Nano indium oxide-catalyzed domino reaction for the synthesis of N-alkoxylated benzimidazoles

Article abstract of DOI:10.1016/j.tetlet.2020.152177

A convenient method has been developed for the selective synthesis of N-alkoxylated benzimidazole derivatives by the cyclocondensation reaction of simple ortho-phenylenediamine, formaldehyde and alcohols in presence of indium oxide nanoparticles as catalyst. The alcohol acts as reactant as well as solvent in this reaction. No other solvents or additives have been used for this reaction. The catalyst can be reused several times without significant loss of catalytic activity. A probable reaction mechanism has been proposed based on some control experiments.

Full text of DOI:10.1016/j.tetlet.2020.152177

Journal Pre-proofs
Nano indium oxide-catalyzed domino reaction for the synthesis of N-alkoxy‐
lated benzimidazoles
Satyajit Samanta, Sachinta Mahato, Rana Chatterjee, Sougata Santra, Grigory
V. Zyryanov, Adinath Majee
PII:
S0040-4039(20)30637-7
DOI:
Reference:
https://doi.org/10.1016/j.tetlet.2020.152177
TETL 152177
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
24 April 2020
22 June 2020
24 June 2020
Please cite this article as: Samanta, S., Mahato, S., Chatterjee, R., Santra, S., Zyryanov, G.V., Majee, A., Nano
indium oxide-catalyzed domino reaction for the synthesis of N-alkoxylated benzimidazoles, Tetrahedron Letters
(2020), doi: https://doi.org/10.1016/j.tetlet.2020.152177
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover
page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version
will undergo additional copyediting, typesetting and review before it is published in its final form, but we are
providing this version to give early visibility of the article. Please note that, during the production process, errors
may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2020 Elsevier Ltd. All rights reserved.

Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Nano indium oxide-catalyzed domino
reaction for the synthesis of N-alkoxylated
benzimidazoles
Leave this area blank for abstract info.
Satyajit Samanta, Sachinta Mahato, Rana Chatterjee, Sougata Santra, Grigory V. Zyryanov, and Adinath
Majee*

1
Tetrahedron Letters
journal homepage: www.elsevier.com
Nano indium oxide-catalyzed domino reaction for the synthesis of N-alkoxylated
benzimidazoles
Satyajit Samanta,a Sachinta Mahato,a Rana Chatterjee,a Sougata Santra,b Grigory V. Zyryanov,b,c and
Adinath Majeea, 
a
Department of Chemistry; Visva-Bharati (A Central University), Santiniketan 731235, India
Department of Organic and Biomolecular Chemistry, Chemical Engineering Institute, Ural Federal University, 19 Mira Street, 620002, Yekaterinburg,
b
Russian Federation
c I. Ya. Postovskiy Institute of Organic Synthesis, Ural Division of the Russian Academy of Sciences, 22 S. Kovalevskoy Street, 620219 Yekaterinburg, Russian
Federation
———
ARTICLE INFO
ABSTRACT
 Corresponding author. e-mail: adinath.majee@visva-bharati.ac.in
Article history:
Received
A convenient method has been developed for the selective synthesis of N-alkoxylated
benzimidazole derivatives by the cyclocondensation reaction of simple ortho-phenylenediamine,
Received in revised form
Accepted
Available online
formaldehyde and alcohols in presence of indium oxide nanoparticles as catalyst. The alcohol
acts as reactant as well as solvent in this reaction. No other solvents or additives have been used
for this reaction. The catalyst can be reused several times without significant loss of catalytic
activity. A probable reaction mechanism has been proposed based on some control experiments.
