ZrCl4/[bmim]BF4-catalyzed condensation of salicylaldehydes and malononitrile: Single-step synthesis of 3-cyanocoumarin derivatives

Article abstract of DOI:10.1002/jhet.593

Figure represented. A versatile and efficient single-step route to 3-cyanocoumarins via Knoevenagel condensation of salicylaldehydes and malononitrile using ZrCl₄ as the catalyst (15 mol %) in ionic liquid 1-(n-butyl)-3-methylimidazolium tetrafluoroborate as reaction medium and catalyst is described. The novel procedure features single step, short reaction time, good yields, and simple workup.

Full text of DOI:10.1002/jhet.593

July 2011
ZrCl /[bmim]BF -Catalyzed Condensation of Salicylaldehydes
4
799
4
and Malononitrile: Single-Step Synthesis of 3-Cyanocoumarin
Derivatives
Hassan Valizadeh,* Manzar Mahmoodian, and Hamid Gholipour
Department of Chemistry, Faculty of Sciences, Azarbaijan University of Tarbiat Moallem,
Tabriz, Iran
*
E-mail: h-valizadeh@azaruniv.edu
Received February 3, 2010
DOI 10.1002/jhet.593
Published online 11 April 2011 in Wiley Online Library (wileyonlinelibrary.com).
A versatile and efficient single-step route to 3-cyanocoumarins via Knoevenagel condensation of sali-
cylaldehydes and malononitrile using ZrCl as the catalyst (15 mol %) in ionic liquid 1-(n-butyl)-3-
4
methylimidazolium tetrafluoroborate as reaction medium and catalyst is described. The novel procedure
features single step, short reaction time, good yields, and simple workup.
J. Heterocyclic Chem., 48, 799 (2011).
INTRODUCTION
ture of the salicylaldehydes and malononitrile [12]. Pro-
en c¸ a and coworkers [13] reported the synthesis of new
dimeric chromene derivatives via Knoevenagel conden-
sation of malononitrile and salicylaldehydes by a deli-
cate control of the experimental conditions. Yamashita
et al. [14] synthesized of 3-cyanocoumarins from Ti(O-
Coumarins and their derivatives are very important
organic compounds. They are the structural unit of sev-
eral natural products [1]. Their applications range from
pharmaceuticals [2], optical brighteners [3], and laser
dyes [4]. Also, coumarins and functionalized coumarins
have shown activity as antimicrobials and chemothera-
peutics [5]. These properties have made coumarins inter-
esting targets for organic chemists. Coumarins have
been synthesized using several synthetic routes such as
Pechmann, Perkin, Knoevenagel, Reformatsky, and Wit-
tig reactions. However, due to simple and relatively
inexpensive starting materials, the Knoevenagel reaction
was widely used for the synthesis of coumarins.
i-Pr) -catalyzed Knoevenagel condensation of malo-
4
nonitrile and salicylaldehydes in isopropyl alcohol as a
solvent. Recently, we reported the synthesis of benzo[b]-
pyran-2-imines via Knoevenagel condensation of malo-
nonitrile and salicylaldehydes over MgO and subsequent
transformation to the coumarins derivatives by hydroly-
sis under acidic conditions [15]. In continuation of our
work [16] on the development of efficient and environ-
mentally benign procedures in synthetic organic chemis-
try, we wish to report the synthesis of 3-cyanocoumarins
from single-step ZrCl /[bmim]BF -catalyzed Knoevena-
Knoevenagel condensation is one of the most impor-
tant methods for carbon–carbon double bond formation
in synthetic chemistry [6]. Generally, Knoevenagel reac-
tions are carried out by the condensation of active meth-
ylene compounds with aldehydes, with some organic
bases, as well as their salts as catalysts. Alternative pro-
tocols for Knoevenagel condensations catalyzed by
Lewis acids and various heterogeneous solid bases have
been reported in literature [7–9]. We reported the syn-
thesis of coumarin derivatives via Knoevenagel reaction
of 2-hydroxybenzaldehyde derivatives with some active
methylene compounds in aqueous media and also in
ionic liquids [10,11].
