An Intramolecular C(sp2)–H Amidation Using N-Iodosuccinimide

Article abstract of DOI:10.1002/ejoc.201800688

An N-iodosuccinimide (NIS) mediated intramolecular dehydrogenative C(sp²)–H amidation is reported for easy and convenient access to 1,2-disubstituted benzimidazoles. The nonprefunctionalized C(sp²)–H and N(sp³)–H bonds wer

Full text of DOI:10.1002/ejoc.201800688

A Journal of
Accepted Article
Title: An Intramolecular C(sp2)-H Amidation using N-Iodosuccinimide
Authors: Md Toufique Alam, Saikat Maiti, and Prasenjit Mal
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800688
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800688
Supported by

10.1002/ejoc.201800688
European Journal of Organic Chemistry
FULL PAPER
An Intramolecular C(sp2)-H Amidation using N-Iodosuccinimide
Md Toufique Alam, Saikat Maiti and Prasenjit Mal*
supramolecular interactions it’s important to understand the
Abstract: Herein, N-iodosuccinimide (NIS) mediated an
intramolecular dehydrogenative C(sp2)-H amidation is reported for an
easy and convenient access to 1,2-disubstituted benzimidazoles. The
non-prefunctionalized C(sp2)-H and N(sp3)-H bonds were directly
coupled using the NIS in trifluoroethanol and proved to be mild
alternative to strong oxidative iodine(III) reagents. The reaction
worked at room temperature, under open atmosphere and any
additive (base) free condition.
reactivity of the system as a whole.[26]
Results and Discussion
In continuation of our research interests towards controlling
chemical reactions using weak interactions[27] in non-
prefunctionalized aromatic systems,[28] we report here an
intramolecular C(sp2)-H amidation reaction (Figure 1c) for 1,2-
disubstituted benzimidazole synthesis using NIS by replacing
strong oxidant like phenyliodine diacetate (PIDA).[29] Till date,
numerous methods have been established for synthesis of N-H
benzimidazoles,[30] but a very few reports are available for metal-
free direct access to N-substituted benzimidazoles.[31]
Introduction
Benzimidazoles are well known heterocyclic systems for their
extensive use in pharmaceutical chemistry and material
science.[1] These molecules have also shown anti-cancer,[2] anti-
infective,[3] anti-inflamatory,[4] anti-hepatitis B,[5] anti-HIV,[6] anti-
depressant,[7]
and
anti-tumor[8]
activities.
Interestingly,
benzimidazole moiety containing drug esomeprazole (Nexium)
was reported to be one of the best-selling drugs in 2009 (Figure
1a).[9] The N-substituted benzimidazole systems are also well
known in various biologically active molecules.[4-5, 10] Therefore,
synthesis of benzimidazoles gained huge attention in organic
synthesis.
The development towards exploring environmentally benign
methods[11] for C-N bond synthesis are of huge significance.[12]
Compared to metal mediated C-N coupling reactions,[13] metal-
free direct C-H amination are of importance to deliver various
amines by sustainable methods.[14] The cost effective and waste
free methods for construction of C-N bonds using metal free
iodine based reagents are popular[15] and therefore various cross-
dehydrogenative coupling (CDC) or oxidative cross C-N coupling
reactions are reported.[16] However, limited examples are
available for C-H amination reaction using N-iodosuccinimide
(NIS).[17]
The small molecules system chemistry approach[18] is gaining
popularity by understanding the complexity of chemical reactions
and towards implementing them in
a simplified manner.
Cooperative multiple weak interactions[19] like hydrophobic
effect,[20] halogen bonding,[21] charge-transfer,[22] cation-π, anion-
π,[23] Soft-Hard Acid Base (SHAB) control,[24] etc. are significantly
being explored in chemical reaction systems.[25] Therefore, in
order to control a chemical reaction within a system through weak
Figure 1. a) Benzimidazole containing drug molecules. b) The reactivity control
of amines in presence of phenyliodine diacetate (PIDA). For example, benzyl
[22]
amine-PIDA explosion was controlled by NaHSO4,
sulphonamides in
[*]
Dr. Prasenjit Mal, Mr. Md Toufique Alam, Dr. Saikat Maiti
School of Chemical Sciences, National Institute of Science
Education and Research (NISER), HBNI, Bhubaneswar, PO
Bhimpur-Padanpur, Via Jatni, District Khurda, Odisha 752050, India.
Email: pmal@niser.ac.in (ORCID: 0000-0002-7830-9812)
Webpage: http://www.niser.ac.in/users/pmal
fluorinated solvents led to carbazoles,[28] styrene was difunctionalized via cation-
π.[32] c) Understanding of the dehydrogenative C(sp2)-H amidation by NIS (this
work).
Amines are highly reactive towards hypervalent iodine reagents
and therefore intra- or intermolecular control of the reactions are
necessary. A successful CDC reaction was done from contact-
explosives mixture primary amines and PIDA under solvent free
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800688
European Journal of Organic Chemistry
FULL PAPER
ball milling condition i.e., at maximum contacts of the reactants
(Figure 1b).[22] Using the acid-salt NaHSO4, charge transfer
basicity of the amine nitrogen was reduced towards the reaction
with iodine(III). We have also recently shown that reactivity of
protected aryl amines i.e., sulphonamides in 2,2,2-trifluoroethanol
(TFE) can be performed towards synthesis of carbazoles,[28] At
mixing certain aryl amines also led to exothermic reactions with
PIDA. It was established that the I+ generated form the PIDA-I2
mixture promoted the olefin-difunctionalization reactions in TFE
or CD3OD via cation-π interaction (Figure 1b).[32] In Figure 1c, we
have shown the intramolecular dehydrogenative C(sp2)-H
amination towards synthesis of 1,2-disubstituted benzimidazoles.
We anticipate that I+ helped to promote the C(sp2)-H – NH
coupling. Being highly polar and non-nucleophilic in nature,
fluorinated solvents are anticipated to stabilize the cationic
intermediates when the reactions are carried out using iodine
reagents.[33]
yield of the 1,2-disubstituted benzimidazoles at room temperature
are the major advantages of this amination protocol.
Table 1 Optimization of reaction condition
Entry
Reagent
(equiv)
Solvent
Time
Yieldb
(%)
1
NIS (1.1)
NIS (1.5)
NIS (1.8 )
NIS (1.8)
NIS (1.8)
NIS (1.8)
NIS (1.8)
NIS (1.8)
NIS (1.8)
NIS (1.8)
NIS (1.8)
NIS (1.8)
NIS (1.8)
I2 (1.8)
TFE
15 min
15 min
10 min
10 min
30 min
20 min
30 min
10 min
25 min
15 min
20 min
30 min
25 min
40 min
1 h
81
91
98
81
85
86
40
56
61
85
61
80
50
50
--b
--b
2
TFE
3
TFE
4
ACN
5
DCE
6
DCM
THF
7
8
DMF
9
EtOAc
EtOH
Acetone
1,4-Dioxane
MeNO2
TFE
10
11
12
13
14
15
16
TBAI (1.8) a
TEAI (1.8) c
TFE
TFE
1 h
Figure 2. Easing the dehydrogenative C(sp2)-H amidation reaction. a) Zeng’s
Pd-catalyzed intramolecular amidation in presence of PIDA oxidant.[34] b) The
iodine(III) mediated Pd-free approach.[29] c) Work on amidation using mild
oxidant NIS.
aTetrabutyl ammonium iodide. bNo Reaction. c Tetraethyl ammonium iodide.
During optimization of the reaction condition, N-(2-((2-
bromobenzylidene)amino)phenyl)-4-methylbenzenesulfonamide
(1a)[34] was used as model substrate. The product 2-(2-
bromophenyl)-1-tosyl-benzo[d]imidazole (2a) was isolated in 98%
yield when 1.8 equiv of NIS was used in solvent 2,2,2-
trifluoroethanol (TFE) at room temperature (Table 1, entry 3).
