Synthesis and characterization of amino glucose-functionalized silica-coated NiFe2O4 nanoparticles: A heterogeneous, new and magnetically separable catalyst for the solvent-free synthesis of 2,4,5–trisubstituted imidazoles, benzo[d]imidazoles, benzo[d] oxazoles and azo-linked benzo[d]oxazoles

Article abstract of DOI:10.1016/j.jorganchem.2018.07.008

Amino glucose-functionalized silica-coated NiFe₂O₄ nanoparticles (NiFe₂O₄@SiO₂@amino glucose) were chemically synthesized and characterized by transmission electron microscope (TEM), X-ray diffraction (XRD), thermal gravimetric analysis (TGA), energy dispersive X-ray analysis (EDX), vibrating sample magnetometer (VSM), Zetasizer and Fourier transform infrared spectroscopy (FT-IR) instruments. NiFe₂O₄@SiO₂@amino glucose supply an environmentally friendly procedure for the synthesis of 2,4,5-trisubstituted imidazoles through one-pot multicomponent condensation of benzil or benzoin, ammonium acetate with aryl aldehydes and for the synthesis of benzoxazoles using condensation reaction of 2-aminophenol with aryl aldehydes under solvent free condition. In the other study, this synthesized magnetically reusable catalyst was introduced as a new avenue for the synthesis of benzo[d]imidazoles using the reaction between aryl aldehydes and 1,2-diaminobenzene. These compounds were obtained in high yields and short reaction times. The catalyst could be easily recovered and reused for five cycles with almost consistent activity. Synthesized compounds were characterized by their physical constant, comparison with authentic samples, FT-IR, ¹H NMR, ¹³C NMR spectroscopy and elemental analysis.

Full text of DOI:10.1016/j.jorganchem.2018.07.008

Accepted Manuscript
Synthesis and characterization of amino glucose‐functionalized silica‐coated NiFe O
2 4
nanoparticles: A heterogeneous, new and magnetically separable catalyst for the
solvent‐free synthesis of 2,4,5–trisubstituted imidazoles, benzo[d]imidazoles, benzo[d]
oxazoles and azo-linked benzo[d]oxazoles
Leila Zare Fekri, Mohammad Nikpassand, Shahab Shariati, Behnaz Aghazadeh,
Reza Zarkeshvari, Nahid Norouz pour
PII:
S0022-328X(18)30594-1
10.1016/j.jorganchem.2018.07.008
JOM 20495
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 3 May 2018
Revised Date: 5 July 2018
Accepted Date: 6 July 2018
Please cite this article as: L.Z. Fekri, M. Nikpassand, S. Shariati, B. Aghazadeh, R. Zarkeshvari, N.
Norouz pour, Synthesis and characterization of amino glucose‐functionalized silica‐coated NiFe O
2 4
nanoparticles: A heterogeneous, new and magnetically separable catalyst for the solvent‐free
synthesis of 2,4,5–trisubstituted imidazoles, benzo[d]imidazoles, benzo[d] oxazoles and azo-linked
benzo[d]oxazoles, Journal of Organometallic Chemistry (2018), doi: 10.1016/j.jorganchem.2018.07.008.
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ACCEPTED MANUSCRIPT
Synthesis and characterization of amino glucose‐functionalized
silica‐coated NiFe2O4 nanoparticles: A heterogeneous, new and
magnetically separable catalyst for the solvent‐free synthesis of
2,4,5–trisubstituted imidazoles, benzo[d]imidazoles, benzo[d]
oxazoles and azo-linked benzo[d]oxazoles
Leila Zare Fekri,*, 1 Mohammad Nikpassand,2 Shahab Shariati, 2 Behnaz Aghazadeh, 2 Reza
Zarkeshvari,1 Nahid Norouz pour1
1Department of Chemistry, Payame Noor University, PO Box 19395-3697 Tehran, Iran
2Department of Chemistry, Rasht Branch, Islamic Azad University, Rasht, Iran
Abstract
Amino glucose‐functionalized silica‐coated NiFe2O4 nanoparticles (NiFe2O4@SiO2@amino
glucose) were chemically synthesized and characterized by transmission electron microscope
(TEM), X‐ray diffraction (XRD), thermal gravimetric analysis (TGA), energy dispersive X-ray
analysis (EDX), vibrating sample magnetometer (VSM), Zetasizer and Fourier transform
infrared spectroscopy (FT-IR) instruments. NiFe2O4@SiO2@amino glucose supply an
environmentally friendly procedure for the synthesis of 2,4,5-trisubstituted imidazoles through
one-pot multicomponent condensation of benzil or benzoin, ammonium acetate with aryl
aldehydes and for the synthesis of benzoxazoles using condensation reaction of 2-aminophenol
with aryl aldehydes under solvent free condition. In the other study, this synthesized
magnetically reusable catalyst was introduced as a new avenue for the synthesis of
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ACCEPTED MANUSCRIPT
benzo[d]imidazoles using the reaction between aryl aldehydes and 1,2-diaminobenzene. These
compounds were obtained in high yields and short reaction times. The catalyst could be easily
recovered and reused for five cycles with almost consistent activity. Synthesized compounds
1
were characterized by their physical constant, comparison with authentic samples, FT-IR, H
NMR, 13C NMR spectroscopy and elemental analysis.
Key Words: oxazoles, imidazoles, NiFe2O4@SiO2@amino glucose, solvent free reaction
Introduction
The imidazole substructures were found in a large number of pharmacologically active
compounds and natural products such as the hypnotic agent etomidate, amino acid histidine [1],
the proton pump inhibitor omeprazole [2], the antiulcerative agent cimetidine [3], the
benzodiazepine antagonist flumazenil [4], the fungicide ketoconazole [5], inhibitors of P38 MAP
kinase [6], glucagon receptor antagonists [7], transforming growth factor b1 (TGF-b1) type 1
active receptor-like kinase (ALK5) [8], B-Raf kinase [9], cyclooxygenase-2 (COX-2) [10],
biosynthesis of interleukin-1 (IL-1) [11], plants growth regulators [12], anti-bacterial [13],
pesticide [14], therapeutic agents [15], antitumor [16], modulators of P-glycoprotein (P-gp)-
mediated multidrug resistance (MDR) [17], and also CB1 cannabinoid receptor antagonists [18].
In 1882, Radziszewski and Japp [19, 20] reported the first synthesis of a highly substituted
imidazole from a 1,2-dicarbonyl compound, aldehydes and ammonia. In addition, they can also
be accessed by the cycloaddition reaction of mesoionic-1,3-oxazolium-5-olates with N-
(arylmethylene)-benzene sulfonamides, [21] hetero-cope rearrangement, [22] four component
condensation of aryl glyoxals, primary amines, carboxylic acids and isocyanides on Wang resin,
[23] condensation of a 1,2-diketone with an aryl nitrile and primary amine under microwave
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irradiation, [24] and reaction of N-(2-oxo)-amides with ammonium trifluoroacetate [25]. Another
method for the synthesis of these compounds is the reaction of 1,2-phenylenediamine with
aldehydes in the presence of acidic catalysts under various reaction conditions [26-34].
