Visible light induced, catalyst free, convenient synthesis of chromene nucleus and its derivatives using water-ethanol mixture as a solvent

Article abstract of DOI:10.1039/c5nj00002e

A highly efficient, green, eco-friendly, one pot protocol has been demonstrated for the synthesis of 2-imino-2H-chromene-3-carbonitrile (3), 2-aminochromene (4) and chromeno(2,3-b)pyridines (5). The synthesis of the chromene nucleus has been carried out under visible light irradiation in a water-ethanol mixture at room temperature using salicylaldehyde and malononitrile in different proportions. The adopted method shows significant advantages such as mild and clean reaction conditions, eco-friendly procedures, absence of catalysts and a short reaction time. This protocol involves the use of CFL as the visible light source and shows high selectivity in the presence of a mixture of ethanol and water. The reaction proceeds with good to excellent yield.

Full text of DOI:10.1039/c5nj00002e

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Visible light induced, catalyst free, convenient
synthesis of chromene nucleus and its derivatives
using water–ethanol mixture as a solvent
Cite this:DOI: 10.1039/c5nj00002e
Snehlata Yadav,a Madhulika Srivastava,a Pratibha Rai,a Jaya Singh,b
Kamla Prasad Tiwaria and Jagdamba Singh*a
A highly efficient, green, eco-friendly, one pot protocol has been demonstrated for the synthesis of
2-imino-2H-chromene-3-carbonitrile (3), 2-aminochromene (4) and chromeno(2,3-b)pyridines (5). The
synthesis of the chromene nucleus has been carried out under visible light irradiation in a water–ethanol
mixture at room temperature using salicylaldehyde and malononitrile in different proportions. The
adopted method shows significant advantages such as mild and clean reaction conditions, eco-friendly
procedures, absence of catalysts and a short reaction time. This protocol involves the use of CFL as the
visible light source and shows high selectivity in the presence of a mixture of ethanol and water. The
reaction proceeds with good to excellent yield.
Received (in Montpellier, France)
8th January 2015,
Accepted 23rd March 2015
DOI: 10.1039/c5nj00002e
www.rsc.org/njc
and for creation of small scaffold ligands with highly noticeable
smooth muscle relaxant properties. The chromene nucleus is also
Introduction
The safety of the environment and consciousness about the broadly found in natural alkaloids, tocopherols, anthocyanins
reduction in global warming inspires the use of renewable and flavanoids.7 In addition, they activate potassium channels
energy resources and minimization of waste products. In the and inhibit dihydrofolate reductase and phosphodiesterase IV.
past several years, the development of a sustainable, eco- Chromene moieties have been able to prevent many diseases,
efficient energy source for the construction of biologically including psoriatic arthritis and rheumatoid arthritis and are also
important heterocycles has become an important research area widely used in cancer therapy.8 They have fluorescence properties,
in the field of synthesis.1 Visible light induced synthesis of and hence are used in brightening agents, optical whiteners and as
heterocycles has evoked the interest of chemists and researchers laser dyes in pharmacy and biology.