4
4
gel reaction of salicylaldehydes and malononitrile at
room temperature.
RESULTS AND DISCUSSION
A typical reaction of salicylaldehyde and malononi-
trile was carried out in the ionic liquid, [bmim]Cl, at
ambient conditions to form benzo[b]pyran-2-imine 3
(Scheme 1).
At room temperature, the reaction did not proceed fur-
ther to afford the product. So, it was carried out at higher
temperatures and the optimum results were obtained at
Several publications report the preparation of 2-imino-
chromene from Knoevenagel condensation of 1:1 mix-
V
C
2011 HeteroCorporation

8
00
H. Valizadeh, M. Mahmoodian, and H. Gholipour
Vol 48
Scheme 1
stituents were reacted efficiently and afforded good yields of
coumarins 4a–i under these conditions (Scheme 2).
CONCLUSIONS
In summary, we have developed a single step, con-
venient, and efficient synthetic approach to synthesize 3-
ꢀ
cyanocoumarins via the ZrCl /[bmim]BF -catalyzed
4 4
7
5 C (32%). For further optimization, several ionic
liquids (ILs) based on butylmethylimidazolium salts,
Knoevenagel condensation of malononitrile with salicy-
laldehyde derivatives at room temperature. Because of
the short reaction times with good yields and simple
work up procedure, this methodology could serve as a
valuable alternative to known methods.
[
bmim]X, with varying anions were screened for the
ꢀ
above typical reaction at 75 C. Evidently, 1-(n-butyl)-3-
methylimidazolium tetrafluoroborate ([bmim]BF ) was
4
found to be superior in terms of yield (42%) and reaction
time (2 h) when compared with other ILs (Table 1).
An experiment to demonstrate the catalytic ability of
ZrCl was carried out in [bmim]BF for this procedure.
EXPERIMENTAL
4
4
General information. All reagents were purchased from
Merck Company and used without further purification. Infrared
spectra were recorded in KBr and were determined on a Perkin
Elmer FTIR spectrometer. H-NMR and C-NMR spectra
were recorded on a Bruker Avance AC-400 MHz using
In contrast, reactions of the salicylaldehyde and malono-
nitrile do not lead just to benzo[b]pyran-2-imine 3 but
also to coumarins 4a (Scheme 2). In the presence of
1
13
equimolar amount of ZrCl , product 4a was produced in
4
5
2% yield for 30 min at room temperature in
bmim]BF4 (entry 11, Table 1). To find an optimal
DMSO-d
6
as the deuterated solvents and tetramethylsilane
[
(TMS) as internal standard. All melting points are uncorrected
and measured in open glass capillaries using Stuart melting
point apparatus. Elemental analyses were carried out on a Per-
kin-Elmer 240C elemental analyzer and are reported in percent
atomic abundance.
amount of catalyst for the model reaction, the amount of
catalyst was reduced from 100 to 0.1% (molar fraction).
The results are collected in Table 1. The reactivity for
the lower amount of ZrCl4 (0.1% molar fraction)
decreased obviously and two products 3 and 4a were
produced under these conditions. According to the
results from Table 1, we choose 15% molar fraction as
an optimal amount of catalyst for further experiments.
General procedure for the synthesis of 3-cyanocoumarins
(
4a–i). Salicylaldehyde derivative (15 mmol) and malononitrile
15 mmol) were added to [bmim]BF (3 mL) and mixed thor-
oughly for 10 min. ZrCl (15 mol %) was added to the mixture
(
4
4
and stirred at room temperature. After completion of the reac-
tion, as indicated by thin layar chromotography (TLC; ethyla-
cetate/n-hexane, 2/5), the mixture was extracted with ethylace-
tate. The extracts were concentrated on a rotary evaporator
and the crude mixture was purified by recrystallization from
ethanol/water to give pure coumarins (4a–i).