Benzoxazoles have been reported to release a wide range of biological activities as antitumor
[35], antibacterial [36], antiviral [37], antibiotic [38], antifungal [39], antiulcer [40],
antihistaminic [41], cyclooxygenase inhibiting [42], anticonvulsant [43], anti-inflammatory [44,
45], anti-tubercular [46], antiparasitics [47], hypoglycemic [48], herbicidal [49], antiallergic
[50], antihelmintic and cytotoxic activity [51]. Benzoxazoles are structural isosteres of the
nucleic bases adenine and guanine, that allow them to interact easily with polymers of living
systems [52] and some of them have found applications as fluorescent whitening agents [53].
Two most common protocols for the synthesis of benzoxazoles are: (1) the direct
condensation of 2-aminophenol with carboxylic acid or aldehyde under harsh conditions, such as
in the presence of strong acid, high temperature [54] and (2) the oxidative cyclization of phenolic
Schiff bases, using various oxidants [55-57].
Most of the repoted procedures for the synthesis of imidazoles and benzoxazoles have some
serious defects, such as tedious work-up and purification, significant amounts of toxic waste
materials, highly acidic conditions, long reaction time, occurrence of side reactions, low yields,
use of expensive reagents or catalysts, low selectivity and high temperatures in refluxing or
microwave condition. Therefore, development of easy, green, effective, high-yielding, and eco-
friendly approaches using novel catalysts for the synthesis of imidazoles and benzoxazoles is an
important research topic for organic chemists.
The main purpose of the present study was to synthesize magnetically separable
NiFe2O4@SiO2@amino glucose nanoparticles (NPs) as a reusable and efficient catalyst for the
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green synthesis of 2,4,5-trisubstituted imidazoles and benzoxazoles using one-pot
multicomponent condensation reactions.
2. Material and methods
2.1. Materials and instruments
All of the used chemicals were purchased from Merck (Darmstadt, Germany), Fluka (Buchs,
Switzerland). All solvents used were dried and distilled according to standard procedures.
Melting points were measured on an Electrothermal IA 9100 melting point apparatus (United
Kingdom). FT-IR spectra were obtained in the range of 400-4000 cm-1 on a Shimadzu FT-IR
1
8600 spectrophotometer (Japan). H and 13C NMR spectra were determined on a Bruker 400
DRX Avance instrument (Germany) at 400 and 100 MHz. Elemental analyses were recorded on
a Carlo-Erba EA1110CNNO-S analyser (Italy). X-ray powder diffraction (XRD) patterns of
nanostructures were obtained using a Philips (Netherlands) Xpert diffractometer (CuKα,
radiation, λ=0.154056), at a scanning speed of 2°/min from 10° to 80° (2θ). Transmission
electron microscopy (TEM) measurements were carried out on a Zeiss-EM10C-100 KV
instrument (Germany). Energy dispersive X-ray spectroscopy (EDX) analysis was performed on
a Sirius SD_scientific equipments (United Kingdom). Investigation of magnetic property of
nanocatalyst was done using a vibrating sample magnetometer (VSM) from Meghnatis Daghigh
Kavir company (model MDKB, Kashan, Iran). A strong magnet with 1.4 Tesla magnetic field
was applied for the magnetic separation of nanocatalyst. A thermal analysis system from
Polymer Laboratories Ltd (United Kingdom) was utilized to study the thermal stability of the
synthesized nanocatalyst. The Zeta potential of the synthesized nanocatalyst was measured using
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a Zetasizer instrument (Malvern, United Kingdom). Thin layer chromatography (TLC) was
carried out with ethyl acetate: n-hexane 1:4 on TLC Silica gel 60 F
.
2.2. Synthesis of NiFe2O4 nanoparticles
The NiFe2O4 nanoparticles were prepared by the co-precipitation method. The starting materials
were iron nitrate [(Fe(NO3)3.9H2O)], nickel nitrate [(Ni(NO3)2.6H2O)], polyethylene oxide
(PEO) [CH2CH2AOA]n and hydrazine hydrate (N2H4-H2O). In a typical synthesis, 0.2 M (20
mL) solution of iron nitrate and 0.1 M (20 mL) solution of nickel nitrate were prepared and
vigorously mixed under stirring for 1 h at 80 °C. PEO was added into the solution as a capping
agent. Here, 0.2 g of PEO capped NiFe2O4 composite was tagged as nanoparticles. Subsequently,
5 mL of hydrazine hydrate was added drop by drop into the solution and brown color precipitates
were formed. Finally, the precipitates were separated by centrifugation and dried in oven for 4 h
at 100 °C. The acquired substances were annealed for 10 h at 300 °C [58].
2.3. Synthesis of silica-coated NiFe2O4 magnetic nanoparticles (NiFe2O4@SiO2 MNPs)
Typically, 500 mg of the NiFe2O4 nanoparticles were dispersed by ultrasonic vibration in a
mixture of ethanol (20 mL), deionized water (3 mL) and 1 mL of 25 wt% concentrated aqueous
ammonia solution for 20 min. Subsequently, 0.7 mL of tetraethylorthosilicate (TEOS) was added
dropwise. After stirring for 12 h at room temperature under N2 atmosphere, the products was
collected from the solution using a magnet, and then washed several times with deionizied water
and ethanol and dried at 25 °C under vacuum.
2.2.
Synthesis of NiFe2O4@SiO2‐Cl MNPs
500 mg NiFe2O4@SiO2 nanoparticles were dispersed into 50 mL toluene and sonicated for 20
min, followed by the addition of 0.5 mL (3-chloropropyl)trimethoxysilane (CPTES). Then, the
mixture was refluxed at 110 °C with continuous stirring for 12 h under a nitrogen flow. The
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resulting NiFe2O4@SiO2‐Cl MNPs were collected by magnetic separation followed by washing
with toluene and ethanol several times and drying at 60 °C for 6 h.
2.3.
Synthesis of NiFe2O4@SiO2@amino glucose
500 mg NiFe2O4@SiO2‐Cl MNPs were dispersed into 50 ml of toluene and sonicated for 30
min, followed by the addition of 0.5 mL glucose amine. Then, the mixture was refluxed at 110
°C with continuous stirring for 12 h under a nitrogen gas flow. The resulting functionalized
NiFe2O4@SiO2@aminoglucose was collected by magnetic separation followed by washing with
toluene and ethanol several times and drying at 80 °C for 8 h.
2.4.
General procedure for preparation of trisubstituted imidazoles 4a-m
A mixture of aldehyde 1 (1.0 mmol), benzyl or benzoin 2 (1.0 mmol), NH4OAc (1mmol) and
0.05 g NiFe2O4@SiO2@aminoglucose were stirred at room temperature under solvent free
condition for the required reaction time according to Table 3. After completion of the reaction,
as indicated by TLC (TLC Silica gel 60 F₂₅₄, ethyl acetate: n-hexane 1: 4), the resulting mixture
was diluted with hot ethanol (10 mL) and the catalyst was separated by the external magnet and
washed with hot distilled water (5 mL) and ethanol (3 mL) two times. The filtrate was cooled
down to room temperature and the precipitated crude products were collected and recrystallized
from ethanol if necessary.
2.5.
General procedure for preparation of benzo[d]imidazoles 6a-k
A mixture of aldehyde 1 (2.0 mmol), 1,2-diaminobenzene (1 mmol) and 0.05 g of
NiFe2O4@SiO2@aminoglucose were stirred at room temperature under solvent free condition for
the required reaction time according to Table 4. After completion of the reaction, as indicated by
TLC (TLC Silica gel 60 F
, ethyl acetate: n-hexane 1: 4), the resulting mixture was diluted
with hot ethanol (10 mL) and the catalyst separated by the external magnet and washed with hot
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distilled water (5 mL) and ethanol (3 mL) two times. The filtrate was cooled down to room
temperature and the precipitated crude products were collected and recrystallized from ethanol if
necessary.
