Sonicated assisted synthesis of benzimidazoles, benzoxazoles and benzothiazoles in aqueous media

Article abstract of DOI:10.4067/S0717-97072014000100020

Ammonium nickel sulphate [(NH4)2SO4.NiSO4.6H2O] was found as a new catalyst to synthesis 2-aryl benzimidazole, 2-aryl benzothiazole and 2-aryl benzoxazole in aqueous media under sonication irradiation. The procedure is an eco-friendly, efficient and provides simple workup and good yield.

Full text of DOI:10.4067/S0717-97072014000100020

J. Chil. Chem. Soc., 59, Nº 1 (2014)
SONICATED ASSISTED SYNTHESIS OF BENZIMIDAZOLES, BENZOXAZOLES AND
BENZOTHIAZOLES IN AQUEOUS MEDIA
SANDEEP D. PARDESHI a, JAYANT P. SONAR a, SHIVAJI S. PAWAR a, DEEPAK DEKHANE a, SUNIL GUPTAa,
ASHOK M. ZINE a, SHIVAJI N. THOREb, *
aDepartment of Chemistry, Vinayakrao Patil Mahavidyalaya, Vaijapur, Maharashtra, India. 423701
bDepartment of Chemistry, Deogiri College, Aurangabad, Maharashtra, India.431005
(Received: June 4, 2013 - Accepted: December 8, 2013)
ABSTRACT
Ammonium nickel sulphate [(NH4) SO4.NiSO4.6H2O] was found as a new catalyst to synthesis 2-aryl benzimidazole, 2-aryl benzothiazole and 2-aryl
benzoxazole in aqueous media under son2ication irradiation. The procedure is an eco-friendly, efficient and provides simple workup and good yield.
Keywords: - Benzimidazole, benzothiazole, benzoxazole, aqueous media, sonication, ammonium nickel sulphate.
Selected spectral data
2-phenyl-1H-benzimidazole 3a
INTRODUCTION
1H NMR(400MHz DMSO) δ12.7 (s, 1H, NH), 7.95(m, 2H, ArH), 7.25-
7.35(m, 5H, ArH), 7.05(2H, ArH); m/z 195(M+H). Elemental analysis Calcd.
for C13H10N2. C, 80.39; H, 5.19; N, 14.42. Found: C, 80.42; H, 5.17; N, 14.41.
The benzimidazoles, benzoxazole and benzthaizoles are an important
1,2
heterocyclic nucleus which has been widely used in medicinal chemistry
.
3,4
These heterocycles are an important pharmacophore in drug discovery and
good intermediate 5 in synthesis of many important organic compounds. These
heterocycles shows different pharmacological properties such as antibacterial
6, antiviral 7, antifugal 8, anticancer 9 , anticonvulsant 10 and immunosuppressant
2-(4-methoxy phenyl)-1H-benzimidazole 3b
1H NMR(400MHz DMSO) δ 3.8(s, 3H, OCH3), 7.09-7.11(d, 2H, J 9.2Hz,
ArH), 7.16-7.18(m, 2H, ArH), 7.53-7.56(m, 2H, ArH), 8.08-8.11(d, 2H, J
8.8Hz, ArH); m/z 225 (M+H) . Elemental analysis Calcd. for C14H12N2O. C,
74.98; H, 5.39; N, 12.49. Found: C, 75.03; H, 5.36; N, 12.45.
11
.
These heterocycles can be prepared by condensing carboxylic acid
13,
18
19-24
12, acid chloride
14, orthoester 15-17, esters
and aldehydes
with
o-phenylenediamine, o-aminophenols and o-aminothaiophenols, dehydration
of o-acylaminophenols 25, reaction of o-quinones with amines 26 and Beckmann
rearrangement of o-acylphenoloximes 27. The most common method of
2-(4-chlorophenyl)-1H-benzimidazole 3c
1H NMR(400MHz DMSO) δ 12.5 (s, 1H, NH), 8.20 (d, 2H, ArH), 7.6
(d, 2H, ArH), 7.3 (m, 2H, ArH), 7.1 (m, 2H, ArH); m/z 229(M+H). Elemental
analysis Calcd. for C13H9N2Cl. C, 68.28; H, 3.97; N, 12.25. Found: C, 68.20;
H, 4.01; N, 12.28.
synthesis of these heterocycles includes condensation of o-phenylenediamine,
28-32
o-aminophenol or o-aminothiophenol with suitable aldehyde
. Most of
these procedure have their own advantages and disadvantages, thus there is
still a need to search better ecofriendly procedure.
5-Chloro-2-(4-methoxyphenyl)-1H-benzimidazole 3d
The toxic and volatile natures of many organic solvents have posed serious
environmental problems. Due to this organic reaction in aqueous media have
attracted much attention in synthetic organic chemistry because water is one of
the most abundant, cheap and environmental friendly solvent however there are
very few reports for synthesis of 1,3 benzazoles in aqueous media.
