A Facile and efficient procedure for the synthesis of new benzimidazole-2-thione derivatives

Article abstract of DOI:10.3390/molecules17078578

A series of benzimidazole-2-thione derivatives was synthesized using a reaction between the macrocyclic aminal 16H,13H-5:12,7:14-dimethanedibenzo[d,i]- [1,3,6,8] tetraazecine (DMDBTA, 5) and various nucleophiles in the presence of carbon disulfide. A full chemical characterization using IR, ¹H-, ₁₃C-NMR and GC-MS analyses of the new compounds is provided. These compounds were separated from the reaction mixture by column chromatography (CC) in highly pure form in 15%-51.4% yield.

Full text of DOI:10.3390/molecules17078578

Molecules 2012, 17, 8578-8586; doi:10.3390/molecules17078578
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
A Facile and Efficient Procedure for the Synthesis of
New Benzimidazole-2-thione Derivatives
Augusto Rivera *, Mauricio Maldonado and Jaime Ríos-Motta
Departamento de Química, Facultad de Ciencias, Universidad Nacional de Colombia, Sede Bogotá,
Cra.30 No.45-03, Bogotá 111321, Colombia; E-Mails: mmaldonadov@unal.edu.co (M.M.);
jariosmo@unal.edu.co (J.R.-M.)
* Author to whom correspondence should be addressed; E-Mail: ariverau@unal.edu.co;
Tel.: +57-1-316-5000; Fax: +57-1-316-5220.
Received: 4 May 2012; in revised form: 27 June 2012 / Accepted: 9 July 2012 /
Published: 17 July 2012
Abstract: A series of benzimidazole-2-thione derivatives was synthesized using a
reaction between the macrocyclic aminal 16H,13H-5:12,7:14-dimethanedibenzo[d,i]-[1,3,6,8]
tetraazecine (DMDBTA, 5) and various nucleophiles in the presence of carbon disulfide. A
1
13
full chemical characterization using IR, H-, C-NMR and GC-MS analyses of the new
compounds is provided. These compounds were separated from the reaction mixture by
column chromatography (CC) in highly pure form in 15%–51.4% yield.
Keywords: benzimidazole-2-thione; benzimidazole; sulfur chemistry; aminal cage
1. Introduction
The reaction between carbon disulfide and amines was originally reported by Hoffmann in the 19th
century [1]. This reaction with primary and secondary aliphatic amines in ethanol yields reactive
dithiocarbamate salt intermediates 1 that can be converted into S-alkyl dithiocarbamates 2, which have
several biological activities, via reaction with electrophiles or into dithiocarbamic acids by treatment
with mineral acids [2]. In the case of aliphatic diamines, the treatment of the dithiocarbamate
intermediate with acid gives cyclic thioureas 3 [3]. In contrast, the reaction with o-phenylenediamine
under basic conditions afforded 2-mercaptobenzimidazole (4) [4,5] (Figure 1). In recent years, cyclic
thioureas and mercaptobenzimidazoles have had important industrial applications as anticorrosive
agents [6–8], friction attenuators [9] and heavy metal adsorbents [10]. Moreover, derivatives of cyclic

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thioureas have important roles in medicinal chemistry owing to their utility as antiseptic [11],
antidepressive [12], antitumour [13], and antibacterial agents [14–16]. In addition, thioureas have been
used as ligands in copper (I)-based complexes [17,18] and in complexes with other metals [19].
Figure 1. The chemical structures of compounds 1–6.
SH
R
N
S
S
S-
R
N
NH
R
R
S
N
R
HN
NH
S
1
2
3
4
S
S
N
N
N
N
N
N
N
N
5
6
In continuation of our work with the benzoaminal 6H,13H-5:12,7:14-dimethanedibenzo
[d,i]-[1,3,6,8]tetraazecine (DMDBTA, 5) [20–24], we recently became interested in synthesizing the
cyclic dithiocarbamate 8H,15H-5:14,9:16-dimethanedibenzo[d,i]-[1,3,6,8,11]thiatetraazatricycledo-
decine-6-thione (6). To obtain this product, we planned to use DMDBTA (5) and carbon disulfide in
ethanol, following the method reported by Donia et al. [25]. In earlier attempts, we found that the
reaction of 5 with carbon disulfide in ethanol did not provide the desired cyclic dithiocarbamate 6.
