Iodine-mediated one-pot synthesis of 3-cyanocoumarins and 3-cyano-4-methylcoumarins

Article abstract of DOI:10.2298/JSC130127140S

2-Hydroxybenzaldehydes 1a-e on reaction with malononitrile (2) in the presence of iodine as catalyst give 3-cyanocoumarins 3a-e in one step under thermal heating as well as under microwave irradiation. The latter conditions are much more efficient in terms of time (2-5 min) and yield as compared to the thermal conditions (2-2.5 h). Following a similar procedure, 3-cyano-4-methylcoumarins 3f-i were also prepared by the reaction of 2-hydroxyacetophenones 1f-i with 2.

Full text of DOI:10.2298/JSC130127140S

J. Serb. Chem. Soc. 79 (5) 527–531 (2014)
JSCS–4604
UDC 547.226+547.261’587.51’49+
542.913:54–732+537.5
Short communication
SHORT COMMUNICATION
Iodine-mediated one-pot synthesis of 3-cyanocoumarins and
3
-cyano-4-methylcoumarins
1
2
DINESH SHARMA * and JAGDISH K. MAKRANDI
1
Department of Chemistry, BRCM College of Engineering & Technology, Bahal-127028,
2
India and Department of Chemistry, Maharshi Dayanand University, Rohtak-124001, India
(
Received 27 January, accepted 21 November 2013)
Abstract: 2-Hydroxybenzaldehydes 1a–e on reaction with malononitrile (2) in
the presence of iodine as catalyst give 3-cyanocoumarins 3a–e in one step
under thermal heating as well as under microwave irradiation. The latter
conditions are much more efficient in terms of time (2–5 min) and yield as
compared to the thermal conditions (2–2.5 h). Following a similar procedure,
3
2
-cyano-4-methylcoumarins 3f–i were also prepared by the reaction of
-hydroxyacetophenones 1f–i with 2.
Keywords: 3-cyanocoumarin/3-cyano-4-methylcoumarin; malononitrile; iod-
ine; microwave irradiation; one-pot reaction.
INTRODUCTION
3
-Cyanocoumarins (2-oxo-2H-chromene-3-carbonitriles) constitute an impor-
1
tant class of compounds because of their biological activities, such as anti-
microbial properties and inhibition of α-chymotripsin. These compounds have
also been used as intermediates for the preparation of methine dyes, cephalo-
sporins, modified pencillins, oxygen-bridged tetrahydropyridones and isou-
reases.
2
3
4
5
6
7
8
3
-Cyanocoumarins were earlier prepared by the reaction of 2-hydroxy-
benzaldehydes with malononitrile or with ethyl cyanoacetate under basic condi-
9
10
11
tions using various bases, such as pyridine, piperidine, aqueous alkali, Mg–Al
12
13
14,15
hydrotalcite, MgO and ionic liquids.
In addition, these reactions have
1
6
been performed under phase transfer catalysed conditions. In recent reports,
these compounds were obtained by the condensation of 2-hydroxybenzaldehydes
1
7
18
with malononitrile using ZrCl /[bmim]BF and SiCl in ethanol.
4
4
4
*
Corresponding author. E-mail: dksharma_84@rediffmail.com
doi: 10.2298/JSC130127140S
5
27
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5
28
SHARMA and MAKRANDI
However, these methods suffer from one or other limitations. The former
reaction between 2-hydroxybenzaldehyde and malononitrile gives 2-imino-2H-
chromene-3-carbonitrile as an intermediate that has to be hydrolysed under acidic
1
6
conditions. In the latter method, 3-carboxycoumarins are also formed along
1
9
with 3-cyanocoumarins.
In recent years, molecular iodine was used as a mild and efficient con-
2
0–23
densing agent in various organic reactions.
Thus, it was thought worthwhile
to study the reaction of 2-hydroxybenzaldehydes and malononitrile using iodine
as catalyst, which led to the synthesis of 3-cyanocoumarins in a single step.
RESULTS AND DISCUSSION
A solution of 2-hydroxybenzaldehyde (1a) and malononitrile (2) in dime-
thylformamide (DMF) was refluxed in the presence of a catalytic amount of iod-
ine, and the reaction was found to proceed to completion in 2 h, as evidenced by
thin layer chromatography (TLC), affording a colourless compound that was
1
13
identified as 3-cyanocoumarin (3a) based on its IR, H-NMR and C-NMR
spectral data.
As the reactions are known to be improved when they are performed under
2
4
microwave irradiations, the above reaction was repeated using microwave irra-
diation and it was found to be completed in 2 min and 3-cyanocoumarin was
obtained in 90 % yield.
Using the above conditions, 3-cyano-4-methylcoumarins 3f–i were also
prepared by the reaction of 2-hydroxyacetophenones 1f–i with 2 using iodine as
catalyst under both thermal and microwave conditions.
The optimum conditions of the reaction were checked by varying the amount
of iodine and 0.12 mmol of iodine was found to be sufficient for completion of
the reaction. No reaction was found to take place in the absence of the catalyst. It
appears that initial condensation between 2-hydroxybenzaldehyde and malono-
nitrile was catalysed by iodine, which is known to act as a condensing agent due
2
5