1H NMR(400MHz DMSO) δ 7.97 (d, J 9.2 Hz, 2H), 7.86 (s, 1H), 7.67 (d,
J 8.1 Hz, 1H), 7.35 (d, J 8.1 Hz,1H), 6.92 (d, J 9.2 Hz, 2H), 3.75 (s, 3H) ; m/z
276 (M+H). Elemental analysis Calcd. for C14H11ClN2O. C, 65.00; H, 4.29; N,
10.83. Found: C, 65.05; H, 4.25; N, 10.80.
Ultrasound irradiation has been established as an important technique
in synthetic organic chemistry. It has been used as an efficient energy source
for the organic reactions. Simple experimental procedure, very high yields,
increased selectivity and clean reaction of many ultrasound induced organic
transformations offers additional convenience in the field of synthetic organic
chemistry 33-36.These finding promotes us to investigate the synthesis of
benzimidazoles, benzoxazole and benzothiazoles in aqueous media.
5-Chloro-2-(4-nitrophenyl)-1H-benzimidazole 3e
1H NMR(400MHz DMSO-d ) δ 8.52 (d, J 9.4 Hz, 2H), 7.96 (d, J 9.4
Hz, 2H), 7.85 (s, 1H), 7.71 (d, J 68.2 Hz, 1H),7.32 (d, J 8.2 Hz, 1H); m/z 274
(M+H). Elemental analysis Calcd. for C H8ClN3O2. C, 57.05; H, 2.95; N,
15.35. Found: C, 56.98; H, 3.01; N, 15.30.13
5-Chloro-2-(4-N,N-dimethylaminophenyl)-1H-benzimidazole: 3f
1H NMR(400MHz DMSO-d6) δ 7.94 (d, J 8.9 Hz, 2H), 7.85 (s, 1H), 7.66
(d, J 8.3 Hz, 1H), 7.37 (d, J 8.3 Hz, 1H), 6.82 (d, J 8.9 Hz, 2H), 3.35 (s, 6H);
m/z 272 (M+H). Elemental analysis Calcd. for C15H14ClN3. C, 66.30; H, 5.19;
N, 15.46. Found: C, 66.38; H, 5.12; N, 15.40.
EXPERIMENTAL
Bandelin Sonorex (35 kHz) ultrasonic bath was used for ultrasonic
irradiation. 1H NMR spectra were recorded on Mercury Plus Varian in DMSO
at 400 MHz using TMS as an internal standard. Mass spectra were recorded on
Micromass Quattro II using electrospray Ionization technique, showing (M+H)
peak as a base peak. The progress of the reactions was monitored by TLC
(silica, 80:20 hexane/ ethyl acetate).
2-(3-nitrophenyl)-1H- benzimidazole 3g
1H NMR(400MHz DMSO-d6) δ 12.9 (s,1H NH), 8.90 (s,1H Ar H), 8.50
(d,1H Ar H), 8.10 (d,1H Ar H), 7.70 (t,1H Ar H), 7.50 (m, 2H ArH), 7.2 (m,
2H ArH); m/z 240(M+H). Elemental analysis Calcd. for C13H9N3O2. C, 65.27;
H, 3.79; N, 17.56. Found: C, 65.32; H, 3.70; N, 17.62.
General Procedure for the Preparation of 3a-3l
o-phenylene diamine (1mmol), aromatic aldehyde (1.1mmol) and
water (10mL) were mixed in 25mL single neck round bottom flask, and to this
Ammonium Nickel Sulphate (10 mol %) was added. The reaction mixture was
sonicated at room temperature (250C) for the appropriate time (Table 2, entries
1-12), and the progress of reaction was monitored by TLC. After completion of
reaction, the mixture was extracted with ethyl acetate (2×10mL). The combined
organic layer was dried over anhydrous Na SO and evaporated under reduced
pressure; the crude material was purified2 by4column chromatography over
silica gel to afford products 3a-3l with high purity.
2-pyridin-3yl-1H-benzimidazole 3h
1H NMR(400MHz DMSO-d6) δ 13.05 (s, 1H NH), 9.35(d,1H ArH),
8.75(m,1H ArH), 8.60(m,1H ArH), 7.70(m,3H ArH) 7.40 (m,2H ArH); m/z
196(M+H). Elemental analysis Calcd. for C12H9N3. C, 73.83; H, 4.65; N, 21.52.
Found: C, 73.90; H, 4.60; N, 21.50.
