Nanozeolite clinoptilolite as a highly efficient heterogeneous catalyst for the synthesis of various 2-amino-4H-chromene derivatives in aqueous media

Article abstract of DOI:10.1039/c3gc41302k

The preparation of pharmaceutically active 2-amino-4H-chromene derivatives has been achieved using a nano powder of natural clinoptilolite (CP) zeolite. A wide range of these worthy structures having diverse substituents on the 4H-chromene ring were effic

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Graphical Abstract
This study represents the applicability of green mechanism for organic
transformations using a natural and efficient catalyst and aqueous medium.

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Nanozeolite clinoptilolite as a highly efficient heterogeneous catalyst for
the synthesis of various 2-amino-4H-chromene derivatives in aqueous
media
Seyed Meysam Baghbanian*a, Niloufar Rezaei a and Hamed Tashakkorian b
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
Preparation of pharmaceutically active 2-amino-4H-chromene derivatives has been achieved using nano
powder of natural clinoptilolite (CP) zeolite. Wide range of these worthy structures having diverse
substituents on the 4H-chromene ring were efficiently synthesized via reaction of an aromatic aldehyde
10 and varity of enolizable C-H activated acidic compounds. Nano sized natural clinoptilolite zeolite was
prepared mechanically by planetary ball mill and confirmed by x-ray diffraction patterns (XRD),
scanning electron microscopy images (SEM) and Transmission electron microscopy (TEM). Catalytic
activity of nano CP was evaluated in aqueous media and the results show its applicability as a novel,
green, reusable and promising catalyst in organic synthesis.
15 Introduction
Suitability for such applications is due to its large cavity size, and
Natural zeolites are hydrated aluminosilicates, comprising of
hydrogen, oxygen, aluminium, and silicon arranged in an
interconnecting, open, three-dimensional structure. The primary
building units are [SiO4]4- and [AlO4]5- tetrahedral linked together
20 by oxygen atoms. One of the characteristics that distinguish
zeolites from other porous materials is their variety of pore sizes
and shapes. Therefore, sizes and shapes of channels/cavities in
zeolites therefore define the structural parameters of a given type
of zeolite. Properties of zeolites, such as ion exchange capability,
25 intercrystalline pores that discriminate between molecules of
different dimension, strong acidic sites, and active reservoirs for
metal-catalyzed reactions have earned them extensive industrial
50 high resistance to extreme temperatures.
Beside these considerable properties which led to number of
industrial usages, employing these structures in organic synthesis
has not been studied thoroughly. Having large surface area and
numerous active sites especially in nano sized zeolite makes it
55 excellent candidate to catalyze organic compounds. To explore its
capability, we intended to investigate on its features as a catalyst
in the synthesis of well known 2-amino-4H-chromene family. 2-
Amino-4H-chromenes are exciting heterocyclic compounds with
various noticeable biological and pharmacological activities
60 including antimicrobial and antifungal,5 antiproliferation,6
antitumor,7 antiallergenic,8 antioxidant 9 and having considerable
central nervous system activities.10 It was found that these
compounds can play an important role in the field of
uses.1 A general formula for a zeolite can be written as: Mx
/n
[(AlO2)x(SiO2)y].wH2O. M represents the cation of valence n, x is
30 general equal, and w is the number of water molecules.2
11
12
biodegradable agrochemicals
65 employed widely since then.
