One-Pot Three-Component Synthesis of New Mono- and Bis-1,2,3-triazole Derivatives of 2-Benzimidazolethiol with a Promising Inhibitory Activity against Acidic Corrosion of Steel

Article abstract of DOI:10.1055/s-0033-1340863

A series of new mono- and bis-1,2,3-triazole derivatives of 2-benzimidazolethiol were synthesized by three-component copper(I)-catalyzed 1,3-dipolar cycloaddition. The desired heterocycles were obtained in good yields and fully characterized. The corrosion inhibition efficiency of new heterocyclic compounds was investigated on steel grade API 5L X52 in 1 M HCl using electrochemical impedance spectroscopy. The results revealed that these new organic compounds show promising inhibition properties for the corrosion of steel in acidic media. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1340863

PAPER
▌1217
pOapnere-Pot Three-Component Synthesis of New Mono- and Bis-1,2,3-triazole
Derivatives of 2-Benzimidazolethiol with a Promising Inhibitory Activity
against Acidic Corrosion of Steel
1
,2,3-Triazole Derivatives of 2-Benzimidazolethiol
a,b
a
a
c
Deysi Y. Cruz-Gonzalez, Rodrigo González-Olvera, Guillermo E. Negrón-Silva,* Leticia Lomas-Romero,
Atilano Gutiérrez-Carrillo, Manuel E. Palomar-Pardavé, Mario A. Romero-Romo, Rosa Santillan, Jorge Uruchurtu
c
b
b
d
e
a
Departamento de Ciencias Básicas, Universidad Autónoma Metropolitana-Azcapotzalco, Av. San Pablo No. 180, México D. F., C. P. 02200,
México
Fax +52(55)53189000; E-mail: gns@correo.azc.uam.mx
b
c
Departamento de Materiales, Universidad Autónoma Metropolitana-Azcapotzalco, Av. San Pablo No. 180, México D. F., C. P. 02200, México
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, Av. San Rafael Atlixco No. 186, México D.F., C. P. 09340,
México
d
e
Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740,
07000 México D.F., México
CIICAp, Universidad Autónoma del Estado de Morelos, Avenida Universidad 1001, Col. Chamilpa, 62209 Cuernavaca, Morelos, México
Received: 30.12.2013; Accepted after revision: 04.02.2014
corrosion but also are important pharmacophores because
of their presence in many compounds displaying pharma-
cological activities. Additionally, our group has reported
Abstract: A series of new mono- and bis-1,2,3-triazole derivatives
of 2-benzimidazolethiol were synthesized by three-component cop-
per(I)-catalyzed 1,3-dipolar cycloaddition. The desired heterocy-
6
cles were obtained in good yields and fully characterized. The the synthesis of 2-benzimidazolethiol and its benzylated
corrosion inhibition efficiency of new heterocyclic compounds was derivative employing reconstructed hydrotalcite and their
investigated on steel grade API 5L X52 in 1 M HCl using electro-
use as efficient acidic corrosion inhibitors of steel grade
chemical impedance spectroscopy. The results revealed that these
new organic compounds show promising inhibition properties for
the corrosion of steel in acidic media.
7,8
API 5L X52.
Therefore, the development and study of new corrosion
inhibitors are of great interest to the academic and indus-
trial fields of corrosion. Herein, we describe the synthesis
of new mono- and bis-1,2,3-triazole derivatives of 2-
benzimidazolethiol and their evaluation as organic inhib-
itors for acidic corrosion of steel grade API 5L X52.
Key words: 1,2,3-triazoles, multicomponent reaction, inhibitors,
acidic corrosion, steel
1,4-Disubstituted 1,2,3-triazoles are a class of heterocy-
clic compounds of much interest because of their ample
1
range of pharmacological activities. In recent years, the
Synthesis
copper(I)-catalyzed 1,3-dipolar cycloaddition (also
known as Huisgen–Meldal–Sharpless reaction) is the
most versatile strategy for synthesizing 1,2,3-triazoles
The first synthesis step involved the preparation of com-
pounds 2 and 3 by propargylation of 1 with propargyl bro-
mide (1 equiv for 2 and 2.3 equiv for 3) in the presence of
reconstructed hydrotalcite (HTr) following our previous
2
from terminal alkynes and azides. Through this reaction,
a wide variety of compounds with a triazole ring could be
3
prepared that are of interest in many areas of research.
7
procedures. After workup and purification through col-
Recently, the inhibition of steel corrosion in acid solutions
by different types of organic inhibitors has been exten-
sively studied. One of the most common types of organic
corrosion inhibitors are heterocyclic compounds compris-
ing mainly a π-system (aromatic rings) and/or nitrogen,
sulfur, or oxygen atoms in their structure. In this regard,
N
S
N
HTr
H
N
propargyl bromide
2
(89%)
SH
1
,2,3-triazoles have been recently studied as effective cor-
EtOH
N
H
4
rosion inhibitors for steel in acidic media.
MW (CoolMate), 25 °C
N
N
1
S
Among the various corrosion inhibitors, benzimidazole
and 2-benzimidazolethiol 1 have been tested as acidic cor-
5
rosion inhibitors of steel. They are not only used to abate
3
(88%)
SYNTHESIS 2014, 46, 1217–1223
Advanced online publication: 25.02.2014
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
Scheme 1 Microwave-assisted synthesis of alkynes 2 and 3 in the
presence of HTr
DOI: 10.1055/s-0033-1340863; Art ID: SS-2013-M0842-OP
Georg Thieme Verlag Stuttgart · New York
©

1218
D. Y. Cruz-Gonzalez et al.
PAPER
Table 1 One-Pot Three-Component Click Reaction for Compounds 4–8
NaN3
Cu(OAc)2⋅H2O (5 mol%)
1,10-Phen⋅H2O (5 mol%)
N
N
+
S
S
N
X
N
N
R
N
EtOH–H O (2:1)
N
H
2
H
Na ascorbate
r.t., 18 h
R
4
–8
Entrya
Product
X
R
Yield (%)b
1
2
3
4
4
5
6
7
8
Cl
Cl
Cl
Br
Br
H
F
94
92
90
90
93
Cl
Br
I
5
a
Reagents: 2 (100 mg, 0.53 mmol), NaN (38 mg, 0.58 mmol), and benzyl halide (0.58 mmol).
