In water–ultrasound-promoted synthesis of tetraketones and 2-substituted-1H-benzimidazoles catalyzed by BiOCl nanoparticles

Article abstract of DOI:10.1007/s11164-017-2924-5

A highly efficient, green protocol has been developed for the synthesis of various structurally diverse 2,2′-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) and 2-substituted-1H-benzimidazole derivatives. The reaction was performed in water under ultrasound irradiation, using BiOCl nanoparticles as a catalyst. The nanocatalyst was found to be reusable for seven subsequent reactions without much loss in activity. Simple methodology with short reaction times and mild reaction conditions with easy work-up procedure are the salient features of this method.

Full text of DOI:10.1007/s11164-017-2924-5

Res Chem Intermed
DOI 10.1007/s11164-017-2924-5
In water–ultrasound-promoted synthesis
of tetraketones and 2-substituted-1H-benzimidazoles
catalyzed by BiOCl nanoparticles
Bharatkumar M. Sapkal1 Prakash K. Labhane1
•
•
Jitendra R. Satam2
Received: 29 October 2016 / Accepted: 24 February 2017
Ó Springer Science+Business Media Dordrecht 2017
Abstract A highly efficient, green protocol has been developed for the synthesis of
various structurally diverse 2,20-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cy-
clohexene-1-one) and 2-substituted-1H-benzimidazole derivatives. The reaction
was performed in water under ultrasound irradiation, using BiOCl nanoparticles as a
catalyst. The nanocatalyst was found to be reusable for seven subsequent reactions
without much loss in activity. Simple methodology with short reaction times and
mild reaction conditions with easy work-up procedure are the salient features of this
method.
Keywords Tetraketones Á 2-Substituted-1-H-benzimidazoles Á BiOCl
nanoparticles Á Ultrasound
Introduction
The development of rapid and selective synthetic routes for functionalized
heterocyclic building blocks is of great importance to both human health and the
environment. During the last few years, increasing environmental consciousness in
chemical research and industry has meant that organic researchers are now directed
to the finding of methods that largely take into account the criterion of sustainable
chemistry [1]. Indeed, due to the demands of clean technology, many recyclable
nano-catalysts have been reported [2–5].
Tetraketones, with four carbonyl functionalities, is an important intermediate in
the preparation of xanthendione, acridinedione [6] and 4H-1-benzopyran derivatives
&
Jitendra R. Satam
jitendrasatam@somaiya.edu
1
2
Department of Chemistry, M.G.S.M’S Arts, Science and Commerce College, Chopda, Jalgaon,
India
K. J. Somaiya College of Engineering, University of Mumbai, Mumbai, India
123

B. M. Sapkal et al.
[7]. 2,20-aryl-methylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) or
tetraketones exhibit a broad spectrum of biological activities, such as lipoxygenase
inhibition, anti-oxidant [8] antibacterial and antiviral [9], and the prevention and
treatment of thrombosis [10]. Because of their biological and chemical importance,
synthesis of tetraketones is under considerable attention of many organic chemists.
Tetraketones have been mainly synthesized through Knoevenagel condensations
and Michael additions of aldehydes with cyclohexane-1,3-diones, dimedones or
various 1,3-cyclic diketones [11]. Various synthetic methodologies have been
developed, involving the use of pyridine [12], metal hydroxides [13, 14], L-proline
[15], HClO4-SiO2 [16], choline chloride [17], and nano-Fe/NaY zeolite [18] as
catalysts, cetyltrimethyl ammonium bromide as surfactant [19], or without any
catalyst in water [11].