and pigments
and so, being
Zeolites may be either obtained from mineral deposits or can be
synthesized. Over 150 species of synthetic zeolite have been
synthesized and six kind of mineral zeolites have been found in
substantial quantity and purity up to now. These resources are
35 known as clinoptilolite (CP), chabazite, mordenite, erionite,
ferrierite and phillipsite.3 Clinoptilolite, one of the most useful
naturally occurring zeolites, is employed as molecular sieve, feed
and food additive, as well as gas and odour absorbent. 4
Generally, 2-amino-4H-chromenes are synthesized by the
condensation of an aromatic/aliphatic aldehyde, malononitrile (or
ethyl cyanoacetate), and broad range of enolizable C-H activated
acidic compounds.13 There are some reports in which preparation
70 of these structures were accomplished using some homogeneous
or heterogeneous catalysts such as chitosan,14 KSF,15 K3PO4,16
K2CO3,17 Na2CO3 under grinding,18 nano-sized MgO,19
heteropolyacid, Mg/Al hydrotalcite,20 TiCl4 ,21 methane sulfonic
40 aDepartment of Chemistry, Ayatollah Amoli Branch, Islamic Azad
University, Amol, Iran
Email: S.M.Baghbanian@iauamol.ac.ir; Tel/fax:(+98)1212517071
bCellular and Molecular Biology Research Center (CMBRC), Babol
University of Medical Science, Babol, Iran
45 †Electronic Supplementary Information Electronic supplementary
information (ESI) available: See DOI: 10.1039/b000000x
[BMIm]BF4,24 [2-aemim][PF6],25
tetrabutylammonium
acid,22 TMG-[bmim][x],23
75 DBU,26
bromide,27
N,N-
28
triethylbenzylammonium
chloride
and
dimethylaminoethylbenzyldimethylammonium chloride.29
Although all of these methods are effective, but having
drawbacks such as tedious work-up procedures, the use of
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2.3. General procedure for synthesis of 2-amino-4H-chromene
derivatives
Nanozeolite CP (0.01 gr) was added to the suspension of an
expensive catalysts and solvents, elevated temperatures, long
reaction times and low yield diminished their importance as
appropriate method. Thus, development of a simple, eco-benign,
low cost protocol, using neutral and reusable catalyst for one-pot
synthesis of 2-amino-4H-chromene derivatives still remains as an
attractive goal for researchers.
In continuation of our studies on the development of new
catalysts and offering novel methodology in organic synthesis,30
herein we report a cheap, benchmark and environmentally
aromatic aldehyde (1 mmol) and malononitrile (1 mmol) in
55 distilled water (5 mL). Then, the reaction mixture was refluxed
for appropriate time as shown in Tables 2-5. After completion of
the reaction which was monitored by TLC (EtOAc/Hexane,
40/60), the catalyst was removed by simple filtration and washed
with hot distilled water (5mL) and ethanol (3 mL) two times. The
60 filtrate was cooled down to room temperature and the crude
products which precipitated quantitavly were collected using
Buchner funnel. To obtain the pure products it was recrystallized
from ethanol if necessary. The products were characterized with
IR, 1HNMR and 13CNMR spectroscopies and also using
65 elemental analysis (CHN) technique.
5
10 friendly procedure for the synthesis of 2-amino-4H-chromene
with diverse substituents in the presence of nanozeolite
clinoptilolite as a green catalyst in aqueous media (Scheme 1).
R
Nanozeolite
X
H
X
O
clinoptilolite
Water,Ref lux
R
H
CN
O
NH2
OH
2
4
1
3
X= CN, CO2Et
3. Results and discussion
Scheme 1: Synthesis of 2-amino-4H-chromene derivatives in the
presence of nanozeolite clinoptilolite as a heterogeneous catalyst.
3.1. Characterization of nanozeolite clinoptilolite
FT-IR spectra obtained using KBr pellets of the zeolite CP and
70 the nanozeolite CP are shown in Figure 1. The zeolite CP
contains bands due to hydrogen bonds in the complex water-
framework oxygen-cation (3741 cm-1), symmetric and
asymmetric stretching vibration of the OH groups (3444 cm-1),
medium intensity band of the bending H-О-H vibration (1645 cm-
75 1), The weak and broad bands of the asymmetric stretching
vibration of the Si-O and Al-O bonds (1087 cm-1) and The weak
bands of bending vibrations of O-Si-O and O-Al-O (470 cm-1).