Keywords:
2009 Elsevier Ltd. All rights reserved.
Nano indium oxide
N-Alkoxylated benzimidazoles
ortho-Phenylenediamine
Formaldehyde
Reusable catalyst
Benzimidazole is fused aromatic heterocyclic compound (i.e.
a couple of benzene and imidazole ring) which is mainly a
derivative of imidazole framework. Among heterocyclic
pharmacophores [1], benzimidazole and its derivatives are very
much highlighted in the synthesis of pharmacologically and
biologically active compounds [2-4]. Benzimidazoles with
different functional group(s) at position(s) on the interior
framework display a wide range of biological activities like anti-
HBV (A) [5], antitubercular (B) [6], non-seadating antihistamine
(C) [7], (GABAA agonists (D) [8], anti-viral (E) [9], anti-
inflammatory and analgesic (F) [10] (Figure 1).
benign manner than conventional procedures by omitting the
steps of separation and purification of the reaction intermediates.
Classically, benzimidazoles are prepared by the two ways i.e.
first, by different cyclocondensation reaction and secondly by
cross dehydrogenative coupling (CDC) via C-H functionalization
and
C-N
bond
formation.
Moreover,
2-substituted
benzimidazoles were synthesized from various ortho-
phenylenediamines (OPDs) which subjected to react with
different functional groups via cyclocondensation pathways [12-
14] or CDC coupling [15-17]. A few protocols have been
reported in the last decade to synthesize 1,2-disubstituted
benzimidazoles like N-alkylation of ortho-nitro [18,19] ortho-
bromo anilide [20,21] followed by cyclocondensation / reductive
cyclization pathway or direct coupling of ortho-
phenylenediamines with aryl, alkyl aldehydes using a variety of
catalysts such as SDS micelles [22], cobalt(II) chloride [23],
trimethylsilyl chloride [24], organocatalyst like L-proline [25],
DMF/TMSCl [26], also indium oxide nano [27] and
dehydrogenative coupling between aromatic diamines and
alcohols using different catalyst like Ir(III) [28], Mn(I) [29],
Ni(II) [30]. In addition, water-assisted tandem N-alkylation-
reduction-condensation process was also developed [31]. Very
recently, several convenient methods have been reported, such as
Fe-catalyzed CDC reaction and aromatization of diarylmethyl-
and dialkyl- benzimidazole precursors [32], dodecylimidazolium
hydrogen sulfate-catalyzed condensation reaction between OPDs
and aldehydes [33], metal-free, aerobic oxidative C-O and C-C
O
Br
N
N
OPNP
N
N
N
N
N
O
S
O
O
O
Ar
S
N
O
PNP
PNP= p-nitrophenol
C
O
B
A
N
N
H
N
H
N
N
CH2CH2COOH
N
N
Ar1
N
N
N
H
N
O
S
O
Ph
O
E
F
D
Cl
F
Figure 1. Some biologically active N-protected benzimidazole scaffold.
Domino reactions are one of the most powerful and atom
economical methodologies in organic synthesis [11]. These
reactions usually proceed in a more efficient and environmentally

2
Tetrahedron Letters
cleavage cascade reaction of alcohols and ethers with OPDs
used only ethanol as a solvent (Table 2, entry 8). So, the
optimized condition was considered by using 10 mol% of In2O3
nano and ethanol as solvent as well as reactant (3b, 2 mL) at 60
°C for 2 h.
[34], cascade oxidation/cyclization/alkylation reaction of meso-
hydrobenzoin or benzyl alcohols with OPD and 2,6-
difluorobenzyl bromide [35], I2-mediated intramolecular C–H
amidation reaction [36] and hydrotalcite supported BINAP-
copper-catalyzed reaction between OPDs and benzyl alcohols
[37]. Most of these methodologies used substituted diamines,
aromatic aldehydes rather than aliphatic aldehydes and also
product selectivity is a major problem due to the formation of
three types of substituted benzimidazole derivatives (N-1
substituted, 2- substituted, 1,2-disubstituted benzimidazoles).
Table 1. Optimization of the reaction conditions a
NH2
NH2
N
N
N
Catalyst (10 mol%)
+
HCHO
N
H
EtOH (3b, 2 mL)
2a
5
O
1a
4b
The use of indium oxide nano (In2O3) mediated in the area of
organic synthesis is very much limited [38-40]. As a continuation
of our previous work on indium oxide nano [27,39,40], here we
are pleased to report a convenient synthesis of N-substituted
benzimidazole derivatives (N-alkoxylated benzimidazoles) by the
multicomponent reaction (MCR) of ortho-phenylenediamines
(OPDs) with formaldehyde and alcohol in presence of indium
oxide nano particles (In2O3) via intermolecular cyclization
(Scheme 1). To the best of our knowledge, this is the first time
report for the synthesis of N-alkoxylated benzimidazoles
derivatives synthesized in a one pot domino fashion.
