Melting point (ꢀC)
Via
Knoevenagel
(from 2a)
Via
Wittig
(from 2b)
Product
Found
Reported
78 [3.5]
52 [5]
49 [5]
263–266
265–267[19]
76 [3.5]
172–173
173–175
173–175[19]
174–175[20]
71 [3]
45 [6]
85 [3]
41 [6.6]
45 [5.5]
40 [6]
94–98
94–97[19]
123–124[20]
233–234[20]
71 [4.5]
75 [4.5]
121–123
230–233
72 [4]
68 [4]
44 [6]
130–133
75–77
132–133[20]
77–78[21]
41 [6.5]
69 [4.5]
66 [4.5]
43 [6]
40 [6]
87–90
88–90[22]
269–272
270–271[20]
(Continued )

1670
H. Valizadeh and S. Vaghefi
Table 1. Continued
Yielda (%) [time (h)]
Melting point (ꢀC)
Via
Knoevenagel
(from 2a)
Via
Wittig
(from 2b)
Product
Found
Reported
68 [4.5]
42 [5.5]
189–192
189–190[20]
aIsolated yield after column chromatography.
at 210 ꢀC for complete conversions as monitored by TLC to afford the
product. The resulꢁts indicated that as in the Knoevenagel reaction, the
IL containing PF6 anion exhibited excellent catalytic activity in terms
of yield (72%) and reaction time (4.5 h).
With optimal conditions in hand, we then examined the generality of
these conditions to other substrates. The results are summarized in
Table 2. As can be seen from Table 2, an electron-donating group such
as a hydroxyl or methoxy at C4 of 2-hydroxybenzaldehyde increases
the yield of coumarin product. All coumarins obtained were character-
1
ized by melting point (MP), infared (IR), H NMR, and 13C NMR,
and the values are in agreement with those reported in literature.
EXPERIMENTAL
1H NMR spectra (400 MHz) and 13C NMR spectra (75 MHz) were
recorded on a Bruker Avance spectrometer using, tetramethysilane
Scheme 2.

Synthesis of Coumarin Derivatives
1671
Table 2. One-pot Wittig reaction in [bmim] PF4 for the synthesis of 3-
unsubstituted coumarin derivatives
Melting point (ꢀC)
Product
Time (h)
4.5
Yielda (%)
72
Found
66–69
Reported
68–70[24]
5.5
88
232–234
234–235[25]
5.5
5
89
67
62
117–120
159–162
181–183
118–119[26]
165–167[27]
181–182[28]
4
5
4
60
65
188–190
135–138
190–191[23]
136.5–137[27]
4
4
67
64
120–124
93–95
122–124[27]
94.5–96.5[27]
aIsolated yield after column chromatography.
(TMS) as internal standard. IR spectra were recorded in KBr and were
determined on a Perkin-Elmer Fourier transform (FT)–IR spectrometer.
All of the melting points are uncorrected, were determined with a Stuart
scientific apparatus, and gave data consistent with those published. All

1672
H. Valizadeh and S. Vaghefi
solvents and chemicals were of research grade and were used as obtained
from Merck. The imidazolium-based ILs investigated were prepared
according to the procedure reported in previous literature.[29]
General Procedure for the Knoevenagel Reaction in [bmim] PF6
To a round-bottom flask (5 cm3) equipped with a magnetic stirrer, [bmim]
PF6 (5.0 g), and sodium methoxide (1 mmol) were added, and the mixture
was heated to 80 ꢀC for 5 min with stirring to form the IL solution of the
catalyst. A mixture of 2-hydroxybenzaldehyde (0.4 mmol) and malonate
ester 2a (0.5 mmol) was added, and the mixture was heated to 95 ꢀC.
The completion of the reaction was monitored by TLC using
EtOAc=petroleum (3:8) as eluent. After completion of the reaction, the
mixture was diluted with 5% HCl extracted with EtOH (15 ml ꢂ 3). The
combined EtOH extracts were concentrated on a rotary evaporator,
and the crude mixture was purified by column chromatography
using hexane=EtOAc (3:1) on silica gel to afford corresponding
3-substituted coumarin (Table 1).
