4-Dialkylaminopyridine modified magnetic nanoparticles: As an efficient nano-organocatalyst for one-pot synthesis of 2-amino-4: H -chromene-3-carbonitrile derivatives in water

Article abstract of DOI:10.1039/c6ra18078g

A novel heterogeneous magnetic nano-organocatalyst was developed using immobilization of 4-dialkylaminopyridine moieties on Fe₃O₄ magnetic nanoparticles (MNP-DMAP). It was synthesized using the reaction of MNP-oxiran (MNPO) with N-methylpyridin-4-amine. The MNPO substrate was produced via oxidation of vinyl groups on the surface of vinyl-functionalized MNP (VMNP) using H₂O₂. To synthesis VMNP, silica-coated magnetic nanoparticles (Fe₃O₄@SiO₂) were reacted with trimethoxy(vinyl)silane. The MNP-DMAP catalyst shows remarkable activity in the synthesis of 2-amino-4H-chromene-3-carbonitrile derivatives using a multicomponent reaction under mild conditions in water as a green solvent. The MNP-DMAP was reusable in this process for at least 10 times without any treatment in its catalytic activity.

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4-Dialkylaminopyridine modified magnetic nanoparticles: as an
efficient nano-organocatalyst for one-pot synthesis of 2-amino-
4H-chromene-3-carbonitrile derivatives in water
Received 00th January 20xx,
Accepted 00th January 20xx
Soheila khajeh Dangolani,a Farhad Panahi,*,b Maryam Nourisefat,a and Ali Khalafi-Nezhad*a
DOI: 10.1039/x0xx00000x
A novel heterogeneous magnetic nano-organocatalyst was developed using immobilization of 4-dialkylaminopyridine
moieties on Fe3O4 magnetic nanoparticles (MNP-DMAP). It was synthesized using the reaction of MNP-oxiran (MNPO) with
N-methylpyridin-4-amine. The MNPO substrate was produced via oxidation of vinyl groups on the surface of vinyl-
functionalized MNP (VMNP) using H2O2. To synthesis VMNP, silica-coated magnetic nanoparticles (Fe3O4@SiO2) were
reacted with trimethoxy(vinyl)silane. The MNP-DMAP catalyst shows remarkable activity in the synthesis of 2-amino-4H-
chromene-3-carbonitrile derivatives using a multicomponent reaction under mild conditions in water as a green solvent.
The MNP-DMAP was reusable in this process at least for 10 times without any treatments in its catalytic activity.
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completion of the reaction. This advantage is resulted from
this fact that MNPs can be removed from the reaction mixture
using an external magnetic field. In order to immobilize
Introduction
Organocatalysis is an exponentially upward research field in
modern organic chemistry that involves the synthesis and
utilization of organocatalyst in organic transformations.1
Recovery and reuse of organocatalysts after catalytic reactions
are important factors in view point of sustainable and green
chemistry.2 Thus, organocatalysts have been immobilized or
grafted onto solid supports to improve their recycling
capability, leading to the appearance of heterogeneous
organocatalysis.3 Up to know different supports such as silica,
polymer, magnetic nanoparticles (MNPs), etc. have been used
and efforts on the finding new support materials for the
heterogenization of organocatalysts to be continued.4 The
choice of MNPs as the substrate for the preparation of
heterogeneous organocatalysts is very intelligently because it
can cover most concerns about heterogeneous catalysts such
as activity, selectivity, work up and recyclability.5 That's the
main reason for the use of magnetic support for the
preparation of heterogeneous organocatalysts.6
organocatalysts on MNPs, they should be covalently
connected to the surface through a chemical process. To
prevent the aggregation of MNPs and also increase the
stability of them, usually a layer of silica is coated on the
surface and they have been used in silica-coated form. Silica
coatings also encompass several advantages originating from
their stability under aqueous conditions, simple surface
modification. Furthermore, easy control of interparticle
interactions of MNPs particles is possible through the variation
of the shell thickness.7 Since the silica-coated magnetic
nanoparticles (Fe3O4@SiO2) surface is covered with hydroxyl
groups, it is possible to graft the organic groups to the MNPs
surface via the reaction of alkoxysilane materials with silanol
groups (Silanization).8 Indeed, the organofunctional
alkoxysilanes create their organic group (such as NH2, SH, etc.)
on
the
surface
for
further
functionalization.
Trimethoxy(vinyl)silane is an alkoxysilane which can be used
for the generation of vinyl group on the surface of MNPs.9
Conversion of vinyl group on the MNPs surface to epoxide
rings opens up our hand for chemically modification through
ring opening by nucleophiles. Thus, reaction of an
organocatalyst containing a nucleophilic position with oxiran
rings on the surface of MNPs, leading the formation of
MNPs have appeared as practical alternatives to other
materials for use as readily available and high-surface-area
solid supports in catalyst science and technology. In addition,
these materials possess the main advantage which is being
magnetically recoverable, thus eliminating the requirement for
either solvent swelling before or catalyst separation after
catalytic sites on its surface and producing
heterogeneous organocatalyst.10
a new
4-(Dimethylamino)pyridine (DMAP) is an important
organocatalyst for a large variety of organic reactions.11 Due to
the importance of DMAP recovery in organic transformations
(in view point of green chemistry and sustainability), many
attempts have been done on its immobilization on different
a Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454,
Iran.
b Department of Polymer Engineering and Color Technology, Amirkabir University of
Technology, Tehran, Iran.
E-mail: fpanahi@aut.ac.ir, khalafi@susc.ac.ir
Electronic Supplementary Information (ESI) available: Copies of 1H and 13C NMR for
all synthesized compounds. See DOI: 10.1039/x0xx00000x
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supports and synthesis of heterogeneous DMAP-based show that it was synthesized successfully and the used
organocatalysts.12
procedure is efficient for chemically modification of MNPs with
In this study, we have introduced a new synthetic pathway to DMAP (see supporting information). In order to show the nano
graft DMAP moiety on MNPs through the ring opening of feature of the catalyst transmission electron microscopy (TEM)
oxiran groups on the MNPs surface with N-methylpyridin-4- images of the catalyst are shown in Figure 1.
amine. In order to show the catalytic applicability of MNP-
DMAP in organic transformations it was used in
a
multicomponent reaction (MCR) for one-pot synthesis of a
class of 2-amino-4H-chromene-3-carbonitrile derivatives.
MCRs are attractive synthetic approaches in organic synthesis,
because target molecules are produced in a single step process
and diversity can be simply obtained by varying the reaction
component.13
2-Amino-4H-chromene-3-carbonitriles
are
important due to
a
range of biological activities and
pharmacological applications.14 For example the following
biological activities have been reported for some of the
derivatives:
anticoagulant,
insecticidal,
anticancer,
antimicrobial, antibacterial, and antiviral.15 For one-pot
synthesis of a class of 2-amino-4H-chromene-3-carbonitrile
usually malononitrile, aldehyde, and beta-diketones were
reacted together in the presence of a catalyst system. In this
study, the catalytic applicability of MNP-DMAP catalyst was
investigated in one-pot synthesis of 2-amino-4H-chromene-3-
carbonitrilederivatives.
Figure 1. The TEM images of different position of the MNP-
DMAP catalyst.
Catalyst particles with near spherical morphology are
observable in the TEM images of the MNP-DMAP. Also the
core-shell structure is clear and nanoparticles are produced in
relatively good monodispersity, while the average size of
nanoparticles is obtained around 5 nm which is suitable for
catalysis purposes. The energy-dispersive X-ray (EDX)
spectroscopy reveals that the amount of N content for the
material is about 2.45%. Thus the amount of grafted DMAP on
the surface of magnetic nanoparticles is estimated to be 1.8
mmol.g-1.
