Magnetic nanoparticles grafted l-carnosine dipeptide: remarkable catalytic activity in water at room temperature

Article abstract of DOI:10.1007/s13738-017-1157-2

Modification of magnetic nanoparticle surface with l-carnosine dipeptide was developed using a simple chemical process. In order to synthesize this catalyst system, first, magnetic nanoparticles were modified with vinyl groups using trimethoxy(vinyl)silan

Full text of DOI:10.1007/s13738-017-1157-2

J IRAN CHEM SOC
DOI 10.1007/s13738-017-1157-2
ORIGINAL PAPER
Magnetic nanoparticles grafted l‑carnosine dipeptide:
remarkable catalytic activity in water at room temperature
Farhad Panahi1,2 · Foroogh Bahrami1 · Ali Khalaf‑Nezhad1
Received: 27 March 2017 / Accepted: 12 June 2017
© Iranian Chemical Society 2017
Abstract Modifcation of magnetic nanoparticle surface
with l-carnosine dipeptide was developed using a sim-
ple chemical process. In order to synthesize this catalyst
system, frst, magnetic nanoparticles were modifed with
vinyl groups using trimethoxy(vinyl)silane. Next, the vinyl
groups were oxidized with H2O2 to give the epoxy-func-
tionalized MNPs. Reaction of l-carnosine with epoxide
rings via amino group resulted in the functionalization of
MNPs surface with l-carnosine, covalently. To explore high
catalytic activity of this material, l-carnosine grafted on
magnetic nanoparticles (Fe3O4@SiO2@LCar; l-CarMNP)
was used as a highly effcient heterogeneous nano-organo-
catalyst in a multicomponent reaction in aqueous medium
at room temperature. It was reusable at least for eight times
without a signifcant decrease in its catalytic activity. The
catalytic activity of l-CarMNP was compared with other
magnetic nano-organocatalyst, and results demonstrate
that l-CarMNP has high catalytic activity related to others
tested.
Keywords Magnetic nanoparticles · l-carnosine ·
Dipeptide · Heterogeneous catalyst · Organocatalyst ·
Water
Introduction
Organocatalysis is of signifcant relevance for contempo-
rary organic chemistry, playing a key role in organic synthe-
sis [1–3]. Different small molecules have been introduced
as organocatalyst to be used in many organic reactions
[4–9]. Amino acids and peptides are an important class of
organic molecules which have been widely used in organic
synthesis as organocatalyst or ligand in transition metal
catalysis [10–16]. Due to many advantages, amino acid
and peptide organocatalysts are able to be used as hetero-
geneous and thus required a solid support of metal oxides
or polymers which both of them are established to be suit-
able for this purpose [17–24]. Although a number of het-
erogeneous organocatalysts based on amino acid have been
synthesized, catalysis under aqueous conditions is desirable
for various reasons, particularly due to the fact that amino
acids have high solubility in water and so offer high activ-
ity [15]. This feature also avoids the unfavorable organic
wastes, which readily occurs under organic solvent condi-
tions, reducing the environmental friendly of the catalysis
process [25, 26]. In the presence of heterogeneous cata-
lysts and in aqueous environments, the solubility of reac-
tants represents challenges in reserve effciency, exacting
because of low interaction of catalyst and substrates [27,
28]. On the other hand, magnetic nanoparticles (MNPs)
have diverse “solubilities” in aqueous and non-aqueous
solvents, depending on their size and the type of modify-
ing organic moiety. The ability to be soluble or dispersed
(for short or long periods) and the constancy of MNPs in
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-017-1157-2) contains supplementary
material, which is available to authorized users.
* Farhad Panahi
fpanahi@aut.ac.ir
* Ali Khalaf-Nezhad
khalaf@susc.ac.ir
1
Department of Chemistry, College of Sciences, Shiraz
University, Shiraz 71454, Iran
2
Department of Polymer Engineering and Color Technology,
Amirkabir University of Technology, Tehran, Iran
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J IRAN CHEM SOC
liquid phase are very important factors in catalysis appli-
cations [29–34]. In this way, extensive efforts have been
made to attain a higher solubility of MNPs, especially in
aqueous media [35]. Highly soluble MNPs-based catalysts
have much greater catalyst activity in organic reactions and
act same as pseudo-homogeneous catalysis. With increase
in water well-matched organic moieties on the surface of
MNPs, their water solubility is enhanced. Amino acids and
peptides due to the polar organic functional groups have
this capability to improve the water solubility of MNPs
[36–39]. In other side, amino acids and peptides have
remarkable catalyst activity in organic transformations.
Thus, by functionalization of MNPs surface with amino
acids and peptides it is possible to synthesize an effcient
heterogeneous magnetic nano-organocatalyst to accom-
plish organic reactions in water. Previously, we reported
an effcient strategy on modifcation of MNPs surface with
organic moieties using the ring opening of generated oxiran
rings on MNPs surface with nucleophile organic molecules
[40–44]. This strategy opens up our hand to graft organic
molecules on MNPs surface simply. In this study, the cata-
lytic activities of three different types of heterogeneous
magnetic nano-organocatalyst were evaluated in a multi-
component reaction in aqueous media (Scheme 1).
