An efficient method for the synthesis of functionalized 4H-chromenes as optical sensor for detection of Fe3+ in ethanol

Article abstract of DOI:10.1016/j.poly.2019.03.042

An efficient method for the synthesis of functionalized 4H-chromenes via a one-pot three-component condensation reaction of a 2-hydroxybenzaldehyde with an active methylene compound and a carbon-based nucleophile in the presence of SrFe₁₂O

Full text of DOI:10.1016/j.poly.2019.03.042

Accepted Manuscript
An efficient method for the synthesis of functionalized 4H-chromenes as optical
sensor for detection of Fe3+in ethanol
Zohreh kheilkordi, Ghodsi Mohammadi Ziarani, Negar Lashgari, Alireza Badiei
PII:
S0277-5387(19)30215-3
https://doi.org/10.1016/j.poly.2019.03.042
POLY 13843
DOI:
Reference:
Polyhedron
To appear in:
Received Date:
Revised Date:
Accepted Date:
6 January 2019
16 March 2019
23 March 2019
Please cite this article as: Z. kheilkordi, G. Mohammadi Ziarani, N. Lashgari, A. Badiei, An efficient method for
the synthesis of functionalized 4H-chromenes as optical sensor for detection of Fe3+in ethanol, Polyhedron (2019),
doi: https://doi.org/10.1016/j.poly.2019.03.042
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An efficient method for the synthesis of functionalized 4H-chromenes as
optical sensor for detection of Fe³⁺in ethanol
Zohreh kheilkordia. Ghodsi Mohammadi Ziarania. Negar Lashgaria. Alireza Badieib
a Department of Chemistry, Alzahra University, Vanak Squqre, Tehran, Iran
b School of Chemistry, College of Science, University of Tehran, Tehran, Iran
Abstract
An efficient method for the synthesis of functionalized 4H-chromenes via a one-pot
three-component condensation reaction of a 2-hydroxybenzaldehyde with an active methylene
compound and a carbon-based nucleophile in the presence of SrFe12O19 as catalyst under
º
solvent-free at 80 C condition has been described. SrFe12O19 was an efficient, green, and
reusable magnetic nanoparticels as heterogeneous catalyst with the average particles size of 70
nm which can be recycled and readily separated from the reaction mixture using an external
magnet. High product yields, simple work-up procedure, solvent-free conditions and
characterization of the sensing properties of compound 4a for detection of Fe³⁺ ion are the main
advantages of this procedure. The sensing ability of compound 4a was examined upon addition
of a wide variety of cations both visually and by UV-Vis spectroscopy. The increase in UV-Vis
absorbance was linearly proportional to the concentration of Fe³⁺with a detection limit of 1.0 ×
-
⁷
10 M. Moreover, the chemosensor exhibited an obvious color change from white to yellow in
the presence of Fe³⁺ in EtOH solution.
Keywords: Chemosensor; SrFe12O19; Magnetic nanoparticles; Nanocatalyst; Three component
reaction; Solvent-free reaction; 4H-chromenes
1. Introduction
Multicomponent reactions (MCRs) as attractive method have used in the medicinal,
combinatorial and organic chemistry. Therefore, MCRs have many advantages including
minimization of chemical waste, lower environmental costs and simple experimental procedures.
1

MCRs have been widely used for the construction of various heterocyclic compounds. Among
the various green reactions, performing MCRs under solvent-free conditions are ideal for
environmentally friendly synthesis of medicinal scaffolds libraries [1-3].
4H-chromene derivatives could be applied as antimicrobial [4-6], anticancer [7-10], antioxidant
[11], and antimicrobial [12] agents. Moreover, functionalized 4H-chromenes are an important
structure in various natural products and pigments [13].
At first, Went and coworkers synthesized strontium hexaferrite or SrFe12O19 as a type of
magnetic ceramics in 1952 [14]. According to the literature, various methods have been
introduced for the preparation of SrFe12O19 magnetic nanoparticles (MNPs) including ball
milling hydrothermal [15], sol-gel [16], chemical co‐precipitation [17] and salt melt methods
[18]. The sol–gel auto‐combustion protocol provides an easy and simple path for this aim.
Iron, as one of the most important elements in biological systems, accomplishes a main role in
the function of various enzymes, hemoglobin in the human body and cellular metabolism [19,
20]. It is necessary to design simple, highly sensitive and selective chemosensors for Fe³⁺
detection and establish a method for the determination of trace Fe³⁺ ions. Before, we have
introduced a number of chemosensors for ions such as Hg²⁺, Fe³⁺, Cr³⁺ and Pb²⁺ [21-24]. In
continuation of our previous studies [25-30], the SrFe12O19 magnetic nanoparticles were used as
catalyst in the synthesis of 4H-chromene derivatives. After that, the chemosensor ability of the
4H-chromen 4a with some metal ions was investigated.
2. Experimental
2.1 Materials and Instruments
The chemical compounds which were employed in this work were obtained from Merck
Company and used with no purification. Melting points were measured by capillary tube method
with an Electrothermal 9200 apparatus. Infrared (IR) spectra were recorded from KBr disks
using a Fourier transform (FT)-IR Bruker Tensor 27 instrument. UV-Vis spectra were recorded
1
13
on an Analytik Jena Specord S600 Spectrophotometer. H NMR (500 MHz) and C NMR (125
MHz) spectra were run on a Bruker DPX using tetramethylsilane (TMS) as internal standard in
CDCl3-d6 solution. Mass spectra were analyzed using Agilent 6890 series with a FID detector,
2

