Expedient synthesis of benzimidazoles using amides

Article abstract of DOI:10.1039/c5ra00021a

In the present report an efficient, rapid, facile and inexpensive route for the synthesis of benzimidazoles using 1,2-arylenediamines and N,N-dimethylformamide in acidic medium under thermal/microwave condition is developed. This reaction was further explored with the different amides to afford a library of 2-substituted benzimidazoles. The advantage of the present synthetic method includes shorter reaction time, easy work up and excellent yields without using catalysts.

Full text of DOI:10.1039/c5ra00021a

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Expedient synthesis of benzimidazoles using amides
Pramod P. Kattimani, Ravindra R. Kamble*, Gangadhar Y. Meti
Department of Studies in Chemistry, Karnatak University, Dharwad – 580003, Karnataka,
India.
E-mail: kamchem9@gmail.com
In the present report an efficient, rapid, facile and inexpensive route for the synthesis of
benzimidazoles using 1,2-arylenediamines and N,N-dimethylformamide in acidic medium
under thermal/microwave condition is developed. This reaction was further explored with the
different amides to afford a library of 2-substituted benzimidazoles. The advantage of the
present synthetic method includes shorter reaction time, easy work up and excellent yields
without using the catalysts.
Introduction
Nitrogen containing heterocyclic compounds have maintained interest of researchers since
their structures have led to several applications in various fields.1-6 Hence, the synthesis of
these compounds has become significantly important in synthetic chemistry. The discovery of
N-ribosyl-dimethylbenzimidazole, a ligand for cobalt in vitamin B12 has boosted the interest
in the development of synthetic strategies for benzimidazole derivatives.7 Benzimidazoles
have evolved as important scaffolds in medicinal chemistry since from the past several years
due to their diverse range of biological activities viz., antiviral,8 antimicrobial,9 antifungal,10
antitumor,11 antihistaminic,12 antihypertensive,13 anti-inflammatory,14 antiulcer15 and
antitubercular.16
The most popular synthetic procedure for the synthesis of benzimidazoles generally
involves condensation reaction of 1,2-phenylenediamine with carboxylic acids17 (Phillips
reaction) or with their derivatives (acid chlorides, nitriles, ortho esters or imidates).18 These
often employ use of strong acids (hydrochloric acid, polyphosphoric acid (PPA), boric acid or
p-toluene sulphonic acid) as catalyst, sometimes combined with high temperatures (i.e., PPA,
1

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180°C). Benzimidazole derivatives have also been generated from the oxidative condensation
of 1,2-arylenediamines with aldehydes using various oxidative and catalytic reagents such as
oxygen,19 nitrobenzene (high boiling oxidant/solvent),20 1,4-benzoquinone,21 benzofuroxan,22
2,3-dichloro-5,6-dicyanobenzoquinone (DDQ),23 Zn-proline,24 Pb(OAc)4,25 MnO2,26
KHSO4,27 NaHSO3,28 IBD (iodobenzene diacetate),29 Na2S2O5,30 oxone,31 FeCl3.6H2O,32
polyaniline-sulfate salt,33 H2O2/CAN,34 HfCl4, ZrCl4,35 ZrOCl2.8H2O,36 In(OTf)3,37
Yb(OTf)3,38 Sc(OTf)3,39 Cu(OTf)2,40 Co(OH)2/CoO(II),41 CdCl2,42 BF3-etherate,43 copper
complex,44 PhI(OAc)2,45(a) NH4OAc,45(b) Pd(TMHD)2 complex,46 NaY-zeolite,47
cholrotrimethylsilane,48 ionic liquid,49 Pd-MgO, Pd-C, Au-CeO2.50 Although the above
mentioned reaction conditions often efficiently prompted, but suffer from one or more
disadvantages such as usage of high boiling solvents, costly catalyst, strong oxidising
reagents, prolonged reaction times, laborious work up and purifications.
The invention of simple, mild, practicable, cheap and eco-benign method for the
synthesis of benzimidazoles have grabbed the attention of researchers. Microwave assisted
organic synthesis has become rapid growing field in organic chemistry as this technique
makes reaction time shorter and tolerate wide range of reactions which are best suited to the
increased demands of industry.51 In view of this, we have developed an efficient, facile and
inexpensive method for the synthesis of benzimidazole derivatives using 1,2-arylenediamines
and N,N-dimethylformamide (both as solvent and reagent) under acidic medium in short
period of time both by thermal as well as microwave reaction. Also, the reactions of 1,2-
phenylenediamine with different amides was carried out under thermal and microwave
conditions to get corresponding 2-substituted benzimidazoles.