Results and discussion
For synthesis of l-CarMNP, frst, trimethoxy(vinyl)silane
was tethered to the surface of iron oxide nanoparticles, and
a subsequent epoxidation of the vinyl group with H2O2
gave the desired epoxy-functionalized MNPs. l-Carnosine
has an amino group which can react with epoxide ring and
open it, because it has nucleophilic power [46]. Ring open-
ing of oxiran rings on the surface of MNPs with l-carno-
sine resulted in the production of Fe3O4@SiO2@LCar
(l-CarMNP) catalyst. The l-CarMNP catalyst was char-
acterized using FTIR, SEM, XRD, and elemental analysis
techniques. A comparison between the FTIR spectra of
Fe3O4, Fe3O4@SiO2, VMNP, l-carnosine, and l-CarMNP
material was made, and results show the existence of l-car-
nosine moiety in the structure of magnetic nanoparticles
(see ESI). In accordance with FTIR spectra, the peak at
1635 cm−1 is confrmed the presence of l-carnosine in the
structure of l-CarMNP catalyst because this peak attributed
to the C=O bond [45]. Also, distinguished peaks observed
at 2923, 2314, 894, and 795 cm−1 establish the presence
of l-carnosine moiety in the structure of synthesized cata-
lyst [47]. The SEM image of the synthesized catalyst was
recorded and is represented in Fig. 1. Considering the SEM
image, it is clear that the l-CarMNPs are regular in shape
and approved in an approximately good arranged mode.
This image also established this point that the l-CarMNPs
are created with near sphere-shaped morphology. Accord-
ing to the particle analyzer result, the average diameter of
the synthesized l-CarMNPs based on the proposed proce-
dure is estimated to be about 18–30 nm.
The LPMNP [40] and L-CyMNP [41] catalysts were
previously synthesized, characterized, and used in
organic transformations. In this work, l-carnosine grafted
on magnetic nanoparticles (l-CarMNP) was synthesized
according to our previous strategy and introduced as an
effcient heterogeneous organocatalyst in organic trans-
formations [45].
Scheme 1 The chemical structures of three different MNPs-supported organocatalyst
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J IRAN CHEM SOC
Fig. 1 The SEM images of l-CarMNP catalyst
The XRD pattern of the l-CarMNP catalyst also shows
the magnetic nanoparticle nature of catalyst after modif-
cation (Fig. 2).
The peaks are indexed as the (220), (311), (400), (422),
(511), (440), and (533) planes of the Fe3O4 nanoparticles
(JCPDS no. 19-0629) [48]. The strongest peaks of the
Fig. 2 The XRD pattern of
l-CarMNP catalyst
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J IRAN CHEM SOC
XRD pattern correspond to SiO2, demonstrating the core–
shell structure of material. Also, the elemental analysis of
the l-CarMNP material demonstrates the presence of C,
N, and H which confrms the presence of l-carnosine on
the surface of magnetic nanoparticles. According to the
data obtained from elemental analysis, it is concluded that
there is about 0.5 mmol of l-carnosine per 1 g of material
using our procedure (catalyst loading is 0.5 mmol/g). The
functional groups in the structure of l-CarMNP are car-
boxylic acid, amino group, hydroxy group, amide bond,
and imidazole ring which can act as organocatalytic cent-
ers for promotion of an organic reaction [16]. In order to
show the catalytic activity of l-CarMNP in organic reac-
tions, it was used as a magnetic reusable organocatalyst in
a multicomponent reaction (MCR). MCRs are known as
an applicable strategy in organic synthesis for synthesis of
complex molecules from simple starting materials [49–54].
The most important classes of organic molecules that can
be synthesized using MCRs are acridine and xanthene
derivatives. Acridine and xanthene derivatives have impor-
tant biological activities such as fungicidal, antimicrobial,
anti-parasitic, anti-infammatory, anticancer, and anti-viral
activities [55–58]. A reaction model was selected and the
catalytic activity of the L-CyMNP, LPMNP, and l-CarMNP
catalysts was evaluated (Table 1).
As given in Table 1, in the absence of catalyst no product
was observed (entry 1). In the presence of Fe3O4@SiO2 as
catalyst, about 18% of product of 4a was detected (Table 1,
entry 2). Then, we applied the l-CarMNP material as cata-
lyst for this reaction and 95% of product was obtained after
2 h (Table 1, entry 3). These results were suitable but were
not satisfactory for us because we followed the accomplish-
ment of reaction in water as green solvent at room tempera-
ture conditions. Thus, we checked reactions under these
conditions, and interestingly, it was observed that in water
solvent at room temperature after 6 h about 92% of prod-
uct was produced. These results were very exciting for us,
demonstrating remarkable catalytic activity of l-CarMNP.