The reaction in the absence of [bmim]BF was so slug-
4
gish that afforded the low yield of the unidentified mix-
ture of products.
With the best reaction conditions in hand, we investigated
the reaction of various salicylaldehyde derivatives with
malononitrile. Salicylaldehydes containing different sub-
3
ꢀ
-Cyano benzo[b]pyran-2-imine (3). White solid; mp: 141–
ꢁ1
ꢀ
143 C (lit. [14] 140–141 C); IR (KBr) (mmax/cm ): 3310,
Table 1
Knoevenagel condensation of salicylaldehyde and malononitrile under different conditions
a
ꢀ
c
Yield (%)
Entry
Ionic liquid
ZrCl
4
(mol %)
Temperature ( C)
Time (min)
Product
1
2
3
4
5
6
7
8
9
[bmim]Cl
[bmim]Cl
[bmim]Br
0
0
0
0
75
75
75
25
25
25
25
25
25
25
180
120
120
120
40
3
3
3
<20
32
38
42
55
72
73
83
75
62
52
[bmim]BF
[bmim]BF
[bmim]BF
[bmim]BF
[bmim]BF
[bmim]BF
[bmim]BF
[bmim]BF
4
4
4
4
4
4
4
4
0
0.1
5
3
3:4a (35:20)
3:4a (20:52)
b
b
40
35
35
30
30
30
10
15
25
50
4a
4a
4a
4a
4a
1
1
0
1
100
a
b
c
Salicylaldehyde (15 mmol) and malononitrile (15 mmol).
Products 3 and 4a were produced under these conditions.
Isolated yield of product.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2011
ZrCl /[bmim]BF -Catalyzed Condensation of Salicylaldehydes and Malononitrile:
4
801
4
Single-Step Synthesis of 3-Cyanocoumarin Derivatives
Scheme 2
1
220, 1651; H-NMR (400 MHz, DMSO-d
2
7
1
1
1
6
) d 7.46 (m, 2H),
157.02, 160.32; Anal. Calcd (%) for C10
H
2.69; N, 7.48. Found (%): C, 64.19; H, 1.67; N, 7.47.
5
NO
3
: C, 64.18; H,
.49 (dd, J ¼ 8.15, 1.44 Hz, 1H), 7.68 (dd, J ¼ 8.05, 1.43 Hz,
1
3
H), 8.14 (s, 1H); C-NMR (100 MHz, DMSO-d ) d 105.13,
7-Methoxy-2-oxo-2H-chromene-3-carbonitrile (4f). Yellow
ꢀ ꢀ
6
17.08, 117.43, 119.09, 119.91, 127.82, 131.81, 139.12,
50.45, 162.32; Anal. Calcd for C10
solid; Yield: (83%); mp: 224–226 C (lit. [14] 225–226 C); IR
ꢁ
1
1
H
6
N
2
O: C, 70.58; H, 3.55;
(KBr) (mmax/cm ): 2227, 1720, 1638; H-NMR (400 MHz,
DMSO-d
) d 3.90 (s, 3H), 7.11 (dd, J ¼ 8.71, 2.39 Hz, 1H),
7.15 (d, J ¼ 2.39 Hz, 1H), 7.76 (d, J ¼ 8.71 Hz, 1H), 8.85 (s,
N, 16.46. Found: C, 71.40; H, 3.58; N, 16.54.