Benzimidazole is one of the important analogues generally found in drugs and
agrochemicals. Hence, its derivatives are being targeted in medicinal chemistry
research due to their pharmacological interest. Benzimidazole shows antibacterial
[20], anti-inflammatory [21], antiviral [22], antiprotozoal [23], anticancer [24] and
antimalarial activity [25].Various strategies employed in the synthesis of substituted
benzimidazoles include the cyclo-condensation reaction of o-phenylenediamines
with carboxylic acids, nitriles and orthoesters [26]. Another protocol is the direct
condensation of 1,2-phenylenediamines with aryl aldehydes using a variety of
catalysts, such as heteropoly acid containing ionic liquids [27], bismuth chloride
[28], polyaniline-sulfate [29], Zn2?-K10-clay [30], (bromodimethyl)sulfonium
bromide [31], TiCl3OTf [32], NaY-zeolite [33], nano-In2O3 [34] Fe(HSO4)3 [35]
and MgCl2Á6H2O [36]. However, these methods suffer from limitations such as
longer reaction times (generally 2–24 h), and the use of expensive catalysts and
organic solvents such as MeCN, CH2Cl2, CHCl3, DMF, etc. Moreover, non-
reusability of catalysts such as MgCl2Á6H2O and harsh reaction conditions decreasea
the efficacy of the reported methods. Therefore, it is important to develop more
efficient catalysts and alternate synthetic methodologies for the preparation of these
compounds. Ultrasound-promoted organic synthesis [37, 38] has attracted consid-
erable attention as it places emphasis on minimizing energy requirements, the
avoidance of toxic reagents, the reduction of waste and increasing reaction
efficiency. Bismuth oxychloride (BiOCl) nano-particles have been successfully
employed as semiconductor photocatalysts [39–44]. The high reactivity of BiOCl
nanoparticles is attributed to their large surface area which enables their use in the
synthesis of organic compounds.
Materials and methods
All the chemicals were purchased from S.D. Fine Chemicals (India) and were used
without further purification. All melting points were measured on a Gallenkamp
1
melting point apparatus and are uncorrected. H NMR spectra were recorded on a
Bruker Avance-400 MHz spectrometer in CDCl3 in the presence of tetramethyl-
silane as an internal standard. IR spectra were recorded using a Perkin-Elmer 843
spectrometer with KBr plates. Sonochemical synthesis was performed with the help
123

In water–ultrasound-promoted synthesis of tetraketones and…
of an ultrasonic instrument (ACE, USA Horn-type). Conditions: diameter of
stainless steel tip of horn: 1.3 9 10-2 m, rated output power: 750 W, operating
frequency: 22 kHz, surface area of ultrasound irradiating face: 1.32 9 10-4 m2 and
intensity: 3.4 9 105 W/m2.
The temperature of the process was maintained at 35 2 °C by means of a
supply of water to the jacketed reactor used for the synthesis. The reactions were
monitored by TLC on silicagel PolyGram SILG/UV 254 plates (Merck). All
products are known compounds and were identified by comparison with those
reported in the literature.
Synthesis and characterization of BiOCl nanoparticles
The BiOCl nanoparticles were prepared by the reported method using bismuth
nitrate pentahydrate Bi(NO3)3Á5H2O as the precursor [45, 46]. Synthesized BiOCl
nanoparticles were characterized by XRD and Fourier transform infrared (FT-
IR).The crystal structure of BiOCl was determined by an X-ray diffractometer
˚
(Bruker D8 Advance Diffractometer) with CuKa radiations (k = 1.5416 A) in the
range of 20°–80° as shown in Fig. 1a. Figure 1b represents the XRD patterns of
reused BiOCl nanoparticles after seven cycles. The prepared BiOCl sample is in
good agreement with the tetragonal structure and matched with the JCPDS data (01-
075-1533). The crystallite size (D) was calculated from the XRD peak using the
Debye–Scherrer formula.
Kk
D ¼
ð1Þ
bcosh
where K is the shape factor, which is a constant taken as 0.9, k is the wavelength of
˚
the X-ray radiation (k = 1.5416 A), b is the full-width at half-maximum (FWHM)
in radians, and h is the Bragg’s angle in degree. The crystallite size of the sample
obtained from Eq. (1) has a grain size between 23 and 29 nm. The FT-IR spectrum
in Fig. 2a shows the characteristic absorption peaks of the as-synthesized sample.
The absorption band at 524 cm-1 is assigned to the stretching vibration of Fourier
transform infrared Bi-O bond in BiOCl. [47] Figure 2b represents Fourier transform
Fig. 1 XRD patterns of BiOCl: (a) initial; (b) after seven cycles of reuse
123

B. M. Sapkal et al.
Fig. 2 FT-IR of BiOCl: (a) initial; (b) after seven cycles of reuse
infrared IR spectra of recycled BiOCl nanoparticles after Fourier transform infrared
seventh reuse.
Optimization of the reaction conditions
The reaction conditions were optimized for the synthesis of 2,20-(4-methoxylphe-
nyl)methylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) (3a) and 2-(4-
nitrophenyl)-1H-benzo[d]imidazole (5b) under ultrasound irradiation (Table 1). The
effects of various solvents on the model reactions were explored. Several organic
solvents such as EtOH, CH3CN, toluene, CHCl3 and DMF were examined (Table 1,
entries 1–5 and 16–20). It is exciting to find that water affords the product in good
yield even better than other solvents for (3a) and (5b) synthesis (Table 1, entries 15
and 29). Water is highly polar, which possibly creates the necessary conditions for
the formation of intermediates and their conversion to final products on the catalyst
surface.