General Procedure for the Synthesis of 3-Unsubstituted Coumarins
To a round-bottom flask (5 cm3) equipped with a magnetic stirrer,
[bmim] PF6(5.0 g) and sodium methoxide (1 mmol) were added, and
the mixture was heated to 80 ꢀC for 5 min with stirring to form the
IL solution of the catalyst. A mixture of triphenylphosphine (0.105 g,
0.40 mmol), 2-hydroxybenzaldehyde (0.4 mmol), and methylchloroace-
tate or chloromalonate ester 2b (0.5 mmol) was added, and the mixture
was heated to 210 ꢀC. The completion of reaction was monitored by
TLC using EtOAc=petroleum (1:8) as eluent. After completion of the
reaction, the mixture was extracted with EtOAc (15 ml ꢂ 3). The com-
bined EtOAc extracts were concentrated on a rotary evaporator, and
the crude mixture was purified by column chromatography using HEX=
EtOAc (9:2) on silica gel to afford corresponding 3-unsubstituted
coumarin (Table 2).
Selected Spectroscopic Data of 3-Substituted Coumarins
Methyl 7-Hydroxy-2-oxo-2H-chromene-3-carboxylate
1
IR nmax=cmꢁ1: 3550, 3470, 1739, 1617; H NMR (300 MHz, DMSO-
d6) d 3.85 (s, 3H), 6.72 (d, J ¼ 1.8 Hz, 1H), 6.88 (dd, J ¼ 8.2 and

Synthesis of Coumarin Derivatives
1673
1.8 Hz, 1H), 7.45 (d, J ¼ 8.2 Hz, 1H), 8.67 (s, 1H); 13C NMR (75 MHz,
DMSO-d6) d 52.5, 110.4, 111.5, 112, 132, 132.8, 150, 150.5, 156.7,
163.8, 165.9.
Ethyl 7-Hydroxy-2-oxo-2H-chromene-3-carboxylate
1
IR nmax=cmꢁ1: 3550, 3470, 1739, 1617; H NMR (300 MHz, DMSO-d6)
d 1.29 (t, J ¼ 7.1 Hz, 3H), 4.26 (q, J ¼ 7.1 Hz, 2H), 6.73 (s, 1H), 6.84 (d,
J ¼ 8.3 Hz, 1H), 7.77 (d, J ¼ 8.3 Hz, 1H), 8.67 (s, 1H); 13C NMR
(75 MHz, DMSO-d6) d 16.0, 60.5, 110.4, 111.5, 112, 132, 132.8, 150,
150.5, 156.7, 163.8, 165.9.
Ethyl 8-Hydroxy-2-oxo-2H-chromene-3-carboxylate
IR nmax=cmꢁ1: 3313, 3030, 2989, 1739, 1672; 1H NMR (300 MHz,
DMSO-d6) d 1.32 (t, J ¼ 7.1 Hz, 3H), 4.31 (q, J ¼ 7.1 Hz, 2H), 7.21–
7.29 (m, 2H), 7.32–7.41 (m, 1H), 8.67 (s, 1H); 13C NMR (75 MHz,
DMSO-d6) d 14.0, 61.1, 117.7, 118.6, 120.0, 120.5, 124.7, 143.1, 144.3,
149.0, 155.9, 162.6.
Ethyl 2-Oxo-2H-chromene-3-carboxylate
IR nmax=cmꢁ1: 3044, 2986, 1628, 1371, 1210; 1H NMR (300 MHz,
CDCl3) d 1.41 (t, J ¼ 7.25 Hz, 3H), 4.36 (q, J ¼ 7.25 Hz, 2H), 6.82–7.55
(m, 4H), 8.48 (s, 1H); 13C NMR (75 MHz, CDCl3) d 18.1, 54.8, 103.2,
115.5, 116.4, 117.9, 133.6, 150.7, 156.0, 162.6, 161.1, 167.5.
Methyl 7-Methoxy-2-oxo-2H-chromene-3-carboxylate
1
IR nmax=cmꢁ1: 3050, 2976, 1620, 1381; H NMR (300 MHz, CDCl3) d
3.78 (s, 3H), 3.85 (s, 3H), 6.79 (d, J ¼ 2.4 Hz, 1H), 6.98 (dd, J ¼ 8.5 and
2.4 Hz, 1H), 7.55 (d, J ¼ 8.5 Hz, 1H), 8.38 (s, 1H); 13C NMR (75 MHz,
CDCl3) d 16.1, 62.5, 104.2, 115.5,116.2, 116.8, 131.6, 148.8, 159.8,
161.5, 164.1, 164.4.
