Synthesis of New Dimeric Chromene DeriVatiVes
Malononitrile (0.26 g, 3.96 mmol) was added to a solution of
3-methoxysalicylaldehyde (0.62 g, 4.05 mmol) in methanol (6 mL).
Triethylamine (2 drops) was added to the reaction mixture, and
the orange solution was stirred at room temperature for 6 h. The
yellow solid, which gradually precipitated from the reaction mixture,
was filtered and washed with diethyl ether. The product (0.57 g)
was identified as a mixture where the 2-iminochromene 1b and
the dimer 8b were the major components, present in a 2:1 ratio.
This solid was solubilized in DMSO (2.5 mL), and the dark red
solution was stirred at room temperature. After 2 h, a yellow solid
started to precipitate from the solution, which was stirred at room
temperature for 21 days.
The thick suspension was filtered, and the pale yellow solid was
washed with diethyl ether and dichloromethane. The product was
identified as the title compound 8b (0.50 g, 1.25 mmol, 63%): mp
150-152 °C;1H NMR (300 MHz, DMSO-d6) δ 3.83 (s, 3H), 3.93
(s, 3H), 5.85 (s, 1H), 6,92 (dd, J ) 7.4 Hz, 1.8 Hz, 1H), 7.00-
7.10 (m, 2H), 7.15-7.20 (m, 3H), 7.25 (t, J ) 8,2 Hz,1H), 7.38
(dd, J ) 8.2 Hz, 1.5 Hz, 1H), 8.36 (s, 1H); 13C NMR (75 MHz,
DMSO-d6) δ 48.6, 55.0, 56.6, 55.8, 104.6, 111.7, 114.9, 117.2,
117.8, 118.0, 120.3, 120.6, 119.6, 124.62, 124.63, 138.3, 142.1,
145.5, 146.5, 146.7, 147.0, 161.5; IR (Nujol mull) 2227, 2189, 1642,
1602, 1585. Anal. Calcd for C22H16N4O4C2H6SO.0.5H2O: C, 59.14;
H, 4.72; N, 11.50. Found: C, 59.36; H, 4.86; N, 11.54.
Malononitrile (1 to 2 molar equiv) was added to a solution of the
aldehyde (0.4 mmol) in aqueous 0.05 M Na2CO3 (1.5 mL), and
the mixture was stirred at room temperature. Within 5 min, a yellow
solid started to precipitate from the reaction mixture, which was
stirred at room temperature. After 2-21 h, concd HCl (3.7 molar
equiv) was added to the yellow suspension. The reaction mixture
was heated at 80-90 °C for 2 to 5.5 h. The suspension was cooled
to room temperature in an ice bath, and the yellow solid was filtered
and washed with water and diethyl ether leading to the pure product
7.
2-Oxo-8-methoxy-2H-chromene-3-carbonitrile 7b: yellow solid;
1
yield 100%; mp 230-232 °C; H NMR (300 MHz, DMSO-d6) δ
3.92 (s, 3H), 7.32 (dd, J ) 7.8 Hz, 1.8 Hz, 1H), 7.36 (t, J ) 7.8
Hz, 1H), 7.49 (dd, J ) 8.0 Hz, 1.8 Hz, 1H), 8.92 (s, 1H); 13C NMR
(75 MHz, DMSO-d6) δ 56.3, 102.4, 114.6, 117.5, 118.0, 120.8,
125.5, 143.4, 146.5, 153.7, 156.6; IR (Nujol mull) 2231, 1713, 1607,
1573. Anal. Calcd for C11H7NO3: C, 65.67; H, 3.48; N, 6.97.
Found: C, 65.85; H, 3.76; N, 7.13.
Synthesis of 2-Amino-4[(3-cyano-2H-chromen-2-ylidene)-
amino]-2H-chromene-3-carbonitrile 8a.
Synthesis of 4,4′-(Cyanomethylylidene)bis(2-amino-8-meth-
oxy-4H-chromene-3-carbonitrile) 9.
Method A. Malononitrile (0.39 g, 5.90 mmol) was added to a
mixture of salicylaldehyde (0.71 g, 5.79 mmol) in methanol (3 mL),
in the presence of 1 drop of triethylamine. The colorless solution
immediately turned yellow and was stirred at room temperature.
After 5 min, a yellow solid precipitated from the solution, which
was stirred at room temperature for 1 day. The solid was filtered,
washed with diethyl ether, and identified as the dimeric species 8a
(0.85 g; 2.50 mmol; 86%).