Results and discussion
The synthetic pathway for the synthesis of the heterogeneous
MNP-DMAP catalyst is shown in Scheme 1. Silica-coated
magnetic nanoparticles (Fe3O4@SiO2) were synthesized using a
known procedure and reacted with trimethoxy(vinyl)silane to
graft vinyl group on MNPs surface.10a Then, it was treated with
hydrogen peroxide in order to convert vinyl groups to oxiran
functionality.10a Ring opening of epoxy groups on the surface
of MNPs with N-methylpyridin-4-amine resulted in the
production of MNP-DMAP catalyst, successfully.
After catalyst characterization, the MNP-DMAP was used as
catalyst in one-pot synthesis of a class of 2-amino-4H-
chromene-3-carbonitrile derivatives. A simple model reaction
including 1,3-cyclohexanedione (1a), benzaldehyde (2a), and
malononitrile (3a) was selected in order to optimize reaction
conditions for one-pot synthesis of 2-amino-5-oxo-4-phenyl-
OH
OH
OH
OH
OH
OH
(MeO)3Si
5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile
MNP-DMAP catalyst (Table 1).
(
4a)
using
Fe3O4@SiO2
Fe3O4@SiO2@vinyl
H2O2
N
N
NH
N
O
O
O
N
N
HO
HO
Fe3O4@SiO2@Oxiran
MNP-DMAP
Scheme 1. Synthetic route for the preparation of MNP-DMAP
catalyst.
The MNP-DMAP catalyst was characterized using some
microscopic and spectroscopic techniques and the results
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Table 1: Optimization of reaction conditions for MNP-DMAP individually. This is a synergetic effect that observable in some
catalyzed one-pot synthesis of 2-amino-4H-chromene-3- of nano-organocatalyst. Indeed, the nano structure nature of
carbonitrilederivativesa
the catalyst affects the activity and we have a new material
with the both capability of high activity and reusability.16
Subsequently, some of the introduced organocatalyst in our
laboratory (LCMNP,9b LPMNP10a and SSLP10b) were used in this
reaction in order to have a comparison between the activity of
MNP-DMAP and them in this reaction (Table 1, entries 14-16).
Results demonstrated that MNP-DMAP catalyst is superior in
activity in this reaction under optimized conditions. Thus, the
MNP-DMAP is introduced as an efficient and magnetic nano-
organocatalyst for one-pot synthesis of 2-amino-4H-
chromene-3-carbonitriles (Table 1, entry 2).
Entry Catalyst (mol%)
Solvent
T
Time
Yield
(%)b
20
(°C) (h)
The generality and scope of the reaction was investigated
using the synthesis of divers 2-amino-4H-chromene-3-
carbonitrile derivatives (Scheme2).
1
2
3
4
5
6
7
none
H2O
80
80
80
100
80
80
80
12
0.5
1
MNP-DMAP (5)
MNP-DMAP (5)
MNP-DMAP (5)
MNP-DMAP (5)
MNP-DMAP (5)
MNP-DMAP
H2O
93
EtOH
DMF
MeOH
none
H2O
85
2
90
R
1
80
O
O
CN
3
70
O
CN
MNP-DMAP (5 mol%)
H2O, 80 o
R
+
+
NC
(3)
C
5
80
O
O
NH2
(2)
(1)
4a-y
(2.5)
8
MNP-DMAP (4)
MNP-DMAP (5)
MNP-DMAP (5)
MNP-DMAP (5)
H2O
H2O
H2O
H2O
80
95
50
rt
2
90
93
89
68
55
R
N
R
O
O
9
0.5
2
O
CN
NH2
CN
NH2
4a: R = H (0.5h, 93%)
4b: R = 4-CN (0.5 h, 95%)
4c: R = 4-Br (1h, 92%)
4d: R = 3-NO2 (0.5h, 97%)
4e: R = 4-NO2 (0.5h, 96%)
4f: R = 4-Cl, (1h, 92%)
4g: R = OH, (1.5h, 90%)
CN
NH2
10
11
12
O
O
O
12
12
4i: R = 4-NO2 (20 min, 96%)
4j: R = 4-CN (20 min, 98%)
4k: R = 3,4-OH (1h, 88%)
4l: R = 4-F (0.5h, 96%)
4m: R = 4-OH (1h, 90%)
4n: R = 2-OMe, (1h, 87%)
4o: R = 2-Cl, (1h, 90%)
4h: 45 min, 89%
Fe3O4@SiO2 (50 H2O
mg)
80
S
O
13
14
15
16
DMAP (5)
LCMNP (5)
LPMNP (5)
SSLP (5)
H2O
H2O
80
80
80
80
6
79
CN
NH2
4q: 0.5h, 91%
12
5
85
O
O
NH2
CN
H2O
88
80
N
H2O
5
O
O
O
a
CN
O
O
Reaction conditions:
solvent (5 mL). b Isolated yield.
1
(1 mmol),
2
(1 mmol),
3
(1 mmol) and
O
NH2
CN
O
O
4p: 1h, 87%
CN NC
O
NH2
NH2
NH2
As shown in Table 1, in the absence of catalyst and in water
solvent at 80 °C, about 20% of product was obtained (entry 1).
While, in the presence of about 5 mol% of catalyst the reaction
yield was enhanced to 93% after 0.5 h, demonstrating high
catalytic activity of the MNP-DMAP catalyst for this process
(Table 1, entry 2).
R
O
4s: 2h, 89%
4r: 2h, 90%
CN
CN
HN
O
O
N
O
NH2
CN
NH2
4x: 1h, 88%
O
H
HN
4t: R = 4-CN (15 min, 95%)
4u: R = 3-NO2 (20 min, 93%)
4v: R = 2,6-Cl (1h, 85%)
CN
NH2
Ph
S
N
O
H
Ph
O
4w: R = 4-OMe, (45 min, 88%)
4y: 2h, 90%
The type of solvent was changed and no superiority was
observed in EtOH, DMF, MeOH related to water (Table 1,
entries 3-5). Also the reaction was checked under solvent-free
conditions and 70% of product was produced (Table 1, entry
6).
Scheme 2. Products of one-pot synthesis of 2-amino-4H-
chromene-3-carbonitrile derivatives using MNP-DMAP
catalyst. Reaction conditions:
1 (1 mmol), 2 (1 mmol), 3 (1
mmol) and H2O (5 mL). All yields are isolated products.
Then, the catalyst loading was changed and 5 mol% of catalyst
was found to be optimum (Table 1, entries 7&8). The reaction
temperature as another parameter was investigated and it
seems that 80 °C is suitable for this transformation (Table 1,
entries 9&10). At room temperature about 68% of product
was isolated after 12h (Table 1, entry 11).
As shown in Scheme 2, different 2-amino-4H-chromene-3-
carbonitrile derivatives can be synthesized in high yields and
relatively short reaction time using MNP-DMAP catalyst.
