Synthesis, anti-proliferative activity, SAR study, and preliminary in vivo toxicity study of substituted N,N′-bis(arylmethyl)benzimidazolium salts against a panel of non-small cell lung cancer cell lines

Article abstract of DOI:10.1016/j.bmc.2016.11.009

A series of N,N′-bis(arylmethyl)benzimidazolium salts have been synthesized and evaluated for their in vitro anti-cancer activity against select non-small cell lung cancer cell lines to create a structure activity relationship profile. The results indicate that hydrophobic substituents on the salts increase the overall anti-proliferative activity. Our data confirms that naphthylmethyl substituents at the nitrogen atoms (N¹(N³)) and highly lipophilic substituents at the carbon atoms (C²and C⁵(C⁶)) can generate benzimidazolium salts with anti-proliferative activity that is comparable to that of cisplatin. The National Cancer Institute's Developmental Therapeutics Program tested 1, 3–5, 10, 11, 13–18, 20–25, and 28–30 in their 60 human tumor cell line screen. Results were supportive of data observed in our lab. Compounds with hydrophobic substituents have higher anti-cancer activity than compounds with hydrophilic substituents.

Full text of DOI:10.1016/j.bmc.2016.11.009

Accepted Manuscript
Synthesis, anti-proliferative activity, SAR study, and preliminary in vivo tox-
icity study of substituted N,N ’-bis(arylmethyl)benzimidazolium salts against a
panel of non-small cell lung cancer cell lines
Kerri L. Shelton, Michael A. DeBord, Patrick O. Wagers, Marie R. Southerland,
Travis M. Williams, Nikki K. Robishaw, Leah P. Shriver, Claire A. Tessier,
Matthew J. Panzner, Wiley J. Youngs
PII:
S0968-0896(16)30785-4
DOI:
http://dx.doi.org/10.1016/j.bmc.2016.11.009
BMC 13375
Reference:
To appear in:
Bioorganic & Medicinal Chemistry
Received Date:
Revised Date:
Accepted Date:
22 September 2016
2 November 2016
3 November 2016
Please cite thisarticle as: Shelton, K.L., DeBord, M.A., Wagers, P.O., Southerland, M.R., Williams, T.M., Robishaw,
N.K., Shriver, L.P., Tessier, C.A., Panzner, M.J., Youngs, W.J., Synthesis, anti-proliferative activity, SAR study,
and preliminary in vivo toxicity study of substituted N,N ’-bis(arylmethyl)benzimidazolium salts against a panel of
non-small cell lung cancer cell lines, Bioorganic & Medicinal Chemistry (2016), doi: http://dx.doi.org/10.1016/
j.bmc.2016.11.009
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Synthesis, anti-proliferative activity, SAR study, and preliminary in vivo
toxicity study of substituted N,N’-bis(arylmethyl)benzimidazolium salts
against a panel of non-small cell lung cancer cell lines
†
†
AUTHOR NAMES: Kerri L. Shelton, Michael A. DeBord, Patrick O. Wagers, Marie R.
Southerland, Travis M. Williams, Nikki K. Robishaw, Leah P. Shriver, Claire A. Tessier,
Matthew J. Panzner*, and Wiley J. Youngs*
*
CORRESPONDING AUTHOR ADDRESS: Center for Silver Therapeutics, Department of
Chemistry, The University of Akron, Akron, OH, 44325-3601, USA, Tel: 330-972-5362,
youngs@uakron.edu
†
These authors contributed equally to the manuscript
KEYWORDS: Lung cancer; Benzimidazolium Salt; Anti-tumor; Anti-cancer; Anti-proliferative

ABSTRACT:
A series of N,N’-bis(arylmethyl)benzimidazolium salts have been synthesized and
evaluated for their in vitro anti-cancer activity against select non-small cell lung cancer cell lines
to create a structure activity relationship profile. The results indicate that hydrophobic
substituents on the salts increase the overall anti-proliferative activity. Our data confirms that
1
3
naphthylmethyl substituents at the nitrogen atoms (N (N )) and highly lipophilic substituents at
2
5
6
the carbon atoms (C and C (C )) can generate benzimidazolium salts with anti-proliferative
activity that is comparable to that of cisplatin. The National Cancer Institute’s Developmental
Therapeutics Program tested 1, 3-5, 10, 11, 13-18, 20-25, and 28-30 in their 60 human tumor
cell line screen. Results were supportive of data observed in our lab. Compounds with
hydrophobic substituents have higher anti-cancer activity than compounds with hydrophilic
substituents.
2

1
. Introduction
Lung cancer is expected to kill over 150,000 people in the United States this year alone,
accounting for one in every four cancer deaths.[1] The treatment of lung cancer is based upon the
type and stage the cancer is in. There are two types of lung cancer including small cell and non-
small cell lung cancer (NSCLC) the latter of which makes up 83% of the diagnosed cases.
Treatments include, surgery, radiation, targeted therapies, and chemotherapy depending on the
stage. Although platinum-based treatments can be effective for certain cancers, the five-year
survival rate for NSCLC is only 21% and platinum agents can cause severe side effects such as
nephrotoxicity.[2] Therefore, there is a need for new treatments for this terrible disease to
increase survival rates and improve quality of life for patients.
Imidazolium salts are a class of compounds that have received attention for their in vitro
anti-cancer activity against a variety of cancers, particularly NSCLC, beginning with the
naturally occurring Lepidline A and Lepidiline B (Figure 1).[3] Also, imidazolium salts with one
naphthylmethyl and one tetrahydrobenzodifuran substituent have shown high anti-cancer activity
against the A549 cell line.[4] Also of interest concerning this class of compounds, the
benzimidazolium and 4,5-dimethyl benzimidazolium salts have higher anti-cancer activity than
the less lipophilic imidazolium salt derivative. This suggests the lipophilicity of the
benzimidazole ring is desirable when fine-tuning the compounds anti-cancer activity against
NSCLC.
3

Figure 1. Examples of imidazolium salts, Lepidiline A, Lepidiline B and tetrahydrobenzodifuran
benzimidazolium salt, with in vitro anti-cancer activity against the A549 NSCLC cell line.
The Youngs’ group has concentrated on enhancing the anti-proliferative properties of
N,N’-bis(naphthylmethyl)imidazolium salts as anti-tumor agents against NSCLC cell lines.[5,6]
The highly lipophilic N,N’-bis(naphthylmethyl)imidazolium salt 1 exhibited high anti-
proliferative activity against several NSCLC cell lines (Figure 2). It was shown that the in vitro
1
anti-tumor activity of 1 was strongly correlated to the two naphthylmethyl substituents at the N
3
and N positions of the imidazole ring. However, the limited water solubility of 1 prohibits the
clinical use of the compound due to anticipated problems with systemic administration. Herein, a
series of N,N’-bis(arylmethyl)benzimidazolium salts with hydrophilic and hydrophobic
substituents at all positions of the benzimidazole ring are presented. Derivatives in this series
were evaluated against a panel of NSCLC cell lines by us and the National Cancer Institute’s
(
NCI) Developmental Therapeutics Program (DTP) to determine the structure activity
relationship of the substituents and the resultant anti-proliferative activity.
Figure 2. Schematic representation of N,N’-bis(naphthylmethyl)imidazolium bromide salt, 1.
4

