Development of homogeneous polyamine organocatalyst for the synthesis of 2-aryl-substituted benzimidazole and benzoxazole derivatives

Article abstract of DOI:10.1002/jhet.4046

A new polyamine was prepared by the ring opening polymerization of epichlorohydrin and properly characterized. The catalytic property of the prepared polymer was assessed by synthesizing 2-aryl-substituted benzimidazole and benzoxazole derivatives by the conjugation of o-phenylenediamine/o-aminophenol with various aromatic aldehydes in the presence of atmospheric oxygen. Significant attributes of the present synthesis include short reaction time, good to excellent yield, high purity, easy reusability, and room temperature reaction. The reaction was carried out in the absence of any metal catalyst and other cooxidants.

Full text of DOI:10.1002/jhet.4046

Received: 4 March 2020
DOI: 10.1002/jhet.4046
Revised: 7 May 2020
Accepted: 29 May 2020
A R T I C L E
Development of homogeneous polyamine organocatalyst for
the synthesis of 2-aryl-substituted benzimidazole and
benzoxazole derivatives
Hiba Kottayil | Shaibuna Machingal | Sherly mole Parackal B. |
Shebitha Alungal M. | Letcy V. Theresa | Avudaiappan Govindan
Sreekumar Krishnapillai
|
Department of Applied Chemistry, Cochin
Abstract
University of Science and Technology,
Cochin, Kerala, India
A new polyamine was prepared by the ring opening polymerization of epichlo-
rohydrin and properly characterized. The catalytic property of the prepared
polymer was assessed by synthesizing 2-aryl-substituted benzimidazole and
benzoxazole derivatives by the conjugation of o-phenylenediamine/o-
aminophenol with various aromatic aldehydes in the presence of atmospheric
oxygen. Significant attributes of the present synthesis include short reaction
time, good to excellent yield, high purity, easy reusability, and room tempera-
ture reaction. The reaction was carried out in the absence of any metal catalyst
and other cooxidants.
Correspondence
Sreekumar Krishnapillai, Department of
Applied Chemistry, Cochin University of
Science and Technology, Cochin 682022,
Kerala, India.
Email: kskpolymer.cusat@gmail.com
Funding information
University Grants Commission, Grant/
Award Number: 113500
1 | INTRODUCTION
present attempt was in the synthesis of a polymer with
large number of telechelic amino functional groups. Its
Organocatalysis is a branch of chemistry developed to
reduce the environmental impact of chemical processes
by the use of less toxic and safer chemicals, introduced in
the context of green chemistry.1–3 It prevents the forma-
tion of metallic waste and avoids traces of metals in the
products, which is an essential requirement for applica-
tion in medicinal chemistry.4,5 The major promising
advantages of organocatalysts over metal catalysts are:
reduction in chemical waste, easy experimental proce-
dure, cost-effective, less time, and lower energy consump-
tion. These benefits are due to the insensitivity of organic
molecules to atmospheric oxygen and moisture. Hence,
there is no need for special reaction vessels, storage con-
tainers, and experimental techniques. Moreover, small
organic molecules are less toxic and environment friendly
than metal-based catalysts.6,7 The main difficulty with
organocatalyst is in the separation, recovery, and reuse of
the catalyst. The prime objective of this study was to
develop easily separable and reusable organopolymer cat-
alyst with high catalytic activity and selectivity. The
application toward the synthesis of 2-aryl-substituted
benzimidazoles and benzoxazoles by the condensation of
o-phenylenediamine/o-aminophenol with various aro-
matic aldehydes was explored.
Aryl-substituted benzimidazoles and benzoxazoles
are prominent class of N-heterocyclic compounds and are
found in pharmacologically active compounds and in
large variety of natural products.8–10 Synthesis of these
compounds is much significant because of their diverse
biological applications such as antitumor, antiviral,
antiinflammatory, antituberculosis, anti-HIV, antimicro-
bial, antibiotic, antifungal, anticonvulsant, antiulcer,
antihelminthic,
agents.11–19
antihypertensive,
and
analgesic
Because of the wide range of pharmacological and
industrial applications of these heterocyclic compounds,
wide variety of catalysts was reported for their synthesis.
Most of the reported methods for the synthesis of these
nitrogen containing heterocyclic compounds suffer from
several disadvantages including the use of toxic catalysts
J Heterocyclic Chem. 2020;1–8.
wileyonlinelibrary.com/journal/jhet
© 2020 Wiley Periodicals LLC.
1