Different
beta-diketones
including
dimedone,
1,3-
cyclohexadione, barbituric acid, thiobarbituric acid and 1,3-
diphenylpropane-1,3-dione were successfully used and
corresponding products were obtained in high yields. Both
aldehydes including electron donating and electron
withdrawing groups were used and the reaction yields for all
of them were high. Nitro, cyano, methoxy, halogen, and
In order to show the high catalytic applicability of MNP-DMAP
catalyst in this reaction some other catalyst was evaluated
(Table 1, entries 12-16). In the presence of core-shell and
DMAP as catalyst about 55% and 79% of product were
obtained, demonstrating the high activity of MNP-DMAP
catalyst in comparison with each of components of catalyst
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hydroxy functional groups on aldehydes tolerated the reaction The level of recyclability of the MNP-DMAP catalyst for this
conditions well. Also for heterocyclic aldehydes good yields of reaction was also investigated by use of model reaction. When
products were obtained. Bis-functionalized aldehydes were the reaction was complete, the catalyst was separated from
also tested and compound 4r and 4s were isolated in 90 and the reaction mixture using an external magnetic field and was
89% isolated yields, respectively. Overall, this catalyst system then washed with hot ethanol. The recycled catalyst was dried
and optimized conditions are useful for synthesis of diverse 2- in oven and used for the next run. The recycled catalyst could
amino-4H-chromene-3-carbonitrile derivative.
be reused 10 times without a significant decrease in its
It should be mentioned that the separation of the catalyst catalytic activity (Fig. 2).
from the reaction mixture is possible using a magnetic field
and work up process is very simple. The 2-amino-4H-
chromene-3-carbonitrile products were obtained in high yield
with less impurity. The pure products were obtained via
recrystallization in hot ethanol.
The reaction mechanism for this process is suggested based on
the previous reports in the literature (Scheme 3).9b The role of
catalyst is attributed to the 4-dialkylaminopyridine part which
is a basic organocatalyst with remarkable nucleophilic power
on pyridine nitrogen atom.
Figure 2. The reusable capability of MNP-DMAP catalyst in
synthesis of 2-amino-4H-chromene-3-carbonitrile.
In order to show that the catalyst activity of the MNP-DMAP
catalyst did not change significantly during the reaction
process, the nitrogen content of recycled catalyst after 10
cycles of reusability was investigated using the elemental
analysis method and the results show that only about 0.2% of
nitrogen was lost. These results are in good agreement with
the reactivity of MNP-DMAP catalyst after recovery.
Conclusions
In conclusion, we have introduced an efficient and simple
method for chemical stabilization of DMAP on magnetic
nanoparticles. The ring opening reaction of exist oxiran rings
on the MNP surface using N-methylpyridin-4-amine resulting
in the production of MNP-DMAP catalyst. This is an efficient
strategy for chemical modification of magnetic nanoparticles
with DMAP. The MNP-DMAP was used as an efficient
heterogeneous organocatalyst in a three-component coupling
reaction of aldehydes, beta diketones and malononitrile for
one-pot synthesis of 2-amino-4H-chromene-3-carbonitrile
under mild and green conditions. This organocatalyst system
was reused 10 times in the designed protocol without any
change in its catalytic activity. The MNP-DMAP provides great
promise toward further useful applications in other organic
transformations.
Scheme 3. The proposed reaction mechanism for MNP-DMAP-
catalyzed one-pot synthesis of 2-amino-4H-chromene-3-
carbonitrile using MCR of malononitrile, aldehydes, and beta-
diketones.
It seems that, the reaction is started by deprotonation of beta
dicarbonyl compound (it is more acidic than malononitrile) and
its conversion to enol/enolate form. The nitrogen atom of the
MNP-DMAP acts as base in this step. The condensation of
aldehydes and beta dicarbonyl compound in enol form
resulted in the production of knoevenagel intermediate (
The Michael addition of DMAP nitrogen to intermediate
I
).
Experimental Section
I
forms intermediated II which is more reactive for nucleophilic
attack of malononitrile. This leads to the formation of a highly
intermediate (III). This complex intermediate is subject to next
intermolecular reactions with help of MNP-DMAP catalyst,
leading to the formation of product. Deprotonation of catalyst
completes the catalytic cycle by releasing the catalyst.
General
Chemicals were purchased from Fluka and Aldrich chemical
companies and used without further purification. The known
products were characterized by comparison of their spectral
and physical data with those reported in the literature. 1H (250
MHz) and 13C NMR (62.5 MHz) spectra were recorded on a
Bruker Avance spectrometer in CDCl3 solution with
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tetramethylsilane (TMS) as an internal standard. Transmission quantitative amount of oxiran group on the substrate was
electron microscopy (TEM) analyses were performed on a identified to be 2.8 mmol/g using elemental analysis, which it
Philips model CM 10 instrument. Melting points were showed that a remarkable amount of vinyl groups is converted
determined in open capillary tubes in a Barnstead Electro- to oxiran under applied conditions.
thermal 9100 BZ circulating oil melting point apparatus. The
reaction monitoring was accomplished by TLC on silica gel Synthesis of 4-dialkylaminopyridinemagnetic nanoparticles
PolyGram SILG/UV254 plates. Column chromatography was (MNP-DMAP) catalyst10c
carried out on columns of silica gel 60 (70-230 mesh).
For the synthesis of MNP-DMAP catalyst, 1.5 g of N-
methylpyridin-4-amine was added in to a prepared solution
containing 5.0 g of VMNP in 30 mL chloroform. Subsequently,
Preparation of Fe3O4 nanoparticles
Magnetic nanoparticles were prepared via co-precipitation of the mixture was stirred for 12h at refluxing temperature of
Fe (III) and Fe (II) ions in the presence of sodium hydroxide.10a,c chloroform. The resulting precipitate was filtered through a
In a canonical flask, a mixture of FeCl2.4H2O (15 mmol, 2.9g) celite pad, washed with water, dried in vacuum to afford the
and FeCl3.6H2O (30 mmol, 8.1 g) was dissolved in 100 mL of MNP-DMAP catalyst (1.8 mmol/g of supported DMAP).
deionized water and put under nitrogen atmosphere for 10
minutes. Then, the pH of this solution was increased to 11 by General Procedure for the synthesis of 2-amino-4H-
adding
a 1M solution of NaOH immediately at 40 °C. chromene-3-carbonitrile compounds
Subsequently, the temperature of mixture was enhanced to 60 A mixture of aldehyde (1 mmol), 1,3-beta-dicarbonyl (1 mmol),
°C and the solution was stirred for 20 minute in this malononitrile (1 mmol)and MNP-DMAP (30 mg, 5 mol %) in
temperature. The magnetic nanoparticles as a dark solid were H2O (4 mL) was stirred at room temperature for appropriate
isolated from the solution by magnetic separation and washed time. The progress of the reaction was monitored by TLC. After
with deionized water until pH 7 reached.
completion of the reaction, as showed by TLC, The catalyst was
recovered magnetically by attaching a general magnet to the
external of the reactor vessel and the reaction mixture was
Preparation of Fe3O4@SiO2 nanoparticles
Fe3O4@SiO2 nanoparticles were prepared based on the filtered and the residual washed with ethanol (3 × 5 mL).
literature:10a,c to a mixture of 125 mL of heptanes, 25 mL of i-
PrOH, 20 mL of PEG-300, and 10 mL of water, 2 g of Fe3O4 was 2-Amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-
added. Then the mixture was stirred by mechanical stirrer chromene-3-carbonitrile (4a)
under N2 gas for 30 minutes. 20 mL of tetraethyl ortho silicate White crystal (Yield: 93%, 0.24 g); Mp: 231-232 oC [Lit. 230-232
(TEOS) was added to the mixture next and then the solution oC].17a IR (KBr): 3394, 3325, 3209, 2885, 2198, 1681, 1666,
was stirred for 12 h at 30 °C. After the specified time, 10 mL of 1604, 1450, 1373, 1249, 1211, 1157, 1033, 1002, 840, 740,
ammonia was added and the solution was stirred continuously 694, 655 cm-1. 1H-NMR (250 MHz, DMSO-d6/TMS) δ (ppm):
for another 12 h. The precipitation was washed with ethanol (3 7.20-7.27 (m, 2H, Ar), 7.12-7.15 (m, 3H, Ar), 6.97 (s, 2H, NH2),
×10) and collected by external magnetic field. The desired 4.15 (s, 1H, CH), 2.48 (s, 2H, CH2), 2.08-2.21 (m, 2H, CH2), 1.00
product was dried under vacuum overnight.