Results and discussions
During the course of our investigation, we actually started with the direct conversion (one
pot) of aryl/alkyl nitriles to benzimidazoles using 1,2-phenylenediamine and HCl in N,N-
2

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dimethylformamide (DMF) as solvent. Initially, we were in the conclusion that the nitrile (-
CN) functional group would get converted into carboxylic acid (-COOH) in presence of HCl
and thereafter it would condense with 1,2-phenylenedamine resulting in the formation of
corresponding 2-substituted benzimidazole derivative.
However, the TLC pattern showed the presence of nitrile, while the spot
corresponding to 1,2-phenylenediamine was missing. By this unusual observation, it was
concluded that only 1,2-phenylenediamine was reacted instead of nitrile. Further, the product
was isolated and analysed using NMR (1H, 13C) and mass spectroscopic techniques.
1
Surprisingly, the H and 13C NMR spectra were found to be identical to the earlier reports in
the literature for benzimidazole. And also the mass spectral data showed the m/z value at 118
corresponding to the molecular mass of benzimidazole. All these observations proved that an
unusual reaction must have occurred between 1,2-phenylenediamine and DMF in presence of
HCl that would lead to the formation of benzimidazole serendipitously. However, we could
find reports for the synthesis of benzimidazoles from amides (not with DMF) using ethylene
glycol (high boiling) as solvent without significant details.52 In the present work we have
successfully synthesized benzimidazoles using 1,2-arylenediamines and DMF in acidic
medium under thermal / microwave condition. Also, we have used a good number of amides
to exhibit the substrate scope and made comparative study between conventional and
microwave assisted reactions.
In order to establish the optimal reaction conditions, we opted 1,2-phenylenediamine
(1a) and DMF (2a) as model substrates (Scheme 1). Initially, we tried the reaction at room
temperature by stirring 1,2-phenylenediamine and DMF in 70% HCl which showed the
formation of the desired product; however, the reaction couldn’t end up with complete
conversion of the reactants into benzimidazole (3a) even after stirring for 24 h. Then, the
same reaction was attempted under thermal conditions at 100°C. The reaction yielded
3

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benzimidazole with the complete conversion of the reactants in 1 h with 82% yield. Similarly,
substituted benzimidazoles (3b-g) were prepared using various substituted 1,2-
arylenediamines (1b-g) and DMF in 1 h with 80-82% yields. Also, we tried to achieve this
reaction under microwave condition where the reaction was irradiated by 150 W microwave
radiations at 150°C, and interestingly we observed completion of the reaction in 2 min with
excellent yields (94-96%) for all 1,2-arylenediamines (1a-g, Table 1). We even obtained
benzimidazole (3a) in 2 min when the mixture of 1,2-phenylenediamine (1a) and formamide
(4a) in 70% HCl was irradiated by 150 W microwave radiations at 150°C with 96% yield.
We have carried out the reactions between 1,2-phenylenediamine (1a) and various C-
substituted amides (4b-n) in order to get the corresponding 2-substituted benzimidazoles (5b-
n) by conventional method, but the reactions ended up with moderately good yields (40-78%)
and time required for the completion of reactions was in the range from 1-12 h. However, it
was surprising to observe that the reactions progressed smoothly under microwave irradiation
(150 W) at 150°C for 40-60 min with 80-95% yields (Table 2).
NH2
NH2
N
H3C
H3C
H
O
i) 100°C
N
70% HCl
or
ii) MWI, 150 W, 150°C
N
H
1a
3a
2a
Scheme 1
The reaction follows a simple concerted mechanism, wherein the use of HCl enhances
the electrophilicity of the carbonyl carbon of amide thereby provoking the attack of lone pair
of electrons on nitrogen atom of diamine resulting in the formation of N-(2-
aminophenyl)formamide (I) intermediate which then immediately undergo intramolecular
cyclodehydration resulting in the formation of benzimidazole (3a, Scheme 2).