2
. Experimental
2
.1. General Considerations
All reactions were carried out under aerobic conditions unless otherwise specified. 5,6-
Dimethylbenzimidazole and 5-carboxylic acid-benzimidazole were purchased from Tokyo
Chemical Industries (TCI), Co. Ltd. Benzimidazole, benzimidazole-5,6-dicarboxylic acid and 5-
methoxybenzimidazole, methyl 2-(benzimidazol-2-yl)acetate, 3-(benzimidazol-2-yl)propanoic
acid, 2-(methylthio)benzimidazole, 2-methylbenzimidazole, o-phenylenediamine and 4,5-
dimethylbenzene-1,2-diamine were purchased from Alfa Aesar. γ-Butyrolactone, 2-
hydroxybenzimidazole and 2-methoxypropionic acid were purchased from Sigma Aldrich. 2-(2-
(
(
2-Methoxyethoxy)ethoxy)acetic acid (synthesis grade, ≥95%) was purchased from Merck. 2-
Bromomethyl)naphthalene and 2-(chloromethyl)quinoline hydrochloride were purchased from
Waterstone Technologies. All solvents were purchased from Fisher Scientific. All reagents were
used as received without purification except for the following materials listed below. 2-
(
Chloromethyl)quinoline was obtained by deprotonating 2-(chloromethyl)quinoline
hydrochloride with sodium bicarbonate. Methyl benzimidazole-5-carboxylate was synthesized
according to literature procedure.[7] Methyl 3-(benzimidazol-2-yl)propanoate was synthesized
by esterification of 3-(benzimidazol-2-yl)propanoic acid. 3-(Benzimidazol-2-yl)propan-1-ol was
synthesized according to literature procedure.[8] 2-((2-(2-
Methoxyethoxy)ethoxy)methyl)benzimidazole (26) was synthesized according to literature
procedure.[9]Column chromatography utilized silica gel (60 Å, ICN Medicals) embedded with
fluorescent indicator green 254 nm (Fluka Analytical). Melting points were obtained on a
1
13
1
MelTemp apparatus. H and C{ H} NMR spectra were collected on a Varian 300, 400 or 500
MHz instrument with spectra referenced to the residual protons in DMSO-d (Cambridge Isotope
6
5

1
13
Laboratories, 2.50 ppm, 39.51 ppm, for H or C NMR respectively) or CD
3
OD-d (Cambridge
4
1
13
Isotope Laboratories, 3.31 ppm, 49.00 ppm, for H or C NMR respectively). Infrared
spectroscopy was performed using a Thermo Scientific ATR-IR Nicolet iS5 FT-IR spectrometer
equipped with an iD5 ATR attachment. Mass spectrometry (ESI-MS) was performed by the
University of Akron mass spectrometry laboratory (Akron, OH). Elemental analysis was
performed by the microanalysis laboratory at Atlantic Microlabs, Inc. (Norcross, GA) or by the
University of Akron Department Of Geology (Akron, OH).
2
.2. X-ray Structure Determination Details
Crystals of the compounds were coated in paratone oil, mounted on a CryoLoop and
placed on a goniometer under a stream of nitrogen. Crystal structure data sets were collected on
either a Bruker SMART APEX I CCD diffractometer with graphite-monochromated Mo Kα
radiation (λ = 0.71073 Å) or a Bruker Kappa APEX II Duo CCD system equipped with a Mo
ImuS source and a Cu ImuS micro-focus source equipped with QUAZAR optics (λ = 1.54178
Å). The unit cells were determined by using reflections from three different orientations. Data
sets were collected using SMART or APEX II software packages. All data sets were processed
using the APEX II software suite.[10,11] The data sets were integrated using SAINT.[12] An
empirical absorption correction and other corrections were applied to the data sets using multi-
scan SADABS.[13] Structure solution, refinement, and modelling were accomplished by using
the Bruker SHELXTL package.[14] The structures were determined by full-matrix least-squares
2
refinement of F and the selection of the appropriate atoms from the generated difference map.
Hydrogen atom positions were calculated and Uiso(H) values were fixed according to a riding
model.
2
.3. Cell Viability Protocol
6

The human non-small cell lung cancer cell lines NCI-H1975, HCC827 and A549 were
donated by Dr. Daniel Lindner from the Cleveland Clinic. The human non-small cell lung cancer
cell line NCI-H460 was purchased from ATCC (Manassas, VA, USA). All cell lines were grown
in RPMI 1640 media supplemented with 10% fetal bovine serum. All cell lines were grown
under physiological conditions, specifically at 37 °C with 5% CO and passed every 2-3 days.
2
Cells were grown to confluency and plated in 96-well plates at 5,000-7,000 cells per well.
Cells were incubated for 24 h prior to adding the compounds. All compounds were dissolved in a
1
% DMSO solution and diluted in fresh media to the desired concentrations of 1, 4, 16, and 32
µM. Compounds were added in sextuplet and cells were incubated for 72 h at which time the
optional MTT assay protocol was followed. MTT reagent (10 µL) was added to each well and
cells were incubated for 3-4 h. Media was removed by vacuum and DMSO (100 µL) was added
to each well. Plates were incubated for 15 min at 37 °C. The optical density was read at 540 nm
on a BioTek Epoch plate reader.
2
.4 In Vivo Toxicity Study
All animal procedures were reviewed and approved by the Institutional Animal Care and
Use Committee at the University of Akron. Eight week old male C57BL/6 mice were obtained
from Charles River laboratories. Animals were housed in a 12h light/dark cycle and food and
water were provided ad libitum (n = 3 animals per cage). Prior to the toxicity testing, animals
were allowed to acclimate for 5 days. Vehicle control mice received injections on days 0, 7, 14,
2
1, and 25 that consisted of a 100 µL solution of a 20% 2-HPβCD sterile PBS solution by IP
injection. Experimental mice received 100 µL of a 4 mg/mL 20% 2-HPβCD sterile PBS solution
0.4 mg/ 100 µL or ~ 20 mg/kg assuming 20 g mice) of 29 by IP injection on day 0. Animals
(
were closely monitored and weighed on a daily basis. On day 2, two of the experimental mice
7

