An efficient green protocol for the synthesis of tetra-substituted imidazoles catalyzed by zeolite BEA: Effect of surface acidity and polarity of zeolite

Article abstract of DOI:10.1039/c7cy01398a

In the present study, the catalytic activity of various medium (H-ZSM-5) and large pore (H-BEA, H-Y, H-MOR) zeolites were studied as solid acid catalysts. The zeolite H-BEA is found to be an efficient catalyst for the synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles through one-pot, 4-component reaction (4-CR) between benzil, NH₄OAc, substituted aromatic aldehydes and benzyl amine. The hydrophobicity, Si/Al ratio and acidic properties of zeolite BEA were well improved by controlled dealumination. The synthesized materials were characterized by various characterization techniques such as XRD, ICP-OES, BET, NH₃-TPD, FT-IR, pyridine FT-IR, ²⁷Al and ¹H MAS NMR. It has been observed that the dealumination of the parent zeolite H-BEA (12) results in the enhanced strength of Br?nsted acidity up to a certain Si/Al ratio which is attributed to the inductive effect of Lewis acidic EFAl species, leading to the higher activity of the zeolite BEA (15) catalyst towards the synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles under thermal solvent-free conditions with good to excellent yields. Using the present catalytic synthetic protocol, diverse tetra-substituted imidazoles, which are among the significant biologically active scaffolds, were synthesized in high yield within a shorter reaction time. The effect of polarity, surface acidity and extra framework Al species of the catalysts has been well demonstrated by means of pyridine FT-IR, and ²⁷Al and ¹H MAS NMR. The solvent-free synthetic protocol makes the process environmentally benign and economically viable.

Full text of DOI:10.1039/c7cy01398a

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An efficient green protocol for the synthesis of
tetra-substituted imidazoles catalyzed by zeolite
Cite this: DOI: 10.1039/c7cy01398a
BEA: effect of surface acidity and polarity of
zeolite†
a
Jenifer J. Gabla, a Sunil R. Mistryb and Kalpana C. Maheria
*
In the present study, the catalytic activity of various medium (H-ZSM-5) and large pore (H-BEA, H-Y, H-
MOR) zeolites were studied as solid acid catalysts. The zeolite H-BEA is found to be an efficient catalyst for
the synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles through one-pot, 4-component reaction (4-CR)
between benzil, NH4OAc, substituted aromatic aldehydes and benzyl amine. The hydrophobicity, Si/Al ratio
and acidic properties of zeolite BEA were well improved by controlled dealumination. The synthesized ma-
terials were characterized by various characterization techniques such as XRD, ICP-OES, BET, NH3-TPD,
1
FT-IR, pyridine FT-IR, 27Al and H MAS NMR. It has been observed that the dealumination of the parent ze-
olite H-BEA (12) results in the enhanced strength of Brønsted acidity up to a certain Si/Al ratio which is at-
tributed to the inductive effect of Lewis acidic EFAl species, leading to the higher activity of the zeolite BEA
(15) catalyst towards the synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles under thermal solvent-free
conditions with good to excellent yields. Using the present catalytic synthetic protocol, diverse tetra-
substituted imidazoles, which are among the significant biologically active scaffolds, were synthesized in
high yield within a shorter reaction time. The effect of polarity, surface acidity and extra framework Al spe-
cies of the catalysts has been well demonstrated by means of pyridine FT-IR, and 27Al and 1H MAS NMR.
The solvent-free synthetic protocol makes the process environmentally benign and economically viable.
Received 12th July 2017,
Accepted 28th September 2017
DOI: 10.1039/c7cy01398a
rsc.li/catalysis
Heterocyclic scaffolds are one of the most important
topics and receive significant attention due to their synthesis,
1. Introduction
In
modern
organic
chemical
synthesis,
one-pot
reactions and biochemical processes. The imidazole heterocy-
cle ring system containing a nitrogen atom is one of the most
imperative motifs found in a large number of natural prod-
ucts and pharmacologically active compounds. The potential
and broad application of the imidazole pharmacophore
might be attributed to its hydrogen bond donor–acceptor ca-
pacity as well as its high affinity for metals. Amongst these,
tetra-substituted imidazoles (TSIs) are important fragments
which possess a wide spectrum of biological activities, cover-
ing anti-allergic, analgesic, anti-fungal, anti-bacterial, anti-tu-
bercular, anti-inflammatory, anti-biotic, anti-mycotic, anti-ul-
cerative, anti-tumour, pesticidal, as a therapeutic agent, anti-
malarial, anti-cancer, anti-HIV and anti-viral.3 Substituted im-
idazoles also act as a glucagon receptor, a kinase inhibitor
and an antagonist of CB1 cannabinoid.4
multicomponent reactions (MCRs)1 have emerged as powerful
and efficient bond-forming tools to prepare biologically active
drug-like molecules with high selectivity and atom economy.
MCRs are well known for successful generation of products
from simple and readily available substrates without isolation
of any intermediate in a single synthetic operation and thus
avoiding disadvantages associated with stepwise sequential
approaches such as energy consumption and hazardous waste
production. These features make MCRs well-suited tools for
the easy production of various valuable heterocyclic scaf-
folds.2 Therefore, the development of new MCRs and the im-
provement of known MCRs are areas of substantial current
interest.
For the 3-component reaction (3-CR) of imidazoles, mostly
variations of the method were first reported in 1882 by
Radziszewski.5a Later, this 3-CR approach was improved ex-
tensively by Drefahl and Herma,5b showing an extra input of
amine for the 4-component reaction (4-CR) of imidazoles. In
the recent past, looking at the significant applications of TSIs
a Applied Chemistry Department, S. V. National Institute of Technology,
Ichchhanath, Surat – 395007, Gujarat, India. E-mail: kcmaheria@gmail.com
b Mandvi Science College, Mandvi – 394160, Surat, Gujarat, India
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c7cy01398a
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in medicinal chemistry, numerous high yielding and efficient
synthetic protocols have been reported on its synthesis which
involve the use of a variety of catalysts. The most common
method for the 4-CR of TSIs involves cyclo-condensation of a
1,2-diketone with aldehyde derivatives, ammonium acetate
(NH4OAc) and amines in the presence of various catalytic sys-
tems such as L-proline,6 carbon-based solid acids,7 SBA-15/
TFE,8 nano-Al-MCM-41,9 CuIJNO3)2/zeolite-HY,10 ZSM-5,3b ZSM-
5-SO3H,11 zeolite-HY,12 sulfated MCM-41,13 H-ZSM-22,14
heteropoly acids,15 SBPPSA,16 SiO2-Pr-SO3H,4 SBA-Pr-SO3H,17
and M/SAPO-34 nanocatalysts18 under solvent-free or classical
heating conditions. This synthetic procedure also involves
the use of microwave irradiation,19 ionic liquids20 and ultra-
sound irradiation.21 In addition, TSIs can also be synthesized
by hetero-Cope rearrangement, cycloaddition reaction of
mesoionic 1,3-oxazolium-5-olates with N-(arymethylene) ben-
zene-sulfonamides, condensation of a 1,2 diketone with an
aryl nitrile and a primary amine under microwave irradiation
and by N-alkylation of tri-substituted imidazoles.22 Despite
their tremendous success, several of these methods are not
environmentally friendly and suffer from one or more draw-
backs which include harsh reaction conditions, tedious work-
up and purification, strongly acidic conditions, high tempera-
ture, moderate yields, occurrence of side reactions, long reac-
tion time, expensive or toxic catalysts and reagents, require-
ments of solvents and tedious separation.