Method B. Salicylaldehyde (0.61 g, 4.97 mmol) was added to a
solution of (2-amino-3-cyano-4H-chromen-4-yl)malononitrile 2a
(0.20 g, 0.86 mmol) in ethanol (3 mL). The mixture was stirred at
room temperature for 7 days, while a yellow solid gradually
precipitated from the reaction mixture.
The solid was filtered, washed with ethanol, and identified as
the title compound (0.20 g, 0.59 mmol, 68.6%): mp 165-168
°C;1H NMR (300 MHz, DMSO-d6) δ 5.85 (s, 1H), 7.05-7.20 (m,
4H), 7.25-7.40 (m, 4H), 7.55-7.70 (m, 2H), 8.33(s, 1H); 13C NMR
(75 MHz, DMSO-d6) δ 48.5, 54.9, 104.5, 115.0, 115.5, 116.0, 117.5,
120.4, 122.1, 124.78, 124.75, 129.0, 129.1, 129.5, 134.2, 146.0,
146.3, 148.8, 153.0, 161.8; IR (Nujol mull) 2225, 2196, 1668, 1650,
1610, 1600, 1578, 1567. Anal. Calcd for C20H12N4O2: C, 70.59;
H, 3.53; N, 16.47. Found: C, 70.24; H, 3.61; N, 16.57.
Synthesis of 2-Amino-8-methoxy-4[(3-cyano-2H-chromen-2-
ylidene)amino]-2H-chromene-3-carbonitrile 8b.
Method A. Triethylamine (0.5 mL) was added to a yellow
suspension of 2-imino-8-methoxy-2H-chromene-3-carbonitrile 1b
(0.10 g, 0.51 mmol) in water (6 mL). The mixture turned orange
after the addition of triethylamine and was stirred at room
temperature. After 2.5 h, methanol (1 mL) was added to the
suspension to promote partial solubilization of the starting chromene.
The beige solid was filtered and washed with water and then with
diethyl ether, after 17.5 h, leading to product 9 (0.04 g, 0.10 mmol,
40%).
Method B. (2-Amino-3-cyano-8-methoxy-4H-chromene-4-yl)-
malononitrile 2b (0.16 g, 0.44 mmol) was added to an orange
suspension of 2-imino-8-methoxy-2H-chromene-3-carbonitrile 1b
(0.08 g, 0.42 mmol) in aqueous NaOH (1 M, 0.8 mL). The reaction
mixture was stirred at room temperature for 16 h, and the yellow
solid was filtered and washed with water and then with diethyl
ether, leading to product 9 (0.14 g, 0.31 mmol, 74%): mp > 300
1
°C; H NMR (300 MHz, DMSO-d6) δ 3.73 (s, 3H), 3.76 (s, 3H),
4.04 (s, 1H), 6.95 (dd, J ) 7.5 Hz, 1.5 Hz, 1H), 7.03 (dd, J ) 8.1
Hz, 1.5 Hz, 1H), 7.10-7.40 (m, 6H), 7.38 (s, 2H); 13C NMR (75
MHz, DMSO-d6) δ 46.6, 47.8, 48.8, 55.9, 56.0, 112.6, 113.4, 119.2,
121.1, 123.9, 124.8, 117.5, 117.8, 119.3, 119.6, 119.9, 120.7, 138.5,
140.7, 146.9, 146.9, 161.9, 164.4; IR (Nujol mull) 2200, 2184, 1645,
1619, 1601, 1579. Anal. Calcd for C24H17N5O40.9H2O: C, 63.27;
H, 4.28; N, 15.94. Found: C, 63.28; H, 4.01; N, 15.95.
Synthesis of 4-Amino-5-imino-2,7-dimethoxy-5H-cromeno-
[3,4-c]pyridine-1-carbonitrile 12.
Method A. Triethylamine (1 drop) was added to a white suspension
of (2-amino-3-cyano-4H-chromene-4-yl)malononitrile 2 (0.10 g,
0.38 mmol) in methanol (7 mL). The mixture turned yellow and
was stirred at 9 °C. The pale orange solid precipitated gradually
from the reaction mixture and was filtered and washed with diethyl
ether, after 5 days. The product was identified as 4-amino-5-imino-
J. Org. Chem, Vol. 73, No. 5, 2008 1961