2.6.
General procedure for preparation of benzo[d]oxazoles 8a-k and 9a-d
A mixture of aldehyde 1 (1.0 mmol), 1,2-aminophenol (1 mmol) and 0.05 g of
NiFe2O4@SiO2@aminoglucose were stirred at room temperature under solvent free condition
for the required reaction time according to Table 7 and 8. After completion of the reaction, as
indicated by TLC (TLC Silica gel 60 F₂₅₄, ethyl acetate: n-hexane 1: 4), the resulting mixture
was diluted with hot ethanol (10 mL) and the catalyst separated by the external magnet and
washed with hot distilled water (5 mL) and ethanol (3 mL) two times. The filtrate was cooled
down to room temperature and the precipitated crude product was recrystallized from ethanol if
necessary.
2.5.1. 2,4,5-Triphenyl-1H-imidazole (4a)
1
m.p.: 269-271°C ; FT-IR (KBr) (vmax/cm-1): 3365, 3046, 1666, 1651, 1496, 1396; H NMR
(DMSO-d6, 400 MHz): δH (ppm) 7.05 (m, 2H), 7.13-7.24 (m, 2H), 7.31-7.39 (m, 2H), 7.43 (t, J=
8.0 Hz, 1H), 7.50 (t, J= 7.6 Hz, 2H), 7.74 (d, J= 6.4Hz, 2H), 7.91 (m, 2H), 8.00 (d, J= 5.2Hz,
2H); Anal calc. for C21H16N2: C, 85.11; H, 5.44; N, 9.45. Found: C, 85.12; H, 5.43, N, 9.45.
2.5.2. N,N-Dimethyl-4-(4,5-diphenyl-1H-imidazol-2-yl)benzenamine (4b)
1
m.p.: 238-240°C; FT-IR (KBr) (vmax/cm-1): 3348, 3193, 1648, 1605, 1448, 1359; H NMR
(DMSO-d6, 400 MHz): δH (ppm) 2.28 (s, 6H), 6.92 (d, J=7.4Hz, 2H), 7.15-7.22 (m, 2H), 7.32-
7.38 (m, 2H), 7.40-7.46 (m, 2H), 7.50-7.52 (m, 2H), 7.53 (d, J= 7.6Hz, 2H), 7.69-7.88 (m, 2H);
Anal Calc. for C23H21N3: C, 81.38; H, 6.24; N, 12.38. Found: C, 81.36; H, 6.26, N, 12.38.
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2.5.3. 4-(4,5-Diphenyl-1H-imidazol-2-yl)phenol (4c)
1
m.p.: 226-228°C; FT-IR (KBr) (vmax/cm-1): 3344, 1658, 1517, 1449, 1402, 1289; H NMR
(DMSO-d6, 400 MHz): δH (ppm) 6.91 (d, J= 8.2Hz, 2H), 6.92 (d, J= 6.4Hz, 2H), 7.13-7.24 (m,
2H), 7.32-7.38 (m, 2H), 7.40-7.51 (m, 2H), 7.53 (d, J= 8.2Hz, 2H), 7.69-7.88 (m, 2H), 9.07 (m,
1H), 10.12 (s, 1H) ppm; Anal Calc. for C21H16N2O: C, 80.75; H, 5.16; N, 8.97. Found: C, 80.72;
H, 5.13, N, 8.99.
2.5.4. 2-(4-Nitrophenyl)-4,5-diphenyl-1H-imidazole (4f)
m.p.: 223-225°C; FT-IR (KBr) (vmax/cm-1): 3443, 3065, 1663, 1591, 1448, 1336, 1517, 1336;
1H NMR (DMSO-d6, 400 MHz): δH (ppm) 7.03-7.06 (m, 2H), 7.21-7.24 (m, 2H), 7.32-7.38 (m,
4H), 7.50-7.53 (m, 2H), 7.81 (d, J= 7.6Hz, 2H), 8.24 (d, J= 7.6Hz, 2H); Anal Calc. for
C21H15N3O2: C, 73.89; H, 4.43; N, 12.31. Found: C, 73.86; H, 4.48, N, 12.29.
2.5.5. 2-(4-Methoxyphenyl)-4,5-diphenyl-1H-imidazole (4g)
1
m.p.: 228-229°C ; FT-IR (KBr) (vmax/cm-1): 3338, 1659, 1600, 1499, 1422, 1274; H NMR
(DMSO-d6, 400 MHz): δH (ppm) 3.94 (s, 3H), 6.98 (d, J=7.6Hz, 2H), 7.04 (m, 2H), 7.13 (d, J=
8.8Hz, 2H), 7.32-7.38 (m, 2H), 7.55 (d, J= 7.6Hz, 2H), 7.87 (d, J= 6.8Hz, 2H), 8.00 (d, J=
8.4Hz, 2H) ; Anal Calc. for C22H18N2O: C, 80.96; H, 5.56; N, 8.58. Found: C, 80.95; H, 5.51, N,
8.54.
2.5.6. 2-(Furan-2-yl)-4,5-diphenyl-1H-imidazole (4k)
1
m.p.: 221-223°C; FT-IR (KBr) (vmax/cm-1): 3325, 1621, 1543, 1472, 1259; H NMR (DMSO-
d6, 400 MHz): δH (ppm) 7.12 (d, J= 7.6Hz, 2H), 7.17-7.23 (m, 2H), 7.31-7.38 (m, 2H), 8.06 (m,
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2H), 7.92 (d, J= 7.2Hz, 1H), 7.90 (d, J= 7.8Hz, 2H), 7.56 (d, J= 7.4Hz, 2H) ppm. Anal Calc. for
C19H14N2O: C, 79.70; H, 4.93; N, 9.78. Found: C, 79.69; H, 4.95, N, 9.75.
2.5.7. 4-(4,5-Diphenyl-1H-imidazol-2-yl)pyridine (4l)
m.p.: 276-278 °C; FT-IR (KBr) (vmax/cm-1): 3098, 2987, 1614, 1543, 1329, 1243; 1H NMR
(DMSO-d6, 400 MHz): δH (ppm) 7.05-7.11 (m, 2H), 7.19-7.26 (m, 2H), 7.30-7.41 (m, 4H), 7.53-
7.56 (m, 2H), 7.73 (d, J= 7.4Hz, 2H), 8.14 (d, J= 7.8Hz, 2H); Anal Calc. for C20H15N3: C, 80.78;
H, 5.08; N, 14.13. Found: C, 80.81; H, 5.11, N, 14.08.
2.5.8. 4,5-diphenyl-2-propyl-1H-imidazole (4m)
1
m.p.: 243-244 °C; FT-IR (KBr) (vmax/cm-1): 3421, 1595, 1514, 1419, 1376, 1242; H NMR
(DMSO-d6, 400 MHz): δH (ppm) 1.32 (t, J= 12.0Hz, 3H), 1.56-1.67 (m, 2H), 2.25 (t, J= 9.6Hz,
2H), 7.19 (d, J= 7.6Hz, 2H), 7.33-7.42 (m, 2H), 7.63 (d, J= 7.6Hz, 2H), 7.83 (d, J= 7.6Hz, 2H),
8.04 (m, 2H); Anal Calc. for C18H18N2: C, 82.41; H, 6.92; N, 10.68. Found: C, 82.41; H, 6.93, N,
10.67.
