High-efficient synthesis of 2-imino-2H-chromenes and dihydropyrano[c]chromenes using novel and green catalyst (CaO@SiO2@AIL)

Article abstract of DOI:10.1007/s11164-020-04295-5

In this work, 1,3,5,7-tetraazaadamantan-1-ium chloride (AIL) functionalized silica-coated calcium oxide hybrid nanocatalyst (CaO@SiO₂@AIL) as a novel, efficient, green and recyclable heterogeneous ionic liquid catalyst was synthesized. Catalytic activity of the CaO@SiO₂@AIL hybrid nanoparticles was investigated for synthesis of the pharmaceutically valuable 2-imino-2H-chromene and dihydropyrano[c]chromene derivatives. A wide range of amines and aromatic aldehydes containing either electron-withdrawing or electron-donating substituent were examined using optimized conditions to produce the desired products. 2-Imino-2H-chromenes were synthesized under solvent-free condition, and dihydropyrano[c]chromenes were prepared in aqueous medium as green conditions within short reaction times, high yields and using easy workup procedures. Structure confirmation and surface properties of the core/shell hybrid nanoparticles were considered via Fourier transform infrared spectroscopy, X-ray powder diffraction, scanning electron microscope, energy-dispersive X-ray spectroscopy, WDS map scan, thermogravimetric and elemental analyses. This IL-supported heterogeneous nanocatalyst can be reused at least six times without considerable loss of its performance.

Full text of DOI:10.1007/s11164-020-04295-5

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04295-5
High‑efcient synthesis of 2‑imino‑2H‑chromenes
and dihydropyrano[c]chromenes using novel and green
catalyst (CaO@SiO2@AIL)
Fatemeh Sameri1,2 · Akbar Mobinikhaledi1,2 · Mohammad Ali Bodaghifard1,2
Received: 12 August 2020 / Accepted: 3 October 2020
© Springer Nature B.V. 2020
Abstract
In this work, 1,3,5,7-tetraazaadamantan-1-ium chloride (AIL) functionalized silica-
coated calcium oxide hybrid nanocatalyst (CaO@SiO2@AIL) as a novel, efcient,
green and recyclable heterogeneous ionic liquid catalyst was synthesized. Catalytic
activity of the CaO@SiO2@AIL hybrid nanoparticles was investigated for synthe-
sis of the pharmaceutically valuable 2-imino-2H-chromene and dihydropyrano[c]
chromene derivatives. A wide range of amines and aromatic aldehydes containing
either electron-withdrawing or electron-donating substituent were examined using
optimized conditions to produce the desired products. 2-Imino-2H-chromenes were
synthesized under solvent-free condition, and dihydropyrano[c]chromenes were
prepared in aqueous medium as green conditions within short reaction times, high
yields and using easy workup procedures. Structure confrmation and surface prop-
erties of the core/shell hybrid nanoparticles were considered via Fourier transform
infrared spectroscopy, X-ray powder difraction, scanning electron microscope,
energy-dispersive X-ray spectroscopy, WDS map scan, thermogravimetric and
elemental analyses. This IL-supported heterogeneous nanocatalyst can be reused at
least six times without considerable loss of its performance.
Keywords Ionic liquid · Eggshells waste · Biocatalyst · 2-Imino-2H-chromenes ·
Dihydropyrano[c]chromenes
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-020-04295-5) contains supplementary material, which is available to authorized users.
* Akbar Mobinikhaledi
akbar_mobini@yahoo.com
1
Department of Chemistry, Faculty of Science, Arak University, Arāk 38156-88138, Iran
2
Institute of Nanosciences and Nanotechnology, Arak University, Arāk 38156-88138, Iran
Vol.:(0123456789)
1 3

F. Sameri et al.
Introduction
Heterocyclic motifs with anticancer and anti-HIV properties play a notable role in
design and synthesis of bioactive molecules [1, 2]. The chromene derivatives are
an important type of heterocyclic compounds, which have received considerable
attention due to their biological and pharmacological properties and critical inter-
mediates in the synthesis of many natural products and medicinal agents [3], such
as anticancer, antibacterial [4], antiviral [5], antimicrobial [6] and anti-HIV [7]
activities. They have also been widely employed as cosmetics, pigments, potent
biodegradable agrochemicals [8] and are found in several natural tocopherols,
alkaloids, anthocyanins and favonoids [9].
In this sense, chromene’s structural matter exists in several signifcant biologi-
cally active compounds like 2-imino-2H-chromenes. Functionalized 2-imino-2H-
chromenes have attracted widespread attention due to their diferent applications,
including tyrosine kinase (PTK) inhibitors [9], as well as anti-Alzheimer, anti-
cancer and antimicrobial [10] agents. Despite these properties, there are a few
reports for synthesis of 2-imino-2H-chromenes. Previous methods for the syn-
thesis of these compounds are the Knoevenagel condensation of salicylaldehydes
with methylene compounds [11] operated by catalysts like NaHCO3 or Na2CO3
[12], potassium phthalimide [13], piperidine in the presence [14] or absence [15]
of microwave irradiation and polyethylene polyamine [16]. Dihydropyrano[c]
chromenes are also another vital class of chromenes structural motif which have
attracted much attention due to their wide range of diverse pharmacological and
biological properties such as spasmolytic [17], diuretic [18], anticoagulant [19],
anticancer [20, 21] and anti-anaphylactic activity [6]. The most reported proce-
dures for the synthesis of dihydropyrano[c]chromenes employ diferent catalytic
systems including sodium dodecyl sulfate (SDS) [22], CuO nanoparticles [23],
4-(dimethylamino)pyridine (DMAP) [24], diammonium hydrogen phosphate
(DAHP) [25].
The green chemistry can be regarded as an attractive feld in the development of
clean and sustainable technology to replace the use of hazardous reagents and cata-
lysts with relatively environmentally benign compounds [26]. Also, “green chem-
istry” emphasizes the optimization of synthetic methodologies to reduce pollution,
costs and tedious workup procedures [27]. Furthermore, new challenges are leading
to the use of natural and biocompounds for organic and inorganic applications.
Recently, immobilization of diferent catalysts onto various nanosized solid sup-
ports has emerged as the most promising alternative strategy to improve their sta-
bility and catalytic activity in the feld of organo-catalysis [28]. The organic–inor-
ganic nanohybrid materials can be regarded as attractive heterogeneous catalysts in
organic synthesis, since these materials feature the functional variety and fexibility
of organic structures combined with easy production and thermal and mechanical
stability of inorganic solids [29, 30]. Also, the nanoheterogeneous catalysts ofer
larger surface area which is responsible for the higher catalytic activity [31].
With attention to the outstanding biologically and therapeutically signifcance
of chromene derivatives and their involvement as useful materials in synthetic
1 3