Isolated yields after purification.
3
b
umn chromatography, alkynes 2 and 3 were isolated in 89 1,2,3-triazolobenzimidazolethiols 4–8 were isolated in
and 88% yield, respectively (Scheme 1). 90–94% yields (Table 1).
With the alkyne derivative of 2-benzimidazolethiol 2, a In order to gain access to the series of bis-1,2,3-triazole
one-pot three-component copper(I)-catalyzed 1,3-dipolar derivatives of 2-benzimidazolethiol, the copper(I)-cata-
cycloaddition was then performed for the regioselective lyzed 1,3-dipolar cycloaddition reaction was carried out
synthesis of heterocyclic compounds 4–8. Based on our with dialkyne 3 (1 equiv), sodium azide (2.1 equiv), and
9
previously reported method, the reaction between 2, so- several benzyl halides (2.1 equiv) under the previous ex-
dium azide, and several benzyl halides was carried out in perimental conditions. In all cases, cycloaddition reac-
the presence of a catalytic amount of cupric acetate mono- tions showed a total conversion (TLC) after 24 hours
1
0
hydrate, 1,10-phenanthroline monohydrate as ligand,
under stirring at room temperature. The corresponding
2a,11
and sodium ascorbate as reducing agent
in EtOH–H O bis-1,2,3-triazoles 9–13 were isolated in 85–92% yields
2
at room temperature for 18 hours. The desired products (Table 2).
Table 2 One-Pot Three-Component Click Reaction for Compounds 9–13
NaN3
Cu(OAc)2⋅H2O (5 mol%)
N
N
N
N
+
1,10-Phen⋅H2O (5 mol%)
S
S
N
X
N
N
R
EtOH–H2O (2:1)
Na ascorbate
r.t., 24 h
R
N
N
9
–13
N
R
R
H
F
Entrya
Product
X
Yield (%)b
1
2
3
4
9
Cl
Cl
Cl
Br
Br
92
86
85
87
89
10
11
12
13
Cl
Br
I
5
a
Reagents: 3 (100 mg, 0.44 mmol), NaN (60 mg, 0.92 mmol), and benzyl halide (0.92 mmol).
Isolated yields after purification.
3
b
Synthesis 2014, 46, 1217–1223
© Georg Thieme Verlag Stuttgart · New York

PAPER
1,2,3-Triazole Derivatives of 2-Benzimidazolethiol
1219
The structures of all newly synthesized compounds were
1
13
confirmed by examination of their H and C NMR, IR,
1
13
and mass spectra. The H and C NMR signals for 1,2,3-
triazole derivatives of 2-benzimidazolethiol were as-
signed with the help of 2D heteronuclear correlation ex-
periments (HETCOR and HMBC). The HMBC spectra
showed a correlation between the CH triazole carbon
atom and both hydrogen atoms of the methylene group ad-
jacent to N-1 triazole nitrogen, whilst the quaternary car-
bon atom of the triazole ring correlates with both
hydrogen atoms of the methylene group adjacent to N-1
1
benzimidazole nitrogen. The signals in the H NMR spec-
tra at δ = 8.04–8.09 (for 4–8) and δ = 8.10–8.16 (for 9–
1
3) corresponding to the triazolyl hydrogen were support-
1
3
ed by the signals in the C NMR spectra at δ = 124.1–
24.3 (for 4–8) and δ = 124.1–124.4 (for 9–13). The sig-
1
nals for the quaternary carbon of the triazole ring ap-
peared at δ = 143.9–144.0 (for 4–8) and δ = 142.7–143.6
1
3
(
for 9–13) in the C NMR spectra. These chemical shift
values are consistent with those reported for 1,4-disubsti-
tuted 1,2,3-triazoles.4
a,9,12
Corrosion Inhibitory Activity
Electrochemical impedance spectroscopy (EIS) is a meth-
od much employed for investigation of corrosion inhibito-
ry properties of organic compounds on metals. The
compounds 4–13, which incorporate the known structural
features of corrosion inhibitory activity such as 2-benz-
imidazolethiol and the 1,2,3-triazole moiety were then
evaluated as corrosion inhibitors on the steel grade API
5L X52 by EIS. The Nyquist plots obtained for the steel
samples in 1M HCl solution in the presence and absence
of the tested heterocycles 4–13 are shown in Figure 1. As
can be seen from the Nyquist plots, all compounds exhib-
ited corrosion inhibitory activity.
The blank response is shown in Figure 1 (a). Note that its
impedance spectrum exhibited one single depressed semi-
circle, which indicates that the steel corrosion is mainly
controlled by a charge transfer process. In contrast, when
compounds 4–13 are present (30 ppm), the impedance
spectra are characterized by two time constants (Figure 1,
b and 1c). We can note from these figures that the spectra
obtained after addition of organic compounds to the cor-
Figure 1 Experimental impedance data, Nyquist plots, recorded in
the systems (a) steel/1 M HCl, (b) steel/1 M HCl + 30 ppm for com-
pounds 4–8, and (c) steel/1 M HCl + 30 ppm for compounds 9–13
roding media increased the impedance value (Z ), and
real
that in most cases, they are characterized by two semicir-
cles or two time constants: one constant at high frequency
and the other at low frequency, which are generally attrib-
uted to the adsorption of the organic compounds onto the
metal surface. The electrochemical parameters obtained
from fitting the recorded EIS data using the appropriate
equivalent circuit model are listed in Table 3.
system, while the decrease in C can be attributed to the
formation of a protective layer on the metal surface.