4

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H
O
H
O
H
CH3
CH3
Cl
CH3
NH
N
NH2
NH2
HN
H
O
H
NH
CH3
-NH(CH3)2
NH2
NH2
I
H
N
N
OH
-H2O
Na2CO3
H
N
N
H
H
3a
Scheme 2
The reaction of 1,2-arylenediamines (1a-g) with DMF (2a) are independent of wide
range of functional groups leading to the formation of corresponding benzimidazole
derivatives (3a-g) with excellent (94-96%) yields by microwave (150 W) heating at 150°C
for 2 min. The same reaction carried out by conventional heating at 150°C for 10 min
afforded only a trace amount and required 1 h at 100°C for completion of reaction with yield
ranging from 80-82%. In the case of reaction carried out at 100°C by microwave heating,
time required was 30 min to accomplish the reaction. The formation of 2-substituted
benzimidazoles (5b-n) from 1,2-phenylenediamine (1a) and C-substituted amides (4b-n)
showed completion of reaction in the range between 1-12 h by conventional heating. When
the reaction was carried out by microwave irradiation at 100°C for 1 h, only compounds 5b-d
were formed in very low yields (40-50%), but the derivatives 5e-n did not form. However,
the same reaction under microwave irradiation at 150°C for 40 min afforded corresponding 2-
susbstituted benzimidazole derivatives (5b-k) with excellent yields (80-95%). It was
interesting to note that benzamides (4g-j) substituted with electron donating groups furnished
reaction with moderate yields when compared to electron withdrawing groups which afforded
lower yields and took more time for completion by conventional heating. However, the same
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reaction by microwave (150 W) heating at 150°C for 40 min proceeded with good yields. The
formation of corresponding bisbenzimidazoles (5l-n) from oxalamide, malonamide and
succinamide by conventional method was achieved by heating for a longer time (18-24 h)
with lower yields (51-55%). But the same reaction was completed in 60 min under
microwave irradiation (150 W) at 150°C with good yields (88-92%). As a result from the
above observation it can be concluded that the reaction condition is independent on N-
substituted amides, whereas, C-substituted amides influence the rate of reaction.
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Table 1 Synthesis of benzimidazoles (3a-g) from 1,2-arylenediamines (1a-g) and DMF (2a)
under optimized conditions
NH2
N
H3C
H
O
i) 100°C
70% HCl
R
N
R
or
ii) MWI, 150 W, 150°C
N
H
H3C
NH2
3a-g
1a-g
2a
Scheme 3
Entry 1,2-Arylenediamines
Products
(3a-g)
Thermal
Microwave
Time
(hr)
Yielda
(%)
Time
(min)
Yielda
(%)
(1a-g)
NH2
N
1
N
1
82
81
82
2
96
95
94
NH2
H
1a
3a
3b
H3C
H3C
NH2
NH2
N
2
3
1
1
2
2
N
H
1b
CH3
CH3
NH2
NH2
N
N
H
H3C
Cl
H3C
1c
3c
NH2
NH2
Cl
N
4
5
1
1
80
80
2
2
95
95
N
H
1d
1e
3d
3e
NH2
NH2
O2N
O2N
N
N
H
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Table 1 contd......
Entry 1,2-Arylenediamines
Products
Thermal
Microwave
Time
Yielda
(%)
Time
Yielda
(%)
(1a-g)
(3a-g)
(hr)
(min)
NH2
NH2
Br
Br
N
6
7
1
81
2
95
96
N
H
N
N
1f
3f
NH2
N
N
1
82
2
NH
CH3
CH3
3g
1g
a Isolated yield
Table 2 Synthesis of 2-substituted benzimidazoles (5b-n) from 1,2-phenylenediamine (1a)
and C-substituted amides (4a-n)
NH2
R'
N
i) 100°C
H2N
R'
70% HCl
or
ii) MWI, 150 W, 150°C
O
N
H
NH2
3a, 5b-n
4a-n
1a
Scheme 4
Entry
Amides
Products
(5a-n)
Thermal
Time
(hr)
Microwave
Yielda
(%)
Time
Yielda
(4a-n)
(min)
(%)
H
H2N
N
1
2
1
81
2
96
N
O
H
4a
3a
CH3
N
CH3
H2N
3
78
40
95
N
H
O
4b
5b
8

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Table 2 contd......
