Multi-component synthesis of 2-amino-4h-chromenes catalyzed by nano zno in water

Article abstract of DOI:10.1135/cccc2011050

Naphthalenediols, 1-and 2-naphthols, and phenols in the presence of nano ZnO as catalyst and water as green solvent react with methylenemalononitrile, generated in situ from aldehyde and malononitrile, to yield 2-amino-4H- chromenes.

Full text of DOI:10.1135/cccc2011050

Multi-Component Synthesis of 2-Amino-4H-chromenes
1285
MULTI-COMPONENT SYNTHESIS OF 2-AMINO-4H-CHROMENES
CATALYZED BY NANO ZnO IN WATER
1
,
2
Mona HOSSEINI-SARVARI * and Sara SHAFIEE-HAGHIGHI
Department of Chemistry, Shiraz University, Shiraz, I. R. Iran;
1
2
e-mail: hossaini@susc.ac.ir, sarashafiee@yahoo.com
Received February 28, 2011
Accepted May 25, 2011
Published online October 23, 2011
Naphthalenediols, 1- and 2-naphthols, and phenols in the presence of nano ZnO as catalyst
and water as green solvent react with methylenemalononitrile, generated in situ from alde-
hyde and malononitrile, to yield 2-amino-4H-chromenes.
Keywords: Heterocycles; Nanostructures; Heterogeneous catalysis; Green chemistry.
2
-Amino-4H-chromene derivatives are an important class of organic com-
pounds because of their uses as drugs, pesticides, analogs of natural com-
pounds, dyes, and other materials with practical importance1 . Substituted
–6
2
-amino-4H-chromenes have shown some biological activities, including
7
8,9
10–12
13
antimicrobial , antiviral , cancer therapy
city and central nervous system activity .
sex pheromone , mutageni-
1
4
15
Chromen-4-one derivatives or their salts can be used as immune modula-
tors and for the prophylaxis and treatment of different diseases of connec-
tive tissues, diabetes, psoriasis, pernicious anemia, ulcerous colitis, and
4
chronic hepatitis . In addition, many compounds containing enaminon-
itrile fragment are used as convenient synthons in the organic synthe-
1
,4–6
sis
.
During the recent years, there are several reporting methods to synthesize
of 2-amino-4H-chromene derivatives. The best method for synthesis of
these compounds involves the three-component condensation of malo-
nitrile, aldehyde, and a phenol or naphthol derivatives1
6–25
. Recently, rela-
2
0
tively benign reagents such as cetyltrimethylammonium chloride basic
alumina19 nanosized MgO and I /K CO
24
23
have also been used. However,
2
2
3
most of the reported methods for the synthesis of 2-amino-4H-chromenes
require prolonged reaction time, reagents in stoichiometric amount, toxic
organic solvents, and generate moderate yields of the product. The develop-
Collect. Czech. Chem. Commun. 2011, Vol. 76, No. 11, pp. 1285–1298
©
2011 Institute of Organic Chemistry and Biochemistry
doi:10.1135/cccc2011050

1
286
Hosseini-Sarvari, Shafiee-Haghighi:
ment of processes that are facile to carry out in the laboratory without
recourse to inert atmosphere or limited solvents especially toxic organic
solvents is an important goal in modern synthetic methodology. The iden-
tification of such processes can serve as a challenging goal that can lead to
the discovery and development of new reaction chemistry. Therefore, the
quest for cheap, environmentally friendly catalysts and mild reaction con-
ditions is still a major challenge.
Zinc oxide (ZnO) is a versatile material that has key applications as an
efficient catalyst in modern organic synthesis. ZnO nano particles can be
active catalyst for different processes. Recently ZnO nano particle were de-
2
6
scribed as catalysts for synthesis of β-phosphono malonates , Knoevenagel
2
7
28
29
condensation , synthesis of tetrazoles , β-acetamido ketones , couma-
3
0
31
32
rines , dimethyl carbonates and ferrocenyl phosphonates . Herein we
wish to report the novel synthesis of 2-amino-4H-chromenes by a multi-
component condensation of an aldehyde, malononitrile and naphthols or
phenols in water as a green solvent. The first step in this multi-component
condensation is the Knoevenagel condensation of an aldehyde and malono-
nitrile to produce the corresponding aryl methylene malononitrile. Re-
cently, we have shown that a mixture of malononitrile and arylaldehydes,
catalyzed by nano flake ZnO, is a synthetic method of aryl methylene
2
7
malononitriles . By this way, a variety of none readily obtained hetero-
cyclic could be synthesized.