The catalytic activity of BiOCl was also studied. When the reaction was
performed at room temperature in the presence of BiOCl nanoparticles and in the
absence of ultrasonic irradiation, 3a was obtained in 45% yield after 150 min
(Table 1, entry 6) and 5b was obtained in 50% yield after 120 min (Table 1, entry
21). In the presence of the catalyst (30 mg) and ultrasonic irradiation (400 W), the
yield of 3a increased to 80% and the reaction time was reduced to 40 min (Table 1,
entry 11) and in the presence of (Table 1, entry 6)catalyst (12 mg) and ultrasonic
irradiation (400 W), the yield of 5b increased to 71% and the reaction time was
reduced to 25 min (Table 1, entry 25). It was verified that the combination method
(ultrasound irradiation and BiOCl nanoparticles) can be regarded as having an
important role in the product yield and reaction time.
123

In water–ultrasound-promoted synthesis of tetraketones and…
Table 1 Optimization condition for the synthesis of 3a and 5b
No. Product Catalyst
Solvent Condition Power (W) Time (min) Yield (%)
1
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
5b
5b
5b
5b
5b
5b
5b
5b
5b
5b
5b
5b
5b
5b
BiOCl nano (30 mg)
BiOCl nano (30 mg)
BiOCl nano (30 mg)
BiOCl nano (30 mg)
BiOCl nano (30 mg)
No catalyst
EtOH
))))
750
750
750
750
750
750
750
750
750
750
400
550
600
650
750
750
750
750
750
750
750
750
750
750
400
550
600
650
750
25
23
30
31
40
150
70
45
35
20
40
35
30
25
15
20
33
80
60
28
120
90
50
25
25
23
20
15
08
70
35
65
20
55
45
60
60
71
83
80
60
65
84
93
79
63
50
70
60
50
75
59
65
71
75
82
85
93
2
CH3CN ))))
3
Tolune
CHCl3
DMF
H2O
))))
4
))))
5
))))
6
Silent
Silent
))))
7
BiOCl nano (30 mg)
BiOCl nano (10 mg)
BiOCl nano (20 mg)
BiOCl nano (25 mg)
BiOCl nano (30 mg)
BiOCl nano (30 mg)
BiOCl nano (30 mg)
BiOCl nano (30 mg)
H2O
8
H2O
9
H2O
))))
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
H2O
))))
H2O
))))
H2O
))))
H2O
))))
H2O
))))
BiOCl nano (30 mg) H2O
))))
BiOCl nano (12 mg)
BiOCl nano (12 mg)
BiOCl nano (12 mg)
BiOCl nano (12 mg)
BiOCl nano (12 mg)
No catalyst
EtOH
))))
CH3CN ))))
Toluene ))))
CHCl3
DMF
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
))))
))))
Silent
Silent
))))
BiOCl nano (12 mg)
BiOCl nano (05 mg)
BiOCl nano (08 mg)
BiOCl nano (12 mg)
BiOCl nano (12 mg)
BiOCl nano (12 mg)
BiOCl nano (12 mg)
))))
))))
))))
))))
))))
BiOCl nano (12 mg) H2O
The two best yields are shown in bold
))))
General procedure for synthesis of 2, 20-arylmethylene bis(3-hydroxy-5,5-
dimethyl-2-cyclohexene-1-one)
A mixture of aldehyde (1 mmol) and dimedone (2 mmol) in the presence of BiOCl
(30 mg) nanoparticles was added to water (5 mL) as solvent. The reaction mixture
was then placed under sonication using an ultrasonic horn (22 kHz frequency) for
the required time with a 5-s ON and 5-s OFF cycle from time t = 0 h. The progress
of the reaction was monitored by TLC (eluent: 7:3 n-hexane–ethyl acetate) for the
time period as indicated in Table 2. After completion of the reaction, the mixture
was diluted by 1:1 H2O: EtOAc (10 mL) stirred at ambient temperature (20 min)
and centrifuged to separate the solid catalyst. The organic layer of the solution was
123