None of the non-fluorinated solvents such as ACN (acetonitrile),
DCM (dichloromethane), DCE (1,2-dichloroethane), THF
(tetrahydrofuran), DMF (N,N-dimethylformamide), ethyl acetate,
EtOH (ethanol), acetone, 1,4-dioxane, nitromethane, etc. led to
better result compared to TFE (Table 1, entries 5-13). Using TFE,
in absence of any base and within 40 min, 50% yield of the
product was obtained using molecular iodine (Table 1, entry 14).
The attempts to use of (tetra)alkyl ammonium iodides as reagent
were also in vain (Table 1, entries 15-16). Use of 1.8 equiv of NIS
as oxidant was standardized as the optimum (Table 1, entry 3).
In the Zeng’s Pd-catalyzed intramolecular amidation in presence
of PIDA oxidant, toluene was used as the solvent and the reaction
was continued for 16 h (Figure 2a).[34] Interestingly, similar
reaction could be performed in absence of any Pd-metal catalyst
and using PIDA or under any base free[35] condition. The reaction
time was dramatically reduced to < 30 min upon changing to the
fluorinated solvent TFE at room temperature (Figure 2b).[29] We
have recently reported that reactions using hypervalent iodine
regents could be performed to its best in fluorinated solvents.[28]
Various coupling reactions are known using I+ as the reagent.[36]
However, in this work the formation of N…I+…π intermediate
might be crucial to bring the imine double bond and nitrogen
center for the oxidative coupling.[26b, 37] As a result the reaction
was done at mild condition (Figure 3c). Hence, this C-N coupling
reaction of non-prefunctionalized C-H and N-H bonds anticipated
to be worked under metal-free, base-free and mild condition.
Operational simplicity, open atmosphere reaction and excellent
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800688
European Journal of Organic Chemistry
FULL PAPER
Using the optimized reaction condition, substrates scope for
this C-H amination protocol was explored for the synthesis of 1,2-
disubstituted benzimidazoles (Figure 3). N-Tosyl substituted
benzimidazoles containing differently substituted aryl group at 2-
position were isolated in excellent yield within relatively shorter
reaction time (ca. 10 min). Multi-substituted benzimidazole
derivatives bearing electron withdrawing halogen groups (2a-f), -
NO2 (2j-k), -CN (2i) groups on aryl rings were isolated in excellent
yields. Likewise, electron donating alkyl (2g-h) or alkoxy (2f)
groups containing benzimidazole products were also synthesized
with high efficiency. Synthesis of benzimidazole derivatives with
fused aromatics such as anthracenyl (2l), pyrenyl (2m) and
heteroaromatic (2n) at 2-position were also found to be successful.
Cyclohexyl substituted benzimidazole derivative (2o) was isolated
with 96% yield. The structure of compound 2h was confirmed by
X-ray crystallographic analysis (Figure 3).
Figure 4. Functional group tolerance in the synthesis of benzimidazole.
Figure 5. Scope of C-H amination reaction. The benzimidazoles a) core-
modified and b) with different protecting groups.
Figure 3. Scope of C-H amidation reaction.
Benzene core substituted benzimidazoles (Figure 5a) were also
efficiently synthesized with substituents like -Cl, -Me, -NO2, -
COOH, etc. The products with electron donating methyl
substituents (2ab-ac) were isolated in better yields than with
electron withdrawing groups (2aa, 2ad-af). Also, benzimidazoles
were synthesized with different N-protecting groups. In addition to
Benzimidazoles having different functional groups like hydroxy,
carbonyl, olefin, alkyne, etc. were also efficiently synthesized
(Figure 4). The yields of the reactions were also found to be good.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800688
European Journal of Organic Chemistry
FULL PAPER
tosyl (Ts) groups, other protecting groups like methane sulfonyl,
benzene sulfonyl and benzoyl groups were also explored towards
1,2-disubstituted benzimidazole synthesis (Figure 5b). Notably,
products with carbonyl protecting groups were isolated in
relatively lower yields (2bd-be) than sulfonyl protecting groups
(2ba-bc).
condition (Figure 7b) did not affect the yield of the reaction. The
kinetic isotopic effect[39] was found to be as kH/kD = 1.45. This
indicate that the C(sp2)-H is actively participating during the
reaction.
Figure 6. a) One pot synthesis approach. b) N-H Benzimidazole synthesis.
Figure 8. a) Plausible mechanism and b) Neutralization of by-product HI.
Based on the control experiments and our previous work,[32]
a
Synthesis of N-substituted benzimidazole could also be achieved
in one-pot approach without going via imine substrate.
Condensation of equimolecular amounts of amine and aldehyde
under reflux in ethanol and followed by treatment with NIS at room
temperature, the benzimidazole 2a could be isolated in good yield
(Figure 7a). For further synthetic utility, the deprotection of the
tosyl (-Ts) from 2a could successfully be done using 5 M NaOH
under refluxing ethanol condition (Figure 6b)[38] and the
corresponding N-H benzimidazole product 2-(2-bromophenyl)-
1H-benzo[d]imidazole(2a') was isolated in 73% yield.
plausible mechanistic pathway for the transformation is shown in
Figure 8a. Iodide center of NIS being electrophilic in nature, is
expected to interact with the electron rich imine bond and N-
center of –NH simultaneously to create an intermediate 3 and lead
to subsequent formation of bridged iodonium intermediate 4.
Following, the C–N bond formation with the generation of another
intermediate 5 was expected. Anion generated from succinimide
would help the abstraction of proton to form 6 and followed by HI
elimination to drive the aromatization of product 2.
One of the by-product of the reaction is hydroiodic acid (HI),
which bear capacity to protonate the N-center of amide group and
the nucleophilicity of N-center would be diminished. Requirement
of excess amount of NIS for the transformation might be justified
by the need of neutralization of by-product HI with the help of
succinimide. Isolation of succinimide was possible using 3:2
(hexane: ethyl acetate) mixture as eluent by column
chromatography during detection of polar compound 2-(2-
nitrophenyl)-1-tosyl-1H-benzo[d]imidazole-6-carboxylic acid (2af,
Figure 5a). Iodine was liberated during the evaporation to dryness
of reaction mixture which proves HI may react with excess NIS
(Figure 8b). Also from 1H NMR spectra of separate reaction
mixtures of deuterated aldimine (1p’) and aldimine (1p), it has
been confirmed that the proton of succinimide comes from NH
proton but not from C (sp2)-H proton of aldimine (see supporting
information).
The role of the use of fluorinated solvent[33, 40] TFE can be
rationalized as follows. Kita and co-workers have successfully
shown that hypervalent iodine reagents when mixed with
fluorinated solvent like hexafluoroisopropanol (HFIP), the radical
cationic intermediate get stabilized due to the high polarity and
low‑nucleophilic nature of the solvent.[40d] Recently, Donohoe and
Compton with co-workers have also demonstrated the role of
HFIP towards activation of the hypervalent iodine reagents.[41]
Similarly trifluoroethanol is also established as one of the potential
fluorinated solvents to stabilize cationic or cation-radical species
Figure 7. Control experiments. a) TEMPO radical experiment. b) Reaction
under dark condition. c) Kinetic isotope effect experiment.
We have shown the control experiments in Figure 7. TEMPO
radical experiment (Figure 7a) and the reactions under dark
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800688
European Journal of Organic Chemistry
FULL PAPER
Kinetic Isotopic Effect (KIE) Experiment.[39] The kinetic isotopic study
shown in Figure 7c, were performed by following the general procedure of
the preparation of N-substituted benzimidazoles. The reaction was done
using equimolar amount of aldimine (1p) and deuterated aldimine (1p’) in
presence of 1.8 equiv NIS in TFE. After that, the reaction mixture was
evaporated to dryness and crude mixture was passed through a short-pad
silica gel column using 9:1 hexane: ethyl acetate mixture as eluent. The
1H NMR spectra of the mixture was recorded for whole sample in CD3Cl
for the determination of kH/kD (Fig. S71, supporting information)
40c, 40e]
generated using iodine regents.[40b,
Therefore we
anticipated that TFE promoted the reaction by stabilizing
intermediate 4 and 5 (Figure 8a).