High‑efcient synthesis of 2‑imino‑2H‑chromenes and…
organic and medicinal chemistry, increasing interest for preparation of these com-
pounds by development of environmentally friendly and selective approaches
using heterogeneous ionic liquid is still in high demand. Although previous meth-
ods for preparation of these chromenes are useful, some of them sufer from dif-
ferent limitations including long reaction times, multiple-step reactions, unsat-
isfactory yields, harsh reaction conditions and the use of relatively expensive
catalysts. To avoid these limitations, attempts have focused on simple reactions
under solvent-free conditions or use of water as a green and suitable solvent, and
use of heterogeneous catalysts with high recyclability and reusability.
Calcium oxide (CaO) as a heterogeneous catalyst has a high stability, high cat-
alytic efciency, facile synthesis and functionalization along with highly specifc
surface. The eggshell waste has been used as raw material, and so the CaO parti-
cles are low cost, biodegradable, recyclable and biocompatible [32–34]. The CaO
nanocatalyst has been synthesized by calcination–hydration–dehydration tech-
nique. The high surface area of CaO nanoparticles can be kept by SiO2 until it
improves its functionality [35]. Hexamethylenetetramine (HMT) is a white crys-
talline compound with a cage-like structure. This compound is easily accessible,
has a low price and is highly soluble in water and polar organic solvents [36].
This polycyclic tertiary amine has applications in plastics, production of explo-
sives, chemical synthesis and pharmacology. In several studies, HMT was used
for reduction of graphene oxide and doping nitrogen into the graphene sheets to
increase nitrogen content and its stability, and also promote the formation of zinc
oxide [37] and ceria nanoparticles [38] where it seems to play a role in control-
ling the nanosizes and shapes.
By emphasizing the development of novel versatile and benign catalysts for
the synthesis of various heterocyclic compounds, we were encouraged to prepare
CaO@SiO2@AIL as a new core–shell hybrid nanocatalyst. The hexamethylene-
tetramine (HMT) with an ionic tag was grafted on silica-coated CaO nanoparti-
cles, and its catalytic performance for the ecofriendly synthesis of 2-imino-2H-
chromenes (Scheme 1) and dihydropyrano[c]chromenes (Scheme 2) was properly
investigated.
Scheme 1 CaO@SiO2@AIL catalyzed synthesis of 2-imino-2H-chromenes
1 3

F. Sameri et al.
Scheme 2 CaO@SiO2@AIL catalyzed synthesis of dihydropyrano[c]chromenes
Experimental
Materials and physicochemical characterization techniques
Chemicals were purchased from Merck chemical company. NMR spectra were
recorded on 300 and 400 MHz Bruker Avance spectrometer using TMS as an
internal standard. Fourier transform infrared (FT-IR) spectra were recorded on
an ALPHA-Bruker and PerkinElmer spectrophotometer from KBr pellets. The
structure of CaO@SiO2@AIL MNPs was characterized by X-ray powder difrac-
tion (XRD), EDX, IR, scanning electron microscope (SEM), elemental analyses
(CHN) and thermogravimetric (TGA) analyses. The X-ray powder difraction
(XRD) was performed on the X’Pert-MPD PRO-PW3040/60 instrument. Energy-
dispersive X-ray (EDX) and scanning electron microscopy (SEM) analysis of the
prepared catalyst were carried out on a MIRA III instrument. Thermogravimetric
analysis (TGA) was performed on a Q600TA instrument.
Synthesis of 1,3,5,7‑tetraazaadamantan‑1‑ium chloride (AIL)
The AIL was synthesized according to previously reported method [36]. Accord-
ingly, (3-chloropropyl)trimethoxysilane (1.8 mL, 10 mmol) was added to a solu-
tion of hexamethylenetetramine (1.4 g, 10 mmol) in dry toluene (20 mL) and
refuxed for 48 h under nitrogen atmosphere. The resulted yellowish solid was
fltered and washed with ethanol and dried at 90 °C for 2 h.
1 3

