Green synthesis of 1-aryl-1,12-dihydrobenzo[h]pyrano[c]chromene derivatives

Article abstract of DOI:10.3184/174751914X13987950600120

An efficient green synthesis of eight 3-amino-12-oxo-1-aryl-1,12- dihydrobenzo[h]pyrano[3,2-c]chromene-2-carbonitriles may be achieved by a three-component, one-pot reaction between 4-hydroxy-2H-benzo[h]chromen-2-one, malononitrile and various araldehydes in water in the presence of NEt ₃.

Full text of DOI:10.3184/174751914X13987950600120

JOURNAL OF CHEMICAL RESEARCH 2014
VOL. 38 JUNE, 341–342
RESEARCH PAPER 341
Green synthesis of 1‑aryl‑1,12‑dihydrobenzo[h]pyrano[c]chromene
derivatives
Maryam Abbasi Eshlaghia, Behrooz Mirzaa and Mohsen Zeebb*
aDepartment of Chemistry, Faculty of Science, Tehran University, Tehran, Iran
bDepartment of Applied Chemistry, Faculty of Science, Islamic Azad University, South Tehran Branch, Tehran, Iran
An efficient green synthesis of eight 3‑amino‑12‑oxo‑1‑aryl‑1,12‑dihydrobenzo[h]pyrano[3,2‑c]chromene‑2‑carbonitriles may
be achieved by a three‑component, one‑pot reaction between 4‑hydroxy‑2H‑benzo[h]chromen‑2‑one, malononitrile and various
araldehydes in water in the presence of NEt3.
Keywords: malononitrile, three-component reaction, 4-hydroxy-2H-benzo[h]chromen-2-one
Multicomponentreactions(MCRs)havereceivedmuchattention
from synthetic organic chemists due to their application in the
construction of highly functionalised organic molecules and
pharmacologically important heterocyclic compounds.1 This
strategy makes it possible for complicated compounds to be
synthesised using a single reaction vessel in a rapid, efficient
and time saving operation without the need for separation of
intermediates.2
The use of water as a green media for organic synthesis has
become an important research area.3 Other than its economic
and environmental benefits, water also exhibits unique physical
and chemical properties that lead to unique reactivity and
selectivity in comparison with organic solvents.
Results and discussion
In a test run, the reaction between 4-hydroxy-2H-benzo[h]
chromen-2-one 1, malononitrile 2 and benzaldehyde (3;
Ar=Ph) in water proceeded smoothly at room temperature in
the presence of NEt3 and the corresponding product (4; Ar=Ph)
was generated in approximately 8 h in 80% yield (Scheme 1).
The scope and generality of this procedure was illustrated with
respect to various araldehydes, some reactions faster than others
(Table 1). The formation of the compounds 4 was assumed to
proceed via formation of a known Michael adduct intermediate
followed by cyclisation. The structures of the products were
established by 1H NMR, 13C NMR, IR and elemental analysis.
Conclusion
In view of the pharmaceutical importance of heterocyclic
compounds containing the chromene moiety, much research has
been undertaken. Dihydropyrano[c]chromene derivatives have
a wide range of biological activities. Some of these compounds
exhibit diuretic, spasmolytic, anti-cancer, anticoagulant
or antianaphylactic activity.4,5 Also there are many natural
products containing the 4H-pyran moiety.6,7
In conclusion, we have developed a practically convenient
and eco-friendly synthesis of 3-amino-12-oxo-1-phenyl-
1,12-dihydrobenzo[h]pyrano[3,2-c]chromene-2-carbonitrile
derivatives from a three-component, one-pot reaction between
4-hydroxy-2H-benzo[h]chromen-2-one, araldehydes and
Recently, syntheses of dihydropyrano[3,2-c]chromene
derivatives have been reported using various methods and
catalysts.8–11 Relevant to our work was the condensation of
4-hydroxycoumarin with araldehydes and malononitrile, either
using as catalyst NEt3 in boiling EtOH8 or DBU in boiling
water.9 As part of our continuing efforts for the expeditious
synthesis of biologically relevant heterocyclic compounds,12 we
report here our recent efforts towards the synthesis of diverse
3-amino-12-oxo-1-phenyl-1,12-dihydrobenzo[h]pyrano[3,2-c]
chromene-2-carbonitrile derivatives by a three-component,
one-pot reaction between 4-hydroxy-2H-benzo[h]chromen-2-
one, araldehydes and malononitrile in the presence of NEt3 in
water at room temperature.