Instead, we found that 5 reacts with carbon disulfide to produce 1,3-bis(ethoxymethyl)-1,3-dihydro-
2H-benzimidazole-2-thione (7b) and 1-(ethoxymethyl)-1H-benzimidazole (8b) (Scheme 1).
Scheme 1. General reaction of 5 with nucleophiles in the presence of CS2.
S
N
N
N
N
N
N
Nu
N
N
Nu
Nu
CS2
+
+
NuH
+
5
7a-f
8a-f
NuH = a) MeOH, b) EtOH, c) n-PrOH, d) n-BuOH, e) HCN, f) BtH
The effects of the solvent on the product yields were examined using 5 as a substrate in various
alcohols, including methanol, ethanol, n-propanol, n-butanol and t-butanol. Contrary to our expectations,
when 5 was treated with t-butanol, the desired derivatives were not obtained. The efficacy of using

Molecules 2012, 17
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other nucleophiles was demonstrated by reacting 5 with CS2 and either hydrogen cyanide or
benzotriazole in the aprotic polar non-nucleophilic solvents 1,4-dioxane and acetonitrile, respectively.
2. Results and Discussion
We found the optimum conditions for the synthesis of compounds 7a–f and 8a–f. These products
1
were obtained in good yields with high purities. Both the analytical and spectral data (IR, H-NMR,
13C-NMR and GC-MS analyses) of all synthesised 1,3-bis(alcoxymethyl)-1,3-dihydro-2H-
benzimidazole-2-thiones 7a–f and 1-(alkoxymethyl)-1,3-dihydro-2H-benzimidazole compounds 8a–f
were in full agreement with the proposed structures.
The IR data for benzimidazole-2-thiones 7a–d clearly indicate the presence of the C=S group, with
υ(C=S) vibrations at 1098, 1099, 1104 and 1108. In the 1H-NMR spectra, the N–CH2–O protons of the
hemiaminal moiety of 1,3-bis(alcoxymethyl)-1,3-dihydro-2H-benzimidazole-2-thione appeared as a
singlet at approximately 5.79–5.82 ppm. In the 13C-NMR spectra, the signal of the thiourea functional
group was clearly observed at 171.8–169.3 ppm, and these signals are consistent with the signals of
analogous molecules [26]. The attributions of the other signals in 13C-NMR spectra were based on the
analysis of the HMQC and HMBC spectra. The molecular ions and fragment ions in the mass spectra
were also consistent with the assigned structures. The reaction with other nucleophiles in the presence
of an inert solvent under the same conditions produces benzimidazole and benzimidazole-2-thione
derivatives. When the reaction was carried out with the cyanide anion, 1,3-bis(cyano-1-ylmethyl)-1,3-
dihydro-2H-benzimidazole-2-thione (7e) and 1H-benzimidazol-1-yl-acetonitrile (8e) were obtained; in
an analogous manner, the reaction with benzotriazole (BtH) afforded 1,3-bis(1H-1,2,3-benzotriazol-
1-ylmethyl)-1,3-dihydro-2H-benzimidazole-2-thione (7f) and 1-(1H-benzimidazol-1-ylmethyl)-1H-
1,2,3-benzotriazole (8f). The structures of these heterocyclic systems were confirmed by the
spectroscopic data.
As shown in Table 1, the results reveal that the yield of the reaction depends on the size of the
nucleophile. Consequently, the use of t-butanol under the same reaction conditions afforded complex
mixtures, from which we were unable to isolate the expected benzimidazole-2-thione and
1-H-benzimidazole derivatives.