High‑efcient synthesis of 2‑imino‑2H‑chromenes and…
Synthesis of nano‑CaO particles
The nano-CaO particles were prepared using eggshells according to the literature
procedure [39]. Briefy, the household waste eggshells were washed with warm
water to remove sand, tissue and other impurities. These clean eggshells were
washed with distilled water and dried at 120 °C for 24 h, which then milled by a
planetary ball mill. As the catalytic activity of particles increased with decreasing
of their size, the milling time process was optimized (5 h) with the average size of
8 nm. Subsequently, nano-CaO particles obtained by eggshells were calcinated in
a mufe furnace at 900 °C for 3 h and refuxed in water for 6 h, and dried in oven
at 100 °C for overnight. The soiled nano-CaO particles were dehydrated by calci-
nation at 870 °C for 3 h to convert the hydroxide groups to oxide form.
Synthesis of CaO@SiO2
CaO@SiO2 was prepared according to the Stober method [40]. Typically, 1 g of
the CaO nanoparticles was dispersed by ultrasonic vibration in a mixture of etha-
nol (40 mL), deionized water (6 mL) and 1.5 mL of aqueous ammonia solution
(25 wt%) for 20 min. Subsequently, 1.4 mL of tetraethylorthosilicate (TEOS) was
added dropwise and stirred for 22 h at room temperature under N2 atmosphere.
The product was fltered of and then washed several times with water and etha-
nol, and dried at 25 °C under vacuum for 24 h.
Synthesis of CaO@SiO2@AIL
A mixture of CaO@SiO2 (0.4 g) and dry toluene (10 mL) was stirred at 100 °C
for 10 min. Then, 0.38 g (1 mmol) of AIL in dry toluene (10 mL) was added
and the mixture stirred under refux condition and nitrogen atmosphere for 24 h.
Afterward, the crude product was fltered of and washed with ethanol three times
and dried at 80 °C in vacuum for overnight.
General procedure for synthesis of 2‑imino‑2H‑chromenes derivatives (4a–4q)
A mixture of alkyl or arylamine (1 mmol), ethyl cyanoacetate (1 mmol),
2-hydroxybenzaldehyde (1 mmol) or 2-hydroxy-1-naphthaldehyde (1 mmol)
and 0.01 g of CaO@SiO2@AIL as a catalyst was stirred at 80 °C under solvent-
free conditions for an appropriate time (Table 2). The progress of the reaction
was monitored by TLC. After completion of the reaction, hot EtOH was added
(10 mL) and the catalyst separated out by centrifuge. After cooling the solution,
the crude product was precipitated and isolated by fltration. The obtained prod-
uct was recrystallized from ethanol to give pure compound.
1 3

F. Sameri et al.
General procedure for synthesis of dihydropyrano[c]chromene derivatives
(8a–8p)
A mixture of aldehyde (1 mmol), 4-hydroxycoumarin (1 mmol), malononitrile or
ethyl cyanoacetate (1 mmol) was added in a 25 mL round-bottomed fask contain-
ing 0.01 g of CaO@SiO2@AIL in H2O (5 mL). The resulting mixture was stirred at
room temperature for an appropriate time (Table 4). Up on completion of reaction
(TLC), the result mixture was diluted with hot ethanol (10 mL) and the solution fl-
tered to remove the catalyst. The crude product was precipitated by cooling the solu-
tion, which was then isolated by fltration and recrystallized from ethanol to give the
pure product.
Results and discussion
Synthesis and structural characterization of CaO@SiO2@AIL
Hexamethylenetetraamine-based ionic liquid stabilized onto silica-coated CaO nan-
oparticles was prepared as a novel nanosized, environmentally friendly and retriev-
able heterogeneous catalyst (Scheme 3). The ionic liquid (AIL) was prepared by pre-
viously reported method [36]. The prepared AIL was then grafted onto the surface
of CaO@SiO2 support to give the CaO@SiO2@AIL as a novel hybrid nanomaterial.
The structure of CaO@SiO2@AIL was determined by Fourier transform infrared
spectroscopy (FT-IR), SEM, CHN, energy-dispersive X-ray spectroscopy (EDS),
WDS map scan, XRD and TGA analyses.
FT‑IR spectra
Figure 1 shows FT-IR spectra of CaO, CaO@SiO2, AIL and CaO@SiO2@AIL. In
Fig. 1a, b, and d, the broad absorption bands around 3400–3600 cm−1 are attributed
to stretching vibration of –OH groups and physically adsorbed water (H2O) [32].
The weak band at 1481 cm−1 typically corresponds to the asymmetric C=O stretch-
ing of carbonate ions. CaO@SiO2 shows characteristic FT-IR absorption bands at
around 968 cm−1 (symmetric stretching), 875 cm−1 (in plane bending) and 462 cm−1
(rocking mode) for the Si–O–Si groups and confrm the formation of SiO2 shell.
The twisting vibration mode of H–O–H in the silica shell is seen at 1641 cm−1,
and broad absorption bands in the range of 3200–3500 cm−1 attributed to stretch-
ing vibration mode of Si–OH bonds and adsorbed H2O [41] (Fig. 1b, d). The pres-
ence of the attached alkyl groups is confrmed by the observed bands at 2936 and
2956 cm−1 related to the symmetric and asymmetric stretching modes of C–H bonds
(Fig. 1c, d). The tertiary amine group is shown at 1467 cm−1 [36] (Fig. 1c, d). These
spectra reveal the functional groups were successfully grafted onto the surface of the
CaO nanoparticles.
1 3

High‑efcient synthesis of 2‑imino‑2H‑chromenes and…
Scheme 3 Preparation of CaO@SiO2@AIL (methods A and B)
Fig. 1 FT-IR spectra of a nano CaO b nano-CaO@SiO2, c AIL, d CaO@SiO2@AIL catalyst
1 3