B. M. Sapkal et al.
Table 2 BiOCl nanoparticles-catalyzed synthesis of 2, 20-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-
cyclohexene-1-one)
O
R
O
O
O
Nano BiOCl
35 0C, H2O
+
R
H
))))
O
(2)
OH
HO
(3)
(1)
(2 mmol)
(1 mmol)
Entry
Product
R
Time (min)
Yield (%)b
M.P (°C)
Found
Reported
1
3a
3b
3c
3d
3e
3f
4-CH3OC6H4
4-NO2 C6H4
3-NO2 C6H4
2-NO2 C6H4
4-Cl C6H4
15
16
12
15
15
17
15
12
17
17
16
15
12
93
83
95
91
90
88
90
92
95
91
91
95
83
141–143
188–190
191–193
188–190
141–143
186–188
200–201
187–189
193–195
164–165
141–143
188–190
201–203
(142–143)
(188–190)
(193–195)
(188–189)
(141–143)
(188–190)
(199–200)
(187–189)
(194–195)
(163–164)
(141–143)
(189–190)
(203–204)
2
3
4
5
6
3-Cl C6H4
7
3g
3h
3i
2-Cl C6H4
8
4-OH C6H4
4-OH,3-CH3O C6H3
3,4-Cl2 C6H3
4-CH3C6H4
C6H5
9
10
11
12
13
3j
3k
3l
3m
3-BrC6H4
The products were characterized by 1H NMR spectroscopy
b
Isolated yields
separated, dried over sodium sulfate, and the organic solvent and other residues
were stripped in a vacuum evaporator. The residue obtained was purified by column
chromatography (silica gel, 60–120 mesh; pet ether) to afford the desired products.
All the products (3a–m) are known compounds and are confirmed by comparison of
their spectroscopic data with literature data.
Spectral data for 2,20-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-
cyclohexene-1-one)
2,20-(4-Methoxylphenyl)methylenebis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one)
1
(3a) IR (KBr, cm-1) tmax = 3050, 2960, 2870, 1725, 1601. H NMR (CDCl3,
400 MHz) d: 11.93 (s, 1H, OH), 11.56 (brs, 1H, OH), 7.02 (d, J = 8.3 Hz, 2H, Ph-
H), 6.82 (d, J = 8.3 Hz, 2H, Ph-H), 5.50 (s, 1H, CH), 3.79 (s, 3H, CH3O),
2.17–2.49 (m, 8H, CH2), 1.24 (s, 6H, CH3), 1.12 (s, 6H, CH3). 13C NMR (400 MHz,
DMSO-d6) d: 27.3, 29.6, 31.4, 32.0, 46.4, 55.2, 113.6, 115.8, 127.8, 129.8, 157.6,
189.3, 190.0
123

In water–ultrasound-promoted synthesis of tetraketones and…
2,20-(4-Nitrophenyl)methylene
bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one)
(3b) IR (KBr, cm-1) tmax = 3062, 2955, 1590, 1510, 1384, 1345.1H NMR
(CDCl3, 400 MHz) d: 11.80 (s, 1H, OH), 11.26 (brs, 1H, OH), 8.10 (d, J = 8.3 Hz,
2H, Ph-H), 7.22 (d, J = 8.3 Hz, 2H, Ph-H), 5.53 (s, 1H, CH), 2.30–2.49 (m, 8H,
CH2), 1.21 (s, 6H, CH3), 1.09 (s, 6H, CH3). 13C NMR (400 MHz, DMSO-d6) d:
27.4, 29.4, 31.4, 33.2, 46.4, 114.8, 123.4, 127.6, 146.0, 146.6, 189.5, 191.0
2,20-(3-Nitrophenyl)methylene
bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one)
(3c) IR (KBr, cm-1) tmax = 3055, 2961, 1592, 1514, 1391, 1340. 1H NMR
(CDCl3, 400 MHz) d: 11.83 (s, 1H, OH), 11.21(brs, 1H, OH), 8.26(m, 2H, Ph-H),
8.01 (s, 1H, Ph-H), 7.37(d, J = 8.6 Hz, 1H, Ph-H) 5.50 (s, 1H, CH), 2.37–2.47 (m,
8H, CH2), 1.22 (s, 6H, CH3), 1.14 (s, 6H, CH3). 13C NMR (400 MHz, DMSO-d6) d:
27.3, 29.6, 31.3, 32.8, 46.3, 46.9, 114.7, 120.9, 122.1, 129.0, 132.8, 140.6, 148.3,
189.5, 191.0
2,20-(2-Nitrophenyl)methylene
bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one)
(3d) IR (KBr, cm-1) tmax = 3052, 2960, 1594, 1510, 1396, 1347. 1H NMR
(CDCl3, 400 MHz) d:11.80 (s, 1H, OH), 11.23(brs, 1H, OH), 7.57 (d, J = 7.9 Hz,
1H, Ph-H), 7.43 (t, J = 7.9 Hz, 1H, Ph-H), 7.31 (t, J = 7.9 Hz, 1H, Ph-H), 7.20 (d,
J = 7.9 Hz, 1H, Ph-H), 5.82 (s, 1H, CH), 2.22–2.50 (m, 8H, CH2), 1.14 (s, 6H,
CH3), 1.07 (s, 6H, CH3).