Conclusions
In conclusion, the above demonstrated chemical reaction system
and the proposed mechanism may suggest an efficient pathway
towards developing designed functional molecules using multiple
weak interactions. Therefore, by choosing appropriate reaction
conditions many difficult reactions can be performed easily.
During the C(sp2)-H amination reaction using N-iodosuccinimide
1,2-disubstituted benzimidazole were synthesized easily. Thus
we could develop a reaction by an operationally simple, metal,
additive and base free methodology. Overall, a library of 1,2-
disubstituted benzimidazoles were accessed from easily
affordable starting materials. We anticipate that this method will
be highly desirable in pharmaceutical chemistry and drug
discovery efforts.
2-(2-Bromophenyl)-1-tosyl-benzo[d]imidazole (2a)[29]: 58.5 mg; Yield:
98%; Rf = 0.5 (hexane:ethyl acetate 4:1); white solid; 1H NMR (400 MHz,
CDCl3): δ 8.17 (d, J = 8 Hz, 1H), 7.8 (d, J = 8 Hz, 1H), 7.66 (d, J = 8 Hz,
1H), 7.54 (d, J = 8 Hz, 2H), 7.48–7.39 (m, 5H), 7.19 (d, J = 8 Hz, 2H), 2.36
(s, 3H); 13C NMR (100 MHz, CDCl3): δ 150.7, 146.1, 142.2, 135.1, 132.8,
132.6, 132.4, 132.0, 131.7, 129.9, 127.5, 126.5, 125.8, 125.1, 124.7, 120.8,
114.2, 21.7.
2-(4-Bromophenyl)-1-tosyl-benzo[d]imidazole (2b): 55 mg; Yield: 93%;
Rf = 0.5 (hexane: ethyl acetate 4:1); white solid; mp 135-136 oC; 1H NMR
(400 MHz, CDCl3): δ 8.19 (d, J = 8 Hz, 1H), 7.10 (d, J = 8 Hz, 1H), 7.61 (d,
J = 8, 2H), 7.50 (d, J = 8, 2H), 7.41 (m, 2H), 7.33 (d, J = 8, 2H), 7.11 (d,
2H), 2.32 (s, 3H); 13C NMR (175 MHz, CDCl3): δ 153.1, 146.0, 142.7, 134.9,
133.9, 132.5, 131.1, 129.9, 129.1, 127.0, 125.8, 125.6, 125.5, 120.5, 115.3,
~
121.7; IR (KBr): 
= 2921, 1562, 1480, 1450, 1377, 12 50, 1189, 1177,
1072, 1057 cm-1; HR-MS (ESI-TOF): m/z = 427.0114, calculated for
C20H15BrN2O2S (M+H+): 427.0110.
Experimental Section
Instrumentation and Chemicals. All the reactions were performed under
open atmosphere and isolated yields after column chromatography are
presented. For NMR spectra the chemical shift values are given in parts
per million (ppm) with respect to residual chloroform (7.26 ppm for 1H and
77.16 for 13C) (in case of DMSO-d6: 2.5 ppm for 1H and 39.5 for 13C). The
peak patterns are indicated as follows: chemical shift in ppm (δ),
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, brs = broad
singlet, m = multiplet). The coupling constants (J) are reported in hertz (Hz).
High-resolution mass spectra (HRMS) were obtained on an ESI-TOF (time
of flight) mass spectrometer. FT-IR spectra were recorded in wave number
(cm-1) after making thin layer of the compounds on the surface of NaCl
crystal using dichloromethane. Melting points of the compounds were
measured using a digital melting point apparatus and are uncorrected.
Thin-layer chromatography (TLC) was done on Merck Silica Gel F254
plates (0.25 mm).
2-(3-Bromophenyl)-1-tosyl-benzo[d]imidazole (2c): 62 mg; Yield: 70%;
Rf = 0.5 (hexane :ethyl acetate 4:1); white semi-solid; 1H NMR (700 MHz,
CDCl3): δ 8.20 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 7.7 Hz, 1H), 7.66 (d, J = 7.7
Hz, 1H), 7.60 (s, 2H), 7.45 (t, J = 7.7 Hz, 1H), 7.40 (t, J = 7.7 Hz, 1H), 7.35
(d, J = 7.7 Hz, 3H), 7.13 (d, J = 8.4 Hz, 2H), 2.34 (s, 3H); 13C NMR (175
MHz, CDCl3): δ 152.2, 146.1, 142.5, 135.0, 133.9, 133.5, 133.4, 132.0,
130.0, 129.7, 129.3, 127.1, 125.8, 125.5, 121.7, 120.3, 115.2, 21.8; IR
~
(KBr): 
= 2924, 2108, 1640, 1536, 1448, 1381, 1253, 1177, 1084, 1012
cm-1; HR-MS (ESI-TOF): m/z = 427.0106, calculated for C20H15BrN2O2S
(M+H+): 427.0110.
2-(4-Fluorophenyl)-1-tosyl-benzo[d]imidazole (2d)[29]: 32 mg; Yield:
90%; Rf = 0.5 (hexane :ethyl acetate 4:1); white solid; 1H NMR (400 MHz,
CDCl3): δ 8.20 (d, J = 8 Hz, 1H), 7.71 (d, J = 8 Hz, 1H), 7.62 (dd, J1 = 8
Hz, J2 = 4 Hz, 2H), 7.46–7.37 (m, 2H), 7.31 (d, J = 8 Hz, 2H), 7.18–7.10
1
(m, 4H), 2.33 (s, 3H); 13C NMR (175 MHz, CDCl3): δ 164.3 (d, JC, F
=
All starting materials (N-substituted imine 1) were prepared by following
literature report.[34]
249.9 Hz), 153.2, 146.0, 142.6, 135.0, 134.0, 131.7 (d,3JC,F = 8. Hz), 129.9,
127.0, 126.1 (d, 4JC, F = 3.5 Hz), 125.7, 125.6, 120.5, 115.3, 115.1 (d, 2JC,
F =21.7 Hz), 21.7.
General Procedure for Preparation of N-Substituted Benzimidazoles.
NIS (0.251 mmol, 1.8 equiv) was added to a stirred solution of N-
substituted imine 1 (0.139 mmol, 1 equiv) in TFE (2,2,2-trifluoroethanol) at
room temperature. The progress of the reaction was monitored by thin
layer chromatography (TLC) using appropriate mixture of ethyl acetate and
hexane as eluent. Upon completion of the reaction, solvent was completely
evaporated to dryness. Then the crude reaction mixture was purified by
silica gel column chromatography using n-hexane and ethyl acetate as
eluent.
2-(4-Chlorophenyl)-1-tosyl-benzo[d]imidazole (2e)[35]: 76 mg; Yield:
1
95%; Rf = 0.5 (hexane:ethyl acetate 4:1); white solid; H NMR (700 MHz,
CDCl3): δ 8.19 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 7.7 Hz, 1H), 7.58 (d, J = 8.4
Hz, 2H), 7.48 – 7.42 (m, 3H), 7.40 (t, J = 7.7 Hz, 1H), 7.33 (d, J = 8.4 Hz,
2H), 7.11 (d, J = 7.7 Hz, 2H), 2.33 (s, 3H); 13C NMR (175 MHz, CDCl3): δ
153.1, 146.1, 142.7, 137.1, 135.0, 134.0, 132.3, 130.0, 128.6, 128.2, 127.0,
125.8, 125.6 120.6, 115.3, 21.8.