F. Sameri et al.
EDX analysis
For comparison, CaO@SiO2@AIL was synthesized by two diferent procedures
and their EDX spectra were properly compared. In method A, the AIL was pre-
pared by employing the previously reported method [36]. The CaO@SiO2 was
separately synthesized and AIL grafted onto the CaO@SiO2 core–shell surface
to produce CaO@SiO2@AIL (Scheme 3, method A). In method B, initially the
CaO@SiO2 was synthesized, and subsequently, the silanol groups on the surface
of CaO@SiO2 nanoparticles were treated with (3-chloropropyl)trimethoxysilane
to produce CaO@SiO2–Cl. Next, the resulted chloropropyl anchored CaO@SiO2
was reacted with hexamethylenetetramine to give the fnal hybrid structure CaO@
SiO2@AIL (Scheme 3 method B).
The energy-dispersive X-ray spectrum (EDX) of CaO@SiO2@AIL is shown in
Fig. 2. This spectrum clearly indicates the expected elemental composition of N
and Cl, which confrms the surface of CaO@SiO2 was successfully coated with
HMTA in two methods. The method A was more efective than B because the
determined percentages of N and Cl are higher in method A. Thus, it indicates
that AIL is more loaded on the CaO@SiO2 surface (Fig. 2 method A).
SEM spectrum and histogram of CaO@SiO2@AIL
The surface morphology and histogram of particle size distribution of the CaO@
SiO2@AIL were characterized by the scanning electronic microscopy (SEM) as
presented in Fig. 3a and b, respectively. It can be seen that the particles of CaO@
SiO2@AIL are well dispersed with almost spherical morphology and the aver-
age size of about 8 nm, which matches well with XRD pattern. Furthermore, the
mesoporous nature and the small size of these nanoparticles lead to the high spe-
cifc surface area and high catalytic activity. The high surface area of these nano-
particles creates a certain degree of aggregation, which demonstrates the success-
ful anchoring ionic liquid part on to CaO@SiO2 nanoparticles (Fig. 3).
Fig. 2 EDX spectrum of CaO@SiO2@AIL (papered by methods A and B)
1 3

High‑efcient synthesis of 2‑imino‑2H‑chromenes and…
Fig. 3 a SEM image of CaO@SiO2@AIL b histogram of CaO@SiO2@AIL
WDX map scan of CaO@SiO2@AIL
The projected distribution of N, O, Si, Ca, Cl and C elements in the catalyst via
WDX images is shown in Fig. 4b–g, respectively, and can provide qualitative data
on the distribution of various chemical elements in the catalyst matrix, coupled with
Fig. 4 a SEM image of CaO@SiO2@AIL and elemental mapping of b N, c O, d Si, e Ca, f Cl and g C
1 3

F. Sameri et al.
SEM image presented in Fig. 4a. From these compositional maps, the homogeneous
distribution of all the elements in the catalyst is clearly determined the regular uni-
formity of the catalyst. These analysis data clearly prove that the organic functional
group is attached onto the surface of CaO@SiO2.
XRD analysis
The XRD measurements were implemented to investigate the presence as well as
the crystallinity degree of CaO, CaO@SiO2 and CaO@SiO2@AIL catalysts (Fig. 5).
CaO nanoparticles appeared difraction peaks at 2θ=32.50°, 37.65°, 54,16°, 64.54°
and 67.71° correspond to the Miller indices (hkl) at (111), (200), (202), (311) and
(222) crystal planes, respectively [39]. These lattice parameters confrm the CaO
nanoparticles are pure with a cubic structure and relative intensities. The results are
in agreement with the standard values given in JCPDS card no.77-9574 for a cal-
cite CaO powder sample. The broad peak around 2θ=18° to 28° is derived from
amorphous silica phase of CaO@SiO2 and CaO@SiO2@AIL [35] (Fig. 5b, c).
The average size of the crystallites can be estimated by applying Scherrer’s for-
mula (D=0.9λ/β cos θ). In this formula, D is defned as the average crystalline size,
where λ is the wavelength of the incident X-rays, β is the full width at half maximum
height in radians and θ belongs to the Bragg angle. The peak at 2θ=37.65° (200) is
selected to calculate the crystallite size. The crystallite size of the nanoparticle was
obtained 8 nm by using Scherrer’s equation, which is in the range of that determined
by using SEM analysis. Besides, the XRD pattern indicates the retention of crystal-
line core structure of cubic CaO through the silica coating procedure.
TGA study
The thermal behavior of CaO@SiO2@AIL reveals the mass loss of organic tags
as they decompose upon heating (Fig. 6). The frst step from room temperature
to 150 °C is attributed to the removal of physically adsorbed water and remained
Fig. 5 XRD patterns of a CaO nanoparticles, b nano-CaO@SiO2 and c nano-CaO@SiO2@AIL
1 3