HP-5, 5% phenylmethylsiloxane capillary and helium as carrier gas and Agilent 5973 network,
mass selective detector, HP-5 MS 6989 network GC system. Scanning electron microscopy
(SEM) analysis was performed with SEM (MV2300). The magnetic measurement of sample was
carried out in a vibrating sample magnetometer (VSM) (Meghnatis Daghigh Kavir Co.; Kashan
Kavir; Iran) at room temperature.
2.2. Synthesis of SrFe12O19
The SrFe12O19 as magnetic nanoparticles was synthesized and characterized according to our
previous report, and SrFe12O19, was used as a magnetic catalyst in the following reaction [24].
2.3. General procedure for the synthesis of 4H-chromene derivatives
Preparation of functionalized 4H-chromenes 4a-j was accomplished via three-component
reaction of 2-hydroxybenzaldehyde 1 (1 mmol) with an active methylene compound 2 (1 mmol)
and a carbon-based nucleophile 3 (1 mmol) in the presence of SrFe12O19 (0.01 gr) as magnetic
nanoparticles under solvent-free conditions at 80 ºC. The progress of the reaction was monitored
by TLC using EtOAc/n-hexane (2:8). After completion of the reaction, the mixture was
dissolved in hot EtOH and then, SrFe12O19 MNPs were easily removed from the reaction mixture
using an external magnet. The remained solution was cooled to gain the pure crystalline product
which was characterized using melting point and FT‐IR spectra. The new compound was
analyzed by the 1H and 13C NMR spectra.
12-(5-Bromo-2-hydroxyphenyl)-9,10-dihydro-2-hydroxy-8H-benzo[a]xanthen-11(12H)-one
º
(4j): White crystalline solid, mp: 258-261 C; IR (KBr, Cm-1) ν: 3446, 2931, 1630, 1591, 1513,
1
1481, 1379, 1264, 1231, 1187, 1129, 1096, 1066, 951,858, 808, 772. H-NMR (500 MHz,
CDCl3): δ (ppm) = 2.44-2.46 (t, 2H, CH2), 2.48-2.51 (t, 2H, CH2), 2.54-2.58 (t, 2H, CH2), 5.70
(s, 1H), 6.61(d, 1H, Ar), 6.89-6.91(d, 1H, Ar), 7.01-7.11 (d.d, 1H, Ar), 7.33-7.34 (d, 1H, Ar),
7.39-7.42(m, 2H, Ar), 7.59-7.61(d, 1H, Ar), 7.78-7.81(m, 2H, Ar), 9.50(s, 1H, OH). GC-Mass:
(m/z) 422, 403, 279, 249, 226, 165, 149, 128, 113, 55.
3

3. Results and discussion
3.1. Synthesis of 4H-chromene derivatives
Synthesis of 4H-chromenes 4a-j were done via one-pot three-component reaction of 2-
hydroxybenzaldehyde, active methylene compound and carbon-based nucleophile in the
º
presence of SrFe12O19 under solvent-free condition at 80 C (Scheme 1). Initially, the solvent
effects investigated for this reaction. Different conditions such as reflux in H2O, EtOH, H2O:
EtOH (1:1) and solvent-free systems were studied in the presence of SrFe12O19 as catalyst. It was
found that the best result was obtained in solvent-free conditions at 80 ºC (Table 1, entry 6).
Scheme 1: The optimization of reaction condition for the synthesis of 4H-chromene 4a.
Table 1:
Optimization of the reaction conditions for the synthesis of 4H-chromene 4a.
Entry
Catalyst
-
Solvent
Temp. (Co)
Reflux
Reflux
Reflux
Reflux
Reflux
80 oC
Time (h)
Yield a (%)
1
2
3
4
5
6
H2O
24
-
-
EtOH
24
-
SrFe12O19
SrFe12O19
SrFe12O19
SrFe12O19
H2O
8
70
85
85
98
EtOH
7
5
EtOH:H2O (1:1)
-
15 min
a Isolated yields
Moreover, different 4H-chromene compounds 4a–j were synthesized successfully under
solvent‐free condition in the presence of SrFe12O19 MNPs (Scheme 2). The present method was
4

