1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-Oxide Hexafluorophosphate (HATU)/Hydroxybenzotriazole (HOBT)-based One-Pot Cyclization of N-Substituted 2-Arylbenzimidazole Derivatives

Article abstract of DOI:10.1134/S107042802005019X

Abstract: A simple one-pot synthesis of N-substituted benzimidazoles from aromatic carboxylic acids and aromatic 1,2-diamines in the presence of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate/hydroxybenzotriazole (HATU/HOBT) and N,N-diisopropylethylamine in DMF at 100°C, featuring good to excellent yields and easy workup, is developed. The protocol can be scaled to gram quantities, and no chromatographic purification is required.

Full text of DOI:10.1134/S107042802005019X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 5, pp. 856–862. © Pleiades Publishing, Ltd., 2020.
1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo-
[4,5-b]pyridinium 3-Oxide Hexafluorophosphate
(HATU)/Hydroxybenzotriazole (HOBT)-based One-Pot
Cyclization of N-Substituted 2-Arylbenzimidazole Derivatives
Y. T. Duana, T. H. Parmarb,*, C. B. Sanganib, A. S. Shahc, and R. K. Ametab,d
a Henan Provincial Key Laboratory of Children’s Genetics and Metabolic Diseases,
Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou Children’s Hospital, Zhengzhou, 450018 China
b Department of Chemistry, Shri Maneklal M Patel Institute of Sciences and Research, Kadi Sarva Vishwavidhyalaya,
Gandhinagar, 382023 India
c Department of Chemistry, Saurashtra University, Rajkot, 36004 India
d School of Chemical Sciences, Central University of Gujarat, Gandhinagar, 382030 India
*e-mail: tejashparmar@gmail.com
Received September 04, 2019; revised October 29, 2019; accepted November 01, 2019
Abstract—A simple one-pot synthesis of N-substituted benzimidazoles from aromatic carboxylic acids and
aromatic 1,2-diamines in the presence of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium
3-oxide hexafluorophosphate/hydroxybenzotriazole (HATU/HOBT) and N,N-diisopropylethylamine in DMF at
100°C, featuring good to excellent yields and easy workup, is developed. The protocol can be scaled to gram
quantities, and no chromatographic purification is required.
Keywords: N-methylbenzene-1,2-diamine, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridini-
um 3-oxide hexafluorophosphate (HATU), hydroxybenzotriazole (HOBT), benzimidazole
DOI: 10.1134/S107042802005019X
INTRODUCTION
generate N-substituted benzimidazoles via condensation
followed by oxidative cyclization [6, 7]. Aromatic esters
react with arylenediamines under Weinreb conditions to
give 2-arylbenzimidazoles. 2-Methylbenzimidazoles
were synthesized from acid anhydrides of monobasic
acids. Cyclic anhydrides of dibasic acids, too, were
used for the synthesis of benzimidazoles, but, however,
to convert the intermediate N-(o-aminophenyl)imide
to target benzimidazoles generally required high tem-
peratures and strong acids [8, 12]. Yang et al. [9, 10]
developed an efficient one-step protocol for the synthesis
of benzimidazoles via the reductive cyclization of
o-nitroaniline with aromatic or aliphatic aldehydes
under the action of Na2S2O4 in methanol at 60°C [9,
10]. The direct Pd-catalyzed arylation of 1-methyl-1H-
benzo[d]imidazole with aryl halides has also been
reported [11, 13].
Benzimidazoles are regarded as an important class
of the heterocyclic compounds due to the wide range
of biological activities associated with this core. A great
number of benzimidazole derivatives have reached the
clinical testing stage and are also present in marketed
drugs. Albendazole, Mebendazole, and Fenbendazole
are used as antigiardiasis agents as effective as
Metronidazole. The benzimidazole core is also present in
such blockbuster drugs as Omeprazole and Lansprazole
[1–5].
Due to the importance of benzimidazoles in medicinal
chemistry many methods were reported in the literature
for their synthesis. One of the most common synthetic
approaches to benzimidazole derivatives involves the
condensation–dehydration of o-phenylenediamine with
acids, carbonyl compounds, or acid chlorides, etc.