High‑efcient synthesis of 2‑imino‑2H‑chromenes and…
Fig. 6 TGA curve of CaO@SiO2@AIL
organic solvents (weight loss 10%). The second step, in the region from 150 to
330 °C, is related to the loss of grafted AIL on the surface of CaO@SiO2. The third
step, the weight loss between 330 and 700 °C, is attributed to degradation of HMTA
groups. Also the total loss weight between 150 and 700 °C is 35%, which can be
related to the grafted organic tags. In accordance with this mass loss, 1.6 mmol of
AIL was loaded on 1 g of CaO@SiO2 catalyst.
Elemental analyses
In order to confrm the successful grafting of organic ionic liquid (AIL) onto surface
of CaO@SiO2, the elemental analysis was performed and revealed the percent of C
(16.8%), H (3.8%), and N (8.6%). The percent of nitrogen was measured in organic
moiety. Using the analytical data, and based on nitrogen content, the grafted organic
moiety was calculated to be about 34% of AIL. It is nearly matched with thermal
gravimetric (TGA) for CaO@SiO2@AIL.
Synthesis of 2‑imino‑2H‑chromenes catalyzed by CaO@SiO2@AIL
After ensuring the successful fabrication of CaO@SiO2@AIL, the catalytic activ-
ity of these nanomaterials for synthesis of 2-imino-2H-chromenes was investi-
gated. To fnd out the optimized conditions, the reaction of 2-hydroxybenzalde-
hyde, phenylmethanamine and ethyl cyanoacetate was selected as a model. To
investigate the efect of solvent, the model reaction was carried out by using dif-
ferent solvents including EtOH/H2O, H2O, MeOH, EtOH, CH3CN and CHCl3.
Fortunately, solvent-free condition at 80 °C was found to be more applicable for
1 3

F. Sameri et al.
this synthesis rather than using the organic solvents according to the principles
of green chemistry. As shown in Table 1, the best result was obtained by using of
0.01 g of the catalyst among diferent amounts of catalyst. Therefore, the reaction
was efciently performed using 0.01 g of the catalyst at 80 °C under solvent-free
conditions to give desired product in high yield over short reaction time (Table 1,
entry 10). To study the scope and limitations of this procedure, a wide range of
amines containing either electron-withdrawing or electron-donating substituent
were used for preparation of 2-imino-2H-chromenes under optimized conditions
(Table 2). The results show the corresponding 2-imino-2H-chromenes were syn-
thesized with good to excellent yields. Thus, CaO@SiO2@AIL was found to be
superior and highly efcient catalyst for this reaction under green and mild condi-
tions. A possible mechanism for synthesis of 2-imino-2H-chromenes in the pres-
ence of CaO@SiO2@AIL is presented in Scheme 4. Firstly, a substitution reac-
tion of amine and ethyl cyanoacetate gives N-alkyl-2-cyanoacetamide which is
followed by a Knoevenagel condensation of N-alkyl-2-cyanoacetamide anion with
2-hydroxybenzaldehyde to produce intermediate A. The cyclization of intermedi-
ate A by OH nucleophilic attack on nitrile group resulted in the desired product.
Table 1 Optimization of reaction conditions for the synthesis of N-benzyl-2-imino-2H-chromene-3-car-
boxamide
Entry
Catalyst (g)
Solvent
Temp (°C)
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
–
–
–
–
–
–
–
–
–
110
110
95
80
110
95
80
110
95
150
60
40
35
30
30
28
10
10
10
10
40
55
30
20
65
45
Trace
63
65
65
72
75
83
90
92
98
94
83
82
80
88
72
75
0.005
0.005
0.005
0.008
0.008
0.008
0.01
0.01
0.01
0.02
0.01
0.01
0.01
0.01
0.01
0.01
9
–
–
–
10
11
12
13
14
15
16
17
80
80
H2O/EtOH
H2O
MeOH
EtOH
CHCl3
CH3CN
Refux
Refux
Refux
Refux
Refux
Refux
Reaction conditions: 2-hydroxybenzaldehyde (1, 1 mmol), phenylmethanamine (2, 1 mmol), ethyl
cyanoacetate (3, 1 mmol)
Bold values indicate the optimized reaction conditions
1 3

High‑efcient synthesis of 2‑imino‑2H‑chromenes and…
Table 2 Synthesis of 2-imino-2H-chromenes via three component condensation reactions in the presence
of CaO@SiO2@AIL
Entry Amine
Product Time (min) Yield (%) MP (°C)
Found
Reported Refs.
1
2
3
4
5
6
7
8
PhNHNH2
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4 m
4n
4o
10
23
20
18
30
10
15
15
35
10
10
10
15
10
10
73
68
85
86
80
90
79
93
94
98
98
90
95
80
92
263–265 266–267 [15]
291–292 293–295 [42]
257–259 253–255 [42]
210–212 213–216 [43]
158–160 157–159 [44]
138–141 146–147 [44]
160–162 164–165 [44]
168–169 171–173 [44]
201–203 207–209 [45]
128–130 133 [14]
1,3-diaminopropane
1,4-diaminobutane
cyclopentylamine
3,4-dimethoxyaniline
4-nitroaniline
4-bromoaniline
3,4-dichloroaniline
cyclohexylamine
phenylmethanamine
semicarbazide
2,4-dinitrophenylhydrazine
2-amino-4-methylpyrimidine
phormilhydrazine
9
10
11
12
13
14
15
219–221
254–255
210–212
219–224
230–232
–
–
–
–
–
4-pyridinecarboxylic acid
hydrazide
16
17
semicarbazide
4p
4q
10
10
83
80
255–257
277–279
–
–
4-pyridinecarboxylic acid
hydrazide
Reaction conditions: 2-hydroxybenzaldehyde (1a–o, 1 mmol) or 2-hydroxy-1-naphthaldehyde (1p,q,
1 mmol), alkyl or arylamine (2, 1 mmol), ethyl cyanoacetate (3, 1 mmol) and catalyst (0.01 g)
Synthesis of dihydropyrano[c]chromenes catalyzed by CaO@SiO2@AIL
Preliminarily, the optimal reaction conditions for synthesis of dihydropyrano[c]
chromenes in the presence of CaO@SiO2@AIL were investigated. The reaction
of 4-chlorobenzaldehyde, 4-hydroxycoumarin and malononitrile was selected as
a model. The reaction was carried out in diferent solvents such as H2O, EtOH,
CHCl3, THF, DMF, EtOAc and CH3CN. As Table 3 shows, H2O was found to be
a suitable solvent for this reaction at room temperature. In addition, the crucial
role of CaO@SiO2@AIL as a catalyst in this reaction was approved by perform-
ing the reaction in the absence of catalyst, which gave only trace amount of the
expected product after a prolonged reaction time (Table 3, entry 1). The best con-
ditions along with high possible yield of product and short reaction time were
obtained by 0.01 g of catalyst (Table 3, entry 10).
After optimization of reaction conditions, to examine the generality of this
procedure, the reaction of several aromatic aldehydes bearing either electron-
withdrawing or electron-donating substituent groups was examined using the
optimized conditions to produce desired products (Table 4). This procedure
for various substrates was very efcient, and the dihydropyrano[c]chromene
1 3