2-(3-Bromo-4-methoxyphenyl)-1-tosyl-benzo[d]imidazole (2f)[29]
: 53
Procedure
benzo[d]imidazole (2a). NIS (57 mg, 0.251 mmol) was added to a stirred
solution of N-(2-((2-bromobenzylidene)amino)phenyl)-4-
methylbenzenesulfonamide 1a (60 mg, 0.139 mmol) in TFE (0.5 mL) at
room temperature. Upon completion (ca. 10 min) of the reaction, TFE was
completely evaporated to dryness. The crude mixture was purified by silica
gel column chromatography using n-hexane and ethyl acetate (92:8) as
eluent to 2-(2-bromophenyl)-1-tosyl-benzo[d]imidazole 2a (58.5 mg, 0.137
mmol, yield: 98%).
for
Preparation
of
2-(2-Bromophenyl)-1-tosyl-
mg; Yield: 89%; Rf = 0.4 (hexane:ethyl acetate 4:1); white solid; 1H NMR
(400 MHz, CDCl3): δ 8.18 (d, J = 8 Hz, 1H), 7.70 (d, J = 8 Hz, 1H), 7.66–
7.64 (m, 2H), 7.44–7.37 (m, 2H), 7.34 (d, J = 8 Hz, 2H), 7.12 (d, J = 8 Hz,
2H), 6.99 (d, J = 8 Hz, 1H), 4.00 (s, 3H), 2.34 (s, 3H); 13C NMR (175 MHz,
CDCl3): δ 157.8, 152.6, 146.0, 142.6, 135.4, 135.0, 134.0, 131.9, 129.9,
127.0, 125.6, 125.5, 123.5, 120.4, 115.3, 110.9, 110.8, 56.5, 21.8.
2-(Ortho-Tolyl)-1-tosyl-benzo[d]imidazole (2g)[29]: 25 mg; Yield: 80%;
Rf = 0.5 (hexane:ethyl acetate 4:1); white solid; 1H NMR (400 MHz, CDCl3):
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800688
European Journal of Organic Chemistry
FULL PAPER
δ 8.27 (d, J = 8 Hz, 1H), 7.79 (d, J= 8 Hz, 1H), 7.50–7.44 (m, 5H), 7.31–
7.28 (m, 2H), 7.22–7.18 (m, 3H), 2.40 (s, 3H), 2.09 (s, 3H); 13C NMR (175
MHz, CDCl3): δ 152.5, 146.0, 142.3, 139.1, 135.4, 133.3, 130.8, 130.5,
130.3, 129.9, 129.8, 127.5, 125.5, 125.0, 124.9, 120.5, 114.5, 21.8, 20.0.
2-Cyclohexyl-1-tosyl-benzo[d]imidazole (2o)[29]: 65 mg; Yield: 96%; Rf
= 0.5 (hexane: ethyl acetate 4:1); white solid; 1H NMR (400 MHz, CDCl3):
δ 8.05–8.03 (m, 1H), 7.75 (d, J = 8 Hz, 2H), 7.68–7.66 (m, 1H), 7.35–7.30
(m, 2H), 7.27 (d, J = 8 Hz, 2H), 3.52–3.45 (m, 1H), 2.38 (s, 3H), 1.93–1.84
(m, 4H), 1.75–1.66 (m, 3H), 1.43–1.30 (m, 3H); 13C NMR (100 MHz,
CDCl3) : δ 159.8, 145.9, 142.1, 136.1, 133.0, 130.3, 126.7, 124.8, 124.7,
119.9, 114.1, 38.3, 32.7, 26.4, 25.9, 21.8.
2-(4-Isopropylphenyl)-1-tosyl-benzo[d]imidazole (2h)[29]
:
(CCDC:
1569701); 48 mg; Yield: 95%; Rf = 0.5 (hexane:ethyl acetate 4:1); white
solid; 1H NMR (400 MHz, CDCl3): δ 8.19 (d, J = 8 Hz, 1H), 7.71 (d, J = 8
Hz, 1H), 7.53 (d, J = 8 Hz, 2H), 7.42–7.29 (m, 6H), 7.07 (d, J = 8 Hz, 2H),
3.01 (sept, J = 8 Hz, 1H), 2.32(s, 3H), 1.32 (d, J = 8 Hz, 6H); 13C NMR
(100 MHz, CDCl3): δ 154.5, 151.8, 145.7, 142.8, 135.1, 134.1, 131.0,
129.8, 127.5,127.2, 125.9, 125.4, 125.3, 120.4, 115.3, 34.3, 24.0, 21.7.
2-Phenyl-1-tosyl-1H-benzo[d]imidazole (2p)[35]: 57 mg; Yield: 96 %; Rf
= 0.4 (hexane:ethyl acetate 4:1): white solid, 1H NMR (400 MHz, CDCl3) δ
8.21 (d, J = 8 Hz, 1H), 7.73 (d, J = 8 Hz, 1H), 7.62 (d, J = 8 Hz, 2H), 7.55
(t, J = 8 Hz, 1H), 7.50 – 7.36 (m, 4H), 7.33 (d, J = 8.0 Hz, 2H), 7.08 (d, J =
8 Hz, 2H), 2.30 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 154.1, 145.8, 142.7,
135.0, 133.9, 130.9, 130.6, 130.1, 129.8, 127.7, 127.0, 125.5, 125.4, 120.5,
115.2, 21.7.
4-(1-Tosyl-benzo[d]imidazol-2-yl)benzonitrile (2i)[29]
: 45 mg; Yield:
1
75%; Rf = 0.4 (hexane:ethyl acetate 4:1); white solid; H NMR (400 MHz,
CDCl3): δ 8.18 (d, J = 8 Hz, 1H), 7.77–7.73 (m, 5H), 7.50–7.44 (m, 2H),
7.34 (d, J = 8 Hz, 2H), 7.13 (d, J = 8 Hz, 2H), 2.34 (s, 3H); 13C NMR (175
MHz, CDCl3): δ 152.0, 146.4, 142.7, 134.8, 134.7,133.9, 131.7, 131.5,
130.1, 126.9, 126.3, 125.9, 120.8, 118.3, 115.2, 114.3, 21.8.
1-(4-(1-Tosyl-1H-benzo[d]imidazol-2-yl)phenyl)ethanone (2q) : 40 mg;
Yield: 72 %; Rf = 4.5 (hexane:ethyl acetate 4:1); white solid; mp 164-165
0C; 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 8.0
Hz, 2H), 7.81 – 7.68 (m, 3H), 7.48-7.39 (m, 2H), 7.35 (d, J = 8.0 Hz, 2H),
7.12 (d, J = 8.0 Hz, 2H), 2.69 (s, 3H), 2.33 (s, 3H). 13C NMR (100 MHz,
2-(2-Nitrophenyl)-1-tosyl-benzo[d]imidazole (2j): 68 mg; Yield: 85%, Rf
= 0.3 (hexane:ethyl acetate 4:1); Yellow solid, mp 80-81 oC ; 1H NMR (700
MHz, CDCl3): δ 8.32 (d, J = 8.4 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 7.76 (d,
J = 7.7 Hz, 3H), 7.54 – 7.45 (m, 4H), 7.42 (t, J = 7.7 Hz, 1H), 7.19 (d, J =
8.4 Hz, 2H), 2.36 (s, 3H); 13C NMR (175 MHz, CDCl3): δ 148.9, 148.5,
CDCl3) δ 197.7, 153.0, 146.1, 142.8, 138.4, 134.9, 134.7, 133.9, 131.3,
130.0, 127.7, 127.0, 126.0, 125.7, 120.8, 115.3, 26.9, 21.8. ; IR (KBr): 
= 2063, 1645, 1380, 1256, 1174, 1080 cm-1; HR-MS (ESI-TOF): m/z =
391.1112, calculated for C22H18N2O3S (M+H+): 391.1111.
146.4, 142.4, 134.9, 133.2, 133.1, 132.9, 131.6, 130.1, 127.4, 126.3, 126.0,
~
125.2, 124.8, 120.8, 114.0, 21.8; IR (KBr): 
= 2924, 1638, 1531, 1448,
1347, 1253, 1176, 1087, 1013 cm-1; HR-MS (ESI-TOF): m/z = 394.0855,
calculated for C20H15N3O4S (M+H+): 394.0856.
4-(1-Tosyl-1H-benzo[d]imidazol-2-yl)phenol (2r)[35]: 48 mg; Yield: 80 %;
Rf = 0.4 (hexane:ethyl acetate 7:3); light brown solid; 1H NMR (400 MHz,
CDCl3) δ 9.00 (s, 1H), 8.22 (d, J = 8 Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.44
– 7.40 (m, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8 Hz, 2H ), 7.08 (d, J
= 8 Hz, 2H), 6.71 (d, J = 8.0 Hz, 2H), 2.29 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 159.4, 154.9, 145.9, 145.8, 141.8, 134.9, 133.8, 132.7, 129.8,
127.2, 125.6, 120.5, 119.8, 115.5, 115.2, 21.7. HR-MS (ESI-TOF): m/z =
365.0984, calculated for C20H16N2O3S (M+H+): 365.0954.