Furthermore, esters, lactones, and anhydrides can
In the present work we have developed a one-pot
protocol for the synthesis of N-methyl-benzimidazoles,
856

1-[BIS(DIMETHYLAMINO)METHYLENE]-1H-1,2,3-TRIAZOLO[4,5-b]PYRIDINIUM 3-OXIDE
857
starting from N-methyl-o-phenylenediamine and
aromatic carboxylic acids in the presence of
1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo-
[4,5-b]pyridinium3-oxidehexafluorophosphate(HATU)
and hydroxybenzotriazole (HOBT). We have also found
that aliphatic, heterocyclic, and some carbocyclic acids
fail to react in similar conditions.
RESULTS AND DISCUSSION
We began our studies with 3-chlorobenzoic acid
as a model substrate. Initially, we attempted one-
pot synthesis of N-substituted benzimidazoles. To
this end, we screened a variety of coupling reagents,
specifically, propanephosphonic acid anhydride (T3P),
N,N,N',N'-tetramethyl-O-(benzotriazol-1-yl)uronium
tetrafluoroborate (TBTU), 3-[bis(dimethylamino)me-
thylene]-3H-benzotriazol-1-oxide hexafluorophosphate
(HBTU), N-(3-dimethylaminopropyl)-N'-ethylcarbo-
diimide hydrochloride (EDC∙HCl), and HATU.
However, we observed formation of an amide inter-
mediate and no cyclized product (Table 1). Moreover, the
reactions of aromatic carboxylic acids with N-substituted
The advantage of the developed procedure over
previously reported methods consists in that it does
not require isolation of the intermediate amide and
also does not require harsh conditions, such as use of
strong mineral acids (HCl, H2SO4, hot glacial acetic
acid, or polyphosphoric acid), high temperatures, or in
microwave irradiation for cyclization [6, 7].
Table 1. Optimization of the reaction parametersa
COOH
H
N
N
Catalyst
Solvent
+
N
NH2
Cl
Cl
1
3a
Solvent
2
Entry no.
Coupling reagentsb
T, °C
Yield of 3a, %
1
2
T3P (50% ethyl acetate)
T3P (50% ethyl acetate)
HBTU
rt
DCM
CH3CN
DMF
CH3CN
DCM
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
–
100
rt
–
3
–
–
4
TBTU
rt
5
EDC∙HCl–HOBT
HATU–HOBT
HATU–HOBT
HATU–HOBT
HBTU–HOBT
T3P (50% ethyl acetate)
TBTU–HOBT
EDC∙HCl–HOBT
HATU–HOBT
HATU–HOBT
rt
–
6
rt
–
7
50
Traces
20
8
70
9
100
100
100
100
100
150
25
10
11
12
13
14c
–
Traces
Traces
80
28d
a N1-Methylbenzene-1,2-diamine (1 equiv), 3-chlorobenzoic acid (1 equiv), DIPEA (3.0 equiv), different catalysts, argon atmosphere, 12 h,
sealed tube.
b Each of the coupling reagents was used in a quantity of 1.5 equiv.
c Reaction time 6 h.
d Yield of crude product estimated by TLC (pure product was not isolated).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 5 2020

858
DUAN et al.
Scheme 1.
H
N
O
HATU (1.5 equiv), HOBT (1.5 equiv)
DIPEA (5.0 equiv), DMF, 100°C, 16 h
N
+
R
R
OH
NH2
N
1
2a–2l
3a–3l
Yields 70–83%
2, 3: R = 3-ClC6H4 (a), 3,4-Cl2C6H3 (b), 3,4-CH3OC6H3 (c), 3-(CF3)C6H4 (d), 3-FC6H4 (e),
4-CNC6H4 (f), 4-CH3CH2C6H3 (g), 4-iso-C3H7C6H4 (h), 4-CH3CH2C6H4 (i), 4-iso-PrOC6H4 (j),
3-Cl-5-FC6H3 (k), 3-CH3O-4-ClC6H3 (l).
o-phenelyenediamines in the presence of HATU or
HOBT along, too, gave an intermediate amide and no
cyclized product. However, the reactions with both
HATU and HOBT (HATU–HOBT) in DMF at 100°C
in the presence of diisopropylethylamine (DIPEA)
resulted in the exclusive formation of benzimidazoles.