Temp.
(°C)
Time
(h)
Yield of Yield of
Entry
Catalyst (mol%)
4b (%)b
5 (%)b
1
In2O3 nano (5)
In2O3 nano (10)
In2O3 nano (20)
In2O3 nano (10)
In2O3 nano (10)
In2O3 nano (10)
In2O3 nano (10)
InCl3 (10)
60
60
60
80
40
60
60
60
60
60
60
60
2
2
2
2
2
4
1
2
2
2
2
2
50
15
2
76
20
3
76
20
4
70
20
5
45
10
6
72
20
7
60
15
NH2
N
N
In2O3 nano (10 mol%)
8
58
21
R1
R1
HCHO
+
2
3
R -OH ( , 2 mL)
9
In(OTf)3 (10)
Zn(OTf)2 (10)
CuO nano (10)
-
55
20
NH2
2
60 °C, 2 h
1
R2O
R2= alkyl, benzyl
10
11
12
<10
55
NRc
20
4
R1 = H, Me, Cl, NO2
NRc
NRc
Scheme 1. Synthesis of N-substituted benzimidazole
derivatives.
aReaction conditions: All the reactions were carried out on 1
mmol scale, 1a (1 equiv.), 37% HCHO (2a, 2 equiv.) in presence
b
c
of catalyst and ethanol (3b, 2 mL). Isolated yield. NR = no
We initiated our observation by using ortho-
phenylenediamine (1a, 0.5 equiv.) and 37% formaldehyde (2a, 2
equiv.) in presence of In2O3 nano (5 mol%) in ethanol solvent
(3b, 2 mL) at 60 °C under the open air. To our delight, the
reaction underwent smoothly and 50% of 1-(ethoxymethyl)-1H-
benzo[d]imidazole (4b) and 15% of 1H-benzo[d]imidazole (5)
were isolated within 2 h (Table 1, entry 1). Inspired by this result
when we increased the amount of In2O3 nano to 10 mol% the
yield of the reaction increased significantly with 76% of 4b and
20% of 5 (Table 1, entry 2). Further increase of catalyst loading
did not improve the yield of the reaction (Table 1, entry 3).
Again, the yield of the reaction did not improve appreciably by
increasing the reaction time but with reducing the reaction time
the yield of both 4b and 5 decreased considerably (Table 1, entry
6 & 7). Increasing temperature from 60 °C to 80 °C no
considerable improvement has been noticed whereas, decreasing
the temperature decreased the yield of both 4b and 5 (Table 1,
entry 4 & 5). We examined other indium catalysts like InCl3,
In(OTf)3 and also other catalysts like Zn(OTf)2, CuO nano but the
yields are not impressive (Table 1, entry 8-11). But in the
absence of any catalyst, the reaction did not proceed at all (Table
1, entry 12).
reaction.
Table 2. Screening of the solvent effectsa
NH2
NH2
In2O3 nano (10 mol%)
N
N
N
HCHO
+
3b
N
H
EtOH ( , 2 mL)
2a
60 °C, 2 h
5
1a
O
4b
Entry
1
Solvents (2 mL)
DCM
Yield of 4b (%)b
Yield of 5 (%)b
25
<10
2
3
4
5
6
7
8
DCE
35
15
THF
20
<5
<8
NDc
<8
<8
20
1,4- dioxane
DMSO
Toluene
DCB
20
trace
15
20
EtOH
76
aReaction conditions: All the reactions were carried out on 1
mmol scale, 1b (1 equiv.), 37% HCHO (2a, 2 equiv.) in presence
of different solvent (2 mL). bIsolated yield. cND = not detected in
TLC.