dl
A perusal of the literature revealed that the organic com-
pounds containing both nitrogen and sulfur atoms in their
structure are of particular importance, since these provide
an excellent inhibition activity in comparison with those
Inspection of the data of compounds 4–13 in Table 3 re-
veals that charge transfer resistance (R ) values increase
13
ct
containing only nitrogen or sulfur atoms. Therefore, it is
prominently, while the double layer capacitance (C ) val-
dl
important to remark that compounds 4–13 displayed cor-
rosion inhibition efficiencies (IE) around 90% at rather
low concentration values (Table 3). However, it is impor-
ues reduced with addition of the organic compounds (30
ppm). A large R is associated with a slower corroding
ct
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1217–1223

1220
D. Y. Cruz-Gonzalez et al.
PAPER
Table 3 Electrochemical Impedance Parameters for Steela
ing electrode was the API 5L X52 steel sample with an exposed area
of approximately 1 cm and a chemical composition (wt%) of C:
2
2
2
2
0.080, Mn: 1.06, Si: 0.26, Ti: 0.003, V: 0.054, Nb: 0.041, P: 0.019,
Compound
R (Ω cm )
R (Ω cm )
C (μF cm ) IE (%)
dl
s
ct
S: 0.003, Al: 0.039, Ni: 0.019, C : 0.274, Fe: balance, which was
eq
prepared using standard metallographic procedures. The corrosion
inhibition efficiency (IE) was evaluated by means of electrochemi-
cal impedance spectroscopy (EIS) on the API 5L X52/1 M HCl sys-
tem containing 0 (blank) or 30 ppm of the organic inhibitor.
Simulation of the impedance data recorded was conducted by
Blank
1.3
1.9
1.2
0.9
0.8
1.2
1.4
1.1
1.5
1.2
1.4
27
194
671
495
440
503
1250
900
756
680
900
201
43
15
31
17
25
19
33
31
51
43
–
4
5
6
7
8
9
86
96
94
94
95
98
97
96
96
97
8
b
means of electrical equivalent circuits and the electrical parame-
ters – solution resistance (R ), charge transfer resistance (R ), and
s
ct
double layer capacitance (C ) – were obtained in this way.
dl
Mono-1,2,3-triazoles Derived from 2-Benzimidazolethiol 2;
General Procedure 1 (GP1)
To a 50 mL round-bottomed flask with a magnetic stirrer, were
charged Cu(OAc) ·H O (5 mg, 0.027 mmol, 5 mol%), 1,10-phenan-
2
2
1
1
1
0
1
2
3
throline monohydrate (5 mg, 0.027 mmol, 5 mol%), and sodium L-
ascorbate (107 mg, 0.54 mmol) in EtOH–H O (2:1 v/v, 6 mL), fol-
2
lowed by stirring for 5 min at r.t. Subsequently, 2 (100 mg, 0.53
mmol), NaN (38 mg, 0.58 mmol), and the required benzyl halide
3
(0.58 mmol) were added to the reaction mixture, which was stirred
for 18 h at r.t. The mixture was extracted with CH Cl (3 × 5 mL).
1
2
2
The combined organic phases were dried (Na SO ) and then the
2
4
a
Measured in 1 M HCl solution in the presence and absence of com-
CH Cl solvent was evaporated under vacuum. The crude product
2 2
pounds 4–13, including the corrosion inhibition efficiencies (IE) at 30
ppm of the organic inhibitor.
was purified by column chromatography (CH Cl –MeOH, 95:5
2 2
v/v) and recrystallized from CH Cl –hexane (1:2 v/v).
2 2
2
-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methylthio]-1H-benzimid-
azole (4)
tant to note that when halogens are included in the struc- The title compound was prepared from 2 (100 mg, 0.53 mmol),
NaN (38 mg, 0.58 mmol), and benzyl chloride (67 μL, 0.58 mmol)
ture of the monotriazoles 4–8, the IEs were always higher
than 93%. Furthermore, for these sorts of monotriazoles
the higher IE was attained by 5, which comprises the hal-
ogen with the largest electronegativity. In contrast, in the
case of the bis-triazoles 9–13, the highest IE was obtained
for compound 9, which does not include halogen atoms in
its structure.
3
according to GP1; yield: 160 mg (94%); white solid; mp 180–
81 °C.
1
IR (ATR): 3140, 3063, 3032, 2957, 2780, 2692, 2603, 1435, 1402,
348, 1271, 1224, 742, 708 cm .
–
1
1
1
H NMR (500 MHz, DMSO-d ): δ = 4.61 (s, 2 H, SCH ), 5.55 (s, 2
H, NCH ), 7.11–7.15 (m, 2 H, ArH), 7.22–7.24 (m, 2 H, ArH),
.28–7.33 (m, 3 H, ArH), 7.46 (br s, 2 H, ArH), 8.08 (s, 1 H, CH,
6
2
2
7
In conclusion, ten new 1,2,3-triazole derivatives of 2- triazole), 12.58 (br s, 1 H, NH).
benzimidazolethiol were successfully synthesized in good
13
C NMR (125.7 MHz, DMSO-d ): δ = 26.5 (SCH ), 53.2 (NCH ),
6
2
2
yields through a one-pot three-component click reaction. 110.9 (ArCH), 117.9 (ArCH), 121.9 (2 × ArCH), 124.1 (CH, tri-
The chemical structures of all synthesized compounds azole), 128.3 (2 × ArCH), 128.5 (ArCH), 129.1 (2 × ArCH), 136.0
(
(
Cipso, benzimidazole), 136.4 (Cipso), 143.9 (Cipso, triazole), 144.1
Cipso, benzimidazole), 149.8 (N=CS).
were confirmed by NMR, IR, and mass spectra. The cor-
rosion inhibition efficiencies measured through EIS meth-
od indicate that all new heterocyclic compounds are
promising corrosion inhibitors for steel in 1 M hydrochlo-
ric acid.
+
HRMS (ESI-TOF): m/z [M + H] calcd for C H N S: 322.1121;
found: 322.1126.
17 15
5
2
-{[1-(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl]methylthio}-1H-
benzimidazole (5)
The title compound was prepared from 2 (100 mg, 0.53 mmol),
Commercially available reagents and solvents were used as re-
ceived. Flash column chromatography was performed on silica gel
NaN (38 mg, 0.58 mmol), and 4-fluorobenzyl chloride (69 μL, 0.58
mmol) according to GP1; yield: 165 mg (92%); white solid; mp
1
3
60 (230–400 mesh). Melting points were determined on a Fisher–
52–153 °C.