2
KOTTAYIL ET AL.
and corrosive acids, occurrence of metal leaching and
side reactions, need of additional oxidation step, use of
reagents in large excess, long reaction time, and so
forth.20–23 Moreover, only a few reports are available for
the base catalyzed synthesis of benzimidazoles and
benzoxazoles.24–26 Consequently, effective, simple, and
environment friendly process for the preparation of
2-aryl-substituted benzimidazoles and benzoxazoles are
in high demand.
for about 15 minutes. The crude reaction mixture was
transferred to a separating funnel and washed with satu-
rated sodium carbonate solution followed by distilled
water. Solvent was removed under reduced pressure. The
formation of ISO-PECH was confirmed by GPC, TG-
1
differential thermogravimetry (TG-DTG), and FTIR, H-
NMR and 13C-NMR techniques.
ꢀ
Yield: 90%; Colorless viscous liquid; GPC Mass (Mn):
2011; polydispersity index (PDI): 1.04; IR (cm−1): 3465,
2921, 1116, and 746.
2 | EXPERIMENTAL SECTION
2.1 | Materials and methods
2.2.2 | Tosylation of hydroxyl group
The ISO-PECH (3 g) was dissolved in chloroform and
cooled. Pyridine (2.17 mL, 27 mmol) was added, followed
by the addition of p-toluenesulfonyl chloride (3.43 g
18 mmol) in small portions with constant stirring. Upon
complete addition, the temperature was held at 0ꢀC for
7 hours and allowed to come to RT overnight. The con-
tents of the flask were quenched by adding ice water.
Excess of ether was added and the organic layer was
washed successively with 2 N HC1, 5% NaHCO3, brine,
water, and dried by using anhydrous MgSO4. Solvent was
removed under reduced pressure to give tosylated ISO-
PECH in high yields.
Thin layer chromatography was done on alumina plates
coated with silica gel. Fourier transform infrared spec-
troscopy (FTIR) spectra were recorded on JASCO model
4100 FTIR spectrometer. CHNS analysis was performed
on Elementar Vario EL III instrument with digestion
temperature in the range 950ꢀC to 1200ꢀC (SAIF-
1
CUSAT). H-NMR and 13C-NMR spectra were recorded
on Bruker 400 MHz instrument in CDCl3/DMSO (SAIF-
CUSAT). Gel permeation chromatography (GPC) was
used to determine molecular mass of synthesized poly-
mers with Shimadzu PL gel 5 μm 10E4Å column. Ther-
mogravimetric (TG) analysis was done using a Perkin
Elmer Diamond TG/DTA system at a heating rate of
10ꢀC minute−1 under an atmosphere of nitrogen using a
ceramic pan. Gas chromatography/mass spectrometry
(GC–MS) analysis was performed on a 1200 L single
Quadrupole, Varian Gas Chromatograph model using
helium gas.
Yield: 87%; Colorless viscous liquid; C = 41.91%,
ꢀ
H = 5.95%, S = 0.61%; GPC Mass (Mn): 2361; PDI: 1.03;
IR (cm−1): 2922, 1603, 1447, 1357, 1186, 1119, and 746.
2.2.3 | Conversion of tosylated ISO-PECH
into polyazide
The tosylated ISO-PECH (3 g) was dissolved in
dimethylformamide (DMF) and was taken in a clean
round-bottomed flask fitted with condenser with cal-
cium chloride guard tube on the top. Sodium azide
(1.75 g, 27 mmol) was added, followed by the addition
of tetrabutylammonium bromide (0.1 mmol, 0.032 g).
The mixture was heated for 48 hours at 110ꢀC. After
completion of the reaction, the polymer solution was
diluted with dichloromethane. The mixture was fil-
tered to remove the unreacted sodium azide. The poly-
mer in dichloromethane was washed several times
with water to remove the traces of sodium azide and
dried over magnesium sulfate. The pure polymer was
obtained by removing the solvent by rotary vacuum
evaporator.
2.2 | Preparation steps for catalysts
2.2.1 | Preparation of isosorbide initiated
polyepichlorohydrin
Epichlorohydrin and isosorbide in the mole ratio 20:1
was used for making ISO-PECH. Isosorbide (0.73 g
0.005 mol) was added to 10 mL dichloromethane taken
in a RB flask. To this solution, BF3 etherate (0.30 mL
2.5 mmol) was slowly added. By the addition of BF3
etherate, the color of the reaction mixture changed from
a clear, colorless liquid to a cloudy liquid. It was stirred
for 1 hour under nitrogen atmosphere at RT. To this mix-
ture, epichlorohydrin (7.8 mL 0.1 mol) was added slowly
and stirred for 5 hours at RT. The polymerization was ter-
minated by adding distilled water and vigorously stirring
Yield: 85%; Honey colored viscous liquid; GPC Mass
(Mn): 2238; PDI: 1.09; IR (cm−1): 2922, 2100, and 1119.
ꢀ