For nanozeolite CP, the region corresponding to (Si-O and Al-O)
and (O-Si-O and O-Al-O) show strong and broad bands that
80 demonstrate the increase in surface area and aluminusilicate
bonds of nanozeolite CP.
15 2. Experimental
2.1. Reagents and materials
All reagents were prepared from analytical reagent grade
chemicals unless specified otherwise and purchased from Merck
Company. The raw zeolite material was an Iranian commercial
20 Clinoptilolite (Afrandtooska Company) obtained from deposits in
the region of Semnan (ca. 1 $ per kg).
2.2. Instrumentation
Ball milling of clinoptilolite zeolite sample was carried out by
25 mean of a planetary ball mill (PM100; Retsch Corporation). In
most of the performed experiments a clinoptilolite powder with
particle size of around 7 μm was applied as the starting material.
Planetary ball milling was performed in dry conditions with time
period of about 60 min, 10 balls of 20 mm per 30 gr of powders
30 and milling speed of 350 rpm. All of the experiments were done
in a 250 ml stainless steel jar with protective jacket of zirconium
oxide. Zirconium oxide balls were utilized for dry milling.
Melting points were measured on an Electrothermal 9100
apparatus. The samples were analyzed using FT-IR spectroscopy
35 (using a Perkin Elmer 65 in KBr matrix). The X-ray powder
diffraction (XRD) of the catalyst was carried out on a Philips PW
1830 X-ray diffractometer with CuKα source (λ=1.5418 Å) in a
range of Bragg’s angle (5-80°) at room temperature. Scanning
electron microscope (SEM) pictures were taken using KYKY-
40 EM3200 microscope (acceleration voltage 26 kV). Particle size
measurements of the ground samples performed by laser beam
scattering technique through means of a Master size 2000
apparatus (MALNERN Instruments). Transmission electron
microscopy (TEM) experiments were conducted on a Zeiss-
45 EM10C microscope operated at 80 kV. The samples for TEM
measurements were suspended in ethanol by sonication and then
drop drying on a copper grid (400 mesh) coated with carbon film.
1H, 13C NMR spectra were recorded on a BRUKER DRX-400
AVANCE spectrometer. Elemental analyses for C, H and N were
50 performed using a Heraeus CHN-O-Rapid analyzer
Figure 1. FT-IR spectra of the zeolite samples: (a) zeolite CP, (b)
nanozeolite C
P
85
To reach the best catalytic activity, preparation of nano sized
zeolite was performed by means of a planetary ball mill in the dry
state. For optimization of the ball milling conditions, at first, we
determined particle size of the raw zeolite material by laser beam
90 scattering technique and found that the median is around 7 µm
(Figure 2).
95
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60 The difference between amorphous surface structures of the
natural zeolite sample and Nanozeolite CP with uniform surface
are apparent according to SEM images (Figure 5 a,b). Due to the
lack of uniformity and wide range of particles dimensions,
determination of particle size distribution cannot be performed
65 accurately for micro sized CP according to figure 5a but for
nanosized particles depicted in figure 5b, spherical structures
with homogeneous pattern, provide a desirable situation for
particle distribution to be graphically analyzed. Distribution
diagram (Figure 5c) illustrates the average particle sizes of
70 nanosized ball milled CP. For further investigation on
determinations of particle size of nanostructure CP, we applied
transmission electron microscopy (TEM). The shapes and
dimensions of the particles can be seen in Figure 6. As
anticipated, the TEM image of nano CP revealed that the
75 previous calculation of the particles size was quietly precious and
is around 70 nm. Both SEM and TEM techniques proved the
XRD patterns in which nano sized zeolite were indicated by
distinctive peaks. These results approve our method for
preparation of the nano sized zeolite.
5
Figure 2. Cumulative distribution curves of particle size
zeolite CP
10 Then by employing speed of 100 rpm and milling duration of 30
min, fine powder was gained and was characterized with SEM to
find the particle size and of course the shape and distribution
images (Figure 3).