2-(2,3-Dimethoxyphenyl)-1H-benzimidazole 3i
1H NMR(400MHz DMSO-d6) δ 12.19 (s, 1H, NH), 7.84 (dd, 1H, J
e-mail: snthore@rediffmail.com
2335

J. Chil. Chem. Soc., 59, Nº 1 (2014)
7.3 Hz,1.1 Hz, ArH), 7.64 (m, 3H, ArH), 7.20 (m, 3H, ArH), 3.90 (s, 3H,
OCH3), 3.85 (s, 3H, OCH3); m/z 255 (M+H). Elemental analysis Calcd. for
C15H14N2O2. C, 70.85; H, 5.55; N, 11.02. Found: C, 70.89; H, 5.49; N, 11.07.
2.42Hz, 7.55 Hz, 2H, ArH), 7.85(d,J 8.15Hz,2H,ArH),7.61(dd, J 7.55Hz,
7.75Hz, 2H, ArH) ;m/z 237(M+H). Elemental analysis Calcd. for C14H8N2S. C,
71.16; H, 3.41; N, 11.86. Found: C, 71.21; H, 3.44; N, 11.80.
2-(3-Fluorophenyl)-1H-benzimidazole 3j
2-(3,4,5 trimethoxy phenyl) benzothiazole 4h
1H NMR(400MHz DMSO-d6) δ 13.00 (s, 1H, NH), 8.02 (d, 1H, J 7.7 Hz,
ArH), 7.96 (m, 1H, ArH), 7.69 (m, 1H, ArH), 7.59 (m, 2H, ArH), 7.34 (m,
1H, ArH), 7.23 (m, 2H, ArH); m/z 213 (M+H). Elemental analysis Calcd. for
C13H9FN2. C, 73.57; H, 4.27; N, 13.20. Found: C, 73.51; H, 4.32; N, 13.28.
1H NMR(400MHz DMSO-d6) δ 8.31(t, 1H, ArH), 8.22(t, 1H, ArH),
7.45(dd J 2.42Hz,7.55Hz, 2H, ArH), 6.57(d, J 2.42Hz, 2H, ArH), 3.61(s, 9H,
OCH3).;m/z 302(M+H). Elemental analysis Calcd. for C16H15NO3S. C, 63.77;
H, 5.02; N, 4.65. Found: C, 63.69; H, 4.99; N, 4.71.
2-(3-chloro phenyl)-1H-benzimidazole 3k
2-(4-chlorophenyl) benzothiazole 4i
1H NMR(400MHz DMSO-d6) δ 8.41(t, 1H, J 1.2Hz, 2.0Hz, ArH), 8.20-
8.29(dd, 1H, J 1.2 ,7.6Hz, ArH), 7.80-7.84(m, 2H, ArH), 7.69-7.77(m, 2H,
ArH), 7.50-7.54(m, 2H,ArH); m/z 229 (M+H). Elemental analysis Calcd. for
C13H9ClN2. C, 68.28; H, 3.97; N, 12.25. Found: C, 68.35; H, 3.92; N, 12.20.
1H NMR(400MHz DMSO-d ) δ 8.15( d, J 7.3Hz, 1H, ArH), 8.05(d, J 8.4
Hz, 2H, ArH), 7.80 (d, J 7.3 Hz, 61H, ArH), 7.41(t, J 7.6 Hz, 1H, ArH), 7.30(t,
J 7.6 Hz, 1H, ArH),7.16(d, J 8.22Hz, 2H, ArH); m/z 246(M+H). Elemental
analysis Calcd. for C13H8ClNS. C, 63.54; H, 3.28; N, 5.70. Found: C, 63.61;
H, 3.30; N, 5.65.
2-(4-nitrophenyl)-1H- benzimidazole 3l
1H NMR(400MHz DMSO-d6) δ 8.37-8.39(d,2H,J 8.4Hz, ArH), 8.14-
8.17(d, 2H, J 8.8Hz, ArH), 7.70-7.72(d,1H,J 7.6 Hz, ArH ), 7.65-7.67(d, 1H,
J 8.4Hz, ArH) 7.32-7.35(m, 1H,ArH), 7.25-7.29(m,1H, ArH); m/z 240(M+H).
Elemental analysis Calcd. for C13H9N3O2. C, 65.27; H, 3.79; N, 17.56. Found:
C, 65.20; H, 3.87; N, 17.50.
6-Chloro-2-phenyl benzothiazole 4j
1H NMR(400MHz DMSO-d6) δ 8.19(d, J 8.3Hz, 1H, ArH), 8.13(d, J
2.12Hz, 1H, ArH), 7.56(dd, J 7.61Hz, 2.17, 2H, ArH), 7.36(t, J 7.61Hz,
2H,ArH),7.16(m, 1H, ArH); m/z 246(M+H). Elemental analysis Calcd. for
C13H8ClNS. C, 63.54; H, 3.28; N, 5.70. Found: C, 63.49; H, 3.32; N, 5.78.