Zeolite H-BEA is gaining particular interest in research
due to its open framework structure with a three-dimensional
system of mutually intersecting 12-membered ring channels,
high thermal stability, surface area, acidity and Si/Al ratio. Ze-
olite H-BEA has been found to be an acidic catalyst because
the acid–base properties of a zeolite are influenced greatly by
the content of Si and Al in its framework. Application of zeo-
lite H-BEA is expected to give better catalytic activity due to
its higher surface area along with its moderate acidity, large
pore opening and more hydrophobic nature. Zeolite H-BEA is
often modified to tune its catalytic properties. Therefore,
modification of zeolite H-BEA is performed via
dealumination processes without destroying the microporous
structure. The synthesis of TSIs via MCRs over zeolite BEA as
a solid acid catalyst has not been reported so far. As a contin-
uation of our work on zeolite catalyzed multicomponent reac-
tions (ZCMCRs),23 the present study deals with the green syn-
thesis of TSIs using various acidic zeolites as heterogeneous
“E” catalysts (eco-friendly, efficient and economical) under
environmentally benign conditions (Scheme 1).
In the present endeavour, we have shown that textural
properties such as topology, acidity and adsorption character-
istics are influencing parameters that affect the activity of ze-
olite catalysts. The effects of dealumination on the textural
properties and concentration of acid sites of zeolite BEA and
therefore its activity toward the synthesis of TSIs have been
studied by means of FT-IR and solid state NMR techniques.
2. Experimental
2.1. Materials and methods
The glassware were rinsed with distilled water followed by ac-
etone prior to use. All the reagents used were of analytical
grade. The reactants including substituted aldehydes, both
amines and solvents were procured from Finar, Merck and
Sigma-Aldrich chemical companies (Surat, India) in the pur-
est form and were used without further purification. Melting
points were determined using open capillary tubes and were
uncorrected. All the reactions were monitored by thin layer
chromatography (TLC) performed on precoated Merck silica
gel 60F254. Compounds were visualized either with UV light
or by placing in an iodine chamber. Product yields refer to
isolated products after purification. The organic products
were characterized by spectral analysis (mass, UV, FT-IR, 1H
&
13C NMR) and elemental analysis (C, H, N) etc. UV mea-
surements were recorded on a Cary 50 Varian UV-vis spectro-
photometer at room temperature using quartz cells with a 1.0
cm path length in the range of 200–800 nm in an ethanol me-
dium. Mass spectra were recorded on a Waters Micromass
ZQ™ 400 mass spectrometer operating at an ionization po-
tential of 10–30 eV. Fourier transform infrared (FT-IR) spectra
were recorded on a DRS (8400-S-Shimadzu) FT-IR spectropho-
tometer using KBr pellets within the spectral range of 4000–
400 cm−1 and 50 scans were acquired for each spectrum. The
sample for the FT-IR measurement was prepared by adding a
small amount of the synthesized product into KBr (1 : 100 ra-
tio) followed by drying to make the pellet. 1H and 13C NMR
spectra were recorded on a Bruker-400 III Avance spectrome-
ter in a DMSO solvent at 400 MHz and 100 MHz, respectively,
using TMS as an internal standard. C, H, N analysis was car-
ried out using an Elementar Vario Micro Cube CHN analyzer.
Scheme 1 Zeolite BEA catalyzed synthesis of TSIs.
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2.2. Catalyst preparation
probe head. The pulse length was 0.58 ps, which corresponds
to π/12, for non-selective excitation. The delay time was 1 s.
The compositions of zeolites Na-BEA [H-BEA (12); Si/Al = 12],
Na-Y [H-Y (2.43); Si/Al = 2.43], Na-mordanite [H-MOR (11); Si/
Al = 11], and Na-ZSM-5 [H-ZSM-5 (15); Si/Al = 15] were
obtained from Sud-Chemie India Pvt. Ltd., India. The
H-forms of the zeolites were prepared through ion-exchange
of the Na-form of the zeolite samples using an aqueous solu-
tion of NH4NO3 (1 M), followed by overnight drying and cal-
cining at 550 °C for 5 h.
H-BEA zeolites with different Si/Al ratios having different
surface areas and acidities were prepared by dealumination
of the parent zeolite [H-BEA (12)p] using HNO3, as per a
reported method.24 In this process, zeolite H-BEA (12)p was
dealuminated by heating at 85 °C with 55 wt% of HNO3 (60 g
acid per 1 g of zeolite) for 12 h. The dealuminated zeolite
was filtered and repeatedly washed with deionised water and
dried at 100 °C. After that, it was washed with dilute ammo-
nia solution (1% solution) to remove residual acid and free
of Al and dried at 100 °C for 2 h. The procedure was repeated
to obtain dealuminated samples to different extents (Si/Al ra-
tio: 15, 25, 34). All the catalysts were calcined in air at 550 °C
for 5 h prior to use in the reactions.
2.4. General procedure for the synthesis of TSIs
All the zeolites were activated by heating at 550 °C for 2–3 h
before placing them into a round bottom flask (RBF).
All the reactions were carried out in a 50 ml RBF attached
to a condenser and equipped with a magnetic stirrer under
heating in an oil bath. In a typical reaction, a mixture of
benzil (1 mmol), ammonium acetate (4 mmol), substituted
aldehydes (1 mmol), both amines (1 mmol) and zeolite
H-BEA (15) (2 wt%) were heated at 100 °C with continuous
stirring for 15 min. The completion of reaction was moni-
tored by TLC (n-hexane : ethyl acetate). Upon completion of re-
action, the reaction mass was allowed to cool at room tem-
perature, followed by addition of ethanol. The spent catalyst
was collected from the residual reaction mixture by filtration
under reduced pressure and then washed with ethanol. The
crude imidazole solid product was recovered by evaporating
the solvent and was further purified via recrystallization with
hot ethanol to obtain the pure 1-benzyl-2,4,5-triphenyl-1H-
imidazole and 1,2,4,5-tetraphenyl-1H-imidazole having melt-
ing points of 160–162 °C and 214–216 °C (reported: 160–165
°C and 215–217 °C) in 99% and 86% yield with benzyl amine
and aniline, respectively.
2.3. Catalyst characterization
The crystalline phase identification and phase purity of all
calcined zeolites with different Si/Al ratios were analyzed
using a powder X-ray diffractometer (XRD, D8 Advance
Bruker AXS, Germany) with Cu-Kα radiation (Kα = 1.5403 Å)
using a nickel filter. The Si/Al ratio of the zeolite samples
were measured using a Perkin Elmer Optima 3300 RL induc-
tively coupled plasma-optical emission spectrometer (ICP-
OES). The specific surface area of the zeolite samples were
measured by the BET method using a Micromeritics Gemini
instrument at −196 °C using N2 adsorption isotherms. Tem-
perature programmed desorption (TPD) of ammonia was
used to determine the acidity of the zeolites using a Micro-
meritics Chemisorb 2720 acidity analyzer. NH3 was
chemisorbed at 120 °C and then desorption was carried out
up to 700 °C at a heating rate of 10 °C min−1. The FT-IR spec-
tra of the zeolite BEA samples were recorded on a Shimadzu
FTIR-8400-S spectrometer. The Lewis and Brønsted acidity of
the zeolite samples were measured by pyridine FT-IR spectro-
scopy in the region 1400–1600 cm−1 after pyridine adsorption
on zeolite samples at 110 °C and the spectra were recorded
on the same FT-IR instrument. Solid state magic angle spin-
ning (MAS) NMR measurements were performed using a
Bruker Avance AMX 400 spectrometer operating at 9.4 T static
fields. 1H MAS NMR measurements were performed at a reso-
nance frequency of 400 MHz. Spectra were recorded using a 4
mm probe head at a spinning rate of 10 kHz, a pulse length
of 2.8 ps (π/4) and a delay time of 10 s. All samples had been
previously dehydrated under vacuum at 350 °C for 6 h. 27A1
MAS NMR spectra were recorded at a resonance frequency of
104 MHz and at a spinning rate of 12 kHz, using a 4 mm
The desired product, 1-benzyl-2,4,5-triphenyl-1H-imidazole
(5a), was confirmed by comparison of their physical and spec-
tral data with those of authentic samples.6,19,22c,25 The spec-
tral data of the novel product synthesized using 4-chloro-3-
nitro benzaldehyde as a new aldehyde functionality (Table 4,
entry 5h) are given below:
2.4.1. 1-Benzyl-2,4,5-triphenyl-1H-imidazole (5a, n = 1).