due to the easy availability of visible radiation. In addition, cost
In addition, iminocoumarins are an elite class of protein
effective radiation is useful and harmless to human beings.2 tyrosine kinase inhibitors of low molecular weight. A number of
Light is a perfect reagent for the environmentally benign, green anti-cancer agents contain the protein tyrosine kinase.9 Similar
synthesis of heterocyclic scaffolds because it activates organic to coumarin, iminocoumarins are used as dyes and fluorescent
molecules, facilitating a smooth completion of the chemical sensors for the evaluation of metal ions in micromolar con-
reaction.3 Solvents also play an important part in organic synthesis. centrations.10 2-Amino-4H-pyrans also show some important
Water is present in abundance in nature and show environment biological activities such as anticancer activity, central nervous
friendly behaviour.4 Therefore, we carried out the synthesis of system activity and anti-microbial activity. They are broadly
bioactive molecules in a mixture of ethanol and water, which is applied in cosmetic and agrochemical industries.11 The examples
observed as a green medium for synthesis.5 Chromenes are an of bioactive compounds synthesized by a multicomponent
important scaffold having oxygen as a heteroatom,6 and the method, involving the iminocoumarin moiety, are diethyl-2-
chromene nucleus commonly forms a part of various tannins amino-3-cyano-4H-chromen-4-ylphosphonate (compound A;
and polyphenols present in tea, vegetables, fruits and red wine. Fig. 1),12 which shows unique pharmacological properties
They show different types of bioactivities, such as antiviral, anti- such as being an anticoagulant; 2-(2-hydroxyphenyl)-3H-chromeno-
HIV, antidepressant, antioxidative, anticoagulant, antimicrobial, [2,3-d]pyrimidin-4(5H)-one (compound B; Fig. 1) and 2-amino-4-(3-
mutagenicity, antiproliferative, antitumor, diuretic, antianaphylactic bromo-4,5-dimethoxyphenyl)-7-(dimethylamino)-4H-chromene-
3-carbonitrile (compound C; Fig. 1) as antitumor agents; and
compound D, which is used in cancer therapy.
Multicomponent reactions show many advantages over con-
ventional multistep synthesis such as short reaction time, cost
a Environmentally Benign Lab, Department of Chemistry, University of Allahabad,
211002, India. E-mail: dr.jdsau@gmail.com; Tel: +91 9415218507
b L R PG College, Sahibabad, UP, India
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Results and discussion
In order to investigate the effect of solvent, we used a number of
polar and nonpolar reaction media to perform the test reac-
tions. It was observed that polar solvents increased the yield of
the product more compared to nonpolar ones (Table 1, entry 3).
We know that cyclisation reactions occur more smoothly in
polar reaction media;17 hence, we shifted our attention towards
the use of water and ethanol as a solvent.
In order to obtain a high yield of the product and to decrease
the overall reaction time, the degree of the polarity of the
reaction medium was optimized by the addition of ethanol as
a co-reaction medium in water in different ratios18 (Table 2).
When the reaction was performed in pure ethanol, the yield of
the product was not satisfactory (Table 2, entry 1). The result
clearly indicates that 50% ethanol in water proved to be the
optimum solvent in which a good yield was obtained in mini-
mum time15a (Table 2, entry 4).
Our next step was to optimize the intensity of visible light in
order to achieve maximum yield (Table 3). The results showed
that the enhancement of illumination intensity of CFL above
22 W does not significantly affect the yield of the product.
Having optimized the reaction conditions, we performed the
reaction with different derivatives of salicylaldehyde to prepare
a series of chromene nuclei (Table 4).
Fig. 1 Some biodynamic chromene nuclei.
effectiveness, energy efficiency and the use of minimum
amounts of raw material. They involve the formation of a
number of bonds in a single step.13 A number of methods14
have been reported for the synthesis of coumarin derivatives.
For example, Somnath Ghosh et al. synthesized a chromene
nucleus using salicylaldehyde and Meldrum’s acid via a photo-
chemical method; Majid M. Heravi also synthesized a chromene
nucleus in the presence of MCM-41; M. N. Elinson used the
grinding method for the synthesis of a chromene nucleus; and
M. Costa and co-workers synthesized new dimeric chromene
derivatives. It has been observed that all the methods require
thermal energy, long reaction time and the use of toxic solvents
for the completion of the reaction.15 Considering these aspects,
and in continuation of our previous work,16 we report a highly
efficient visible light catalyzed synthesis of bioactive hetero-
cycles (Scheme 1).
To extend the scope of this protocol, we used different ratios
of reactant molecules. First, the reaction of salicylaldehyde (1)
was carried out with 2 equivalents of malononitrile (2) under
Salicylaldehyde (1c) and malononitrile (2) were added in
stoichiometric amounts to a mixture of water and ethanol (1 : 1,
20 ml) and irradiated under visible light (22 W, CFL) at rt.