General Procedure for the Preparation of 4a-4m
6-chloro-2(3-methoxy phenyl) benzothaizole 4k
o-amino thiophenol (1mmol), aromatic aldehyde (1.1mmol) and
water (10mL) were mixed in 25mL single neck round bottom flask, and
to this Ammonium Nickel Sulphate (10 mol %) was added. The reaction
mixture was sonicated at room temperature (250C) for the appropriate time
(Table 2, entries 13-25), and the progress of reaction was monitored by TLC.
After completion of reaction, the mixture was extracted with ethyl acetate
(2×10mL). The combined organic layer was dried over anhydrous Na2SO4 and
evaporated under reduced pressure; the crude material was purified by column
chromatography over silica gel to afford products 4a-4m with high purity.
Selected spectral data
1H NMR(400MHz DMSO-d ) δ 7.99(d, J 2.5Hz, 1H,ArH), 7.77(d, J
7.7Hz, 1H, ArH), 7.60-7.70(m, 62H,ArH), 7.32-7.50(m, 2H,ArH), 7.16(dd
J 2.5Hz, 7.8 Hz, 1H, ArH), 3.91(s 3H, OCH3); m/z 276(M+H). Elemental
analysis Calcd. for C14H10ClNOS. C, 60.98; H, 3.66; N, 5.08. Found: C, 61.05;
H, 3.58; N, 5.13.
6-chloro-2-(4-chlorophenyl) benzothiazole 4l
1H NMR(400MHz DMSO-d6) δ 8.17(d, J 7.9Hz, 1H, ArH), 8.13(d, J
2.2Hz, 1H, ArH), 7.56(dt, J 7.9Hz, 2.2Hz, 1H, ArH), 7.41(d, J 8.1Hz, 2H,
ArH), 7.32(d, J 8.1Hz, 2H, ArH); m/z 280(M+H). Elemental analysis Calcd.
for C13H7Cl2NS. C, 55.73; H, 2.52; N, 5.00. Found: C, 55.70; H, 2.48; N, 5.06.
2-Phenyl-1,3-benzothiazole 4a
1H NMR(400MHz DMSO) δ 8.12(d, J 7.38Hz, 1H, ArH), 8.02(t, J 7.42
Hz, 1H, ArH), 7.65(t, J 7.42Hz, 1H, ArH), 7.33-7.39(m, 3H, ArH), 7.19-
7.25(m, 3H, ArH).;m/z 212(M+H). Elemental analysis Calcd. for C13H9NS. C,
73.90; H, 4.29; N, 6.63. Found: C, 73.82; H, 4.35; N, 6.58.
2-(4-(piperidin-1-yl)phenyl)benzothiazole 4m
1H NMR(400MHz DMSO-d6) δ 7.92-8.00(m, 2H, ArH), 7.84-7.90(d,
J 7.6Hz, 2H,ArH), 7.25(m,2H, ArH), 6.94-6.97(d, J 7.6Hz, 2H,ArH), 3.31-
3.34(m, 4H,piperidine N-CH2,), 1.53-1.71(m, 6H, piperidine CH2); m/z
295(M+H). Elemental analysis Calcd. for C18H18N2S. C, 73.43; H, 6.16; N,
9.51. Found: C, 73.50; H, 6.20; N, 9.45.
2-(4-Methoxyphenyl)- 1,3-benzothiazole 4b
1H NMR(400MHz DMSO) δ 8.19(d, J 8.22Hz, 1H,ArH), 8.05(d, J 8.22Hz,
1H, ArH), 7.07(d, J 7.75Hz, 2H, ArH), 7.12-7.41(m, 4H, ArH), 3.92(s 3H,
OCH3); m/z 242(M+H). Elemental analysis Calcd. for C14H11NOS. C, 69.68;
H, 4.59; N, 5.80. Found: C, 69.59; H, 4.65; N, 5.85.
General Procedure for the Preparation of 5a-5f
o-amino phenol (1mmol), aromatic aldehyde (1.1mmol) and water (10mL)
were mixed in 25mL single neck round bottom flask, and to this Ammonium
Nickel Sulphate (10 mol %) was added. The reaction mixture was sonicated at
room temperature (250c) for the appropriate time (Table 2, entries 26-31), and
the progress of reaction was monitored by TLC. After completion of reaction,
the mixture was extracted with ethyl acetate (2×10mL). The combined organic
layer was dried over anhydrous Na2SO and evaporated under reduced pressure;
the crude material was purified by co4lumn chromatography over silica gel to
afford products 5a-5f with high purity.
2-(4-Nitrophenyl) benzothiazole 4c
1H NMR(400MHz DMSO-d ) δ 8.9 (d, J 8.0 Hz, 2H, Ar-H); 8.32 (d, J
8.0 Hz, 2H, Ar- H); 8.23 (d, J 8.60 Hz, 1H, Ar-H); 8.02 (d, J 8.0 Hz, 1H, Ar-
H); 7.44-7.53 (m, 2H, Ar-H); m/z 256 (M+H). Elemental analysis Calcd. for
C13H8N2O2S. C, 60.93; H, 3.15; N, 10.93. Found: C, 61.03; H, 3.20; N, 10.85.