Johns apparatus and are uncorrected. IR spectra were recorded on a
Bruker Alpha FT-IR/ATR spectrophotometer. NMR spectra were
obtained with a Jeol ECA-500 (500 MHz) and Bruker Avance
DMX-500 (500 MHz) spectrometers. Chemical shifts (δ) are given
IR (ATR): 3136, 3063, 2957, 2785, 2692, 2614, 1717, 1608, 1510,
1
–
1
434, 1402, 1224, 748 cm .
1
H NMR (500 MHz, DMSO-d ): δ = 4.60 (s, 2 H, SCH ), 5.54 (s, 2
6
2
in ppm downfield from Me Si as an internal reference; coupling
H, NCH ), 7.11–7.16 (m, 4 H, ArH), 7.29–7.32 (m, 2 H, ArH), 7.46
(br s, 2 H, ArH), 8.08 (s, 1 H, CH, triazole), 12.58 (br s, 1 H, NH).
4
2
13
constants J are given in hertz. The C NMR spectra of compounds
–8 were recorded overnight. High-resolution mass spectra
HRMS) were recorded on a Jeol JMS-SX 102a and Agilent-MSD-
4
(
13
C NMR (125.7 MHz, DMSO-d ): δ = 26.4 (SCH ), 52.4 (NCH ),
6
2
2
1
1
10.9 (ArCH), 116.0 (d, JC,F = 21.5 Hz, 2 × ArCH), 117.9 (ArCH),
21.8 (2 × ArCH), 124.1 (CH, triazole), 130.6 (d, JC,F = 8.3 Hz, 2 ×
TOF-1069A spectrometers. The electrochemical impedance study
was performed at room temperature using the ZENNIUM-ZAHN-
ER electrochemical workstation (ZAHNER-Elektrik GmbH & Co.
KG), applying a sinusoidal ± 10 mV perturbation, within the 100
KHz to 0.1 Hz frequency range to an electrochemical cell with a
three-electrode setup. A saturated Ag/AgCl electrode was used as
reference, with a graphite bar as counter electrode, while the work-
ArCH), 132.6 (d, JC,F = 1.9 Hz, Cipso), 135.9 (Cipso, benzimidazole),
44.0 (2 × Cipso, benzimidazole, triazole), 149.7 (N=CS), 162.3
JC,F = 244.3 Hz, FCipso).
1
(
+
HRMS (ESI-TOF): m/z [M + H] calcd for C H FN S: 340.1027;
17 14
5
found: 340.1031.
Synthesis 2014, 46, 1217–1223
© Georg Thieme Verlag Stuttgart · New York

PAPER
1,2,3-Triazole Derivatives of 2-Benzimidazolethiol
1221
2
-{[1-(4-Chlorobenzyl)-1H-1,2,3-triazol-4-yl]methylthio}-1H-
L-ascorbate (87 mg, 0.44 mmol) in EtOH–H O (2:1 v/v, 6 mL), fol-
lowed by stirring for 5 min at r.t. Subsequently, 3 (100 mg, 0.44
2
benzimidazole (6)
The title compound was prepared from 2 (100 mg, 0.53 mmol),
NaN (38 mg, 0.58 mmol), and 4-chlorobenzyl chloride (93 mg,
mmol), NaN (60 mg, 0.92 mmol), and benzyl halide (0.92 mmol)
3
3
were added to the reaction mixture, which was stirred for 24 h at r.t.
The mixture was extracted with CH Cl (3 × 5 mL). The combined
0.58 mmol) according to GP1; yield: 170 mg (90%); white solid;
2
2
mp 116–117 °C.
organic phase was dried (Na SO ) and then the solvent was evapo-
2
4
rated under vacuum. The crude product was purified by column
chromatography (CH Cl –MeOH, 90:10 v/v) and recrystallized
IR (ATR): 3132, 3071, 2967, 2883, 2808, 2697, 1719, 1490, 1420,
–
1
1404, 1348, 1269, 1225, 783, 747 cm .
2
2
from CH Cl –hexane (1:2 v/v).
1
2
2
H NMR (500 MHz, DMSO-d ): δ = 4.60 (SCH ), 5.55 (NCH ),
6
2
2
7
.11–7.15 (m, 2 H, ArH), 7.25 (d, J = 8.6 Hz, 2 H, ArH), 7.37 (d,
1
-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl]-2-[(1-benzyl-1H-
J = 8.5 Hz, 2 H, ArH), 7.53 (br s, 2 H, ArH), 8.08 (s, 1 H, CH, tri-
azole), 12.58 (br s, 1 H, NH).
1,2,3-triazol-4-yl)methylthio]-1H-benzimidazole (9)
The title compound was prepared from 3 (100 mg, 0.44 mmol),
1
3
NaN
mmol) according to GP2; yield: 200 mg (92%); white solid; mp
61–162 °C.
3
(60 mg, 0.92 mmol), and benzyl chloride (106 μL, 0.92
C NMR (125.7 MHz, DMSO-d ): δ = 26.4 (SCH ), 52.4 (NCH ),
6
2
2
1
(
(
10.8 (ArCH), 117.9 (ArCH), 121.6 (ArCH), 122.1 (ArCH), 124.2
CH, triazole), 129.1 (2 × ArCH), 130.2 (2 × ArCH), 133.3
ClCipso), 135.4 (Cipso), 135.9 (Cipso, benzimidazole), 144.0 (2 ×
1
IR (ATR): 3136, 3064, 3022, 2940, 1719, 1494, 1447, 1378, 1045,
–
1
Cipso, benzimidazole, triazole), 149.7 (N=CS).
740, 713, 691 cm .
+
1
HRMS (ESI-TOF): m/z [M + H] calcd for C H ClN S: 356.0731;
H NMR (500 MHz, DMSO-d ): δ = 4.65 (s, 2 H, SCH ), 5.40 (s, 2
1
7
14
5
6
2
found: 356.0735.
H, NCH ), 5.53 (s, 2 H, NCH Ph), 5.56 (s, 2 H, NCH Ph), 7.16–7.22
2
2
2
(
8
m, 2 H, ArH), 7.24–7.36 (m, 10 H, ArH), 7.56–760 (m, 2 H, ArH),
.12 (s, 1 H, CH, triazole), 8.15 (s, 1 H, CH, triazole).