2-(4-Nitrophenyl)-1-tosyl-benzo[d]imidazole (2k)[35]
: 65 mg; Yield:
82%; Rf = 0.4 (hexane:ethyl acetate 4:1): Yellow solid, 1H NMR (700 MHz,
CDCl3) δ 8.34 (d, J = 7.7 Hz, 2H), 8.20 (d, J = 7.7 Hz, 1H), 7.85 (d, J = 7.7
Hz, 2H), 7.75 (d, J = 7.7 Hz, 1H), 7.50−7.43 (m, 2H), 7.35 (d, J = 6.3 Hz,
2H), 7.15 (d, J = 6.3 Hz, 2H), 2.35 (s, 3H); 13C NMR (175 MHz, CDCl3): δ
151.7, 149.0, 146.4, 142.7, 136.5, 134.8, 133.9, 132.1, 130.1, 126.9, 126.4,
125.9, 122.9, 120.9, 115.3, 21.8.
(E)-2-(4-styrylphenyl)-1-tosyl-1H-benzo[d]imidazole (2s): 54 mg; Yield:
90%; Rf = 0.5 (hexane:ethyl acetate 9:1); white solid; mp 170 – 172 0C; 1H
NMR (400 MHz, CDCl3) δ 8.22 (d, J = 7.6 Hz, 1H), 7.73 (d, J = 7.2 Hz, 1H),
7.66 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 7.6 Hz, 2H),
7.47 – 7.41 (m, 2H), 7.41 – 7.27 (m, 5H), 7.26 (d, J = 8 Hz, 1H), 7.19 (d, J
= 16.4 Hz, 1H), 7.10 (d, J = 8.2 Hz, 2H), 2.32 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 154.2, 145.8, 142.9, 139.7, 137.1, 135.1, 134.1, 131.4, 130.6,
2-(Anthracen-9-yl)-1-tosyl-benzo[d]imidazole (2l)[29]
: 54 mg; Yield:
91%; Rf = 0.45 (hexane:ethyl acetate 4:1); yellow solid; 1H NMR (400 MHz,
CDCl3): δ 8.63 (s, 1H), 8.36 (d, J = 8 Hz, 1H), 8.05 (d, J = 8 Hz, 2H), 7.89
(d, J = 8 Hz, 1H), 7.56–7.50 (m, 2H), 7.44-7.40 (m, 2H), 7.23–7.17 (m, 4H),
6.97 (d, J = 8 Hz, 2H), 6.77 (d, J = 8 Hz, 2H), 2.22 (s, 3H); 13C NMR (175
MHz, CDCl3): δ 150.3, 145.6, 142.6, 134.4, 133.6, 131.9, 130.9, 130.4,
130.1, 129.5, 128.5, 127.5, 127.2, 126.6, 125.8, 125.7, 125.3, 125.0, 123.6,
120.8, 114.5, 21.7.
129.83, 129.0, 128.9, 128.2, 127.9, 127.1, 126.9, 125.8, 125.6, 125.5,

120.5, 115.4, 21.7. IR (KBr):
1072 cm-1; HR-MS (ESI-TOF): m/z
C28H22N2O2S (M+H+): 451.1475.
= 2081, 1629, 1378, 1187, 1172, 1117
= 451.1471, calculated for
2-(4-(Phenylethynyl)phenyl)-1-tosyl-1H-benzo[d]imidazole (2t)[42]: 48
mg; Yield: 81 %; Rf = 0.5 (hexane:ethyl acetate 9:1); white solid; 1H NMR
(400 MHz, CDCl3) δ 8.22 (d, J = 8 Hz, 1H), 7.74 (d, J = 7.2 Hz, 1H), 7.64
(m, 4H), 7.59 (dd, J 1 = 7.6, J 2 = 4 Hz, 2H), 7.51 – 7.41 (m, 2H), 7.41 –
7.32 (m, 5H), 7.11 (d, J = 8.4 Hz, 2H), 2.32 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 153.6 145.9, 142.8, 135.0, 134.1, 131.8, 131.0, 130.9, 129.9,
129.7, 128.8, 128.6, 127.0, 125.7, 125.5, 123.0, 120.5, 115.4, 91.7, 88.9,
21.7. HR-MS (ESI-TOF): m/z = 449.1333, calculated for C28H20N2O2S
(M+H+): 449.1318
2-(Pyren-1-yl)-1-tosyl-benzo[d]imidazole (2m)[29]: 42 mg; Yield: 81%;
Rf = 0.45 (hexane:ethyl acetate 4:1); white solid; 1H NMR (400 MHz,
CDCl3): δ 8.36 (d, J = 8 Hz, 1H), 8.26 (d, J = 8 Hz, 2H), 8.20–8.13 (m, 4H),
8.04 (t, J = 8 Hz, 1H), 7.90 (d, J = 8 Hz, 1H), 7.82 (d, J = 9.2 Hz, 1H), 7.57–
7.49 (m, 3H), 7.08 (d, J = 8.4 Hz, 2H), 6.65 (d, J = 8.4 Hz, 2H), 1.98 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 152.1, 145.7, 142.6, 134.8, 133.8,
132.8, 131.2, 131.0, 130.6, 129.4, 129.3, 129.0, 128.4, 127.4, 127.2, 126.4,
126.0, 125.8, 125.7, 125.2, 124.4, 124.29, 124.26, 124.1, 123.6, 120.7,
114.9, 21.3.
2-(4-Bromophenyl)-5,6-dichloro-1-tosyl-benzo[d]imidazole (2aa)[29]
:
2-Chloro-6-methoxy-3-(1-tosyl-benzo[d]imidazol-2-yl)-quinolone
(2n)[29]: 57 mg; Yield: 95%; Rf = 0.4 (hexane:ethyl acetate 3:1); white solid;
1H NMR (700 MHz, CDCl3): δ 8.17 (s, 2H), 8.02 (d, J = 9.1 Hz, 1H), 7.82
(d, J = 8.4 Hz, 1H), 7.51-7.45 (m, 5H), 7.19 (d, J = 7.7 Hz, 2H), 7.12 (s,
1H), 3.96 (s, 3H), 2.37 (s, 3H) ; 13C NMR (175 MHz, CDCl3): δ 158.8, 148.2,
146.7, 146.4, 144.2, 142.3, 140.5, 134.9, 133.0, 130.2, 130.1 127.4, 126.9,
126.2, 125.3, 124.8, 124.3, 121.0, 114.3, 105.6, 55.9, 21.8.
57 mg; Yield: 95%; Rf = 0.7 (hexane:ethyl acetate 4:1); white solid; 1H NMR
(400 MHz, CDCl3) δ 8.33 (s, 1H), 7.79 (s, 1H), 7.62 (d, J = 8 Hz, 2H), 7.47
(d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8 Hz, 2H), 2.20
(s, 3H); 13C NMR (175, MHz, CDCl3): δ 154.8, 146.7, 142.0, 134.5, 133.1,
132.5, 131.3, 130.2, 130.00, 129.9, 128.2, 127.1, 126.1, 121.7, 116.8, 21.6.
2-(2-Bromo-5-fluorophenyl)-5,6-dimethyl-1-tosyl-benzo[d]imidazole
(2ab)[29]: 59 mg; Yield: 98%; Rf = 0.5 (hexane:ethyl acetate 4:1); white
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800688
European Journal of Organic Chemistry
FULL PAPER
solid; 1H NMR (400 MHz, CDCl3): δ 7.92 (s, 1H), 7.63 – 7.58 (m, 1H), 7.56
(s, 1H), 7.54 (d, J = 4.0 Hz, 2H), 7.22 (d, J = 8 Hz, 2H), 7.16 – 7.10 (m,
1448, 1382, 1311, 1253, 1187, 1125, 1187, 1079, 1018 cm-1; HR-MS (ESI-
TOF): m/z = 353.0767, calculated for C19H13FN2O2S (M+H+): 353.0755.