Ethyl 7,8-Dihydroxy-2-oxo-2H-chromene-3-carboxylate
IR nmax=cmꢁ1: 3466, 3221, 2973, 1728, 1698, 1615, 1579; 1H NMR
(300 MHz, CDCl3) d 1.29 (t, J ¼ 7.24 Hz, 3H), 4.20 (q, J ¼ 7.24 Hz, 2H),

1674
H. Valizadeh and S. Vaghefi
6.61–7.41 (m, 2H), 8.36 (s, 1H); 13C NMR (75 MHz, CDCl3) d 17.3, 59.2,
110.4, 111.1, 114.5, 120.9, 131.8, 146.2, 151.1, 153.6, 155.9, 161.8.
Ethyl 7-Methoxy-2-oxo-2H-chromene-3-carboxylate
IR nmax=cmꢁ1: 3052, 2986, 1619, 1381, 1216; 1H NMR (300 MHz,
CDCl3) d 1.35 (t, J ¼ 7.3 Hz, 3H), 3.85 (s, 3H), 4.40 (q, J ¼ 7.3 Hz, 2H),
6.80 (d, J ¼ 2.5 Hz, 1H), 6.90 (dd, J ¼ 8.8 and 2.5 Hz, 1H), 7.50 (d,
J ¼ 8.8 Hz, 1H), 8.48 (s, 1H); 13C NMR (75 MHz, CDCl3) d 16.1, 54.8,
62.5, 103.2, 114.4,115.4, 116.9, 132.6, 149.7, 159.0, 160.4, 163.1, 165.5.
Ethyl 7-Diethylamino-2-oxo-2H-chromene-3-carboxylate
1
IR nmax=cmꢁ1: 3031, 2980, 1624; H NMR (300 MHz, CDCl3) d 1.31 (t,
J ¼ 7.1 Hz, 3H), 3.85 (s, 3H), 4.36 (q, J ¼ 7.1 Hz, 2H), 6.81 (d, J ¼ 2.2 Hz,
1H), 6.95 (dd, J ¼ 8.1 and 2.2 Hz,1H), 7.58 (d, J ¼ 8.1 Hz, 1H), 8.48 (s,
1H); 13C NMR (75 MHz, CDCl3) d 15.1, 16.1, 51.2, 62.5, 102.4, 115.0,
116.3, 117.1, 133.1, 148.9, 158.9, 162.4, 165.0, 166.1.
Ethyl 8-Methoxy-2-oxo-2H-chromene-3-carboxylate
IR nmax=cmꢁ1: 3052, 2986, 1619, 1381, 1216; 1H NMR (300 MHz,
CDCl3) d 1.38 (t, J ¼ 7.1 Hz, 3H), 3.79 (s, 3H), 4.39 (q, J ¼ 7.1 Hz, 2H),
7.20–7.30 (m, 2H), 7.34–7.43 (m, 1H), 8.36 (s, 1H); 13C NMR
(75 MHz, CDCl3) d 18.1, 55.8, 63.6, 105.1, 115.8, 116.4, 116.9, 132.6,
149.7, 159.1, 160.6, 163.4, 165.9.
Ethyl 8-Bromo-7-hydroxy-2-oxo-2H-chromene-3-carboxylate
IR nmax=cmꢁ1: 3490, 3478, 1729, 1627; 1H NMR (300 MHz, DMSO-d6) d
1.31 (t, J ¼ 7.15 Hz, 3H), 4.21 (q, J ¼ 7.15 Hz, 2H), 6.84 (d, J ¼ 8.21 Hz,
1H), 7.77 (d, J ¼ 8.21 Hz, 1H), 8.67 (s, 1H); 13C NMR (75 MHz,
DMSO-d6) d 17.6, 62.5, 111.4, 110.8, 111, 131.5, 132.1, 149.8, 150.8,
156.1, 164.2, 166.3.
Ethyl 8-Bromo-7-methoxy-2-oxo-2H-chromene-3-carboxylate
1
IR nmax=cmꢁ1: 3041, 2980, 1621, 1390; H NMR (300 MHz, CDCl3) d
1.28 (t, J ¼ 7.12 Hz, 3H), 3.79 (s, 3H), 4.38 (q, J ¼ 7.12 Hz, 2H), 6.81
(d, J ¼ 8.15 Hz, 1H), 7.71 (d, J ¼ 8.15 Hz, 1H), 8.41 (s, 1H); 13C NMR

Synthesis of Coumarin Derivatives
1675
(75 MHz, CDCl3) d 16.1, 54.8, 62.5, 103.2, 114.4, 115.4, 116.9, 132.6,
149.7, 159.0, 160.4, 163.1, 165.5.