2
-{[1-(4-Bromobenzyl)-1H-1,2,3-triazol-4-yl]methylthio}-1H-
benzimidazole (7)
13
C NMR (125.7 MHz, DMSO-d ): δ = 27.3 (SCH ), 39.2 (NCH ),
The title compound was prepared from 2 (100 mg, 0.53 mmol),
NaN (38 mg, 0.58 mmol), and 4-bromobenzyl bromide (145 mg,
6
2
2
5
1
3.25 (NCH Ph), 53.26 (NCH Ph), 110.5 (ArCH), 118.3 (ArCH),
2
2
3
22.2 (ArCH), 122.3 (ArCH), 124.1 (CH, triazole), 124.4 (CH, tri-
0.58 mmol) according to GP1; yield: 190 mg (90%); white solid;
azole), 128.28 (2 × ArCH), 128.29 (2 × ArCH), 128.53 (ArCH),
1
1
mp 130–131 °C.
28.56 (ArCH), 129.2 (4 × ArCH), 136.34 (Cipso), 136.37 (Cipso),
IR (ATR): 3125, 3063, 2972, 2879, 2807, 2692, 1718, 1488, 1397,
36.4 (Cipso, benzimidazole), 142.7 (Cipso, triazole), 143.4 (Cipso
,
–
1
1345, 1269, 1224, 784, 745 cm .
benzimidazole), 143.5 (Cipso, triazole), 150.9 (N=CS).
1
H NMR (500 MHz, DMSO-d ): δ = 4.61 (s, 2 H, SCH ), 5.54 (s, 2
+
6
2
HRMS (ESI-TOF): m/z [M + H] calcd for C H N S: 493.1917;
found: 493.1913.
2
7
24
8
H, NCH ), 7.12–7.16 (m, 2 H, ArH), 7.19 (d, J = 8.6 Hz, 2 H, ArH),
2
7.40 (br s, 1 H, ArH), 7.50 (d, J = 8.6 Hz, 2 H, ArH), 7.53 (br s, 1
H, ArH), 8.09 (s, 1 H, CH, triazole), 12.58 (br s, 1 H, NH).
1
-{[(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl]methyl}-2-{[(1-(4-
13
fluorobenzyl)-1H-1,2,3-triazol-4-yl]methylthio}-1H-benzimid-
azole (10)
C NMR (125.7 MHz, DMSO-d ): δ = 26.4 (SCH ), 52.5 (NCH ),
6
2
2
1
(
1
10.8 (ArCH), 117.9 (ArCH), 121.7 (ArCH), 121.8 (BrCipso), 122.1
ArCH), 124.2 (CH, triazole), 130.5 (2 × ArCH), 132.1 (2 × ArCH),
35.8 (Cipso), 136.0 (Cipso, benzimidazole), 144.0 (2 × Cipso, benz-
The title compound was prepared from 3 (100 mg, 0.44 mmol),
NaN (60 mg, 0.92 mmol), and 4-fluorobenzyl chloride (110 μL,
3
0.92 mmol) according to GP2; yield: 200 mg (86%); white solid;
imidazole, triazole), 149.7 (N=CS).
mp 174–175 °C.
+
HRMS (ESI-TOF): m/z [M + H] calcd for C H BrN S: 400.0226;
1
7
14
5
IR (ATR): 3147, 3127, 3069, 3021, 2979, 1718, 1608, 1509, 1448,
1
found: 400.0218.
–1
434, 1378, 1229, 815, 788, 739 cm .
1
2
-{[1-(4-Iodobenzyl)-1H-1,2,3-triazol-4-yl]methylthio}-1H-
H NMR (500 MHz, DMSO-d ): δ = 4.64 (s, 2 H, SCH ), 5.39 (s, 2
6 2
benzimidazole (8)
H, NCH ), 5.52 (s, 2 H, NCH Ar), 5.54 (s, 2 H, NCH Ar), 7.12–7.20
(
8.11 (s, 1 H, CH, triazole), 8.15 (s, 1 H, CH, triazole).
2
2
2
The title compound was prepared from 2 (100 mg, 0.53 mmol),
NaN (38 mg, 0.58 mmol), and 4-iodobenzyl bromide (172 mg, 0.58
mmol) according to GP1; yield: 220 mg (93%); white solid; mp
m, 6 H, ArH), 7.29–7.35 (m, 4 H, ArH), 7.56–7.59 (m, 2 H, ArH),
3
13
C NMR (125.7 MHz, DMSO-d ): δ = 27.3 (SCH ), 39.2 (NCH ),
168–169 °C.
6
2
2
5
2.44 (NCH Ar), 52.46 (NCH Ar), 110.4 (ArCH), 115.98 (d,
2
2
IR (ATR): 3129, 3075, 2968, 2887, 2812, 2693, 1719, 1484, 1417,
JC,F = 21.6 Hz, 2 × ArCH), 116.0 (d, JC,F = 21.6 Hz, 2 × ArCH),
18.2 (ArCH), 122.2 (ArCH), 122.3 (ArCH), 124.1 (CH, triazole),
124.3 (CH, triazole), 130.6 (d, JC,F = 8.4 Hz, 2 × ArCH), 130.64 (d,
–
1
1398, 1269, 1226, 801, 746 cm .
1
1
H NMR (500 MHz, DMSO-d ): δ = 4.56 (s, 2 H, SCH ), 5.47 (s,
6
2
2H, NCH ), 6.99 (d, J = 8.1 Hz, 2 H, ArH), 7.09–7.11 (m, 2 H,
J
J
C,F = 8.4 Hz, 2 × ArCH), 132.57 (d, JC,F = 3.1 Hz, Cipso), 132.62 (d,
C,F = 3.1 Hz, Cipso), 136.4 (Cipso), 142.7 (Cipso, triazole), 143.4
2
ArH), 7.32–7.36 (m, 1 H, ArH), 7.49–7.53 (m, 1 H, ArH), 7.63 (d,
J = 8.1 Hz, 2 H, ArH), 8.04 (s, 1 H, CH, triazole), 12.56 (br s, 1 H,
NH).