Table 1 Yields of 3‑amino‑12‑oxo‑1‑aryl‑1,12‑dihydrobenzo[h]pyrano
[3,2‑c]chromene‑2‑carbonitriles 4a–h from the reaction of 4‑hydroxy‑2H‑
benzo[h]chromen‑2‑one 1,araldehydes 2a–h and malononitrile 3 in water
in the presence of NEt3 (Scheme 1)
Product
Ar
Time/h
Yield/%
M.p./°C
4a
4b
4c
4d
4e
4e
4g
4h
C6H5
9
6
5
10
9
10
8
80
83
85
80
71
69
73
80
280–281
245–247
201–203
278–279
272–274
290–291
262–264
243–245
2‑NO2C6H4
4‑NO2C6H4
2‑MeOC6H4
4‑MeOC6H4
3,4,5‑MeOC6H2
2‑ClC6H4
4‑ClC6H5
8
O
Ar
O
O
CN
O
NEt3
H2O
O
NH2
OH
+ CH2(CN)2
+ ArCHO
1
3
2
4
Scheme 1
* Correspondent. E-mail: Zeeb.mohsen@gmail.com
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342 JOURNAL OF CHEMICAL RESEARCH 2014
124.6, 126.2, 127.1, 128.5, 129.0, 129.4, 131.5, 133.5, 148.1, 153.0, 156.1,
158.0., 159.2; Anal. calcd for C24H16N2O4: C, 72.72; H, 4.07; N, 7.07;
found: C, 72.98; H, 4.36; N, 7.32%.
malononitrile in an aqueous medium using NEt3 as a catalyst.
The results (Table 1) indicated that substrates 3 bearing both
electron-donating groups (such as alkoxy) and electron-
withdrawing groups (such as halide or nitro) can be involved
in this one-pot synthesis to afford desired products 4 with high
yields.
3-Amino-1-(4-methoxyphenyl)-12-oxo-1,12-dihydrobenzo[h]
pyrano[3,2-c]chromene-2 carbonitrile (4e): Pale brown solid, yield
71%; m.p. 272–274 °C, (EtOH); IR (υ): 3356, 3310 (NH2), 2180 (CN),
1
1721 (CO) cm–1; H NMR: δ ppm 3.82 (s, 3H), 4.48 (s, 1H), 6.84 (d,
J=7.7 Hz, 2H), 7.29 (d, J=7.7 Hz), 7.41 (s, 2H), 7.65–7.70 (m, 2H),
7.87 (d, J=8.3 Hz), 7.90 (d, J=8.3 Hz), 8.15 (d, J=7.5 Hz), 8.27 (d,
J=7.5 Hz). Anal. calcd for C24H16N2O4: C, 72.72; H, 4.07; N, 7.07;
found: C, 72.48; H, 4.30; N, 6.90%.
3-Amino-12-oxo-1-(3,4,5-trimethoxyphenyl)-1,12-dihydrobenzo[h]
pyrano[3,2-c]chromene-2-carbonitrile (4f): Pale brown solid, yield
69%; m.p. 290–291 °C, (EtOH); IR (υ): 3400, 3300 (NH2), 2150 (CN),
1705 (CO) cm–1; 1H NMR: δ ppm 3.51 (s, 3H), 3.81 (s, 6H), 4.29(s, 1H),
6.90 (s, 2H), 7.41 (s, 2H, NH2), 7.70–7.75 (m, 2H), 7.85 (d, J=2 8.7 Hz,
2H), 7.90 (d, J=8.7 Hz,2H), 8.04 (d, J=8.0 Hz), 8.15 (d, J=8.0 Hz, 1H).
Anal. calcd for C26H20N2O6: C, 68.42; H, 4.42; N, 6.14; found: C, 68.15;
H, 4.17; N, 5.90%.