were sacrificed. On day 16, the lone surviving experimental mouse was sacrificed. On day 29,
the vehicle control animals were sacrificed.
2
.4. General Synthesis
2
.4.1. Synthesis of 5-methoxy-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium bromide (2)
5
-Methoxybenzimidazole (0.50 g, 3.37 mmol) was dissolved in acetonitrile (5 mL),
potassium hydroxide (0.39 g, 6.95 mmol) was added, and the mixture was refluxed for 30 min.
-(Bromomethyl)naphthalene (0.76 g, 3.44 mmol) was added, and the mixture was refluxed
2
overnight. The reaction was filtered hot via vacuum filtration to remove a white solid, presumed
to be potassium bromide. The filtrate was stirred with 2-(bromomethyl)naphthalene (0.76 g, 3.44
mmol) and refluxed overnight. The resulting precipitate was isolated via vacuum filtration of the
hot reaction mixture. The solid was purified by column chromatography on silica gel using a
mobile phase of methanol/chloroform (10:90) to yield a white solid 2 (1.26 g, 73%). Mp: 217 –
+
+
+
2
20 °C. HRMS (ESI ) calcd for C30
H
25
N
2
O [M-Br] m/z = 429.1967, found at m/z = 429.1926.
) δ = 10.02 (s, 1H), 8.16 (s, 1H), 8.11 (s, 1H), 8.01 – 7.90 (m,
H), 7.67 (m, 2H), 7.61 (m, 1H), 7.58 – 7.53 (m, 4H), 7.24 – 7.21 (m, 1H), 5.98 (s, 2H), 5.96 (s,
1
H NMR (500 MHz, DMSO-d
6
7
2
1
1
2
1
3
1
H), 3.83 (s, 3H). C{ H} NMR (125 MHz, DMSO-d ) δ = 158.7, 142.0, 132.68, 132.67,
6
32.66, 132.6, 132.5, 131.5, 131.4, 128.8, 128.7, 127.81, 127.79, 127.62, 127.61, 127.58, 127.4,
26.7, 125.7, 125.5, 125.3, 116.5, 114.9, 96.7, 56.3, 50.2, 49.9.
.4.2. Synthesis of 5-(methoxycarbonyl)-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium
bromide (3)
Methyl benzimidazole-6-carboxylate (0.38 g, 2.16 mmol) was stirred with sodium
carbonate (0.34 g, 3.21 mmol) in acetonitrile (3 mL) for 30 min. 2-(Bromomethyl)-naphthalene
(
1.13 g, 5.11 mmol) was added and the mixture was refluxed overnight, during which a white
8

precipitate formed. The volatile components of the reaction mixture were removed under
reduced pressure. The white residue was dissolved in methanol and gravity filtered to remove
any inorganic salts. The filtrate was concentrated under reduced pressure to produce a cream
solid. The solid was purified by column chromatography on silica gel using a mobile phase of
methanol/chloroform (5:95) to yield a white solid 3 (0.23 g, 19%). Mp: 133 – 136 °C. HRMS
+
+
+
1
(
ESI ) calcd for C31
MHz, DMSO-d ) δ = 10.24 (s, 1H), 8.62 (m, 1H), 8.17 (m, 2H), 8.13 – 8.10 (m, 2H), 8.02 – 7.91
m, 6H), 7.66 – 7.63 (m, 2H), 7.59 – 7.56 (m, 4H), 6.09 (s, 2H), 6.01 (s, 2H), 3.87 (s, 3H).
H
25
N
2
O
2
[M-Br] m/z = 457.1916, found m/z = 457.1882. H NMR (300
6
(
1
3
1
C{ H} NMR (125 MHz, DMSO-d
6
) δ = 165.1, 145.4, 134.1, 132.72, 132.69, 132.66, 131.3,
1
1
2
31.2, 131.1, 128.79, 128.76, 128.0, 127.83, 127.81, 127.7, 127.64, 127.60, 127.4, 127.2, 126.74,
-1
26.72, 126.69, 125.64, 125.62, 115.6, 114.6, 52.7, 50.5, 50.4. ATR-IR (cm ): 1720 (C=O).
.4.3. Synthesis of 5,6-dimethyl-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium bromide (4)
5
,6-Dimethylbenzimidazole (1.11 g, 7.59 mmol) was dissolved in acetonitrile (8 mL),
potassium hydroxide (0.61 g, 10.87 mmol) was added, and the mixture was refluxed for 30 min.
-(Bromomethyl)naphthalene (1.66 g, 7.51 mmol) was added, and the mixture was refluxed
2
overnight, during which a white precipitate formed. The reaction mixture was filtered hot to
remove a white solid, presumed to be potassium bromide, and the volatile components of the
filtrate were removed under reduced pressure. The residue was combined with 2-(bromomethyl)-
naphthalene (1.68 g, 7.60 mmol) in chloroform (17 mL) and refluxed overnight. The volatile
components were removed under reduced pressure to form a solid. The solid was stirred at RT
with diethyl ether (15 mL). The product was isolated via vacuum filtration, washed with diethyl
+
ether and air dried to yield a cream solid 4 (3.14 g, 81%). Mp: 167 – 170 °C. HRMS (ESI ) calcd
+
2
+
1
for C31
H
27
N
[M-Br] of m/z = 427.2174, found m/z = 427.2138. H NMR (500 MHz, DMSO-
9

6
d ) δ = 10.12 (s, 1H), 8.10 (s, 2H), 7.98 (m, 2H), 7.93 (m, 4H), 7.85 (m, 2H), 7.63 (m, 2H), 7.56
1
3
1
(
m, 4H), 5.94 (s, 4H), 2.31 (s, 6H). C{ H} NMR (125 MHz, DMSO-d
6
) δ = 141.7, 136.6,
32.69, 132.68, 131.6, 129.7, 128.8, 127.8, 127.7, 127.3, 126.7, 125.5, 113.4, 50.0, 20.0.
.4.4. Synthesis of 5,6-bis(methoxycarbonyl)-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium
1
2
bromide (5)
Dimethyl benzimidazole-5,6-dicarboxylate (0.25 g, 1.07 mmol) was dissolved in
acetonitrile (3 mL), sodium carbonate (0.18 g, 1.70 mmol) was added, and the mixture was
refluxed for 30 min. 2-(Bromomethyl)naphthalene (0.38 g, 1.72 mmol) was added and the
mixture was refluxed overnight. The reaction mixture was filtered hot to remove a white solid,
presumed to be sodium bromide. The filtrate was refluxed overnight with 2-(bromomethyl)-
naphthalene (0.38 g, 1.72 mmol). The volatile components of the reaction mixture were removed
under reduced pressure, and the residue was dissolved in hot methanol and gravity filtered. The
volatile components of the filtrate were removed under reduced pressure to yield a white solid 5
(
0.40 g, 62%). Mp: 169 – 172 °C. Anal. Calcd. for C33
H
27BrN
2
O
4
: C, 66.56; H, 4.57; N, 4.70%.
) δ = 10.30 (s, 1H), 8.53 (s,
1
Found: C, 66.08; H, 4.41; N, 4.54%. H NMR (300 MHz, DMSO- d
6
2
H), 8.08 (m, 2H), 8.02 – 7.90 (m, 6H), 7.63 (m, 2H), 7.57 (m, 4H), 6.05 (s, 4H), 3.84 (s, 6H).
1
3
1
C{ H} NMR (125 MHz, DMSO-d
6
) δ = 166.2, 146.6, 132.73, 132.68, 132.5, 131.0, 129.8,
+
1
28.8, 127.8, 127.7, 127.5, 126.8, 126.7, 125.6, 115.4, 53.1, 50.5. MS (ESI ) calcd for
+
4
+
-1
C
33
H
27
N
2
O [M-Br] of m/z = 515.5, found m/z = 515.1. ATR-IR (cm ): 1733 (C=O).
2
.4.5. Synthesis of 5-((naphthalen-2-ylmethoxy)carbonyl)-1,3-bis(naphthalen-2-
ylmethyl)benzimidazolium bromide (6)
Benzimidazole-6-carboxylic acid (0.50 g, 3.08 mmol) was dissolved in acetonitrile (150
mL), sodium bicarbonate (1.11 g, 13.2 mmol) was added, and the mixture was refluxed for 1 h.
1
0