2-Thienyl-1,3-benzothiazole 4d
1H NMR(400MHz DMSO) δ 8.22 (d, J 8.0 Hz, 1H, ArH); 8.13 (d, J 8.0
Hz, 1H, ArH); 7.74 (d, J 4.0 Hz, 1H, thiophene CH); 7.69 (d, J 4.0 Hz, 1H,
thiophene CH); 7.54-7.63 (m, 2H, Ar-H);7.33 (t, J 4.0 Hz, 1H, thiophene CH);
m/z 217(M+H). Elemental analysis Calcd. for C11H7NS2. C, 60.80; H, 3.25; N,
6.45. Found: C, 60.84; H, 3.20; N, 6.52.
Selected spectral data
2- phenyl benzoxazole 5a
1H NMR(400MHz DMSO-d ) δ 8.32(dd, J 5.6Hz, 2.1Hz, 2H, ArH),
7.79-7.86(m, 1H, ArH), 7.53-7.676(m, 4H, ArH), 7.36-7.44(m, 2H, ArH).; m/z
196(M+H). Elemental analysis Calcd. for C13H9NO. C, 79.98; H, 4.65; N, 7.17.
Found: C, 79.91; H, 4.70; N, 7.20.
2-(4-Fluoro phenyl) benzothiazole 4e
1H NMR(400MHz DMSO-d6) δ 8.7 (s, 1H, pyrazolyl-H), 8.03 (d, J 6 Hz,
2H), 7.74 7.85 (m, 5H, Ar-H), 7.45-7.60 (m, 5H, Ar-H), 7.31-7.38 (dd, J 8Hz ,
6 Hz, 2H); m/z 230 (M+H). Elemental analysis Calcd. for C13H8FNS. C, 68.16;
H, 3.52; N, 6.11. Found: C, 68.16; H, 3.45; N, 6.18.
2-(4-methoxyphenyl)benzoxazole 5b
1H NMR(400MHz DMSO) δ 8.22(d, J 8.2Hz, 2H, ArH), 7.85 (m, 1H,
ArH), 7.61(m, 1H, ArH), 7.37-7.42(m, 2H, ArH), 7.16(d, J 8.2Hz, 2H, ArH),
3.89(s, 3H, OCH3); m/z 226(M+H). Elemental analysis Calcd. for C14H11NO2.
C, 74.65; H, 4.92; N, 6.22. Found: C, 74.70; H, 4.88; N, 6.17.
2-(4 methyl phenyl) benzothiazole 4f
1H NMR(400MHz DMSO-d6) δ 7.92-8.10(m 3H Ar H), 7.41(t J 7.38Hz,
1H Ar H), 7.30 (t J 7.38Hz, 1H Ar H), 7.26(d J 8.12Hz 2H Ar H),2.45(s 3H
CH3) ;m/z 226(M+H). Elemental analysis Calcd. for C14H11NS. C, 74.63; H,
4.92; N, 6.22. Found: C, 74.69; H, 4.88; N, 6.28.
2-(4-cyanophenyl)benzoxazole 5c
1H NMR(400MHz DMSO-d6) δ 8.32( d, J8.5Hz, 2H, ArH), 7.81-
7.97(m,3H, ArH), 7.51(m, 1H, ArH), 7.31-7.49(m, 2H,ArH); m/z 221(M+H).
Elemental analysis Calcd. for C14H8N2O. C, 76.35; H, 3.66; N, 12.72. Found:
C, 76.28; H, 3.70; N, 12.68.
2-(4-cyanophenyl) benzothiazole 4g
1H NMR(400MHz DMSO-d6) δ 8.09(d, J 8.15Hz, 2H, ArH), 8.05(dd, J
2336

J. Chil. Chem. Soc., 59, Nº 1 (2014)
2-(3,4- dichlorophenyl)benzoxazole 5d
o-phenylene diamine (1) and anisaldehyde (2). We first conducted the reaction
of 1 (1 equivalent) and 2 (1.1 equivalent) in the presence of Ammonium Nickel
Sulfate in water at different temperature (Table 1 entries 10 to12). The yield
increases from 30% to 50% up to 80oC in 8hours. With the aim to reduce
reaction time and temperature, we move to non-conventional energy source
i.e. ultrasound energy, so we carried the reaction under ultrasound, to afford
the corresponding 2-(4-methoxy phenyl)benzimidazole (3b) in 85% yield (
Table 1 entry 13 )in much shorter time at room temperature. To know the effect
of solvent, We kept the catalyst constant and used different solvent CH Cl ,
CH3CN, THF, CHCl3, DMF, EtOH ,DMSO and Dioxane but all afford a2ve2ry
low yield ( Table 1 entries 1-8 ). These indicate that water is the best solvent for
the synthesis of 3b; it may be due to solubility of catalyst, varying the amount
of catalyst did not improve the yield (Table 1 entries14, 15)
1H NMR(400MHz DMSO) δ 8.37(d J 8.1Hz, 1H, ArH), 8.19(dd, J 8.2Hz,
1.8Hz, 1H, ArH), 7.72-7.83(m, 1H, ArH), 7.62-7.71(m, 2H, ArH), 7.40-
7.45(m, 2H, ArH); m/z 264(M+H). Elemental analysis Calcd. for C13H7Cl2NO.