Entry
Amides
Products
Thermal
Microwave
Time
Yield
(%)
Time
Yield
(%)
(4a-n)
(5a-n)
(hr)
4
(min)
40
O
N
CH2CH3
CH3CH2
C
NH2
NH2
NH2
3
75
72
70
65
74
70
60
92
94
91
90
92
86
84
N
H
4c
5c
O
N
CH2Cl
Cl-CH2
C
4
5
6
7
8
9
4
5
40
40
50
50
50
50
N
H
4d
5d
O
N
H
C
CH=CH2
H2C
C
N
H
4e
5e
O
N
5
NH2
N
H
4f
5f
O
N
OCH3
H3CO
6
NH2
N
H
5g
5h
4g
4h
O
NH2
N
Cl
Cl
7
N
H
O
N
10
NH2
N
H
Cl
Cl
5i
4i
9

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Table 2 contd......
Entry
Amides
Products
Thermal
Microwave
Yielda
(%)
Time
(min)
Yielda
(%)
(4a-n)
(5a-n)
Time
O
N
NO2
O2N
10
12
40
50
80
92
NH2
N
H
5j
4j
H2N
N
O
11
8
70
40
N
H
5k
4k
O
O
N
N
C
C
12
13
24
18
51
55
60
60
88
92
N
H
N
H
H2N
NH2
5l
4l
O
O
C
C
N
N
NH2
NH2
N
N
H
H
4m
5m
5n
O
O
N
N
C
C
14
18
54
60
91
N
H2N
NH2
N
H
H
4n
a Isolated yield
10

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Conclusion
A facile and inexpensive method for the synthesis of benzimidazoles using 1,2-
arylenediamines and DMF in 70% HCl by conventional as well as microwave condition is
reported. The synthesis of 2-substituted benzimidazoles from various C-substituted amides is
demonstrated successfully. The reactions carried out under microwave irradiation afforded
benzimidazoles in short period of time with excellent yields. Hence, this methodology would
make an interesting strategy for the synthesis of various substituted benzimidazoles.
Experimental
General information
All the reagents were of analytical grade and were used directly when required. Microwave
irradiation experiments were carried out using CEM Discover SP Microwave Synthesizer
equipped with IR sensor to monitor reaction temperatures. Thin-layer chromatography (TLC)
was performed on 0.20mm Aluchrosep silica gel 60 F254 plates (S.D. Fine, Mumbai). Melting
points were determined in open capillaries and are uncorrected. The IR spectra were recorded
1
on Nicolet Impact 410 FT IR spectrometer using KBr pellets. The H NMR spectra were
recorded at 400 MHz on Bruker Avance FT NMR spectrometer in DMSO-d6 with TMS as
13
internal standard. C NMR spectra were recorded at 100 MHz on Bruker Avance FT NMR
spectrometer in DMSO-d6 with TMS as internal standard. The mass spectra were recorded on
Shimadzu GC-MS operating at 70 eV.
Conventional method for the synthesis of benzimidazoles (3a-g)
1,2-Arylenediamine (1a-g, 4.62 mmol), DMF (1 ml, 13.87 mmol) and 70% HCl (10 ml) were
heated in a round bottom flask at 100°C for 1 h. The completion of the reaction was
monitored by TLC using mixture of ethyl acetate, hexane (1:1) as eluent. The reaction
mixture was cooled to room temperature and quenched by adding water (10 ml). The aqueous
solution was neutralised by adding solid Na2CO3 till slightly basic pH (8-9) to get the
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precipitate. The solid separated was filtered, washed repeatedly with water, dried and
recrystallized using ethanol to afford pure benzimidazole derivatives (3a-g) in excellent
yields. Synthesis of benzimidazole (3a) from 1,2-phenylenediamine (1a) and formamide (4a
was carried out using similar procedure.
)
Conventional method for the synthesis of 2-substituted benzimidazoles (5b-n)
1,2-Phenylenediamine (1a, 0.50 g, 4.62 mmol), substituted amide (4b-n, 4.62 mmol) and
70% HCl (10 ml) were heated in a round bottom flask at 100°C. The completion of the
reaction was monitored by TLC using mixture of ethyl acetate, hexane (1:1) as eluent. The
reaction mixture was cooled to room temperature and water (10 ml) was added. Then, the
aqueous solution was neutralised by adding solid Na2CO3 till slightly basic pH (8-9) to get the
precipitate. The solid separated was filtered, washed repeatedly with water, dried and
recrystallized using ethanol to afford 5b-n
.
Microwave assisted procedure for the synthesis of benzimidazoles (3a-g)
1,2-Arylenediamine (1a-g, 0.92 mmol), DMF (1 ml, 2.78 mmol) and 70% HCl (5 ml) was
introduced into a CEM microwave reaction vessel (10 ml) equipped with magnetic stirrer.