Table 1. Yields of benzimidazole-2-thione (7a–f) and 1-H-benzimidazole (8a–f) derivatives.
Entry
NuH
MeOH
EtOH
7 (%)
48.5
30.1
23.3
15.0
25.3
35.2
8 (%)
51.4
32.3
24.5
16.7
26.0
36.7
t (h)
24
a
b
c
d
e
f
30
n-PrOH
n-BuOH
HCN
34
40
24
BtH
24
According to these results, in the presence of an adequate nucleophile, the reactions efficiently
proceed to provide the ring opening of the benzoaminal. Thus, the first step of the reaction between 5
and CS2 might be fast, and the second step, involving the nucleophilic attack of the dithiocarbamate
salt, is slower and consequently should be the rate-limiting step. The onset of the reaction is indicated

Molecules 2012, 17
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by the evolution of hydrogen sulphide, whose odour was noticeable during the reaction. Based on these
results, we propose a possible pathway for the formation of the products (Scheme 2).
Scheme 2. Proposed pathway for the formation of 7a–f and 8a–f.
Nu
N
N
N
N
N
N
N
N
N
N
CS2
NuH
N+
CH
N
3
S
CH
H
-
3S
10
S
S
5
9
NuH
Nu
S
S
-
N
Nu
S
HS
N
NH+
NH
N
Nu
N
Nu
N
N
H
12
11
NuH
S
HS
NH
N
Nu
NH
N
+
Nu
Nu
14
13
O2
-H2S
S
N
N
Nu
Nu
N
N
Nu
8a-f
7a-f
We assumed that carbon disulfide first reacts with 5 to form the expected dithiocarbamate salt 9 as a
very active intermediate. This intermediate then reacts with one equivalent of the nucleophile, a
reaction that includes a proton shift, to produce a second intermediate 10 that is able to form S–H···N
intramolecular hydrogen bonds. This intramolecular interaction in this intermediate decreases the
relative stability of the intermediate and induces the attack of a second equivalent of nucleophile to
give a 1-substituted-3-aryl-2,3,4,5-tetrahydro-1H-1,3,5-benzotriazepine intermediate 11, in which a
proton transfer induces an intramolecular rearrangement to give 12. The presence of a positive charge

Molecules 2012, 17
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on the 1H-benzimidazole ring of 12 makes this adduct fairly labile, and the central NCH2N moiety in
12 undergoes a regioselective cleavage involving the preferential attack by a third equivalent of
nucleophile to give 13 and 14. Then, the benzimidazole-2-thiones 7a–f are obtained by cyclisation of
the acyclic intermediate 13 with the elimination of a molecule of H2S. Monosubstituted-benzimidazolines
14a–f, the other products formed from 12 under these reaction conditions, smoothly undergo oxidation
in air to yield the 1-(alkoxymethyl)-1,3-dihydro-2H-benzimidazole derivatives 8a–f, as observed
previously for other benzimidazoline derivatives [27]. Alcohols and cyclic ethers are good solvents for
this oxidative process [28–30].
3. Experimental
3.1. General
Melting points were determined on an Electrothermal 9100 melting point apparatus and are
uncorrected. Chemicals were used without further purification. FT-IR spectra were recorded in
1
potassium bromide pellets using Thermo Nicolet IS10 spectrophotometer. H-NMR and 13C-NMR
spectra were recorded in CDCl3 using a Bruker Avance AV-400 MHz spectrometer operates at 400
1
MHz for H and 100 MHz for 13C. Elemental analyses (C, H, N) were determined in a Thermo
Scientific Flash 2000. Combined GC–MS analysis was performed on a Hewlett–Packard 5973 mass
spectrometer at 70 eV coupled to a Hewlett–Packard 6890 gas chromatograph.