Corresponding iminocoumarins (3c) were obtained in good to
excellent yield (Scheme 2).
Table 1 Optimization of solvents
Entry
Solvent
Time (min)
Yielda (%)
1
2
3
4
5
6
7
Water
Ethanol
Ethanol : water (1 : 1)
Acetonitrile
DMSO
DCM
Neat
15
20
5
20
25
22
12
86
88
92
72
74
76
89
a
Isolated yield in % salicylaldehyde (1 mmol), malononitrile (1 mmol)
in ethanol:water mixture.
Table 2 Effect of solvent ratio on the yield
Entry
Solvent
Time (min)
Yielda (%)
Scheme 1 Visible light catalyzed synthesis of chromene derivatives.
1
2
3
4
5
6
7
100% ethanol
5
5
5
5
5
5
5
78
79
80
94
92
90
89
80% ethanol in water
70% ethanol in water
50% ethanol in water
30% ethanol in water
10% ethanol in water
5% ethanol in water
a
Isolated yield in % salicylaldehyde (1 mmol), malononitrile (1 mmol)
in ethanol:water mixture.
Scheme 2 Synthesis of 2-imino-2H-chromene-3-carbonitrile.
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Table 3 Optimization of reaction conditions
Table 6 Substrate scope for the formation of compound (5)
Entry
Reaction condition
Time (min)
Yielda (%)
1
1
2
3
3
4
CFL (18 W)
CFL (22 W)
CFL (24 W)
CFL (36 W)
Daylight
9
5
9
5
12
15
94
97
97
97
88
64
Entry
R1
R2
Time (min)
Yielda
M.P. (1C)
a
b
c
d
e
f
Br
H
H
Br
H
CH3
OCH3
OCH3
H
H
OEt
H
12
10
8
15
15
15
88
89
97
89
90
96
4300
4300
4300
4300
4300
4300
Dark
a
Isolated yield in % salicylaldehyde (1 mmol), malononitrile (1 mmol)
in ethanol:water mixture.
Table 4 Substrate scope for the formation of compound (3a–g)
Reaction between one mole salicylaldehyde and 3 mole of malononitrile.
Isolated yield in %.
a
Entry
R1
R2
Time (min)
Yielda (%)
M.P. (1C)
a
b
c
d
e
f
H
OH
H
Br
H
CH3
Cl
OCH3
H
H
H
OH
H
9
10
5
8
7
8
10
92
88
97
89
98
90
91
4260
4260
138–140
192–194
4260
—
g
H
—
a
Reaction between one mole salicylaldehyde and malononitrile. Is
isolated yield in %.
Table 5 Substrate scope for the formation of compound (4a–h)
Entry
R1
R2
Time (min)
Yielda (%)
M.P. (1C)
a
b
c
d
e
f
H
H
H
CH3
Br
OH
Cl
OCH3
OEt
H
H
H
H
H
OCH3
8
7
9
7
10
8
96
98
96
98
89
95
88
87
171–172
96–99
150–151
138–142
163–165
—
Scheme 3 A plausible mechanism for the synthesis of chromene and its
derivatives.
g
h
10
9
154–157
161–162
Br
Reaction between one mole salicylaldehyde and two moles of malono- water and the formation of the corresponding benzylidene
a
nitrile. Isolated yield in %.
malononitrile (B). The subsequent intramolecular cyclization of
the Knoevenagel adduct (B) gives substituted 2-imino-2H-
chromene-3-carbonitriles (I).
Furthermore, the addition of a 2nd mole of malononitrile
to (I) gives (4H-chromene-4-yl)malononitrile (II), while the
addition of a 3rd mole of malononitrile to (II) gives (4-H-
chromene-4-yl) malononitrile (III) by an attack on the nitrile
group of the pyran ring of (II) followed by cyclization.
the same reaction conditions, resulting in 2-amino chromene
(4) (Table 5). This product was obtained due to Michael addi-
tion of malononitrile and iminocoumarins.