2.6.1.1-Benzyl-2-phenyl-1H-benzo[d]imidazole (6a)
1
m.p.: 130-132°C ; FT-IR (KBr) (vmax/cm-1): 3058, 2934, 1614, , 1547, 1434, 1321, 1145; H
NMR (DMSO-d6, 400 MHz): δH (ppm) 5.76 (s, 2H), 7.18 (d, J = 8.1 Hz, 1H), 7.29-7.45 (m,
3H), 7.50-7.68(m, 2H), 7.76-7.96 (m, 7H), 8.50 (d, J = 8.6 Hz, 1H); 13C NMR (DMSO-d6, 100
MHz): δC (ppm) 45.2, 111.6, 119.6, 121.6, 125.8, 127.8, 128.8, 128.9, 129.0, 129.7, 134.6,
135.8, 146.0, 149.5, 156.9; Anal Calc. for C20H16N2: C, 84.48; H, 5.67; N, 9.85. Found: C, 84.50;
H, 5.69, N, 9.82.
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2.6.2.4-(1-(4-(Dimethylamino)benzyl)-1H-benzo[d]imidazol-2-yl)-N,N-dimethyl benzenamine
(6b)
1
m.p.: 252-254°C ; FT-IR (KBr) (vmax/cm-1): 1609 , 1556, 1445 , 1376 , 1209, 1111 ; H NMR
(DMSO-d6, 400 MHz): δH (ppm) 2.56 (s, 6H), 2.75 (s, 6H), 5.45 (s, 2H), 6.58-7.18 (m, 12H); 13C
NMR (DMSO-d6, 100 MHz): δC (ppm) 40.0, 41.5, 47.5, 110.9, 112.1, 112.9, 118.2, 119.1, 124.5,
124.6, 128.9, 130.5, 135.6, 145.7, 149.4, 154.4, 155.7; Anal Calc. for C24H26N4: C, 77.80; H,
7.07; N, 15.12. Found: C, 77.78; H, 7.05, N, 15.14.
2.6.3.1-(4-Chlorobenzyl)-2-(4-chlorophenyl)-1H-benzo[d]imidazole (6c)
1
m.p.: 137-139°C ; FT-IR (KBr) (vmax/cm-1): 1628 , 1279, 1406, 1095 ; H NMR (DMSO-d6,
400 MHz): δH (ppm) 5.61 (s, 2H), 7.20-7.25 (m, 3H), 7.30-7.40 (m, 1H), 7.52-7.61 (m, 4H),
7.69-7.76 (m, 2H), 8.20-8.23 (m, 2H); 13C NMR (DMSO-d6, 100 MHz): δC (ppm) 46.7, 110.6,
120.4, 122.4, 123.5, 126.5, 127.7, 128.6, 129.5, 130.1, 133.9, 133.2, 135.0, 135.7, 142.1,
152.1;Anal Calc. for C20H14Cl2N2: C, 68.00; H, 3.99; N, 7.93. Found: C, 68.02; H, 3.96, N, 7.91.
2.6.4.1-(4-Bromobenzyl)-2-(4-bromophenyl)-1H-benzo[d]imidazole (6d)
1
m.p.: 200-201°C ; FT-IR (KBr) (vmax/cm-1): 3021, 1987, 1617, 1556, 1403 , 1076 ; H NMR
(DMSO-d6, 400 MHz): δH (ppm) 5.54 (s, 2H), 7.21-7.37 (m, 2H), 7.44-7.47 (m, 2H), 7.62 (brs,
2H), 7.75 (brs, 2H), 7.89 (d, J = 8.3 Hz, 2H), 8.28 (d, J = 8.5 Hz, 2H); 13C NMR (DMSO-d6, 100
MHz): δC (ppm) 45.5, 118.2, 121.8, 123.8, 126.1, 127.3, 127.5, 128.9, 129.2, 131.2, 132.8,
134.5, 134.5, 135.2, 147.8, 154.1; Anal Calc. for C20H14Br2N2: C, 54.33; H, 3.19; N, 6.34.
Found: C, 54.30; H, 3.17, N, 6.37.
2.6.5.1-(4-Methoxybenzyl)-2-(4-methoxyphenyl)-1H-benzo[d]imidazole (6e)
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m.p.: 131-133°C ; FT-IR (KBr) (vmax/cm-1): 1625, 1511, 1452 , 1410, 1246 ; 1H NMR (DMSO-
d6, 400 MHz): δH (ppm) 3.77 (s, 3H), 3.92 (s, 3H), 5.47 (s, 2H), 6.75-7.86 (m, 12H); 13C NMR
(DMSO-d6, 100 MHz): δC (ppm) 45.8, 55.2, 55.5, 111.2, 114.4, 114.9, 116.2, 121.7, 122.0,
128.0, 128.7, 130.7, 135.9, 144.7, 154.4, 157.6, 159.6; Anal Calc. for C23H24N2O3: C, 73.38; H,
6.43; N, 7.44. Found: C, 73.41; H, 6.40, N, 7.45.
2.6.6. 1-(2-Chlorobenzyl)-2-(2-chlorophenyl)-1H-benzo[d]imidazole (6f)
m.p.: 154-155°C ; FT-IR (KBr) (vmax/cm-1): 3017, 2936 , 1613 , 1562, 1447 , 1387 , 1221,
1
13
1057, 10438 ; H NMR (DMSO-d6, 400 MHz): δH (ppm) 5.43 (s, 2H), 6.51-7.94 (m, 12H); C
NMR (DMSO-d6, 100 MHz): δC (ppm) 45.9, 115.6, 122.4, 122.9, 125.6, 126.9, 127.3, 127.8,
129.1, 129.6, 129.7, 131.5, 131.9, 132.5, 133.9, 1343.5, 135.5, 137.9, 146.0, 155.8; Anal Calc.
for C20H14Cl2N2: C, 68.00; H, 3.99; N, 7.93. Found: C, 68.03; H, 4.01, N, 7.93.
2.6.7. 2-((2-(2-Hydroxyphenyl)-1H-benzo[d]imidazol-1-yl)methyl)phenol (6g)
1
m.p.: 200-202°C ; FT-IR (KBr) (vmax/cm-1): 1621,1514, 1472, 1418, 1241, 1159; H NMR
(DMSO-d6, 400 MHz): δH (ppm) 5.53 (s, 2H), 6.21-7.28 (m, 12H), 9.52 (brs., 1H), 10.18 (s, br.,
13
1H); C NMR (DMSO-d6, 100 MHz): δC (ppm) 45.8, 110.2, 120.7, 121.7, 123.5, 125.7, 126.3,
127.4, 128.2, 129.0, 129.6, 130.5, 131.5, 132.8, 133.2, 133.8, 134.7, 135.0, 142.3, 151.2. Anal
Calc. for C20H16N2O2: C, 75.93; H, 5.10; N, 8.86. Found: C, 75.90; H, 5.12, N, 8.89.