General procedure for the reaction of DMDBTA with CS2 in alcohols: Following the general
procedure described in the literature [25], carbon disulfide (0.95 mmol, 0.07 mL) was added dropwise
over 30 min to a shaking solution of DMDBTA (0.95 mmol) in the desired alcohol (30 mL). This
yellow solution was stirred at room temperature in the dark until the DMDBTA had dissolved
completely. The reaction was monitored by TLC. The removal of the solvent at reduced pressure
(50 mmHg) resulted in the collection of a resinous solid that was then purified via column
chromatography on silica gel (elution using benzene:ethyl acetate in a 9:1 mixture).
Procedure for the reaction of DMDBTA with benzotriazole and CS2: A mixture of DMDBTA
(0.95 mmol, 0.25 g), 1H-benzotriazole (2.85 mmol, 0.34 g) and carbon disulfide (0.95 mmol, 0.07 mL)
was stirred in 1,4-dioxane (30 mL) for 24 h. at room temperature in the dark yielding a resinous solid.
The precipitated solid was collected and purified via column chromatography on silica gel (elution
using benzene: ethyl acetate in a 9:1 mixture).
Procedure for the reaction of DMDBTA with cyanide anion and CS2: To a solution of DMDBTA
(0.95 mmol, 0.25 g) and carbon disulfide (0.95 mmol, 0.07 mL) in acetonitrile (15 mL), an excess of
hydrogen cyanide was bubbled in slowly. The reaction mixture was stirred at room temperature in the
dark for 24 h. The removal of the solvent at reduced pressure (50 mmHg) resulted in the collection of a
resinous product that was then purified via column chromatography on silica gel (elution using
benzene:ethyl acetate in a 9:1 mixture).

Molecules 2012, 17
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3.2. Physical and Spectral Data
1,3-Bis(methoxymethyl)-1,3-dihydro-2H-benzimidazole-2-thione (7a): White solid; m.p. 99–101 °C;
1H-NMR : 3.24 (6H, s, –CH3), 5.79 (4H, s, N-CH2-O), 7.24 (2H, m), 7.35 (2H, m); 13C-NMR : 52.6,
74.3, 111.5, 121.9, 132.5, 171.8; IR νmax (cm–1): 1,108 (C=S), 1,285 (C-O); EIMS, 70 eV, m/z: 238
(M+); Anal. Calcd. for C11H14N2O2S (238.36): C, 55.44; H, 5.92; N, 11.76; S, 13.46. Found: C, 55.23;
H, 5.96; N, 11.46; S, 13.22.
1,3-Bis(ethoxymethyl)-1,3-dihydro-2H-benzimidazole-2-thione (7b): Melting point 103–104 C (lit. [31]
104–106 C).
1,3-Bis(propoxymethyl)-1,3-dihydro-2H-benzimidazole-2-thione (7c): White solid; m.p. 120–122 C;
1H-NMR : 0.91 (6H, t, J = 6.9 Hz, –CH3), 1.59 (4H, s, J = 6.9 Hz, O-CH2CH2CH3), 3.46 (4H, q,
13
J = 6.9 Hz, O-CH2CH2CH3), 5.82 (4H, s, N–CH2–O), 7.27 (2H, m), 7.39 (2H, m); C-NMR : 10.7,
22.5, 64.9, 73.7, 110.3, 123.8, 132.4, 169.3; IR νmax (cm–1): 1,098 (C=S), 1,289 (C-O); EIMS, 70 eV,
m/z: 294 (M+); Anal. Calcd. for C15H22N2O2S (294.40): C, 61.19; H, 7.53; N, 9.52; S, 10.89. Found: C,
61.05; H, 7.66; N, 9.48; S, 10.85.
1,3-Bis(butoxymethyl)-1,3-dihydro-2H-benzimidazole-2-thione (7d): White solid; m.p. 124–126 C;
1H-NMR : 0.84 (6H, t, J = 6.7 Hz, –CH3), 1.65–1.68 (8H, m, O-CH2CH2CH2CH3), 3.59 (4H, t,
J = 6.7 Hz, O-CH2CH2 CH2CH3), 5.82 (4H, s, N-CH2-O), 7.30 (2H, m), 7.43 (2H, m); 13C-NMR : 14.3,
18.3, 30.9, 67.4, 72.4, 110.3, 123.6, 131.8, 171.1; IR νmax (cm–1): 1099 (C=S), 1288 (C-O); EIMS,
70 eV, m/z: 322 (M+); Anal. Calcd. for C17H26N2O2S (322.46): C, 63.32; H, 8.13; N, 8.69; S, 9.94.