6
2
-Oxo-2H-chromene-3-carbonitrile
ꢀ
(4a). White
ꢀ
solid;
Yield: (83%); mp: 183–185 C (lit. [17] 184–185 C); IR (KBr)
m
13
1H);
115.25, 116.63, 120.20, 127.87, 130.36, 137.74, 153.56,
158.36, 159.16; Anal. Calcd (%) for C11 NO : C, 65.67; H,
C-NMR (100 MHz, DMSO-d ) d 63.71, 105.52,
6
ꢁ
1
max/cm ): 2220, 1712, 1645; H-NMR (400 MHz, DMSO-
1
(
d
6
) d 7.44 (m, 2H), 7.65 (dd, J ¼ 7.46, 1.62 Hz, 1H), 7.75
H
7
3
1
3
(
dd, J ¼ 7.54, 1.45 Hz, 1H), 8.30 (s, 1H); C-NMR (100
3.51; N, 6.96. Found (%): C, 65.85; H, 3.56; N, 6.60.
8-Methoxy-2-oxo-2H-chromene-3-carbonitrile (4g). Yellow
MHz, DMSO-d ) d 103.61, 112.00, 117.56, 117.22, 128.15,
6
ꢀ
ꢀ
1
28.21, 136.50, 152.11, 155.20, 156.88; Anal. Calcd (%) for
NO : C, 70.18; H, 2.94; N, 8.18. Found (%): C, 70.23;
H, 2.95; N, 8.21.
-Hydroxy-2-oxo-2H-chromene-3-carbonitrile (4b). Yellow
solid; Yield: (84%); mp: 224–226 C (lit. [17] 225–226 C); IR
ꢁ
1
1
C
10
H
5
2
(KBr) (mmax/cm ): 2253, 1745, 1641; H-NMR (400 MHz,
DMSO-d ) d 3.90 (s, 3H), 7.20–7.41 (m, 3H), 8.88 (s, 1H);
C-NMR (100 MHz, DMSO-d ) d 67,11, 102.23, 115.56,
6
13
5
6
ꢀ
ꢁ1
solid; Yield: (81%); mp: 229–232 C; IR (KBr) (mmax/cm ):
116.23, 120.54, 127.89, 132.23, 137.63, 153.63, 158.85,
160.36; Anal. Calcd (%) for C H NO : C, 65.67; H, 3.51; N,
1
383 (broad), 2223, 1719, 1611; H-NMR (400 MHz, DMSO-
3
d
1
8
1
1
11
7
3
6
): d 7.29 (dd, J ¼ 7.98, 8.11 Hz, 1H), 7.33 (dd, J ¼ 7.98,
6.96. Found (%): C, 65.80; H, 3.55; N, 6.71.
7-Diethylamino-2-oxo-2H-chromene-3-carbonitrile
.31 Hz, 1H), 7.60 (dd, J ¼ 8.11, 1.31 Hz, 1H), 8.12 (s, 1H),
1
3
ꢀ
.79 (s, 1H, OH); C-NMR (100 MHz, DMSO-d ) d 109.71,
(4h). Yellow solid; Yield: (79%); mp: 210–213 C (lit. [14]
ꢁ1
6
ꢀ
1
18.80, 119.08, 121.65, 124.31, 131.32, 136.45, 145.85,
56.63, 164.24; Anal. Calcd for C H NO : C, 64.18; H, 2.69;
211–212 C); IR (KBr) (mmax/cm ): 2217, 1715, 1640; H-
NMR (400 MHz, DMSO-d ) d 1.23 (t, J ¼ 6.87 Hz, 6H), 3.45
1
0
5
3
6
N, 7.48. Found: C, 64.29; H, 2.73; N, 7.52.
-Hydroxy-2-oxo-2H-chromene-3-carbonitrile (4c). Yellow
(q, J ¼ 6.87 Hz, 4H), 6.47 (d, J ¼ 2.3 Hz, 1H), 6.60 (dd, J ¼
13
6
solid; Yield: (80%); mp: 236–239 C (lit. [14] 237–238 C); IR
8.89, 2.45 Hz, 1H), 7.31 (d, J ¼ 8.89 Hz, 1H), 7.99 (s, 1H);
ꢀ
ꢀ
C-NMR (100 MHz, DMSO-d ) d 15.21, 56.63, 105.52,
6
ꢁ
1
1
(
(
KBr) (mmax/cm ): 3391 (broad), 2250, 1710, 1645; H-NMR
400 MHz, DMSO-d
) d 7.12 (d, J ¼ 2.01 Hz, 1H), 7.20 (dd, J
7.68, 2.01 Hz, 1H), 7.35 (d, J ¼ 7.68 Hz, 1H), 8.85 (s, 1H),
115.25, 116.63, 120.20, 127.87, 130.36, 137.74, 153.56,
6
14 2 2
158.36, 159.16; Anal. Calcd (%) for C14H N O : C, 69.41; H,
¼
5.82; N, 11.56. Found (%): C, 69.22; H, 5.84; N, 11.67.