2.6.8.1-(4-Nitrobenzyl)-2-(4-nitrophenyl)-1H-benzo[d]imidazole (6h)
m.p.: 117-119°C ; FT-IR (KBr) (vmax/cm-1): 2975, 1612, 1535, 1344, 1222, 1108;1H NMR
(DMSO-d6, 400 MHz): δH (ppm) 5.61 (s, 2H), 7.29-7.34 (m, 3H), 7.51 (brs, 1H), 7.64-7.66 (brs,
2H), 8.42 (d, J = 8.0 Hz, 2H), 8.49 (d, J = 7.6 Hz, 2H); 13C NMR (DMSO-d6, 100 MHz): δC
11

ACCEPTED MANUSCRIPT
(ppm) 47.6, 112.4, 121.5, 122.0, 123.9, 124.6, 124.8, 125.9, 132.5, 135.2, 136.0, 141.0, 142.7,
149.0, 149.1, 155.0; Anal Calc. for C20H14N4O4: C, 64.17; H, 3.77; N, 14.97. Found: C, 64.18; H,
3.80, N, 14.94.
2.6.9. 1-(4-Hydroxybenzyl)-2-(4-hydroxyphenyl)-1H-benzo[d]imidazole (6i)
1
m.p.: 255°C ; FT-IR (KBr) (vmax/cm-1): 1632, 1548, 1462, 1421, 1381, 1263, 1098. H NMR
(DMSO-d6, 400 MHz): δH (ppm) 5.44 (s, 2H), 7.28 (s, 2H), 6.67 (d, J = 8.2 Hz, 2H), 6.90 (t, J =
8.9 Hz, 4H), 7.56 (d, J = 8.0 Hz, 4H), 8.14 (d, J = 7.6 Hz, 2H); 13C NMR (DMSO-d6, 100 MHz):
δC (ppm) 45.6, 111.6, 121.7, 122.7, 124.8, 125.3, 127.9, 128.2, 129.1, 131.5, 133.5, 133.9,
137.2, 137.8, 145.3, 153.8. Anal Calc. for C20H16N2O2: C, 75.93; H, 5.10; N, 8.86. Found: C,
75.98; H, 5.05, N, 8.89.
2.6.10. 2-(2-Furyl)-1-(2-furylmethyl)-1H-benzimidazole (6j)
m.p.: 94-95°C ; FT-IR (KBr) (vmax/cm-1): 3017, 2943, 1617, 1593, 1518, 1477 , 1335 , 1231 ;
1H NMR (DMSO-d6, 400 MHz): δH (ppm) 5.42 (s, 2H), 6.26-7.58 (m, 10H). 13C NMR (DMSO-
d6, 100 MHz): δC (ppm) 45.1, 111.7, 111.9, 113.4, 113.8, 113.9, 115.2, 119.3, 121.0, 123.3,
137.5, 142.9, 144.2, 144.5, 145.7, 151.2. Anal Calc. for C16H12N2O2: C, 72.72; H, 4.58; N, 10.60.
Found: C, 72.73; H, 4.52; N, 10.58.
2.6.11. 2-(Pyridin-2-yl)-1-(pyridin-2-ylmethyl)-1H-benzo[d]imidazole (6k)
m.p.: 132-133°C ; °C; FT-IR (KBr) (vmax/cm-1): 3012, 2978, 1578 , 1563, 1519, 1429 , 1316
1
13
,1143 ; H NMR (DMSO-d6, 400 MHz): δH (ppm) 5.54 (s, 2H), 6.42–7.52 (m, 12H); C NMR
(DMSO-d6, 100 MHz): δC (ppm) 46.4, 110.5, 121.7, 123.6, 123.9, 124.8, 124.9, 125.9, 128.0,
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128.9, 131.9, 132.6, 133.5, 134.2, 137.6, 146.3, 147.8, 149.0, 151.9; Anal Calc. for C18H14N4: C,
75.50; H, 4.93; N, 19.57. Found: C, 75.48; H, 4.93; N, 19.55.
2.7.1. 2-(4-Methoxyphenyl)benzo[d]oxazole (8b)
m.p.: 100-102°C ; FT-IR (KBr) (vmax/cm-1): 3100, 2980, 1635, 1607, 1508, 1282; 1HNMR
(DMSO-d6, 400 MHz): δH (ppm) 3.80 (s, 3H), 6.84 (t, J=7.4Hz, 2H), 7.10 (d, J= 7.9Hz,2H),
7.20 (t, J=7.4 Hz, 2H), 7.40 (d, J=7.5Hz, 2H) ; Anal Calc. for C14H11NO2: C, 74.65; H, 4.92; N,
6.22; Found: 74.63; H, 4.94; N, 6.21.
2.7.2. 4-(Benzo[d]oxazol-2-yl)phenol (8c)
1
m.p.: 98-99°C; FT-IR (KBr) (vmax/cm-1): 3435, 3114, 1648, 1601, 1418, 1243; HNMR
(DMSO-d6, 400 MHz): δH (ppm) 6.87 (t, J= 7.5Hz, 1H), 6.97 (d, J= 8.4Hz, 2H), 7.07 (8, J=
8.0Hz, 1H), 7.23 (t, J=7.7Hz, 1H), 7.37 (d, J= 7.7Hz, 1H), 7.75 (d, J= 8.4Hz, 2H); Anal Calc. for
C13H9NO2: C, 73.92; H, 4.29; N, 6.63; Found: C, 73.90; H, 4.30; N, 6.65.
2.7.3. 2-(Benzo[d]oxazol-2-yl)phenol (8e)
1
m.p.: 154-155 °C; FT-IR (KBr) (vmax/cm-1): 3414, 3052, 1641, 1609, 1466, 1228; HNMR
(DMSO-d6, 400 MHz): δH (ppm) 6.85 (t, J=7.1Hz, 1H), 6.91-6.98 (m, 1H), 7.10 (d, J= 7.9Hz,
1H), 7.15-7.26 (m, 1H), 7.40 (d, J= 7.3Hz, 1H), 7.48-7.53 (m, 1H), 7.59-7.73 (m, 1H), 7.87 (d,
J= 7.7Hz, 1H) ; Anal Calc. for C13H9NO2: C, 73.92; H, 4.29; N, 6.63; Found: C, 73.89; H, 4.32;
N, 6.63.
2.7.4. 2-(3-Bromophenyl)benzo[d]oxazole (8f)
m.p.: 187-188 °C; FT-IR (KBr) (vmax/cm-1): 1633, 1434, 1295, 1122; 1HNMR (DMSO-d6, 400
MHz): δH (ppm) 7.25-7.35 (m, 2H), 7.40-7.48 (m, 2H), 7.50-7.57 (m, 2H), 7.61-7.64 (m, 1H),
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7.78 (d, J= 7.8Hz, 1H); cm-1 Anal Calc. for C13H8BrNO: C, 56.96; H, 2.94; N, 5.11; Found: C,
.
56.98; H, 2.92; N, 5.09.
2.7.5. 2-(Pyridin-4-yl)benzo[d]oxazole (8j)
1
m.p.: 134-135°C; FT-IR (KBr) (vmax/cm-1): 3012, 1605, 1463, 1272, 1125; HNMR (DMSO-
d6, 400 MHz): δH (ppm) 7.32 (d, J= 8.0Hz, 1H), 7.37 (d, J= 7.8Hz, 1H), 7.45 (m, 1H), 7.53 (t, J=
8.0Hz,1H), 7.61 (d, J= 7.2Hz, 2H), 7.63 (d, J= 7.2Hz, 2H) ; Anal Calc. for C12H8N2O: C, 73.46;
H, 4.11; N, 14.28; Found: C, 73.44; H, 4.13; N, 14.30.