Found: C, 63.24; H, 8.16; N, 8.67; S, 9.91.
1
1,3-bis(Cyano-1-methyl)-1,3-dihydro-2H-benzimidazole-2-thione (7e): Oily product; H-NMR : 5.32
(4H, s, N-CH2-CN), 7.56 (2H, m), 7.73 (2H, m); 13C-NMR : 31.9, 111.9, 118.3, 119.4, 134.7, 179.4; IR
νmax (cm–1): 2,236 (CN) 1,102 (C=S), 1,285; EIMS, 70 eV, m/z: 228 (M+); Anal. Calcd. for C11H8N4S
(228.27): C, 57.88; H, 3.53; N, 24.54; S, 14.05. Found: C, 57.91; H, 3.56; N, 24.48; S, 13.91.
1,3-bis(1H-1,2,3-Benzotriazol-1-ylmethyl)-1,3-dihydro-2H-benzimidazole-2-thione (7f): Yellow Solid;
1
m.p. 142–144 C; H-NMR : 7.07 (4H, s, N-CH2-Bt), 7.21 (4H, m, benzimidazoline nucleus), 7.35
(2H, t, J = 7.8 Hz, benzotriazole nucleus), 7.52 (2H, t, J = 7.8 Hz, benzotriazole nucleus), 8.08 (2H, d,
J = 7.8 Hz, benzotriazole nucleus), 8.43 (2H, d, J = 7.8 Hz, benzotriazole nucleus); 13C-NMR : 55.3,
110.1, 111.7, 119.9, 124.0, 124.6, 128.5, 130.2, 132.6, 146.2, 169.6. IR νmax (cm−1): 1108 (C=S), 1,271
(C=N); EIMS, 70 eV, m/z: 412 (M+); Anal. Calcd. for C21H16N8S (412.45): C, 61.15; H, 3.91; N,
27.17; S, 7.77. Found: C, 61.23; H, 3.96; N, 27.26; S, 7.55.
4. Conclusions
In conclusion, the reported synthesis is reasonably efficient, direct, and operationally simple. We
believe that the methodology presented herein can have wide applications for the development of
synthetically useful benzimidazole-2-thiones that were previously inaccessible by other routes.

Molecules 2012, 17
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Acknowledgments
We acknowledge the Dirección de Investigaciones Sede Bogotá (DIB) of Universidad Nacional de
Colombia for financial support.
References
1. Hofmann, A.W. Noch einige Bemerkungen über Senföle. Ber. Dtsch. Chem. Ges. 1875, 8,
105–109.
2. Wolf-Dieter, R. Reactions of carbon disulfide with Nnucleophiles. J. Sulfur Chem. 2007, 28,
295–339.
3. Johnson, T.B.; Edens, C.O. Complex Formations between iodine and μ-mercapto-dihydroglyoxalines.
J. Am. Chem. Soc. 1942, 64, 2706–2708.
4. Wang, M.-L.; Liu, B.-L. Reaction of carbon disulfide and o-phenylenediamine catalyzed by
tertiary amine in a homogeneous solution. Ind. Eng. Chem. Res. 1995, 34, 3688–3695.
5. Wang, M.-L.; Liu, B.-L. Homogeneous catalyzed reaction of carbon disulfide and
o-phenylenediamine by tetrabutylammonium hydroxide in the presence of potassium hydroxide.
J. Chin. Inst. Chem. Eng. 2007, 38, 85–90.
6. Xue, G.; Huang, X.-Y.; Dong, J.; Zhang, J. The formation of an effective anti-corrosion film on
copper surfaces from 2-mercaptobenzimidazole solution. J. Electroanal. Chem. Interfacial
Electrochem. 1991, 310, 139–148.