The reaction vessel was sealed and the reaction mixture was pre-stirred for 1 min at room
temperature. Then, the reaction mixture was irradiated by 150 W microwave radiations for 2
min at 150°C. The completion of reaction was monitored by TLC using ethyl acetate, hexane
(1:1) solvent mixture as eluent. The reaction mixture was cooled to room temperature and
water (10 ml) was added. Then, the reaction mixture was neutralised by solid Na2CO3 till
slightly basic pH (8-9) to get the precipitate. The solid separated was filtered, washed
repeatedly with water, dried and recrystallized using ethanol to afford 5b-n. Synthesis of
benzimidazole (3a) from 1,2-phenylenediamine (1a) and formamide (4a) was carried out
using similar procedure.
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Microwave assisted procedure for the synthesis of 2-substituted benzimidazoles (5b-n)
1,2-Phenylenediamine (1a, 0.10 g, 0.92 mmol), substituted amide (4b-n, 0.92 mmol) and
70% HCl was introduced into a 10 ml CEM microwave reaction vessel equipped with
magnetic stirrer. The reaction vessel was sealed and the reaction mixture was pre-stirred for 1
min at room temperature. Further, the reaction mixture was irradiated y by 150 W microwave
radiations for 40 min at 150°C for compounds 5b-k and 60 min for compounds 5l-n. The
completion of reaction was monitored by TLC using ethyl acetate, hexane (1:1) solvent
mixture as eluent. The reaction mixture was cooled to room temperature and similar work up
procedure was followed as mentioned above for the benzimidazoles (3a-g).
The physical data (mp, NMR) of all the known compounds were found to be identical
with those reported earlier in the literature.
1
H
-Benzo[d]imidazole (3a)
1
White solid; mp: 169-171°C (lit.53: 172°C). IR (KBr): 3112 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
δ
12.43 (s, 1H, NH), 8.19 (s, 1H, C2H), 7.58-7.56 (dd, 2H, J = 2.8 Hz, C4H &
13
C7H), 7.19-7.15 (m, 2H, C5H & C6H). C NMR (100 MHz, DMSO-d6):
δ 141.85, 138.08,
121.63, 115.44. m/z 118 (M+, 100%), 91 (24), 78 (40), 63 (64).
5-Methyl-1H-benzo[d]imidazole (3b)
1
White solid; mp: 114-116°C (lit.53: 116°C). IR (KBr): 3154 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
1H, C4H), 6.98 (d, 1H, J = 6.4 Hz, C6H), 2.39 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6):
141.49, 130.75, 123.08, 114.83, 21.17. m/z 132 (M+, 89%), 131 (100), 78 (43), 63 (47).
δ 12.28 (s, 1H, NH), 8.01 (s, 1H, C2H), 7.44 (d, 1H, J = 6.4 Hz, C7H), 7.34 (s,
δ
4,6-Dimethyl-1
H-benzo[d]imidazole (3c)
1
White solid; mp: 142-144°C (lit.54: 146°C). IR (KBr): 3114 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
δ
12.52 (s, 1H, NH), 8.14 (s, 1H, C2H), 7.16 (s, 1H, C7H), 6.81 (s, 1H, C5H),
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2.46 (s, 3H, CH3), 2.35 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6):
δ 140.73, 138.69,
135.51, 130.93, 124.74, 123.73, 111.77, 21.15, 16.60. m/z 146 (M+, 100%), 145 (65), 91 (18),
78 (10), 63 (19).
5-Chloro-1
H-benzo[d]imidazole (3d)
1
White solid; mp: 121-123°C (lit.53: 125°C). IR (KBr): 3127 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
δ 12.60 (s, 1H, NH), 8.26 (s, 1H, C2H), 7.68 (s, 1H, C4), 7.62 (d, 1H, J = 15.6
Hz, C6H), 7.20 (d, 1H, J = 15.6 Hz, C7H). 13C NMR (100 MHz, DMSO-d6):
δ
143.41,
121.96, 120.18, 118.48, 113.01, 111.55. m/z 154 (M+2, 32%), 152 (M+, 100), 127 (7), 125
(19), 90 (19), 78 (29), 63 (57).