6-Bromo-2-oxo-2H-chromene-3-carbonitrile
1
3
8
1
1
7
.85 (s, 1H, OH); C-NMR (100 MHz, DMSO-d
6
) d 102.56,
(4i). White
ꢀ
ꢀ
13.54, 116.23, 117.02, 127.89, 130.23, 138.63, 151.56, 156.54,
58.02; Anal. Calcd (%) for C H NO : C, 64.18; H, 2.69; N,
solid; Yield: (88%); mp: 201–202 C (lit. [17] 200–201 C); IR
ꢁ
1
1
(KBr) (mmax/cm ): 2223, 1732, 1641; H-NMR (400 MHz,
DMSO-d
) d 7.15 (d, J ¼ 7.36 Hz, 1H), 7.25 (dd, J ¼ 7.36,
1.96 Hz, 1H), 7.41 (d, J ¼ 1.96 Hz, 1H), 8.82 (s, 1H); C-
NMR (100 MHz, DMSO-d ) d 105.52, 114.32, 116.02, 119.98,
1
0
5
3
.48. Found (%): C, 64.22; H, 2.71; N, 7.45.
-Hydroxy-2-oxo-2H-chromene-3-carbonitrile (4d). Yellow
6
13
7
solid; Yield: (84%); mp: 246–248 C (lit. [18] 249–251 C); IR
ꢀ
ꢀ
6
ꢁ
1
1
(
(
KBr) (mmax/cm ): 3395 (broad), 2227, 1720, 1638; H-NMR
128.63, 131.08, 138.78, 152.42, 157.86, 160.32; Anal. Calcd
(%) for C H BrNO : C, 48.03; H, 1.61; N, 5.60. Found (%):
C, 48.20; H, 1.64; N, 5.65.
400 MHz, DMSO-d ) d 7.13 (dd, J ¼ 8.85, 2.41 Hz, 1H),
6
10
4
2
7
1
1
1
2
.15 (d, J ¼ 2.41 Hz, 1H), 7.78 (d, J ¼ 8.85 Hz, 1H), 8.78 (s,
1
3
6
H), 8.81 (s, 1H, OH); C-NMR (100 MHz, DMSO-d ) d
04.25, 114.45, 117.85, 121.12, 128.05, 133.32, 138.68, 154.58,
59.46, 161.09; Anal. Calcd (%) for C H NO : C, 64.18; H,
Acknowledgments. The partial financial assistance from the
Research Vice Chancellor of Azarbaijan University of Tarbiat
Moallem is gratefully acknowledged.
1
0
5
3
.69; N, 7.48. Found (%): C, 64.25; H, 2.71; N, 7.51.
-Hydroxy-2-oxo-2H-chromene-3-carbonitrile (4e). Yellow
8
solid; Yield: (80%); mp: 228–230 C (lit. [14] 228–230 C); IR
KBr) (mmax/cm ): 3385 (broad), 2253, 1745, 1641; H-NMR
ꢀ
ꢀ
ꢁ
1
1
(
(
(
REFERENCES AND NOTES
400 MHz, DMSO-d ) d 7.21–7.38 (m, 3H), 8.75 (s, 1H), 8.89
6
13
s, 1H, OH); C-NMR (100 MHz, DMSO-d
6
) d 104.54,
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