Notably, in the reactions with HATU–HOBT at room
temperature we isolated an amide intermediate, but, as
the reaction temperature was raised, the benzimidazole
yield gradually increased from traces at 50°C to 20% at
70°C, and, finally, 80% at 100°C (Table 1).
With the optimized reaction conditions in hand, we
checked the substrate scope of the reaction and obtained
good results with a variety of aromatic carboxylic acids
(Scheme 1 and Experimental).
However, the reactions with heterocyclic carboxylic
acids 4 and 5 and substituted phenylacetic acids 6 gave
no cyclization products (Scheme 2).
Scheme 2.
Amide intermediate
Not formed
Amide intermediate
Not formed
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1-[BIS(DIMETHYLAMINO)METHYLENE]-1H-1,2,3-TRIAZOLO[4,5-b]PYRIDINIUM 3-OXIDE
859
Scheme 3.
O
OH
HATU, HOBT,
100°C,16 h
N
N
NH2
+
R
N
R
H
R = Et, Ph, H.
Further, we have studied the scope of optimized
method on N-ethyl and N-phenyl substituted
o-phenylenediamine but observed formation of the
amide intermediate only and no cyclization products
(Scheme 3).
In a summary, we have developed an efficient one-
pot protocol for the synthesis of 2-aryl-1-methyl-1H-
benzo[d]imidazoles using a 1-[bis(dimethylamino)-
methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide
hexafluorophosphate–hydroxybenzotriazole
system
(HATU–HOBT) in DMF in the presence of DIPEA.
This method works well with a wide range of aromatic
carboxylic acids. The method provides an alternative
protocol for the synthesis of benzimidazoles in good
yields, which requires no chromatographic purification
of the target products and can be used on a gram scale.
2-Aminophenol and 2-thiophenol were treated with
benzoic acid in same conditions. The first reaction gave
an amide intermediate and no the expected cyclization
product 2-phenylbenzo[d]oxazole, whereas the second
reaction formed neither the intermediate carbamate nor
2-phenylbenzo[d]thiazole (Scheme 4).
EXPERIMENTAL
Our method provides easy access to N-substituted
2-arylbenzimidazolesundermildconditionsbyascalable
eco-friendly procedure using commercially available
reagents. The resulting products are easily isolable and
require no chromatographic purification. Under the
optimized conditions, successful reaction takes place
with differently substituted aromatic carboxylic acids.
However, monosubstituted aromatic carboxylic acids
with electron-withdrawing substituents give better
yields of N-substituted-2-aryl benzimidazoles compared
with carboxylic acids with electron-donor substituents.
All reagents were of reagent grade and used as
received unless specified otherwise. Solvents for
reactions were distilled prior to use. All reactions were
conducted under nitrogen or argon in flame-dried or
oven-dried glassware with magnetic stirring. Thin-
layer chromatography was performed on analytical
silica gel 60 F254–coated TLC plates (Purchased from
Merck Chemicals), eluent 50% EtOAc in n-hexane,
and were visualized with UV light or by treatment
with the TLC reagents such as KMnO4, ninhydrin,
Dragandroff’sorphosphomolybdicacid(PMA).Column
chromatography was carried out on silica gel (60–
120 mesh). Technical grade ethyl acetate and hexane
used for column chromatography were distilled prior
to use. Commercially available starting materials were
used without further purification.
Inviewofthedatain[9,10],wecanproposeaplausible
reaction pathway, which involves amide formation with
an aryl benzoic acid and subsequent cyclodehydration
to yield the corresponding N-substituted benzimidazole
(Scheme 5).
Scheme 4.
O
OH
HATU (1.5 equiv), HOBT (1.5 equiv)
DIPEA (5.0 equiv), DMF, 100°C, 16 h
NH2
OH
N
O
+
+
O
OH
HATU (1.5 equiv), HOBT (1.5 equiv)
DIPEA (5.0 equiv), DMF, 100°C, 16 h
NH2
SH
N
S
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 5 2020

860
DUAN et al.
Scheme 5.