KOTTAYIL ET AL.
3
2.2.4 | Conversion of polyazide to
polyamine by reduction
dried. The product was recrystallized from ethanol if
necessary to afford the pure benzimidazoles and
benzoxazoles.
Polyazide (2 g) was dissolved in dry tetrahydrofuran
(THF; 20 mL) and the reaction mixture was cooled in ice
bath. Slurry of LiAlH4 (0.759 g 20 mmol) in THF (10 mL)
was added drop wise with constant stirring to the poly-
azide solution. The reaction mixture was stirred at 0ꢀC
for 2 hours. The temperature was allowed to rise to RT
and gently refluxed for 1 hour. Ethyl acetate was added
to break up the complex. The polymer was filtered using
methanol and dried under vacuum.
3 | RESULTS AND DISCUSSION
3.1 | Synthesis and characterization of
catalyst
The synthesis of ISO-PECH polyamine (isosorbide-initiated
polyepichlorohydrin-cored polyamine) organocatalyst is
illustrated in Scheme 1. ISO-PECH was prepared by the
cationic ring opening polymerization of epichlorohydrin in
the presence of the catalyst BF3 etherate.27,28 The number
Yield: 80%; yellow colored waxy solid; C = 41.63%,
ꢀ
H = 7.63%, N = 5.43%; GPC Mass (Mn): 1709; PDI: 1.09;
IR (cm−1): 3388, 2922, 1581, and 1044.
ꢀ
average molecular weight (M n) of ISO-PECH from GPC
was found to be 2011 with PDI of 1.04. The FTIR spec-
trum contains peaks at 746, 1116, and 3465 cm−1
corresponding to chloromethyl group, ether linkage, and
hydroxyl groups, respectively. TG-DTG curve showed
that ISO-PECH underwent weight loss only after 330ꢀC,
which indicated that ISO-PECH was highly stable and
was applicable for further reaction. The hydroxyl group
of the polymer reacted with p-toluenesulfonyl chloride in
2.3 | Synthesis of 2-aryl substituted
benzimidazoles and benzoxazoles
A
mixture of o-phenylenediamine/o-aminophenol
(3 mmol), aldehyde (3 mmol), and the ISO-PECH poly-
amine catalyst (8 mg) in methanol (5 mL) was stirred at
RT. The reaction mixture was analyzed by thin layer
chromatography (hexane: ethyl acetate, v/v) and GC–MS.
After completion of the reaction, the solvent was evapo-
rated and the mixture was poured into ice cold distilled
water and the product was precipitated as pale yellow
solid which was filtered, washed with plenty of water and
ꢀ
the presence of pyridine. From GPC, M n of tosylated
1
ISO-PECH was found to be 2361 with PDI of 1.03. H-
NMR and 13C-NMR spectra clearly confirmed that
hydroxyl group was converted into tosyl group. The
azidation of the tosylated ISO-PECH was carried out
HO
Cl
O
O
Cl
OH
n
O
BF3Et2O
O
n
O
O
Cl
Cl
O
O
O
HO
HO
Cl
TsO
Cl
O
O
O
Cl
n
p-toluenesulfonyl chloride
NaN3
DMF
O
n
O
Cl
Pyridine
O
TsO
N3
Cl
H2N
NH2
N3
LiAlH4
THF
O
O
O
NH2
O
n
N3
n
O
O
n
O
NH2
O
N3
n
O
O
O
O
H2N
N3
NH2
N3
SCHEME 1 Synthesis of ISO-PECH polyamine organocatalyst by ring opening polymerization of epichlorohydrin

