Application of N,N′-diiodo-N,N′-1,2-ethandiylbis(p-toluene sulfonamide) as a new reagent for synthesis of 2-arylbenzimidazoles and 2-arylbenzothiazoles under solvent-free conditions

Article abstract of DOI:10.1002/cjoc.201090372

N,N′-Diiodo-N,N′-1,2-ethandiylbis(p-toluene sulfonamide) (NIBTS) is a good and new reagent for synthesis of 2-arylbenzimidazoles and 2-arylbenzothiazoles at room temperature under solvent-free condition with good to high yield. Absence of solvent, short reaction times, non-corrosive, operational simplicity and environmentally friendliness are the main advantages of this procedure. Copyright

Full text of DOI:10.1002/cjoc.201090372

FULL PAPER
Application of N,N'-Diiodo-N,N'-1,2-ethandiylbis(p-toluene
sulfonamide) as a New Reagent for Synthesis of
-Arylbenzimidazoles and 2-Arylbenzothiazoles under
Solvent-free Conditions
2
,a
b
b
c,d
Veisi, Hojat*
Ghorbani-Vaghei, Ramin
Faraji, Alireza
Ozturk, Turan
a
Department of Chemistry, Payame Noor University (PNU), Iran
b
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan, Iran
c
Science Faculty, Chemistry Department, Organic Chemistry, ITU, Istanbul, Turkey
d
TUBITAK UME, Chemistry Group Laboratories, Pbox 54, 41470, Gebze-kocaeli, Turkey
N,N'-Diiodo-N,N'-1,2-ethandiylbis(p-toluene sulfonamide) (NIBTS) is a good and new reagent for synthesis of
2-arylbenzimidazoles and 2-arylbenzothiazoles at room temperature under solvent-free condition with good to high
yield. Absence of solvent, short reaction times, non-corrosive, operational simplicity and environmentally friendli-
ness are the main advantages of this procedure.
Keywords 2-arylbenzimidazoles, 2-arylbenzothiazoles, NIBTS, solvent-free
Introduction
agents and/or chlorinated organic solvents and harsh
reaction conditions.
Benzimidazoles and benzothiazoles are very useful
building blocks for the development of molecules that
are important in medicinal chemistry. Consequently,
1
Experimental
the synthesis of the heterocyclic nucleus contained in
such compounds has gained importance. Substituted
benzimidazole and benzothiazoles derivatives have been
found to be used as diverse therapeutic agents, including
antiulcers, antihypertensives, antivirals, antifungals,
anticancers and antihistaminics. These bicyclic com-
pounds consist of the fusion of benzene and imidazole.
The most prominent benzimidazole compound in nature
Materials
All commercially available chemicals were obtained
from Merck and Fluka companies, and used without
further purifications unless otherwise stated. Nuclear
magnetic resonance (NMR) spectra were recorded on a
Jeol 90 MHz FT NMR spectrometer. Infrared (IR) was
conducted on a Perkin Elmer GX FT-IR spectrometer.
All yields refer to isolated products.
5
-7
is N-ribosyl-dimethylbenzimidazole, which serves as an
2
axial ligand for cobalt in vitamin B12
.
General
procedure
for
the
synthesis
of
Benzimidazoles, in an extension of the well-elabo-
rated imidazole system, have been used as carbon
skeletons for N-heterocyclic carbenes. The N-hetero-
cyclic carbenes are usually used as ligands for transition
metal complexes. They are often prepared by deproto-
nating an N,N'-disubstituted benzimidazolium salt at the
2
-arylbenzimidazoles with NIBTS
A mixture of o-phenylenediamine (1 mmol) and aryl
aldehyde (1.1 mmol) was well stirred with N,N'-diiodo-
N,N'-1,2-ethandiylbis(p-toluene sulfonamide) (0.5 mmol)
at room temperature for a period time specified in Table
3
,4
1
. The reaction was monitored by TLC [3 ∶
V(n-hexane)/V(acetone)]. After completion of the reac-
tion, CH Cl (5 mL) was added, and the sulphonamide
1
2
-position with a base. Because of their importance,
the synthesis of substituted benzimidazoles has gotten a
focus of synthetic organic chemistry. Various oxidative
2
2
8
9
10
11
15
reagents such as DDQ, MnO
2
, Pb(OAc)
4
,
Oxone,
was removed by filtration. Evaporation of the solvent
under reduced pressure gives the product. Further puri-
fication was achieved by preparative thin-layer chro-
matography using n-hexane/acetone (V∶ V＝ 7∶ 3) as
the eluent system to afford the benzimidazoles.
1
2
13
14
IBD, Yb(OTf)
3
,
H
2
O
2
/HCl, silica sulfuric acid
1
6
and oxalic acid have been use to effect this transfor-
mation.
However, a number of these methods have some
drawbacks such as low yields, the use of expensive re-
*
E-mail: hojatveisi@yahoo.com; Tel./Fax: 0098-838-4233338
Received February 24, 2010; revised May 6, 2010; accepted July 8, 2010.
Chin. J. Chem. 2010, 28, 2249— 2254
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
2249