Off-white solid; m.p.: 160–162 °C; anal. calcd. for C28H22N2:
C, 87.01, H, 5.74, N, 7.25%. Found: C, 87.13, H, 5.70, N,
7.19%; UV (λmax, ethanol) = 280 nm; FT-IR (KBr, cm−1): 3060
(C–H stretch), 3031, 1600 (CN), 1497, 1483, 1447 (CC),
1
1352 (C–N stretch), 769, 697 (C–H band); H NMR (400 MHz,
DMSO): 5.16 (s, 2H, CH2), 6.74–7.67 (m, 20H, Ar–H) ppm; 13C
NMR (100 MHz, DMSO): 47.6 (CH2, C8), 125.1 (CHarom, C28),
126.0 (CHarom, C26), 126.2 (CHarom, C30), 126.4 (CHarom, C11),
127.0 (CHarom, C15), 127.1 (CHarom, C16), 127.7 (CHarom, C20),
128.0 (CHarom, C21), 128.1 (CHarom, C25), 128.4 (CHarom, C13),
128.5 (CHarom, C18), 128.6 (CHarom, C27), 128.8 (C1), 128.8
(CHarom, C12), 128.9 (CHarom, C14), 130.1 (CHarom, C17), 130.3
(CHarom, C19), 130.5 (CHarom, C22), 130.7 (CHarom, C24), 131.0
(CHarom, C29), 134.4 (CHarom, C9), 135.1 (CHarom, C23), 136.8
(CHarom, C7), 137.0 (CHarom, C10), 137.2 (CHarom, C6), 145.4
(C2), 147.0 (C4) ppm; MS: m/z = 387.5 (M + H)+.
2.4.2. 1,2,4,5-Tetraphenyl-1H-imidazole (5a, n = 0). Off-
white solid; m.p.: 214–216 °C; anal. calcd. for C27H20N2: C,
87.07, H, 5.41, N, 7.52%. Found: C, 87.11, H, 5.39, N, 7.45%;
UV (λmax, ethanol) = 286 nm; FT-IR (KBr, cm−1): 3061 (C–H
stretch), 3030, 1601 (CN), 1497, 1481, 1447 (CC), 1352
(C–N stretch), 760, 697 (C–H band); 1H NMR (400 MHz,
DMSO): 7.15–8.11 (m, 20H, Ar–H) ppm; 13C NMR (100 MHz,
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Table 1 Physicochemical properties of various zeolites used in the synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles
Ammonia uptake (mmol g−1
)
Si/Al ratio
(wt%)
SBET
Pore volume
Pore structure
(nm)
Entry
1
Catalysts
(m2 g−1
)
(cm3 g−1
0.27
)
Weak
0.70
Strong
0.89
Total
H-BEA (12)pa
12
680
0.76 × 0.64
0.55 × 0.55
—
—
—
0.74 × 0.74
0.65 × 0.70
0.53 × 0.56
1.60
2
3
4
5
6
7
H-BEA (15)
H-BEA (25)
H-BEA (34)
H-Y (2.43)
H-MOR (11)
H-ZSM-5 (15)
15
25
34
2.43
11
710
732
750
480
412
320
0.30
0.34
0.36
0.34
0.22
—
0.57
0.35
0.22
2.30
2.02
1.95
0.70
0.40
0.30
—
2.39
1.40
1.27
0.75
0.52
2.30
4.41
3.35
15
a
The parent zeolite.
DMSO): 125.1 (CHarom, C25 & C29), 126.3 (CHarom, C10), 126.4
(CHarom, C14), 127.2 (CHarom, C15), 128.0 (CHarom, C19), 128.1
(CHarom, C20), 128.2 (CHarom, C24), 128.2 (CHarom, C27), 128.3
(CHarom, C12), 128.4 (CHarom, C17), 128.6 (CHarom, C11), 128.7
(CHarom, C13), 129.1 (CHarom, C16), 129.4 (CHarom, C18), 129.5
(CHarom, C21), 130.3 (CHarom, C23), 131.0 (CHarom, C26), 131.2
C28H21ClN2: C, 79.89, H, 5.03, N, 6.66%. Found: C, 79.92, H,
5.07, N, 6.61%; FT-IR (KBr, cm−1): 3057 (C–H stretch), 2936,
1610, 1598 (CN), 1477, 1448, 1414 (CC), 1357 (C–N
stretch), 757 (C–Cl stretch); 1H NMR (400 MHz, DMSO-d6):
5.09 (s, 2H, CH2), 6.72–7.60 (m, 19H, Ar–H) ppm; 13C NMR
(100 MHz, DMSO): 48.3 (CH2, C25), 125.5 (CHarom, C29), 126.0
(CHarom, C7), 126.2 (CHarom, C11), 126.4 (CHarom, C13), 126.5
(CHarom, C17), 126.6 (CHarom, C27), 127.3 (CHarom, C31), 127.9
(CHarom, C28), 128.0 (CHarom, C30), 128.1 (CHarom, C9), 128.2
(CHarom, C15), 128.5 (CHarom, C18), 128.7 (CHarom, C19), 128.8
(CHarom, C28), 131.3 (CHarom, C22), 132.1 (C1), 134.3 (CHarom
,
C7), 135.5 (CHarom, C6), 136.6 (CHarom, C8), 136.8 (C2), 145.4
(CHarom, C9), 145.9 (C4) ppm; MS: m/z = 373.0 (M + H)+.
2.4.3. 1-Benzyl-2-(3-nitrophenyl)-4,5-diphenyl-1H-imidazole
(5b, n = 1). Pale yellow solid; m.p.: 151–153 °C; anal. calcd.
for C28H21N3O2: C, 77.94, H, 4.91, N, 9.74%. Found: C, 77.88,
H, 4.85, N, 9.60%; FT-IR (KBr, cm−1): 3058 (C–H stretch),
2972, 1600 (CN), 1520 (N–O stretch), 1497, 1480, 1450
(CC), 1350 (C–N stretch), 735, 696 (C–H band); 1H NMR
(400 MHz, DMSO-d6): 5.15 (s, 2H, CH2), 6.8–8.5 (m, 19H, Ar–
H) ppm; 13C NMR (100 MHz, DMSO): 48.4 (CH2, C8), 125.6
(CHarom, C23), 125.6 (CHarom, C25), 126.0 (CHarom, C28), 126.6
(CHarom, C23), 129.2 (CHarom, C8 & C10), 129.2 (CHarom, C14
&
C16), 129.5 (CHarom, C20), 130.4 (CHarom, C22), 131.1 (C2),
134.1 (CHarom, C6), 134.3 (CHarom, C21), 137.4 (CHarom, C26),
138.8 (CHarom, C12),142.3 (C4), 147.9 (C1) ppm; MS: m/z = 421
(M + H)+.