7. Perrin, F.X.; Pagetti, J. Characterization and mechanism of direct film formation on a Cu electrode
through electro-oxidation of 1-mercaptobenzimidazole. Corros. Sci. 1998, 40, 1647–1662.
8. Zhang, J.; Liu, W.; Xue, Q. Tribological study of a Mannich compound of
2-mercaptobenzimidazole in liquid paraffin. Tribol. Int. 1998, 31, 767–770.
9. Zhang, J.; Liu, W.; Xue, Q. The effect of molecular structure of heterocyclic compounds
containing N, O and S on their tribological performance. Wear 1999, 231, 65–70.
10. Moreira, J.C.; Pavan, L.C.; Gushikem, Y. Adsorption of Cu(II), Zn(II), Cd(II), Hg(II) and Pb(II)
from aqueous solutions on a 2-mercaptobenzimidazole-modified silica gel. Microchim. Acta 1990,
102, 107–115.
11. Dalal, D.S.; Pawar, N.S.; Mahulikar, P.P. Synthesis of 2-mercaptobenzothiazole and of
2-mercaptobenzimidazole derivatives using polymer-supported anions. Org. Prep. Proced. Int.
2005, 37, 539–545.
12. Bell, S.C.; Wei, P.H. Synthesis of heterocyclic fused thiazole acetic acids 2. J. Med. Chem. 1976,
19, 524–530.
13. Lin, S.; Lombardo, M.; Malkani, S.; Hale, J.J.; Mills, S.G.; Chapman, K.; Thompson, J.E.;
Zhang, W.-X.; Wang, R.; Cubbon, R.M. Novel 1-(2-aminopyrazin-3-yl)methyl-2-thioureas as
potent inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2).
Bioorg. Med. Chem. Lett. 2009, 19, 3238–3242.
14. De Almeida, M.V.; Cardoso, S.H.; De Assis, J.V.; De Souza, M.V.N. Synthesis of
2-mercaptobenzothiazole and 2-mercaptobenzimidazole derivatives condensed with carbohydrates
as a potential antimicrobial agents. J. Sulfur Chem. 2007, 28, 17–22.

Molecules 2012, 17
8585
15. Desai, K.G.; Desai, K.R. Green route for the heterocyclization of 2-mercaptobenzimidazole into
β-lactum segment derivatives containing –CONH–bridge with benzimidazole: Screening in vitro
antimicrobial activity with various microorganisms. Bioorg. Med. Chem. 2006, 14, 8271–8279.
16. Proksa, B.; Turdiková, M.; Ertík, M.; Miroslav, K.; Preizingerová, T.; Fuska, J. Effects of
derivatives of 2-mercaptobenzimidazole on polyketide biosynthesis in Penicillium frequentans.
Biotechnol. Appl. Biochem. 1997, 25, 169–172.
17. Lobana, T.S.; Sharma, R.; Hundal, G.; Butcher, R.J. Synthesis of 1D {Cu6(3-SC3H6N2)4(μ-
SC3H6N2)2(mu-I)2I4}n and 3D {Cu2(-SC3H6N2)2(-SCN)2}n polymers with 1,3-imidazolidine-2-
thione: Bond isomerism in polymers. Inorg. Chem. 2006, 45, 9402–9409.
18. Lobana, T.S.; Sharma, R.; Sharma, R.; Mehra, S.; Castineiras, A.; Turner, P. Versatility of
heterocyclic thioamides in the construction of a trinuclear cluster [Cu3I3(dppe)3 (SC5H4NH)] and
Cu(I) linear polymers {Cu6(SC5H4NH)6I6}nx2nCH3CN and {Cu(I)6 (SC3H6N2)6X6}n (X = Br, I).
Inorg. Chem. 2005, 44, 1914–1921.