5-Nitro-1
H-benzo[d]imidazole (3e)
1
Pale yellow solid; mp: 207-209°C (lit.53: 208°C). IR (KBr): 3125 (NH) cm-1. H NMR (400
MHz, DMSO-d6):
δ
13.01 (s, 1H, NH), 8.54 (s, 1H, C2H), 8.51 (s, 1H, C4H), 8.11 (d, 1H, J =
13
6.8 Hz, C6H), 7.77 (d, 1H, J = 6.8 Hz, C7H). C NMR (100 MHz, DMSO-d6):
δ 146.72,
143.01, 142.58, 117.52, 114.96, 112.66. m/z 163 (M+, 47%), 133 (25), 117 (26), 90 (42), 78
(63), 63 (100).
6-Bromo-1
H-imidazo[4,5-b]pyridine (3f)
1
Light brown solid; mp: 222-224°C (lit.55: 227°C). IR (KBr): 3136 (NH) cm-1. H NMR (400
MHz, DMSO-d6):
δ
13.14 (s, 1H, NH), 8.48 (s, 1H, C2H), 8.42 (s, 1H, C7H), 8.28 (s, 1H,
150.02, 145.49, 143.99, 133.15, 126.25, 112.67.
13
C5H). C NMR (100 MHz, DMSO-d6):
δ
m/z 199 (M+2, 97%), 197 (M+, 100), 172 (17), 170 (18), 118 (50), 91 (25), 78 (24), 63 (58).
1-Methyl-1
H-benzo[d]imidazole (3g)
Brown semisolid; mp: 59-62°C (lit.56: 60°C). IR (KBr): 3152 (NH) cm-1. 1H NMR (400 MHz,
DMSO-d6):
δ 7.82 (s, 1H, C2H), 7.80 (d, 1H, C4H), 7.36 (d, 1H, C7H), 7.31-7.28 (m, 2H, C5H
& C7H), 3.68 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6):
δ
143.81, 143.52, 134.58,
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123.20, 122.02, 121.55, 112.65, 30.96. m/z 132 (M+, 100%), 131 (55), 104 (35), 90 (9), 78
(29), 63 (46).
2-Methyl-1
H-benzo[d]imidazole (5b)
1
White solid; mp: 173-175°C (lit.53: 177°C). IR (KBr): 3185 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
C6H), 2.46 (s, 1H, CH3). 13C NMR (100 MHz, DMSO-d6):
14.54. m/z 132 (M+, 71%), 131 (52), 104 (9), 90 (7), 78 (72), 63 (100).
δ 12.20 (s, 1H, NH), 7.48-7.42 (dd, 2H, C4H & C7H), 7.09-7.06 (m, 2H, C5H &
δ
151.15, 138.91, 130.90, 114.17,
2-Ethyl-1
H-benzo[d]imidazole (5c)
1
White solid; mp: 176-178°C (lit.53: 176°C). IR (KBr): 3192 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
C6H), 2.83-2.78 (q, 2H, J = 6.0 Hz, CH2), 1.31-1.28 (t, 3H, J = 6.0 Hz, CH3). 13C NMR (100
156.05, 141.02, 120.94, 115.38, 21.89, 12.14. m/z 146 (M+, 59%), 145
δ 12.13 (s, 1H, NH), 7.47-7.40 (dd, 2H, C4H & C7H), 7.07-7.09 (m, 2H, C5H &
MHz, DMSO-d6):
δ
(100), 131 (20), 118 (10), 104 (7), 92 (8), 78 (35), 63 (60).
2-(Chloromethyl)-1
H-benzo[d]imidazole (5d)
Yellow solid; mp: 156-158°C (lit.57: 160°C). IR (KBr): 3211 (NH) cm-1. 1H NMR (400 MHz,
DMSO-d6):
C7H), 4.91 (s, 2H, CH2). 13C NMR (100 MHz, DMSO-d6):
116.52, 42.06. m/z 168 (M+2, 10%), 166 (M+, 30%), 131 (100), 104 (14), 77 (18), 63 (19).
