J. Chil. Chem. Soc., 62, Nº 1 (2017)
GRINDING SYNTHESIS OF 2-AMINO-4H-CHROMENES USING 3,3-(BUTANE-1,4-DIYL) BIS (1,2-DIMETHYL-
1
H-IMIDAZOLE-3-IUM)Br-CAN AS A NOVEL REAGENT
*
,a
b
c
MOHAMMAD NIKPASSAND , LEILA ZARE FEKRI , PARVIN AHMADI
a
Department of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran
b
Department of Chemistry, Payame Noor University, PO Box 19395-3697 Tehran, Iran
ABSTRACT
A clean and environmentally benign route to 2-amino-4H-chromenes has been developed via three-component condensation reaction of various benzyl
alcohols, malononitrile and 1-naphthol, using a catalytical amount of CAN and a reusable ionic liquid 3,3-(Butane-1,4-diyl)bis(1,2-dimethyl-1H-imidazole-3-ium)
bromide ([BDBDMIm]Br) as a catalyst at room temperature. The present methodology offers several advantages such as solvent-free conditions, excellent yields,
simple procedure, mild conditions and reduced environmental consequences. The ionic liquid was recovered and reused. All of synthesized compounds were
characterized by IR, NMR and elemental analyses.
Keywords: Chromenes, Benzyl alcohols, Ionic Liquid, Multicomponent reaction, 1-Naphthol, Malononitrile.
INTRODUCTION
5.12 (s, 1H) , 6.83 (d, 1H, J = 8.2Hz,), 7.42 (d, 1H, J = 8.4 Hz), 7.54-7.67 (m,
H), 7.87 (d, 1H, J = 7.8 Hz), 8.19 (d, 2H, J = 8.4 Hz), 8.22 (d, 1H, J = 8.2Hz)
3
1
3
Chromene and its derivatives belong to a major class of natural heterocyclic
compounds, which they occur widely in edible vegetables and fruits . They
frequently expose a variety of biological and pharmacological activities . Based
ppm. C NMR (CDCl , 100 MHz): δ = 41.3, 61.6, 117.4, 119.8, 121.6, 123.8,
3
1
, 2
125.4, 125.6, 125.8, 127.3, 128.1, 128.7, 129.2, 130.6, 133.7, 147.8, 151.9,
159.3 ppm. Anal Calc. for C H N O : C, 69.96; H, 3.82; N, 12.24. Found: C,
3
2
0
13
3
3
on the extensive researches, it has been observed that chromene derivatives
include biological, such as antioxidant, spamolytic, anti-HIV, anticancer, anti-
anaphylactic, antibacterial activity antihypertensive, anti-tubulin, antiviral,
activator of potassium channels and inhibition of phosphodiesterase IV or
70.09; H, 3.92; N, 12.37.
2-Amino-3-cyano-4-(4-chlorphenyl)-4H-benzo[h]chromene (4b)
Yellow solid, mp 231-233°C; FT-IR (KBr): ν 3320, 3420, 2200, 1670,
-1 1
1600, 1570 cm . H NMR (CDCl 400 MHz): δ = 4.79 (s, 2H, NH ), 4.96 (s,
3
,
2
4
-12
dihydrofolate reductase, etc. . As a result, a number of methodologies have
1H), 7.09 (d, 1H, J = 8.4 Hz), 7.27 (d, 2H, J = 8.4 Hz), 7.38 (d, 2H, J = 8.4
Hz), 7.57-7.66 (m, 3H), 7.89 (d, 1H, J = 8.0 Hz), 8.23 (d, 1H, J = 8.0Hz)
1
3
been developed to synthesize chromene compounds
.
1
3
Several methods have been reported for the synthesis of 2-amino-4H-
ppm; C NMR (CDC ,100 MHz): δ = 41.2, 61.2, 117.5, 119.2, 120.6, 122.6,
l3
chromene derivatives using malononitrile, resorcinol and aldehyde. Various
123.3, 125.2, 127.4, 128.4, 128.9, 129.2, 130.2, 132.8, 133.4, 141.5, 142.7,
158.6 ppm. Anal Calc. for C H ClN O: C, 72.18; H, 3.94; N, 8.42. Found: C,
72.31; H, 3.76; N, 8.53.
1
4
15
catalysts such as TFE , MgAl/HT , cetyltrimethylammonium bromide
2
0
13
2
16
17
(
CTABr) and tungstic acid functionalized mesoporous SBA-15 have been
used for these reactions. Most of these reported methods require a long reaction
time, high temperature, and unsatisfactory yields.
2-Amino-4-(3-hydroxyphenyl)-4H-benzo[h]chromene-3-carbonitrile
(4c)
The use of ionic liquids as reaction media and catalyst can offer a
solution to solvent emission and catalyst recycling problems. Ionic liquids
are accompanied with some pluses or let us call them advantages; some of
which are negligible vapor pressure, non-flammability, non- miscibility with
non-polar solvents, reasonable thermal and chemical stability and recyclability
Yellow solid, mp 252-254°C; FT-IR (KBr): ν 3370, 3420, 3320, 2200,
-1 1
1580, 1650 cm . H NMR (CDCl , 400 MHz,): δ = 4.77 (s, 1H), 6.62-6.67 (m,
3
2H), 6.76 (d, 1H, J = 7.6 Hz), 7.03-7.18 (m, 2H), 7.17 (s, 2H, NH ), 7.58-7.68
2
(m, 3H), 7.84 (d, 1H, J = 8.0 Hz), 8.25 (d, 1H, J = 8.4 Hz), 9.39 (s, 1H, OH)
ppm. 13C NMR (CDCl , 100 MHz): δ = 48.6, 61.7, 116.9, 119.2, 121.8, 123.3,
3
18, 19
.