2, 20-(4-Chlorophenyl)methylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one)
1
(3e) IR (KBr, cm-1) tmax = 3465, 3010, 2975, 1733, 1594. H NMR (CDCl3,
400 MHz) d: 11.86 (s, 1H, OH), 11.47 (brs, 1H, OH), 7.21 (d, J = 8.1 Hz, 2H, Ph-
H), 7.00 (d, J = 8.1 Hz, 2H, Ph-H), 5.46 (s, 1H, CH), 2.28–2.47 (m, 8H, CH2), 1.21
(s, 6H, CH3), 1.09 (s, 6H, CH3). 13C NMR (400 MHz, DMSO-d6) d: 27.4, 29.6,
31.4, 32.4, 46.4, 47.0, 47.04, 115.3, 128.2, 128.3, 131.5, 136.7, 189.4, 190.6
2, 20-(3-Chlorophenyl)methylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one)
1
(3f) IR (KBr, cm-1) tmax = 3469, 3017, 2970, 1735, 1591. H NMR (CDCl3,
400 MHz) d: 11.91(s, 1H, OH), 11.50 (brs, 1H, OH), 7.19–7.31 (m, 2H, Ph-H), 7.04
(s, 1H, Ph-H), 6.95 (d, J = 7.8 Hz, 1H, Ph-H), 5.41 (s, 1H, CH), 2.21–2.36 (m, 8H,
CH2), 1.22 (s, 6H, CH3), 1.10 (s, 6H, CH3). 13C NMR (400 MHz, DMSO-d6) d:
27.2, 29.4, 31.3, 32.5, 46.2, 47.1, 115.2, 124.8, 126.1, 127.0, 129.3, 134.0, 140.3,
189.3, 190.5.
2, 20-(2-Chlorophenyl)methylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one)
1
(3g) IR (KBr, cm-1) tmax = 3461, 3022, 2972, 1729, 1596. H NMR (CDCl3,
400 MHz) d: 11.84(s, 1H, OH), 11.38 (brs, 1H, OH), 7.31 (d, J = 7.9 Hz, 1H, Ph-
H), 7.27 (d, J = 7.9 Hz, 1H, Ph-H), 7.20 (t, J = 7.9 Hz, 1H, Ph-H), 7.13 (t,
J = 7.9 Hz, 1H, Ph-H), 5.50 (s, 1H, CH), 2.23–2.43 (m, 8H, CH2), 1.18 (s, 6H,
CH3), 1.09 (s, 6H, CH3).
2,20-(4-Hydroxyphenyl)methylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one)
(3h) 1H NMR (CDCl3, 400 MHz) d: 11.81 (s, 1H, OH), 11.49 (brs, 1H, OH), 7.33
(d, J = 8.4 Hz, 2H, Ph-H), 7.24 (d, J = 8.4 Hz, 2H, Ph-H), 5.50 (s, 1H, OH), 5.42
(s, 1H, CH), 2.21–2.44 (m, 8H, CH2), 1.22 (s, 6H, CH3), 1.11 (s, 6H, CH3).
123

B. M. Sapkal et al.
2,20-(4-Hydroxy-3-methoxyphenyl)methylenebis(3-hydroxy-5,5-dimethyl-2-cyclo-
hexene-1-one) (3i) 1H NMR (CDCl3, 400 MHz) d: 11.77 (s, 1H, OH), 11.26 (brs,
1H, OH), 6.98 (d, J = 8.2 Hz, 1H, Ph-H), 6.67 (s, 1H, Ph-H), 6.59 (d, J = 8.2 Hz,
1H, Ph-H), 5.47 (s, 1H, OH), 5.44 (s, 1H, CH), 3.81 (s, 3H, CH3O), 2.31–2.44 (m,
8H, CH2), 1.24 (s, 6H, CH3), 1.12 (s, 6H, CH3).
2,20-(2,4-Dichlorophenyl)methylenebis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-
one) (3j) 1H NMR (CDCl3, 400 MHz) d: 11.81 (brs, 1H, OH), 10.67 (s, 1H, OH).