15
80
20
25
85
Figure 3. SEM images of zeolite CP after milling in speed of 100 rpm.
30 The different kinds of shapes as well as broad range of particle
sizes can be detected in this image. Utilizing this speed and
milling duration could not fulfill our needs for preparing a
catalyst with homogenous structure. Therefore, more powerful
condition was needed to improve the catalyst shape and size. So,
35 350 rpm and milling duration of 1 hr was selected. Again, size,
shape and morphology of the nanozeolite CP were investigated
using X-ray diffraction (XRD) patterns and scanning electron
microscopy (SEM) imaging techniques. With Regards to the
intensity ratio of major peak observed at 2θ equal to 22.49°, the
40 crystalline structure of the zeolite can clearly be recognized. The
average crystallite size (L) was calculated from the excess of
width line of the diffraction pack in radians (β), Bragg angle in
degrees (θ), and Debye-Sherrer’s equation; L=0.89λ/βcosθ; β is
the FWHF of the diffraction pack and λ is the wavelength. By
45 calculation the average crystallite sizes of prepared nanozeolite
CP lays around 70 nm (Figure 4).
90
95
1
50
00
Figure 5. a) SEM image of the original zeolite CP, b) SEM image of the
nanozeolite CP, c) The size distributions of the nanozeolite CP according
105 to SEM image of 5b
55
Figure 4. XRD patterns of nanozeolite CP
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50 Also, the use of water as solvent, improved the yield of the
desired product 6a slightly (Table 1, entries 3 and 4). Obviously,
using CP as a catalyst increased the yield of product 6a from 35%
to 70% in water at 95 °C (Table 1, entry 5). Interestingly,
employing just 0.1 gr nano CP instead of CP can increase the
55 yields up to 85% under similar conditions (Table 1, entries 6). It
was observed that a decrease in the amount of nano CP from 0.1
to 0.01g can raise the yield even more and up to 98% and reduce
the reaction time from 60 to 15 min simultaneously (Table 1,
entries 6-9). Industrial solvents such as EtOH, MeCN and
60 CH2Cl2, besides instead of aqueous media, Moreover their
undesirable effects on environment afforded lower yields for the
desired product 6a under similar conditions (Table 1, entries 10-
12).
5
10
15
20
25
65 Table 1. Optimization of the three-component reaction of dimedone
(1),
4-chlorobenzaldehyde (5), and malononitrile (3) under various conditionsa
Catalyst
loading
(gr)
Yieldb
(%)
Time
(min)
Entry
Catalyst
Solvent
1c
2
-
-
-
-
-
-
60
60
Trace
Trace
3c
-
-
H2O
60
20
4
5
6
7
8
-
CP
-
0.1
0.1
0.08
0.04
0.01
0.01
0.01
0.01
H2O
H2O
H2O
H2O
H2O
60
90
60
45
35
15
20
20
20
35
70
85
90
95
98
85
80
65
Figure 6. TEM images of the nanozeolite CP
Nano CP
Nano CP
Nano CP
Nano CP
Nano CP
Nano CP
Nano CP
3.2 Catalytic studies
30 To find the optimized condition, the reaction of dimedone 1 (1
mmol), 4-chlorobenzaldehyde 5 (1 mmol) and malononitrile 3 (1
mmol) in aqueous medium as a model reaction in the presence of
different amounts of nanozeolite CP was examined (Scheme 2)
and variables affecting on the reaction yields were studied.
35 In the absence of catalyst, only a trace amount of desired 2-
amino-4-(4-chlorophenyl)-3-cyano-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene 6a was obtained under solvent-free
conditions even at 100 °C (Table 1, entries 1 and 2).