2
-(Bromomethyl)naphthalene (3.86 g, 17.5 mmol) was added, and the mixture was refluxed for 3
d. The volatile components were removed under reduced pressure. The slurry was dissolved in
dichloromethane (200 mL) and filtered to remove a white solid, presumed to be sodium bromide.
The filtrate was concentrated under reduced pressure to generate a white solid. The solid was
purified by column chromatography on silica gel using a mobile phase of methanol/chloroform
(
10:90) to yield a cream solid 6 (1.68 g, 82%). Mp: 139 – 142 °C. Anal. Calcd. for
1
C
41
H31BrN
2
O
2
: C, 74.21; H, 4.71; N, 4.22%. Found: C, 74.04; H, 4.70; N, 4.20%. H NMR (300
MHz, DMSO-d ) δ = 10.22 (s, 1H), 8.65 (s, 1H), 8.23 (m, 1H), 8.17 – 8.11 (m, 3H), 8.01 – 7.83
6
13
1
(
m, 10H), 7.65 – 7.50 (m, 8H), 6.08 (s, 2H), 6.00 (s, 2H), 5.53 (s, 2H). C{ H} NMR (125 MHz,
DMSO-d ) δ = 164.5, 145.5, 134.3, 133.3, 132.8, 132.73, 132.69, 132.67, 132.65, 132.6, 131.3,
6
1
1
31.2, 131.1, 128.8, 128.2, 128.0, 127.9, 127.81, 126.81, 127.80, 127.69, 127.66, 127.6, 127.3,
26.9, 126.8, 126.7, 126.41, 126.36, 125.8, 125.74, 125.70, 115.9, 114.7, 67.0, 50.6, 50.5. MS
+
+
+
-1
(
ESI ) calcd for C41
H
31
N
2
O [M-Br] of m/z = 583.2, found m/z = 583.1. ATR-IR (cm ): 1719
2
(
C=O).
2
.4.6. Synthesis of 5,6-dicarboxy-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium chloride (7)
Compound 5 (0.38 g, 0.64 mmol) in 11 M aqueous hydrochloric acid (10 mL) was heated
at reflux for 3 d. The hydrochloride salt was isolated via vacuum filtration to yield a white solid
7
(0.20 g, 60%). Mp: 210 – 213 °C. Anal. Calcd. for C31
H
23ClN
2
O
4
: C, 70.72; H, 4.43; N, 5.26%.
) δ = 13.63 (s, 2H), 10.28 (s,
1
Found: C, 71.20; H, 4.43; N, 5.36%. H NMR (300 MHz, DMSO-d
6
1
3
1
1
H), 8.40 (s, 2H), 8.08 (s, 2H), 8.02 – 7.90 (m, 6H), 7.63 – 7.55 (m, 6H), 6.03 (s, 4H). C{ H}
NMR (125 MHz, DMSO-d ) δ = 167.4, 146.0, 132.73, 132.68, 132.1, 131.7, 131.1, 128.8, 127.8,
6
+
+
+
1
27.7, 127.4, 126.76, 126.74, 125.6, 114.8, 50.4. MS (ESI ) calcd for C31
H
23
N
2
O [M-Cl] of
4
-1
m/z = 487.2, found m/z = 486.9. ATR-IR (cm ): 1690 (C=O).
1
1

2
.4.7. Synthesis of 5-carboxy-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium chloride/bromide
(
8)
Compound 6 (2.01 g, 3.03 mmol) in 6 M aqueous HCl (46 mL) was refluxed for 3 d. The
product was filtered, and the salt was stirredwith a mixture of de-ionized water and acetone (1:1,
v/v, 30 mL). The blue-grey solid was filtered and purified by column chromatography on silica
gel using a mobile phase of methanol/chloroform (10:90) to yield a white solid 8 (0.98 g, 66%).
Mp: 217 – 220 °C. Anal. Calcd. for C30
H23Cl0.68Br0.32
N
2
O
2
: C, 73.06; H, 4.70; N, 5.68%. Found:
+
+
+
C, 72.60; H, 5.24; N, 5.34 %. HRMS (ESI ) calcd for C30
H
23
N
2
O
2
[M-Cl0.68Br0.32] = 443.1760,
1
found m/z = 443.1573. H NMR (300 MHz, CD
3
OD-d ) δ = 9.84 (s, 1H), 8.26 (s, 1H), 8.03 (m,
4
13
1
2
H), 7.93 – 7.87 (m, 7H), 7.55 – 7.51 (m, 7H), 5.95 (2H, s), 5.93 (2H, s). C{ H} NMR (125
MHz, DMSO-d ) δ = 166.0, 145.4, 133.9, 132.74, 132.72, 132.70, 131.4, 131.3, 129.4, 128.81,
6
1
1
2
28.79, 127.89, 127.85, 127.71, 127.68, 127.6, 127.5, 127.4, 126.8, 126.7, 125.72, 125.67, 115.6,
-1
14.4, 50.5, 50.3. ATR-IR (cm ): 1703 (C=O).
.4.8. Synthesis of 2-(2-methoxy-2-oxoethyl)-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium
bromide (9)
Methyl 2-(benzimidazol-2-yl)acetate (1.00 g, 5.26 mmol) and sodium carbonate (0.86 g,
.11 mmol) was dissolved in acetonitrile (7.5 mL), and the mixture was refluxed for 30 min. 2-
Bromomethyl)naphthalene (1.29 g, 5.83 mmol) was added, and the mixture was refluxed
8
(
overnight. The reaction mixture was filtered hot to remove a white solid, presumed to be sodium
bromide. 2-(Bromomethyl)naphthalene (1.29 g, 5.83 mmol) was added to the filtrate and the
mixture was refluxed overnight. The volatile components were removed under reduced pressure
to yield a residue. The residue was stirred in diethyl ether (10 mL) at RT. The solid was isolated
via vacuum filtration, washed with diethyl ether and air-dried to yield a white solid 9 (0.78 g,
1
2