(Cipso, benzimidazole), 143.5 (Cipso, triazole), 150.9 (N=CS), 162.3
(d, JC,F = 244.3 Hz, FCipso), 163.3 (d, JC,F = 244.4 Hz, FCipso).
1
3
+
C NMR (125.7 MHz, DMSO-d ): δ = 26.5 (SCH ), 52.7 (NCH ),
HRMS (ESI-TOF): m/z [M + H] calcd for C27
found: 529.1728.
H
22
F
2
N
8
S: 529.1729;
6
2
2
9
4.9 (ICipso), 110.9 (ArCH), 118.0 (ArCH), 121.7 (ArCH), 122.3
ArCH), 124.3 (CH, triazole), 130.6 (2 × ArCH), 136.0 (Cipso, benz-
imidazole), 136.3 (Cipso), 138.0 (2 × ArCH), 144.09 (Cipso, triazole),
(
1
-{[(1-(4-Chlorobenzyl)-1H-1,2,3-triazol-4-yl]methyl}-2-{[1-(4-
chlorobenzyl)-1H-1,2,3-triazol-4-yl]methylthio}-1H-benzimid-
azole (11)
1
44.15 (Cipso, benzimidazole), 149.8 (N=CS).
+
HRMS (ESI-TOF): m/z [M + H] calcd for C H IN S: 448.0087;
The title compound was prepared from 3 (100 mg, 0.44 mmol),
17
14
5
found: 448.0090.
NaN (60 mg, 0.92 mmol), and 4-chlorobenzyl chloride (148 mg,
3
0.92 mmol) according to GP2; yield: 210 mg (85%); white solid;
Bis-1,2,3-triazoles Derived from 2-Benzimidazolethiol 3; Gen-
eral Procedure 2 (GP2)
To a 50 mL round-bottomed flask with a magnetic stirrer, were
charged Cu(OAc) ·H O (4 mg, 0.022 mmol, 5 mol%), 1,10-phenan-
mp 141–142 °C.
IR (ATR): 3148, 3125, 3065, 3016, 2956, 1716, 1491, 1448, 1434,
–1
1
376, 804, 786, 738 cm .
2
2
throline monohydrate (4.4 mg, 0.022 mmol, 5 mol%), and sodium
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1217–1223

1222
D. Y. Cruz-Gonzalez et al.
PAPER
1
H NMR (500 MHz, DMSO-d ): δ = 4.64 (s, 2 H, SCH ), 5.40 (s, 2 Acknowledgment
6
2
H, NCH ), 5.54 (s, 2 H, NCH Ar), 5.56 (s, 2 H, NCH Ar), 7.16–7.21
2
2
2
The authors would like to thank Consejo Nacional de Ciencia y
Tecnología, CONACyT (project 181448) for financial support.
RGO, GENS, LLR, MEPP, MARR, RS, and JU wish to acknow-
ledge the SNI (Sistema Nacional de Investigadores) for the distinc-
tion of their membership and the stipend received. We also wish to
thank Rebeca Yépez for her technical assistance, Teresa Cortez for
her help with NMR experiments, Dr. Delia Soto-Castro and Geiser
Cuéllar for the mass measurements.
(
2
m, 2 H, ArH), 7.26 (d, J = 8.8 Hz, 2 H, ArH), 7.28 (d, J = 8.8 Hz,
H, ArH), 7.37 (d, J = 8.7 Hz, 2 H, ArH), 7.40 (d, J = 8.7 Hz, 2 H,
ArH), 7.56–7.59 (m, 2 H, ArH), 8.12 (s, 1 H, CH, triazole), 8.16 (s,
1
H, CH, triazole).
13
C NMR (125.7 MHz, DMSO-d ): δ = 27.3 (SCH ), 39.2 (NCH ),
6
2
2
5
1
2.4 (NCH Ar), 52.5 (NCH Ar), 110.4 (ArCH), 118.3 (ArCH),
2
2
22.2 (ArCH), 122.3 (ArCH), 124.2 (CH, triazole), 124.4 (CH, tri-
azole), 129.14 (2 × ArCH), 129.16 (2 × ArCH), 130.20 (2 × ArCH),
30.24 (2 × ArCH), 133.29 (ClCipso), 133.34 (ClCipso), 135.31
Cipso), 135.36 (Cipso), 136.4 (Cipso, benzimidazole), 142.7 (Cipso, tri-
1
(
Supporting Information for this article is available online at
azole), 143.4 (Cipso), 143.6 (Cipso, triazole), 150.9 (N=CS).
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
HRMS (ESI-TOF): m/z [M + H]+ calcd for C H Cl N S:
2
7
22
2
8
5
61.1138; found: 561.1135.
References
1
-{[(4-Bromobenzyl)-1H-1,2,3-triazol-4-yl]methyl}-2-{[(1-(4-
bromobenzyl)-1H-1,2,3-triazol-4-yl]methylthio}-1H-benzimid-
azole (12)
(1) (a) Ganesh, A. Int. J. Chem. Sci. 2013, 11, 573. (b) Agalave,
S. G.; Maujan, S. R.; Pore, V. S. Chem. Asian J. 2011, 6,
The title compound was prepared from 3 (100 mg, 0.44 mmol),
2
696.
NaN (60 mg, 0.92 mmol), and 4-bromobenzyl bromide (230 mg,
3
(2) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless,
K. B. Angew. Chem. Int. Ed. 2002, 41, 2596. (b) Tornøe, C.
W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67,
3057.
(3) (a) Bock, V. D.; Hiemstra, H.; van Maarseveen, J. H. Eur. J.
Org. Chem. 2006, 51. (b) Meldal, M.; Tornøe, C. W. Chem.
Rev. 2008, 108, 2952. (c) Gramlich, P. M. E.; Wirges, C. T.;
Manetto, A.; Carell, T. Angew. Chem. Int. Ed. 2008, 47,
0.92 mmol) according to GP2; yield: 250 mg (87%); white solid;
mp 138–139 °C.
IR (ATR): 3148, 3119, 3067, 2988, 2950, 1717, 1488, 1449, 1434,
–
1
1377, 1012, 785, 737 cm .