7.34–7.31(m, 2H, Ph-H), 7.20–7.18 (dd, J = 7.6 Hz, J = 2.5 Hz, 1H, Ph-H), 5.51
(s, 1H, CH), 2.24–2.41 (m, 8H, CH2), 1.12 (s, 6H, CH3), 1.08 (s, 6H, CH3).
2,20-(4-Methylphenyl)methylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one)
(3k) 1H NMR (CDCl3, 400 MHz) d: 11.56 (brs, 1H, OH), 10.67 (s, 1H, OH).
7.11 (d, J = 8.2 Hz, 2H, Ph-H), 6.99 (d, J = 8.2 Hz, 2H, Ph-H), 5.49 (s, 1H, CH),
2.36–2.44 (m, 8H, CH2), 2.31 (s, 3H, CH3), 1.14 (s, 6H, CH3), 1.07 (s, 6H, CH3).
2,20-Phenylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) (3l) 1H
NMR (CDCl3, 400 MHz) d: 11.66 (brs, 1H, OH), 11.07 (s, 1H, OH) 7.27–7.45
(m, 5H, Ph-H), 5.44 (s, 1H, CH), 2.30–2.41 (m, 8H, CH2), 1.15 (s, 6H, CH3), 1.10
(s, 6H, CH3).
2,20-(3-Bromophenyl)methylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one)
(3m) 1H NMR (CDCl3, 400 MHz) d: 11.87(s, 1H, OH), 11.22 (brs, 1H, OH),
7.17–7.30 (m, 2H, Ph-1.21 (s, 6H, CH3), 1.16 (s, 6H, CH3).
General procedure for synthesis of 2-substituted-1H-benzimidazoles
1, 2-phenylenediamine derivative (1 mmol), aryl aldehyde (1 mmol) and BiOCl
nanoparticles (12 mg) were added to water (5 mL) as solvent. The reaction mixture
was then placed under sonication using an ultrasonic horn (22 kHz frequency) for
the required time with a 5-s ON and 5-s OFF cycle from time t = 0 h. The progress
of the reaction was monitored by TLC (eluent: 7:3 n-hexane–ethyl acetate) for the
time period as indicated in Table 3. After completion of the reaction, the mixture
was diluted by 1:1 H2O: EtOAc (10 mL) stirred at ambient temperature (20 min)
and centrifuged to separate the solid catalyst. The organic layer of the solution was
separated, dried over sodium sulfate, and the organic solvent and other residues
were stripped in a vacuum evaporator. The residue obtained was recrystallized using
1
the appropriate solvent. The products (5a–l) are known compounds and their H
NMR and melting points compared with those were reported in literature.
Spectral data for 2-substituted-1H-benzimidazoles
2-Phenyl-1H-benzimidazole (5a) 1H NMR (DMSO-d6, 400 MHz) d: 13.01 (br,
1H, NH), 8.11–8.23 (m, 2H, Ph-H), 7.48–7.56 (m, 5H, Ph-H), 7.15–7.21 (m, 2H, Ph-
H). 13C NMR (400 MHz, DMSO-d6) d: 111.84, 119.39, 122.1, 122.9, 126.8, 129.3,
130.2, 130.5, 135.4, 143.9, 151.6
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In water–ultrasound-promoted synthesis of tetraketones and…
Table 3 BiOCl nanoparticles catalyzed synthesis of 2-substituted-1H-benzimidazoles
NH2
N
O
Nano BiOCl
R
+
35 0C, H2O
R
H
N
H
))))
(2)
NH2
(4)
(5)
(1 mmol)
(1 mmol)
Entry
Product
R
Time (min)
Yield (%)a
M.P (°C)
Found
Reported
1
5a
5b
5c
5d
5e
5f
C6H5
12
08
05
10
15
07
07
15
12
15
17
17
88
93
91
93
89
95
93
94