Next, for enrichment of our present methodology and to get a
better knowledge of the solvent effects, we have screened a series
of mix-solvent as summarized in Table 2. For polar aprotic
solvents like DCE, THF, 1,4-dioxane and DCM in the presence
of ethanol (3b) the targeted product (4b) was found in 20-35%
yields (Table 2, entry 1-4). When we used nonpolar aprotic
solvent like toluene, DCB and also polar aprotic solvent like
DMSO with ethanol (3b) we got lower and a trace amount of
yield of the products (Table 2, entry 5-7). We acquired the best
result affording 76% yield of our desired product (4b) when we
After optimization, we explored the substrate scope of this
methodology and the results are summarized in Table 3 & 4. A
library of N-alkoxylated benzimidazole derivatives was
synthesized by varying different alcohols. At first, we used
different primary as well as saturated alcohols like methanol (3a),
propanol (3c), butanol (3d) and isobutanol (3e) which were

3
subjected to react with 1,2-phenylenediamine (1) and it was
observed that the corresponding desired products were obtained
in 68-76% yields (Table 3, 4a-4e). Next, in case of secondary and
tertiary alcohols (3f & 3g), the corresponding desired products
were obtained in moderate yields (Table 3, 4f & 4g).
Remarkably, unsaturated alcohols like prop-2-en-1-ol (3h), but-
3-en-1-ol (3i) and propargyl alcohol (3j) were also examined and
the reactions underwent without any difficulty to produce the
products (60-70% yields) (Table 3, 4h-4j). Even, trifluoroethanol
(3k) responded for this present protocol affording moderate yield
(4k). Moreover, benzyl alcohol and 4-methyl benzyl alcohol also
gave the alkoxylated products in 52% and 55% yields (4l, 4m).
For all these reactions no additional solvent was needed but the
alcohols themselves acted as solvent and reactant.
Table 4. Substrates scope using substituted ortho-
phenylenediamines a,b
NH2
N
N
In2O3 nano (10 mol%)
R1
R1
HCHO
+
2
3
R -OH ( , 2 mL)
60 °C, 2 h
NH2
R2O
Cl
4
1
2
Cl
N
N
N
N
N
+
+
N
N
N
Cl
Cl
O
O
O
O
4n
(1:1), 85%
N
4o
(1:1), 86%
Cl
N
N
Table 3. Substrates scope using different alcoholsa,b
N
N
+
N
Cl
N
N
O2N
NH2
Me
N
In2O3 nano (10 mol%)
O
O
HCHO
O
O
2
N
3
R -OH ( , 2 mL)
NH2
4q
, 0%
4r,
0%
60 oC, 2 h
2
1
R2O
4
4p
(1:1), 84%
aReaction conditions: All the reactions were carried out on 1
mmol scale, 1 (1 equiv.), 37% HCHO (2a, 2 equiv.) in presence
of In2O3 nano and ethanol (3b, 2 mL). bIsolated yield.
N
N
N
N
N
N
N
N
N
N
O
O
O
O
O
Moreover, the synthetic applicability of this protocol was
investigated on the gram scale using the model reaction in our
laboratory setup. As shown in Scheme 2, the reaction could
afford 1.27 g of 4b in 72% yield without any significant loss of
its efficiency, demonstrating the potential applications of the
present method for a large-scale synthesis of N-alkoxylated
benzimidazole derivatives.
4c
, 74%
4b
4d
, 72%
4a
, 76%
, 75%
4e
, 68%
N
N
N
N
N
N
N
N
N
N
O
O
O
O
O
NH2
NH2
N
N
In2O3 nano (10 mol%)
+
HCHO
3b
EtOH ( , 20 mL)
4f
, 64%
4h
, 70%
60 oC, 2 h
4g
, 55%
4j
2a
, 60%
1a
(10 mmol)
O
4i
, 66%
(10 mmol)
N
N
N
N
N
N
4b
, 1.27 g, 72% yield
Scheme 2. Gram-scale reaction.