(s, 3H, CH3), 0.92 (s, 3H, CH3). 13C-NMR (62.5 MHz, DMSO-
d6/TMS) δ (ppm): 183.7, 162.4, 157.6, 152.5, 149.6, 149.4,
132.2, 128.5, 118.8, 118.7, 109.4, 87.3, 57.5, 35.7. Anal. Calcd.
Synthesis of vinyl magnetic nanoparticle (VMNP)10a,c
In a three-necked flask (100 mL) containing 70 mL of dry for C18H18N2O2: C, 73.45; H, 6.16; N, 9.52. Found: C, 73.41; H,
chloroform, 10 of Fe3O4 was charged. Then 6.03; N, 9.48.
g
trimethoxy(vinyl)silane (3.54 g, 0.02 mol) was added to the 2-Amino-4-(4-cyanophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-
reaction mixture drop-wise over a period of 5 min at room tetrahydro-4H-chromene-3-carbonitrile (4b)
temperature. When the addition was completed, the mixture White crystal (Yield: 95%, 0.27 g); Mp: 230-232oC [Lit. 227-
was stirred for 12
h
at the refluxing temperature of 229oC].17b IR (KBr): 3471, 3355, 3193, 2962, 2877, 2229, 2191,
chloroform. Then, the reaction mixture was filtered and the 1689, 1666, 1604, 1504, 1465, 1411, 1365, 1249, 1211, 1157,
obtained solid was dried in a vacuum at 50 °C to obtain a vinyl 1141, 1041, 856, 632, 563 cm-1. 1H-NMR (250 MHz, DMSO-
MNP (VMNP) substrate. The amount of vinyl group on the d6/TMS) δ (ppm): 7.74 (d, J = 8.2 Hz, 2H, Ar), 7.33 (d, J = 8.0 Hz,
surface of MNPs was estimated to be 3.42 mmol/g according 2H, Ar), 4.27 (s, 1H, CH), 2.50 (s, 2H, CH2), 2.05-2.26 (m, 2H,
to the elemental analysis.
CH2), 1.01 (s, 3H, CH3), 0.93 (s, 3H, CH3). 13C-NMR (62.5 MHz,
DMSO-d6/TMS) δ (ppm): 195.7, 163.0, 158.4, 150.1, 132.3,
128.2, 119.3, 118.7, 111.6, 109.3, 57.0, 49.7, 35.7, 31.7, 28.1,
Synthesis of MNP-oxiran (MNPO)10a,c
A solution of 5g vinyl MNP (VMNP), and H2O2 30% (20 mL) 26.8. Anal. Calcd. for C19H17N3O2: C, 71.46; H, 5.37; N, 13.16.
were stirred at 50 °C for 12 h. The resulting precipitate was Found: C, 71.39; H, 5.30; N,13.20.
filtered through a celite pad, washed with water, dried in 2-Amino-4-(4-bromophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-
vacuum to afford the MNPO substrate (5.52 g). The presence tetrahydro-4H-chromene-3-carbonitrile (4c)
of ethylene oxide group on the silica substrate was detected White crystal (Yield: 92%, 0.30 g); Mp: 208-210 oC [Lit. 207-209
by the bright pink color of the phenolphthalein (as indicator) oC].17c IR (KBr): 3394, 3317, 3209, 2873, 2191, 1681, 1654,
when air passed through an aqueous solution of NaCl. The 1604, 1485, 1407, 1369, 1253, 1215, 1161, 1141, 1072, 1037,
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1010, 844, 771, 563 cm-1. 1H-NMR (250 MHz, DMSO-d6/TMS) δ C18H18N2O3: C, 69.66; H, 5.85; N, 9.03. Found: C, 69.59; H, 5.91;
(ppm): 7.45 (d, J = 7.7 Hz, 2H,Ar), 7.08 (d, J = 8.2 Hz, N, 8.90.
2H,Ar),7.04 (s, 2H, NH2),4.15 (s, 1H, CH), 2.48 (s, 2H, CH2), 2.04- 2-Amino-7,7-dimethyl-5-oxo-4-(pyridin-3-yl)-5,6,7,8-
2.25 (m, 2H, CH2), 1.00 (s, 3H, CH3), 0.92 (s, 3H, CH3). 13C-NMR tetrahydro-4H-chromene-3-carbonitrile (4h)
(62.5 MHz, DMSO-d6/TMS) δ (ppm): 195.6, 162.5, 158.4, 144.1, White crystal (yield: 89%, 0.23 g); Mp: 227-229oC [Lit. 225-226
131.1, 129.4, 119.6, 119.5, 112.1, 57.6, 55.9, 49.8, 35.1, 31.7, oC].17f IR (KBr): 3317, 3178, 2962, 2183, 1651, 1604, 1427,
28.2, 26.7, 18.4. Anal. Calcd. for C18H17BrN2O2: C, 57.92; H, 1373, 1249, 1218, 1141, 1033, 840, 709, 563 cm-1. 1H-NMR
4.59; N, 7.51. Found: C, 57.88; H, 4.53; N, 7.46.
2-Amino-7,7-dimethyl-4-(3-nitrophenyl)-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (4d)
(250 MHz, DMSO-d6/TMS) δ (ppm): 8.36 (s, 2H, Ar), 7.49-7.52
(m, 1H, Ar), 7.27-7.31 (m, 1H, Ar),7.09 (s, 2H, NH2), 4.21 (s, 1H,
CH), 2.49 (s, 2H, CH2), 2.05-2.25 (m, 2H, CH2), 1.00 (s, 3H, CH3),
White crystal (Yield: 97%, 0.29 g); Mp: 212-214 oC [Lit. 213-214 0.91 (s, 3H, CH3). 13C-NMR (62.5 MHz, DMSO-d6/TMS) δ (ppm):
oC].17d IR (KBr): 3433, 3332, 3201, 2869, 2183, 1681, 1596, 195.6, 162.9, 158.5, 148.6, 147.7, 139.9, 134.6, 123.5, 119.4,
1527, 1350, 1249, 1211, 1157, 1134, 1041, 902, 825, 686 cm-1. 111.6, 57.2, 49.8, 33.3, 31.7, 28.1, 26.8. Anal. Calcd. for
1H-NMR (250 MHz, DMSO-d6/TMS) δ (ppm): 8.02-8.07 (m, 1H, C17H17N3O2: C, 69.14; H, 5.80; N, 14.23. Found: C, 68.95; H,
Ar), 7.94-7.95 (m, 1H, Ar),7.55-7.62 (m, 2H, Ar), 7.15 (s, 2H, 5.67; N, 14.35.