simple and easy. The results were good in two terms including reaction times and yields. The
new compound was studied by FT‐IR, GC-Mass and NMR spectroscopy data.
Scheme 2: The modified this reaction in the presence of SrFe12O19 nanoparticles.
Table 2:
Synthesis of 4H-chromene derivatives 4a–j in the presence of SrFe12O19 MNPs.
Active
Mp (ºC)
[Ref.]
carbon-based methylene
nucleophile compound
Time
(min)
Yield
(%)
Entry
1
R
H
Product
Mp (ºC)
15
15
10
95
90
93
226-228 220-222 [31]
245-247 254-258 [32]
275-277 245-247 [32]
4a
2
3
3-OMe
5-Br
4b
4c
5

4
H
15
87
254-256 265-267 [31]
4d
5
6
H
H
20
15
80
85
235-237 254-258 [32]
196-198 199-201 [32]
4e
4f
7
8
H
H
12
12
89
90
258-260 267-269 [32]
212-216 208-211 [32]
243-244 254-258 [32]
4g
4h
9
H
15
10
87
95
4i
10
5-Br
258-261
New
6

4j
According to literature different organic reactions catalyzed by Strontium [33,34]. In organic
reactions strontium metal as an alkaline earth metal can active carbonyl groups via the gneration
of Sr‐O bond [35]. Initially, Sr atoms of SrFe12O19 MNPs activate both carbonyl groups of 2-
hydroxybenzaldehyde 1 and dimedone 3. Dimedone 3' reacted with 2-hydroxybenzaldehyde 1
which with removal of water to form intermediate 5. Then, via a Michael addition of the β-
naphtol 2 to the α-β unsaturated compound 5, the intermadiate 6 was achieved and then by
elimination of water, 4H-chromene 4a was obtained (Scheme 3).
7

Scheme 3: Proposed mechanism for the synthesis of 4H-chromene 4a.
This one-pot three-component reaction has been considered under two different conditions in
previous reports as shown in Table 3. The present methodology has several advantages such as
the use of inexpensive magnetic catalyst, simple procedure, shorter reaction time and excellent
yields with high purity of the products. The main advantage of the present method is, that the
magnetic nanoparticles catalyst is separable from the reaction mixture by the use of an external
magnet.
Table 3:
Comparison of different conditions in the synthesis of compound 4a.
Entry
Catalyst
TCAOS*
Solvent Conditions
Time (min)
18 h
Yield (%) Year [Ref.]
1
2
3
H2O
H2O
-
Reflux
55 ºC
80 ºC
85
95
95
2018 [31]
2018 [32]
This work
ZrOCl2.8H2O
12 h
SrFe12O19
15 min
* Tetracationic acidic organic salts
3.2. Characterization of the SrFe12O19 MNPs
The SrFe12O19 MNPs were characterized by different methods such as FT-IR, XRD, SEM, and
VSM techniques [25,26]. The shape, size, and morphology of SrFe12O19 MNPs were investigated
by X-ray difraction (XRD). The SEM image Fig. 1 of SrFe12O19 MNPs show spherical
nanoparticles with average size of 70 nm [25].
8

Fig 1. The SEM image of SrFe12O19 nanoparticles.
As shown in Fig. 2, the magnetic behavior of SrFe12O19 nanoparticles was studied using
vibrating sample magnetometry (VSM) at room temperature. The magnetic saturation of
SrFe12O19 MNPs is about 79 emu/g.
100
50
0
-50
-100
-15000
-5000
5000
15000
Applied field (Oe)
Fig 2. The room temperature hysteresis loops of SrFe12O19 MNPs.
The reusability of the catalyst was investigated in the model reaction under optimized conditions
for the preparation of compound 4a. The process of recycling was accomplished three times and
no decrease in activity was apperceived. As shown in Table 4, the yields for the three times were
to be 95, 89, and 80 %, respectively.
Table 4:
Reuse of SrFe12O19 MNPs for the synthesis of 4a.
Entry
Time (min)
Yield (%)
1
2
3
15
15
15
95
89
80
3.3. Spectrophotometric studies
Among compounds synthesized, compound 4a was studied. According to Fig 4, for this purpose,
the sensing ability of 2.5 mL of chemosensor 4a (10ˉ⁴M) was investigated by UV–Vis
spectroscopy in EtOH solution with various cations, including Ag⁺, Cd²⁺, Co²⁺, Cr³⁺, Cu²⁺, Fe³⁺,
9