They dissolve many organic and inorganic substrates and are tunable to
123.5, 123.7, 125.1, 125.2, 127.1, 127.3, 129.5, 131.5, 133.3, 134.1, 145.7,
146.5, 148.9, 160.2 ppm. Anal Calc. for C H N O : C, 76.42; H, 4.49; N, 8.91.
2
0
specific chemical tasks
.
2
0
14
2
2
Found: C, 76.49; H, 4.56; N, 8.76.
2-Amino-3-cyano-4-(4-methylphenyl)-4H-benzo[h]chromene (4d)
EXPERIMENTAL
-1
Yellow solid, mp 206-208°C; FT-IR (KBr): ν 3435, 3320, 2180, 1657 cm .
H NMR (CDCl , 400 MHz): δ = 2.32 (s, 3H, CH3), 4.73 (s, 2H, NH ), 4.84 (s,
1
Materials and measurements
3
2
Chemicals were purchased from Merck and Fluka. All solvents used
were dried and distilled according to standard procedures. Thin Layer
Chromatography (TLC) was done withTLC Silica gel 60;Aluminum sheet from
Merck. Melting points were measured on an Electrothermal 9100 apparatus.
IR spectra were determined on a Shimadzu FT-IR 8600 spectrophotometer.
1H), 7.05 (d, 1H, J = 8.2 Hz), 7.13-7.45 (m, 4H), 7.47-7.66 (m, 3H), 7.74 (d,
1H, J = 8.2 Hz), 8.23 (d, 1H, J = 8.4Hz) ppm. C NMR (100 MHz, CDCl3):
13
δ = 22.9 (CH ), 42.6, 61.8, 116.6, 119.0, 120.8, 122.9, 124.4, 126.6, 126.8,
3
127.2, 128.0, 128.5, 128.9, 130.4, 133.6, 137.7, 142.5, 159.6 ppm. Anal Calc.
for C H N O: C, 80.75; H, 5.16; N, 8.97. Found: C, 80.61; H, 5.24; N, 9.07.
2
1
16
2
1
13
H and C NMR spectra were determined on a Bruker 400 DRX Avance
2-Amino-3-cyano-4-(3-nitrophenyl)-4H-benzo[h]chromene (4e)
instrument at 500 and 125 MHz. Elemental analyses were done on a Carlo-
Erba EA1110CNNO-S analyzer and agreed with the calculated values.
General procedure for the synthesis of 2-amino-4H-chromene 4a-p
A mixture containing benzyl alcohol (2.0 mmol), 1-naphthol (2.2 mmol),
Yellow solid, mp 211-213°C; FT-IR (KBr): ν 3320, 3450, 2210, 1660,
-1
1
1600, 1520, 1350 cm ; H NMR (CDCl , 400 MHz): δ = 4.93 (s, 2H, NH ),
3
2
5.12 (s, 1H, s), 6.83 (d, 1H, J = 8.4 Hz), 7.51-7.63 (m, 5H), 7.82 (d, 1H, J =
1
3
7.6 Hz), 8.20 (m, 2H), 8.25 (d, 1H, J = 7.8 Hz) ppm. C NMR (CDCl3, 100
MHz): δ = 41.4, 61.3, 116.6, 119.6, 121.4, 123.3, 123.7, 123.8, 125.3, 125.6,
127.3, 127.6, 129.6, 130.3, 133.7, 134.5, 145.3, 147.5, 149.2, 159.7 ppm. Anal
Calc. for C H N O : C, 69.96; H, 3.82; N, 12.24. Found: C, 70.02; H, 3.93;
2
1
malononitrile (2.0 mmol) and 4mmol% of [BDBDMIm]Br and 0.05g of CAN
was stirred at room temperature for the required reaction times. The progress
of the reaction was monitored by TLC (EtOAc: petroleum ether 1:2). After
completion of the reaction, we extracted the product with CHCl /H O. After
2
0
13
3
3
N, 12.35.
3
2
separation of phases and evaporation of the organic phase and recrystallization
of the residue, the pure product was obtained. The aqueous phase was
2-amino-4-(2-nitrophenyl)-4H-benzo[h]chromene-3-carbonitrile (4f)
Dark yellow solid, mp 234-236°C; FT-IR (KBr): ν 3346, 2202, 1666, 1525
-1
1
concentrated under reduced pressure, washed with Et O, and evaporated under
cm ; H NMR (CDCl ,400 MHz): δ = 1.55 (s, 2H, NH ), 4.87 (s, 1H), 7.13 (d,
2
3
2
reduced pressure to recover the ionic liquid for subsequent use.
1H, J = 8.4 Hz), 7.33-7.87 (m, 7H), 7.85 (d, 1H, J = 8.4 Hz), 8.19 (d, 1H, J =
13
Selected data:
8.4 Hz) ppm. C NMR (CDCl , 100 MHz): δ = 46.8, 61.6, 117.8, 119.2, 121.1,
3
2
-Amino-3-cyano-4-(4-nitrophenyl)-4H-benzo[h]chromene(4a):
123.4, 123.7, 123.8, 125.3, 125.6, 127.7, 127.8, 129.2, 130.4, 133.3, 134.8,
145.7, 147.0, 149.2, 159.9 ppm. Anal Calc. for C H N O : C, 69.96; H, 3.82;
N, 12.24. Found: C, 69.85; H, 3.94; N, 12.18.
Yellow solid, mp 239-241°C; FT-IR (KBr): ν 3350, 3550, 2200, 1600,
2
0
13
3
3
-1
1
1
670, 1510, 1350 cm . H NMR (400 MHz, CDCl ): δ = 4.87 (s, 2H, NH ),
3
2
e-mail: nikpassand@iaurasht.ac.ir
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