δ 12.50 (s, 1H, NH), 7.56-7.52 (dd, 2H, C4H & C7H), 7.22-7.11 (m, 2H, C5H &
δ
150.09, 141.59, 138.00, 124.10,
2-Vinyl-1
H-benzo[d]imidazole (5e)
1
White solid; mp: 180-182°C (lit.58: 184°C). IR (KBr): 3223 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
δ 12.27 (s, 1H, NH), 7.62-7.56 (dd, 2H, C4H & C7H), 7.12-7.10 (m, 2H, C5H &
C6H), 6.77-6.73 (dd, 1H, Jtrans = 16.8 Hz, Jcis = 9.7 Hz), 6.26 (dd, 1H, Jtrans = 16.8 Hz, Jgem
1.8 Hz), 5.66 (dd, 1H, Jcis = 9.7 Hz, Jgem = 1.8 Hz). 13C NMR (100 MHz, DMSO-d6):
=
δ
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141.68, 138.79, 123.20, 122.02, 121.55, 112.65. m/z 144 (M+, 83%), 143 (100), 117 (23), 104
(7), 91 (11), 63 (46).
2-Phenyl-1
H-benzo[d]imidazole (5f)
1
White solid; mp: 294-296°C (lit.59: 292°C). IR (KBr): 3223 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
C7H, C3’H, C4’H & C5’H), 7.23-7.19 (m, 2H, C5H & C6H). 13C NMR (100 MHz, DMSO-d6):
151.14, 143.17, 130.10, 129.76, 128.86, 128.50, 127.36, 122.03. m/z 194 (M+, 100%), 166
δ 12.95 (s, 1H, NH), 8.20-8.17 (dd, 2H, C2’H & C6’H), 7.63-7.48 (m, 5H, C4H,
δ
(7), 104 (6), 90 (10), 78 (46), 63 (70).
2-(4-Methoxyphenyl)-1
H-benzo[d]imidazole (5g)
1
White solid; mp: 222-224°C (lit.59: 226°C). IR (KBr): 3158 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
δ 12.86 (s, 1H, NH), 7.98 (d, 2H, J = 7.2 Hz, C2’H & C6’H), 7.72-7.68 (dd, 2H,
C4H & C7H), 7.20-7.14 (m, 2H, C5H & C6H), 6.85 (d, 2H, J = 7.2 Hz, C3’H & C5’H), 3.75 (s,
3H, OCH3). 13C NMR (100 MHz, DMSO-d6):
δ
160.75, 153.02, 142.28, 130.86, 129.68,
128.72, 128.55, 122.59, 56.07. m/z 224 (M+, 100%), 193 (54), 117 (32), 104 (8), 91 (10), 78
(31), 63 (63).
2-(4-Chlorophenyl)-1
H-benzo[d]imidazole (5h)
1
White solid; mp: 295-297°C (lit.59: 294°C). IR (KBr): 3211 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
δ
13.02 (s, 1H, NH), 8.16 (d, 2H, J = 7.6 Hz, C2’H & C6’H), 7.82-7.78 (dd, 2H,
13
C4H & C7H), 7.66 (d, 2H, J = 7.6 Hz, C3’H & C5’H), 7.26-7.22 (m, 2H, C5H & C6H). C
NMR (100 MHz, DMSO-d6):
δ 150.28, 143.63, 134.66, 129.88, 128.98, 128.27, 122.64,
118.59. m/z 230 (M+2, 23%), 228 (M+, 70%), 193 (45), 117 (12), 104 (12), 91 (23), 78 (45),
63 (100).
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2-(2-Chlorophenyl)-1
H-benzo[d]imidazole (5i)
1
White solid; mp: 236-238°C (lit.59: 234°C). IR (KBr): 3209 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
δ 13.11 (s, 1H, NH), 7.94 (d, 1H, J = 7.8 Hz, C6’H), 7.74-7.72 (dd, 2H, C4H &
C7H), 7.55-7.51 (m, 3H, C5H, C6H & C5’H), 7.27-7.18 (m, 2H, C2’H & C3’H). 13C NMR (100
MHz, DMSO-d6):
δ 151.09, 143.72, 139.47, 132.77, 130.58, 129.09, 128.97, 126.61, 123.59,
120.46, 118.74. m/z 230 (M+2, 22), 228 (M+, 65%), 117 (9), 104 (29), 91 (7), 78 (15), 63
(100).