C, 59.12; H, 2.67; N, 5.30. Found: C, 59.20; H, 2.62; N, 5.24.
6-methyl-2phenyl benzoxazole 5e
1H NMR(400MHz DMSO-d6) δ 8.26-8.39(m, 2H, ArH), 7.70(d, J 8.2Hz,
1H,ArH), 7.55-7.62(m, 3H, ArH), 7.35(m, 1H, ArH), 7.09(m, 1H, ArH), 2.51(s,
3H, CH3); m/z 210(M+H). Elemental analysis Calcd. for C14H11NO. C, 80.36;
H, 5.30; N, 6.69. Found: C, 80.43; H, 5.26; N, 6.60.
6-fluoro -2-phenyl benzoxzole 5f
1H NMR(400MHz DMSO) δ 8.20-8.28(m, 2H, ArH), 7.79(dd, J 8.8Hz,
4.9Hz, 1H,ArH), 7.52-7.61(m, 3H,ArH), 7.29(dd, J 8.0, 2.3Hz, 1H, ArH),
7.11(m, 1H, ArH); m/z 214(M+H). Elemental analysis Calcd. for C13H8FNO.
C, 73.23; H, 3.78; N, 6.57. Found: C, 73.20; H, 3.83; N, 6.50.
RESULT AND DISCUSSION
We developed an ecofriendly, one potAmmonium Nickel Sulfate catalyzed
synthesis of 2-aryl substituted benzimidazole, benzoxazole and benzothiazole
in water.
2-(4-methoxy phenyl)benzimidazole (3b)(scheme 1) was selected as
a proto type compound to optimize the reaction condition (Table 1) from
Scheme 1
With optimal condition in hand, we reacted various substituted o-phenylene diamine 1 and aromatic aldehyde 2 to give the corresponding substituted 2-aryl
benzimidazole product 3a to 3l (Table 2 entries1-12). A wide variety of aldehydes were used, which have both electron donating and electron withdrawing
substituents along with substituted o-phenylene diamine. The method is also suitable for heteroaromatic aldehyde.
Table 1. Solvent effect on the reaction of anisaldehyde and o-phenylene diamine in presence of ammonium nickel sulphate.
Entry
1
solvent
CH2Cl2
CHCl3
DMSO
DMF
EtOH
CH3CN
Dioxane
THF
catalyst
10
Temp./0C
RT*
RT*
RT*
RT*
RT*
RT*
RT*
RT*
RT
Time/min
120
Producta
Yield (%)b
Traces
Traces
45
3b
2
10
120
3b
3
10
120
3b
4
10
120
3b
45
5
10
120
3b
30
6
10
120
3b
40
7
10
120
3b
38
8
10
120
3b
36
9
H2O
10
8Hours
8 Hours
8 Hours
8 Hours
120
3b
Traces
25
10
11
12
13
14
15
H2O
10
40
3b
H2O
10
60
3b
40
H2O
10
80
3b
50
H2O
10
RT*
RT*
RT*
3b
85
H2O
05
120
3b
65
H2O
15
120
3b
85
* Under ultra-sonication.
a1mmole of o-phenylene diamine , 1.1mmol anisaldehyde, 10mol% catalyst, solvent, room temperature. bIsolated yield based on starting o-phenylene diamine.
The scope of above procedure was expanded to the synthesis of2-
aryl benzoxazole from o-amino phenol and 2-aryl benzothiazole from
o-aminothiophenol, the results are summarized in Table 2. Aromatic aldehyde
with electron donating as well as electron withdrawing groups participated
in the reaction, the nature and position of substituent on the aryl ring does
not make much difference in reactivity. The structures of the products were
confirmed by 1H NMR, mass spectra.