1
H NMR (500 MHz, DMSO-d ): δ = 4.64 (s, 2 H, SCH ), 5.40 (s, 2
6
2
H, NCH ), 5.52 (s, 2 H, NCH Ar), 5.54 (s, 2 H, NCH Ar), 7.16–7.23
2
2
2
(m, 6 H, ArH), 7.50 (d, J = 8.6 Hz, 2 H, ArH), 7.53 (d, J = 8.6 Hz,
8350. (d) Amblard, F.; Cho, J. H.; Schinazi, R. F. Chem.
2
8
H, ArH), 7.56–7.59 (m, 2 H, ArH), 8.12 (s, 1 H, CH, triazole),
.16 (s, 1 H, CH, triazole).
Rev. 2009, 109, 4207. (e) Hein, J. E.; Fokin, V. V. Chem.
Soc. Rev. 2010, 39, 1302. (f) Struthers, H.; Mindt, T. L.;
Schibli, R. Dalton Trans. 2010, 39, 675. (g) Lallana, E.;
Riguera, R.; Fernandez-Mejia, E. Angew. Chem. Int. Ed.
2011, 50, 8794. (h) Pedersen, D. S.; Abell, A. Eur. J. Org.
Chem. 2011, 2399. (i) Efthymiou, T.; Gong, W.;
13
C NMR (125.7 MHz, DMSO-d ): δ = 27.3 (SCH ), 39.2 (NCH ),
6
2
2
52.49 (NCH Ar), 52.52 (NCH Ar), 110.4 (ArCH), 118.3 (ArCH),
2
2
121.8 (BrCipso), 121.9 (BrCipso), 122.2 (ArCH), 122.3 (ArCH), 124.2
(CH, triazole), 124.4 (CH, triazole), 130.51 (2 × ArCH), 130.55 (2
×
ArCH), 132.08 (2 × ArCH), 132.09 (2 × ArCH), 135.72 (Cipso),
Desaulniers, J.-P. Molecules 2012, 17, 12665. (j) He, X.-P.;
Xie, J.; Tang, Y.; Li, J.; Chen, G.-R. Curr. Med. Chem. 2012,
1
1
35.78 (Cipso), 136.4 (Cipso, benzimidazole), 142.7 (Cipso, triazole),
43.3 (Cipso, benzimidazole), 143.6 (Cipso, triazole), 150.9 (N=CS).
1
9, 2399. (k) Pasini, D. Molecules 2013, 18, 9512. (l) Avti,
HRMS (ESI-TOF): m/z [M + H]+ calcd for C H Br N S:
2
7
22
2
8
P. V.; Maysinger, D.; Kakkar, A. Molecules 2013, 18, 9531.
(m) Li, H.; Aneja, R.; Chaiken, I. Molecules 2013, 18, 9797.
649.0128; found: 649.0133.
(
n) Ahmad Fuaad, A. A. H.; Azmi, F.; Skwarczynski, M.;
1
-{[(4-Iodobenzyl)-1H-1,2,3-triazol-4-yl]methyl}-2-{[(1-(4-io-
Toth, I. Molecules 2013, 18, 13148.
dobenzyl)-1H-1,2,3-triazol-4-yl]methylthio}-1H-benzimidazole
(
4) (a) González-Olvera, R.; Espinoza-Vázquez, A.; Negrón-
Silva, G. E.; Palomar-Pardavé, M. E.; Romero-Romo, M.
A.; Santillan, R. Molecules 2013, 18, 15064. (b) Deng, Q.;
He, X.-P.; Shi, H.-W.; Chen, B.-Q.; Liu, G.; Tang, Y.; Long,
Y.-T.; Chen, G. R.; Chen, K. Ind. Eng. Chem. Res. 2012, 51,
(
13)
The title compound was prepared from 3 (100 mg, 0.44 mmol),
NaN (60 mg, 0.92 mmol), and 4-iodobenzyl bromide (273 mg, 0.92
mmol) according to GP2; yield: 290 mg (89%); white solid; mp
3
135–136 °C.
7
160. (c) Deng, Q.; Ding, N.-N.; Wei, X.-L.; Cai, L.; He, X.-
P.; Long, Y.-T.; Chen, G.-R.; Chen, K. Corros. Sci. 2012,
4, 64. (d) Deng, Q.; Shi, H.-W.; Ding, N.-N.; Chen, B.-Q.;
IR (ATR): 3123, 3063, 2958, 2930, 1717, 1485, 1448, 1433, 1009,
–
1
779, 735 cm .
6
1
H NMR (500 MHz, DMSO-d ): δ = 4.63 (s, 2 H, SCH ), 5.39 (s, 2
He, X.-P.; Liu, G.; Tang, Y.; Long, Y.-T.; Chen, G.-R.
Corros. Sci. 2012, 57, 220. (e) Zhang, H.-L.; He, X.-P.;
Deng, Q.; Long, Y.-T.; Chen, G.-R.; Chen, K. Carbohydr.
Res. 2012, 354, 32. (f) Babić-Samardžija, K.; Hacherman,
N. J. Solid State Electrochem. 2005, 9, 483. (g) Abdennabi,
A. M. S.; Abdulhadi, A. I.; Abu-Orani, S. T.; Saricimen, H.
Corros. Sci. 1996, 38, 1791.
6
2
H, NCH ), 5.49 (s, 2 H, NCH Ar), 5.51 (s, 2 H, NCH Ar), 7.04 (d,
J = 8.6 Hz, 2 H, ArH), 7.06 (d, J = 8.6 Hz, 2 H, ArH), 7.16–7.21 (m,
2
2
2
2
H, ArH), 7.55–7.58 (m, 2 H, ArH), 7.67 (d, J = 8.5 Hz, 2 H, ArH),
7.70 (d, J = 8.5 Hz, 2 H, ArH), 8.10 (s, 1 H, CH triazole), 8.14 (s, 1
H, CH triazole).
13
C NMR (125.7 MHz, DMSO-d ): δ = 27.3 (SCH ), 39.2 (NCH ),
6
2
2
(
5) (a) Olvera-Martinez, M. E.; Mendoza-Flores, J.; Rodriguez-
Gomez, F. J.; Palomar-Pardave, M. E.; Genesca, J. Mater.