NH2), 4.39 (s, 1H, CH), 2.52 (s, 2H, CH2), 2.06-2.27 (m, 2H, CH2), 2-Amino-4-(4-nitrophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-
1.01 (s, 3H, CH3), 0.93 (s, 3H, CH3). 13C-NMR (62.5 MHz, DMSO- chromene-3-carbonitrile (4i)
d6/TMS) δ (ppm): 195.7, 163.1, 158.5, 147.7, 146.9, 134.1, Yellow crystal (yield: 96%, 0.25 g); Mp: 236-239 oC [Lit. 235-
o
129.9, 121.7, 121.5, 119.3, 111.7, 57.1, 49,7, 35.3, 31.7, 28.2, 236 C].17g IR (KBr): 3417, 3332, 3217, 2862, 2198, 1651, 1596,
26.6. Anal. Calcd. for C18H17N3O4: C, 63.71; H, 5.05; N, 12.38. 1519, 1419, 1342, 1257, 1211, 1172, 1134, 1072, 1002, 910,
1
Found: C, 63.59; H, 4.89; N, 12.20.
817, 732, 694, 732, 694cm-1. H-NMR(250 MHz, DMSO-d6): δ
(ppm): δ (ppm): 8.13 (d, J = 7.2 Hz, 2H, Ar), 7.44 (d, J = 7.5 Hz,
2H, Ar),7.15 (s, 2H, NH2), 4.34 (s, 1H, CH), 2.61 (s, 2H, CH2),
2-Amino-7,7-dimethyl-4-(4-nitrophenyl)-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (4e)
White crystal (yield: 96%, 0.28 g); Mp: 174-176 oC [Lit. 177-178 2.24 (s, 2H, CH2), 1.91-1.92 (m, 2H, CH2). 13C-NMR (62.5 MHz,
oC].17d IR (KBr): 3386, 3325, 3209, 2962, 2191, 1651, 1604, DMSO-d6/TMS) δ (ppm): 195.8, 165.0, 158.4, 152.2, 146.1,
1519, 1365, 1211, 1041, 864, 825 cm-1. 1H NMR (250 MHz, 128.5, 123.5, 119.3, 112.6, 56.8, 36.1, 35.4, 26.4, 19.6. Anal.
DMSO-d6/TMS) δ (ppm): 8.14 (d, J = 8.7 Hz, 2H, Ar), 7.41 (d, J = Calcd. for C16H13N3O4: C, 61.73; H, 4.21; N, 13.50. Found:
8.7 Hz, 2H, Ar), 7.16 (s, 2H, NH2), 4.34 (s, 1H, CH), 2.47 (s, 2H, 61.68; H, 4.16; N, 13.43.
CH2), 2.04-2.20 (m, 2H, CH2), 1.01 (s, 3H, CH3), 0.93 (s, 3H, 2-Amino-4-(4-cyanophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-
CH3). 13C-NMR (62.5 MHz, DMSO-d6/TMS) δ (ppm): 195.6, chromene-3-carbonitrile (4j)
163.0, 158.5, 152.2, 146.1, 128.5, 123.6, 119.2, 111.6, 56.9, White crystal (yield: 98%, 0.26 g); Mp: 230-232oC. IR (KBr):
55.9, 49.7, 35.5, 31.7, 28.1, 26.8, 18.4. Anal. Calcd. for 3425, 3332, 3217, 2862, 2221, 2198, 1651, 1604, 1496, 1411,
1
C18H17N3O4: C, 63.71; H, 5.05; N, 12.38. Found: C, 63.62; H, 1365, 1257, 1211, 1164, 1126, 1064, 1002, 910, 840 cm-1. H-
5.12; N, 12.29.
NMR (250 MHz, DMSO-d6/TMS) δ (ppm): 7.73 (d, J = 8.2 Hz,
2H, Ar), 7.35 (d, J = 8.0 Hz, 2H, Ar),7.11 (s, 2H, NH2), 4.26 (s, 1H,
CH), 2.60 (s, 2H, CH2), 2.24-2.29 (m, 2H, CH2), 1.90-1.92 (m, 2H,
2-Amino-4-(4-chlorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (4f)
White crystal (Yield: 92%, 0.26 g); Mp: 210-212 oC [Lit. 209– CH2). 13C-NMR (62.5 MHz, DMSO-d6/TMS) δ (ppm): 195.8,
210 oC].17d IR (KBr): 3379, 3178, 2962, 2191, 1674, 1635, 1488, 165.0, 158.4, 150.2, 132.3, 128.2, 119.3, 118.7, 112.6, 109.3,
1365, 1218, 1033, 771 cm-1. 1H-NMR (250 MHz, DMSO- 56.9, 36.1, 35.6, 26.4, 19.6. Anal. Calcd. for C17H13N3O2: C,
d6/TMS) δ (ppm): 7.31 (d, J = 8.2 Hz, 2H, Ar), 7.14 (d, J = 8.5 Hz, 70.09; H, 4.50; N, 14.42. Found: C, 70.18; H, 4.39; N, 14.35.
2H, Ar),7.03 (s, 2H, NH2), 4.16 (s, 1H, CH), 2.47 (s, 2H, CH2), 2-Amino-4-(3,4-dihydroxyphenyl)-5-oxo-5,6,7,8-tetrahydro-
2.03-2.25 (m, 2H, CH2), 0.99 (s, 3H, CH3), 0.91 (s, 3H, CH3). 13C- 4H-chromene-3-carbonitrile(4k)
NMR (62.5 MHz, DMSO-d6/TMS) δ (ppm): 195.6, 162.5, 158.4, Yellow crystal (yield: 88%, 0.22 g); Mp: 267-269 oC. IR (KBr):
143.6, 131.0, 129.0, 128.2, 119.5, 112.2, 57.6, 55.9, 49.8, 35.0, 3456, 3186, 2920, 2850, 2192, 1617, 1593, 1473, 1365, 1238,
31.7, 28.2, 26.7, 18.4. Anal. Calcd. for C18H17ClN2O2: C, 65.75; 1180, 1137, 1110, 964 cm-1. 1H-NMR (250 MHz, DMSO-
H, 5.21; N, 8.52. Found: C, 65.62; H, 5.28; N, 8.46.
2-Amino-4-(4-hydroxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile(4g)
d6/TMS) δ (ppm): 9.32 (s, 1H), 8.66-8.78 (m, 1H), 8.55 (s, 1H),
8.39 (s, 1H), 6.54-6.56 (m, 1H), 6.44-6.45 (m, 1H), 6.31-6.35 (m,
1H), 4.72 (s, 1H, CH), 2.46-2.48 (m, 2H, CH2), 2.17 (s, 2H, CH2),
White crystal (yield: 90%, 0.24 g); Mp: 200-203 oC [Lit. 205-206 1.86-1.87 (m, 2H, CH2). 13C-NMR (62.5 MHz, DMSO-d6/TMS) δ
oC].17e IR (KBr): 3436, 3271, 3193, 2950, 2931, 2349, 2202, (ppm): 194.7, 150.7, 144.2, 142.9, 138.5, 117.9, 115.1, 114.8,
1612, 1558, 1508, 1373, 1257, 1222, 1172, 1137, 837 cm-1. 1H- 112.8, 56.9, 36.8, 30.7, 26.2, 20.7. Anal. Calcd. for C16H14N2O4:
NMR (250 MHz, DMSO-d6/TMS) δ (ppm): 9.25 (s, 1H, OH), C, 64.42; H, 4.73; N, 9.39. Found: C, 64.34; H, 4.80; N, 9.28.