Experimental
All chemicals used in this work were purchased from Merck or
Aldrich. All the reactions were checked by TLC using silica-coated
plates. All the synthesised compounds were new and full spectral
data and elemental analyses are provided. IR spectra were recorded
as KBr discs on a Jasco IR-680 spectrophotometer. NMR spectra
were obtained on a Bruker-Avance AQS 500 MHz spectrometer
(1H NMR at 500 Hz, 13C NMR at 125 Hz) in DMSO-d6 using TMS as
internal standard. Chemical shifts (δ) were given in ppm and coupling
constants (J) in Hz. Elemental analyses were carried out with a
PerkinElmer model 240-C apparatus.
Synthesis of 3-amino-12-oxo-1-phenyl-1,12-dihydrobenzo[h]pyrano
[3,2-c]chromene-2-carbonitrile (4a–h); general procedure
3-Amino-1-(2-chlorophenyl)-12-oxo-1,12-dihydrobenzo[h]
pyrano[3,2-c]chromene-2-carbonitrile (4g): Pale brown solid, yield
73%; m.p. 262–264 °C, (EtOH); IR (υ): 3420, 3317 (NH2), 2210 (CN),
1723 (CO) cm–1; 1H NMR: δ ppm: 5.22 (s, 1H, CH), 7.15–7.24 (m, 2H),
7.31–7.34 (m, 1H), 7.40–7.43 (m, 1H), 7.49 (s, 2H, NH2), 7.70–7.76 (m,
2H), 7.82 (d, J=8.5 Hz, 1H), 7.93 (d, J=8.5 Hz, 1H), 8.04 (d, J=7.8 Hz,
1H), 8.26 (d, J=7.8 Hz, 1H); 13C NMR: δ ppm 33.4, 55.6, 101.3, 107.4,
116.8, 117.7, 120.3, 120.7, 123.4, 126.5, 126.7, 127.1, 127.7, 128.1, 128.4,
130.7, 131.5, 133.5, 141.3, 148.4, 155.8, 159.0, 159.2. Anal. calcd for
C23H13ClN2O3: C, 68.92; H, 3.27; N, 6.99; found: C, 69.17; H, 2.95; N,
7.21%.
3-Amino-1-(4-chlorophenyl)-12-oxo-1,12-dihydrobenzo[h]
pyrano[3,2-c]chromene-2-carbonitrile (4h): Pale brown solid, yield
80%; m.p. 243–245 °C, (EtOH); IR (υ): 3353, 3311 (NH2), 2133 (CN),
1730 (CO) cm–1; 1H NMR: δ ppm 4.43 (s, 1H, CH), 7.29 (d, J=7.3 Hz,
2H), 7.33 (d, J=7.3 Hz, 2H), 7.51 (s, 2H, NH2), 7.69–7.75 (m, 2H),7.89
(d, J=8.5 Hz, 1H), 7.85 (d, J=8.5 Hz, 1H), 8.03 (d, J=8.0 Hz, 1H), 8.30
(d, J=8.0 Hz, 1H). Anal. calcd for C23H13ClN2O3: C, 68.92; H, 3.27; N,
6.99; found: C, 68.66; H, 3.53; N, 7.3%.
A mixture of 4-hydroxy-2H-benzo[h]chromen-2-one (1, 2 mmol),
araldehyde (2, 2 mmol), malononitrile (3, 2 mmol) and NEt3 (5 μL) in
water (10 mL) was stirred for an appropriate time at room temperature.
The reaction mixture was extracted with ethyl acetate (2×10 mL) and
the organic phase was dried, filtered, and excess ethyl acetate was
distilled off. The residue was purified by column chromatography
using EtOAc/n-hexane (4/1) as eluent. Then, the resulting precipitates
were recrystallised from ethanol to give the pure products.
3-Amino-12-oxo-1-phenyl-1,12-dihydrobenzo[h]pyrano[3,2-c]
chromene-2-carbonitrile (4a): Pale brown solid, yield 80%; m.p.