1H), 7.07 (dd, J = 8.4, J2 = 3.2 Hz, 1H), 2.46 (s, 3H), 2.38 (s, 6H); 13C
1
NMR (175 MHz, CDCl3): δ 160.5 (d, 1JC, F = 247.1 Hz), 148.6, 146.3, 140.4,
2-Phenyl-1-(phenylsulfonyl)-benzo[d]imidazole (2bc)[35]: 72 mg; Yield:
3
3
1
135.7, 135.2, 134.6, 134.0 (d, JC, F = 8.0 Hz), 133.6 (d, JC, F = 8.4 Hz),
131.2, 130.1, 127.5, 120.9, 119.9 (d, 2JC,F = 23.6 Hz), 119.5 (d, 4JC,F = 3.0
Hz), 119.1 (d, 2JC,F =21.7 Hz), 114.4, 21.9, 21.0, 20.3.
92%; Rf = 0.5 (hexane:ethyl acetate 4:1); white solid; H NMR (400 MHz,
CDCl3): δ 8.22 (d, J = 8 Hz, 1H), 7.73 (d, J = 8 Hz, 1H), 7.59 (d, J = 8 Hz,
2H), 7.53 (m , 1H), 7.50 – 7.45 (m, 2H), 7.50 – 7.39 (m, 5H), 7.28 (t, J = 8
Hz, 2H); 13C NMR (175 MHz, CDCl3): δ 154.0, 142.6, 137.9, 134.5, 133.9,
130.9, 130.6, 129.9, 129.2, 127.7, 126.9, 125.6, 125.4, 120.5, 115.2.
2-(3-Bromo-4-methoxyphenyl)-5,6-dimethyl-1-tosyl-
benzo[d]imidazole (2ac): 59 mg; Yield: 97 %; Rf = 0.4 (hexane: ethyl
acetate 4:1), white solid; mp 140-141 oC; 1H NMR (400 MHz, CDCl3): δ
7.95 (s, 1H), 7.68 – 7.56 (m, 2H), 7.46 (s, 1H), 7.31 (d, J = 8.4 Hz, 2H),
7.12 (d, J = 8 Hz, 2H), 6.98 (d, J = 9.2 Hz, 1H), 4.00 (s, 3H), 2.45 (s, 3H),
2.36 (s, 3H), 2.34 (s, 2H); 13C NMR (175 MHz, CDCl3) δ 157.6, 151.8,
2-(Ortho-Tolyl)-1-benzoyl-benzo[d]imidazole (2bd): 25 mg; Yield: 65%;
Rf = 0.5 (hexane:ethyl acetate 4:1); yellow semi-solid; 1H NMR (700 MHz,
CDCl3): δ 7.88 (d, J = 8.4 Hz, 1H), 7.61 (d, J = 7.7 Hz, 2H), 7.50 (d, J = 8.4
Hz, 1H), 7.47 (t, J = 7.7 Hz, 1H), 7.40 (t, J = 7.7 Hz, 1H), 7.31 (dt, J1 = 21.0,
J2 = 7.7 Hz, 4H), 7.17 (t, J = 7.7 Hz, 1H), 7.07-7.10 (m, 2H), 2.37 (s, 3H).
13C NMR (175 MHz, CDCl3): δ 168.8, 153.6, 142.9, 137.1, 134.1, 133.6,
145.8, 135.4, 135.2, 135.1, 134.7, 132.4, 131.9, 130.4, 129.8, 127.0, 123.6,
~
120.4, 115.5, 110.9, 110.8, 56.5, 21.8, 20.9, 20.3; IR (KBr): 
= 2920,
1847, 1629, 1487, 1377, 1269, 1175, 1081, 1019 cm-1; HR-MS (ESI-TOF):
m/z = 485.0534, calculated for C23H21BrN2O3S (M+H+): 485.0529.
133.3, 130.8, 130.5, 130.5, 130.1, 129.8, 128.5, 125.6, 124.8, 124.6, 120.3,
~
113.7, 20.2; IR (KBr): 
= 2107, 1641, 1311, 1259, 1223, 1146, 1101,
1073 cm-1; HR-MS (ESI-TOF): m/z
C21H16BrN2O (M+H+): 313.1335.
= 313.1308, calculated for
2-(2-Bromophenyl)-6-nitro-1-tosyl-benzo[d]imidazole (2ad): 42 mg;
Yield: 90%; Rf = 0.4 (hexane:ethyl acetate 4:1); white solid; mp 150-152
oC; 1H NMR (700 MHz, CDCl3): δ 9.10 (s, 1H), 8.36 (dd, J = 8.4 Hz, 1H),
7.88 (d, J = 9.1 Hz, 1H), 7.67 (d, J = 7.7 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H),
7.49 – 7.42 (m, 3H), 7.30 – 7.19 (m, 2H), 2.40 (s, 3H); 13C NMR (175 MHz,
2-(2-Bromophenyl)-1-benzoyl-benzo[d]imidazole (2be): 16 mg; Yield:
40%; Rf = 0.6 (hexane:ethyl acetate 4:1); semi-solid; 1H NMR (700 MHz,
CDCl3): δ 7.90 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 7.7 Hz, 2H), 7.59 (d, J = 7.7
Hz, 1H), 7.51 (t, J = 7.7 Hz, 1H), 7.45 – 7.38 (m, 3H), 7.35 (d, J = 8.4 Hz,
4H), 7.19 (t, J = 7.7 Hz, 1H); 13C NMR (175 MHz, CDCl3): δ 168.2, 152.2,
CDCl3): δ 155.1, 147.1, 146.2, 145.7, 134.3, 132.8, 132.5, 132.4, 132.3,
~
131.0, 130.4, 128.0, 126.8, 124.5, 121.2, 120.7, 111.2, 22.0; IR (KBr): 
= 2097, 1641, 1595, 1523, 1461, 1385, 1271, 1176, 1086, 1012; HR-MS
(ESI-TOF): m/z = 471.9937, calculated for C20H14BrN3O4S (M+H+):
471.9961.
142.3, 133.9, 133.8, 132.9, 132.8, 132.6, 131.4, 130.7, 128.5, 127.5, 125.4,
~
124.9, 123.0, 120.6, 114.1; IR (KBr): 
= 2093.07, 1642, 1448, 1310,
1225, 1147 cm-1; HR-MS (ESI-TOF): m/z = 377.0271, calculated for
C20H13BrN2O (M+H+): 377.0284.
2-(4-Ethylphenyl)-5, 6-dichloro-1-tosyl-benzo[d]imidazole (2ae): 51
mg; Yield: 85%; Rf = 0.6 (hexane:ethyl acetate 4:1) white solid; mp 170-
172 oC; 1H NMR (400 MHz, CDCl3): δ 8.33 (s, 1H), 7.78 (s, 1H), 7.49 (d, J
= 8 Hz, 2H), 7.37 – 7.21 (m, 4H), 7.11 (d, J = 8 Hz, 2H), 2.76 (q, J = 8 Hz,
2H), 2.34 (s, 3H), 1.31 (t, J = 8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
2-(2-Bromophenyl)-1H-benzo[d]imidazole (2a')[43]: 37 mg; Yield: 73%;
Rf = 0.4 (hexane:ethyl acetate 4:1); white solid; 1H NMR (700 MHz,
DMSO-D6): δ 7.82 (d, J = 7.7 Hz, 1H), 7.77 (d, J = 7.7 Hz, 1H), 7.65 – 7.60
(m, 2H), 7.56 (t, J = 7.7 Hz, 1H), 7.48 (t, J = 7.7 Hz, 1H), 7.29 – 7.23 (m,
2H); 13C NMR (175 MHz, DMSO-D6): δ 150.3, 133.4, 132.3, 132.1, 131.5,
127.8, 122.4, 121.6.