2.7.6. 2-Propylbenzo[d]oxazole (8k)
m.p.: 178-179 °C; FT-IR (KBr) (vmax/cm-1): 3024, 2943, 1553, 1462, 1431, 1225; 1HNMR
(DMSO-d6, 400 MHz): δH (ppm) 1.59 (t, 3H), 1.82-1.85 (m, 2H), 2.72 (t, 2H), 7.34 (d, J=8.0Hz,
1H), 7.40 (t, J= 7.2Hz, 1H), 7.44 (m, 1H), 7.54 (m, 1H); Anal Calc. for C10H11NO: C, 74.51; H,
6.88; N, 8.69; Found: C, 74.52; H, 6.90; N, 8.70.
2.7.7. 4-(2-Phenyldiazenyl)-2-(5-chlorobenzo[d]oxazol-2-yl)phenol (9a)
m.p. 246-248 °C; FT-IR (KBr) (vmax/cm-1): 3344, 1678, 1612, 1449, 1234; 1H NMR (400MHz,
CDCl3): δH (ppm) 7.27 (dd, J = 7.8 Hz, J = 2.1 Hz, 1H), 7.37 (t, J = 8.7 Hz, 1H), 7.42- 7.57 (m,
4H), 7.73 (d, J = 7.8Hz, 1H), 8.34- 8.43 (m, 2H), 8.63 (s, 2H), 8.97 (s, 1H); 13C NMR (125 MHz,
CDCl3): δC (ppm) 104.6, 112.3, 119.1, 120.1, 120.7, 121.3, 126.8, 128.1, 128.9, 131.2, 131.7,
136.8, 145.2, 146.3, 151.5, 156.8, 175.3. Anal. Calcd. for C19H12ClN3O2: C, 65.24; H, 3.46; N,
12.01. Found: C, 65.21; H, 3.47; N, 12.02.
2.7.8. 4-(2-(2-Chloro-4-nitrophenyl)diazenyl)-2-(5-chlorobenzo[d]oxazol-2-yl)phenol (9b)
1
m.p. 241-242°C; FT-IR (KBr) (vmax/cm-1): 3356, 1634, 1617, 1559, 1348, 1176; H NMR
(400MHz, CDCl3): δH (ppm) 7.23 (t, J = 8. 8 Hz, 2H), 7.37-7-54 (m, 3H), 7.69 (d, J = 8.2 Hz,
1H), 8.01 (d, J = 7.6 Hz, 2H), 8.42 (dd, J = 7.6Hz, J = 1.2Hz, 1H), 8.69 (s, 1H), 8.91 (s, 1H)
14

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ppm; 13C NMR (100 MHz, CDCl3) δC (ppm) 115.1, 120.0, 121.9, 123.2, 123.6, 124.1, 124.9,
126.4, 127.1, 129.9, 131.1, 135.2, 139.8, 143.1, 145.7, 155.1, 159.0, 164.2, 175.0. Anal. Calcd.
for C19H10Cl2N4O4: C, 53.17; H, 2.35; N, 13.05. Found: C, 53.15; H, 2.32; N, 13.04.
2.7.9. 4-(2-(2-Nitrophenyl)diazenyl)-2-(5-chlorobenzo[d]oxazol-2-yl)phenol (8c)
m.p. 280- 282 °C; FT-IR (KBr) (vmax/cm-1): 3357, 1679, 1628, 1604, 1533, 1341, 1126 cm-1; 1H
NMR (400MHz, CDCl3) δH (ppm) 7.5 (t, J = 8.5Hz, 1H), 7.56 (d, J = 8.5 Hz, 1H), 7.67 (t, J =
8.0 Hz, 1H), 7.69-7.79 (m, 3H), 7.89 (d, J = 7.8 Hz, 1H), 8.09 (t, J = 7.5Hz, 1H), 8.5 (s, 1H),
8.63 (s, 1H), 8.89 (t, J = 8.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): δC (ppm) 111.7, 116.2,
119.1, 122.7, 128.0, 128.5, 128.9, 129.5, 129.9, 131.8, 132.0, 132.8, 135.3, 146.0, 148.2, 149.2,
155.1, 158.1, 165.3. Anal. Calcd. for C19H11ClN4O4: C, 57.81; H, 2.81; N, 14.19. Found: C,
57.82; H, 2.80; N, 14.22.
2.7.10. 4-(2-(2-Chlorophenyl)diazenyl)-2-(5-chlorobenzo[d]oxazol-2-yl)phenol (8d)
m.p. 238-240 ̊
C; FT-IR (KBr) (vmax/cm-1): 3409, 1678, 1609, 1575, 1325, 1124 cm-1; 1H NMR
(400MHz, CDCl3): δH (ppm) 7.13 (d, J = 8.6 Hz, 2H), 7.24 (d, J = 8.6 Hz, 1H), 7.33-7.54 (m,
4H), 7.64 (d, J = 8.6 Hz, 1H), 8.06 (t, J = 8.4 Hz, 1H), 8.56 (s, 1H), 8.68 (d, J = 2.0 Hz, 1H); 13C
NMR (100 MHz, CDCl3): δC (ppm) 110.7, 119.9, 120.1, 124.2, 125.7, 128.1, 128.8, 129.1,
129.7, 130.1, 130.7, 130.8, 130.9, 136.5, 145.1, 155.8, 156.6, 159.5, 171.2. Anal. Calcd. for
C19H11Cl2N3O2: C, 59.39; H, 2.89; N, 10.94. Found: C, 59.41; H, 2.90; N, 10.92.
3. Results and Discussion
3.1 Synthesis and structural characterization of amino glucose‐functionalized silica‐coated
NiFe2O4 nanoparticles (NiFe2O4@SiO2@amino glucose) as catalyst
In continuation of our research for the green synthesis of organic compounds [59a-h], we
describe here the use of acidic amino glucose‐functionalized silica‐coated NiFe2O4 nanoparticles
15

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(NiFe2O4@SiO2@amino glucose) as a new, reusable and effective nanocatalyst for the synthesis
of trisubstituted benzimidazoles, benzo[d]imidazoles and benzoxazoles.
As shown in Scheme 1, the NiFe2O4@SiO2@amino glucose magnetic nanoparticles were
synthesized in three steps from commercially available materials. NiFe2O4 NPs were coated by
silica using a sol–gel process. The NiFe2O4@SiO2 core‐shell structures were then sequentially
treated with 3‐chloropropyltrimethoxysilane. Next, it was treated with aminoglucose to obtain
the amino glucose‐functionalized silica‐coated NiFe2O4 nanoparticles.
Scheme 1. Stepwise synthesis pathway of NiFe2O4@SiO2@glucoseamine
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The FT-IR spectra of NiFe2O4, NiFe2O4@SiO2 and NiFe2O4@SiO2@amino glucose MNPs are
shown in Figure 1. The absorption band in 594 cm-1 is related to the stretching vibration of the
Fe–O bond of bare NiFe2O4 that was appeared in 590 cm-1 in the FT-IR spectrum of the
NiFe2O4@SiO2@amino glucose MNPs. The absorption bands of Si-O-Si vibrations in SiO2 shell
were appeared in 1045 and 1130 cm-1 in NiFe2O4@SiO2 spectra that seemed at 1033, 1137 and
767 cm-1 in the spectrum of the NiFe2O4@SiO2@amino glucose MNPs. Also, the peaks at 1645
and 3429 cm-1 (in the spectrum of the NiFe2O4) and at 1645 and 3423 cm-1 (in the spectrum of
the NiFe2O4@SiO2@amino glucose MNPs) are attributed to the stretching vibrations of the
hydroxyl (–OH) groups on the surface of MNPs. The peaks in region 2950 and 3120 cm-1 refer to
the stretching band of C-H aliphatic and NH stretching in NiFe2O4@SiO2@amino glucose
MNPs.