2.4.5. 1-Benzyl-2-(4-methylphenyl)-4,5-diphenyl-1H-imidaz-
ole (5f, n = 1). Off-white solid; m.p.: 158–160 °C; anal. calcd.
for C29H24N2: C, 86.97, H, 6.04, N, 6.99%. Found: C, 86.88, H,
6.00, N, 6.80%; FT-IR (KBr, cm−1): 3059 (C–H stretch), 3027,
1600 (CN), 1496, 1481, 1446 (CC), 1359 (C–N stretch),
(CHarom, C11 & C15), 127.1 (CHarom, C16 & C26), 127.7 (CHarom
C20 & C30), 128.2 (CHarom, C27 & C29), 128.5 (CHarom, C13
C18), 129.3 (CHarom, C12, C14, C17 & C19), 130.4 (CHarom, C22),
132.1 (CHarom, C9), 134.3 (CHarom, C7 & C21), 137.2 (CHarom
,
&
1
768, 694 (C–H band); H NMR (400 MHz, DMSO): 2.06 (s, 3H,
,
CH3), 5.0 (s, 2H, CH2), 6.7–7.6 (m, 19H, Ar–H) ppm; 13C NMR
(100 MHz, DMSO): 23.4 (CH3, C24), 48.4 (CH2, C24), 125.1
(CHarom, C19), 126.0 (CHarom, C23), 126.2 (CHarom, C29), 126.4
(CHarom, C7), 127.0 (CHarom, C11), 127.1 (CHarom, C13), 127.7
(CHarom, C17), 128.0 (CHarom, C18), 128.1 (CHarom, C27), 128.4
(CHarom, C31), 128.5 (CHarom, C28), 128.6 (CHarom, C30), 128.8
(CHarom, C9), 128.8 (CHarom, C15), 128.9 (CHarom, C8), 130.1
(CHarom, C10), 130.3 (CHarom, C14), 130.5 (CHarom, C16), 130.7
C6 C10), 129.6 (C1), 144.4 (C2), 147.8 (CHarom, C24), 150.9
&
(C4) ppm; MS: m/z = 430.4 (M + H)+.
2.4.4. 1-Benzyl-2-(4-chlorophenyl)-4,5-diphenyl-1H-imidaz-
ole (5c, n = 1). White solid; m.p.: 161–163 °C; anal. calcd. for
Table
2 Synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles using
various modified zeolitesa
(CHarom, C20), 131.0 (CHarom, C22), 134.4 (C2), 135.1 (CHarom
C21), 136.8 (CHarom, C6), 137.0 (CHarom, C26), 137.2 (CHarom
C12), 145.4 (C4), 147.0 (C1) ppm; MS: m/z = 401.0 (M + H)+.
,
,
Entry
Catalyst
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
No catalyst
H-BEA (12)p
H-BEA (15)
H-BEA (25)
H-BEA (34)
H-Y (2.43)
720
60
60
60
60
165
140
165
N. R.c
86
95
83
75
83
80
70
2.4.6. 1-Benzyl-2-(4-chloro-3-nitrophenyl)-4,5-diphenyl-1H-
imidazole (5h, n = 1). Pale yellow solid; m.p.: 168–170 °C;
anal. calcd. for C28H20ClN3O2: C, 72.18, H, 4.33, N, 9.02%.
Found: C, 71.10, H, 4.51, N, 8.98%; (λmax, ethanol) = 301 nm;
FT-IR (KBr, cm−1): 3098 (C–H stretch), 3062, 1602 (CN),
1533 (N–O stretch), 1448 (CC), 1352 (C–N stretch), 732 (C–
H-MOR (11)
H-ZSM-5 (15)
1
H band), 699 (C–Cl stretch); H NMR (400 MHz, DMSO): 5.24
a
Reaction conditions: benzil (1 mmol), NH4OAc (4 mmol),
benzaldehyde (1 mmol), benzyl amine (1 mmol), catalyst (2 wt%)
(s, 2H, CH2), 6.81–8.35 (m, 18H, Ar–H) ppm; 13C NMR (100
MHz, DMSO): 47.8 (CHarom, C8), 124.3 (CHarom, C24), 125.7
(CHarom, C30), 126.1 (CHarom, C10), 126.5 (CHarom, C15), 126.9
b
under ethanol reflux conditions, oil bath. The yield refers to the
pure isolated products. c No reaction.
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Table 3 Effect of solvent on the synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazolesa
Entry
Solvents
Reflux temperature (°C)
Time (min)
Yieldb (%)
1
2
Water
Ethanol
100
70
420
60
N. R.c
95
3
Methanol
65
60
86
4
5
6
7
8
9
10
Glacial acetic acid
Acetonitrile
Acetone
115
80
54
105
60
38
60
82
50
60
94
150
150
360
360
360
15
Toluene
Chloroform
Dichloromethane
Solvent-free
48
N. R.c
99
100
a
Reaction conditions: benzil (1 mmol), NH4OAc (4 mmol), benzaldehyde (1 mmol), benzyl amine (1 mmol), catalyst (2 wt%) under reflux
conditions, oil bath. The yield refers to the pure isolated products. c No reaction.
b
Table 4 Synthesis of TSIs using a catalytic amount of zeolite BEA (15) under solvent-free conditionsa
M.P. (°C)
Time
(min)
Yieldc
(%)
Entryb
–R
n
Found
Reported
5a
–CHO
1
0
1
0
1
0
1
0
1
0
1
0
1
0
1
0
15
30
25
50
25
50
20
30
25
50
25
30
30
60
15
35
99
86
88
81
94
93
93
85
90
89
92
83
86
78
91
84
160–162
216–218
152–154
250–252
160–162
148–150
133–135
280–282
158–160
152–154
163–165
188–190
176–178
150–152
168–170
190–192
160–165 (ref. 3c)
217–218 (ref. 3c)
150–152 (ref. 25)
248–250 (ref. 17)
160–162 (ref. 27)
148–151 (ref. 3c)
131–132 (ref. 27)
282–284 (ref. 3b)
157–160 (ref. 22c)
—
164–166 (ref. 27)
189–190 (ref. 27)
175–178 (ref. 30)
149–152 (ref. 30)
Present work
5b
5c
5d
5e
5f
3-NO2–CHO
4-Cl–CHO
4-OH–CHO
3-Br–CHO
4-CH3–CHO
2-OCH3–CHO
4-Cl-3-NO2–CHO
5g
5h
a
Reaction conditions: benzil (1 mmol), NH4OAc (4 mmol), aldehydes (1 mmol), benzyl amine or aniline (1 mmol) and catalyst (2 wt%) under
b
c
solvent-free conditions, oil bath. Products (5a–g) were characterized and compared for their physical properties with authentic samples. The
yield refers to the pure isolated products.