19. Beheshti, A.; Clegg, W.; Dale, S.H.; Hyvadi, R. Synthesis, crystal structures, and spectroscopic
characterization of the neutral monomeric tetrahedral [M(Diap)2(OAc)2]H2O complexes (M = Zn,
Cd; Diap = 1,3-diazepane-2-thione; OAc = acetate) with N-H…O and O-H…O intra- and
intermolecular hydrogen bonding interactions. Inorg. Chim. Acta 2007, 360, 2967–2972.
20. Rivera, A.; Maldonado, M.; Núñez, M.; Joseph-Nathan, P. Nucleophilic substitution at the
aminalic carbon of some macrocyclic polyaminals. Heterocycl. Commun. 2004, 10, 77–80.
21. Rivera, A.; Maldonado, M. Unexpected behavior of 6H,13H-5:12,7:14-dimethane-
dibenzo[d,i][1,3,6,8]tetraazecine (DMDBTA) toward phenols. Tetrahedron Lett. 2006, 47,
7467–7471.
22. Rivera, A.; Navarro, M.; Rios-Motta, J. Solvent-Free Synthesis of 2-(1H-benzimidazol-1-yl-
methyl)-4-substituted-1-hydroxyaryl by the two component Mannich reaction between 6H,13H-
5:12,7:14-Dimethanedibenzo[d,i][1,3,6,8]tetraazecine (DMDBTA) and phenols. Heterocycles
2008, 75, 1651–1658.
23. Rivera, A.; Moyano, D.; Maldonado, M.; Ríos-Motta, J.; Reyes, A. FT-IR and DFT studies of the
proton affinity of small aminal cages. Spectrochim. Acta A 2009, 74, 588–590.
24. Rivera, A.; Maldonado, M.; Ríos-Motta, J.; Navarro, M.; González-Salas, D. Novel access to
1-substituted-benzimidazoles via benzotriazole-mediated synthesis. Tetrahedron Lett. 2010, 51,
102–104.
25. Donia, R.A.; Shotton, J.A.; Bentz, L.O.; Smith, G.E.P., Jr. Reactions of mono- and di-amines
with carbon disulphide. II. Methylenediamine and imidazolidine-carbon disulphide reactions.
J. Org. Chem. 1949, 14, 952–961.
26. Mohamed, T.A.; Mustafa, A.M.; Zoghaib, W.M.; Afifi, M.S.; Farag, R.S.; Badr, Y. Infrared,
Raman and temperature-dependent NMR spectra, vibrational assignments, normal coordinate
analysis, and DFT calculations of benzoxazoline-2-thione. Vib. Spectrosc. 2010, 52, 128–136.
27. Lin, S.; Yang, L. A simple and efficient procedure for the synthesis of benzimidazoles using air as
the oxidant. Tetrahedron Lett. 2005, 46, 4315–4319.
28. Ivanova, N.V.; Sviridov, S.I.; Stepanov, A.E.Parallel solution-phase synthesis of substituted
2-(1,2,4-triazol-3-yl)benzimidazoles. Tetrahedron Lett. 2006, 47, 8025–8027.

Molecules 2012, 17
8586
29. Vojtech, M.; Petrušová, M.; Sláviková, E.; Bekešová, S.; Petruš, L. One-pot synthesis of 2-C-
glycosylated benzimidazoles from the corresponding methanal dimethyl acetals. Carbohydr. Res.
2007, 342, 119–123.
30. Gallant, A.J.; Patrick, B.O.; MacLachlan, M.J. Mild and selective reduction of imines: Formation
of an unsymmetrical macrocycle. J. Org. Chem. 2004, 69, 8739–8744.
31. Rivera, A.; Mejia-Camacho, A.; Ríos-Motta, J.; Dušek, M.; Fejfarová, K. 1,3-bis(ethoxymethyl)-
1H-benzimidazole-2(3H)-thione. Acta Cryst. 2010, E 66, o1135–o1136.
Sample Availability: Samples of the compounds 7a–f are available from the authors.
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