Furthermore, in order to enlarge the scope of our reaction,
we carried out the reaction of salicylaldehyde with 3 equivalents
of malononitrile, which led to the formation of chromeno-
(2,3-b)pyridines (5) (Table 6).
A mechanistic rationalization for the reaction is proposed in
Conclusion
(Scheme 3). This plausible mechanism12a shows that the active
methylene compound, malononitrile, undergoes tautomerisation19 To conclude, herein, we have put forward a method in which
in the presence of visible light and the solvent (i.e., water and the target products could be isolated by a simple filtration
alcohol), which gives (A). Knoevenagel condensation of (A) and method due to a difference in the solubility of product and
salicylaldehyde takes place in a solution with the elimination of reactant materials. To our delight, the products obtained were
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analytically so pure that there was no need for further purifica-
6-Bromo-2-imino-2H-chromene-3-carbonitrile (3d)14b,15f
.
tion, which avoided multiple extraction steps and separation by Yellowish white solid. mp 192–194 1C. IR (KBr) (nmax/cmÀ1
)
1
chromatography. Hence, the choice of the mixture water and 3338, 2250, 1651, 1585, 1556. H NMR d = 7.14 (d, J = 9.0 Hz,
ethanol as a solvent over other toxic solvents minimized the 1H), 7.71 (dd, J = 8.7 Hz, 2.4 Hz, 1H), 7.78 (d, J = 2.4 Hz, 1H),
impurity of the products, and thereby reduced the generation of 8.27 (s, 1H), 9.01 (s, 1H). 13C NMR d = 105.53, 114.97, 115.45,
waste by chromatographic separation.20
117.83, 119.31, 131.30, 136.22, 145.65, 150.81 Anal. Calc. for
C
10H5N2OBr; C, 48.19; H, 2.01; N, 11.24. Found: C, 47.95; H,
2.03; N, 11.15. EIMS 247 (M)+, 249 (M + 2)+.
8-Hydroxy-2-imino-2H-chromene-3-carbonitrile (3e)15f. Yellow
solid. mp 4260 1C. IR (KBr) (nmax/cmÀ1) 3330, 2222, 1640.
1H NMR d = 6.95–7.45 (m, 3H), 8.31 (s, 1H), 8.65 (s, 1H), 10.20
(brs, 1H). 13C NMR d = 104.11, 113.76, 115.23, 116.35, 117.54,
121.42, 146.83, 146.93, 152.02, 153.46. Anal. Calc. for C10H6N2O2;
C, 64.52; H, 3.23; N, 15.05. Found: C, 64.35; H, 3.40; N, 15.10.
EIMS 186 (M)+.
Experimental section
A. General information
Reagents were obtained from commercial suppliers, and used
without further purification unless otherwise specified by a
reference. All the reactions were performed using oven-dried
glassware. Organic solutions were concentrated using a Buchi
rotary evaporator. TLC was performed using silica gel GF254
(Merck) plates. Melting points were determined by open glass
capillary method and are uncorrected. IR spectra in KBr were
recorded on an Perkin-Elmer 993 IR spectrophotometer,
1H NMR spectra were recorded on a Bruker AVII 300 spectro-
meter in CDCl3 using TMS as an internal reference with
chemical shift values being reported in ppm. All the coupling
constants ( J) are reported in Hertz (Hz). Mass (EI) spectra were
recorded on a JEOL D-300 mass spectrometer. Elemental analyses
were carried out in a Coleman automatic carbon, hydrogen and
nitrogen analyzer.