F. Sameri et al.
Scheme 4 Possible mechanism for one-pot synthesis of 2-imino-2H-chromenes using CaO@SiO2@AIL
as a catalyst
Table 3 Optimization of
Entry Catalyst (g) Solvent Temp (°C) Time (min) Yield (%)
reaction conditions for synthesis
of 2-amino-4-(4-chlorophenyl)-
1
–
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
THF
DMF
25
80
50
25
80
50
25
80
50
25
25
25
25
240
45
40
35
35
30
30
25
25
20
20
80
70
85
35
75
50
Trace
60
62
65
85
88
90
92
93
96
94
20
32
20
80
30
70
5-oxo-4H,5H-pyrano[3,2-c]
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
0.005
0.005
0.005
0.008
0.008
0.008
0.01
0.01
0.01
0.02
0.01
0.01
0.01
0.01
0.01
0.01
chromene-3-carbonitrile
EtOAc 25
EtOH 25
CHCl3 25
CH3CN 25
Reaction conditions 4-chlorobenzaldehyde (5, 1 mmol), 4-hydroxy-
coumarin (6, 1 mmol) and malononitrile (7, 1 mmol)
Bold values indicate the optimized reaction conditions
1 3

High‑efcient synthesis of 2‑imino‑2H‑chromenes and…
Table 4 Synthesis of dihydropyrano[c]chromenes via three component condensation reactions using
CaO@SiO2@AIL
Entry Aldehyde
Product Time (min) Yield (%) MP (°C)
Found
Reported Refs.
1
2
3
4
5
6
7
8
2,4-(Cl)2C6H3
4-ClC6H4
3-NO2C6H4
2-ClC6H4
2-BrC6H4
8a
8b
8c
8d
8e
8f
8g
8h
8i
7
20
10
16
10
25
9
10
30
10
15
15
60
93
96
90
80
93
75
95
90
80
96
85
80
88
280–281 283–284 [27]
255–257 256–258 [46]
230–232 229–231 [46]
269–271 273–274 [27]
288–290 293–296 [47]
258–260 262–263 [25]
260–262 263–264 [48]
250–252 255–256 [27]
218–220 228–230 [23]
244–246 245–247 [49]
240–242 248–250 [50]
3-OHC6H4
4-NO2C6H4
2-NO2C6H4
2,5-(MeO)2C6H3
4-FC6H4
3-EtO-4-OH-C6H3
3-Phenoxy-C6H4
9
10
11
12
13
8j
8 k
8l
254–255
210–212
–
–
2,2′-(butane-1,4-diylbis(oxy))
8 m
dibenzaldehyde
14
4,4′,4′′-((1,3,5-Triazine-2,4,6-triyl) 8n
45
93
219–224
–
tris(oxy))tribenzaldehyde
15
16
4-FC6H4
8o
8p
10
8
95
95
230–232 223–225 [51]
245–247 241–243 [24]
4-NO2C6H4
Reaction conditions: arylaldehyde (5a–p, 1 mmol), 4-hydroxycoumarin (6, 1 mmol), malononitrile (7a–n,
1 mmol) or ethyl cyanoacetate (7o, p, 1 mmol) and catalyst (0.01 g)
derivatives were obtained in good to excellent yields in relatively short reaction
times, without formation of byproducts. A plausible mechanism, similar to that
reported in literature, Ref. [32] is presented for the synthesis of dihydropyrano[c]
chromenes (Scheme 5). As shown in Scheme 5, frstly, the formation of the prod-
ucts can be rationalized by initial standard Knoevenagel condensation reaction
between an aldehyde and malononitrile anion to form arylidene malononitrile as
intermediate A′ under the catalytic efect of the CaO@SiO2@AIL. Subsequently,
4-hydroxycumarin anion attacks catalyst-activated arylidene malononitrile via a
Michael addition and the subsequent cyclization produce the intermediate B. At
the last step, the H-abstraction by catalyst and following tautomerization gives the
desired product. The efciency of CaO@SiO2@AIL catalyst is comparable with
that of other reported catalysts for the synthesis of 2-amino-4-(4-chlorophenyl)-
5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile under optimized conditions
(Table 5). As shown in Table 5, the CaO@SiO2@AIL is an efcient catalyst for
this reaction in terms of short reaction time, high yield, and green chemistry. This
efciency may be related to the inherent properties of CaO in inorganic part, the
cage-like structure of HMTA in organic part, high active surface area and ionic
liquid properties of CaO@SiO2@AIL.
1 3