Different amounts of catalyst were checked in order to fnd
optimized catalyst loading. It was observed that by increas-
ing the amount of catalyst the yield of product remained
unchanged and as result of reducing the amount of catalyst
Table 1 Optimization of reaction conditions for synthesis of acridines
Entry
Catalyst (mol %)
Solvent
T (°C)
Time (h)
Yield 4a (%)a
1
None
EtOH
EtOH
EtOH
H2O
80
80
80
80
rt
12
12
2
0
18c
95
93
92
93
89
60
55
80
30
73
20
75
60
30
28
2
Fe3O4@SiO2
l-CarMNP (5)
l-CarMNP (5)
l-CarMNP (5)
l-CarMNP (6)
l-CarMNP (4)
l-CarMNP (5)
l-CarMNP (5)
l-CarMNP (5)
L-CyMNP (5)
L-CyMNP (5)
LPMNP (5)
LPMNP (5)
l-carnosine
3
4
2
5
H2O
6
6
H2O
rt
6
7
H2O
rt
8
8
CH3CN
PhCH3
DMF
H2O
70
80
100
rt
12
12
12
12
6
9
10
11
12
13
14
15
16
17
H2O
80
rt
H2O
12
5
H2O
80
rt
H2O
12
12
12
l-Proline
H2O
rt
l-Cysteine
H2O
rt
Reaction conditions: 1a (1 mmol), 2a (1 mmol), 3a (2.2 mmol), and solvent (3 mL)
a
Isolated yield
b
0.05 g of catalyst was used
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J IRAN CHEM SOC
Table 2 Synthesis of diverse xanthene and acridine derivatives using l-CarMNP under optimized conditionsa
Entry
Ar1
X
Prod.
Time (h)
Yield (%)b
1
3-NO2-Ph
4-Cl-Ph
4-F-Ph-N
4b
4c
4d
4e
4f
6
6
89
92
94
92
90
91
89
90
92
88
90
85
87
1
4-Cl-Ph-N
2
4-NO2-Ph
4-Cl-Ph
4-OMe-Ph-N
5
3
4-OMe-Ph-N
5
4
4-Cl-Ph
4-F-Ph-N
6
5
4-NO2-Ph
4-OH-Ph
4-NO2-Ph
4-Cl-Ph
4-F-Ph-N
4g
4h
4i
6
6
4-OMe-Ph-N
8
7
O
O
O
O
O
O
6
8
4j
6
9
3-Cl-Ph
4k
4l
8
10
11
12
a
4-F-Ph
7
4-OH-Ph
3-CH3-Ph
4m
4n
12
10
Reaction conditions: aldehyde (1 mmol), amine (1 mmol), 3a (2.2 mmol), catalyst (5 mol %), and solvent (3 mL)
Isolated yield
b
reduction in yield was observed (Table 1, entries 6, 7). The
reaction yields for these catalyst systems were in the range
of 75% at higher temperate. Interestingly, l-carnosine in
comparison with two other amino acids (l-cysteine and
l-proline) has higher activity in water at room tempera-
ture. More importantly, the catalytic activity of l-carnosine
is less than supported counterpart, demonstrating syner-
getic effect between MNPs support and l-carnosine. Fur-
thermore, the separation of product from reaction mixture
is diffcult. These results also show that the connection of
l-carnosine via NH group to the surface of magnetic nan-
oparticles improves its catalytic activity and applicability.
activity of l-CarMNP in other solvents was also tested,
but a signifcant decreasing in reaction yield was observed
(Table 1, entries 8–10).
A
comparison between the catalytic activity of
l-CarMNP and some other catalyst systems was made,
and results demonstrating amazing catalytic activity of
l-CarMNP related to other catalyst systems were investi-
gated (Table 1, entries 11–17). For example, less than 30%
of product was isolated using LPMNP [40] and L-CyMNP
[41] catalysts at room temperature in water solvent. The
Fig. 3 Catalytic recovery times
of l-CarMNP catalyst for eight
runs
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J IRAN CHEM SOC
(A)
(B)
(C)
Fig. 4 The chemical structures of l-CarMNP catalyst and its catalytic sites
The catalytic activity of l-CarMNP was tested for synthe-
sis of diverse xanthene and acridine derivatives under opti-
mized conditions (Table 2).
The optimized structure of organic part of l-CarMNP
shows that there are possibilities of two internal hydrogen
bonding interactions in this molecule (Fig. 4) [66].
As given in Table 2, by selection of different amines
and aldehyde it is possible to synthesize diverse deriva-
tives of this class of acridine and xanthene in good to excel-
lent yields by using l-CarMNP catalyst. Both amines and
aldehyde with electron-donating and electron-withdrawing
groups were used, and all of the products were obtained in
high yields. Also, the reusability of l-CarMNP was checked
in model reaction (synthesis of 4a) under optimized reac-
tion conditions (Table 1, entry 5), and it was reusable at
least for eight times without signifcant decreasing in its
catalytic activity (Fig. 3).