4
KOTTAYIL ET AL.
using sodium azide in DMF at 120ꢀC. In the FTIR spec-
trum, the presence of intense peak at 2100 cm−1 indicated
ꢀ
the azide functionality. From GPC, M n of ISO-GAP
(Polyazide) was found to be 2238 with PDI of 1.09. ISO-
GAP on reduction with lithium aluminum hydride got
converted to ISO-PECH polyamine. The conversion of
ISO-GAP to polyamine was first examined by conducting
the Kaiser ninhydrin test and further by GPC analysis. In
ꢀ
GPC analysis, the molecular weight (M n) of amine
functionalized polymer was found to be 1709 with PDI of
1.09. CHN analysis showed the percentage of carbon,
hydrogen and nitrogen as 41.63%, 7.63%, and 5.43%,
respectively. In the FTIR spectrum (Figure 1) of the poly-
amine, the peak at 2100 cm−1disappeared completely,
indicating total conversion of azide functionality and
new peaks corresponding to amine functionality were
observed at 3388 cm−1. The TG-DTG plot of ISO-PECH
polyamine showed that it was stable at working tempera-
ture up to 120ꢀC. With increasing temperature, the main
weight loss around 200ꢀC was due to the degradation of
FIGURE 1 FTIR spectrum of ISO-PECH polyamine
1
polyether chain (Figure 2). H-NMR and 13C-NMR spec-
tra were also in agreement with the proposed structure
for the polyamine product. In the 1H-NMR spectrum
(CDCl3), the C-H protons common to the two tetrahydro-
furan rings gave peaks at 3.86 to 3.88 ppm. The peaks at
3.73 to 3.75 ppm were assigned to other protons of iso-
sorbide ring. The methylene and methine protons of the
polymer backbone gave a multiplet in the range 3.69 to
3.73 ppm. A multiplet between 1.43 and 2.05 ppm indi-
cated the methylene protons directly attached to the
amine group. In the 13C-NMR spectrum (CDCl3), the sig-
nals at 28.7, 29.9, 30.0, 31.6, and 32.1 ppm indicated the
carbon atoms attached to the nitrogen in the polymer.
The carbon atoms of the polymer backbone showed sig-
nals at 42.9, 43.2, 60.9, and 61.4 ppm. The signals at 62.8,
64.5, 64.7, and 68.0 ppm are corresponding to other car-
bon atoms.
FIGURE 2 TG-DTG plot of ISO-PECH polyamine
of the desired product was obtained even after long reac-
tion time (Table 1, entry 1), but with 4 mg of catalyst,
87% yield was obtained (Table 1, entry 2). To get better
result, the process was repeated with different amounts
of the catalyst and found that 8 mg of catalyst gave the
product with excellent yield (99%; Table 1, entry 4). Fur-
ther optimization study confirmed that, within 4 minutes,
ISO-PECH polyamine catalyst gave excellent yield at RT
(Table 1, entry 7). The data shown in the table also indi-
cated that the yield obtained in the reaction with metha-
nol as solvent was higher than other selected solvents.
Thus, the optimized conditions selected for the transfor-
3.2 | Synthesis of 2-arylbenzimidazoles
and 2-arylbenzoxazoles
Synthesis of aryl-substituted benzimidazoles and ben-
zoxazoles were selected to evaluate the catalytic activity
of ISO-PECH polyamine as a homogeneous catalyst at
room temperature (RT; Scheme 2).
o-Phenylenediamine and benzaldehyde were chosen
as the model substrates to evaluate the reaction condi-
tions. The synthesis was carried out by varying parame-
ters like, amount of catalyst (0-10 mg) and solvent
(CH3CN, CH2Cl2, DMF, MeOH, and THF) at RT. The
necessity of the catalyst in this reaction was evaluated by
performing the reaction without catalyst; only 20% yield
mation was, by stirring 1:1
M ratio of o-phe-
nylenediamine:benzaldehyde in 4 minutes, in methanol
with 8 mg catalyst, at RT.