F. Sameri et al.
Scheme 5 Possible mechanism for one-pot synthesis of dihydropyrano[c]chromenes using CaO@SiO2@
AIL as a catalyst
Table 5 Comparison of CaO@SiO2@AIL with other catalysts reported in the literatures for synthesis of
2-amino-4-(4-chlorophenyl)-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile
Entry
Catalyst
Condition
Time (min)
Yield (%)
Ref.
1
2
3
4
5
6
7
p-TSA
Nano-Al(OH)3
S-proline
H2O/EtOH-refux
EtOH/refux
H2O/EtOH-refux
H2O/60 °C
EtOH/refux
EtOH/refux
H2O/r.t
60
120
360
150
90
120
20
35
73
78
88
49
71
96
[52]
[52]
[25]
[22]
[53]
[54]
Present work
SDS
Nano NiO
Nano Al2O3
CaO@SiO2@AIL
Reaction conditions: 4-chlorobenzaldehyde (1 mmol), 4-hydroxycoumarin (1 mmol), malononitrile
(1 mmol) and catalyst (0.01 g)
1 3

High‑efcient synthesis of 2‑imino‑2H‑chromenes and…
Fig. 7 Recyclability test of CaO@SiO2@AIL
Fig. 8 FT-IR spectra of the fresh catalyst and the six-times reused catalyst
Catalyst recovery and reusability
As separation and reusability of catalyst are very important factors in viewpoints of
green chemistry, the recovery and reusability of CaO@SiO2@AIL was investigated
in reaction of 2-hydroxybenzaldehyde (1 mmol), phenylmethanamine (1 mmol), ethyl
cyanoacetate (1 mmol) and catalyst (0.01 g) under solvent-free condition. The results
confrmed that the catalyst could be reused for six consecutive times without signifcant
loss in the yield of the reaction (Fig. 7). The recovered catalyst was purifed by washing
with hot ethanol and drying in an oven. As shown in Fig. 8, the stability and integrity
of the recovered catalyst were examined and confrmed to be as active as the originally
used catalyst.
1 3

F. Sameri et al.
Conclusion
In this study, novel nanoparticles (CaO@SiO2@AIL) were prepared by using a
simple and inexpensive method. The size and structure of these nanomaterials
were confrmed by FT-IR, EDX, SEM, WDX, XRD, TGA and elemental analyses.
These CaO@SiO2@AIL nanoparticles were used as a heterogeneous catalyst for
synthesis of 2-imino-2H-chromenes and dihydropyrano[c]chromenes under mild
and green conditions. A wide range of amines and aromatic aldehydes contain-
ing either electron-withdrawing or electron-donating substituent were used for
synthesis of the 2-imino-2H-chromenes and dihydropyrano[c]chromenes, respec-
tively, which gave corresponding products in high to excellent yields within short
reaction times. Furthermore, the mild and green nature of reaction conditions,
easy workup procedures and reusability of the catalyst are some other advantages
of these methods.
Acknowledgements We gratefully acknowledge the fnancial support of this work by the research coun-
cil of Arak University.
References
1. A. Mobinikhaledi, S. Asadbegi, M.A. Bodaghifard, Synth. Commun. 46, 1605 (2016)
2. G.M. Ziarani, R. Moradi, T. Ahmadi, N. Lashgari, RSC Adv. 8, 12069 (2018)
3. D. Azarifar, R. Nejat-Yami, F. Sameri, Z. Akrami, Lett. Org. Chem. 9, 435 (2012)
4. M. Zendehdel, M.A. Bodaghifard, H. Behyar, Z. Mortezaei, Microporous Mesoporous Mater.
266, 83 (2018)
5. A. Jooya, A. Davoodnia, M. Fattahi, N. Tavakoli-Hoseini, Org. Prep. Proced. Int. 50, 565 (2018)
6. A. Mobinikhaledi, H. Moghanian, Z. Souri, Lett. Org. Chem. 11, 432 (2014)
7. A. Mobinikhaledi, A. Yazdanipour, M. Ghashang, Green Process. Synth. 5, 289 (2016)
8. L. Nazemi Nasirmahale, O. Goli Jolodar, F. Shirini, H. Tajik, Polycycl. Aromat. Compd. (2019).
https://doi.org/10.1080/10406638.2019.1576748
9. Q. Ren, W.Y. Siau, Z. Du, K. Zhang, J. Wang, Chem. Eur. J. 17, 7781 (2011)
10. M.A. Bodaghifard, M. Solimannejad, S. Asadbegi, S. Dolatabadifarahani, Res. Chem. Intermed.
42, 1165 (2016)
11. A. Sakurai, Y. Motomura, H. Midorikawa, J. Org. Chem. 37, 1523 (1972)
12. F. Areias, M. Costa, M. Castro, J. Brea, E. Gregori-Puigjané, M.F. Proença, J. Mestres, M.I.
Loza, Eur. J. Med. Chem. 54, 303 (2012)
13. H. Kiyani, M.D. Daroonkala, Bull. Chem. Soc. Ethiop. 29, 449 (2015)
14. D. Guo, T. Chen, D. Ye, J. Xu, H. Jiang, K. Chen, H. Wang, H. Liu, Org. Lett. 13, 2884 (2011)
15. S. Kovalenko, I. Bylov, K. Sytnik, V. Chernykh, Y. Bilokin, Molecules 5, 1146 (2000)
16. X.L. Shi, X. Xing, H. Lin, W. Zhang, Adv. Synth. Catal. 356, 2349 (2014)
17. Y. Wang, H. Ye, G. Zuo, J. Luo, J. Mol. Liq. 212, 418 (2015)
18. Z. Vafajoo, H. Veisi, M.T. Maghsoodlou, H. Ahmadian, C. R. Chim. 17, 301 (2014)
19. J. Safaei-Ghomi, F. Eshteghal, H. Shahbazi-Alavi, Polycycl. Aromat. Compd. 1, 2 (2017)
20. M. Cheraghipoor, M.T. Maghsoodlou, M.R. Faghihi, Polycycl. Aromat. Compd. 1 (2019)
21. A. Kakanejadifard, F. Azarbani, N. Khosravani, B. Notash, J. Mol. Liq. 221, 211 (2016)
22. H. Mehrabi, H. Abusaidi, J. Iran. Chem. Soc. 7, 890 (2010)
23. H. Mehrabi, M. Kazemi-Mireki, Chin. Chem. Lett. 22, 1419 (2011)
24. A.T. Khan, M. Lal, S. Ali, M.M. Khan, Tetrahedron Lett. 52, 5327 (2011)
25. S. Abdolmohammadi, S. Balalaie, Tetrahedron Lett. 48, 3299 (2007)
26. R. Mohammadipour, A. Bamoniri, B. Mirjalili, Sci. Iran. 27, 1216 (2020)
1 3