Fe²⁺, Hg²⁺, Mn²⁺, Ni²⁺, Pb²⁺, Na⁺, Al³⁺, Mg²⁺, K⁺, Ca²⁺ and Zn²⁺ at 25 ºC. Most of the metal
cations showed no serious influence on the UV-Vis absorption spectra of the chemosensor 4a
solution, while Fe³⁺ ion produced additional peaks at 342 nm attended with the color change
from white to yellow. As shown in Fig 3, such a characteristic color change and absorption
response indicate that chemosensor 4a can be used as a sensitive and colorimetric ‘naked-eye’
chemosensor 4a for Fe³⁺ ion.
Fig 3. Color variations of 2.5 mL 10ˉ⁴ M EtOH solution of chemosensor 4a in the presence of
different cations 100 μL, 10-² M.
Fig 4. Absorption spectra of (2.5 mL, 10−⁴ M EtOH solution) of chemosensor 4a upon addition
of different cations (100 μL, 10-²M).
10

The competition experiment, which was carried out by adding Fe³⁺ to chemosensor 4a in the
presence of other metal ions, showed that the Fe³⁺ induced UV-Vis response was not interfered
by the commonly coexistent ions. According to Fig 5, the results suggested that chemosensor 4a
showed a remarkable selectivity toward Fe³⁺ over other competitive ions.
Fig 5. Selectivity of chemosensor 4a (2.5 mL, 10-⁴M EtOH solution) for Fe³⁺ in the presence of
different metal cations (100 μL, 10-² M).
For investigation of concentration effect on the absorption of compound 4a, the absorption
titration experiment was performed by addition of 50 μL of 1×10-³ M solution of Fe³⁺ to 2.5 mL
10-⁴M of compound 4a. According to Fig 6, as the concentration of Fe³⁺ ion is gradually
increased, the absorption intensity of compound 4a at 342 nm increases. Also as demoustrated in
Fig 7, the absorption chart against the concentrations of Fe³⁺ ions showed a linear relationship.
As Fe³⁺ ion can be detected by changes in the concentration. The detection limit of 1.0 × 10ˉ⁷ M
was calculated for chemosensor 4a in EtOH on the basis of 3σ/m, where σ is the standard
deviation and m is the slope of the calibration curve.
11

Fig 6. Absorption spectra of compound 4a (2.5 mL, 10⁻⁴) upon the addition of different
concentrations of Fe³⁺ (2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 and 40)
× 10-5 M.
2.5
y = 0.0804x - 1.0929
2
R² = 0.993
1.5
1
0.5
0
22
27
32
37
42
Fe³⁺/Chemosensor 4a*10¯⁵
Fig 7. Absorbance at 342 nm as a function of Fe³⁺ ion concentration.
12

The proposed mechanism for Fe³⁺ ione addition to chemosensor 4a was shown in Scheme 4. It is
proposed that the absorption enhancement in the presence of Fe³⁺ is probably due to the
interaction of chemosensor 4a with Fe³⁺ chemosensor 4a is most likely to bind with Fe³⁺ ion via
the corresponding hydroxyl and carbonyl groups.
Scheme 4: The proposed mechanism for Fe³⁺ ion addition to chemosensor 4a.
3.4. Comparison of chemosensor 4a with other colorimetric chemosensors
The chemosensor 4a has been compared with some other recently reported colorimetric
chemosensors (Table 4). This chemosensor has some advantages over the other works. In our
work, chemosensor 4a has been prepared by a convenient, efficient and ecofriendly method and
without chromatographic purification. It has very quick response time and wide linear response
range. The chemosensor property of compound 4a has been investigated in EtOH as a green
solvent. The detection limit for Fe³⁺ in comparison with other works were calculated at 1.0×10ˉ⁷
M .
Table 4:
Comparison of compound 4a with some reported chemosensors.
Entry
1
Structure
Solvent
Detection Limit Year [Ref.]
5.2610-6
2009 [36]
MeOH:H2O (1:1)
13

2
MeOH:H2O (4.5:5.5)
2012 [37]
5×10ˉ⁶
3
4
DMSO:H2O (1:1)
EtOH
2014 [38]
This work
3.49×10ˉ⁶
1.0×10ˉ⁷
Conclusion
In conclusion, we have developed a convenient, efficient, and ecofriendly method for the
synthesis of 4H-chromenes using SrFe12O19 through the one-pot three-component reaction of
salicylaldehydes, active methylene compounds and a carbon-based nucleophile under solvent
free conditions at 80 ºC. Furthermore colorimetric and chemosensor ability of 4H-chromenes for
a wide range of metal cations was successfully investigated. The chemosensor 4a could act as a
colorimetric sensor for detection of Fe³⁺ ion. The detection limit for Fe³⁺ was calculated as 1.0 ×
10ˉ⁷ M .
Acknowledgments
We gratefully acknowledge the financial support from the Research Council of Alzahra
University and the University of Tehran.
Conflict of interest
The authors have declared no conflict of interest.
14

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Graphical abstract
18