O
O
O
F3C
4k
To check the recyclability of the catalyst, it was separated
from the reaction mixture by ultra centrifugation, washed with
water, dried under vacuum followed by drying at 110 °C and
reused for further reactions. The catalyst maintained its high level
of activity even after being recycled five times for synthesizing
4b as shown in Table 4.
, 58%
4l
, 52%
4m
, 55%
aReaction conditions: All reactions were carried out on 1
mmol scale, 1 (1 equiv.), 37% HCHO (2a, 2 equiv.) in presence
of In2O3 nano (10 mol%) and ethanol (3b, 2 mL). bIsolated yield.
Next, our attention was turned to the use of substituted
phenylenediamine to expand the general applicability of the
present procedure (Table 4). Surprisingly, 4-chlorobenzene-1,2-
diamine reacted well with ethanol but produced the N-
alkoxylated product (86%) with 1:1 mixture of isomers (4o). We
have also changed alcoholic part like methanol, propanol but we
get the same mixture of the product (4n, 4p) with good yields
(85% and 84% respectively). However, 4-methylbenzene-1,2-
diamine (1b) and 4-nitrobenzene-1,2-diamine (1c) did not
undergo to afford the corresponding products under the present
reaction conditions.
Table 4. Recycling of In2O3 nanoparticles for synthesizing
4ba
No. of cycle
Yields (%)b
Catalyst recovery (%)
1
2
3
4
5
76
75
75
72
71
97
95
93
90
87
aCarried out with 1 mmol of 1a and 1 mmol of 2a in the
b
presence of catalyst in ethanol (2 mL) at 60 °C for 2 h. Isolated
yields.

4
Tetrahedron Letters
NH2
NH2
In2O3 nano (10 mol%)
EtOH, 60 oC, 2 h
4b
37% HCHO
+
a)
0%
2a,
0%
1a
In2O3 nano (10 mol%)
60 oC, 2 h
NH2
NH2
N
4b
+
37% HCHO
+
b)
c)
N
H
, 30%
2a,
4 equiv.
0%
1a
5a
N
In2O3 nano (10 mol%)
EtOH, 60 oC, 2 h
4b
0%
Figure 2. HRTEM images of (a) fresh In2O3 nanoparticles and (b) In2O3
37% HCHO
+
N
H
nanoparticles after the fifth cycle.
2a,
4 equiv.
5a
The morphology of nano-In2O3 was determined by HRTEM.
A comparative study of the HRTEM of the fresh catalyst and the
recovered catalyst after five cycles shows that the catalyst does
not undergo agglomeration during the recycling process (Figure
2).
N
In2O3 nano (10 mol%)
EtOH, 60 oC, 2 h
4b
d)
N
H
0%
5a
All reactions were carried out on a 1 mmol scale.
For the mechanistic investigation of our present protocol, we
performed some control experiments (Scheme 3). When the
reaction was carried out in absence of formaldehyde no desired
product was obtained (Scheme 3a). Again, the targeted product
was not formed in the absence of ethanol but we got only
benzimidazole product (5a) in 30% yield (Scheme 3b). Next, by
taking only synthesized benzimidazole (5a) instead of 1,2-
phenylenediamine (1a) and formaldehyde, no desired product
was obtained under the optimized reaction conditions (Scheme
3c). Similarly, the present reaction did not proceed when
benzimidazole (5a) reacted with ethanol in the absence of
formaldehyde under the same reaction conditions (Scheme 3d).
So, from the above observations, it is clear that the reaction does
not proceed via the formation of benzimidazole as intermediate.
Scheme 3. Control experiments.
On the basis of these experimental observations, literature
reports [41] and our previous experience in In2O3 nano
[27,39,40], a probable mechanistic pathway has been proposed
for the synthesis of N-alkoxylated benzimidazole derivatives as
shown in Scheme 4. Initially, ortho-phenylenediamine (1a) reacts
with formaldehyde (2a) to form 1,2-diimine intermediate (A).
In2O3 nano might activate the formaldehyde through the co-
ordination with the oxygen of the corresponding carbonyl group
which facilitates the subsequent nucleophilic attack by the
nitrogen atom on the carbonyl carbon. The addition of alcohol (3)
with one imine produces the nucleophilic nitrogen which by
intra-molecular imine cyclization furnish the intermediate (B).