High‑efcient synthesis of 2‑imino‑2H‑chromenes and…
27. N.N. Pesyan, G.R. Bardajee, E. Kashani, M. Mohammadi, H. Batmani, Res. Chem. Intermed. 46,
347 (2020)
28. N. Koukabi, E. Kolvari, A. Khazaei, M.A. Zolfgol, B. Shirmardi-Shaghasemi, H.R. Khavasi, Chem.
Comm. 47, 9230 (2011)
29. M. Bodaghifard, A. Mobinikhaledi, S. Asadbegi, Appl. Organomet. Chem. 31, e3557 (2017)
30. S. Asadbegi, M.A. Bodaghifard, A. Mobinikhaledi, Res. Chem. Intermed. 46, 1629 (2020)
31. M.A. Nasseri, M. Sadeghzadeh, J. Chem. Sci. 125, 537 (2013)
32. E. Mosaddegh, A. Hassankhani, Chin. J. Catal. 35, 351 (2014)
33. A.O. Etim, P. Musonge, A.C. Eloka-Eboka, Biofuel Bioprod. Biorefn. 14, 620 (2020)
34. C. Harripersadth, P. Musonge, Y.M. Isa, M.G. Morales, A. Sayago, S. Afr. J. Chem. Eng. 34, 142–
150 (2020)
35. C.T. Yamashita, J. So, M. Fuji, J. Ceram. Soc. Jpn. 124, 55 (2016)
36. R. Ghorbani-Vaghei, N. Sarmast, Res. Chem. Intermed. 44, 4483 (2018)
37. K. Lu, J. Zhao, Chem. Eng. J. 160, 788 (2010)
38. O. Polezhaeva, N. Yaroshinskaya, V. Ivanov, Inorg. Mater. 44, 51 (2008)
39. P.R. Pandit, M. Fulekar, J. Environ. Manag. 198, 319 (2017)
40. W. Stöber, A. Fink, E. Bohn, J. Colloid Interface Sci. 26, 62 (1968)
41. A. Mobinikhaledi, H. Moghanian, M. Ghanbari, Appl. Organomet. Chem. 32, e4108 (2018)
42. T.A. Hill, A. Mariana, C.P. Gordon, L.R. Odell, M.J. Robertson, A.B. McGeachie, N. Chau, J.A.
Daniel, N.N. Gorgani, P.J. Robinson, J. Med. Chem. 53, 4094 (2010)
43. A. Filipe, C. Marta, C. Marian, B. José, G. Ellisabet, P. Fernanda, M. Jordi, I. Maria, Eur. J. Med.
Chem. 54, 303 (2012)
44. N. Edraki, A. Iraji, O. Firuzi, Y. Fattahi, M. Mahdavi, A. Foroumadi, M. Khoshneviszadeh, A.
Shafee, R. Miri, J. Iran. Chem. Soc. 13, 2163 (2016)
45. M.H. Helal, E.-H. Ali, A. Gameel, A.A. Ali, Y.A. Ammar, J. Chem. Res. 34, 465 (2010)
46. Z. Karimi-Jaberi, M.S. Moaddeli, M. Setoodehkhah, M.R. Nazarifar, Res. Chem. Intermed. 42,
4641 (2016)
47. M. Abaszadeh, M. Seif, Res. Chem. Intermed. 41, 7715 (2015)
48. S.M. Habibi-Khorassani, M.T. Maghsoodlou, M. Shahraki, S. Talaiefar, M.A. Kazemian, J. Aboon-
ajmi, Res. Chem. Intermed. 41, 5821 (2015)
49. P. Rezaee, S. Elahi, J. Davarpanah, J. Porous Mater. 26, 541 (2019)
50. M. Safaiee, M.A. Zolfgol, F. Afsharnadery, S. Baghery, RSC Adv. 5, 102340 (2015)
51. D.-Q. Shi, N. Wu, Q.-Y. Zhuang, J. Chem. Res. 2008, 542 (2008)
52. H.-J. Wang, J. Lu, Z.-H. Zhang, Monatsh. Chem. 141, 1107 (2010)
53. J.M. Khurana, K. Vij, J. Chem. Sci. 124, 907 (2012)
54. A. Montaghami, N. Montazeri, Orient. J. Chem. 30, 1361 (2014)
Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published
maps and institutional afliations.
1 3