70
67
60
90
288–290
296–298
203–204
205–207
220–223
288–290
264–266
233–234
176–177
217–219
287–289
181–182
(289–290)
(297–298)
(203)
2
4-NO2C6H4
3-NO2 C6H4
2-NO2 C6H4
4-CH3OC6H4
4-ClC6H4
3
4
–
5
(223–226)
(289–290)
(265)
6
7
5g
5h
5i
4-CN C6H4
4-(Me2N)C6H4
4-CH3C6H4
2-Pyridyl
8
(232)
9
(174–176)
(218)
10
11
12
5j
5k
5l
2-Furyl
(288)
4-F C6H4
(180–183)
The products were characterized by 1H NMR spectroscopy
a
Isolated yields
2-(4-Nitrophenyl)-1H-benzo[d]imidazole (5b) 1H NMR (CDCl3, 400 MHz) d:
13.04 (br, 1H, NH), 8.30 (d, J = 8.6 Hz, 2H, Ph-H), 8.03 (d, J = 8.6 Hz, 2H, Ph-
H), 7.33–7.38 (m, 2H, Ph-H), 7.27–7.30(m, 2H, Ph-H). 13C NMR (400 MHz,
DMSO-d6) d: 112.41, 120.07, 123.09, 124.90, 128.03, 136.71, 148.45, 149.66
2-(3-Nitrophenyl)-1H-benzo[d]imidazole (5c) 1H NMR (DMSO-d6, 400 MHz) d:
12.81 (br, 1H, NH), 8.22 (m, 2H, Ph-H), 8.10 (s, 1H, Ph-H), 7.34 (d, J = 8.5 Hz,
1H, Ph-H), 7.31–7.37 (m, 2H, Ph-H), 7.20–7.28 (m, 2H, Ph-H). 13C NMR
(400 MHz, DMSO-d6) d: 115.7, 116.9, 118.4, 123.0, 125.2, 128.8, 129.7, 134.0,
135.6, 138.2, 142.9, 148.7, 153.8
2-(2-Nitrophenyl)-1H-benzo[d]imidazole (5d) 1H NMR (DMSO-d6, 400 MHz) d:
12.89 (br, 1H, NH), 7.77 (d, J = 8.1 Hz, 1H, Ph-H), 7.40 (t, J = 8.0 Hz, 1H, Ph-H),
7.33 (t, J = 8.0 Hz, 1H, Ph-H), 7.21–7.27 (m, 2H, Ph-H), 7.11 (d, J = 8.1 Hz, 1H,
Ph-H), 6.85–6.95 (m, 2H, Ph-H).
2-(4-Methoxyphenyl)-1H-benzo[d]imidazole (5e) 1H NMR (DMSO-d6, 400 MHz)
d: 13.14 (br, 1H, NH), 8.26 (d, J = 8.1 Hz, 2H, Ph-H), 7.50–7.59 (m, 4H, Ph-H),
123

B. M. Sapkal et al.
7.30 (d, J = 8.1 Hz, 2H, Ph-H), 3.82 (s, 3H, CH3O). 13C NMR (400 MHz, DMSO-
d6) d: 55.84, 114.0, 121.9, 132.1, 128.4, 129.4, 151.7, 161.0.
2-(4-Chlorophenyl)-1H-benzo[d]imidazole (5f) 1H NMR (DMSO-d6, 400 MHz)
d: 13.04 (br, 1H, NH), 8.19 (d, J = 8.1 Hz, 2H, Ph-H), 7.58–7.63 (m, 4H, Ph-H),
7.33 (d, J = 8.1 Hz, 2H, Ph-H). 13C NMR (400 MHz, DMSO-d6) d: 111.0, 118.5,
121.8, 126.1, 128.5, 129.4, 129.1, 134.7, 143.4, 151.0
2-(4-Cyanophenyl)-1H-benzimidazole (5g) 1H NMR (CDCl3, 400 MHz) d: 12.92
(br, 1H, NH), 8.36 (d, J = 8.5 Hz, 2H, Ph-H), 8.11 (d, J = 8.5 Hz, 2H, Ph-H),
7.35–7.37 (m, 2H, Ph-H), 7.21–7.27 (m, 2H, Ph-H).
2-(4-N,N-dimethylbenzenamine)-1H-benzimidazole (5h) 1H NMR (CDCl3,
400 MHz) d: 11.89 (br, 1H, NH), 8.36 (d, J = 8.4 Hz, 2H, Ph-H), 8.23 (m, 2H,
Ph-H), 7.30–7.35 (d, J = 8.4 Hz, 2H, Ph-H), 7.22–7.26(m, 2H, Ph-H), 2.13 (s, 6H,
N(CH3)2. 13C NMR (400 MHz, DMSO-d6) d: 21.40, 40.38, 111.79, 116.11,
170.02,119.41, 127.19, 130.43, 136.11, 136.58, 142.01, 152.53, 156.91
2-(4-Tolyl)-1H-benzimidazole (5i) 1H NMR (CDCl3, 400 MHz) d: 11.91 (br, 1H,
NH), 8.15 (d, 2H, J = 8.0 Hz, Ph-H), 7.56 (m, 2H, Ph-H), 7.30 (d, 2H, J = 8.0 Hz,
Ph-H), 7.12 (m, 2H, Ph-H), 2.31 (s, 3H, CH3).