to its Lewis acidity. Excessive amounts of iodine (20–40 mol %) were found
excessive, as no further improvement of the reaction was found either in terms of
the yield or the reaction time.
The methods reported earlier could not be used successfully for the prepa-
ration of 3-cyano-4-methylcoumarins involving reaction of 2-hydroxyacetophe-
nones with malononitrile as it required stringent conditions and the yields were
very poor. However, these compounds could be obtained in excellent yield (85–
–
90 %) using the present method. The success of the method was established by
the synthesis of various substituted 3-cyanocoumarins and 3-cyano-4-methylcou-
1
marins 3a–i. The identity of all the compounds was checked by their IR and H-
-
NMR spectral data, given in the Supplementary material to this paper, and com-
parison of the melting points with literature values, Table I.
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ONE-POT SYNTHESIS OF 3-CYANO-4-METHYLCOUMARINS
529
EXPERIMENTAL
The melting points of 3a–i were determined in open capillaries. The IR spectra were
recorded on a Perkin-Elmer spectrum BX series FT-IR spectrophotometer using the KBr
1
13
pellets technique. The H- and C-NMR spectra were recorded on a Bruker Avance (400
MHz) instrument using TMS as an internal standard. The reactions were performed in a
microwave oven (Samsung, model CE1031LFB, output energy 900 W, frequency 2450 MHz)
with a temperature control arrangement maintaining the temperature of the oven at 100 °C
using 50 % power for all the experiments.
TABLE I. Physical data of 3-cyanocoumarins and 3-cyano-4-methylcoumarins; method A:
thermal conditions; method B: microwave conditions
Compound
Structure
Compound
Structure
1a
3a
1
b
3b
3c
3d
1c
1
d
1
e
f
3e
3f
O
O
1
CN
CH3
1g
3g
1
1
h
i
3h
3i
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5
30
SHARMA and MAKRANDI
TABLE I. Continued
Method A
Method B
Compound
R
R1
R2
M.p. / °C
Time, h Yield, % Time, min Yield, %
1
2
2
2
2
3
2
2
2
0
3
3
3
3
3
3
3
3
3
a
b
c
d
e
f
g
h
i
H
H
H
H
H
CH3
CH3
CH3
H
H
H
H
OCH3
H
H
Br
Cl
CH3
H
2
2
2
2
2
2.5
2.5
2.5
2.5
85
92
86
80
82
86
90
90
85
2
2.5
2.5
3
3
4
5
4
5
90
95
92
85
86
92
95
95
87
179–181
195–196
190–192
204–206
223–226
190–192
200–201
178–180
220–222
6
7
8
9
0
6
6
9
H
H
H
CH3
Br
H
CH3 OCH3
General procedure for the synthesis of 3-cyano-/3-cyano-4-methyl-coumarins 3a–i
Method A (thermal conditions). A mixture of 2-hydroxybenzaldehydes/2-hydroxyaceto-
phenones 1a–i (4.71 mmol), malononitrile (2, 0.32 g, 4.71 mmol), iodine (0.03 g, 0.12 mmol)
and dimethylformamide (10 mL) in a round bottom flask (50 ml) was heated in an oil bath at
1
40–145 °C for 2–2.5 h. Completion of the reaction was monitored by thin layer chromato-
graphy (silica gel plates using the solvent benzene: acetone, 1:1). The reaction mixture was
cooled and ice-cold sodium thiosulphate solution (10 %, 30 mL) was added to remove any
iodine present in the reaction mixture. The solid that separated out was filtered, washed with
water and recrystallised from aqueous ethanol to give 3a–i.
Method B (microwave conditions): A mixture of 2-hydroxybenzaldehydes/2-hydroxy-
acetophenones 1a–i (4.71 mmol), malononitrile (2, 0.32 g, 4.71 mmol), iodine (0.03 g, 0.12
mmol) and dimethylformamide (5 mL) taken in a loosely stoppered round bottom flask was
subjected to microwave irradiation for 2–5 min. Completion of the reaction was controlled by
thin layer chromatography and the work-up was as described above to give 3a–i.
CONCLUSION
In conclusion, the presented method appears to be extremely simple and highly
efficient giving 3-cyano- and 3-cyano-4-methyl-coumarins in a single step.
SUPPLEMENTARY MATERIAL
Spectral data for the synthesised coumarins are available electronically from http://
/
/www.shd.org.rs/JSCS/, or from the corresponding author on request.
И З В О Д
ЈЕДНОСТАВНА СИНТЕЗА 3-ЦИЈАНОКУМАРИНА И 3-ЦИЈАНО-4-МЕТИЛКУМАРИНА
У ПРИСУСТВУ ЈОДА
1
2
DINESH SHARMA и JAGDISH K. MAKRANDI
1
2
Department of Chemistry, BRCM College of Engineering & Technology, Bahal-127028, India и Department
of Chemistry, Maharshi Dayanand University, Rohtak-124001, India
2-Хидроксибензалдехиди 1a–e у реакцији са малондинитрилом (2), у присуству
јода као катализатора, под условима термалног загревања или микроталасног озрачи-
вања, као производ дају 3-цијанокумарине 3a–e. Реакције под микроталасима трају
знатно краће време (2–5 min) у поређењу са термичким загревањем (2–2,5 h). При-
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_
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ONE-POT SYNTHESIS OF 3-CYANO-4-METHYLCOUMARINS
531
меном сличних реакционих услова, 3-цијано-4-метилкумарини 3f–i су добијени пола-
зећи од 2-хидроксиацетофенона 1f–i и 2.
(
Примљено 27. јануара, прихваћено 21. новембра 2013)
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