Corros. 2013, 64, 522. (b) Benabdellah, M.; Tounsi, A.;
Khaled, K. F.; Hammouti, B. Arabian J. Chem. 2011, 4, 17;
Chem. Abstr. 2010, 154, 289472. (c) Mahdavian, M.;
Ashhari, S. Electrochim. Acta 2010, 55, 1720. (d) Forsal, I.;
Ebn Touhami, M.; Mernari, B.; El Hajri, J.; Filali Baba, M.
Port. Electrochim. Acta 2010, 28, 203. (e) Aljourani, J.;
Raeissi, K.; Golozar, M. A. Corros. Sci. 2009, 51, 1836.
5
2.65 (NCH Ar), 52.67 (NCH Ar), 94.81 (ICipso), 94.87 (ICipso),
2
2
110.4 (ArCH), 118.3 (ArCH), 122.2 (ArCH), 122.3 (ArCH), 124.2
(CH, triazole), 124.4 (CH, triazole), 130.5 (2 × ArCH), 130.6 (2 ×
ArCH), 136.08 (Cipso), 136.13 (Cipso), 136.3 (Cipso, benzimidazole),
137.94 (2 × ArCH), 137.95 (2 × ArCH), 142.7 (Cipso, triazole),
143.3 (Cipso, benzimidazole), 143.6 (Cipso, triazole), 150.8 (N=CS).
+
HRMS (ESI-TOF): m/z [M + H] calcd for C H I N S: 744.9850;
found: 744.9854.
2
7
22 2
8
(
f) Popova, A.; Christov, M.; Raicheva, S.; Sokolova, E.
Synthesis 2014, 46, 1217–1223
© Georg Thieme Verlag Stuttgart · New York

PAPER
Corros. Sci. 2004, 46, 1333. (g) Popova, A.; Sokolova, E.;
1,2,3-Triazole Derivatives of 2-Benzimidazolethiol
1223
(10) (a) Hwang, S.; Bae, H.; Kim, S.; Kim, S. Tetrahedron 2012,
68, 1460. (b) Lewis, W. G.; Magallon, F. G.; Fokin, V. V.;
Finn, M. G. J. Am. Chem. Soc. 2004, 126, 9152.
(11) Creutz, C. Inorg. Chem. 1981, 20, 4449.
(12) Creary, X.; Anderson, A.; Brophy, C.; Crowell, F.; Funk, Z.
J. Org. Chem. 2012, 77, 8756.
Raicheva, S.; Christov, M. Corros. Sci. 2003, 45, 33.
6) (a) Shah, K.; Chhabra, S.; Shrivastava, S. K.; Mishra, P.
Med. Chem. Res. 2013, 22, 5077. (b) Narasimhan, B.;
Sharma, D.; Kumar, P. Med. Chem. Res. 2012, 21, 269.
(
(c) Bansal, Y.; Silakari, O. Bioorg. Med. Chem. 2012, 20,
6
208. (d) Chawla, A.; Kaur, R.; Goyal, A. J. Chem. Pharm.
(13) (a) Yadav, M.; Behera, D.; Kumar, S.; Sinha, R. R. Ind. Eng.
Chem. Res. 2013, 52, 6318. (b) Ouici, H. B.; Benali, O.;
Harek, Y.; Larabi, L.; Hammouti, B.; Guendouzi, A. Res.
Chem. Intermed. 2013, 39, 2777. (c) Ansari, K. R.; Yadav,
D. K.; Ebenso, E. E.; Quraishi, M. A. Int. J. Electrochem.
Sci. 2012, 7, 4780. (d) Kumar, M. S.; Kumar, S. L.;
Sreekanth, A. Ind. Eng. Chem. Res. 2012, 51, 5408.
(e) Nataraja, S. E.; Venkatesha, T. V.; Manjunatha, K.;
Poojary, B.; Pavithra, M. K.; Tandon, H. C. Corros. Sci.
2011, 53, 2651. (f) Khadom, A. A.; Musa, A. Y.; Kadhum,
A. A. H.; Mohamed, A. B.; Takriff, M. S. Port. Electrochim.
Acta 2010, 28, 221. (g) Álvarez-Bustamante, R.; Negrón-
Silva, G.; Abreu-Quijano, M.; Herrera-Hernández, H.;
Romero-Romo, M.; Cuán, A.; Palomar-Pardavé, M.
Electrochim. Acta 2009, 54, 5393. (h) Hassan, H. H.;
Abdelghani, E.; Amin, M. A. Electrochim. Acta 2007, 52,
6359. (i) Quraishi, M. A.; Sharma, H. K. Mater. Chem. Phys.
2002, 78, 18.
Res. 2011, 3, 925.
(
7) Cruz-Gonzalez, D. Y.; González-Olvera, R.; Angeles-
Beltrán, D.; Negrón-Silva, G. E.; Santillan, R. Synthesis
2
013, 45, 3281.
(
8) (a) Cruz-Gonzalez, D. Y.; Negrón-Silva, G.; Angeles-
Beltrán, D.; Palomar-Pardavé, M.; Romero-Romo, M.;
Uruchurtu-Chavarín, J. ECS Trans. 2011, 36, 197.
(b) Espinoza, A.; Negrón, G.; Palomar-Pardavé, M.;
Romero-Romo, M. A.; Rodríguez-Torres, I.; Herrera-
Hernández, H. ECS Trans. 2009, 20, 543. (c) Morales-Gil,
P.; Negrón-Silva, G.; Romero-Romo, M.; Ángeles-Chávez,
C.; Palomar-Pardavé, M. Electrochim. Acta 2004, 49, 4733.
9) (a) Negrón-Silva, G. E.; González-Olvera, R.; Angeles-
Beltrán, D.; Maldonado-Carmona, N.; Espinoza-Vázquez,
A.; Palomar-Pardavé, M. E.; Romero-Romo, M. A.;
Santillan, R. Molecules 2013, 18, 4613. (b) Mendoza-
Espinosa, D.; Negrón-Silva, G. E.; Lomas-Romero, L.;
Gutiérrez-Carrillo, A.; Soto-Castro, D. Synthesis 2013, 45,
(
2
431.
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1217–1223