6.89-6.92 (m, 4H), 6.63 (d, J = 8.2 Hz, 2H, Ar), 4.04 (s, 1H, CH), 2-Amino-4-(4-fluorophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-
2.46 (s, 2H, CH2), 2.03-2.25 (m, 2H, CH2), 1.00 (s, 3H, CH3), 0.92 chromene-3-carbonitrile (4l)
o
(s, 3H, CH3). 13C-NMR (62.5 MHz, DMSO-d6/TMS) δ (ppm): White crystal (yield: 96%, 0.24 g); Mp: 215-217 C [Lit.213-215
195.7, 163.1, 158.5, 147.7, 146.9, 134.1, 129.9, 121.7, 121.6, oC].17h IR (KBr): 3417, 3332, 3217, 2931, 2360, 2191, 1651,
119.3, 111.7, 57.1, 49.7, 35.3, 31.7, 28.2, 26.6. Anal. Calcd. for 1604, 1504, 1419, 1365, 1211, 1157, 1072, 1002, 840, 532 cm-
6 | J. Name., 2012, 00, 1-3
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1. H NMR (250 MHz, DMSO-d6/TMS) δ (ppm):7.17 (d, J = 2.7 57.1, 36.1, 33.2, 26.4, 19.6. Anal. Calcd for C15H13N3O2: C,
Hz, 2H, Ar), 7.07 (d, J = 2.7 Hz, 2H, Ar), 7.00 (s, 2H, NH2), 4.19 67.40; H, 4.90; N, 15.72. Found: C, 67.15; H, 4.86; N, 15.68.
(s, 1H, CH), 2.57 (s, 2H, CH2), 2.23 (s, 2H, CH2), 1.87-1.90 (m, 2-Amino-5-oxo-4-(thiophen-2-yl)-5,6,7,8-tetrahydro-4H-
2H, CH2). 13C-NMR (62.5 MHz, DMSO-d6/TMS) δ (ppm): 195.8, chromene-3-carbonitrile (4q)
164.4, 162.7, 158.9, 158.3, 140.9, 129.0, 119.6, 115.1, 113.5, White crystal (yield: 91%, 0.22 g); Mp: 205-207 oC [Lit. 205–206
57.9, 36.2, 34.7, 26.4, 19.7. Anal. Calcd. for C16H13FN2O2: C, oC].17i IR (KBr): 3321, 3174, 2866, 2191, 1681, 1651, 1608,
67.60; H, 4.61; N, 9.85. Found: C, 67.53; H, 4.50; N, 9.69.
2-Amino-4-(4-hydroxyphenyl)-5-oxo-5,6,7,8-tetrahydro-4H-
chromene-3-carbonitrile (4m)
1361, 1245, 1211, 1161, 1134, 1114, 1064, 1002, 852, 709, 536
cm-1. 1H-NMR (250 MHz, DMSO-d6/TMS) δ (ppm): 7.26-7.28
(m, 1H, Ar), 7.09 (s, 2H, NH2), 6.80-6.87 (m, 2H, Ar), 4.49 (s, 1H,
White crystal (yield: 90%, 0.22 g); Mp: 237-238 oC [Lit. 234- CH), 2.46-2.48 (m, 2H, CH2), 2.28 (s, 2H, CH2), 1.83-1.93 (m, 2H,
236oC].17h IR (KBr): 3379, 3321, 3193, 3012, 2815, 2198, 1674, CH2). 13C-NMR (62.5 MHz, DMSO-d6/TMS) δ (ppm): 195.7,
1647, 1604, 1539, 1512, 1454, 1419, 1377, 1253, 1199, 1168, 164.2, 158.9, 149.1, 126.7, 124.3, 123.9, 119.6, 113.9, 57.7,
1
1141, 1068, 1010, 914, 894, 837, 783, 624, 536 cm-1. H-NMR 36.1, 30.2, 26.3, 19.6. Anal. Calcd. for C14H12N2O2S: C, 61.75; H,
(250 MHz, DMSO-d6/TMS) δ (ppm): 9.22 (s, 1H, OH), 6.89 (s, 4.44; N, 10.29. Found: C, 61.60; H, 4.36; N, 10.18.
4H), 6.62 (d, J = 8.0 Hz, 2H, Ar), 4.05 (s, 1H, CH), 2.47- 2.56 (m, 4,4'-(1,3-phenylene)bis(2-amino-5-oxo-5,6,7,8-tetrahydro-4H-
2H, CH2), 2.23 (s, 2H, CH2), 1.86- 1.90 (m, 2H, CH2). 13C-NMR chromene-3-carbonitrile) (4r)
(62.5 MHz, DMSO-d6/TMS) δ (ppm): 195.8, 163.9, 158.3, 155.9, White crystal (yield: 90%, 0.37 g); Mp: 315-317 oC. IR (KBr):
135.1, 128.0, 119.8, 114.9, 114.1, 58.5, 36.3, 34.4, 26.3, 19.7.
3394, 3325, 3209, 2931, 2191, 1651, 1596, 1365, 1242, 1203,
Anal. Calcd. for C16H14N2O3: C, 68.08; H, 5.00; N, 9.92. Found: 1164, 1134, 1002, 910, 709, 540 cm-1. 1H-NMR (250 MHz,
C, 67.93; H, 4.80; N, 9.82.
DMSO-d6/TMS) δ (ppm): 7.13-7.16 (m, 1H), 6.92-6.97 (m, 7H),
4.13 (s, 2H, CH), 2.57 (s, 4H, CH2), 2.23-2.25 (m, 4H, CH2), 1.92-
1.93 (m, 4H, CH2). 13C-NMR (62.5 MHz, DMSO-d6/TMS) δ
2-Amino-4-(2-methoxyphenyl)-5-oxo-5,6,7,8-tetrahydro-4H-
chromene-3-carbonitrile (4n)
White crystal (yield: 87%, 0.22 g); Mp: 215-217 oC. IR (KBr): (ppm): 195.7, 195.6, 164.7, 164.3, 158.8, 158.2, 144.6, 128.1,
3379, 3313, 3159, 2962, 2835, 2187, 1681, 1651, 1577, 1542, 125.5, 125.1, 124.8, 119.7, 114.1, 113.4, 58.2, 57.6, 36.2, 34.9,
1488, 1458, 1369, 1253, 1211, 1164, 1134, 1068, 1049, 999, 34.7, 26.4, 19.7. Anal. Calcd. for C26H22N4O4: C, 68.71; H, 4.88;
829, 752, 702, 609, 536 cm-1. 1H-NMR (250 MHz, DMSO- N, 12.33. Found: C, 68.80; H, 4.76; N, 12.26.
d6/TMS) δ (ppm): 7.11-7.13 (m, 1H), 6.92-6.95 (m, 2H), 6.80- 2-Amino-4-(4-(2-amino-3-cyano-5-oxo-5,6,7,8-tetrahydro-4H-
6.82 (m, 3H), 4.53 (s, 1H, CH), 3.75 (s, 3H, CH3), 2.57-2.58 (m, chromen-4-yl)phenyl)-8-oxo-5,6,7,8-tetrahydro-4H-
2H, CH2), 2.22-2.28 (m, 2H, CH2), 1.90-1.94 (m, 2H, CH2). 13C- chromene-3-carbonitril (4s)
NMR (62.5 MHz, DMSO-d6/TMS) δ (ppm): 195.7, 165.0, 158.8, White crystal (yield: 89%, 0.36 g); Mp: >320 oC [Lit. >300 oC].17j
156.7, 132.4, 128.0, 127.6, 120.4, 119.7, 113.0, 111.5, 57.5, IR (KBr): 3452, 3328, 3201, 2896, 2191, 1681, 1600, 1558,
55.6, 36.3, 29.5, 26.4, 19.8. Anal.Calcd.for C17H16N2O3: C, 1365, 1245, 1203, 1137, 1068, 999, 810 cm-1. 1H-NMR (250
68.91; H, 5.44; N, 9.45. Found: C, 68.80; H, 5.49; N, 9.32.