What is important here is that which functionality in the
structure of l-CarMNP catalyst system is engaged in the
activation of organic components to undergo in the reaction.
The catalytic activity action of amino acids is essentially
originated from amino and carboxylic acid groups [59, 60].
Carboxylic acid group can protonate functionalities in mole-
cule that can abstract hydrogen, resulting in the activation of
molecule [61]. The amino group has nucleophilicity power
and can help in the activation of molecules via iminium for-
mation and Michael addition [62]. It should be mentioned
that both amino and carboxylic acid groups can activate
molecules through hydrogen bonding [63]. Other functional
groups in the structure of amino acid may participate in the
activation of molecule in parallel with amino acid group. By
the use of peptides as catalyst, in addition to the mentioned
functions associated with amino acids the hydrogen bond-
ing of amid bonds is very important factor in the activation
of molecules [64]. Also, peptides can act as enzymes and
participate in the activation of molecules by interaction of
organic groups and also structure folding [65].
It is obvious that the functional groups of l-CarMNP
that are peptide bonds, carboxylic group, imidazole ring,
amino and hydroxy groups underwent in catalytic induction
of molecules in order to participate in reaction. These func-
tionalities can engage in the activation of molecule together
and have synergetic effect in accomplishment of a reaction
same as enzymes in biosystems [64]. The l-CarMNP cata-
lyst has several hydrogen bond donor sites and can cata-
lyze these MCRs using hydrogen bonding catalysis. The
hydrogen bonding catalysis activity of l-CarMNP can be
confrmed by deactivation test using urea [67]. Interest-
ingly, addition of some urea (equal to mol % of catalyst) in
the reaction mixture completely stops the reaction progress,
demonstrating that the peptide nature of the catalyst and
hydrogen bonding of l-CarMNP is important in its cata-
lytic activity.
Conclusions
In summary, l-carnosine was grafted to magnetic nano-
particle surface chemically using an effcient synthetic
approach, and it was used as a new nano-organocatalyst
for reaction in water media at room temperatures. The
catalytic activity of l-CarMNP was compared with some
other catalyst systems, and results demonstrate that it has
high activity in aqueous reaction media at room tempera-
ture in comparison with others. The catalyst was synthe-
sized according to a well-defned reaction pathway using
functionalization of magnetic nanoparticle surface via
oxiran chemistry. Also, l-CarMNP is a magnetic reusable
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J IRAN CHEM SOC
organocatalyst which can be separated from the reaction
mixture using an external magnetic feld and has high
potential to be used in other organic transformations in
future.
was stirred by mechanical stirrer under N2 gas for 30 min.
20 mL of tetraethyl orthosilicate (TEOS) was added to the
mixture next and then the solution was stirred for 12 h at
30 °C. After the specifed time, 10 mL of ammonia was
added and the solution was stirred continuously for another
12 h. The precipitation was washed with ethanol (3 × 10)
and collected by an external magnetic feld. The desired
product was dried under vacuum overnight.
Experimental section
General
Synthesis of vinyl magnetic nanoparticle (VMNP)
Chemicals were purchased from Fluka and Aldrich
Chemical Companies and used without further purifca-
tion. 1H and 13C NMR spectra were recorded on a Bruker
Avance 250 MHz spectrometer in DMSO-d6 or CDCl3
solution with TMS as an internal standard. FTIR spec-
troscopy (Shimadzu FTIR 8300 spectrophotometer) was
employed for the characterization of the compounds.
Melting points were determined in open capillary tubes in
a Barnstead Electrothermal 9100 BZ circulating oil melt-
ing point apparatus. The reaction monitoring was accom-
plished by TLC on silica gel PolyGram SILG/UV254
plates. X-ray diffraction (XRD, D8, Advance, Bruker,
axs) was employed for characterization of the l-CarMNP
catalyst. The scanning electron micrograph (SEM) for the
l-CarMNP catalyst was obtained by SEM instrumenta-
tion (SEM, XL-30 FEG SEM, Philips, at 20 kV).
In a three-necked fask (100 mL) containing 70 mL of
dry chloroform, 5 g of Fe3O4@SiO2 was charged. Then,
trimethoxy(vinyl)silane (0.44 g, 3 mmol) was added to the
reaction mixture dropwise over a period of 5 min at room
temperature. When the addition was completed, the mixture
was stirred for 12 h under refux condition. Then, the reac-
tion mixture was fltered and the obtained solid was dried
in a vacuum at 50 °C to obtain a vinyl MNP (VMNP) sub-
strate (5.31 g). The presence of vinyl group on the surface
of MNPs was recognized using bromine test. The amount
of supported vinyl groups on the surface of MNPs was
determined using elemental analysis which was in good
agreement with the value that estimated with an iodine
test. The results showed that there are 5.6 mmol/g ethylene
groups on the surface of MNPs.