H2O
9
10
11
12
EtOH
MeCN
CH2Cl2
a
Reaction conditions: 4-chlorobenzaldehyde (1 mmol), dimedone (1
mmol), malononitrile (1 mmol), water (5 mL), and required amount of the
b
c
70 catalysts at 95 °C. The yields refer to the isolated product. at room
temperature.
Encouraged by the remarkable results, and in order to show
generality and scope of this new protocol, a variety of 2-amino-
75 tetrahydrobenzo[b]pyran derivatives were synthesized from the
three-component reaction of dimedone, appropriate aldehyde and
malononitrile or ethyl cyanoacetate in the presence of a catalytic
amount of nanozeolite CP (0.01 gr) in aqueous medium under
reflux conditions. The results have been summarized in Table 2.
80 The reaction time of aromatic aldehydes having electron
withdrawing groups (Table 2, entries 1-6) were somewhat faster
than electron donating groups, because of the ease in the first step
of cyclization reaction between aldehyde and nucleophilic group
(Table 2, entries 8-13). The heterocyclic and alkenyl aldehydes
85 underwent the reaction cleanly in excellent yields (Table 2,
entries 14-16). Though meta- and para- substituted aromatic
aldehydes gave excellent results, ortho-substituted aromatic
aldehydes gave slightly lower yields because of the steric effects.
40
Cl
O
H
O
O
O
CN
CN
Nanozeolite CP
ater, Reflux
CN
W
O
NH2
Cl
6a
1
3
5
Scheme 2. The reaction of dimedone (1 mmol), 4-chlorobenzaldehyde (1
45 mmol) and malononitrile (1 mmol) as model reaction catalyzed by
nanozeolite CP in water
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Table 2. Synthesis of derivatives of 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-benzo[b]pyran in the presence of nanozeolite CP.a
Yield c
(%)
Mp (obsd)
(°C)
Mp (lit.)
(°C)
Time
(min)
Product b
Ref.
Entry
RCHO
Carbon acid
Cl
CHO
O
1
CN
15
25
15
98
213-214
212-213
178-180
215-217
214-215
179-180
31a
CN
Cl
O
NH2
6a
CHO
O
Cl
Cl
CN
2
CN
98
31b
O
NH2
6b
NO
2
CHO
NO2
O
3
CN
90
31c
CN
O
NH2
NO2
6c
CHO
O
4
CN
20
92
179-182
179-180
31a
CN
NO2
O
NH2
6d
Cl
CHO
O
5
COOEt
45
90
152-153
153-154
31e
COO Et
Cl
O
NH2
NO2
6e
CHO
O
6
COOEt
40
92
152-154
154-156
31g
COOEt
NH2
NO2
O
6f
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CHO
O
O
O
15
95
233-235
234-235
31d
7
CN
CN
O
NH2
6g
CH
3
CHO
8
CN
25
95
221-223
220-222
31e
CN
CH3
O
NH2
6h
OH
CHO
9
CN
25
92
223-225
224-226
31d
CN
OH
O
NH2
6i
OMe
CHO
O
10
CN
30
90
198-202
201-202
31d
CN
OMe
O
NH2
6j
OMe
CHO
O
OMe
CN
OMe
11
35
95
216-217
216-218
31f
CN
OMe
O
NH2
6k
H3C
CH
3
N
CHO
O
12
CN
30
92
210-213
210-212
31g
CN
N
H3C
CH3
O
NH2
6l
CH3
CHO
CH3
O
13
COOEt
60
90
152-153
151-152
31g
COOEt
NH2
O
6m
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O
O
H
14
CN
25
92
183-185
182-184
31h
CN
O
NH2
6n
O
O
O
O
CN
15
16
CN
CN
30
30
95
95
220-223
223-225
220-223
224-226
31i
31j
H
O
NH2
6o
S
O
O
S
CN
H
O
NH2
6p
a Reaction conditions: dimedone (1 mmol), aldehyde (1mmol), malononitrile or ethyl cyanoacetate (1 mmol), water (5 mL, reflux), nanozeolite CP (0.01
gr). b All compounds are known and their structures were established from their spectral data and melting points as compared with literature values. c The
yields refer to isolated products.