Figure 1. FT‐IR spectra of (a) NiFe2O4, (b) NiFe2O4@SiO2, (c) NiFe2O4@SiO2@ aminoglucose
MNPs
Next, the morphology and nanoparticle size of the synthesized magnetic catalyst were
characterized by transmission electron microscope (TEM) (Figure 2). As shown in Figure 2, the
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catalyst particles possess near spherical morphology with average diameter of about 20–40 nm.
Furthermore, TEM images show some aggregation, which was illustrated the successful grafting
of the polymer on to magnetic nanoparticles.
Figure 2. The TEM image of synthesized NiFe2O4@SiO2@ aminoglucose
The structure of NiFe2O4@SiO2@aminoglucose was also confirmed by XRD analysis. In
Figure 3, the XRD patterns of NiFe2O4@SiO2@aminoglucose MNPs and pure NiFe2O4 (from
JCPDS No. 54-0964) are illustrated. The comparison of the XRD patterns indicated that both
patterns exhibits peaks with 2θ at 30°,36°, 45°, 50°, 54°, 58° and 62° which are representative of
the structure and broad peak in 10-30° is related to NiFe2O4 covered by SiO2.
Figure 3. The XRD patterns of a) NiFe2O4@SiO2@ aminoglucose and b) NiFe2O4
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The results of energy dispersive X-ray spectroscopy (EDX) analysis of the synthesized
NiFe2O4@SiO2@aminoglucose MNPs (Figure 4) proved existence of Fe (30.17 w/w %), O
(16.21 w/w %), Si (2.2 w/w %), N (0.45 w/w %), C (5.30 w/w %) and Ni (31.12 w/w %) atoms
in the structure that confirms the presence of NiFe2O4 core in the structure of MNP.
Figure 4. EDX results of the synthesized NiFe2O4@SiO2@ aminoglucose MNPs
In order to investigate the thermal stability of the synthesized nanocatalyst, thermal gravimetric
and derivative thermal gravimetric analysis (TGA and DTG) of the NiFe2O4@SiO2@
aminoglucose MNPs were carried out from 50–700 °C at a heating rate of 10 °C min–1 under air
atmosphere (Figure 5). The synthesized MNPs showed no weight losses at temperatures below
108.5 °C. Therefore, they are stable at working temperatures up to 108.5 oC. With increasing the
temperature, a little weight losses observed with a maximum in 131.8 oC that could be due to the
removal of physically adsorbed water molecules which were adsorbed during the synthesis of
nanoparticles. Further increase in temperature causes more weight losses in different steps that
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ACCEPTED MANUSCRIPT
can be related to the desorption of the chemisorbed water on the MNPs surface and also,
complete removal of aminoglucose groups from the MNPs.
Figure 5. Thermogram of TGA (blue colour) and DTG (red colour) analysis of the synthesized
NiFe2O4@SiO2@ aminoglucose MNPs.
Figure 6 shows the hysteresis loop of the synthesized NiFe2O4@SiO2@ aminoglucose MNPs.
VSM measurements were carried out at room temperature by taking the solid sample on the tips
of the vibrating rod and analyzing in an applied magnetic field sweeping from −20 to 20 kOe.
The curve confirms the magnetic property of synthesized nanocatalyst that is in agreement with
other studies [60].
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1.5
1
0.5
0
-20000 -15000 -10000 -5000
0
5000
10000 15000 20000
-0.5
-1
-1.5
Applied field (Oe)
Figure 6. Vibrating scanning magnetometery (VSM) curve of the synthesized nanocatalyst
In order to investigate the surface charge of MNPs that influences their physical stability in
solution, zeta potential values were measure using the Zetasizer instrument. Zeta potential values
provide an indirect measurement of the net charge on the nanoparticle surface and often used as
an indicator of dispersion stability. It value can be used as a criteria to determine particles
tendency to aggregate in aqueous media. In the present study, the zeta potential and mobility
were measured as -31.3 mv and -2.45 µmcm/Vs, respectively at 298 K with count rate of 94.4
kcps (Figure 7). The large zeta potential obtained in this study predicts a more stable dispersion
of synthesized MNPs.
Figure 7. Statistics graph of zeta potential measurement
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3.2. Catalytic studies
In order to evaluate the catalytic capability of the synthesized heterogeneous catalyst
(NiFe2O4@SiO2@ glucose amine) in organic reactions, we chose to examine its activity in a
one‐pot reaction for the synthesis of 2,4,5-triaryl-1H-imidazoles using the reaction between
aldehyde 1, 1,2-Diketone 2 or α-hydroxyketone 3 and ammonium acetate (Scheme 2).
Scheme 2. Synthesis of trisubstituted imidazoles using NiFe2O4@SiO2@amino glucose
Initially, we observed that the reaction of 4-nitrobenzaldehyde with benzil and ammonium
acetate in the presence of NiFe2O4@SiO2@aminoglucose could be a suitable choice for the
synthesis of trisubstituted imidazoles. This protocol proceeds fairly at room temperature to afford
product 4f in high yield. We have also carried out the sample reaction in the presence of
NiFe2O4, NiFe2O4@SiO2, SiO2 or in the absence of catalyst. On the other hand, variables
affecting on the reaction yields such as the type of solvent, the amount of catalyst, different
temperatures, and solvent-free conditions were studied (Table 1). As shown in Table 1, the
reaction under solvent‐free conditions is more efficient.
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Table 1. Screening the reaction parameters for the synthesis of trisubstituted imidazoles
entry
1
catalyst
Catalyst
amount
-
Reaction
condition
Reflux in
EtOH
Time (min) Yield (%)
-
720
trace
SiO2
NiFe2O4
NiFe2O4@SiO2
0.05 g
0.05g
0.05g
Stir, rt, EtOH 750
Stir,rt, EtOH 720
15
24
53
2
3
4
Stirr, rt,
EtOH
300
NiFe2O4@SiO2@
aminoglucose
NiFe2O4@SiO2@
aminoglucose
NiFe2O4@SiO2@
aminoglucose
NiFe2O4@SiO2@
aminoglucose
NiFe2O4@SiO2@
aminoglucose
NiFe2O4@SiO2@
aminoglucose
NiFe2O4@SiO2@
aminoglucose
0.05g
0.07g
0.03g
0.05g
0.05g
0.05g
0.05g
Stir, rt, EtOH 40
Stir, rt, EtOH 40
Stir, rt, EtOH 60
90
87
85
76
84
97
98
5
6
7
Stir, rt,
CH3CN
Stir, rt, H2O
60
25
8
9
Solvent free, 10
rt
Solvent free, 10
80°C
10
11
To present the efficiency and generality of the reaction, various aldehydes were reacted with
benzil or benzoin and ammonium acetate in the presence of NiFe2O4@SiO2@aminoglucose
under solvent free condition. The results are summarized in Table 2.