RESULTS AND DISCUSSION
Structural Properties and Characterization of the Nano ZnO
In this work, the structural properties of nano ZnO was analyzed by X-ray
diffraction (XRD), scanning electron microscopy (SEM), transmission elec-
tron microscopy (TEM), and FTIR spectroscopy. Figure 1 shows XRD pattern
of the nano ZnO, which is a typical zincite peak pattern with lattice con-
stants a = 3.249 Å and c = 5.206 Å 33. According to this pattern, no
impurities could be find in the powder, indicating that they have been
completely removed using the washing procedure. The mean particle size
was calculated for the crystallized ZnO using the Scherrer equation using
3
4
the corresponding peaks . The (002) peak at 2θ = 34° was used for particle
size measurement. The average crystallite size was determined of about
2
5–50 nm.
SEM and TEM determined the morphology of the nano ZnO. Figure 2
shows SEM and TEM images of nano ZnO prepared with the sol method.
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Multi-Component Synthesis of 2-Amino-4H-chromenes
1287
It was observed that the synthesized product was ZnO nano-flake and the
wall of the flake is about 20–30 nm, thickness as shown in Fig. 2b.
FIG. 1
XRD patterns of nano ZnO
a
b
FIG. 2
SEM (a) and TEM (b) images of nano ZnO
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Hosseini-Sarvari, Shafiee-Haghighi:
In this work, the FTIR spectroscopy is also adopted as an applicable tech-
nique for further structural properties of nano ZnO. Infrared transmission
–
1
spectrum of nano ZnO was recorded to be in the range of 4500–400 cm .
–
1
35
The adsorption band at 463 cm is the stretching mode of ZnO . In addi-
tion, the peak at 3421 cm–1 is due to the stretching of –OH groups present
on the surface of the catalyst, caused during the absorption of water
(
Fig. 3). In this study, the adsorption of water molecules was also approved
using thermo gravimetric (TG) analysis. The thermal behavior of nano ZnO
and commercial ZnO (which was purchased from Merck Company) are
shown in Fig. 4. A significant decrease in the weight percentage of the nano
ZnO at temperatures to ~100 °C is related to the desorption ion of water
3
2
2
1
1
0
5
0
5
0
5
0
0
500
1000 1500 2000 2500
3000 3500
4000
4500
–
1
cm
FIG. 3
FTIR spectrum of nano ZnO
1
00
1
9
9
9
8
2
9
9
9
7
6
5
9
4
9
0
100
110
Temperature, °C
120
FIG. 4
Thermograms revealing the thermal stability of commercial ZnO (1) and nano ZnO (2)
Collect. Czech. Chem. Commun. 2011, Vol. 76, No. 11, pp. 1285–1298

Multi-Component Synthesis of 2-Amino-4H-chromenes
1289
molecules from the catalyst substrate. This was evaluated to ~0.7% accord-
ing to the TG analysis. The catalyst surface is so much reactive that gain
water from the air after calcinated.
Evaluation of Catalytic Activity of Nano ZnO for Synthesis of
Chromene Derivatives
In conjunction to this work, we report results of our investigations on reac-
tivity of nano ZnO as a perfect catalyst in the synthesis of some 2-amino-
4
H-chromenes.
Thus, it has been found that 1-naphthol reacts with arylaldehydes and
malononitrile to yield 2-amino-4H-chromenes 4a–4i (Scheme 1). These
compounds are assumed to be formed via addition of 1-naphthol to aryl
methylene malononitrile, generated in situ from aldehyde and malono-
nitrile. Then the resulting acyclic Michael adducts spontaneously cyclized
into the final isolable products 4. The results are summarized in Table I.