KOTTAYIL ET AL.
5
CHO
SCHEME 2 Synthesis of
2-arylbenzimidazoles/2-arylbenzoxazoles using ISO-
PECH polyamine organocatalyst
XH
Catalyst, air
X
..
NH2
Methanol, RT
N
R
R
X=NH,O
X= NH, O
TABLE 1 Optimization of the
reaction conditions
1
Entry
Amount of catalyst (mg)
Solvent
Time (min)
Yield (%)a,b
…
4
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
THF
180
10
10
10
10
5
20
87
92
99
99
99
99
75
92
70
93
2
3
6
4
8
5
10
8
6
7
8
4
8
8
15
8
9
8
CH3CN
CH2Cl2
DMF
10
11
8
15
8
8
aReaction conditions: benzaldehyde (3 mmol), o-phenylenediamine (3 mmol), solvent, and
room temperature.
bGas chromatography yield.
TABLE 2 Synthesized 2-arylbenzimidazoles
H
N
H
N
H
N
Cl
Br
N
N
N
(2 min, 95 %)
(4 min, 99 %)
(2 min, 99 %)
H
N
H
N
H
N
OMe
NO2
N
N
N
(4 min 96 %)
NO2
OMe
(2 min, 99 %)
(2 min, 92 %)
H
N
H
N
H
N
N
N
N
MeO
OMe
HO
(4 min, 94 %)
(5 min, 96 %)
(3 min, 93 %)
H
N
H
N
H
N
CH3
N
OH
CH3
N
N
N
(5 min, 98 %)
(3 min, 98 %)
(5 min, 95 %)
Note: Aldehyde (3 mmol), o-phenylenediamine (3 mmol), methanol, catalyst (8 mg), room temperature, and isolated yield.

6
KOTTAYIL ET AL.
TABLE 3 Synthesized 2-arylbenzoxazoles
O
N
O
O
Cl
Br
N
N
(4 min, 99 %)
(2 min, 99 %)
(2 min, 99 %)
O
O
O
OMe
CH3
N
N
N
NO2
OMe
MeO
(4 min, 98 %)
(3 min, 97 %)
(5 min, 98 %)
O
O
O
N
N
N
CH3
N
OMe
HO
(4 min, 98 %)
(5 min, 98 %)
(3 min, 98 %)
O
O
N
O
OH
NO2
OH
N
N
OCH3
(4 min, 96 %)
(2 min, 99 %)
(5 min, 96 %)
Note: Aldehyde (3 mmol), o-aminophenol (3 mmol), methanol, catalyst (8 mg), room temperature, and isolated yield.
13
characterized using 1H-NMR and
scopic techniques.
C-NMR spectro-
After completion of the reaction, the product was
thoroughly washed with distilled water and filtered off.
To the filtrate, ethyl acetate was added and the organic
layer was separated. The aqueous layer was vacuum
distilled to regenerate the catalyst. Recyclability of the
catalyst was checked for the synthesis of
2-phenylbenzoxazole and 2-phenylbenzimidazole, which
revealed that the reusability of the catalyst was achieved
up to six runs, without significant loss in the catalytic
activity (Figure 3).
3.3 | Comparative study
FIGURE 3 Reusability of the catalyst for the synthesis of
2-phenylbenzoxazole and 2-phenylbenzimidazole
The comparison of efficiency of the present catalyst with
already reported ones, on the synthesis of benzimid-
azoles and benzoxazoles are presented in Table 4. From
the table it was clear that many catalysts were able to
produce comparable yields, but most of them are toxic,
metal based, and the reactions required drastic condi-
tions or use of highly volatile organic solvents, which
indicated the superiority of ISO-PECH polyamine
organocatalyst. The stable and nontoxic ISO-PECH
polyamine is a reusable catalyst which allows the syn-
thesis of 2-arylbenzimidazoles and 2-arylbenzoxazoles
by a simple, economical, and green experimental
procedure.
Under the optimized reaction conditions established,
heterocyclisation of differently substituted aromatic alde-
hydes with o-phenylenediamine/o-aminophenol were
carried out (Tables 2 and 3). As shown in the tables, vari-
ous aromatic aldehydes including electron withdrawing
(eg, -NO2) and electron donating groups (eg, -OH and
-OMe) were rapidly and efficiently converted to the
related 2-aryl substituted benzimidazoles/benzoxazoles
in the presence of ISO-PECH polyamine catalyst in good
to excellent yield. All the products were characterized by
melting point and GC–MS. The products were also