2-(2-Pyridinyl)-1H-benzoimidazole (5j) 1H NMR (CDCl3, 400 MHz) d: 12.33 (br,
1H, NH), 7.80–7.84(m, 2H, Ph-H), 7.53–7.57 (m, 2H, Ph-H), 7.12 (m, 2H, Ph-H),
6.92–6.96 (m, 2H, Ph-H).
2-(2-Furanyl)-1H-benzoimidazole (5k) 1H NMR (CDCl3, 400 MHz) d: 12.18 (br,
1H, NH), 7.87(d, J = 4.4 Hz, 1H,Ph-H), 7.53–7.50 (m, 2H, Ph-H), 7.25 (dd, 1H,
J = 4.4 Hz &J = 2.0 Hz, Ph-H), 6.63 (d, 1H, J = 2.0 Hz, Ph-H), 6.36–6.40 (m,
2H, Ph-H).
2-(2-Flurophenyl)-1H-benzo[d]imidazole (5l) 1H NMR (CDCl3, 400 MHz) d:
12.41 (br, 1H, NH), 8.32 (d, J = 8.2 Hz, 2H, Ph-H), 8.21 (d, J = 8.2 Hz, 2H, Ph-
H), 7.36–7.38 (m, 2H, Ph-H), 7.27–7.30 (m, 2H, Ph-H).
Results and discussion
To explore the scope and limitations of the protocol under optimized conditions
(Table 1, entry 15), the reaction of dimedone (1) with various aromatic aldehydes
3(a–m) bearing electron-donating and electron-withdrawing groups gives rise to the
corresponding 2,20-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-
one) 3a–m in good to excellent yields (83–95%) at 35 °C within 12–17 min
(Table 2). As is indicated in Table 2, both aromatic aldehydes bearing electron-
donating and ithdrawing groups react at a faster rate with dimedone.
Encouraged by these excellent results, we then decided to test the generality and
versatility of optimized reaction conditions (Table 1, entry 29) in the synthesis of
substituted benzimidazoles, and several substituted aromatic aldehydes and
123

In water–ultrasound-promoted synthesis of tetraketones and…
99
98
97
Fig. 3 Reusability study of the
catalyst
93
91
90
100
80
60
40
20
0
8787
86
85
84
81 81
80
1
2
3
Number of Run
Tetraketones
1H-benzimidazoles
4
5
6
7
heteroaromatic aldehydes 5(a–l) were reacted with o-phenylenediamine (4). These
results are shown in Table 3. Aromatic aldehydes bearing electron-donating and -
withdrawing groups undergo smooth conversion to afford various benzimidazoles
(5a–i, l) in good to excellent yields. When heteroaromatic aldehydes such as
pyridine-2-aldehyde and 2-furfural (Table 3, entries 10, 11) were reacted with o-
phenylenediamine under similar reaction conditions they gave corresponding
benzimidazoles (5j, 5k) in lower yield compared to benzimidazole derivatives
obtained from aromatic aldehydes.
Reusability of BiOCl nano-catalyst
Ther catalytic efficiency of the BiOCl nano-catalyst was estimated by a reusability
study. We have conducted the experiments using the recycled BiOCl catalyst for the
synthesis of 2,20-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one)
and 2-substituted-1H-benzimidazoles. The recovered catalyst was purified after
each run by filtration, washed with acetone and dried at 100 °C for 2 h in an oven
before use in the next catalytic cycle. The BiOCl catalyst was found to be reusable
for seven times without any significant loss in activity (Fig. 3). After each
subsequent run, more than 95% of the catalyst was easily recovered from the
reaction mixture.
Conclusion
In summary, BiOCl nanoparticles (NPs) provide an alternative and efficient
pathway for the production of heterocyclic intermediates. We have developed a
practical and convenient synthetic method in aqueous media by using BiOCl NPs as
the catalyst for the facile synthesis of 2,20-arylmethylene bis(3-hydroxy-5,5-
dimethyl-2-cyclohexene-1-one) and 2-substituted-1H-benzimidazoles under ultra-
sound irradiation. Milder conditions, easy recovery and reusability of the BiOCl
NPs catalyst make the method highly efficient.
123

B. M. Sapkal et al.
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