N
H
N
N
Cl
Cl
–
O
O
NH2
O
NH2
NH2
N
N
O
N
H
N
N
N
N
N
Heat, 100°C
–H2O
Cl
The H and 13C NMR spectra were recorded in
Rf 0.63. 1H NMR spectrum (DMSO-d6), δ, ppm: 3.89 s
(3H), 7.24–7.33 m (2H), 7.59–7.65 m (3H), 7.68–
7.70 d (1H, J 7.6 Hz), 7.91 s (1H), 7.84–7.82 m (1H). 13C
NMR spectrum, δ, ppm: 32.14, 111.19, 119.62, 122.59,
123.15, 128.40, 129.38, 130.02, 131.06, 132.65, 133.86,
137.07, 142.8, 151.9. Mass spectrum (ESI-HRMS), m/z:
243.0689 [M + H]+. C14H11ClN2. [M + H]+ 243.0695.
1
DMSO-d6 on a Bruker Avance-400 MHz at ambient
temperature. The high-resolution mass spectral analysis
was performed on Agilent 1290 UHPLC connected to
an Agilent 6538 QTOF (Santa Clara, CA, USA).
Benzimidazoles 3a–3l (general procedure). 1-[Bis-
(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]-
pyridinium 3-oxide hexafluorophosphate (1.227 mmol),
HOBT (1.227 mmol), and DIPEA (2.454 mmol)
were added to a magnetically stirred solution of N-1-
methylbenzene-1,2-diamine (1, 0.818 mmol) and
arylcarboxylic acid 2 (0.818 mmol) in DMF (3 mL) in
a Biotage reaction tube. The tube was sealed with an
aluminum cap with a septum, and the reaction mixture
was stirred at 100°C for 16 h. Progress of the reaction
was monitored by TLC of samples of the reaction
mixture, taken with a 1-mL syringe through the cap
septum. Used the sealed tube which having aluminium
cap with septa (purchased from Biotage) and sample
took via 1 mL syringe. Upon completion of the reaction,
the reaction mixture was cooled to room temperature
and poured into water (15 mL) and treated with ethyl
acetate (3 × 15 mL), and the combined organic extracts
were dried over anhydrous sodium sulphate and filtered.
The solvent was distilled off from the filtrate under
reduced pressure to leave a crude product, which was
purified by recrystallization or trituration with diethyl
ether or pentane.
2-(3,4-Dichlorophenyl)-1-methyl-1H-benzo[d]-
imidazole (3b). Yield 75.4%, brown solid, mp 102–
103°C, Rf 0.70. 1H NMR spectrum, δ, ppm: 3.92 s (3H),
7.26–7.36 m (2H), 7.65–7.67 d (1H, J 8.0 Hz), 7.70–
7.72 d (1H, J 8.0 Hz), 7.85–7.87 m (2H), 8.14 s (1H).
13C NMR spectrum, δ, ppm: 32.16, 111.25, 119.68,
122.71, 123.31, 129.86, 131.21, 131.41, 131.44, 132.03,
133.03, 137.12, 142.76 151.05. Mass spectrum (ESI-
HRMS), m/z: 277.0299 [M + H]+. C14H10Cl2N2. [M +
H]+ 277.0302.
2-(3,4-Dimethoxyphenyl)-1-methyl-1H-benzo[d]-
imidazole (3c). Yield 70.5%, brown solid, mp 200°C,
1
Rf 0.68. H NMR spectrum, δ, ppm: 3.89 s (3H),
3.92 s (3H), 3.92 s (3H), 4.06 s (2H), 7.31–7.33 d (1H,
J 8.0 Hz), 7.53–7.66 m (4H), 7.85 d (1H, J 8.0 Hz),
8.03 d (1H, J 8.0 Hz). 13C NMR spectrum, δ, ppm: 32.21,
56.08, 56.12, 110.87, 111.97, 113.18, 119.16, 122.31,
122.45, 122.57, 122.86, 137.08, 142.80, 149.14, 150.50,
153.53. Mass spectrum (ESI-HRMS), m/z: 269.1290
[M + H]+. C16H16N2O2. [M + H]+ 269.1299.