2-Amino-4-(2-chlorophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-
chromene-3-carbonitrile (4o)
MHz, DMSO-d6/TMS)δ (ppm): 7.03 (s, 4H), 6.95 (s, 4H), 4.12 (s,
2H, CH), 2.58 (s, 4H, CH2), 2.25-2.27 (m, 4H, CH2), 1.90-1.92 (m,
4H, CH2). 13C-NMR (62.5 MHz, DMSO/TMS) δ (ppm): 195.9,
White crystal (yield: 90%, 0.23 g); Mp: 213-215 oC. IR (KBr): 164.6, 158.6, 157.4, 154.5, 142.8, 126.9, 124.4, 119.8, 113.7,
3328, 3182, 2935, 2191, 1681, 1647, 1600, 1365, 1261, 1245, 108.7, 58.9, 58.1, 36.2, 34.8, 34.7, 28.6, 21.5. Anal. Calcd. for
1211, 1164, 1137, 1068, 1002, 910, 748, 536 cm-1. 1H-NMR C26H22N4O4: C, 68.71; H, 4.88; N, 12.33. Found: C, 68.64; H,
(250 MHz, DMSO-d6/TMS) δ (ppm): 7.31-7.34 (m, 1H, Ar), 7.14- 4.78; N, 12.26.
7.24 (m, 3H, Ar), 6.99 (s, 2H, NH2), 4.68 (s, 1H, CH), 2.60 (s, 2H, 7-Amino-5-(4-cyanophenyl)-2,4-dioxo-1,3,4,5-tetrahydro-2H-
CH2), 2.21-2.24 (m, 2H, CH2), 1.90-1.94 (m, 2H, CH2). 13C-NMR pyrano[2,3-d]pyrimidine-6-carbonitrile (4t)
(62.5 MHz, DMSO-d6/TMS) δ (ppm): 195.6, 165.0, 158.4, 141.6, White crystal (yield: 95%, 0.26g); Mp: 254-257 oC [Lit.254-
132.0, 128.8, 128.0, 127.4, 119.2, 112.8, 109.8, 56.7, 36.2, 256oC].17k IR (KBr): 3379, 3178, 3101, 2854, 2198, 1720, 1674,
1
32.6, 26.4, 19.7. Anal. Calcd. for C16H13ClN2O2: C, 63.90; H, 1635, 1527, 1404, 1342, 1280, 1188, 1103, 987, 609 cm-1. H
4.36; N, 9.31. Found: C, 63.65; H, 4.19; N, 9.20.
2-Amino-5-oxo-4-(pyridin-3-yl)-5,6,7,8-tetrahydro-4H-
chromene-3-carbonitrile (4p)
NMR (250 MHz, DMSO-d6/TMS) δ (ppm): 12.11 (s, 1H, NH),
11.07 (s, 1H, NH), 7.74 (d, J = 7.7 Hz, 2H, Ar), 7.41 (d, J = 8.0 Hz,
2H, Ar),7.21 (s, 2H, NH2), 4.32 (s, 1H, CH). 13C-NMR (62.5 MHz,
White crystal (yield: 87%, 0.20 g); Mp: 183-184 oC. IR (KBr): DMSO-d6/TMS) δ (ppm): 171.0, 162.5, 158.4, 143.6, 131.0,
3363, 3305, 3035, 2970, 2881, 2191, 2360, 1662, 1612, 1589, 129.0, 128.2, 119.4, 112.2, 92.0, 57.6, 35.0. Anal. Calcd. for
1477, 1431, 1365, 1261, 1242, 1215, 1176, 1134, 1068, 1045, C15H9N5O3: C, 58.63; H, 2.95; N, 22.79. Found: C, 58.70; H, 2.89;
1
1029, 1002, 894, 840, 713, 632, 540 cm-1. H-NMR (250 MHz, N, 22.71.
DMSO-d6/TMS) δ (ppm): 8.36-8.39 (m, 2H, Ar), 7.51- 7.55 (m, 7-Amino-5-(3-nitrophenyl)-2,4-dioxo-1,3,4,5-tetrahydro-2H-
1H, Ar), 7.27-7.32 (m, 1H, Ar), 7.10 (s, 2H, NH2), 4.23 (s, 1H, pyrano[2,3-d]pyrimidine-6-carbonitrile (4u)
CH), 2.57- 2.60 (m, 2H, CH2), 2.22- 2.30 (m, 2H, CH2), 1.90-1.94 Orange crystal (yield: 93%, 0.28 g); Mp: 264-265 oC [Lit. 265
(m, 2H, CH2). 13C-NMR (62.5 MHz, DMSO-d6/TMS) δ (ppm): oC].17l IR (KBr): 3417, 3317, 3201, 3101, 3024, 2854, 2191,
195.8, 164.9, 158.4, 148.6, 147.7, 140.0, 134.6, 123.5, 119.4, 1666, 1535, 1404, 1350, 1280, 1218, 1103, 987, 794, 717, 678
cm-1. 1H-NMR (250 MHz, DMSO-d6/TMS) δ (ppm): 12.15 (s, 1H,
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NH), 11.08 (s, 1H, NH), 8.04 (s, 2H, Ar), 7.70 (s, 1H, Ar), 7.55-
7.61 (m, 1H, Ar), 7.25 (s, 2H, NH2), 4.45 (s, 1H, CH). 13C-NMR
(62.5 MHz, DMSO-d6/TMS) δ (ppm): 162.4, 157.7, 152.5, 149.4,
147.6, 146.3, 134.4, 129.8, 122.0, 121.8, 118.8, 87.4, 57.5,
35.3. Anal. Calcd. for C14H9N5O5: C, 51.38; H, 2.77; N, 21.40.
Found: C, 51.28; H, 2.85; N, 21.34.
Notes and references
1 a) B. List, Chem. Rev. 2007, 107, 5413; b) K. N. Houk and B.
List, Acc. Chem. Res. 2004, 37, 487; c) L. S. J. Hegedus,
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Niemeier and A. Henseler, Chem. Rev. 2007, 107, 5606;
(e) M. K. Kiesewetter, E. J. Shin, J. L. Hedrick and R. M.
Waymouth, Macromolecules, 2010, 43, 2093; f) T.
7-Amino-5-(2,6-dichlorophenyl)-2,4-dioxo-1,3,4,5-tetrahydro-
2H-pyrano[2,3-d]pyrimidine-6-carbonitrile(4v)
James, M. Gemmeren and B. List Chem. Rev. 2015, 115,
9388; g) T. Ooi, ACS Catal. 2015, , 6980; h) P. H.
5
White crystal (yield: 85%, 0.26 g); Mp: 250-252 oC. IR (KBr):
3463, 3352, 3163, 3001, 2584, 2198, 1701, 1635, 1608, 1577,
1508, 1400, 1280, 1199, 1107, 1049, 983, 771, 605, 559 cm-1.