(CHarom, C14), 127.1 (CHarom, C12), 127.3 (CHarom, C31), 127.6
(CHarom, C28), 127.9 (CHarom, C22), 128.3 (CHarom, C32), 128.5
(CHarom, C29), 128.6 (CHarom, C19), 128.9 (CHarom, C17), 129.1
(CHarom, C18), 129.4 (CHarom, C16), 129.5 (CHarom, C13), 129.9
(CHarom, C10), 128.2 (CHarom, C27), 128.5 (CHarom, C22), 128.6
(CHarom, C17), 129.3 (CHarom, C12), 129.5 (CHarom, C18), 129.7
(CHarom, C16), 129.8 (CHarom, C11), 130.3 (CHarom, C13), 130.4
(CHarom, C21), 131.0 (CHarom, C23), 131.7 (CHarom, C9), 132.3
(CHarom, C11), 130.7 (C1), 131.5 (CHarom, C9), 131.9 (CHarom
C21), 132.9 (CHarom, C7), 133.9 (CHarom, C20), 135.5 (CHarom
C27), 136.7 (CHarom, C6), 137.4 (C2), 143.6 (CHarom, C23), 147.4
(C4) ppm; MS: m/z = 466.0 (M + H)+.
,
,
(CHarom, C26), 132.4 (C1), 133.8 (CHarom, C7), 135.8 (CHarom,
C25), 137.4 (CHarom, C6), 142.4 (CHarom, C8), 142.7 (C2), 147.1
(C4), 147.7 (CHarom, C28) ppm; MS: m/z = 452.0 (M + H)+.
The reusability of the catalyst was investigated for each
recycling by separating the spent catalyst from the reaction
mixture by filtration under reduced pressure, followed by
washing with ethanol, drying overnight at 100 °C and re-
activating it by heating in a stream of air at 550 °C for 5 h.
2.4.7. 2-(4-Chloro-3-nitrophenyl)-1,4,5-triphenyl-1H-imidaz-
ole (5h, n = 0). Pale yellow solid; m.p.: 189–191 °C; anal.
calcd. for C27H18ClN3O2: C, 71.76, H, 4.01, N, 9.30%. Found:
C, 70.96, H, 4.22, N, 9.02%; (λmax, ethanol) = 299 nm; FT-IR
(KBr, cm−1): 3060 (C–H stretch), 1599 (CN), 1538 (N–O
stretch), 1497, 1447 (CC), 1356 (C–N stretch), 767 (C–H
band), 698 (C–Cl stretch); 1H NMR (400 MHz, DMSO): 7.18–
8.74 (m, 18H, Ar–H) ppm; 13C NMR (100 MHz, DMSO): 121.6
(CHarom, C24), 124.1 (CHarom, C20), 124.6 (CHarom, C29), 126.3
(CHarom, C19), 126.7 (CHarom, C15), 127.2 (CHarom, C14), 127.6
3. Results and discussion
3.1. Catalyst characterization
3.1.1. Physicochemical characterization of zeolites. The
physicochemical characterization data for various types of
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zeolites, such as medium and large pore size and modified
via dealumination, are provided in Table 1. It is observed that
the surface area of zeolite H-BEA and dealuminated BEA are
higher than that of the rest of the zeolites and the concentra-
tion of the acid centre for zeolite H-MOR is found to be
higher than that for the rest of the zeolites. Moreover, upon
controlled dealumination, the pore volume and surface area
slightly increased and the total acidity decreased with the in-
crease in Si/Al ratio.
3.1.2. XRD of the zeolite BEA. The powder XRD patterns of
parent zeolite H-BEA and all dealuminated zeolite BEA syn-
thesized via acid treatment are depicted in Fig. 1. The well-
developed diffraction lines of the zeolite H-BEA including
dealuminated zeolite BEA were discerned and they are well
resolved. The crystallinity of the samples was evaluated by
comparing the most intense diffraction peak at 22.3° (2θ) to
that of the parent zeolite taken as 100% crystalline. The
dealuminated zeolite BEA was compared with the corre-
sponding counterpart of H-BEA zeolite and found similar to
the parent zeolite indicating that the framework structure of
zeolite BEA is not affected or remains intact upon controlled
dealumination of the zeolite by aqueous HNO3. Moreover,
the position of the main intense peak did not change signifi-
cantly upon controlled dealumination but the relative crystal-
linity of the zeolite BEA showed a negligible decrease with
the increase in dealumination of the BEA zeolite. All samples
exhibited the typical pattern of highly crystalline zeolite BEA
with broad and sharp reflection and the characteristics of an
intergrowth of different polymorphs, and no other phase im-
purities were observed after the dealumination.
cm−1 attributed to the strong acidic bridged Si(OH)Al and at
3726 cm−1 assigned to weak acidic terminal Si–OH groups.
Two vibrational bands of small intensities at 3661 cm−1
&
3795 cm−1 were assigned to hydroxyl groups associated with
extra-framework aluminium species (EFAl). A band at 3250
cm−1 with a very small intensity was found for the hydrogen
bonded bridging –OH group. The IR spectrum of the
dealuminated BEA zeolite shows that the intensities of the
bands observed at 3611 cm−1 attributed to the Brønsted
acidic Si(OH)Al and at 3661 cm−1 and 3795 cm−1 attributed
to the Lewis acidic sites (LAS) of EFAl (OH) considerably de-
creased for BEA (15) and BEA (25) as compared to the par-
ent zeolite H-BEA (12)p, and these two bands almost
disappeared for BEA (34) (Fig. 2a).
The FT-IR study of the catalysts was carried out after pyri-
dine adsorption in order to investigate the acidic properties
of the catalyst materials. The result obtained has proved the
presence of LAS and BAS in the H-BEA zeolite. The spectrum
of pyridine adsorbed on the samples shows characteristic
bands corresponding to the C–C stretching vibrations of pyri-
dine. All the zeolite BEA samples exhibit well resolved bands
at about 1540, 1490 and 1447 cm−1. The bands at 1540 and
1447 cm−1 are assigned to pyridinium ions adsorbed onto
BAS (protonic) and LAS (coordinatively unsaturated Al3+ or
EFAl), respectively, while the band at 1490 cm−1 is attributed
to the adsorbed pyridinium ion species on both BAS and LAS
(B + L).
Fig. 2(b) shows that, in the case of parent H-BEA (12)p,
the band intensities of B + L and LAS are found to be higher
as compared to BAS. In contrast, the band intensity of BAS is
found to increase with the gradual decrease in B + L and LAS
for dealuminated zeolite BEA (15). Further, upon controlled
dealumination, the band intensities of LAS and B + L were
found to decrease for H-BEA (25) and H-BEA (34) due to the
removal of Al from the zeolite framework. It has been
suggested that on dealumination of the H-BEA (12)p zeolite,
some positively charged EFAl species could neutralize the
3.1.3. FT-IR and 1H MAS NMR of the zeolite BEA. The
acidic hydroxyl protons acting as catalytically active Brønsted
acid sites (BAS) which can be investigated in a direct
manner by FT-IR26 and 1H MAS NMR spectroscopy. The
spectra of zeolite H-BEA and dealuminated BEA are shown
in Fig. 2(a) and 3, respectively. Zeolite H-BEA has two main
bands and these were identified in the IR spectrum at 3611
Fig. 1 XRD patterns of (a) parent zeolite H-BEA (12)p and (b–d) dealuminated BEA.
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Fig. 2 (a) FT-IR and (b) pyridine FT-IR spectra of zeolite H-BEA and dealuminated BEA.
negative charge of the tetrahedra and AlO4 consequently de-
creases the intensity of dealuminated zeolite acid sites. Thus,
it should be concluded that removal of Al from the zeolite
framework upon controlled dealumination slightly increases
the BAS with a decrease in LAS and B + L. A corresponding
3.2. Synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles
(effect of geometry and surface acidity of zeolite)
Zeolites as solid acid catalysts with different physicochemical
characteristics were used to elucidate the role of the zeolite
channel system in their activity and selectivity towards the
synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles (Table 1).