Synthesis of MNP‑oxiran (MNPO)
Procedure for synthesis of l‑carnosine‑modifed
magnetic nanoparticles (l‑carnosine MNPS)
A solution of 5 g vinyl MNP (VMNP) and H2O2 30%
(20 mL) were stirred at 50 °C for 12 h. The resulting pre-
cipitate was fltered through a Celite pad, washed with
water, and dried in a vacuum to afford the MNPO sub-
strate (5.52 g). The presence of ethylene oxide group on
the silica substrate was detected by the bright pink color
of the phenolphthalein (as indicator) when air passed
through an aqueous solution of NaCl. The quantitative
amount of oxirane groups on the substrate was identifed to
be 5.4 mmol/g using elemental analysis, which it showed
that a remarkable amount of vinyl groups is converted to
oxirane under applied conditions.
Preparation of Fe3O4 nanoparticles
Magnetic nanoparticles were prepared via co-precipita-
tion of Fe(III) and Fe(II) ions in the presence of sodium
hydroxide. In a canonical fask, a mixture of FeCl2.2H2O
(16 mmol, 2.6 g) and FeCl3.6H2O (30 mmol, 8.1 g) was
dissolved in 100 mL of deionized water. Then, the pH of
this solution was increased to 11 by adding a 3 M solu-
tion of NaOH as dropwise (in a period of 5 min) at 40 °C.
Subsequently, the temperature of mixture was enhanced
to 80 °C and the solution was stirred for 20 min in this
temperature. The magnetic nanoparticles as a dark solid
were isolated from the solution by magnetic separation
and washed with deionized water until pH 7 reached.
Synthesis of l‑carnosine magnetic nanoparticles (l‑carnos‑
ine MNPs) catalyst
For the synthesis of l-carnosine MNPs catalyst, 0.6 g of
l-carnosine was added to a prepared solution containing 5 g
of MNPO in 30 mL chloroform. Then, two or three drops
of Et3N were added to the reaction mixture. Subsequently,
the mixture was stirred for 12 h under refux condition.
The resulting precipitate was fltered through a Celite pad,
washed with water, and dried in a vacuum.
Preparation of Fe3O4@SiO2 nanoparticles
Fe3O4@SiO2 nanoparticles were prepared based on the lit-
erature with some modifcation: 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 added. Then, the mixture
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J IRAN CHEM SOC
General procedure for synthesis of xanthene derivatives
using l‑CarMNP catalyst
CDCl3/TMS): 1.10 (s, 12H), 2.21 (s, 4H), 2.46 (s, 4H), 4.7
(s, 1H), 7.18 (d, J = 2.5 Hz, 2H), 7.21 (d, J = 2.5 Hz, 2H),
7.25 (d, J = 2.5 Hz, 4H). 13C NMR (62.5 MHz, CDCl3/
TMS): δ = 51.8, 53.6, 55.3, 60.3, 64.2, 64.9, 141.2, 143.0,
145.3, 148.5, 150.1, 153.4, 156.1, 156.3, 158.7, 162.4,
190.8. Anal. Calcd for: C29H29Cl2NO2: C, 70.44; H, 5.91;
N, 2.83. Found: C, 70.35; H, 5.84; N, 2.78.
A mixture of 5,5-dimethyl-cyclohexane-dione (0.308 g,
2.2 mmol) and aldehyde (1 mmol) in l-CarMNP
(5 mol %) at room temperature was stirred in a round-
bottomed fask for the specifed time for each compound.
After completion of the reaction was confrmed by TLC,
the l-CarMNP catalyst was isolated from the reaction
mixture using an external magnetic feld. The catalyst
was washed with hot ethanol (2 × 5 mL) and used for
next run. The products were purifed by recrystallization
in ethanol.
10‑(4‑Methoxyphenyl)‑3,3,6,6‑tetrame‑
thyl‑9‑(4‑nitrophenyl)‑3,4,6,7,9,10‑hexahydroacrid‑
ine‑1,8(2H,5H)‑dione (4d)
Yield: (94%, 470 mg), white crystals, mp 264–265 °C.
IR (KBr): 2934, 2849, 2360, 1676, 1655, 1508, 1448,
1
1365, 1165, 1141, 1087, 1976, 887,710 cm−1. HNMR
General procedure for synthesis of acridine in the presence
of l‑CarMNP catalyst
(250 MHz, CDCl3/TMS): 0.67 (s, 4H), 0.86 (s, 4H), 2.47
(s, 12H), 3.83 (s, 3H), 5.09 (s, 1H), 7.10 (d, J = 10 Hz,
2H), 7.35 (d, J = 7.5 Hz, 2H), 7.54 (d, J = 10 Hz, 2H),
8.11 (d, J = 7.5 Hz, 2H). 13C NMR (62.5 MHz, CDCl3/
TMS): δ = 29.3, 29.8, 47.1, 49.2, 58.0, 61.8, 71.4, 136.4,
140.5, 144.0, 149.4, 150.4, 151.0, 152.9, 154.9, 155.7,
156.7, 190.8. Anal. Calcd for C30H32N2O5 (500.23); C,
71.98; H, 6.44; N, 5.60. Found: C, 71.93; H, 6.38; N, 5.55.