1H-NMR (250 MHz, DMSO-d6/TMS) δ (ppm): 10.96 (s, 2H, NH),
7.30-7.42 (m, 3H, Ar), 7.21 (s, 2H, NH2), 3.89 (s, 1H, CH). 13C-
NMR (62.5 MHz, DMSO-d6/TMS) δ (ppm): 170.7, 162.1, 158.6,
153.3, 149.7, 135.8, 135.7, 130.2, 129.1, 128.4, 118.4, 85.8,
59.7, 32.0. Anal. Calcd. for C14H8Cl2N4O3: C, 47.89; H, 2.30; N,
15.96. Found: C, 47.97; H, 2.19; N, 15.85.
Poulsen, S. Vergura, A. Monleón, D. K. B. Jørgensen and
K. A. Jørgensen, J. Am. Chem. Soc. 2016, 138, 6412; i) S.
E. Wheeler, T. J. Seguin, Y. Guan and A. C. Doney, Acc.
Chem. Res. 2016, 49, 1061; j) D. M. Walden, O. M.
Ogba, R. C. Johnston and P. H.-Y. Cheong, Acc. Chem.
Res. 2016, 49, 1279; k) S. Wang, Y. Jiang, S. Wu, G.
Dong, Z. Miao, W. Zhang and C. Sheng, Org. Lett. 2016,
18, 1028.
2 a) R. C. Wende and P. R. Schreiner, Green Chem. 2012, 14
1821; b) M. Ferré, R. Pleixats, M. W. C. Man and X.
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Cattoën, Green Chem. 2016, 18, 881.
3 a) P. MacLellan, Nat. Chem. 2013, 5, 896; b) J. Y. Shi, C. A.
7-Amino-5-(4-methoxyphenyl)-2,4-dioxo-1,3,4,5-tetrahydro-
2H-pyrano[2,3-d]pyrimidine-6-carbonitrile (4w)
Wang, Z. J. Li, Q. Wang, Y. Zhang and W. Wang, Chem.
Eur. J. 2011, 17, 6206; c) K. Schulz, L. Ratjen, J. Martens,
Tetrahedron, 2011, 67, 546.
Yellow crystal (yield: 88%, 0.24 g); Mp: 282-285oC [Lit. 280–
284oC].17m IR (KBr): 3398, 3186, 3008, 2835, 2194, 1716, 1678,
1635, 1508, 1396, 1342, 1276, 1245, 1172, 1099, 1037, 987,
4 a) S. Ranjbar, P. Riente, C. Rodríguez-Escrich, J. Yadav, K.
Ramineni and M. A. Pericàs, Org. Lett. 2016, 18, 1602;
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Commun. 2012, 48, 3188; c) P. Riente, J. Yadav and M.
A. Pericàs, Org. Lett. 2012, 14, 3668; d) A. M. Goldys,
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e) S. Itsuno, T. Oonami, N. Takenaka and N. Haraguchi,
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Benaglia, R. Annunziata, V. Chiroli, R. Porta and A.
Gervasini, J. Org. Chem. 2013, 78, 11326.
1
848, 655, 605, 543 cm-1. H-NMR (250 MHz, DMSO-d6/TMS) δ
(ppm): 11.09 (s, 2H, NH), 7.03-7.09 (m, 4H), 6.81 (d, J = 8.2 Hz,
2H, Ar), 4.13 (s, 1H, CH), 3.68 (s, 3H, CH3). 13C-NMR (62.5 MHz,
DMSO-d6/TMS) δ (ppm): 167.7, 162.3, 157.4, 151.6, 149.4,
136.1, 128.2, 119.2, 113.5, 88.6, 59.0, 54.9, 34.8. Anal. Calcd.
for C15H12N4O4: C, 57.69; H, 3.87; N, 17.94. Found: C, 57.58; H,
3.71; N, 17.86.
5 a) D. Wang and D. Astruc, Chem. Rev. 2014, 114, 6949; b)
D. Wang, C. Deraedt, J. Ruiz, D. Astruc, Acc. Chem. Res.
2015, 48, 1871; c) R. B. N. Baig, M. N. Nadagouda and
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Gawande, Y. Monga, R. Zboril and R. K. Sharma Coord.
Chem. Rev. 2015, 288, 118.
7-Amino-4-oxo-5-phenyl-2-thioxo-1,3,4,5-tetrahydro-2H-
pyrano[2,3-d]pyrimidine-6-carbonitrile (4x)
Yellow crystal (yield: 88%, 0.23 g); Mp: >330 oC. IR (KBr): 3070,
2889, 2192, 1647, 1596, 1558, 1454, 1400, 1299, 1191, 1014,
1
991, 891, 794, 532 cm-1. H-NMR (250 MHz, DMSO-d6/TMS) δ
6 a) R. Mrówczyński, A. Nan and J. Liebscher, RSC Adv. 2014,
(ppm): 10.33 (s, 2H, NH), 7.22-7.27 (m, 2H), 7.12-7.15 (m, 3H),
6.97-6.99 (m, 2H), 3.96(s, 1H, CH). 13C-NMR (62.5 MHz, DMSO-
d6/TMS) δ (ppm): 174.1, 173.2, 163.7, 162.5, 140.3, 130.3,
127.0, 124.6, 120.6, 79.1, 60.7, 34.0. Anal. Calcd for
C14H10N4O2S: C, 56.37; H, 3.38; N, 18.78. Found: C, 56.29; H,
3.31; N, 18.64.
4
, 5927; b) Z. Yacob, A. Nan and J. Liebscher, Adv.
Synth. Catal. 2012, 354, 3259; c) Y. Huang and W.
Zhang, Green Process Synth. 2013, , 603
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Kundaliya and J. Y. Ying, J. Am. Chem. Soc. 2005, 127
2
,
4990; b) W.-Y. Rho, H.-M. Kim, S. Kyeong, Y.-L. Kang,
D.-H. Kim, H. Kang, C. Jeong, D.-E. Kim, Y.-S. Lee and B.-
H. Jun, J. Industrial Eng. Chem. 2014, 20, 2646; c) S.
Shylesh, V. Schnemann and Werner R. Thiel, Angew.
Chem. Int. Ed. 2010, 49, 3428; d) A.-H. Lu, E. L. Salabas,
and F. Schuth, Angew. Chem. Int. Ed. 2007, 46, 1222.
2-Amino-5-benzoyl-4-(4-cyanophenyl)-6-phenyl-4H-pyran-3-
carbonitrile (4y)
Yellow crystal (yield: 90%, 0.34 g); Mp: 270-272oC. IR (KBr):
3328, 3190, 2866, 2198, 1685, 1647, 1604, 1577, 1496, 1446,
1415, 1326, 1261, 1222, 1149, 1114, 1029, 902, 852, 810, 767,
698 cm-1. 1H-NMR (250 MHz, DMSO-d6/TMS) δ (ppm): 7.44-
7.54 (m, 7H), 7.27-7.29 (m, 2H), 7.13-7.20 (m, 6H), 6.81 (s, 1H),
4.67 (s, 1H, CH). 13C-NMR (62.5 MHz, DMSO-d6/TMS) δ (ppm):
194.8, 159.7, 151.5, 149.0, 136.5, 132.7, 132.5, 131.8, 128.8,
128.6, 128.5, 128.1, 128.0, 127.7, 119.4, 109.8, 55.7, 41.3.
Anal. Calcd. for C26H17N3O2: C, 77.41; H, 4.25; N, 10.42. Found:
C, 77.34; H, 4.48; N, 10.32.
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Shahidzadeh, S. Sarikhani and F. Panahi, J. Molecul.
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Zipse, Chem. Eur. J. 2005, 11, 4751; b) N. D. Rycke, F.
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The financial supports of research councils of Shiraz University
are gratefully acknowledged.
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A new DMAP-based magnetic nano-organocatalyst was developed for efficient one-pot synthesis of
2-amino-4H-chromene-3-carbonitrile derivatives in water as a green solvent.