156.2, 147.8, 146.3, 142.1, 134.6, 133.2, 131.0, 130.0, 129.6, 129.5, 127.5,
~
127.2, 126.6, 121.5, 116.8, 29.0, 21.8, 15.5; IR (KBr): 
= 2965, 2362,
1624, 1595, 1433, 1383, 1281, 1190, 1177, 1075, 1018 cm-1; HR-MS (ESI-
TOF): m/z = 445.0539, calculated for C22H18Cl2N2O2S (M+H+): 445.0539.
1p’: Mp 102-104 0C; 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8 Hz, 2H),
7.72 (s, 1H), 7.63 (d, J = 8 Hz, 1H), 7.58 (d, J = 8 Hz, 2H), 7.53-7.48 (m,
3H), 7.22 (dd, J1 = 16, J2 = 8 Hz, 1H), 7.12-7.08 (m,1H), 7.03 (d, J = 8. Hz,
3H), 2.27 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.4 (t, J = 25.0 Hz),
143.7, 140.9, 136.1, 135.5, 132.3, 132.2, 129.5, 129.1, 128.9, 127.8, 127.2,
2-(2-nitrophenyl)-1-tosyl-1H-benzo[d]imidazole-6-carboxylic
acid
(2af)[29]: 56 mg; Yield: 94%; Rf = 0.3 (hexane:ethyl acetate 1:1); white
solid; 1H NMR (400 MHz, DMSO-D6) δ 8.58 (s, 1H), 8.41 (m, 1H), 8.05 (d,
J = 8.0 Hz, 1H), 7.96 (m, 2H), 7.89 (d, J = 8.0, 1H), 7.71 (m, 1H), 7.48 (d,
J = 7.6 Hz, 2H), 7.39 (d, J = 7.6 Hz, 2H), 2.34 (s, 3H). 13C NMR (100 MHz,
DMSO-D6) δ 166.9, 151.2, 147.7, 147.0, 145.0, 134.3, 133.3, 132.9, 132.6,
131.9, 130.6, 128.3, 126.9, 126.3, 124.8, 124.8, 120.5, 114.8, 21.2.
125.5, 121.3, 117.0, 21.6; IR (KBr): 
=3285, 2165, 1916, 1613, 1485,
1337, 1165, 1215 cm-1; HR-MS (ESI-TOF): m/z = 352.1215, calculated for
C20H17DN2O2S (M+H+): 352.1225.
2-(2-Bromophenyl)-1-methylsulfonyl-benzo[d]imidazole (2ba): 78 mg;
Yield: 97%; Rf = 0.3 (hexane:ethyl acetate 4:1); yellow solid; mp 155-156
oC; 1H NMR (400 MHz, CDCl3): δ 7.94 (dd, J1 = 6.8, J2 = 2 Hz, 1H), 7.89 –
7.84 (m, 1H), 7.69 (d, J = 7.6 Hz, 1H), 7.53 – 7.46 (m, 3H), 7.45 – 7.37 (m,
2H), 3.28 (s, 3H); 13C NMR (175 MHz, CDCl3): δ 150.7, 132.5, 132.4, 132.3,
Acknowledgements
We thank DST (New Delhi, India) for support and Dr. Milan Kr.
Barman (NISER) for crystallography. M.T.A. and S.M. thank UGC
(India) and CSIR (India), respectively, for fellowships.
132.3, 131.8, 127.1, 126.1, 125.4, 123.5, 121.2, 113.5, 42.27; IR (KBr):
~

= 1604, 1641, 1462, 1450, 1185, 1049 cm-1; HR-MS (ESI-TOF): m/z
= 350.9791, calculated for C14H11BrN2O2S (M+H+): 350.9797.
Keywords: C(sp2)-H Amidation• C-N coupling• 1,2-
Disubstituted Benzimidazole • N-Iodosuccinimide • Weak
Interactions
2-(2-Fluorophenyl)-1-(phenylsulfonyl)-benzo[d]imidazole (2bb): 76
1
mg; Yield: 96%; Rf = 0.5 (hexane:ethyl acetate 4:1); white semi-solid, H
NMR (700 MHz, CDCl3): δ 8.14 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 8.4 Hz,
1H), 7.60 (d, J = 8.4 Hz, 2H), 7.57 – 7.51 (m, 2H), 7.47 – 7.42 (m, 2H),
7.38 (dt, J1= 21.0, J2 = 7.7 Hz, 3H), 7.30 – 7.24 (m, 1H), 7.18 - 7.16 (m,
[1]
[2]
D. A. Horton, G. T. Bourne, M. L. Smythe, Chem. Rev. 2003, 103, 893-
930.
1
1H); 13C NMR (175 MHz, CDCl3): δ 161.1 (d, JC, F = 250.25 Hz), 147.9,
Y. Tong, J. J. Bouska, P. A. Ellis, E. F. Johnson, J. Leverson, X. Liu, P.
A. Marcotte, A. M. Olson, D. J. Osterling, M. Przytulinska, L. E. Rodriguez,
Y. Shi, N. Soni, J. Stavropoulos, S. Thomas, C. K. Donawho, D. J. Frost,
143.0, 137.9, 134.6, 133.3, 132.8 (d, 3JC, F = 8.75 Hz), 132.2, 129.4, 127.1,
4
125.9, 125.3, 123.7 (d, JC, F = 3.5 Hz), 120.8, 118.8 (d, 3JC, F = 14 Hz),
~
= 21 Hz), 114.4; IR (KBr): 
115.7 (d, 2JC, F
= 2096, 1624, 1583, 1482,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800688
European Journal of Organic Chemistry
FULL PAPER
Y. Luo, V. L. Giranda, T. D. Penning, J. Med. Chem. 2009, 52, 6803-
[28] a) S. Maiti, P. Mal, Org. Lett. 2017, 19, 2454-2457; b) S. Maiti, T. K. Achar,
P. Mal, Org. Lett. 2017, 19, 2006-2009.
6813.
[3]
[4]
[5]
Ö. Ö. Güven, T. Erdoğan, H. Göker, S. Yıldız, Bioorg. Med. Chem. Lett.
2007, 17, 2233-2236.
[29] S. Maiti, P. Mal, Adv. Synth. Catal. 2015, 357, 1416-1424.
[30] M. Jonušis, I. Čikotienė, Chem. Heterocycl. Compd. 2016, 52, 776-778.
[31] a) R. Chebolu, D. N. Kommi, D. Kumar, N. Bollineni, A. K. Chakraborti,
J. Org. Chem. 2012, 77, 10158-10167; b) S. I. Alaqeel, J. Saudi Chem.
Soc. 2017, 21, 229-237; c) K. Bahrami, M. M. Khodaei, A. Nejati, Green
Chem. 2010, 12, 1237-1241; d) G. A. Molander, K. Ajayi, Org. Lett. 2012,
14, 4242-4245.
S. M. Sondhi, S. Rajvanshi, M. Johar, N. Bharti, A. Azam, A. K. Singh,
Eur. J. Med. Chem. 2002, 37, 835-843.
Y.-F. Li, G.-F. Wang, P.-L. He, W.-G. Huang, F.-H. Zhu, H.-Y. Gao, W.
Tang, Y. Luo, C.-L. Feng, L.-P. Shi, Y.-D. Ren, W. Lu, J.-P. Zuo, J. Med.
Chem. 2006, 49, 4790-4794.
[6]
[7]
M. L. Barreca, A. Rao, L. D. Luca, N. Iraci, A.-M. Monforte, G. Maga, E.
D. Clercq, C. Pannecouque, J. Balzarini, A. Chimirri, Bioorg. Med. Chem.
Lett. 2007, 17, 1956-1960.
[32] T. K. Achar, S. Maiti, P. Mal, Org. Biomol. Chem. 2016, 14, 4654–4663.
[33] I. Colomer, A. E. R. Chamberlain, M. B. Haughey, T. J. Donohoe, Nat.
Rev. Chem. 2017, 1, 0088.
T. de la Fuente, M. Martꢀn-Fontecha, J. Sallander, B. Benhamꢁ, M.
Campillo, R. o. A. Medina, L. P. Pellissier, S. Claeysen, A. Dumuis, L.
Pardo, M. a. L. Lꢂpez-Rodrꢀguez, J. Med. Chem. 2010, 53, 1357-1369.