Table 1 shows the effect of various structural features such as
the Si/Al ratio, acidity, surface area and geometry (pore struc-
ture and dimension) of zeolites on the synthesis of 1-benzyl-
2,4,5-triphenyl-1H-imidazoles.
1
decrease is observed in the intensity of H MAS NMR signals
at 4.0 and 35.1 ppm which are assigned to free bridged and
hydrogen bonded bridged hydroxyls of Si(OH)Al, respectively,
in the case of zeolite BEA (15) as compared to parent H-BEA
(12)p. A decreased intensity is also observed in the 2.7 ppm
signal which is attributed to the presence of EFAl(OH) species
for BEA (15) and disappeared for BEA (25) and BEA (34)
(Fig. 3).
Initially, the 4-CR of 1-benzyl-2,4,5-triphenyl-1H-imidazoles
was carried out using benzil (1 mmol), NH4OAc (4 mmol),
Fig. 3 1H MAS NMR spectra of zeolite H-BEA and dealuminated BEA.
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benzaldehyde (1 mmol), and benzyl amine (1 mmol) in the
absence of zeolite catalysts. It is noteworthy that no forma-
tion of products was observed in the absence of a zeolite cata-
lyst, indicating that a catalyst is necessary for the formation
of the corresponding product (Table 2, entry 1). For our in-
vestigations, subsequently, various large (H-BEA, H-Y, H-
MOR) and medium (H-ZSM-5) pore size zeolites were used
and we found that a micro-porous structure, strong acidity
and a unidirectional channel structure do not highly favour
MCRs as compared to the large pore zeolite H-BEA with a
higher surface area and low to moderate acidity. As per our
previous investigation on ZCMCRs,23 it has also been found
that the hydrophobic character of zeolite H-BEA due to the
higher Si/Al ratio as compared to the other zeolites shows
better catalytic activity towards MCRs particularly when
subjected to highly polar solvents, reactants and products as
well. Hence, it is concluded in the present case that low to
moderate acidity, along with a higher surface area and a
higher Si/Al ratio of zeolite H-BEA (Table 1), are prime factors
for higher catalytic activity towards the synthesis of 1-benzyl-
2,4,5-triphenyl-1H-imidazoles. Thus, the preferential order to
yield 1-benzyl-2,4,5-triphenyl-1H-imidazoles was found to be:
H-BEA > H-Y > H-MOR > H-ZSM-5.
the non-polar solvent toluene was found to be more efficient
along with zeolite BEA (15). Whereas, in the present case, sur-
prisingly, the polar solvent ethanol shows better catalytic ac-
tivity towards the synthesis of 1-benzyl-2,4,5-triphenyl-1H-
imidazoles using zeolite BEA (15) as a solid acid catalyst. In
this context, in order to investigate the effect of the polarity
of products with the highly polar solvent ethanol, the log P
values of DHPMs, DAPMs, 2,4,5-trisubstituted imidazoles
(work under study) have been compared with that 1-benzyl-
2,4,5-trisubstituted imidazoles (Fig. 4). It has been seen that
DHPMs and DAPMs possess lower log P values (polar) as
compared to the 2,4,5-trisubstituted imidazoles and 1-benzyl-
2,4,5-triphenyl-1H-imidazoles. As a consequence, the non-
polar solvent toluene is found to be more suitable for the syn-
thesis of DHPMs and DAPMs via MCRs. Meanwhile, the polar
solvent ethanol is found to be a more suitable solvent for the
synthesis of 2,4,5-trisubstituted imidazoles and 1-benzyl-2,4,5-
triphenyl-1H-imidazoles as it has a high log P value (less po-
lar). Further, the effects of various polar and non-polar sol-
vents on the synthesis of 1-benzyl-2,4,5-trisubstituted imidaz-
oles via ZCMCRs were also investigated. Many reports
concerning the synthesis of 1-benzyl-2,4,5-triphenyl-1H-
imidazoles shows that this reaction is highly favoured in po-
lar solvents such as ethanol and methanol.3a,b,11,15a,21,27,28 In
the present study, the expected results were obtained and are
depicted in Table 3, which shows that polar solvents are
found to be more efficient as compared to the non-polar sol-
vents in the synthesis of 1-benzyl-2,4,5-triphenyl-1H-
imidazoles.
3.3. Effect of surface polarity (Si/Al ratio) of zeolites
It is worth noting that the catalyst becomes more hydropho-
bic with increasing Si/Al framework ratio and the concentra-
tion of acid sites decreases with enhanced strength of
remaining sites. According to the results and conclusions
presented above, we could expect that the less polar zeolite
should favour the desorption of adsorbed polar products.
Hence, zeolites H-Y and H-MOR were found to be less effec-
tive towards the synthesis of 1-benzyl-2,4,5-triphenyl-1H-
imidazoles compared to H-BEA although they also contain
large pores and exhibit higher acidity. In this context, the
synthesis of 1-benzyl-2,4,5-teiphenyl-1H-imidazoles has been
carried out using zeolite H-BEA with varied Si/Al ratios (12,
15, 25 and 34) in order to study the effect of the polarity of
zeolite (Table 2). The results shown in Table 2 show the maxi-
mum activity for the zeolite with a Si/Al ratio of 15 which
contains a much lower concentration of acid sites than the
zeolite with a Si/Al ratio of 12 (Table 1). From these results, it
seems that a larger number of acid sites does not guarantee a
higher catalytic activity due to the adsorption inhibiting ef-
fect of reactants and products. Thus, in the present case, a
less polar zeolite with a lower concentration of acid sites per-
forms better. In fact, a yield of 95% (entry 5a) was obtained
with 2 wt% of BEA (15) after 60 min.
3.4. 27Al MAS NMR of zeolite BEA (effect of EFAl or LAS
insights from the FT-IR and 1H NMR studies of zeolite BEA)
In general, framework defects, tricoordinated and EFAl spe-
cies contribute to LAS and are strongly affected by
dealumination of zeolite H-BEA as indicated by the FT-IR and
solid state NMR spectra of zeolite H-BEA and dealuminated
zeolite BEA (Fig. 2 and 3). The perturbed Al(OH) hydroxyl
band at 3661 cm−1 and the very high frequency (VHF) hy-
droxyl band at 3795 cm−1 generally assigned to the EFAl of
transient or partially hydrolyzed coordinatively unsaturated
Al species considerably decreased for the dealuminated BEA
(25) and totally disappeared for BEA (34). The 27Al MAS NMR
spectrum of the zeolite is visualized in Fig. 5. As shown, a
strong signal at 54 ppm indicates the presence of a tetrahe-
drally (Td) coordinated Al framework in the zeolite BEA.
There is also a weak signal at 0.6 ppm due to the residual
EFAl with an octahedral (Oh) coordination. Most of Al, as
shown in Fig. 5, are located in the zeolite tetrahedral frame-
work positions, giving rise to bridging OH acid centres. More-
over, the spectra of all BEA zeolites show that the intensity of
the peak assigned to the extra framework octahedral Al con-
siderably decreases in all dealuminated BEA zeolites as com-
pared to the parent zeolite H-BEA (12)p. The results indicate
that increasing the rate of dealumination of zeolite H-BEA
with a mineral acid (HNO3) causes either substantial or total
Moreover, the polarity of the solvent should also be taken
into account when a zeolite catalyst is to be subjected to any
organic transformations. Generally, the non-polar solvent tol-
uene is more effective towards reactions that contain more
polar reactants or produce highly polar products. In our pre-
vious study concerning ZCMCRs for the synthesis of dihydro-
pyrimidinones (DHPMs) and diarylpyrimidinones (DAPMs),
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Fig. 4 Log P values of different biologically active moieties.