The intermediate B after protonation gives intermediate (C)
which on aromatization by dehydrogenation produce the final
product.
O
H
H
H
N
-H2
N
NH2
NH2
ROH
N
N
N
2a
CH2
CH2
N
N
3
ROH ( )
N
H
H
1a
OR
C
OR
A
OR
B
2a
O
4
= In2O3 nano
Scheme 4. Plausible mechanistic pathway.
In conclusion, a convenient method has been developed for
the synthesis of N-alkoxylated benzimidazoles by the reaction
between readily available 1,2-phenylenediamine, formaldehyde
and alcohol in the presence of indium oxide nano as catalyst. To
the best of our knowledge, this is the first-time report for the
synthesis of N-alkoxylated benzimidazoles derivatives
synthesized in a one-pot tandem fashion. Furthermore, the
present methodology is also applicable for the gram-scale
synthesis without any significant loss of its efficiency,
demonstrating the potential applications of the present method
for a large-scale synthesis of N-alkoxylated benzimidazole
derivatives. Easily accessible reagents, gram-scale synthesis,
general applicability, simple operation, mild reaction conditions
and reusability of the catalyst are the remarkable advantages of
the present methodology. We believe that our new protocol using
In2O3 nano will find widespread applications in academic
laboratories and industry.
Acknowledgments
A. Majee acknowledges financial support from the CSIR-
Major Research Project (Ref. No. 02(0383)/19/EMR-II). S.
Santra acknowledges the Russian Science Foundation – Russia
(Ref. # 18-73-00301) for funding. We are thankful to the DST-
FIST and UGC-SAP programmes.

5
24. Wan J-P, Gan S-F, Wu J-M, Pan Y. Green Chem. 2009; 11:
1633–1637.
References and notes
25. Varala R, Nasreen A, Enugala R, Adapa SR. Tetrahedron Lett.
2007; 48: 69–72.
26. Ryabukhin S V, Plaskon AS, Volochnyuk DM, Tolmachev AA.
Synthesis (Stuttg). 2006; 2006: 3715–3726.
27. Santra S, Majee A, Hajra A. Tetrahedron Lett. 2012; 53: 1974–
1977.
28. Sharma AK, Joshi H, Bhaskar R, Singh AK. Dalt Trans. 2017; 46:
2228–2237.
29. Das K, Mondal A, Srimani D. J Org Chem. 2018; 83: 9553–9560.
30. Bera A, Sk M, Singh K, Banerjee D. Chem Commun. 2019; 55:
5958–5961.
31. Kommi DN, Kumar D, Bansal R, Chebolu R, Chakraborti AK.
Green Chem. 2012; 14: 3329-3335.
32. Thapa P, Palacios PM, Tran T, Pierce BS, Foss FW, Jr. J. Org.
Chem. 2020, 85: 1991-2009.
33. Senapak W, Saeeng R, Jaratjaroonphong J, Promarak V, Sirion U.
Tetrahedron 2019, 75: 3543-3552.
34. Senadi GC, Kudale VS, Wang J-J. Green Chem .2019, 21: 979-
985.
35. Bi X, Meng X, Chen G, Chen B, Zhao P. Catal. Commun. 2018,
116: 27-31.
36. Hu Z, Zhao T, Wang M, Wu J, Yu W, Chang J. J. Org. Chem.
2017, 82: 3152-3158.
37. Xu Z, Yu X, Sang X, Wang D. Green Chem. 2018, 20: 2571-
2577.
38. Reddy VP, Kumar AV, Swapna K, Rao KR. Org Lett. 2009; 11:
1697–1700.
39. Santra S, Majee A, Hajra A. Catal. Commun. 2014; 49: 52-57.
40. Mitra S, Bagdi AK, Majee A, Hajra A, Tetrahedron Lett. 2013;
54: 4982-4985.
41. Xu Z, Yu X, Sang X, Wang D, Green Chem. 2018; 20: 2571-
2577.