1-Methyl-2-[3-(trifluoromethyl)phenyl]-1H-
benzo[d]imidazole (3d). Yield 73.8%, yellow solid, mp
2-(3-Chlorophenyl)-1-methyl-1H-benzo[d]-
imidazole (3a). Yield 83.2%, brown solid, mp 92–94°C,
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1-[BIS(DIMETHYLAMINO)METHYLENE]-1H-1,2,3-TRIAZOLO[4,5-b]PYRIDINIUM 3-OXIDE
861
97°C, Rf 0.65. 1H NMR spectrum, δ, ppm: 3.92 s (3H),
7.27–7.33 m (2H), 7.64 d (1H, J 8.0 Hz), 7.71 d (1H, J
8.0 Hz), 7.83–7.85 m (1H), 7.93–7.95 d (1H, J 8.0 Hz),
Rf 0.45. 1H NMR spectrum, δ, ppm: 1.37–1.40 m (3H),
3.87 s (3H), 4.11–4.16 m (2H), 7.12 d (2H, J 8.0 Hz),
7.21–7.29 m (2H), 7.58–7.60 m (2H), 7.79 d (2H, J
12.0 Hz). 13C NMR spectrum, δ, ppm: 15.02, 15.09,
32.14, 63.75, 110.84, 119.19, 122.23, 122.48, 122.71,
132.72, 137.06, 142.96, 153.50, 160.05. Mass spectrum
(ESI-HRMS), m/z: 253.13354 [M + H]+. C16H16N2O.
[M + H]+ 253.13348.
13
8.18–8.19 m (2H). C NMR spectrum, δ, ppm: 32.15,
111.25, 119.69, 122.67, 123.26, 125.81, 126.29, 126.34,
126.37, 130.50, 133.59, 131.72, 137.15, 142.85, 151.91.
Mass spectrum (ESI-HRMS), m/z: 277.09471 [M + H]+.
C15H11F3N2. [M + H]+ 277.09476.
2-(3-Fluorophenyl)-1-methyl-1H-benzo[d]-
imidazole (3e). Yield 75.6%, off-white solid, mp
90°C, Rf 0.6. H NMR spectrum, δ, ppm: 3.92 s (3H),
7.26–7.35 m (2H), 7.41–7.45 m (1H), 7.62–7.67 m
(2H), 7.70–7.74 m (3H). 13C NMR spectrum, δ, ppm:
32.15, 111.19, 117.17, 119.58, 122.61, 123.15, 125.99,
131.34, 132.80, 137.05, 142.69, 152.07, 161.25, 163.67.
Mass spectrum (ESI-HRMS), m/z: 227.0979 [M + H]+.
C14H11FN2. [M + H]+ 227.09780.
2-(4-Isopropoxyphenyl)-1-methyl-1H-benzo[d]-
imidazole (3j). Yield 75.6%, yellow solid, mp 128°C,
Rf 0.54. 1H NMR spectrum, δ, ppm: 1.20–1.32 m (6H),
3.86 s (3H), 4.70–4.76 m (1H), 7.09 d (2H, J 8.0 Hz),
7.20–7.28 m (2H), 7.57 d (1H, J 8.0 Hz), 7.63 d (1H,
J 4.0 Hz), 7.77 d (2H, J 8.0 Hz). 13C NMR spectrum,
δ, ppm: 22.27, 32.13, 32.17, 69.82, 110.84, 115.91,
119.17, 122.23, 122.48, 122.52, 131.29, 137.05, 142.95,
153.51, 159.03. Mass spectrum (ESI-HRMS), m/z:
267.14919 [M + H]+. C17H18N2O. [M + H]+ 267.14921.
1
4-(1-Methyl-1H-benzo[d]imidazol-2-yl)ben-
zonitrile (3f). Yield 75.9%, off-white solid, mp 205°C,
Rf 0.43. 1H NMR spectrum, δ, ppm: 3.93 s (3H), 7.28–
7.38 m (2H), 7.67–7.69 d (1H, J 8.0 Hz), 7.73–7.74 d
(1H, J 7.6 Hz), 8.05–8.11 m (4H). 13C NMR spectrum,
δ, ppm: 32.30, 111.34, 112.54, 119.02, 119.83, 122.80,
123.49, 130.54, 133.06, 135.03, 137.24, 142.89, 151.66.
Mass spectrum (ESI-HRMS), m/z: 234.10257 [M + H]+.
C15H11N3. [M + H]+ 234.10252.