Veisi et al.
FULL PAPER
Table 1 Reaction of aryl aldehydes with o-phenylenediamine
a
b
Entry
1
Substrate
Product
Time/min
Yield /%
20
96
90
92
90
82
2
3
4
5
25
20
30
80
6
7
8
9
65
45
85
75
90
85
92
96
90
70
75
35
60
10
11
12
13
14
25
20
45
120
145
a
The products were characterized by comparison of their spectroscopic and physical data with those of samples synthesized by reported
b
procedures. Yield refer to pure isolated products.
2
250
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Chin. J. Chem. 2010, 28, 2249— 2254

Application of N,N'-Diiodo-N,N'-1,2-ethandiylbis(p-toluene sulfonamide) as a New Reagent
General procedure for the synthesis of 2-arylbenzo-
thiazoles with NIBTS
Spectra data for selected products
-(2-Chlorophenyl)-1H-benzimidazole (Table 1,
2
1
A mixture of 2-aminothiophenol (1.1 mmol) and
aryl aldehyde (1 mmol) was well stirred with
N,N'-diiodo-N,N'-1,2-ethandiylbis(p-toluene sulfonamide)
Entry 10) m.p. 232—233 ℃; H NMR (DMSO-d ,
6
200 MHz) δ: 7.26—7.32 (m, 2H), 7.56—7.73 (m, 5H),
13
7.93—7.96 (m, 1H), 12.78 (br, 1H, NH); C NMR
(
0.5 mmol) at 40 ℃ for a period time specified in Ta-
(DMSO-d , 50 MHz) δ: 112.1, 119.4, 122.1, 123.1,
6
ble 2. The reaction was monitored by TLC [3∶1
V(n-hexane)/V(acetone)]. After completion of the reac-
127.8, 130.3, 130.7, 131.6, 132.4, 149.4; IR (KBr) ν:
－
1
＋
3442, 1620 cm ; MS (eV) m/z: 228 [M ]. Anal. calcd
tion, CH
2
Cl
2
(5 mL) was added, and the sulphonamides
for C1 H ClN : C 68.28, H 3.97, N 12.25; found C
3
9
2
was removed by filtration. Evaporation of the solvent
under reduced pressure gives the product. Further puri-
fication was achieved by preparative thin-layer chro-
matography using n-hexane/acetone (V∶V＝7∶3) as
the eluent system to afford the benzothiazoles.
67.95, H 3.80, N 12.13.
2-(4-Methoxyphenyl)-1H-benzimidazole (Table 1,
1
Entry 3) m.p. 225—227 ℃; H NMR (DMSO-d , 90
6
MHz) δ: 12.72 (s, 1H), 7.14—8.11 (m, 8H), 3.75 (s, 3H);
1
3
C NMR (DMSO-d , 75 MHz) δ: 56.3, 115.6, 119.1,
6
Table 2 Reaction of aryl aldehydes with 2-aminothiophenol
a
b
Entry
1
Substrate
Product
Time/h
Yield /%
1.5
90
90
96
98
80
85
2
3
4
5
6
2
1
1
3
2
7
1.7
82
8
9
1.2
3.5
1.1
92
70
96
1
1
1
0
1
2
1
1
95
92
a
The products were characterized by comparison of their spectroscopic and physical data with those of samples synthesized by reported
b
procedures. Yield refer to pure isolated products.
Chin. J. Chem. 2010, 28, 2249— 2254
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Veisi et al.
FULL PAPER
1
1
21.9, 122.6, 126.7, 127.8, 129.8, 135.3, 139.9, 144.1,
o-phenylenediamine (1mmol) in the presence of NIBTS
(0.5 mmol) in 96% yield (Table 1, Entry 1). In the same
manner, a variety of aldehydes were coupled with
o-phenylenediamine in the presence of N,N'-diiodo-
N,N'-1,2-ethandiylbis(p-toluene sulfonamide) (NIBTS)
as an efficient reagent and oxidant at room temperature
to give the corresponding 2-substituted benzimidazoles
in good to excellent yields (Table 1). We also observed
that the reaction in DCM, methanol, ethanol, acetonitrile,
or THF takes longer times than in the neat conditions.
This acceleration is probably attributable to the concen-
tration effect.
－
1
51.7; IR (KBr) ν: 3447, 1624 cm ; MS (eV) m/z: 193
＋
[
M ]. Anal. calcd for C13
H
9
N
2
: C 80.81, H 4.69, N
1
4.59; found C 80.64, H 4.42, N 14.25.
-(4-Methylphenyl)benzothiazole (Table 2, Entry
2
1
2
7
7
1
3
) m.p. 86—88 ℃; H NMR (DMSO-d
6
, 90 MHz) δ:
1
3
.25—8.09 (m, 8H), 2.56 (s, 3H); C NMR (DMSO-d
6
,
5 MHz) δ: 22.2, 123.0, 124.5, 125.5, 127.4, 128.4,
30.8, 132.1, 135.9, 150.2, 1555.2, 169.2; IR (KBr) ν:
－
1
＋
050, 1635 cm ; MS (eV) m/z: 225 [M ]. Anal. calcd
for C14H11NS: C 74.63, H 4.92, N 6.22; found C 74.24,
H 5.06, N 5.95.
As shown in Table 1, both electron-rich and elec-
tron-deficient aldehydes react without any significant
difference to give the corresponding benzimidazoles in
good yield (Table 1, Entries 1—12).
Results and discussion
In continuation of our interest in the application of
N,N'-diiodo-N,N'-1,2-ethandiylbis(p-toluene
sulfona-
we report a
1
7
17-19
We have also developed this synthetic method for
the preparation of 2-arylbenzothiazoles derivatives in a
1.1∶1∶0.5 molar ratio of 2-aminothiophenol to alde-
hyde and NIBTS at 40 ℃ for appropriate times under
solvent-free conditions (Scheme 1).
mide) (NIBTS) in organic synthesis,
new and efficient method for the one step synthesis of
-substituted benzimidazoles by the condensation of
2
o-phenylenediamine with arylaldehydes using NIBTS as
an efficient reagent and oxidant at room temperature
(
Scheme 1).
After optimizing the conditions, the generality of
this procedure was examined by the reaction of several
substituted aryl aldehydes with 2-aminothiophenol. As
shown in Table 2, a variety of substituted aromatic al-
dehydes, bearing either electron-donating or elec-
tron-withdrawing substituents, afforded the correspond-
ing 2-arylbenzothiazoles in excellent yields. It was
pleasing to observe the remarkable stability of a variety
of functional groups such as ether, nitro, hydroxyl, hal-
ides and conjugated carbon-carbon double bond under
the reaction conditions.
Scheme 1
Nevertheless, this protocol has its limitations. Oc-
tanal, an aliphatic aldehyde, only provided 30% yield of
the desired product.
The reaction was carried out in neat at room tem-
perature for 20 min, using aldehyde (1.1 mmol) and
Table 3 Comparison of methods for the synthesis of 2-arylbenzimidazoles and 2-arylbenzothiazoles
Entry
1
Ar
XH
Condition
Time
Yield/%
NIBTS, solvent-free, r.t.
20 min
6 h
5h
96
90
85
79
2
3
DDQ, MeCN, r.t.
Ph
NH
2
＋
＋
－
2
4
Me
2
S Br Br , MeCN, r.t.
2
5
PS-PPh
3
, CCl
3
CN, MeCN MW, 150 ℃
15 min
NIBTS, solvent-free, r.t.
25 min
18 h
45 min
10 min
90
80
75
84
2
6
Pyridine, SOCl
2
, CH
2
Cl
2
, 0—20 ℃
2
3
4-MeC
6
H
4
NH
2
2
7
I
2
, KI, K CO , H
2
3
2
2
O, PhNO
2
, SiO
2
, 90 ℃
8
MW, 110 ℃
NIBTS, solvent-free, r.t.
1
4
.5 h
h
90
90
Ph
SH
SH
30
H
3
PO
4
, solvent-free, 250 ℃
NIBTS, solvent-free, r.t.
1 h
8 min
4 min
96
61
91
3
1
4
-MeOC
6
H
4
PhNO , SiO , MW
2
2
2
9
MnO
2
, SiO
2
, MW, 110 ℃
2
252
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Chin. J. Chem. 2010, 28, 2249— 2254