In a round-bottomed fask, a mixture of aldehyde (1 mmol),
dimedone (0.308 g, 2.2 mmol), amine (1 mmol), and
l-CarMNP (5 mol %) was stirred at room temperature for
the specifed time for each compound. When the reaction
was completed (confrmed by TLC), the catalyst was sepa-
rated using an external magnetic feld and it was washed
with hot ethanol (2 × 5 mL). The separated solid after fl-
tration was recrystallized in ethanol to obtain pure product.
9‑(4‑Chlorophenyl)‑10‑(4‑methoxyphenyl)‑3,3,6,6‑tetrame‑
thyl‑3,4,6,7,9,10‑hexahydroacridine‑1,8(2H,5H)‑dione (4e)
Yield: (92%, 450 mg), white crystals, mp 233–234 °C.
IR (KBr): 2934, 2879, 2360, 1716, 1675, 1508, 1438,
Spectral data of synthesized compounds
1
1365, 1165, 1141, 1087, 1916, 897,690 cm−1. HNMR
10‑(4‑Fluorophenyl)‑3,3,6,6‑tetrame‑
thyl‑9‑(3‑nitrophenyl)‑3,4,6,7,9,10‑hexahydroacrid‑
ine‑1,8(2H,5H)‑dione (4a)
(250 MHz, CDCl3/TMS): 0.94 (s, 12H), 1.80 (s, 4H), 1.87
(s, 4H), 3,91 (s, 3H), 5.22 (s, 1H), 7.2(d, J = 7.5 Hz, 2H),
7.10 (d, J = 7.5 Hz, 2H), 7.19 (d, J = 7.5 Hz, 2H), 7.34
(d, J = 7.5, 2H). 13C NMR (62.5 MHz, CDCl3/TMS):
δ = 29.3, 29.8, 44.1, 47.1, 49.2, 53.5, 70.8, 134.8, 136.4,
139.3, 140.5, 144.0, 149.4, 150.4, 151.0, 152.9, 154.9,
188.2. Anal. Calcd for: C30H32ClNO3 (489.2): C, 73.53; H,
6.58; N, 2.86. Found: C, 73.47; H, 6.52; N, 2.80.
Yield: 89% (4.33 g), white crystals, mp 243–244 °C. IR
(KBr): 2984, 2849, 2370, 1712, 1695, 1578, 1488, 1365,
1
1141, 1110, 837,718 cm−1. HNMR (250 MHz, CDCl3/
TMS): 0.97 (s, 12H), 2.16 (s, 4H), 2.20 (s, 4H), 5.35 (s,
1H), 7.26 (s, 3H), 7.42 (t, J = 7.5, 2H), 7.95–8.00 (m,
2H), 8.18 (s, 1H). 13C NMR (62.5 MHz, CDCl3/TMS):
δ = 33.4, 37.3, 44.0, 44.2, 57.4, 61.2, 132.4, 132.9,
139.5, 140.1, 141.2, 143.0, 144.1, 145.3, 148.5, 149.8,
150.1, 150.8, 153.4, 189.7. Anal. Calcd for: C29H29FN2O4
(487.2): C, 71.30; H, 5.98; N, 5.73. Found: C, 71.21; H,
5.90; N, 5.64.
9‑(4‑Chlorophenyl)‑10‑(4‑fuorophenyl)‑3,3,6,6‑tetrame‑
thyl‑3,4,6,7,9,10‑hexahydroacridine‑1,8(2H,5H)‑dione (4f)
Yield: (90%, 429 mg), white crystals, mp 234–235 °C. IR
(KBr): 2954, 2869, 2360, 1666, 1645, 1578, 1488, 1365,
1
1195, 1141, 1087, 1010, 887 cm−1. HNMR (250 MHz,
CDCl3/TMS): 1.09 (s, 12H), 2.18 (s, 4H), 2.43 (s,
4H), 4.69 (s, 1H), 7.19 (s, 4H), 7.23 (s, 4H). 13C NMR
(62.5 MHz, CDCl3/TMS): δ = 44.4, 44.8, 47.5, 50.5,
57.7, 62.3, 130.1, 131.4, 131.7, 134.3, 137.3, 139.4, 143.5,
145.1, 147.1, 162.0, 191.8. Anal. Calcd for C29H29ClFNO2
(477.19): C, 72.87; H, 6.12; N, 2.93. Found: C, 72.79; H,
6.03; N, 5.84.