2
7
8
6%). Mp: 197 – 200 °C. Anal. Calcd for C32
H
27BrN
2
O
2
: C, 69.69; H, 4.94; N, 5.08%. Found: C,
) δ = 8.05 (m, 2H), 7.95 – 7.86 (m,
1
0.09; H, 5.17; N, 4.95%. H NMR (300 MHz, DMSO- d
6
13
1
H), 7.67 (m, 2H), 7.55 (m, 4H), 7.42 (m, 2H), 6.11 (s, 4H), 5.03 (s, 2H), 2.98 (s, 3H). C{ H}
NMR (125 MHz, DMSO-d
6
) δ = 165.2, 148.2, 132.54, 132.48, 131.29, 131.28, 128.6, 127.7,
+
1
27.6, 127.1, 126.7, 126.6, 126.5, 125.0, 114.0, 52.4, 49.0, 30.7. MS (ESI ) calcd for
+
2
+
-1
C
32
H
27
N
2
O [M-Br] of m/z = 471.2, found m/z = 471.1. ATR-IR (cm ): 1748 (C=O).
2
.4.9. Synthesis of 2-(3-methoxy-3-oxopropyl)-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium
bromide (10)
Methyl 3-(benzimidazol-2-yl)propanoate (0.31 g, 1.52 mmol) and sodium carbonate (0.27
g, 2.55 mmol) were stirred in acetonitrile (4 mL) for 30 min. 2-(Bromomethyl)naphthalene (0.41
g, 1.84 mmol) was added, and the mixture was refluxed overnight. The reaction mixture was
filtered hot to remove a white solid, presumed to be sodium bromide. 2-
(
Bromomethyl)naphthalene (0.41 g, 1.84 mmol) was added to the filtrate and the mixture was
refluxed overnight. The volatile components were removed under reduced pressure to yield a
residue. The residue was washed in diethyl ether (10 mL) at RT. The solid was isolated via
vacuum filtration, washed with diethyl ether and air-dried to yield a colorless solid 10 (0.57 g,
6
6
4
3
1
4
6%). Mp: 179 – 181 °C. Anal. Calcd for C33
H
29BrN
2
O
2
: C, 70.09; H, 5.17; N, 4.95%. Found: C,
) δ = 7.99-7.94 (m, 6H), 7.87-7.84 (m,
1
9.18; H, 5.29; N, 5.01%. H NMR (500 MHz, DMSO- d
6
H), 7.62 (m, 2H), 7.54 (m. 6H), 7.47 (m, 2H), 6.11 (s, 4H), 3.72 (t, 2H, J = 7.6 Hz), 3.44 (s,
13
1
H), 2.62 (t, 2H, J = 7.6 Hz). C{ H} NMR (125 MHz, DMSO-d
6
) δ = 171.0, 153.6, 132.7,
33.0, 132.7, 132.5, 131.8, 131.4, 128.7, 127.65, 127.62, 126.7, 126.5, 125.6, 124.7, 113.6, 51.6,
+
+
+
8.7, 30.0, 19.3. MS (ESI ) calcd for C33
H
29
N
2
O
2
[M-Br] of m/z = 485.2, found m/z = 485.0.
-1
ATR-IR (cm ): 1727 (C=O).
1
3

2
.4.10. Synthesis of 2-methyl-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium bromide (11)
-Methyl-benzimidazole (0.50 g, 3.78 mmol) was dissolved in acetonitrile (6 mL),
potassium hydroxide (0.25 g, 4.46 mmol) was added and the mixture was refluxed for 30 min. 2-
Bromomethyl)naphthalene (0.84 g, 3.80 mmol) was added, and the mixture was refluxed
2
(
overnight. The reaction mixture was filtered hot to remove a white solid, presumed to be
potassium bromide. 2-(Bromomethyl)naphthalene (0.84 g, 3.80 mmol) was added to the filtrate
and refluxed overnight. The resulting precipitate was collected via vacuum filtration of the hot
reaction mixture. The solid in the funnel was washed with diethyl ether and air dried to yield a
white solid 11 (1.54 g, 82%). Mp: 279 – 282 °C. Anal. Calcd for C30
H
25BrN
2
: C, 73.02; H, 5.11;
) 8.02 – 7.89 (m,
1
N, 5.68%. Found: C, 72.74; H, 5.32; N, 5.64%. H NMR (500 MHz, DMSO- d
6
1
3
1
1
1
4
0H), 7.60 – 7.52 (m, 8H), 6.05 (s, 4H), 3.13 (s, 3H). C{ H} NMR (125 MHz, DMSO-d
6
)
52.8, 132.7, 132.5, 131.6, 131.2, 128.7, 127.7, 127.6, 126.6, 126.5, 126.3, 126.1, 125.0, 113.4,
+
+
+
8.6, 11.3. MS (ESI ) calcd for C30
H
25
N
2
[M-Br] of m/z = 413.2, found m/z= 413.3.
Crystal data for the solvate of 11-Cl: C30
H
25Cl
1
N
2
•H O, M = 466.99, triclinic, a =
2
1
7
4
0.1897(17) Å, b = 10.4212(17) Å, c = 11.4397(19) Å, α = 80.323(2)°, β = 86.985(2)°, γ =
3
6.344(2)°,V = 1163.5(2) Å , T = 100(2) K, space group P-1, Z = 2, 9361 reflections measured,
658 independent reflections (Rint = 0.0250).The final R
1
values were 0.0396 (I > 2σ(I)). The
2
final wR(F ) values were 0.1052 (I > 2σ(I)). The final R
1
values were 0.0451 (all data). The final
2
wR(F ) values were 0.1099 (all data). A single crystal was obtained by slow evaporation of a
concentrated solution of 11-Cl in acetone/water (1:1).
2
.4.11. Synthesis of 2-(2-carboxyethyl)-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium
chloride (12)
1
4

A solution of 10 (0.25 g, 0.442 mmol) in 9 M aqueous HCl (6 mL) was heated at reflux for
3
d. The solution was filtered via vacuum filtration to isolate the precipitate, and the solid was
air-dried to yield a white powder 12 (0.15 g, 66%). Mp: 242 – 245 °C. Anal. Calcd for
•H O: C, 73.20; H, 5.57; N, 5.34%. Found: C, 74.22; H, 5.48; N, 5.45%. HRMS
ESI ) calcd for C32
C
32
H27ClN
2
O
2
2
+
+
+
1
(
H
27
N
2
O
2
[M-Cl] of m/z = 471.2072, found m/z = 471.2096. H NMR (500
MHz, DMSO- d
6
) 12.60 (bs, 1H), 7.99 (s, 1H), 7.98 (s, 1H), 7.95 (m, 4H), 7.87 (m, 4H), 7.59 (m,
2
H), 7.55 (m, 4H), 7.49 (m, 2H), 6.14 (s, 4H), 3.71 (t, 2H, J = 7.7 Hz), 2.62 (t, 2H, J = 7.7 Hz).
1
3
1
C{ H} NMR (125 MHz, DMSO-d
6
) 172.0, 154.0, 132.7, 132.5, 131.9, 131.4, 128.7, 127.7,
-1
1
27.6, 126.7, 126.6, 126.5, 125.6, 124.7, 113.6, 48.8, 30.5, 19.5. ATR-IR (cm ): 1704 (C=O).
Crystal data for 12: C32
H
27Cl
1
N
2
O
2
, M = 507.01, triclinic, a = 8.0368(6) Å, b = 12.690(2)
3
Å, c = 12.996(3) Å, α = 106.523(7)°, β = 100.163(7)°, γ = 92.637(7)°,V = 1244.2(4) Å , T =
1
00(2) K, space group P-1, Z = 2, 19911 reflections measured, 5013 independent reflections (Rint
2
=
0.0379).The final R
1
values were 0.0390 (I > 2σ(I)). The final wR(F ) values were 0.0902 (I >
2
2
σ(I)). The final R
1
values were 0.0545 (all data). The final wR(F ) values were 0.0989 (all data).
A single crystal was obtained by slow evaporation of a concentrated solution of 12 in
acetonitrile/methanol (1:1).
2
.4.12. Synthesis of 2-ethyl-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium bromide (13)
o-Phenylenediamine (0.40 g, 3.70 mmol) and propionic acid (0.34 mL, 4.54 mmol) were
added to 4 M aqueous hydrochloric acid (5 mL) to synthesize 2-ethylbenzimidazole according to
literature procedure.[15] 2-Ethyl-benzimidazole (0.11 g, 0.75 mmol) was dissolved in
acetonitrile (6 mL), potassium hydroxide (70.0 mg, 1.25 mmol) was added, and the mixture was
refluxed for 30 min. 2-(Bromomethyl)naphthalene (0.17 g, 0.77 mmol) was added and the
mixture was refluxed overnight. The reaction mixture was filtered hot to remove a white solid,
1
5