5
For more exploration, various derivatives of 2-amino-4,8-
dihydropyrano[3,2-b]pyran-3-carbonitrile were synthesized
from the aqueous reaction mixture of kojic acid 7, aromatic
aldehydes 2 and malononitrile 3 in the presence of catalytic
amount of nanozeolite CP (0.01 gr) at 95 °C (Scheme 3). The
10 results were summarized in Table 3
R
O
O
O
O
CN
Nanozeolite CP
Water, Reflux
HO
HO
NC
CN
R
H
15
OH
O
8
NH2
3
2
O
7
Scheme 3. Three-component synthesis of pyrano[3,2-b]pyrans
Table 3. Synthesis of derivatives of pyrano[3,2-b]pyran in the presence of nanozeolite CPa
Y
ieldc
(%)
Mp (obsd) (°C) Mp (lit.) (°C)
ref
32
Entry
RCHO
Product b
Time (min)
CHO
O
CN
HO
1
25
95
98
221-224
198-203
220–222
O
NH2
O
8a
Cl
CHO
O
CN
2
18
New
32
HO
O
NH2
Cl
O
8b
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CHO
Cl
O
O
CN
Cl
HO
3
30
35
88
85
212-215
240-241
210-213
240-242
32
32
O
NH2
8c
Cl
CHO
Cl
Cl
O
O
CN
4
HO
O
NH2
Br
Cl
8d
CHO
O
O
CN
5
6
7
HO
25
15
20
95
96
95
243-245
247-250
220-222
242–244
248–250
219–221
32
32
O
F
NH2
Br
8e
CHO
O
CN
HO
O
NH2
F
O
8f
CH3
CHO
O
O
CN
32
32
HO
HO
HO
O
O
O
NH2
CH3
8g
O
O
H
O
CN
20
18
97
92
221-223
234-236
223–225
235–237
8
9
NH2
O
O
8h
S
O
H
O
O
CN
32
NH2
S
8i
b
a Reaction conditions: kojic acid (1 mmol), aldehyde (1mmol), malononitrile (1 mmol), water (5 mL, reflux), nanozeolite CP (0.01 gr). All compounds
are known and their structures were established from their spectral data and melting points as compared with literature values. c The yields refer to isolated
products.
Moreover, 4-hydroxy-1-methylquinolin-2(1H)-one 9 was used
as enolic component to synthesize pyrano-[3,2-c]-quinolone
derivatives 10 under the optimized conditions mentioned above
(Scheme 4). The results were represented in Table 4.
5
15
NH2
CN
O
OH
O
Nanozeol ite CP
Water, Reflux
R
10
H
R
CN
NC
N
O
N
O
2
20
3
CH
3
CH3
9
10
Scheme 4. Three-component synthesis of pyrano[3,2-c]pyridones
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Table 4. Synthesis of derivatives of pyrano[3,2-c]pyridone in the presence of nanozeolite CP a
Yield b
(%)
Mp
(°C)
Time
(min)
Ref.
Entry
RCHO
Product
NH2
CN
O
CHO
1
30
25
35
30
95
92
94
92
255-258
280-282
285-286
260-262
33
33
33
33
N
O
CH3
10a
NH2
CHO
CN
O
2
3
4
N
O
Cl
CH3
Cl
10b
NH2
CN
O
N
CHO
Cl
O
Cl
CH3
10c
NH2
CN
O
CHO
Br
N
O
Br
CH3
10d
NH2
CN
CHO
O
NO2
5
6
7
25
30
30
85
88
90
274-276
267-268
262-263
33
33
33
N
O
NO 2
CH3
10e
NH2
CHO
CN
O
OMe
OMe
N
O
MeO
OMe
CH3
O Me
OMe
10f
2
NH
CHO
CN
O
OH
N
O
OMe
OH
CH3
OMe
10g
NH2
CN
O
O
H
O
8
35
85
282-283
33
O
N
O
CH3
10h
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Green Chemistry
NH2
CN
O
CHO
9
35
90
287-289
33
N
N
O
N
CH3
10i
a Reaction conditions: 4-hydroxy-1-methylquinolin-2(1H)-one (1 mmol), aldehyde (1mmol), malononitrile (1 mmol), water (5 mL, reflux), nanozeolite CP
(0.01 gr). b The yields refer to isolated products.