SCHEME 1
2
-Amino-4H-chromene synthesis catalyzed by nano ZnO
It is important to note that in all cases, the formation of 4H-pyran 4
structures were preferred over a possible 2H-pyran structure. The former
might result from the addition of the naphthol oxygen atom to the double
bond in aryl methylene malononitriles (Knoevenagel adduct) and subse-
1
quent cyclization. H NMR shows methylene proton signal at δ 4–5.5 ppm
which is comparable with the expected one for 4H-pyran derivative. In ad-
dition, if the reaction product was 2H-pyran derivative, signals would ap-
pear at lower δ values, δ 3–4 ppm 36
.
As indicated in the Table I, wide range of aromatic aldehydes bearing
both electron-donating and electron-withdrawing substituents, afforded
the corresponding 2-amino-4H-chromenes in good yields. Aromatic alde-
hydes carrying electron-withdrawing substituents reacted well with high
yields. Mention must be made here that para-substituted aromatic alde-
hydes gave higher yields of 2-amino-4H-chromenes than ortho- and meta-
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Hosseini-Sarvari, Shafiee-Haghighi:
TABLE I
Three-component condensation of various aldehydes (1 mmol) with malononitrile (1 mmol)
and 1-naphthol (1 mmol) catalyzed by nano ZnO (0.5 mmol) at 80 °C in water
Entry
Ar
Product 4
Time, h
Yield, %a
1
4-NO -C H -
4a
4b
4c
4d
0.5
98
2
6
4
1
a
2
3
4
C H -
3
5
85
85
50
6
5
1
b
4-HO-C H -
6
4
1
c
4-MeO-C H -
12
6
4
1
d
5
6
7
8
9
4-Cl-C H -
4e
4f
1.5
5
95
75
80
90
60
6
4
1
e
3-Cl-C H -
6
4
1
f
2-Cl-C H -
4g
4h
4i
4
6
4
1
g
2-thiophenyl
6
1
h
2-furan
10
1
i
a
Isolated yield.
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Multi-Component Synthesis of 2-Amino-4H-chromenes
1291
substituted aromatic aldehydes did. However, aromatic aldehydes with
electron-donating substituents give the expected compounds in a longer
time and lesser yields. We propose, as an explanation for the result, that
electron-donating substituents on the aromatic ring develop the electron
density of C=C double bond in the intermediate (Knoevenagel adduct),
which may be disadvantageous to the reaction of the phenol ortho
C-alkylation with electrophilic C=C double bond.
The use of naphthalenediols attracted our attention because the reactions
of these compounds with aromatic aldehydes 1 and malononitrile 2 can af-
ford various naphthopyrans. In addition, to our knowledge, the synthesis
3
7–41
aspect of such naphthopyrans was only partially exploited
. Previous
attempt3
7–41
to synthesize benzochromenes from 2,7- 2,3- 1,5- and 1,6-
naphthalenediols 5–8 by a three-component reaction has failed. Herein,
using nano ZnO in water as solvent in very mild and efficient reaction con-
ditions, we succeeded in synthesis of 2-amino-4H-chromenes 9–12 by
three-component condensation (Scheme 2). In addition, we found that the
SCHEME 2
Synthesis of 2-amino-4H-chromenes 9–12 by three-component condensation catalyzed by
nano ZnO
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Hosseini-Sarvari, Shafiee-Haghighi:
reaction of naphthalenediols 5–8 with 4-chlorobenzaldehyde 1e and
malononitrile 2 afforded only benzochromenes 9–12 regardless of the sub-
strates ratio (1:1:1 or 1:2:2). The addition of double amounts of 4-chloro-
benzaldehyde and malononitrile to these naphthalenediols yielded only
2
-amino-4H-chromenes 9–12 and the corresponding naphthalene dipyrans
was not observed.
It has been shown that 1,6-naphthalenediol 7 reacted with 4-chlorobenz-
aldehyde 1e and malononitrile 2 in a molar ratio of 1:2:2 or 1:1:1 to give
1
13
the benzochromene 11 regioselectively. The H and C NMR spectra of 11
are in good agreement with this structure (see Experimental).