Selected Spectroscopic Data of 3-Unsubstituted Coumarins
2-Oxo-2H-chromene
1
IR nmax=cmꢁ1: 3020, 1710, 1415; H NMR (300 MHz, CDCl3) d 6.70
(d, J ¼ 8.87, 1H), 7.35–7.55 (m, 4H), 7.85 (d, J ¼ 8.87, 1H). 13C NMR
(75 MHz, CDCl3) d 108, 111.1, 113.3, 126, 127.2, 146.8, 148.8, 157.1,
160.9.
7-Hydroxy-2-oxo-2H-chromene
1
IR nmax=cmꢁ1: 3313, 3025, 1719, 1435; H NMR (300 MHz, CDCl3) d
6.59 (d, J ¼ 8.78, 1H), 7.00 (d, J ¼ 7.18, 1H), 7.85 (d, J ¼ 8.78, 1H),
7.05 (dd, J ¼ 1.30 Hz, J ¼ 7.18 1H), 7.12 (d, 1.30 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 108, 111.1, 113.3, 126, 127.2, 146.8, 148.8, 157.1,
160.9.
7-Methoxy-2-oxo-2H-chromene
1
IR nmax=cmꢁ1: 3035, 1726, 1445; H NMR (300 MHz, CDCl3) d 6.39 (d,
J ¼ 8.98, 1H), 7.01 (d, J ¼ 7.28, 1H), 7.95 (d, J ¼ 8.98, 1H), 7.15 (dd,
J ¼ 1.31 Hz, J ¼ 7.28 1H), 7.32 (d, 1.31 Hz, 1H); 13C NMR (75 MHz,
CDCl3) d 108, 111.1, 113.3, 126, 127.2, 146.8, 148.8, 157.1, 160.9.
6-Bromo-2-oxo-2H-chromene
1
IR nmax=cmꢁ1: 3035, 1726, 1385; H NMR (300 MHz, CDCl3) d 6.49
(d, J ¼ 8.95, 1H), 7.15 (d, J ¼ 7.24, 1H), 7.75 (d, J ¼ 8.95, 1H), 7.75
(d, J ¼ 1.36 Hz, 1H), 7.82 (dd, J ¼ 7.24 and 1.36 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 111, 115.1, 118.3, 129, 130.2, 149.8, 151.8, 160.1,
163.9.
6-Nitro-2-oxo-2H-chromene
1
IR nmax=cmꢁ1: 3035, 1726, 1349, 1545; H NMR (300 MHz, CDCl3) d
6.40 (d, J ¼ 9.15, 1H), 7.25 (d, J ¼ 7.34, 1H), 7.78 (d, J ¼ 9.15, 1H),

1676
H. Valizadeh and S. Vaghefi
7.90 (d, J ¼ 1.35 Hz, 1H), 8.04 (dd, J ¼ 7.34 and 1.35 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 111.5, 112.1, 113.3, 129.1, 129.2, 148.6, 150.5, 159.1,
163.3.
8-Nitro-2-oxo-2H-chromene
1
IR nmax=cmꢁ1: 3041, 1739, 1345, 1535; H NMR (300 MHz, CDCl3) d
6.43 (d, J ¼ 9.4, 1H), 7.15 (t, J ¼ 7.84, 1H), 7.68 (d, J ¼ 9.4, 1H), 7.94
(dd, J ¼ 7.3 and 1.3 Hz, 1H), 8.15 (dd, J ¼ 7.3 and 1.3 Hz, 1H); 13C
NMR (75 MHz, CDCl3) d 110.4, 111.5, 112, 128, 129.8, 148, 149.5,
159.8, 165.9.
8-Bromo-2-oxo-2H-chromene
1
IR nmax=cmꢁ1: 3041, 1739, 1385; H NMR (300 MHz, CDCl3) d 6.45
(d, J ¼ 9.4, 1H), 7.15 (t, J ¼ 7.4, 1H), 7.44 (dd, J ¼ 7.6 and 1.4 Hz, 1H),
7.70 (d, J ¼ 9.4, 1H), 7.75 (dd, J ¼ 7.6 and 1.4 Hz, 1H); 13C NMR
(75 MHz, DMSO-d6) d 110.4, 111.5, 112, 132, 132.8, 150, 150.5, 163.8,
165.9.