Application of N,N'-Diiodo-N,N'-1,2-ethandiylbis(p-toluene sulfonamide) as a New Reagent
A comparison of the efficiency of this method with
selected previous methods is collected in Table 3. The
results show that this method is superior to some previ-
ously reported methods in terms of yields and reaction
times.
After the reaction of NIBTS with [I＋II], the sul-
phonamide is recovered and can be reused many times
without decreasing yield.
In conclusion, NIBTS was found to be mild and
effective new reagent for the convenient synthesis of
2-arylbenzimidazoles and 2-arylbenzothiazoles in ex-
cellent yields from 1,2-phenylenediamine and 2-amino-
thiophenol and a wide variety of aryl aldehydes under
solvent-free conditions. Moreover, the method has ad-
vantages in terms of product yields, absence of solvent,
short reaction times, non-corrosive, operational simplic-
ity, operational simplicity (easy work up of reactions).
Since NIBTS contain iodine atoms which are at-
tached to nitrogen atoms, it is very possible that they
＋
release I in situ which can act as catalyst and oxidant
in the reaction medium. Therefore, the mechanism
shown in Scheme 2 can be suggested for the formation
1
2,14
of benzimidazoles.
Scheme 2
Acknowledgments
We are thankful to Bu-Ali Sina University, Payame
Noor University for financial support, and the Univer-
sity of Sheffield for NMR, Mass spectra and CHN.
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Chin. J. Chem. 2010, 28, 2249— 2254