Other aromatic enolizable compounds such as resorcinol 11,
and also ones containing fused aromatic rings such as 1-
naphthol 12 and 2-naphthol 13 were also used in the synthesis
of 2-amino-7-hydroxy-4H-chromenes (14-16) (Scheme 5).
According to the data given in Table 5, aromatic and hetero-
aromatic aldehydes bearing sensitive substituents were also
20 fruitfully being applied in this reaction protocol, without
producing by-products or drawbacks.
5
10
15
R
25
CN
14
HO
OH
11
HO
O
NH2
NH2
CN
R
O
OH
O
2
Nanozeolite CP
Wat er, Reflux
R
H
NC
CN
15
3
CN
12
R
NH2
O
30
OH
16
13
Scheme 5. Three-component synthesis of 2-amino-4H-chromenes
35
Table 5. Synthesis of derivatives of 2-amino-7-hydroxy-4H-chromene (14-16) in the presence of nanozeolite CP a
Yield c
(%)
Mp (obsd)
(°C)
Mp (lit.)
(°C)
Time
(min)
Product b
Ref.
34a
Entry
RCHO
CHO
1
15
92
233-235
232-234
CN
HO
O
14a
Cl
NH2
CHO
2
15
95
162-164
162-163
34a
CN
Cl
HO
O
NH2
14b
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Page 12 of 15
Br
CHO
3
20
90
227-230
225-227
34a
CN
Br
HO
O
NH2
14c
Me
CHO
4
35
92
186-188
185-187
34a
CN
Me
HO
O
NH2
14d
O
O
H
CN
5
6
30
20
90
92
188-190
177-179
189-191
178-180
34b
O
HO
O
NH2
14e
NH2
CN
CHO
O
19
15a
NH2
CHO
CN
O
7
8
20
15
25
30
95
95
85
88
230-233
233-235
247-248
203-205
230-232
231-234
247-249
204-206
19
19
35
35
Cl
Cl
15b
NH2
CHO
CN
O
NO2
OH
Me
NO2
15c
NH2
CHO
CN
O
9
OH
15d
NH2
CHO
CN
O
10
Me
15e
CN
CHO
NH2
11
20
95
273-276
274–276
36
O
16a
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Green Chemistry
Cl
CN
CHO
NH2
12
20
92
90
205-207
257-259
205–206
258–260
36
36
O
Cl
16b
Cl
CN
CHO
NH2
Cl
22
13
O
16c
16d
O2N
CN
CHO
NH2
14
15
15
18
95
90
185-188
258-260
186–187
258–259
36
36
O
NO2
NC
CN
CHO
NH2
O
CN
16e
a Reaction conditions: resorcinol, 2-naphthol or 1-naphthol (1 mmol), aldehyde (1mmol), malononitrile (1 mmol), water (5 mL, reflux), nanozeolite C
P
(0.01
b
gr). All compounds are known and their structures were established from their spectral data and melting points as compared with literature values. c
The yields refer to isolated products.
5
The reusability of the nano sized zeolite CP was checked in the
reaction of 4-chlorobenzaldehyde, dimedone, and malononitrile
under the present reaction condition (Table 2, entry 1). After
completion of the reaction which was monitored by TLC
(EtOAc/Hexane, 40/60), the catalyst was removed by simple
the synthesis of 2-amino-4-(4-chlorophenyl)-7,7-dimethyl-5-
oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile. The very
15 slight loss in the reaction yields were because of some blocked
pores in the zeolite structure which were inaccessible by the
association of reaction impurities. These results represent the
practical recyclability of this catalyst and will intensify its
potential role in modern organic synthesis (Table 6).