2-(2-Amino-3-cyano-8-methoxy-4H-chromen-4-yl)malono-
nitrile (4a)14c. White solid. mp 171–172 1C. IR (KBr)
(nmax/cmÀ1) 3420, 2930, 2227. 1H NMR d = 3.39 (s, 3H), 4.56
(d, J = 3.9 Hz, 1H), 5.02 (d, J = 3.9 Hz, 1H), 7.01 (dd, J =
8.0 Hz, 1.5 Hz, 1H), 7.10 (dd, J = 8.1 Hz, 1.5 Hz, 1H), 7.18
(t, J = 8.1 Hz, 1H), 7.51 (s, 2H). Anal. Calc. for C14H10N4O2;
C; 63.16; H, 3.59; N, 21.05. Found: C, 63.30; H, 3.70; N,
20.80. EIMS 266 (M)+.
2-(2-Amino-3-cyano-4H-chromen-4-yl)malononitrile (4c)15f
.
White solid. mp 150–151 1C IR (KBr) (nmax/cmÀ1) 3320, 2228,
1652, 1641. 1H NMR d = 4.57 (d, J = 3.9 Hz, 1H), 5.05 (d, J =
3.9 Hz, 1H), 7.14 (dd, J = 8.1 Hz, 0.9 Hz, 1H), 7.27 (dt, J = 7.5 Hz,
0.9 Hz, 1H), 7.41 (dt, J = 7.8 Hz, 1.2 Hz, 1H), 7.46 (dd, J = 7.7 Hz,
B. General method
A mixture of 1 mole of salicyladehyde (1) and malononitrile (2) 1.2 Hz, 1H), 7.51 (s, 2H). Anal. Calc. for C13H8N4O; C, 66.10;
(1 mol for 3a–g, 2 mol for 4a–h and 3 mol for 5a–f) was added in H, 3.39; N, 23.73. Found: C, 65.80; H, 3.45; N, 23.78. EIMS
water and ethanol (1 : 1, 20 ml). The mixture was irradiated with 236 (M)+.
22 W CFL with stirring at rt. for 5–15 min. After the completion
2-(2-Amino-6-bromo-3-cyano-4H-chromen-4-yl)malononitrile
of the reaction (monitored by TLC), water (10 ml) was added (4e)14c,15f. White solid. mp 163–165 1C; IR (KBr) (nmax/cmÀ1) 2255,
and the mixture was filtered. The resulting product was recrys- 2148, 2130, 1655, 1638, 1590, 1565 cmÀ. 1H NMR d = 4.62
tallized using hot ethanol and a yield of 88–98% was obtained. (d, J = 3.6 Hz, 1H), 5.14 (d, J = 3.9 Hz, 1H), 7.12 (d, J = 9.0 Hz, 1H),
All the compounds that were obtained are known and were 7.52–7.61 (m, 3H), 7.71 (d, J = 2.4 Hz, 1H). 13C NMR d = 32.41,
characterised by comparison of their spectral data with those 36.73, 48.45, 112.74, 112.93, 116.45, 118.63, 119.13, 120.30,
reported in literature.
131.42, 131.95, 149.01, 163.23. Anal. Calc. for C13H7N4OBr; C,
2-Imino-8-methoxy-2H-chromene-3-carbonitrile (3a)15f. Yellow 48.83; H, 2.35; N, 17.53. Found: C, 49.12; H, 2.40; N, 17.20. EIMS
solid. mp 4260 1C. IR (KBr) (nmax/cmÀ1) 3420, 2940, 2228, 1650, 313 (M)+, 315 (M + 2)+.
1620. 1H NMR d = 3.80 (s, 3H), 7.13 (dd, J = 7.6 Hz, 1.5 Hz, 1H),
2-(2-Amino-6-bromo-3-cyano-8-methoxy-4H-chromen-4-yl)-
7.120 (t, J = 7.8 Hz, 1H), 7.31 (dd, J = 8.1 Hz, 1.8 Hz, 1H), malononitrile (4h)15f. White solid. mp 161–162 1C. IR (KBr)
8.34 (s, 1H), 8.91 (s, 1H). Anal. Calc. for C11H8N2O2; C, 65.41; (nmax/cmÀ1) 2248, 2189, 2120, 1675, 1651, 1626, 1590, 1572.