To assess the efficiency of nano sized ZnO as catalyst in inducing these
reactions, the reactions of phenol 13, resorcinol 14 and 2-naphthol 15 with
4
-chlorobenzaldehyde 1e and malononitrile 2 were also studied. Phenol 13
reacted smoothly in the presence of nano ZnO to afford the corresponding
-amino-4H-chromene 16 in moderate yield, while the reactions of resor-
2
cinol 14 and 2-naphthol 15 were good in time and yields that, afforded se-
lectively 2-amino-4H-chromenes 17 and 18, respectively (Scheme 3). We
propose, as an explanation for the selectivity of these reactions, that benzo-
pyrans 17 and 18 were formed by addition of the more anion of phenolic
C-2 with electrophilic C=C double bonds.
SCHEME 3
Synthesis of 2-amino-4H-chromenes 16–18 by three-component condensation catalyzed by
nano ZnO
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Multi-Component Synthesis of 2-Amino-4H-chromenes
1293
Structures of all compounds were characterized by 1H NMR, FTIR,
microanalysis, and mass spectroscopy.
A mechanistic proposal for the formation of 2-amino-4H-chromenes from
the reaction of aldehyde, malononitrile, and a naphthol was proposed to
involve through a two-step process: (i) The nucleophilic addition of the
malononitrile to the carbonyl group of aldehyde forming a Knoevenagel
product followed by (ii) the nucleophilic addition of the naphthol to the
2
+
Knoevenagel product. The nano ZnO has Lewis acid sites (Zn ) and Lewis
2
– 42
basic sites (O ) . A number of methods for determining acidity and acid
4
3
strength of ZnO as well as nano sized ZnO have been reported . Tanabe
et al.44 was shown that ZnO has a slight acidity of 0.004 mmol/g at acid
strength H < +6.8, and ca. 0.010 mmol/g at the same acid strength when
o
heated in air or in vacuum. Therefore we concluded that ZnO has a slight
acidity properties and it could act as an acid catalyst.
2
–
In the first step (i) the Lewis base sites (O ) of nano ZnO takes up a pro-
ton of the malononitrile, and the resulting carbanions form a complex with
the Zn2+ sites (Lewis acid-type) and the Lewis acid sites (Zn ) of nano ZnO
is coordinated to the oxygen of the carbonyl group, resulting in the in-
creased reactivity of aldehyde. To argument with this step, Knoevenagel
product formation was observed (IR, NMR, MS) when aldehyde was treated
with malononitrile in the presence of nano ZnO (10 mole %) at 80 °C for
2+
1
h. In the second step (ii), we propose that the Lewis basic sites of nano
2
–
ZnO (O ) coordinate to the –OH group of naphthol and then it could be
attack to the electrophilic C=C double bond (Scheme 4).
Reactions were carried out under the same reaction conditions to obtain
a comparative evaluation of the efficacy of nano ZnO with that of other
catalysts reported recently for the synthesis of 2-amino-4H-chromenes
SCHEME 4
Proposed mechanism
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Hosseini-Sarvari, Shafiee-Haghighi:
(
Table II). The Table shows that the yield of desired product in the presence
of nano ZnO is comparably higher than other catalysts used. Consequently,
our method can be certainly considered as a convenient alternative to the
other eco-friendly catalytic methods used for one-pot three-component syn-
thesis of 2-amino-4H-chromenes, specially, hydroxyl-2-amino-4H-chromenes.