KOTTAYIL ET AL.
7
TABLE 4 Comparison with previous reports for the synthesis of benzimidazole and benzoxazole derivatives
Catalyst
Time/temperature
2-5 min, RT
Solvent
MeOH
Toluene
EtOH
Yield (%)
92-99
ISO-PECH polyamine (present work)
ZnBr2/ABM (100 mg)a
ZnO NPs (10 mg)b
10-25 min, 111ꢀC
83-9629
90-9930
85-9322
91-9831
80-9023
79-9232
78-9233
68-9334
65-9235
2-8 min, RT
TiO2-ZrO2 (10 mol%)b
15-25 min, 60ꢀC
15-30 min, ultrasonic irradiation
1–5 h, reflux
CH3CN
H2O
Nano NiEuFe2O4 (6 mol%)a
PPh3, trichloroisocyanuric acida
Fe(III)-Schiff base/SBA-15, (0.01 g)a
Indion 190 resin (10%/weight)a
CuO-np/SiO2 (10 mol%)a
t-Butylhypochloride (2 mmol)b
1,4-dioxane
H2O
3 h, reflux
4 h, 70ꢀC
EtOH
4-14 h, RT
MeOH
CH3CN
1-4 h, reflux
Abbreviations: ISO-PECH, isosorbide-initiated polyepichlorohydrin; RT, room temperature.
aBoth for benzoxazoles and benzimidazoles.
bOnly for benzoxazoles.
..
SCHEME 3 Proposed mechanism
for the formation of benzimidazole/
benzoxazole
NH2
H2N
HN
..
NH2
NH2
NH2
H2N
NH2
NH2
H
HN
H
..
O
XH
XH
XH
OH
..
+
Ph
CH
H
-H2O
NH2
CH Ph
N
N
H
Ph
..
X=NH,O
NH2
H2N
NH2
NH2
H2N
[O]
X
X
N
Ph
Ph
H2O
N
H
3.4 | The proposed mechanism
phenylenediamine/o-aminophenol respectively. Subse-
quently, the product formed underwent aromatization
under air oxidation to give benzimidazole/benzoxazole.
The data of Table 1 (entries 1 and 4) indicated that the
yield of the condensation product was appreciably higher
in the presence of the catalyst rather than that of the
reaction carried out without the ISO-PECH polyamine
catalyst. This may be attributed to the fact that ISO-
PECH polyamine being a base catalyst could increase the
rate of the reaction by increasing the rate of formation of
the intermediate. Smith and Ho deliberated the mecha-
4 | CONCLUSION
From the detailed experimental investigations carried out
and the discussions presented above, the following can
be concluded. A new organopolymer catalyst was devel-
oped by the ring opening polymerization of epichlorohy-
drin and was characterized. The homogeneous,
organopolymer catalyst synthesized was highly efficient,
nism of oxygen catalyzed coupling reaction in detail.36
A
possible mechanism has been outlined in Scheme 3.
Here, the reaction most probably proceeded via the acti-
vation of aldehyde by the catalyst through hydrogen bond
followed by imine formation, which was converted to
dihydrobenzimidazole/dihydrobenzoxazole by the reac-
tion of the second -NH2/-OH group present in o-
reusable,
nontoxic,
and
environment
friendly.
The catalyst was used for one pot synthesis of
2-arylbenzimidazoles and 2-arylbenzoxazoles via the con-
densation of o-phenylenediamine/o-aminophenol with

8
KOTTAYIL ET AL.
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various aromatic aldehydes. Simple work up procedure,
low catalyst loading, small reaction time, RT reaction,
high yield of the products, easy purification method,
inexpensive, reusable, and environmentally friendly cata-
lyst are the prominent advantages of the present protocol.
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ACKNOWLEDGEMENTS
Authors acknowledge SAIF-CUSAT and CLIF-University
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spectroscopic
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H.K. acknowledges University Grants Commission
(UGC) for providing financial assistance.
ORCID
Avudaiappan Govindan https://orcid.org/0000-0002-
1036-0056
Sreekumar Krishnapillai https://orcid.org/0000-0002-
5716-2567
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SUPPORTING INFORMATION
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How to cite this article: Kottayil H, Machingal S,
Parackal B. Sm, et al. Development of
homogeneous polyamine organocatalyst for the
synthesis of 2-aryl-substituted benzimidazole and
benzoxazole derivatives. J Heterocyclic Chem. 2020;
1–8. https://doi.org/10.1002/jhet.4046