H, 3.96; N, 13.88. Found: C, 65.78; H, 4.09; N, 13.66. EIMS 1H NMR d = 3.87 (s, 3H), 4.58 (d, J = 3.9 Hz, 1H), 5.09 (d, J =
200 (M)+.
6-Hydroxy-2-imino-2H-chromene-3-carbonitrile (3b)14b,15f
3.9 Hz, 1H), 7.25 (d, J = 2.1 Hz, 1H), 7.32 (d, J = 2.1 Hz, 1H),
7.61 (s, 2H). 13C NMR d = 32.34, 36.82, 48.56, 56.44, 112.76,
.
Yellowish solid. mp 4260 1C. IR (KBr) (nmax/cmÀ1) 3245, 112.93, 115.8, 116.34, 119.12, 120.55, 122.03, 138.65, 148.11,
1
2222, 1656. H NMR d = 6.45–7.01 (m, 3H), 8.32 (s, 1H), 8.60 163.13. Anal. Calc. for C14H9N4O2Br; C, 48.70; H, 2.61;
(s, 1H), 9.76 (1H). Anal. Calc. for C10H6N2O2; C, 64.52; H, 3.25; N, 16.23. Found: C, 48.75; H, 2.89; N, 16.30. EIMS 343 (M)+,
N, 15.05. Found: C, 64.45; H, 3.30; N, 15.10. EIMS: 186 (M)+.
345 (M + 2)+.
2-Imino-2H-chromene-3-carbonitrile (3c)14b,15f
.
Yellowish
(2,4-Diamino-7-bromo-3-cyano-9-methoxy-5H-chromeno[2,3-b]-
white solid. mp 138–140 1C. IR (KBr) (nmax/cmÀ1) 3285, 2225, pyridin-5-yl) malononitrile (5a)12a. White Yellow solid. mp
1658, 1H NMR d = 7.16–7.20 (m, 1H), 7.27 (td, J = 7.5 Hz, 0.9 Hz, 4300 1C. IR (KBr) (nmax/cmÀ1) 3442, 3348, 2948, 2259, 2205,
1H), 7.52–7.60 (m, 2H), 8.36 (d, J = 1.5 Hz, 1H), 8.85 (s, 1H). 1627, 1563, 1489, 1403, 1236. 1H NMR d = 3.89 (s, 3H), 4.90–
Anal. Calc. for C10H6N2O; C, 69.85; H, 3.49; N, 16.30. Found: C, 4.92 (m, 2H), 6.72 (s, 2H), 7.05–7.9 (m, 3H), 7.32 (s, 1H). 13C NMR
70.02; H, 3.55; N, 16.20. EIMS 170 (M)+.
d = 30.31, 34.53, 56.40, 70.73, 83.24, 112.72, 113.21, 115.13,
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115.85, 116.11, 120.24, 122.26, 140.58, 148.62, 156.95, 160.01, Notes and references
160.42. Anal. Calc. for C17H12BrN6O2; C, 49.65; H, 2.70; N, 20.44.
Found: C, 49.70; H, 2.80; N, 20.48. EIMS 411 (M)+, 413 (M + 2)+.
(2,4-Diamino-3-cyano-9-methoxy-5H-chromeno[2,3-b]pyridin-
5-yl)malononitrile (5b)12a. Whitish yellow solid. mp 4300 1C. IR
(KBr) (nmax/cmÀ1) 3460, 3336, 2958, 2254, 2198, 1643, 1599, 1561,
1 (a) M. Costa, F. Areias, L. Abrunhosa, A. Venancio and
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1
1493, 1412. H NMR d = 3.84 (s, 3H), 4.86 (d, 1H, J = 3.9 Hz),
4.98 (d, 1H, J = 3.9 Hz), 6.67 (s, 2H), 6.96 (d, 1H, J = 7.3 Hz),
7.05 (s, 2H) 7.12–7.14 (m, 3H). 13C NMR d = 30.31, 34.83, 55.95,
70.62, 83.87, 112.71, 112.90, 113.42, 116.34, 118.78, 120.01,
123.98, 141.64, 156.91, 160.43. Anal. Calc. for C17H13N6O2;
C, 61.44; H, 3.64; N, 25.29. Found: C, 61.55; H, 3.75; N, 25.35.