2-(4-Nitrophenyl)-1
H-benzo[d]imidazole (5j)
Yellow solid; mp: 312-314°C (lit.59: 316°C). IR (KBr): 3196 (NH) cm-1. 1H NMR (400 MHz,
DMSO-d6):
δ 13.02 (s, 1H, NH), 8.44 (d, 2H, J = 6.8 Hz, C3’H & C5’H), 7.76 (d, 2H, J = 6.8
Hz, C2’H & C6’H), 7.72-7.70 (dd, 2H, C4H & C7H), 7.26-7.22 (m, 2H, C5H & C6H). 13C
NMR (100 MHz, DMSO-d6):
δ 152.64, 148.37, 143.69, 135.64, 128.34, 122.72, 119.61. m/z
239 (M+2, 100%), 193 (38), 117 (27), 104 (8), 91 (11), 78 (29), 63 (49).
2-Benzyl-1
H-benzo[d]imidazole (5k)
1
White solid; mp: 184-186°C (lit.57: 187°C). IR (KBr): 3119 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
δ 12.26 (s, 1H, NH), 7.52-7.50 (dd, 2H, C4H & C7H), 7.40-7.38 (dd, 2H, C3’H &
C5’H), 7.23-7.20 (m, 2H, C2’H & C6’H), 7.12-7.07 (m, 2H, C5H & C6H), 4.15 (s, 2H, CH2).
13C NMR (100 MHz, DMSO-d6):
δ
153.43, 143.37, 137.61, 134.83, 134.38, 128.69, 128.40,
126.44, 121.53, 120.85, 118.19, 110.84, 34.88. m/z 208 (M+2, 54%), 207 (79), 131 (7), 103
(19), 91 (17), 78 (55), 63 (100).
2-(1
H-Benzo[d]imidazol-2-yl)-1H-benzo[d]imidazole (5l)
1
Pale yellow solid; mp: >370°C (lit.52: 400°C). IR (KBr): 3216 (NH) cm-1. H NMR (400
MHz, DMSO-d6):
δ
12.27 (s, 2H, NH), 7.78-7.55 (dd, 4H, C4H & C7H), 7.17-7.08 (m, 4H,
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C5H & C6H). 13C NMR (100 MHz, DMSO-d6):
234 (M+2, 8%), 162 (28), 134 (20), 118 (10), 106 (31), 91 (19), 78 (50), 63 (61), 44 (100).
δ 153.29, 141.59, 138.00, 124.89, 116.25. m/z
Bis(1
H-benzo[d]imidazol-2-yl)methane (5m)
1
White solid; mp: >370°C (lit.52: 389°C). IR (KBr): 3230 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
C6H), 3.79 (s, 2H, CH2). 13C NMR (100 MHz, DMSO-d6):
116.00, 39.00. m/z 248 (M+2, 22%), 131 (9), 118 (8), 78 (73), 63 (100).
δ 12.07 (s, 2H, NH), 7.73-7.62 (dd, 4H, C4H & C7H), 7.21-7.11(m, 4H, C5H &
δ
152.88, 143.82, 138.12, 124.20,
2-(2-(1
H-Benzo[d]imidazol-2-yl)ethyl)-1H-benzo[d]imidazole (5n)
1
White solid; mp: 316-318°C (lit.60: 315°C). IR (KBr): 3217 (NH) cm-1. H NMR (400 MHz,
DMSO-d6):
δ 12.15 (s, 2H, NH), 7.76-7.66 (dd, 4H, C4H & C7H), 7.29-7.21 (m, 4H, C5H &
C6H), 2.84-2.76 (t, 4H, J = 15.6 Hz, CH2). 13C NMR (100 MHz, DMSO-d6):
δ
151.05,
142.95, 139.62, 123.59, 115.65, 33.03. m/z 262 (M+2, 7%), 196 (33), 132 (100), 104 (31), 90
(9), 77 (31), 63 (21).
Acknowledgements
The authors are grateful to University Scientific Instrumentation Centre (USIC), Karnatak
University, Dharwad for providing mass spectral and IR data. The authors are thankful to
Indian Institute of Science (IISc), Bengaluru for carrying out NMR analyses and to UGC,
New Delhi for the financial assistance under UPE programme vide no. [F. No. 14-3/2012
(NS/PE) Dated: 14-03-2012]. One of the authors (PPK) acknowledges University grants
Commission (UGC), New Delhi for fellowship under RFSMS programme.
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Graphical Abstract
Expedient synthesis of benzimidazoles using amides
Pramod P. Kattimani, Ravindra R. Kamble, Gangadhar Y. Meti
In the present report an efficient, rapid, facile and inexpensive route for the synthesis of
benzimidazoles using 1,2-arylenediamines and amides in acidic medium under
thermal/microwave conditions is developed.