9,10‑Bis(4‑chlorophenyl)‑3,3,6,6‑tetrame‑
thyl‑3,4,6,7,9,10‑hexahydroacridine‑1,8(2H,5H)‑dione (4c)
Yield: (92%, 389 mg), white crystals, mp 204–205 °C. IR
(KBr): 2974, 2819, 2360, 1710, 1685, 1578, 1488, 1365,
1195, 1141, 1067, 910, 837,768 cm−1. 1HNMR (250 MHz,
1 3

J IRAN CHEM SOC
10‑(4‑Fluorophenyl)‑3,3,6,6‑tetrame‑
thyl‑9‑(4‑nitrophenyl)‑3,4,6,7,9,10‑hexahydroanthra‑
cene‑1,8(2H,5H)‑dione (4g)
(250 MHz, CDCl3/TMS): 1.10 (s, 12H), 2.20 (s, 4H),
2.46 (s, 4H), 4.69 (s, 1H), 7.18- 7.24 (m, 4H). 13C NMR
(62.5 MHz, CDCl3/TMS): δ = 29.2, 36.4, 40.8, 46.2, 50.7,
55.6, 130.2, 141.7, 150.6, 152.0, 157.0, 162.2. 189.7. Anal.
Calcd for C23H25ClO3 (384.15): C, 71.77; H, 6.55. Found:
C, 71.70; H, 6.48.
Yield: (91%, 443 mg), white crystals, mp 233–234 °C. IR
(KBr): 2954, 2829, 2370, 1715, 1695, 1578, 1488, 1365,
1
1195, 1141, 1110, 837, 758 cm−1. HNMR (250 MHz,
CDCl3/TMS): 1.12 (s, 12H), 1.55 (s, 4H), 2.49 (s,
4H), 4.82 (s, 1H), 7.24 (d, J = 7.5 Hz, 4H), 7.46 (d,
J = 7.5 Hz, 2H), 8.09 (d, J = 7.5 Hz, 2H). 13C NMR
(62.5 MHz, CDCl3/TMS): δ = 33.4, 37.3, 39.0, 51.8,
58.2, 60.3, 132.4, 139.5, 140.1, 143.0, 145.3, 145.8,
149.8, 153.4, 154.7, 156.1, 191.9. Anal. Calcd for:
C30H30FNO4 (487.2): C, 73.90; H, 6.20; N, 2.87. Found:
C, 73.82; H, 6.14; N, 2.81.
9‑(3‑Chlorophenyl)‑3,3,6,6‑tetramethyl‑3,4,5,6,7,9‑hexahy‑
dro‑1H‑xanthene‑1,8(2H)‑dione (4k)
Yield: (88%, 338 mg), white crystals, mp 202–203 °C. IR
(KBr): ν = 2954, 2869, 2314, 1720, 1604, 1473, 1419,
1380, 1288, 1226, 1141, 1072, 987, 948, 856, 748, 694,
1
655 cm−1. H NMR (250 MHz, CDCl3/TMS): 1.10 (s,
12H), 2.17 (s, 4H), 2.40 (s, 4H), 5.62 (s, 1H), 7.14–7.21
(m, 1H), 7.26 (s, 1H), 7.37 (d, J = 7.5 Hz, 2H). 13C NMR
(62.5 MHz, CDCl3/TMS): δ = 32.0, 32.1, 40.5, 42.2, 44.7,
45.8, 126.4, 126.8, 127.6, 129.3, 130.3, 142.3, 154.2,
158.8, 189.7. Anal. Calcd for C23H25ClO3(384.15): C,
71.77; H, 6.55; Cl, 9.21; O, 12.47.
9‑(4‑Hydroxyphenyl)‑10‑(4‑methoxyphenyl)‑3,3,6,6‑tetra‑
methyl‑3,4,6,7,9,10‑hexahydroacridine‑1,8(2H,5H)‑dione
(4h)
Yield: (89%, 434 mg), white crystals, mp 265–266 °C. IR
(KBr): 2974, 2859, 2390, 1692, 1655, 1538, 1468, 1315,
9‑(4‑Fluorophenyl)‑3,3,6,6‑tetramethyl‑3,4,5,6,7,9‑hexahy‑
dro‑1H‑xanthene‑1,8(2H)‑dione (4l)
1
1141, 1110, 827,699 cm−1. HNMR (250 MHz, CDCl3/
TMS): 0.95 (s, 4H), 1.56 (s, 12H), 2.15 (s, 4H), 3.92 (s,
3H), 5.20 (s, 1H), 6.66 (d, J = 7.5 Hz, 2H), 7.05 (s, 2H),
7.11 (s, 2H), 7.26 (s, 2H). 13C NMR (62.5 MHz, CDCl3/
TMS): δ = 33.5, 34.7, 47.5, 52.9, 57.7, 60.9, 62.3, 139.4,
141.7, 145.1, 145.9, 146.2, 147.7, 147.9, 148.7, 150.4,
150.9, 190.5. Anal. Calcd for: C30H33NO4 (487.22): C,
76.41; H, 7.05; N, 2.97. Found: C, 76.35; H, 6.98; N, 2.91.
Yield: 90% (3.31 g), white crystals, mp 234–235 °C. IR
(KBr): 2956, 2849, 2324, 1660, 1603, 1419, 1300, 1208,
1141, 1072, 987, 856, 748, 699, 645 cm−1 1H NMR
.