EIMS 332 (M)+.
(2,4-Diamino-3-cyano-5H-chromeno[2,3-b]pyridin-5-yl)malono-
nitrile (5c)12a. Yellowish solid. mp 4300 1C. (KBr) (nmax/cmÀ1
)
4 A. Chanda and V. V. Fokin, Chem. Rev., 2009, 109, 725.
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3387, 3180, 2895, 2259, 2202, 1643, 1569, 1491, 1409, 1348.
1H NMR d = 4.87 (d, 1H, J = 3.6 Hz), 4.94 (d, 1H, J = 3.6 Hz),
6.87 (s, 2H), 7.07 (s, 2H), 7.22–7.31 (m, 2H), 7.42–7.48 (m, 2H). 13
C
6 N. Thomus and S. M. Zachariah, Asian J. Pharm. Clin. Res.,
2013, 6, 11.
NMR d = 30.12, 34.84, 70.81, 84.03, 112.96, 113.52, 116.91, 117.94,
124.12, 130.20, 151.11, 157.14, 160.45, 160.52. Anal. Calc. for
C16H11N6O; C, 63.57; H, 3.33; N, 27.80. Found: C, 63.65; H, 3.43;
N, 27.85. EIMS 303 (M)+.
7 Y. Abrouki, A. Anouzla, H. Loukili, A. Chakir, M. Idrissi,
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J. Chem., 2009, 48B, 1319.
(2,4-Diamino-3-cyano-9-ethoxy-5H-chromeno[2,3-b]pyridin-
5-yl)malononitrile (5e)12a. Yellowish solid. mp 4300. IR (KBr)
(nmax/cmÀ1) 3445, 3365, 2970, 2247, 2210, 1652, 1628, 1567,
1475, 1416 cmÀ1 1H d = 1.37 (t, 3H, J = 6.9 Hz), 4.05–4.13
.
9 (a) J. Mori, M. Iwashima, M. Takeuchi and H. Saito, Chem.
Pharm. Bull., 2006, 54, 391; (b) C. K. Denish, K. P. Hetal and
K. G. Nilesh, Asian J. Biochem. Pharm. Res., 2012, 2, 126;
(c) D. S. Raghuvanshi and K. N. Singh, ARKIVOC, 2010,
10, 305.
10 (a) J. Volmajer, R. Toplak, I. Leban, A. Majcen and
L. Marechal, Tetrahedron, 2005, 61, 7012; (b) G. murugavel
and T. Punniyamurthy, Org. Lett., 2013, 15, 3828.
11 (a) S. Makarem, A. A. Mohammadi and A. R. Fakhari, Tetra-
hedron Lett., 2008, 49, 7194; (b) M. M. Heravi, M. M. Heravi,
K. Bakhtiari, V. Zadsirjan, F. F. Bamoharram and O. M.
Heravi, Bioorg. Med. Chem. Lett., 2007, 17, 4265; (c) R. Ballini,
G. Bosica, M. L. Confort, R. Maggi, A. Mazzacani, P. Righi and
G. Sartori, Tetrahedron, 2001, 57, 1395; (d) D. Kumar,
V. B. Reddy, B. G. Mishra, R. K. Rana, M. N. Nadagouda
and R. S. Varma, Tetrahedron, 2007, 63, 3093.