presumed to be potassium bromide. 2-(Bromomethyl)naphthalene (0.17 g, 0.77 mmol) was
added to the filtrate and refluxed overnight. The resulting precipitate was collected via vacuum
filtration of the hot reaction mixture. The solid was washed with diethyl ether and air dried to
yield a white solid 13 (0.15 g, 39%). Mp: 268 – 270 °C. Anal. Calcd for C31
H
27BrN
2
: C, 73.37;
) 7.98 –
1
H, 5.36; N, 5.52 %. Found: C, 72.44; H, 53.49; N, 5.48. H NMR (500 MHz, DMSO- d
6
7
3
1
.89 (m, 10H), 7.59 – 7.54 (m, 8H), 7.48 (m, 2H), 6.10 (s, 4H), 3.53 (q, 2H, J = 7.3 Hz), 1.07 (t,
1
3
1
H, J = 7.5 Hz). C{ H} NMR (125 MHz, DMSO-d ) 156.0, 132.7, 132.5, 131.9, 131.4, 128.7,
6
+
+
27.7, 127.6, 126.7, 126.5, 125.7, 124.7, 113.6, 48.6, 17.6, 11.3. MS (ESI ) calcd for C31
H
27
N
2
+
[
M-Br] of m/z = 427.6, found m/z = 427.4.
Crystal data for 13: C31
H27Br
1
N
2
, M = 507.46, triclinic, a = 9.5820(10) Å, b = 10.1627(11)
3
Å, c = 14.0507(15) Å, α = 79.7760(10)°, β = 89.5660(10)°, γ = 64.9650(10)°,V = 1216.5(2) Å ,
T = 100(2) K, space group P-1, Z = 2, 9895 reflections measured, 4898 independent reflections
2
(
Rint = 0.0124).The final R
1
values were 0.0210 (I > 2σ(I)). The final wR(F ) values were 0.0547
2
(
I > 2σ(I)). The final R
1
values were 0.0215 (all data). The final wR(F ) values were 0.0551 (all
data). A single crystal was obtained by slow evaporation of a concentrated solution of 13 in
acetonitrile/methanol (1:1).
2
.4.13. Synthesis of 1,3-bis(naphthalen-2-ylmethyl)-2-propylbenzimidazolium bromide (14)
o-Phenylenediamine (0.40 g, 3.70 mmol) and butyric acid (0.42 mL, 4.57 mmol) were
added to 4 M aqueous hydrochloric acid (5 mL) to synthesize 2-propylbenzimidazole according
to literature procedure.[15] 2-Propyl-benzimidazole (0.30 g, 1.87 mmol) was dissolved in
acetonitrile (7 mL), potassium hydroxide (0.17 g, 3.03 mmol) was added, and the mixture was
refluxed for 30 min. 2-(Bromomethyl)naphthalene (0.42 g, 1.90 mmol) was added and the
mixture was refluxed overnight. The reaction mixture was filtered hot to remove a white solid,
1
6

presumed to be potassium bromide. 2-(Bromomethyl)naphthalene (0.42 g, 1.90 mmol) was
added to the filtrate and refluxed overnight. The resulting precipitate was collected via vacuum
filtration of the hot reaction mixture. The solid was washed with diethyl ether and air dried to
yield a white solid 14 (0.23 g, 23%). Mp: 264 – 266 °C. Anal. Calcd for C32
H
29BrN
2
: C, 73.70;
) 7.98 –
1
H, 5.61; N, 5.37%. Found: C, 73.18; H, 5.57; N, 5.40%. H NMR (500 MHz, DMSO- d
6
7
.88 (m, 10H), 7.60 – 7.54 (m, 6H), 7.48 (m, 2H), 6.09 (s, 4H), 3.47 (m, 2H), 1.44 (m, 2H), 0.88
1
3
1
(
t, 3H, J = 7.3 Hz). C{ H} NMR (125 MHz, DMSO-d
6
) 154.9, 132.7, 132.5, 131.9, 131.4,
+
1
28.7, 127.7, 127.6, 126.7, 126.5, 125.8, 124.7, 113.7, 48.7, 25.4, 20.5, 13.4. MS (ESI ) calcd
+
2
+
for C32
H
29
N [M-Br] of m/z = 441.6, found m/z = 441.4.
2
.4.14. Synthesis of 2-butyl-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium bromide (15)
o-Phenylenediamine (0.40 g, 3.70 mmol) and pentanoic acid (0.50 mL, 4.60 mmol) were
added to 4 M aqueous hydrochloric acid (5 mL) to synthesize 2-butylbenzimidazole according to
literature procedure.[15] 2-Butyl-benzimidazole (0.17 g, 0.98 mmol) was dissolved in
acetonitrile (5 mL), potassium hydroxide (0.09 g, 1.60 mmol) was added and the mixture was
refluxed for 30 min. 2-(Bromomethyl)naphthalene (0.22 g, 1.00 mmol) was added and the
mixture was refluxed overnight. The reaction mixture was filtered hot to remove a white solid,
presumed to be potassium bromide. 2-(Bromomethyl)-naphthalene (0.22 g, 1.00 mmol) was
added to the filtrate and refluxed overnight. The resulting precipitate was collected via vacuum
filtration of the hot reaction mixture. The solid was washed with diethyl ether and air dried to
yield a cream solid 15 (0.29 g, 55%). Mp: 266 – 268 °C. Anal. Calculated for C33
H
31BrN : C,
2
1
7
8
4.01; H, 5.83; N, 5.23%. Found: C, 73.74; H, 5.82; N, 5.25%. H NMR (500 MHz, DMSO- d
6
)
.00 – 7.88 (m, 10H), 7.61 (m, 2H), 7.55 (m, 4H), 7.46 (m, 2H), 6.09 (s, 4H), 3.45 (m, 2H), 1.25
1
3
1
(
m, 4H), 0.53 (t, 3H, J = 6.5 Hz). C{ H} NMR (125 MHz, DMSO-d ) 155.0, 132.7, 132.5,
6
1
7