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Table 2. Synthesis of trisubstituted imidazoles
benzil
Time
(min)
8
benzoin
Time
(min)
12
Mp(°C)
Entry Aldehyde
Product
Yield
(%)a,b
98
Yield
(%)a,b
99
Found
Reported
269-271
238-240
272-274 [61]
-
Benzaldehyde
1
2
4a
4b
11
93
15
96
4-N,N-
Dimethylbenzaldehyde
13
8
92
95
90
97
92
94
91
92
93
92
90
15
10
17
13
16
13
17
11
15
13
18
95
96
93
99
94
97
93
95
95
96
93
226-228
265-267
187-188
223-225
228-229
257-259
226-227
>300
-
4-Hydroxybenzaldehyde
4-Chlorobenzaldehyde
2-Chlorobenzaldehyde
4-Nitrobenzaldehyde
4-Methoxybenzaldehyde
4-Bromobenzaldehyde
4-Methylbenzaldehyde
3-Nitrobenzaldehyde
Furfural
3
4c
4d
4e
4f
262-264 [61]
4
13
10
13
10
15
8
190-191 [61]
5
-
6
228-231 [61]
7
4g
4h
4i
263-265 [62]
8
230-232 [62]
9
>300 [62]
10
11
12
13
4j
11
11
15
221-223
276-278
243-244
-
-
-
4k
4l
4-Pyridinecarbaldehyde
Propanal
4m
aAll the isolated products were characterized on the basis of their physical properties and IR, 1H- spectra and
elemental analysis and by direct comparison with authentic materials if there are; bIsolated yields
To check the efficiency of this method, the comparison between this method and some of
previous reported methods for the synthesis of 4f was carried out (Table 3).
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Table 3. Comparison of synthesis of compound 4f in this method with some of previous reported
methods
Catalyst
Condition
Heat, 120 °C
Heat, 80 °C
Time /
min
50
Yield, %
Ref.
[63]
[64]
89
97
NBS
30
ZrOCl2.8H2O
Stir, rt
498
30
82
90
[65]
[66]
InCl3.3H2O
Fe3O4 nanoparticles
Stir, 80 o C
Heat, 80 °C
30
10
97
97
[67]
[Hmim]TFA
Solvent free, rt
This work
NiFe2O4@SiO2@
aminoglucose
Anomeric effect has found its influential position in the field of chemistry and it can be
defined as stereoelectronic stabilizing effect that favor the placement of electronegative
substituents in the axial, rather than equatorial, position in a pyranoid ring system at C1 [68].
Recently, Zolfigol et al. have introduced a new mechanistic outlook for the oxidative
aromatization of some heterocyclic compounds based on anomeric effect and present the term of
“anomeric based oxidation (ABO)” as an explanation for the final step of aromatization
mechanism [68-70]. In the proposed mechanism Described based of anomeric based oxidation
(Scheme 3), initially aldehyde and benzil were activated by NiFe2O4@SiO2@aminoglucose and
converted to corresponding imine followed by nucleophilic attack of iminium species of
aldehyde to the imine produced from benzil, intramolecular cyclization and departure of
ammonia lead to product 4.
The recyclability and reusability of catalyst were studied in the model one‐pot three‐component
reaction between 4‐nitrobenzaldehyde, benzil and NH4OAc. At the end of the reaction, the
separated catalyst can be reused after being washed with warm EtOH and drying at 80 °C.
25

ACCEPTED MANUSCRIPT
NiFe2O4@SiO2@aminoglucose was used again for subsequent experiments under similar
reaction conditions. The catalyst could be reused for the next cycle without any notable loss of
its activity. Yields of the product decreased only slightly after reusing the catalyst five times
(Figure 8).
NH
HO
NH3
O
OH
H
-H2O
NH4OAc
H
H
R
R
O
R
NH
OH
O
-2H2O
NH4OAc
NH
O
HO
HO
NH2
OH
NH
N
NH2
H
H
O
N
NH
NH
NH
H
O
N
H
R
-NH3
4
Scheme 3. The proposed mechanism for the synthesis of trisubstituted imidazoles
26

ACCEPTED MANUSCRIPT
100
50
0
5
4
3
2
1
run of recyclability
Figure 8. The recyclability of NiFe2O4@SiO2@ glucose amine MNPs for the synthesis of tri-
substituted benzimidazoles
Figure 4. Representation of reaction and reusability of catalyst
27

ACCEPTED MANUSCRIPT
As a part of our program, seeking at development NiFe2O4@SiO2@glucose amine for the
preparation of pharmaceutical and heterocyclic compounds, we check the efficiency of
NiFe2O4@SiO2@ aminoglucose for the synthesis of benzo[d]imidazole via two component
reaction of aldehydes and 1,2- diaminobenzene under solvent free reaction (Scheme 4).
Scheme 4. Synthesis of benzo[d]oxazoles using NiFe2O4@SiO2@ aminoglucose
To present the efficiency and generality of the reaction, various aldehydes were reacted with
1,2-diaminobenzene in the presence of NiFe2O4@SiO2@aminoglucose MNPs under solvent free
condition. The results are summarized in Table 4.
Table 4. Synthesis of benzo[d]imidazoles using NiFe2O4@SiO2@ aminoglucose
Entry Aldehyde
Product Time
(min)
Yield
(%)a,b
98
Mp (°C)
Found
130-132
252-254
Reported[59h]
132
Benzaldehyde
6a
6b
5
7
1
2
252
4-N,N-
96
Dimethylbenzaldehyde
4-Chlorobenzaldehyde
4-Bromobenzaldehyde
4-Methoxybenzaldehyde
2-Chlorobenzaldehyde
2-Hydroxybenzaldehyde
4-Nitrobenzaldehyde
4-Hydroxybenzaldehyde
Furfural
137-139
200-201
131-133
154-155
200-202
117-119
255
137
6c
6d
6e
6f
6g
6h
6i
5
5
7
9
10
5
10
7
97
98
95
93
90
97
94
95
96
3
4
5
6
7
8
9
10
196-198
131
155
207-208
118
253-254
96
94-95
6j
6k
132-133
130
2-Pyridincarbaldehyde
7
11
a
All products were characterized by their physical constant, comparison with authentic samples, IR, NMR
spectroscopy and elemental analysis. bYields based upon starting aldehyde
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ACCEPTED MANUSCRIPT
In the proposed mechanism, initially aldehyde and 1,2-diaminobenzene were activated by
NiFe2O4@SiO2@ glucose amine and converted to corresponding imine. Then, the diimine was
activated by NiFe2O4@SiO2@glucoseamine MNPs to iminium spiece followed by cyclization
lead to final product (Scheme 5).
N
HO
H2N
O
N
N
-2H2O
N
H
H
H2N
O
6
Scheme 5. Mechanistic pathway for the synthesis of benzo[d]imidazoles
To check the efficiency of this method, the comparison between this method and some of
previous reported methods for the synthesis of 6a was carried out (Table 5).
Table 5. Comparison of synthesis of compound 6a in this method with some of previous
reported methods
Entry
1
Reagent
Condition
Time
Yield (%)
Ref.
silica sulfuric rt
acid
1.5 h
75
[71]
RuCl2(PPh3)3
AcOH, O2
AcOH, O2
100 °C
20 h
90
97
92
[72]
[73]
[74]
2
3
4
MW, 50°C
4 min
25 min
Reflux, 80 °C
29