280–281 °C, (EtOH); IR (υ): 3350, 3315 (NH2), 2240 (CN), 1732 (CO)
1
cm–1; H NMR: δ ppm 4.48 (s, 1H,), 7.18–7.33 (m, 5H), 7.55 (s, 2H),
7.75–7.81 (m, 2H), 7.90 (d, J=8.8 Hz, 1H), 7.93 (d, J=8.8 Hz, 1H,),
8.07 (d, J=8.0 Hz, 1H,), 8.27 (d, J=8.0 Hz, 1H,); 13C NMR δ ppm: 35.1,
60.01, 105.5, 107.5, 116.7, 117.8, 120.2, 121.7, 121.9, 123.5, 127.1, 127.4,
127.8, 128.2, 128.8, 129.2, 134.6, 143.5, 150.4, 153.2, 157.5, 160.4. Anal.
calcd for C23H14N2O3: C, 75.40; H, 3.85; N, 7.65; found: C, 75.58; H,
4.07; N, 7.28%.
3-Amino-1-(2-nitrophenyl)-12-oxo-1,12-dihydrobenzo[h]
pyrano[3,2-c]chromene-2-carbonitrile (4b): Yellow solid, yield
83%; m.p. 245–247 °C, (EtOH); IR (υ): 3400, 3315 (NH2), 2225 (CN),
1730 (CO), 1470, 1358 (NO2) cm–1; 1H NMR: δ ppm 5.42 (s, 1H,), 7.45
(t, J=7.51 Hz, 1H), 7.51(d, J=7.51 Hz, 1H), 7.59 (s, 1H, NH2), 7.66
(t, J=7.4 Hz, 1H), 7.71–7.79 (m, 2H), 7.82 (d, J=8.4 Hz, 1H), 7.90 (d,
J=8.0 Hz, 1H), 7.95 (d, J=8.4 Hz, 1H), 8.03 (d, J=8.0 Hz, 1H), 8.52 (d,
1H, J=8.1 Hz). Anal. calcd for C23H13N3O5: C, 67.15; H, 3.19; N, 10.21;
found: C, 66.88; H, 3.34; N, 10.34%.
Support of this investigation by the Islamic Azad University
Tehran South Branch through
acknowledged.
a grant is gratefully
Received 22 February 2014; accepted 2 April 2014
Paper 1402483 doi: 10.3184/174751914X13987950600120
Published online: 10 June 2014
3-Amino-1-(4-nitrophenyl)-12-oxo-1,12-dihydrobenzo[h]
pyrano[3,2-c]chromene-2-carbonitrile (4c): Yellow solid, yield
85%; m.p. 201–203 °C, (EtOH); IR (υ): 3450, 3407 (NH2), 2150 (CN),
1725 (CO), 1471, 1360 (NO2) cm–1; 1H NMR: δ ppm 4.51 (s, 1H, CH),
7.42 (s, 2H, NH2), 7.65 (d, J=8.5 Hz, 2H), 7.70–7.76 (m, 2H), 7.85 (d,
J=8.5 Hz), 7.92 (d, J=8.5 Hz), 8.06 (d, J=8.3 Hz), 8.15 (d, J=8.5 Hz,
2H), 8.35 (d, J=8.3 Hz, 1H,). Anal. calcd for C23H13N3O5: C, 67.15; H,
3.19; N, 10.21; found: C, 67.46; H, 3.33; N, 10.42%.
3-Amino-1-(2-methoxyphenyl)-12-oxo-1,12-dihydrobenzo[h]
pyrano[3,2-c]chromene-2 carbonitrile (4d): Pale brown solid, yield
80%; m.p. 278–279 °C, (EtOH); IR (υ): 3350, 3320 (NH2), 2210 (CN),
1710 (CO) cm–1; 1H NMR: δ ppm 3.81 (s, 3H), 4.60 (s, 1H, CH), 6.71 (t,
J=7.5 Hz, 1H), 6.92 (d, J=7.5 Hz, 1H), 7.20 (d, J=7.5 Hz, 1H), 7.24 (t,
J=7.5 Hz, 1H), 7.26 (s, 2H, NH2), 7.69–7.76 (m, 2H), 7.89 (d, J=8.7 Hz),
7.92 (d, J=8.7 Hz), 8.02 (d, J=8.0 Hz), 8.25 (d, J=8.0 Hz); 13C NMR: δ
ppm 31.3, 54.8, 55.8, 101.9, 107.5, 110.9, 116.9, 118.8, 120.7, 121.3, 121.6,
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