2337

J. Chil. Chem. Soc., 59, Nº 1 (2014)
Table 2. Ammonium nickel sulphate [(NH4)2SO4.NiSO4.6H2O] catalyzed of 2-arylbenzimidazole, 2-arylbenzothiazole and 2-arylbenzoxazole under
ultrasonication in water
Standard condition: 1mmole of o-phenylene diamine or o-aminothiophenol or o-aminophenol, 1.1mmol ArCHO, 10mol% catalyst(ammonium nickel
sulphate) , water , room temperature. Isolated yield based on starting o-phenylene diamine or o-aminothiophenol or o-aminophenol
M.Pt 0C
entry
R
H
H
Ar
X
N
N
product
3a
Time(min)
135
yield
80
observed
287-288
reported
292 37
1
2
3b
120
85
228-230
288-291
276-279
258-259
311-313
226 37
OMe
Cl
3
4
5
6
H
N
N
N
N
3c
3d
3e
3f
110
140
105
150
89
86
87
85
294 37
5-Cl
5-Cl
5-Cl
278-279 40
260-261 40
310-312 43
OMe
NO2
NMe2
NO2
7
8
H
H
N
N
3g
95
85
88
200-202
243-246
204-206 38
245-248 42
3h
110
N
OMe
MeO
9
H
H
H
N
N
N
3i
3j
145
120
125
83
87
88
175-177
219-221
230-231
178-179 39
220-222 39
F
10
11
Cl
3k
234 37
316 37
12
13
14
H
H
H
N
S
S
3l
4a
4b
110
90
90
91
90
308-310
110-112
121-124
NO2
113 – 114
40
120 – 122
95
40
OMe
NO2
226 – 228
15
H
S
4c
85
86
224-227
40
2338

J. Chil. Chem. Soc., 59, Nº 1 (2014)
100 – 102
16
H
S
4d
110
83
101-104
40
S
101 – 102
17
18
19
H
H
H
S
S
S
4e
4f
95
105
90
86
85
86
98-100
F
41
83-84
98-99
85-87 41
Me
CN
4g
100-102 31
OMe
OMe
Color less
20
H
S
4h
115
83
----------
oil
OMe
116 – 118
21
22
H
S
S
4i
4j
90
95
91
85
115-118
102-103
40
Cl
6-Cl
104-105 31
72-74 31
OMe
23
24
6-Cl
6-Cl
S
S
4k
4l
110
90
85
86
71-74
141-142
140-142 31
Cl
N
25
26
27
H
H
H
S
O
O
4m
5a
100
130
135
85
83
85
72-74
100-101
96-97
--------
101-102 31
98 31
5b
OMe
28
29
H
H
O
O
5c
5d
120
120
83
83
200-202
140-143
201-204 31
142-144 31
CN
Cl
Cl
30
31
6-Me
O
O
5e
5f
130
120
85
86
93-96
95 31
6-F
110-112
108-111 31
2339

J. Chil. Chem. Soc., 59, Nº 1 (2014)
17. D. Villemin, M. Hammadi, B. Martin, Synthetic Commun., 1996, 26,
2895.
CONCLUSIONS
18. A. K. Chakraborti, S. Rudrawar, G. Kaur, L. Sharma, Synlett., 2004, 1533.
19. A. Hari, C. Karan, W. C. Rodridues, B. L. Miller, J. Org. Chem., 2001, 66,
991.
20. P. L. Beaulieu, B. Hache, E. Von Moss, Synthesis, 2003, 1683.
21. M. Curini, F. Epifano, F. Montanari, O. Rosati, S. Taccone, Synlett., 2004,
1832.
Ammonium Nickel Sulphate as a catalyst provides cheap, safe and
environment friendly procedure for the synthesis of 2-aryl substituted
benzimidazole, benzoxazole and benzothiazole derivatives from various
aromatic aldehydes with o-phenylene diamine, o-amino phenol and o-amino
thiophenol. The advantages offered by this method are operational simplicity,
good yield of product.
22. P. Gogoi, D. Konwar, Tetrahedron Lett., 2006, 47, 79.
23. R. Trivedi, S. K. De, R. A. Gibbs, J. Mol. Catal. A: Chem., 2006, 245, 8.
24. V. G. Navarrete, D. H. Moreno, C. F. Aguirre, R. I. Leon, M. R. Villalobos,
M. O. Munoz, S. S. Estrada, Bioorg. Med. Chem. Lett., 2006, 16, 4169.
25. G. V. Boyd, A. R. Katritzky, C. W. Rees, K. T. Potts, Comprehensive
Heterocyclic Chemistry, Pregamon Press: New York, 1984, 177.
26. X. Z. Bu, Z. S. Huang, M. Zhang, L. Ma, G. W. Xiao, L. Q. Gu, Tetrahedron
Lett., 2001, 42, 5737.
27. B. M. Bhaval, S. P. Mayabhate, A. P. Likhite, A. R. Deshmukh, Synthetic
Commun., 1995, 25, 3315.
28. Y. Riadi, R. Mamouni, R. Azzalou, M. El Haddad, S. Routier, G.
Guillaumet, S. Lazar, Tetrahedron Lett., 2011, 52, 3492.
29. H. M. Bachhav, S. B. Bhagat, V. N. Telvekar, Tetrahedron Lett. ,2011, 52,
5697.