(250 MHz, CDCl3/TMS): 1.10 (s, 12H), 2.21 (s, 4H),
2.46 (s, 4H), 4.72 (s, 1H), 6.86–6.93 (m, 2H), 7.26 (d,
J = 2.5 Hz, 2H). 13C NMR (62.5 MHz, CDCl3/TMS):
δ = 32.2, 32.3, 40.1, 40.8, 44.9, 50.5, 114.5, 123.4, 129.3,
134.3, 162.9, 164.4, 190.3. Anal. Calcd for C23H25FO3
(368.18): C, 74.98; H, 6.84. Found: C, 74.91; H, 6.75.
3,3,6,6‑Tetramethyl‑9‑(4‑nitrophenyl)‑3,4,5,6,7,9‑hexahy‑
dro‑1H‑xanthene‑1,8(2H)‑dione (4i)
9‑(4‑Hydroxyphenyl)‑3,3,6,6‑tetramethyl‑3,4,5,6,7,9‑hexa‑
hydro‑1H‑xanthene‑1,8(2H)‑dione (4m)
Yield: (90%, 356 mg), white crystals, mp 234–235 °C. IR
(KBr): ν = 2954, 2869, 2360, 1666, 1620, 1512, 1465,
1365, 1203, 1141, 1002, 864, 833, 740, 694 cm−1. 1H NMR
(250 MHz, CDCl3/TMS): 1.11 (s, 12H), 2.20 (s, 4H), 2.49
(s, 4H), 4.82 (s, 1H), 7.46 (d, J = 10 Hz, 2H), 8.08 (d,
J = 7.5, 2H). 13C NMR (62.5 MHz, CDCl3/TMS): δ = 19.7,
29.2, 37.2, 37.7, 40.1, 40.8 122.3, 123.4, 129.3, 134.3, 153.9,
162.9, 184.7. Anal. Calcd for C23H25NO5 (395.17): C, 69.86;
H, 6.37; N, 3.54. Found: C, 69.80; H, 6.31; N, 3.47.
Yield: (85%, 311 mg), white crystals, mp 259–260 °C.
IR (KBr): 3409, 2869, 2823, 2715, 2360, 1651, 1612,
1
1521, 1450, 1357, 1203, 1002, 840, 609 cm−1. H NMR
(250 MHz, CDCl3/TMS): 1.09 (s, 12H), 2.21 (s, 4H),
2.45 (s, 4H), 4.67 (s, 1H), 6.59 (d, J = 10 Hz, 2H),
7.10 (d, J = 10 Hz, 2H). 13C NMR (62.5 MHz, CDCl3/
TMS): δ = 30.9, 32.2, 40.8, 44.8, 53.9, 62.6, 124.1,
125.6, 128.2, 129.4, 140.4, 149.3, 191.9. Anal. Calcd for
C23H26O4 (366.18): C, 75.38; H, 7.15. Found: C, 75.33;
H, 7.08.
9‑(4‑Chlorophenyl)‑3,3,6,6‑tetramethyl‑3,4,5,6,7,9‑hexahy‑
dro‑1H‑xanthene‑1,8(2H)‑dione (4j)
3,3,6,6‑Tetramethyl‑9‑(p‑tolyl)‑3,4,5,6,7,9‑hexahy‑
dro‑1H‑xanthene‑1,8(2H)‑dione (4n)
Yield: (92%, 353 mg), white crystals, mp 205–206 °C. IR
(KBr): ν = 2962, 2869, 2360, 1666, 1640, 1357, 1296,
Yield: (87%, 320 mg), white crystals, mp 189–190 °C. IR
(KBr): 2859, 2833, 2360, 1656, 1634, 1526, 1450, 1357,
1
1196, 1164, 1087, 1002, 848, 717, 671 cm−1. H NMR
1 3

J IRAN CHEM SOC
1
32. M.B. Gawande, Y. Monga, R.K. Sharma, Coord. Chem. Rev.
288, 118 (2015)
33. R.K. Sharma, S. Dutta, S. Sharma, R. Zboril, R.S. Varma, M.B.
1273, 1002, 840, 740. H NMR (250 MHz, CDCl3/TMS):
1.09 (s, 12H), 2.20 (s, 4H), 2.23 (s, 2H), 2.43 (s, 3H), 4.7
(s, 1H), 6.99 (d, J = 7.5 Hz, 2H), 7.16 (d, J = 7.5 Hz, 2H).
13C NMR (62.5 MHz, CDCl3/TMS): δ = 27.3, 29.2, 32.1,
36.4, 40.8, 46.2, 47.0, 124.3, 128.2, 128.7, 129.1, 130.2,
137.0, 191.7. Anal. Calcd for C24H28O3 (368.18): C, 79.09;
H, 7.74. Found: C, 79.00; H, 7.68.
Gawande, Green Chem. 18, 3184 (2016)
34. D. Wang, D. Astruc, Chem. Rev. 114, 6949 (2014)
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Acknowledgements Financial support from the research councils of
Shiraz University is gratefully acknowledged.
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