1
31.9, 131.4, 128.7, 127.7, 127.6, 126.7, 126.5, 125.9, 124.7, 113.6, 48.7, 28.5, 23.7, 21.7, 13.1.
+
+
+
MS (ESI ) calcd for C33
H
31
N [M-Br] of m/z = 455.6, found m/z = 455.4.
2
Crystal data for 15: C33
H31Br
1
N
2
, M = 535.51, monoclinic, a = 27.1716(10) Å, b =
3
9
.7618(3) Å, c = 19.4068(7) Å, α = 90°, β = 92.1326(17)°, γ = 90°,V = 5144.0(3) Å , T = 100(2)
K, space group P2(1)/c, Z = 8, 41594 reflections measured, 10427 independent reflections (Rint
=
2
0
.1032).The final R
σ(I)). The final R
1
values were 0.0694 (I > 2σ(I)). The final wR(F ) values were 0.1356 (I >
2
2
1
values were 0.1215 (all data). The final wR(F ) values were 0.1521 (all data).
A single crystal was obtained by slow evaporation of a concentrated solution of 15 in
acetonitrile/methanol (1:1).
2
.4.15. Synthesis of 2-heptyl-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium bromide (16)
o-Phenylenediamine (0.40 g, 3.70 mmol) and octanoic acid (0.44 mL, 3.35 mmol) were
added to 4 M aqueous hydrochloric acid (3 mL) to synthesize 2-heptylbenzimidazole. 2-Heptyl-
benzimidazole (0.09 g, 0.42 mmol) was dissolved in acetonitrile (5 mL), potassium hydroxide
(
(
0.03 g, 0.53 mmol) was added and the mixture was refluxed for 30 min. 2-
Bromomethyl)naphthalene (0.11 g, 0.50 mmol) was added and the mixture was refluxed
overnight. The reaction mixture was filtered hot to remove a white solid, presumed to be
potassium bromide. 2-(Bromomethyl)naphthalene (0.11 g, 0.50 mmol) was added to the filtrate
and refluxed overnight. The resulting precipitate was collected via vacuum filtration of the hot
reaction mixture. The solid was washed with diethyl ether and air dried to yield a cream solid 16
(
0.14 g, 57%). Mp: 229 – 232 °C. Anal. Calcd for C36
H37BrN
2
•H O: C, 72.60; H, 6.60; N,
2
+
+
+
4
4
4
.70%. Found: C, 72.68; H, 6.34; N, 4.78%. HRMS (ESI ) calcd for C36
H
37
N
2
[M-Br] of m/z =
) 8.02 – 7.91 (m, 6H), 7.88 (m,
H), 7.63 (m, 2H), 7.56 – 7.53 (m, 4H), 7.44 (dd, 2H, J = 8.6, 1.7 Hz), 6.06 (s, 4H), 3.41 (m,
1
97.2957, found m/z = 497.2950. H NMR (500 MHz, DMSO- d
6
1
8

1
3
1
2
H), 1.15 (m, 4H), 0.95 (m, 2H), 0.77 (m, 4H), 0.63 (t, 3H, J = 7.3 Hz). C{ H} NMR (125
MHz, DMSO-d ) 155.1, 132.7, 132.5, 132.0, 131.5, 128.7, 127.6, 126.7, 126.6, 126.5, 125.8,
24.6, 113.6, 48.6, 30.5, 28.4, 27.9, 26.5, 24.0, 21.7, 13.6.
.4.16. Synthesis of 2-(2-methoxyethyl)-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium
6
1
2
bromide (17)
2
-(2-Methoxyethyl)-benzimidazole (0.21 g, 1.19 mmol) was dissolved in acetonitrile (6
mL), sodium carbonate (0.21 g, 1.98 mmol) was added and the mixture was refluxed for 30 min.
2
-(Bromomethyl)naphthalene (0.27 g, 1.22 mmol) was added and the mixture was refluxed
overnight. The reaction mixture was filtered hot to remove a white solid, presumed to be sodium
bromide. 2-(Bromomethyl)naphthalene (0.27 g, 1.22 mmol) was added to the filtrate and
refluxed overnight. The resulting precipitate was collected via vacuum filtration of the hot
reaction mixture. The solid was washed with diethyl ether and air dried to yield a cream solid 17
(
0.20 g, 31%). Mp: 243 – 246 °C. Anal. Calcd for C32
H29BrN
2
O•H
2
O: C, 69.19; H, 5.63; N,
+
+
+
5
4
7
2
1
.04%. Found: C, 69.54; H, 5.36; N, 5.10%. HRMS (ESI ) calculated for C32
H
29
N
2
O [M-Br] =
1
57.2280, found m/z = 457.2278. H NMR (500 MHz, DMSO- d
6
) 8.00 – 7.94 (m, 4H), 7.89 –
.84 (m, 6H), 7.57 – 7.54 (m, 5H), 7.48 (m, 3H), 6.12 (s, 4H), 3.88 (t, 2H, J = 5.6 Hz), 3.56 (t,
1
3
1
H, J = 5.6 Hz), 3.03 (s, 3H). C{ H} NMR (125 MHz, DMSO-d
6
) 153.3, 132.7, 132.4, 131.9,
31.2, 128.7, 127.7, 127.7, 127.6, 126.7, 126.6, 126.5, 125.6, 124.6, 113.7, 68.0, 58.2, 48.9, 24.9.
Crystal data for 17: C32
H29Br
1
N
2
O, M = 537.48, triclinic, a = 8.8985(8) Å, b = 17.1053(15)
3
Å, c = 18.9826(16) Å, α = 63.486(4)°, β = 88.991(4)°, γ = 88.822(4)°,V = 2584.8(4) Å , T =
1
00(2) K, space group P-1, Z = 4, 38791 reflections measured, 10457 independent reflections
2
(
Rint = 0.0648).The final R
1
values were 0.0776 (I > 2σ(I)). The final wR(F ) values were 0.1958
2
(
I > 2σ(I)). The final R
1
values were 0.1094 (all data). The final wR(F ) values were 0.2143 (all
1
9

data). A single crystal was obtained by slow evaporation of a concentrated solution of 17 in
acetone/methanol/ethyl acetate (1:1:1).
2
.4.17. Synthesis of 2-(3-hydroxypropyl)-1,3-bis(naphthalen-2-ylmethyl)benzimidazolium
bromide (18)
3
-(Benzimidazol-2-yl)propan-1-ol (1.50 g, 8.51 mmol) was dissolved in acetonitrile (40
mL), potassium hydroxide (0.90 g, 16.0 mmol) was added, and the mixture was refluxed for 30
min. 2-(Bromomethyl)naphthalene (1.90 g, 8.59 mmol) was added and the mixture was refluxed
overnight. The reaction mixture was filtered hot to remove a white solid, presumed to be
potassium bromide. 2-(Bromomethyl)naphthalene (1.90 g, 8.59 mmol) was added to the filtrate,
which was refluxed overnight. The resulting precipitate was collected via vacuum filtration of
the hot mixture. The solid was washed with diethyl ether (10 mL) and air dried to yield a white
powder 18 (2.20 g, 48 %). Mp: 229 – 231 °C. Anal. Calcd for C32
H
29BrN
2
O: C, 71.51; H, 5.44;
) 7.99 – 7.88 (m,
1
N, 5.21%. Found: C, 71.02; H, 5.61; N, 5.08%. H NMR (500 MHz, DMSO- d
6
1
0H), 7.58 – 7.50 (m, 8H), 6.09 (s, 4H), 4.78 (bs, 1H), 3.54 (m, 2H), 3.49 (m, 2H), 1.76 (m, 2H).
1
3
1
C{ H} NMR (125 MHz, DMSO-d
6
) 155.3, 132.7, 132.5, 131.8, 131.4, 128.7, 127.7, 127.6,
+
1
26.7, 126.51, 126.45, 125.7, 124.7, 113.6, 59.2, 48.7, 29.7, 21.0. MS (ESI ) calcd for
+
+
C
32
H
29
N O [M-Br] : m/z = 457.2, found m/z = 457.1.
2
Crystal data for 18: C32
H29Br
1
N
2
O, M = 537.48, triclinic, a = 10.3959(6) Å, b = 10.4438(6)
3
Å, c = 12.8557(7) Å, α = 67.842(2)°, β = 76.321(2)°, γ = 79.887(2)°,V = 1250.23(12) Å , T =
1
00(2) K, space group P-1, Z = 2, 27063 reflections measured, 5022 independent reflections (Rint
2
=
0.0277).The final R
1
values were 0.0221 (I > 2σ(I)). The final wR(F ) values were 0.0552 (I >
2
2
σ(I)). The final R
1
values were 0.0237 (all data). The final wR(F ) values were 0.0561 (all data).
A single crystal was obtained by slow evaporation of a concentrated solution of 18 in methanol.
2
0