W. A. Denny, G. W. Rewcastle, B. C. Baguley, J. Med. Chem. 1990, 33,
814-819.
[34] S. Fu, H. Jiang, Y. Deng, W. Zeng, Adv. Synth. Catal. 2011, 353, 2795-
2804.
[35] Z. Hu, T. Zhao, M. Wang, J. Wu, W. Yu, J. Chang, J. Org. Chem. 2017,
82, 3152-3158.
[8]
[9]
[36] a) J. Barluenga, in Pure Appl. Chem., Vol. 71, 1999, p. 431; b) P. J.
Campos, J. Arranz, M. A. Rodríguez, Tetrahedron Lett. 1997, 38, 8397-
8400.
L. C. R. Carvalho, E. Fernandes, M. M. B. Marques, Chem. Eur. J. 2011,
17, 12544-12555.
[10] J. Valdez, R. Cedillo, A. Hernández-Campos, L. Yépez, F. Hernández-
Luis, G. Navarrete-Vázquez, A. Tapia, R. Cortés, M. Hernández, R.
Castillo, Bioorg. Med. Chem. Lett. 2002, 12, 2221-2224.
[37] L. Turunen, U. Warzok, R. Puttreddy, N. K. Beyeh, C. A. Schalley, K.
Rissanen, Angew. Chem. Int. Ed. 2016, 55, 14033-14036.
[38] S. H. Cho, J. Yoon, S. Chang, J. Am. Chem. Soc. 2011, 133, 5996-6005.
[39] E. M. Simmons, J. F. Hartwig, Angew. Chem. Int. Ed. Engl. 2012, 51,
3066-3072.
[11] a) C.-J. Li, Chem 2016, 1, 423-437; b) G. N. Hermann, C. Bolm, ACS
Catal. 2017, 7, 4592-4596.
[12] a) J. Bariwal, E. Van der Eycken, Chem. Soc. Rev. 2013, 42, 9283-9303;
b) J. F. Hartwig, Acc. Chem. Res. 2008, 41, 1534-1544; c) B. Majumdar,
D. Sarma, T. Bhattacharya, T. K. Sarma, ACS Sustainable Chem. Eng.
2017, 5, 9286-9294.
[40] a) D. Gimenez, A. Dose, N. L. Robson, G. Sandford, S. L. Cobb, C. R.
Coxon, Org. Biomol. Chem. 2017, 15, 4081-4085; b) T. Dohi, M. Ito, K.
Morimoto, Y. Minamitsuji, N. Takenaga, Y. Kita, Chem. Commun. 2007,
4152-4154; c) T. Dohi, A. Maruyama, Y. Minamitsuji, N. Takenaga, Y.
Kita, Chem. Commun. 2007, 1224-1226; d) Y. Kita, H. Tohma, M. Inagaki,
K. Hatanaka, T. Yakura, Tetrahedron Lett. 1991, 32, 4321-4324; e) T.
Dohi, N. Yamaoka, Y. Kita, Tetrahedron 2010, 66, 5775-5785.
[41] I. Colomer, C. Batchelor-McAuley, B. Odell, T. J. Donohoe, R. G.
Compton, J. Am. Chem. Soc. 2016, 138, 8855-8861.
[13] P. Ruiz-Castillo, S. L. Buchwald, Chem. Rev. 2016, 116, 12564-12649.
[14] a) C.-L. Sun, Z.-J. Shi, Chem. Rev. 2014, 114, 9219-9280; b) M.-L.
Louillat, F. W. Patureau, Chem. Soc. Rev. 2014, 43, 901-910.
[15] a) A. Yoshimura, V. V. Zhdankin, Chem. Rev. 2016, 116, 3328-3435; b)
K. Muñiz, Top. Curr. Chem. 2016, 373, 105-133.
[16] a) S. A. Girard, T. Knauber, C.-J. Li, in From C-H to C-C Bonds: Cross-
Dehydrogenative-Coupling, The Royal Society of Chemistry, 2015, pp.
1-32; b) R. Narayan, S. Manna, A. P. Antonchick, Synlett 2015, 26, 1785-
1803; c) S. A. Girard, T. Knauber, C.-J. Li, Angew. Chem. Int. Ed. 2014,
53, 74-100; d) C.-J. Li, Acc. Chem. Res. 2009, 42, 335-344; e) K.
Pericherla, P. Khedar, B. Khungar, A. Kumar, Chem. Commun. 2013, 49,
2924-2926; f) S. Satishkumar, M. K. Lakshman, Chem. Commun. 2017,
53, 2226-2229.
[42] R. Vinodkumar, S. D. Vaidya, B. V. Siva Kumar, U. N. Bhise, S. B. Bhirud,
U. C. Mashelkar, Eur. J. Med. Chem. 2008, 43, 986-995.
[43] M. R. Marri, S. Peraka, A. K. Macharla, N. Mameda, S. Kodumuri, N.
Nama, Tetrahedron Lett. 2014, 55, 6520-6525.
[17] a) J. Santhi, B. Baire, Adv. Synth. Catal. 2016, 358, 3817-3823; b) S.
Badigenchala, G. Sekar, J. Org. Chem. 2017, 82, 7657-7665; c) Y.-N.
Ma, M.-X. Cheng, S.-D. Yang, Org. Lett. 2017, 19, 600-603; d) C. Q.
O’Broin, P. Fernández, C. Martꢀnez, K. Muñiz, Org. Lett. 2016, 18, 436-
439; e) Y.-L. Li, J. Li, A.-L. Ma, Y.-N. Huang, J. Deng, J. Org. Chem. 2015,
80, 3841-3851.
[18] a) O. Š. Miljanić, Chem 2017, 2, 502-524; b) Q. Ji, R. C. Lirag, O. S.
Miljanic, Chem. Soc. Rev. 2014, 43, 1873-1884.
[19] a) A. S. Mahadevi, G. N. Sastry, Chem. Rev. 2016, 116, 2775-2825; b)
X. Zhang, G.-p. Lu, Z.-b. Xu, C. Cai, ACS Sustainable Chem. Eng. 2017,
5, 9279-9285.
[20] C.-J. Li, Chem. Rev. 2005, 105, 3095-3166.
[21] a) D. Bulfield, S. M. Huber, Chem. - Eur. J. 2016, 22, 14434-14450; b) L.
Turunen, U. Warzok, C. A. Schalley, K. Rissanen, Chem 2017.
[22] T. K. Achar, P. Mal, Adv. Synth. Catal. 2015, 357, 3977-3985.
[23] M. Giese, M. Albrecht, K. Rissanen, Chem. Rev. 2015, 115, 8867-8895.
[24] a) S. Maiti, P. Mal, J. Org. Chem. 2018, 83, 1340-1347; b) S. Maiti, M. T.
Alam, P. Mal, Asian J. Org. Chem. 2018, 7, 715-719.
[25] a) S. E. Wheeler, T. J. Seguin, Y. Guan, A. C. Doney, Acc. Chem. Res.
2016, 49, 1061-1069; b) M. Breugst, D. von der Heiden, J. Schmauck,
Synthesis 2017, 49, 3224-3236.
[26] a) S. Zarra, D. M. Wood, D. A. Roberts, J. R. Nitschke, Chem. Soc. Rev.
2015, 44, 419-432; b) K. Rissanen, Chem. Soc. Rev. 2017, 46, 2638-
2648.
[27] a) A. Bose, P. Mal, Chem. Commun. 2017, 53, 11368-11371; b) T. K.
Achar, P. K. Sahoo, P. Mal, ChemistrySelect 2017, 2, 1944-1949.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800688
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents
FULL PAPER
An intramolecular dehydrogenative
C(sp2)H-NH coupling reaction is being
reported by using N-iodosuccinimide
as the metal-free and sole reagent.
The reactions were carried out in
trifluoroethanol as solvent to access
several N-substituted benzimidazoles
with very high yields and in short
reaction times.
Synthetic Methods
Md Toufique Alam, Saikat Maiti and
Prasenjit Mal*
Page No. – Page No.
An Intramolecular C(sp2)-H Amidation
by N-Iodosuccinimide
This article is protected by copyright. All rights reserved.