Fig. 5 27Al MAS NMR spectra of zeolite H-BEA and dealuminated BEA.
removal of framework and EFAl species which consequently
leads to a decrease in the concentration of LAS and BAS of
zeolite BEA.
ity. As a consequence, zeolite H-BEA (12)p and BEA (15) show
higher activity towards the synthesis of 1-benzyl-2,4,5-
triphenyl-1H-imidazoles (86% and 95% yield) as compared to
the highly dealuminated BEA (25) and BEA (34).
In general, the higher activity of zeolite BEA may be attrib-
uted to the higher hydrophobicity and a positive effect of the
EFAL species present on H-BEA (12)p and BEA (15), which is
due to an inductive effect of the LAS of EFAL species on the
protonic sites. Further, dealumination increases the diffusiv-
ity of the reactants and/or products thereby enhancing acces-
sibility of the acid sites to the reactant molecules by creating
mesopores in the crystallites.
Furthermore, the dealumination of zeolite resulted in the
enhanced strength of the remaining Brønsted acidity up to a
certain Si/Al ratio of zeolite by decreasing the total number of
acid sites. The enhanced strength of this Brønsted acidity can
be attributed to the partially hydrolyzed, coordinatively unsat-
urated Al species of LAS which inductively leads to a greater
negative charge delocalization in the remaining Si–O–Al
bridge, thus, creating a BAS of enhanced strength of acidity.29
Thus, it can be said that the interaction between BAS and LAS
may lead to the formation of BAS of enhanced strength of
acidity. These observations have led to the conclusion that the
decrease or removal of LAS or EFAl species not only results in
lowering the concentration of Lewis acidity but also results in
the decrease of the strength of the remaining Brønsted acid-
3.5. Synthesis of TSIs
In order to optimize the catalyst concentration and reaction
conditions, the reaction of benzil, NH4OAc, benzaldehyde
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and benzyl amine was carried out using varied amounts of
zeolite BEA (15) (1, 2 up to 5 wt%) under ethanol reflux as
well as thermal solvent-free conditions. The best result was
obtained by carrying out the reaction with a 1 : 4 : 1 : 1 molar
ratio between benzil, NH4OAc, benzaldehyde and benzyl
amine and 2 wt% of zeolite BEA (15) under solvent-free con-
ditions at 100 °C with a 99% yield within 15 min (Fig. 6).
Thus, an attempt has been made to prepare a wide range
of TSIs derivatives using the optimized reaction conditions. A
series of TSI derivatives were prepared in high to excellent
yields in thermal solvent-free conditions. The results are
summarized in Table 4. It is observed that various aromatic
aldehydes having both electron-withdrawing and electron-
donating substituents reacted efficiently with benzil, NH4OAc
and benzil amine in the presence of a catalytic amount of ze-
olite BEA (15) (2 wt%) under thermal solvent-free conditions
to give the corresponding TSI derivatives in moderate to high
(88–99%) yields. Various -o, m- and p- directing functional
groups of aromatic aldehydes were found to be compatible
under the optimized reaction conditions. The procedure
worked well for all the substituted aldehyde derivatives with-
out the formation of any side products. The novel bulkier
aldehyde substituent (Table 4, entry 5 h, n = 1) also gives an
excellent yield (91%) as compared to the other aldehyde sub-
stituents. All the reactions of aldehyde substituents have also
been repeated with aniline instead of benzyl amine as a reac-
tant in the synthesis of 1,2,4,5-tetraphenyl-1H-imidazoles and
yielded the desired product efficiently. In this case, the reac-
tion time was found to be nearly double and the % yield was
found to be lower as compared to the benzyl amine reactant.
The novel bulkier aldehyde substituent (Table 4, entry 5 h, n
= 0) also gives a good yield (85%) with the aniline reactant.
A plausible mechanism for the zeolite catalyzed synthesis
of TSIs via MCRs is outlined in Scheme 2. The zeolite cata-
lysts have several accessible LAS and BAS to promote the re-
action. As seen in Scheme 2, initially, we assumed that the
acidic sites of zeolite stimulate the carbonyl group of aro-
matic aldehydes. Subsequently, nucleophilic attack of the ni-
trogen atoms of ammonia obtained from NH4OAc and
amines on the activated carbonyl group facilitates the forma-
tion of a di-imine intermediate (I) to increase the electrophi-
licity of the carbonyl group of the aldehydes. Now, acidic
sites of the zeolite activate the carbonyl group of benzil to de-
crease the energy of the transition state. Then condensation
of the di-imine intermediate (I) with the protonated form of
benzil occurs to form intermediate (II) which in turn removes
the H2O molecule from a crude adduct and finally rearranges
to give the desired TSIs product.
3.6. Merits of method
In order to investigate the merits of method, a few represen-
tative examples are tabulated in Table 5, in which the effi-
ciency of other reported methods is compared with that of ze-
olite BEA (15) for the synthesis of TSIs. The result shows the
promising features of the zeolite BEA (15) catalyst in terms of
reaction conditions and the yield of the product compared
with those of various heterogeneous catalysts recently
reported in the literature.
Furthermore, a comparison of the FT-IR spectra of the
starting reactants and the synthesized product (Fig. 7) shows
the key advantage of the multicomponent one-pot synthesis
that it does not produce any side product. The IR spectra of
the starting raw materials such as benzaldehyde and benzil
exhibit characteristic sharp bands of CO with strong inten-
sities at 1696 and 1646 cm−1, respectively, two bands of N–H
stretching with medium intensities at 3373 and 3290 cm−1
and one medium sharp band of N–H bending at 1605 cm−1
for benzyl amine, a sharp band of CO with a strong inten-
sity at 1750 cm−1 and a medium band of C–O with a small
Fig. 6 (a) Optimization of the catalyst concentration. Reaction conditions: benzil (1 mmol), NH4OAc (4 mmol), benzaldehyde (1 mmol), benzyl
amine (1 mmol) using reflux as well as solvent-free conditions (100 °C), oil bath. (b) Effect of various temperatures. Reaction conditions: benzil (1
mmol), NH4OAc (4 mmol), benzaldehyde (1 mmol), benzyl amine (1 mmol), catalyst (2 wt%) using solvent-free conditions, oil bath. * The yield re-
fers to the pure isolated products.
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Scheme 2 Plausible mechanism for the formation of TSIs catalyzed by zeolite BEA.