Finally, in order to correlate between the catalyst properties and its activ-
ity, the reactions were carried out under the same reaction conditions to
obtain a comparative evaluation of the efficacy of nano flake ZnO with that
of other metal oxide catalysts for the synthesis of 4e (Table III). Nano parti-
cles ZnO, nano-TiO , and nano-MgO, were simply prepared according to
2
2
7
the literature or in our laboratory . Our studies showed that nano-flake
ZnO is an efficient catalyst and is more reactive than other commercial and
nano metal oxides in the synthesis of 4e (Table III). The catalytic activity
was observed in the following order: nano-flake ZnO > nano-particles ZnO
>
commercial ZnO > different metal oxides with bulky and nano dimen-
sions. The observed trend could be explained in terms the sized of the cata-
lyst that, also contribute in making the reaction more feasible due to easy
diffusion of reactants and product molecules. Nano-flakes ZnO used in the
TABLE II
Comparison of catalytic activity of nano ZnO catalyst with several other catalysts
2
-amino-4H-
Reaction
conditions
Time
h
Yield
%
Entry
1
a
chromenes
Nano ZnO (0.5 mmol)/H O/80 °C
1.5
3
95
52
72
59
93
97
2
Bulky ZnO (0.5 mmol)/H O/80 °C
2
2
9
Et N (0.5 mmol)/EtOH (25 ml)/reflux
2
3
Piperidine (0.02 mol)/EtOH (50 ml)/reflux32
3
3
1
KF/Al O /EtOH (15 ml)/80 °C
5–6
1
2
3
2
3
I /K CO /H O/100 °C
2
2
3
2
2
Nano ZnO/80 °C
Bulky ZnO
5
85
trace
74
0
24
3
2
9
Et N (0.5 mmol)/EtOH (25 ml)/reflux
3
Piperidine (0.02 mol)/EtOH (50 ml)/reflux32
3
3
1
KF/Al O /EtOH (15 ml)/80 °C
5–6
4–6
0
2
3
2
3
I /K CO /H O/100 °C
0
2
2
3
2
a
Isolated yields.
Collect. Czech. Chem. Commun. 2011, Vol. 76, No. 11, pp. 1285–1298

Multi-Component Synthesis of 2-Amino-4H-chromenes
1295
2
present study is found to have large surface area (380 ± 0.8 m /g), compared
to the other nano metal oxides.
TABLE III
Comparison of catalytic activity of nano-flake ZnO catalyst with other nano and bulky ZnO
and several other catalyst for the synthesis of 4ea
Yield of 4e Time
Surface area
m /g
Crystal size
nm
Catalyst
Entry
b
2
%
h
9
7
5
4
4
4
4
5
1.5
2
380±0.8
420±0.5
2.5–12
250±0.6
35
20–30
35±5
Nano-flake ZnO
1
2
3
4
5
6
7
c
0
2
0
0
0
5
Nano-particles ZnO
3
1500–2000
18–30
Commercial ZnO
Nano MgOd
Nano TiO2d
4
4
122
5
10–40
5–20
500–700
1000
Commercial MgO
Commercial TiO2
5
a
Reaction condition: 4-Chlorobenzaldehyde (1 mmol), malononitrile (1 mmol), 1-naphthol
b
c
(
1 mmol), Catalyst (0.5 mmol), 80 °C, water. Isolated yield. Nano particles ZnO were syn-
2
7 d
thesized as described previously
ries.
.
Nano MgO and TiO2 were synthesized in our laborato-
CONCLUSION
In conclusion, nano ZnO can serve as an efficient catalyst for the synthesis
of 2-amino-4H-chromenes. In addition, various naphthalenediols can be re-
acted with aldehydes and malononitrile to produce various naphtho-
pyranes. Finally, this procedure offers several advantages such as using
water as a green and economical solvent, simple reaction set up, easy work
up and crystallization, and good yields.
EXPERIMENTAL
1H and 13C NMR spectra (δ, ppm; J, Hz) were measured on Bruker Advance DPX FT 250 and
–
1
6
2.9 MHz spectrometer with TMS as an internal standard. IR spectra (ν, cm ) were obtained
on a Perkin–Elmer or FTIR-800 instrument. Mass spectra were obtained on a Shimadzu
GCMS0QP 1000EX at 20 and/or 70 eV. Elemental analyses were performed on Thermo
Finnigan, Flash EA 1112 series microanalyzer by the head of the CHN laboratory.
Preparation of the Catalyst
In a typical experiment for the synthesis of nano ZnO, Zn(OAc) ·2H O (10 mmol) and
2
2
CO(NH2)2 (0.2 mol) were dissolved in 200 ml deionized water at room temperature to form
a transparent solution. Then the mixture was refluxed for 12 h. It was cooled by cold water
Collect. Czech. Chem. Commun. 2011, Vol. 76, No. 11, pp. 1285–1298

1
296
Hosseini-Sarvari, Shafiee-Haghighi:
to stop the reaction. The product was centrifuged and washed with deionized water and ab-
solute ethanol, and dried at 80 °C for 8 h. The nano ZnO was obtained by calcining the pre-
2
7
cursor in a furnace in air at 400 °C for 2 h
.