7-Bromo-2-oxo-2H-chromene
1
IR nmax=cmꢁ1: 3035, 1726, 1445; H NMR (300 MHz, CDCl3) d 6.49 (d,
J ¼ 8.88, 1H), 7.21 (d, J ¼ 7.28, 1H), 7.80 (d, J ¼ 8.88, 1H), 7.35 (dd,
J ¼ 1.31 Hz, J ¼ 7.28, 1H), 7.27 (d, J ¼ 1.31 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 109, 110.8, 114.7, 127.3, 128.2, 145.1, 149, 159, 160.
5-Bromo-2-oxo-2H-chromene
1
IR nmax=cmꢁ1: 3021, 1730, 1365; H NMR (300 MHz, CDCl3) d 6.66 (d,
J ¼ 9.05, 1H), 7.25 (t, J ¼ 7.32, 1H), 7.34 (dd, J ¼ 7.2 and 1.35 Hz, 1H),
7.90 (d, J ¼ 9.05, 1H), 7.71 (dd, J ¼ 7.2 and 1.35 Hz, 1H); 13C NMR
(75 MHz, DMSO-d6) d 109.4, 110.21, 111.11, 130, 130.8, 151, 151.1,
160.6, 161.9.
ACKNOWLEDGMENT
The office of the Research Vice Chancellor of Azerbaijan University of
Tarbiat-Moallem is gratefully acknowledged.

Synthesis of Coumarin Derivatives
REFERENCES
1677
1. Domling, A.; Ugi, I. Multicomponent reactions with isocyanides. Angew.
Chem., Int. Ed. 2000, 39, 3168–3210.
2. Terret, N. K.; Gardener, M.; Gordon, D. W.; Kobylecki, R. J.; Steele, J.
Combinatorial synthesis—The design of compound libraries and their appli-
cation to drug discovery. Tetrahedron 1995, 51, 8135–8173.
3. Anastas, P.; Williamson, T. Green Chemistry: Frontiers in Benign Chemical
Synthesis and Procedures; Oxford Science: Oxford, 1998.
4. Welton, T. Room-temperature ionic liquids: Solvents for synthesis and cata-
lysis. Chem. Rev., 1999, 99, 2071, and references cited therein.
5. Suarez, P. A. Z.; Dullius, J. E. L.; Einloft, S.; De Souza, R.; Dupont, J. The
use of new ionic liquids in two-phase catalytic hydrogenation reaction by rho-
dium complexes. Polyhedron, 1996, 15, 1217.
6. Dyson, P. J.; Ellis, D. J.; Parker, D. G.; Welton, T. Arene hydrogenation in a
room-temperature ionic liquid using a ruthenium cluster catalyst. Chem.
Commun. 1999, 25.
7. Carmichael, A. J.; Earle, M. J.; Holbrey, J. D.; McCormac, P. B.; Seddon, K.
R. The Heck reaction in ionic liquids: A multiphasic catalyst system. Org.
Lett. 1999, 1, 997.
8. Naser-Hijazi, B.; Stolze, B.; Zanker, K. S. Second Proceedings of the Interna-
tional Society of Coumarin Investigators; Springer: Berlin, 1994.
9. Cottiglia, F.; Loy, G.; Garau, D.; Floris, C.; Casu, M.; Pompei, R.;
Bonsignore, L.; Antimicrobial evaluation of coumarins and flavonoids from
the stems of Daphne gnidium L. Phytomedicine 2001, 8 (4), 302–305.
10. Cook, C. E.; Corley, R. C.; Wall, M. E.; Flavonoids, I. Synthesis of 2,2-
dialkyl-D3-isoflavenes from coumarins. J. Org. Chem. 1965, 30 (12),
4114–4120.
11. Trost, B. M.; Toste, F. D. A new palladium-catalyzed addition: A mild
method for the synthesis of coumarins. J. Am. Chem. Soc. 1996, 118 (2),
6305–6306.
12. Scott, J. L.; Raston, C. L. Solvent-free synthesis of 3-carboxycoumarins.
Green Chem. 2000, 2, 245–247.