Table 5 Comparison of various catalysts with zeolite BEA (15) for the one-pot synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles
Entry
Catalysts
Conditions
Time (min)
Yield (%)
References
1
2
3
4
7
8
9
10
11
12
14
15
16
17
18
L-Proline
MeOH/reflux
SF/130 °C
SF/130 °C
SF/100 °C
SF/90 °C
SF/120 °C
EtOH/reflux
MeOH/65 °C
SF/110 °C
MW
SF/100 °C
EtOH/140 °C
SF/90 °C
EtOH/reflux
SF/100 °C
510–600
60–120
15–60
15–240
210
50
8
180
40
6
60
30
32
76–88
86–94
87–97
68–96
92
92
88
56
86
85
93
81
80
92
99
Samai et al., 2009 (ref. 6)
Carbon based solid acid
FE3O4@SiO2–OSO3H
β-CD-Pr–SO3H
SBA-15/TFE
Nano-Al-MCM-41
H4ijPMo11VO40
CuIJNO3)2/zeolite-HY
ZSM-5-SO3H
Zeolite-HY
Sulfated MCM-41
H-ZSM-22
Tavakoli-Hoseini et al., 2011 (ref. 7)
Yadegarian et al., 2015 (ref. 31)
Ran et al., 2015 (ref. 27)
Rostamnia et al., 2012 (ref. 8)
Olyaei et al., 2016 (ref. 9)
Heravi et al., 20 007 (ref. 15a)
Sivakumar et al., 2010 (ref. 10)
Vosoughi et al., 2015 (ref. 11)
Balalaei et al., 2000 (ref. 12)
Vadivel et al., 2013 (ref. 13)
Bhat et al., 2016 (ref. 14)
Moosavi-Zare et al., 2014 (ref. 32)
Teimouri et al., 2011 (ref. 3b)
Present work
]
TrCl or Ph3CCl
ZSM-5
Zeolite BEA (15)
80
15
SF = Solvent-free, MW = micro-wave.
intensity at 1070 cm−1 for NH4OAc, which completely
disappeared in the IR spectrum of the synthesized final prod-
uct, indicating that the synthesis of 1-benzyl-2,4,5-triphenyl-
1H-imidazoles via MCRs took place without forming any side
product.
reusability study of the solid acid catalyst was carried out via
the reaction of benzil, NH4OAc, benzaldehyde and benzyl
amine in the presence of zeolite BEA (15) under solvent-free
conditions. The catalyst was separated from the crude prod-
uct by addition of ethanol followed by filtration. It was
washed consequently with ethanol to remove the product
completely from the catalyst under reduced pressure followed
by drying overnight at 100 °C and re-activating by heating in
a stream of air at 550 °C for 5 h and weighed. The regene-
rated catalyst was found to be reusable up to six consecutive
runs and is shown in Fig. 8. The yields for the six runs were
found to be 99%, 98%, 98%, 96%, 95% and 95%,
3.7. Reusability of solid acid catalyst for the synthesis of
1-benzyl-2,4,5-triphenyl-1H-imidazoles
In view of an environmentally friendly approach, reusability
is a very significant feature for heterogeneous catalysts. The
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Fig. 7 Comparison of the characteristic IR bands of the starting raw materials and the synthesized product.
Fig. 8 (a) Reusability of the dealuminated BEA (15) zeolite; (b) XRD patterns of fresh (black) and spent (after six runs – red) catalyst.
respectively. Furthermore, retention of the structure of the 4. Conclusion
catalyst was confirmed by comparing the XRD pattern of the
recovered catalysts with that of the fresh catalysts, for the
model reaction. The XRD pattern of the fresh zeolite was
found to be the same as that of the spent zeolite (after six
runs), indicating retention of the framework structure of the
zeolite throughout the course of the reaction, and hence it
can be reused.
The synthesis of biologically active 1-benzyl-2,4,5-triphenyl-
1H-imidazoles over various large pore zeolites (H-Y, H-MOR,
H-BEA and dealuminated BEA) has been studied. Zeolite
BEA (15) has been found to be an efficient and reusable cat-
alyst for one-pot, 4-CR of benzil, NH4OAc, substituted aro-
matic aldehydes and benzyl amine for the synthesis of
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1-benzyl-2,4,5-triphenyl-1H-imidazoles under solvent-free
conditions.
7 N. Tavakoli-Hoseini and A. Davoodnia, Chin. J. Chem.,
2011, 29, 203–206.
Moreover, the FT-IR and solid state NMR spectroscopy of
zeolite H-BEA and dealuminated BEA gave further insights
into the effect of the nature of acid sites on the synthesis of
1-benzyl-2,4,5-triphenyl-1H-imidazoles. It has been found that
the dealumination of parent zeolite BEA results in enhanced
strength of Brønsted acidity up to a certain Si/Al ratio due to
the inductive effect of Lewis acidic EFAl species, conse-
quently leading to the higher activity of H-BEA (15) towards
the synthesis of 1-benzyl-2,4,5-triphenyl-1H-imidazoles. This
procedure provided the desired products in high yields over a
short reaction time with a low catalyst loading. The solvent-
free protocol makes the process environmentally benign and
economically viable. The present protocol will serve as a
green tool and opens a new avenue in the area of environ-
mentally benign synthesis of biologically active drug-like
molecules.
8 S. Rostamnia and A. Zabardasti, J. Fluorine Chem., 2012, 144,
69–72.
9 A. Olyaei, Z. Derikvand, F. Noruzian and M. Sadeghpour,
Iran. Chem. Commun., 2016, 4, 337–346.
10 K. Sivakumar, A. Kathirvel and A. Lalitha, Tetrahedron Lett.,
2010, 51, 3018–3021.
11 M. Vosoughi, F. Mohebali, A. Bonakdar, A. Lordegani and A.
Massah, Bulg. Chem. Commun., 2015, 47, 607–612.
12 S. Balalaei and A. Arabanian, Green Chem., 2000, 2,
274–276.
13 P. Vadivel, P. Sivaguru and A. Lalitha, Int. J. Chem., 2013, 34,
1167–1172.
14 S. Bhat, R. Naikoo and R. Tomar, Int. Res. J. Pure Appl.
Chem., 2016, 11, 1–10.
15 (a) M. Heravi, F. Derikvand and F. Bamoharram, J. Mol.
Catal. A: Chem., 2007, 263, 112–114; (b) A. Karimi, Z.
Alimohammadi and M. Amini, Mol. Diversity, 2010, 14,
635–641.
Conflicts of interest
16 K. Niknam, A. Deris, F. Naeimi and F. Majleci, Tetrahedron
Lett., 2011, 52, 642–4645.
17 G. Ziarani, A. Badiei, N. Lashgari and Z. Farahani, J. Saudi
Chem. Soc., 2016, 20, 419–427.
There are no conflicts to declare.
18 K. Safa, M. Allahvirdinesbat, H. Namazi and P. Nakhostin
Panahi, C. R. Chim., 2015, 18, 883–890.
Acknowledgements
19 P. Reddy, K. Mukkanti and K. Purandhar, Rasayan J. Chem.,
2010, 3, 335–340.
20 H. Shaterian and M. Ranjbar, J. Mol. Liq., 2011, 160, 40–49.
21 J. Safari, S. Gandomi-Ravandi and Z. Akbari, J. Adv. Res.,
2013, 4, 509–514.
22 (a) I. Lantos, W. Zang, X. Shui and D. Eggleston, J. Org.
Chem., 1993, 58, 7092–7095; (b) R. Consonni, P. Croce and
R. Ferraccioli, J. Chem. Res., 1991, 7, 188–189; (c) S. Balalaie,
M. Hashemi and M. Akhbari, Tetrahedron Lett., 2003, 44,
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Farmaco, 2001, 56, 285–290.
The authors are grateful to the Director, SVNIT, Surat, for pro-
viding research and financial assistance. This research was
supported by research grant for assistant professor No: Dean
(R&C)/1503/2013-14 from the Sardar Vallabhbhai National In-
stitute of Technology, Surat (SVNIT, Surat). The authors would
also like to thank Sud-Chemie India Pvt. Ltd., India, for pro-
viding zeolites.
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