Synthesis of Chromene Derivatives by Nano ZnO. General Procedure
A mixture of aromatic aldehyde (1 mmol), malonitrile (1 mmol), phenol or naphthol deriva-
tive (1 mmol) and nano ZnO (0.5 mmol, 0.04 g) was added to a test tube and heated in an
oil bath at 80 °C in water (2 ml). The progress of the reaction was monitored by TLC. After
the reaction was completed, the catalyst was filtered off and the precipitate was recrystalized
by EtOH. All synthesized compounds were stable as colorless to yellowish powders. Their
structures were confirmed by spectroscopic methods and elemental analyses. It is worth to
note that this conclusion is significant since there is no literature precedence for the synthe-
ses of compounds 4h and 9–12. The structures of products were confirmed by NMR, elemen-
tal analyses and compared with authentic samples obtained commercially or prepared by
1
reported methods. Products 4a–4g and 16–18 are known and were characterized by H,
1
3
C NMR and HRMS spectral data found to be identical with those described in refs16–25. For
new compounds, the complete spectroscopic data are described bellow.
2
-Amino-4-(thiophen-2-yl)-4H-benzo[h]chromene-3-carbonitrile (4h). Yellow powder (yield
1
9
8
0%); m.p.193–194 °C. IR (KBr): 3440, 3328, 1670, 2194. H NMR (DMSO-d , 250 MHz):
6
.19 (d, J = 8.50, 1 H), 7.85 (d, J = 8.20, 1 H), 7.13–7.57 (m, 8 H, Ar-H, NH ), 6.88 (m, 1 H,
2
1
3
Ar-H), 4.99 (s, 1 H, CH-Ar). C NMR (DMSO-d , 62.9 MHz): 36.03, 55.78, 117.60, 120.56,
6
1
1
7
20.63, 121.40, 122.69, 123.81, 126.04, 126.59, 126.69, 126.83, 126.94, 127.59, 132.64,
+
42.60, 146.22, 160.26. ESI-MS m/z: [M + H] 304. For C18H12N OS (304.37) calculated:
2
1.03% C, 3.97% H; found: 70.93% C, 3.90% H.
2
-Amino-4-(furan-2-yl)-4H-benzo[h]chromene-3-carbonitrile (4i). Yellow powder (yield 60%);
1
m.p. 168–170 °C. IR (KBr): 3440, 3328, 1658, 2202. H NMR (DMSO-d , 250 MHz): 8.28 (d,
6
J = 8.30, 1 H), 7.95 (d, J = 8.40, 1 H), 7.49–7.72 (m, 4 H, Ar-H), 7.29 (m, 3 H, Ar-H, NH ),
2
1
3
6
5
1
7
.41 (m, 1 H, Ar-H), 6.31 (m, 1 H, Ar-H), 5.10 (s, 1 H). C NMR (DMSO-d , 62.9 MHz): 34.5,
6
3.1, 106.0, 110.3, 115.3, 120.2, 120.5, 122.6, 123.8, 125.7, 126.6, 126.8, 127.6, 132.8,
+
42.6, 143.0, 156.2, 160.8. ESI-MS m/z: [M + H] 288. For C18H12N O (288.09) calculated:
2
2
4.99% C, 4.20% H; found: 74.87% C, 4.13% H.
3
-Amino-1-(4chlorophenyl)-5-hydroxy-1H-benzo[f]chromene-2-carbonitrile (9). Yellow powder
1
(
yield 80%); m.p. 208–210 °C. IR (KBr): 3475, 3359, 3257, 1649, 2185. H NMR (DMSO-d6,
2
6
1
1
6
50 MHz): 10.28 (s, 1 H, OH), 7.93 (d, J = 8.10, 1 H), 7.63–7.71 (m, 2 H), 7.19–7.32 (m, 6 H),
1
3
.93 (s, 2 H, NH ), 5.29 (s, 1 H). C NMR (DMSO-d , 62.9 MHz): 37.4, 57.3, 109.9, 116.6,
2
6
20.2, 123.2, 123.7, 124.0, 125.1, 126.4, 128.6, 128.6, 129.6, 130.0, 131.0, 131.2, 132.0,
+
39.0, 144.5, 160.0. ESI-MS m/z: [M + H] 348. For C20H13ClN O (348.78) calculated:
2
2
8.87% C, 3.76% H; found: 68.80% C, 3.71% H.