13. Ramani, A.; Chanda, B. M.; Velu, S.; Sivasanker, S. One-pot synthesis of
coumarins: Catalysis by the solid base, calcined Mg-Al hydrotalcite. Green
Chem. 1999, 1, 163–165.
14. Saunders, J. Top Drugs: Top Synthetic Routes; Oxford University Press:
Oxford, 2000; Chapter 3.
15. Corma, A.; Martin-Aranda, R. M.; Sanchez, F. In: Heterogeneous Catalysis
and Fine Chemicals II: Proceedings of the 2nd International Symposium: M.
Poitiers, Guisnet, et al. (Eds.); Elsevier: Amsterdam, 1991; p. 503.
16. Valizadeh, H.; Mamaghani, M.; Badrian, A. Effect of microwave irradiation
on reaction of arylaldehyde derivatives with some active methylene com-
pounds in aqueous media. Synth. Commun. 2005, 35 (6), 785–790.
17. Valizadeh, H.; Shockravi, A. An efficient procedure for the synthesis of
coumarin derivatives using TiCl4 as catalyst under solvent-free conditions.
Tetrahedron Lett. 2005, 46 (20), 3501–3503.

1678
H. Valizadeh and S. Vaghefi
18. Valizadeh, H.; Shockravi, A. Microwave-assisted Claisen rearrangement:
Application to the synthesis of angelicin derivatives. J. Heterocycl. Chem.
2006, 43, 763–765.
19. Shockravi, A.; Shargi, H.; Valizadeh, H.; Heravi, M. M. Solvent-free synth-
esis of coumarins. Phosphorus, Sulfur Silicon Relat. Elem. 2002, 177, 2555–
2559.
ˆ
20. Alvim, J. Jr.; Dias, R. L. A.; Castilho, M. S.; Glaucius, O.; Correa, A. G.
Preparation and evaluation of a coumarin library towards the inhibitory
activity of the enzyme gGAPDH from Trypanosoma cruzi. J. Braz. Chem.
Soc. 2005, 16 (4), 763–773.
21. Corrie, J. E. T. Thiol-reactive fluorescent probes for protein labeling.
J. Chem. Soc., Perkin Trans. 1 1994, 20, 2975–2982.
22. Horning, E. C.; Horning, M. G. Coumarins from 2-hydroxy-3-methoxyben-
zaldehyde. J. Am. Chem. Soc. 1947, 69 (4), 968–969.
23. Harayama, T.; Nakatsuka, K.; Nishioka, H.; Murakami, K.; Ohmori, Y.;
Takeuchi, Y.; Ishii, H.; Kenmotsu, K. Convenient synthesis of a simple cou-
marin from salicylaldehyde and Wittig reagent (III): Synthesis of nitrocou-
marins. Heterocycles 1994, 38 (12), 2729–2738.
24. Villieras, J.; Ramband, M.; Graft, M. La reaction de Wittig–Horner en milieu
heterogene VI: Selectivite de la reaction sur des composes bifonctionnels.
Tetrahedron Lett. 1985, 26 (1), 53–56.
¨
25. Gramer, F. D.; Windel, H. Uber Einschlußverbindungen, X. Mitteil.: Die
blauen jodverbindungen der cumarine und anderer verwandter verbindungen.
Chem. Ber. 1956, 89, 354–365.
26. Shockravi, A.; Valizadeh, H.; Heravi, M. M. A one-pot and convenient
synthesis of coumarins in solventless system. Phosphorus, Sulfur Silicon Relat.
Elem. 2003, 178, 2555–2559.
27. Harayama, T.; Nakatsuka, K.; Nishioka, H.; Murakami, K.; Hayashida, N.;
Ishii, H. Convenient synthesis of a simple coumarin from salicylaldehyde and
Wittig reagent (II): synthesis of bromo- and methoxycarbonylcoumarins.
Chem. Pharm. Bull. 1994, 42 (10), 2170–2173.
28. Morgan, G.T.; Mickletwait, M. G. F. 6-Aminocoumarin. J. Chem. Soc. 1904,
85, 1230.
29. Palimkar, S. S.; Siddiqui, S. A.; Thomas, D.; Lahoti, R. J.; Srinivasan, K. V.
Ionic liquid–promoted regiospecific Friedlander annulation: Novel synthesis
of quinolines and fused polycyclic quinolines. J. Org. Chem. 2003, 68,
9371–9378.