2-(3-Chloro-5-fluorophenyl)-1-methyl-1H-ben-
zo[d]imidazole (3k). Yield 74.9%, yellow solid, mp
62°C, Rf 0.78. 1H NMR spectrum, δ, ppm: 3.93 s (3H),
13
7.27–7.37 m (2H), 7.66–7.76 m (4H), 7.81 s (1H). C
NMR spectrum, δ, ppm: 32.12, 111.29, 115.77, 117.77,
119.76, 123.43, 125.91, 133.98, 134.91, 137.09, 142.66,
150.76, 161.22, 163.69. Mass spectrum (ESI-HRMS),
m/z: 261.05893 [M + H]+. C14H10ClFN2. [M + H]+
261.05901.
2-(4-Ethylphenyl)-1-methyl-1H-benzo[d]-
imidazole (3g). Yield 76.5%, off-white solid, mp 94°C,
Rf 0.63. 1H NMR spectrum, δ, ppm: 1.26 t (3H), 2.70–
2.76 m (2H), 3.89 s (3H), 7.23–7.37 m (2H), 7.43 d (2H,
J 8.0 Hz), 7.62 d (1H, J 8.0 Hz), 7.68 d (1H J 7.6 Hz),
7.79 d (2H, J 8 Hz). 13C NMR spectrum, δ, ppm: 15.90,
28.51, 32.14, 110.96, 119.36, 122.32, 122.68, 128.05,
128.54, 129.77, 137.07, 142.97, 145.96, 153.58. Mass
spectrum (ESI-HRMS), m/z: 237.13863 [M + H]+.
C16H16N2. [M + H]+ 237.13839.
2-(4-Chloro-3-methoxyphenyl)-1-methyl-1H-
benzo[d]imidazole (3l). Yield 73.0%, mp 110°C, Rf
1
0.78, yellow solid. H NMR spectrum, δ, ppm: 3.91 s
(3H), 3.97 s (3H), 7.25–7.34 m (2H), 7.44 d (1H, J
8.0 Hz), 7.58 s (1H), 7.63 d (2H, J 4.0 Hz), 7.71 d (1H,
J 8.0 Hz). 13C NMR spectrum, δ, ppm: 32.20, 56.81,
111.12, 114.04, 119.54, 122.55, 122.59, 123.05,123.13,
130.50, 130.75, 137.12, 142.81, 152.51,155.01. Mass
spectrum (ESI-HRMS), m/z: 273.07892 [M + H]+.
C15H13ClN2O. [M + H]+ 273.07896.
2-(4-Isopropylphenyl)-1-methyl-1H-benzo[d]-
imidazole (3h). Yield 76.6%, brown solid, mp 112°C,
1
Rf 0.68. H NMR spectrum, δ, ppm: 1.26 d (6H, J
ACKNOWLEDGMENTS
6.8 Hz), 2.96–3.03 m (1H), 3.87 s (3H), 7.21–7.30 m
(2H), 7.45 d (2H, J 8.0 Hz), 7.60 d (1H, J 7.6 Hz),
7.66 d (1H, J 8.0 Hz), 7.78 d (2H, J 8.0 Hz). 13C NMR
spectrum, δ, ppm: 24.20, 32.15, 33.71, 110.95, 119.37,
122.32, 122.67, 126.41, 126.76, 127.08, 128.20, 129.79,
137.08, 142.99, 150.50, 153.56, Mass spectrum (ESI+),
m/z: 251.3 [M + H]+.
Authors are highly grateful to Kadi SarvaVishwavidyalaya
Gandhinagar, Gujarat, India for providing infrastructure and
laboratory facilities.
FUNDING
This work was supported by the National Natural Science
Foundation of China (grant no. 81903623), China Postdoctoral
Science Foundation (grant no. 2019M652586), Postdoctoral
Research Grants in Henan Province nos. 1902001 and
2-(4-Ethoxyphenyl)-1-methyl-1H-benzo[d]-
imidazole (3i). Yield 82.3%, yellow solid, mp 84°C,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 5 2020

862
DUAN et al.
19030008, and Henan Medical Science and Technology
Program (grant no. 2018020601).
6. John, B., Chem. Rev., 1951, vol. 48, p. 397.
https://doi.org/10.1021/cr60151a002
7. Preston, P.N., Chem. Rev., 1974, vol. 74, p. 279.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
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