10 filtration and washed with hot distilled water (5mL) and
ethanol (3 mL) two times, dried in an oven and reused
successively 5 times without any significant loss of activity for
20
Table 6 Reusability of catalyst for the synthesis of 2-amino-4H-chromene 6a (Table 2, entry 1)a.
Number of experiments
Isolated yield (%)b
1
96
2
94
3
94
4
92
5
90
6
90
a Reaction condition: 4-chlorobenzaldehyde 1mmol, malononitrile 1mmol and dimedone 1mmol, nanozeolite CP as a catalyst 0.01 gr, water, reflux.
b Isolated yield.
In order to show the accessibility of the present work, we
25 compared this method with respect to the previously reported
catalysts for the preparation of 2-amino-4H-chromene
derivatives. The results for the preparation of 6a were
represented in Table 7.
30
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Page 14 of 15
Table 7 Comparison of the catalytic activity of the nanozeolite CP with some reported catalysts for the synthesis of 6a
Temp
(°C)
Reflux
Reflux
Reflux
90
Reflux
Reflux
Reflux
r.t.
Time
(min)
15
30
Yield
(%)
Entry
Ref
Catalyst
55
60
65
1
2
3
4
5
6
7
8
9
LiBr, H2O, 0.02 gr
95
94
88
94
94
98
97
97
94
90
98
37
31d
38
39
40
41
42
43
44
45
-
Tetrabutylammoniumfluoride (TBAF), H2O, 10 mol%
Nickel nitrate hexahydrate (Ni(NO3)2.6H2O), H2O, 10 mol%
Triethylbenzylammonium chloride (TEBA), H2O, 100 mol%
1,4-Diazabicyclo[2.2.2]octane (DABCO), H2O, 10 mol%
poly(4-vinylpyridine)/MCM-48 (P4VP/MCM-48), H2O, 0.12 gr
Na2SeO4, EtOH/H2O, 0.1 gr
20
420
120
120
60
120
60
5
(NH4)2HPO4, H2O, 0.013 gr or 10 mol%
Lipase, EtOH/H2O, 0.03 gr
r.t.
r.t.
Reflux
N-Methylimidazole, H2O, 20 mol%
Nanozeolite CP, H2O, 0.01 gr
10
11
90
15
70
10 4. Conclusions
6. M. Brunavs, C.P. Dell, P.T. Gallagher, W.M. Owton and C.W.
Smith, Eur. Pat. Appl. EP 557075 A1 19930825, 1993.
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8. K. Gorlitzer, A. Dehre and E. Engler, Arch. Pharm. Weinheim Ger.
1983, 316, 264-270.
We have introduced a one pot and applicable procedure for
preparation of novel and highly efficient method for the
synthesis of 2-amino-4H-chromene derivatives in the presence
of the nanozeolite clinoptilolite as a green heterogeneous
15 reusable natural catalyst in aqueous media. Herein, we
employed this valuable and reusable catalyst for the synthesis
of biological and pharmaceutical compounds, 2-amino-4H-
chromene derivatives and demonstrated its preference to other
catalysts. This method has the advantages of high yield, simple
20 methodology, green reaction conditions and easy work-up in
which the chromatographic separation is not necessary to get
the pure compounds. Moreover, from the both industrial and
economical point of view, low cost as well as promoting the
chemical transformations with appreciable conversion of the
25 substrates are the main goals, which we achieved by using this
nanocatalyst. So, the proposed methodology to use the
nanozeolite clinoptilolite with attractive capabilities was
accomplished.
75
9. a) L. Alvey, S. Prado, V. Huteau, B. Saint-Joanis, S. Michel,
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