2
-Amino-4-(4-chlorophenyl)-7-hydroxy-4H-benzo[h]chromene-3-carbonitrile (10). Yellow pow-
1
der (yield 70%); m.p. 223–225 °C. IR (KBr): 3508–3208, 1660, 2200. H NMR (DMSO-d6,
2
(
50 MHz): 10.23 (s, 1 H, OH), 7.77 (m, 1 H), 7.63 (m, 1 H), 7.26 (m, 7 H, Ar-H, NH ), 6.92
2
m, 2 H), 4.89 (s, 1 H). 13C NMR (DMSO-d , 62.9 MHz): 37.9, 55.7, 109.2, 111.3, 117.4,
6
1
18.3, 120.4, 124.0, 124.3, 127.4, 128.6, 129.4, 131.5, 142.5, 144.5, 153.0, 160.2. ESI-MS
+
m/z: [M + H] 348. For C20H13ClN O (348.78) calculated: 68.87% C, 3.76% H; found:
2
2
6
8.81% C, 3.70% H.
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Multi-Component Synthesis of 2-Amino-4H-chromenes
1297
2
-Amino-4-(4-chlorophenyl)-8-hydroxy-4H-benzo[h]chromene-3-carbonitrile (11). Yellow pow-
1
der (yield 90%); m.p. 194–196 °C. IR (KBr): 3500–3200, 1660, 2192. H NMR (DMSO-d6,
2
7
6
1
50 MHz): 9.93 (s, 1 H, OH), 8.28 (d, J = 8.66, 1 H), 8.07 (d, J = 9.01, 1 H), 7.36 (m, 2 H),
1
3
.07–7.29 (m, 6 H, Ar-H, NH ), 6.94 (d, J = 8.50, 1 H), 4.83 (s, 1 H). C NMR (DMSO-d6,
2
2.9 MHz): 14.0, 55.9, 108.9, 114.0, 116.9, 118.8, 120.4, 122.4, 126.3, 127.9, 128.3, 128.5,
29.4, 130.8, 131.3, 134.6, 142.6, 142.9, 144.8, 156.1, 160.1. ESI-MS m/z: [M + H]+ 348. For
C20H13ClN O (348.78) calculated: 68.87% C, 3.76% H; found: 68.84% C, 3.70% H.
2
2
3
-Amino-1-(4-chlorophenyl)-9-hydroxy-1H-benzo[f]chromene-2-carbonitrile (12). Yellow powder
1
(
yield 85%); m.p. > 280 °C. IR (KBr): 3402, 3305, 1647, 2190. H NMR (DMSO-d , 250 MHz):
6
9
.59 (s, 1 H, OH), 7.77 (d, J = 9.20, 1 H), 7.69 (d, J = 10.36, 1 H), 7.31 (d, J = 8.35, 2 H), 7.14
1
3
(
(
d, J = 8.35, 2 H), 7.06 (s, 1 H), 6.92–6.95 (m, 4 H, Ar-H, NH ), 5.03 (s, 1 H). C NMR
DMSO-d , 62.9 MHz): 37.7, 57.4, 105.5, 113.0, 117.0, 120.3, 125.1, 128.6, 128.7, 129.38,
2
6
+
1
3
29.6, 130.1, 131.0, 131.9, 132.0, 144.4, 147.2, 156.3, 159.5, 160.03. ESI-MS m/z: [M + H]
48. For C20H13ClN O (348.78) calculated: 68.87% C, 3.76% H; found: 68.79% C, 3.71% H.
2
2
We thank the Shiraz University Research Council and the Iran National Science Foundation
(
Grant No. 87040564) for financial support.
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