(m, 2H), 4.84 (d, 1H, J = 3.9 Hz), 4.92 (d, 1H, J = 3.9 Hz), 6.70 (s,
2H), 7.05 (s, 2H), 7.12–7.21 (m, 3H). 13C NMR d = 14.63, 30.30,
34.84, 64.21, 70.68, 83.73, 112.97, 113.40, 113.64, 116.27,
118.71, 119.90, 123.93, 141.11, 146.90, 156.95, 160.43. Anal.
Calc. for C18H14N6O2; C, 62.92; H, 4.07; N, 24.27. Found: C,
62.98; H, 4.12; N, 24.32. EIMS 346 (M)+.
(2,4-Diamino-3-cyano-7-methyl-5H-chromeno[2,3-b]pyridin-
5-yl)malononitrile (5f)12a. Yellowish solid. mp 4300 1C. IR
(KBr) (nmax/cmÀ1) 3386, 3168, 2260, 2202, 1637, 1608, 1566,
1490, 1403, 1230. 1H NMR d = 2.34 (s, 3H), 4.83 (d, 1H, J =
3.9 Hz), 4.87 (d, 1H, J = 3.9 Hz), 6.66 (s, 2H), 7.05 (s, 2H), 7.11
(d, 1H, J = 8.3 Hz), 7.21 (s, 1H), 7.27 (d, 1H, J = 8.3 Hz). 13C NMR
d = 20.32, 30.45, 34.63, 70.54, 83.88, 112.81, 113.44, 116.23,
116.58, 117.52, 129.01, 130.65, 133.17, 149.8, 156.93, 160.47,
160.51. Anal. Calc. for C17H13N6O; C, 64.55; H, 3.82; N, 26.57.
Found: C, 64.52; H, 3.90; N, 26.62. EIMS 317 (M)+.
12 (a) M. N. Elinson, S. V. Gorbuno, A. N. Vereshchagin,
R. F. Nasybullin, A. S. Goloveshkin, I. S. Bushmarinov and
M. P. Egorov, Tetrahedron, 2014, 70, 8559; (b) T. S. Shaikh,
J. D. Patil, D. S. Gaikwad, P. G. Hegade, P. B. Patil,
M. M. Mane and D. M. Pore, Indian J. Chem., 2014, 53, 1288.
13 (a) M. S. Singh and S. Chowdhury, RSC Adv., 2012, 2, 4547;
(b) Y. Gu, Green Chem., 2012, 14, 2091; (c) R. Ballini,
G. Bosica, M. L. Confortio, R. Maggi, A. Mazzacani, P. Righi
and G. Sartori, Tetrahedron, 2001, 57, 1395.
14 (a) M. M. Heravi, N. Poormohammad, Y. S. Beheshtiha,
B. Baghernejad and R. Malakooti, Bull. Chem. Soc. Ethiop.,
2010, 24(2), 273; (b) J. Volmajer, R. Toplak, I. Leban and
A. Majcen LeMarechal, Tetrahedron, 2005, 61, 7012; (c) M. N.
Elinson, A. S. Dorofeev, S. K. Feducovich, R. F. Nasybullin,
(4b) 14.54, 32.37, 37.35, 48.89, 64.42, 112.91, 113.06,
114.01.118.92, 119.34, 119.71, 124.91, 139.42, 146.37, 163.37 ppm.
(4d) 20.33, 32.43, 37.14, 48.78, 112.91, 113.07, 116.10,
117.56, 119.45, 128.84, 130.61, 134.15, 147.70, 163.53 ppm.
(4g) 32.30, 36.85, 48.46, 112.69, 112.85, 118.29, 119.08,
119.89, 128.46, 128.51, 130.02, 148.56, 163.22 ppm.
Acknowledgements
The author Snehlata Yadav is thankful to UGC, New Delhi, for
the award of a Research Fellowship, Madhulika Srivastava and
Pratibha Rai are grateful to UGC, New Delhi, for the award of
senior Research Fellowships.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015
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