1.
2.
Alaqeel SI. J Saudi Chem Soc. 2017; 21: 229–237.
Bhattacharya S, Chaudhuri P. Curr Med Chem. 2008; 15: 1762–
1777.
Boiani M, González M. Mini Rev Med Chem. 2005; 5: 409–424.
Horton DA, Bourne GT, Smythe ML. Chem Rev. 2003; 103: 893–
930.
Li Y-F, Wang G-F, He P-L, Huang W-G, Zhu F-H, Gao H-Y,
Tang W, Luo Y, Feng C-L, Shi L-P. J Med Chem. 2006; 49:
4790–4794.
Ranjith PK, Rajeesh P, Haridas KR, Susanta NK, Row TNG,
Rishikesan R, Kumari NS. Bioorg Med Chem Lett. 2013; 23:
5228–5234.
Prakash A, Lamb HM. BioDrugs. 1998; 10: 41–63.
Yuen J, Fang Y-Q, Lautens M. Org Lett. 2006; 8: 653–656.
Tewari AK, Mishra A. Indian J. Chem., Sect. B 2006; 45: 489–
493.
3.
4.
5.
6.
7.
8.
9.
10. Gaba M, Singh D, Singh S, Sharma V, Gaba P. Eur J Med Chem.
11. Tietze LF, Brasche G, Gericke K., in Domino Reactions in
Organic Synthesis, Wiley-VCH, Weinheim, 2006.
12. Wright JB. Chem Rev. 1951; 48: 397–541.
13. Li L, Luo Q, Cui H, Li R, Zhang J, Peng T. ChemCatChem. 2018;
10: 1607–1613.
14. Sharma R, Abdullaha M, Bharate SB. Asian J Org Chem. 2017; 6:
1370–1374.
15. Daw P, Ben-David Y, Milstein D. ACS Catal. 2017; 7: 7456–
7460.
16. Tateyama K, Wada K, Miura H, Hosokawa S, Abe R, Inoue M.
Catal Sci Technol. 2016; 6: 1677–1684.
17. Chaudhari C, Siddiki SMAH, Shimizu K. Tetrahedron Lett. 2015;
56: 4885–4888.
18. Takeuchi K, Bastian JA, Gifford-Moore DS, Harper RW, Miller
SC, Mullaney JT, Sall DJ, Smith GF, Zhang M, Fisher MJ. Bioorg
Med Chem Lett. 2000; 10: 2347–2351.
Supplementary Material
19. Evindar G, Batey RA. Org Lett. 2003; 5: 133–136.
20. Brain CT, Steer JT. J Org Chem. 2003; 68: 6814–6816.
21. Saha P, Ali MA, Ghosh P, Punniyamurthy T. Org Biomol Chem.
2010; 8: 5692–5699.
22. Bahrami K, Khodaei MM, Nejati A. Green Chem. 2010; 12:
1237–1241.
Supplementary material to this article can be found online.
Click here to remove instruction text...
23. Khan AT, Parvin T, Choudhury LH. Synth Commun. 2009; 39:
2339–2346.
Highlights
Declaration of interests
 Nano-In2O3 is found to be an efficient
catalyst for three-component condensation.
X The authors declare that they have no known
 In2
O3
nan
opa
rtic
les
competing financial interests or personal
relationships that could have appeared to influence
the work reported in this paper.
are recyclable without significant loss of
catalytic activities.
 Applicable to gram-scale synthesis of N-
alkoxylated benzimidazoles.
 Control experiments were done for
mechanism studies.
☐The authors declare the following financial
interests/personal relationships which may be
considered as potential competing interests:

6
Tetrahedron Letters
Graphical Abstract
To create your abstract, type over the instructions in the
template box below.
Fonts or abstract dimensions should not be changed or altered.
Nano indium oxide-catalyzed domino
Leave this area blank for abstract info.
reaction for the synthesis of N-alkoxylated
benzimidazoles
Satyajit Samanta, Sachinta Mahato, Rana Chatterjee, Sougata Santra, Grigory V. Zyryanov, and Adinath
Majee*