ACKNOWLEDGMENTS
The authors are grateful to the Head, Department of Chemistry, Vinayakrao
Patil Mahavidyalaya, Vaijapur for providing the laboratory facility and Director,
SAIF, Chandigarh for providing spectral analysis of synthesized compounds.
REFERENCES
1. D. A. Horton, G. T. Bourne, M. L. Smythe, Chem.Rev., 2003, 103, 893.
2. A. A. Weekes, A. D. Westwell, Curr.Med.Chem., 2009, 16, 2430.
3. B. Gong, F. Hong, C. Kohm, L. Bonham, P. Klein, Bioorg.Med.Chem.
Lett.2004,14,1455.
4. S. M. Sodhi, N. Singh, A. Kumar, O. Lozach, L. Meijer, Bioorg.Med.
Chem., 2006, 14, 3758.
5. J. Vinsona, K. Cermakova, A. Tomeckova, M. Ceckova, J. Jampilek, P.
Cermak, J. Kunes, M. Dolezal, F. Staud, Bioorg. Med.Chem., 2006, 14,
5850.
30. A. J. Blacker, M. M. Farah, M. L. Hall, S. P. Marsden, O. Saidi, J. M.
Williams, Org.Lett., 2009, 11, 2039.
31. S. S. Pawar, D. V. Dekhane, M. S. Shingare, S. N. Thore, Australian J.
Chem., 2008, 61, 905.
32. S. S. Pawar, D. V. Dekhane, M. S. Shingare, S. N. Thore, Chinese
Chemical Letters , 2008, 19, 1055.
6. I. O. Yildiz, I. Yalcin, E. Akisener, N. Ueartark, Eur.J.Med.Chem., 2004,
39, 291.
33. T. J.Mason, J. P. Lorimer, Sonochemistry: Theory, Application and Uses of
Ultrasound in Chemistry; John Wiley and Son: New York, 1988.
34. K. S. Suslick, Ultrasound, its Chemical, Physical and Biological Effects;
VCH: Weinheim, 1988.
35. A. Gaplovsky, M. Gaplovsky, S. Toma, J. L. Luche, J. Org. Chem., 2000,
65, 8444.
36. R. R. Deshmukh, R. Rajagopal, K. V. Srinivasan, Chem. Commun., 2001,
1544.
37. A. Ben-Alloum, K. Bougrin, M. Soufiaoui, Tetrahedron Lett., 2003, 44,
5935.
7. X. Song, B. S. Vig, P. L. Lorenzi, J. C. Drach, L. B. Townsend, G. L.
Amidon, J.Med.Chem., 2005, 48, 1274.
8. M. Yamoto, J.Pharm.Soc.Jpn., 1992, 112, 81.
9. D. Kumar, M. R. Jacob, M. B. Rcynold, S. M. Karvin, Bioorg.Med.Chem.,
2002, 10, 3997.
10. A. Benazzouz, T. Boraud, P. Dubedat, A. Bioreau, J. M. Stutzmann, C.
Gross, Eur.J.Pharmacol., 1995, 284, 299.
11. A. R. Katritzky, C. A. Ramsden, E. F. V. Scriven, R. J. K. Taylor,
Comprehensive Heterocyclic Chemistry III, Vol. 3; ed. 1; Elsevier : London
, 2008
38. M. R. DeLuca, S. M. Kerwin, Tetrahedron, 1997, 53, 457.
39. S. E. López, J. Restrepo, B. Pérez, S. Ortiz, J. Salazar, Bull. Korean Chem.
Soc., 2009, 30, 7.
40. K. S. Niralwad, B. B. Shingate, M. S. Shingare, Bull. Korean Chem. Soc.,
2010, 31, 981.
12. E. Alcalde, I. Dinares, L. Perez-Garcia, T. Roca, T.; Synthesis, 1992, 395.
13. R. S. Pottorf, N. K. Chadha, M. Katkevics, V. Ozola, E. Suna, H. Ghane, T.
Regberg, M. R. Player, Tetrahedron Lett., 2003, 44, 175.
14. R. N. Nadaf, S. A. Siddiqui, T. Daniel, R. J. Lahoti, K. V. Srinivasan, J.
Mol. Catal. A: Chem., 2004, 214, 155.
41. D. Azarifar, B. Maleki, M. Setayeshnazar, Phosphorus, Sulfur Silicon
Relat. Elem., 2009, 184, 2097.
42. H. J. Myung, M. P. Jung, C. L. Ihl-Young, A. Miya, J. Heterocyclic Chem.,
15. G. L. Jenkins, A. M. Knevel, C. S. Davis, J. Org. Chem., 1961, 26, 274.
16. M. Doise, F. Dennin, D. Blondeau, H. Sliwa, Tetrahetron Lett., 1990, 31,
1155.
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