2
.4.18. Synthesis of 2-(3-hydroxypropyl)-1-(naphthalen-2-ylmethyl)-3-(quinolin-2-
ylmethyl)benzimidazolium bromide (19)
-(Benzimidazol-2-yl)propan-1-ol (0.40 g, 2.27 mmol) was dissolved in acetonitrile (11
3
mL) potassium hydroxide (0.15 g, 2.67 mmol) was added, and the mixture was refluxed for 30
min. 2-(Chloromethyl)quinoline (0.40 g, 2.26 mmol) was added, and the mixture was refluxed
overnight. The reaction mixture was filtered hot to remove a white solid, presumed to be
potassium chloride. 2-(Bromomethyl)naphthalene (0.50 g, 2.26 mmol) was added to the filtrate,
which was refluxed overnight. The precipitate was collected via vacuum filtration of the hot
mixture. The solid was washed with diethyl ether (5 mL) and air dried. The solid was triturated
in a hot mixture of acetone and dichloromethane (1:1 v/v, 6 mL) and gravity filtered to yield a
white powder 19 (0.57 g, 46%). Mp: 246 – 250 °C. Anal. Calcd for C31
H
28BrN
3
O: C, 69.15; H,
) 8.50 (d,
1
5
1
.24; N, 7.80%. Found: C, 69.07; H, 5.15; N, 7.72%. H NMR (500 MHz, DMSO- d
6
H, J = 8.3 Hz), 8.03 – 7.78 (m, 8H), 7.71 – 7.47 (m, 7H), 6.28 (s, 2H), 6.15 (s, 2H), 4.75 (t, 1H,
1
3
1
J = 4.8 Hz), 3.53 – 3.48 (m, 4H), 1.86 (m, 2H). C{ H} NMR (125 MHz, DMSO-d
6
) 156.0,
53.6, 146.6, 137.5, 132.7, 132.5, 132.0, 131.6, 131.1, 130.1, 128.8, 128.0, 127.7, 127.2, 126.9,
26.8, 126.6, 126.42, 126.39, 125.7, 124.5, 120.0, 113.5, 113.4, 59.2, 49.5, 48.4, 29.8.
1
1
Crystal data for 19: C31
H28Br
1
N
3
O, M = 538.47, triclinic, a = 10.4596(3) Å, b = 10.4601(3)
3
Å, c = 12.7946(4) Å, α = 113.0640(10)°, β = 97.215(2)°, γ = 99.6430(10)°,V = 1241.21(6) Å , T
=
100(2) K, space group P-1, Z = 2, 29636 reflections measured, 5003 independent reflections
2
(
Rint = 0.0271).The final R
1
values were 0.0295 (I > 2σ(I)). The final wR(F ) values were 0.0741
2
(
I > 2σ(I)). The final R
1
values were 0.0310 (all data). The final wR(F ) values were 0.0750 (all
data). A single crystal was obtained by slow evaporation of a concentrated solution of 19 in
acetone/methanol/ethyl acetate (1:1:1).
2
1

2
.4.19. Synthesis of 2-(3-hydroxypropyl)-1,3-bis(quinolin-2-ylmethyl)benzimidazolium chloride
(
20)
3
-(Benzimidazol-2-yl)propan-1-ol (0.39 g, 2.21 mmol) was dissolved in acetonitrile (5
mL), sodium carbonate (0.24 g, 2.26 mmol) was added, and the mixture was refluxed for 30 min.
-(Chloromethyl)quinoline (0.60 g, 3.38 mmol) was added and the mixture was refluxed
2
overnight. The reaction mixture was filtered hot to remove a white solid, presumed to be sodium
chloride. 2-(Chloromethyl)quinoline (0.60 g, 3.38 mmol) was added to the filtrate, which was
refluxed overnight. The precipitate was collected via vacuum filtration of the hot mixture. The
solid was washed with diethyl ether (5 mL) and air dried yield a white powder 20 (0.81 g, 72%).
+
+
+
Mp: 256 – 260 °C. HRMS (ESI ) calcd for C30
H
27
N O [M-Cl] : m/z = 459.2185, found m/z =
4
1
4
59.2193. H NMR (500 MHz, DMSO- d
6
) 8.51 (d, 2H, J = 8.3 Hz), 8.02 – 7.97 (m, 4H), 7.79
(
d, 2H, J = 8.6 Hz), 7.72 – 7.67 (m, 4H), 7.62 – 7.59 (m, 2H), 7.55 – 7.52 (m, 2H), 6.35 (s, 4H),
1
3
1
4
.95 (t, 1H, J = 5.1 Hz), 3.58 (t, 2H, J = 7.7 Hz), 3.46 (q, 2H, J = 5.4 Hz), 1.92 (m, 2H). C{ H}
) 156.5, 153.9, 146.7, 137.5, 131.4, 130.1, 128.4, 128.0, 127.2,
26.9, 126.3, 119.9, 113.4, 59.2, 49.7, 29.8, 21.0.
Crystal data for 20•H O•H
NMR (125 MHz, DMSO-d
6
1
2
O: C30
H
27Cl
1
N
4
2
O, M = 513.02, monoclinic, a = 13.0575(11) Å,
3
b = 19.4079(13) Å, c = 10.2667(8) Å, α = 90°, β = 90.609(3)°, γ = 90°,V = 2601.6(3) Å , T =
1
00(2) K, space group P2(1)/c, Z = 4, 41453 reflections measured, 5281 independent reflections
2
(
Rint = 0.0376).The final R
1
values were 0.0336 (I > 2σ(I)). The final wR(F ) values were 0.0814
2
(
I > 2σ(I)). The final R
1
values were 0.0421 (all data). The final wR(F ) values were 0.0866 (all
data). A single crystal was obtained by slow evaporation of a concentrated solution of 20 in
water/acetone (1:1).
2
.4.20. Synthesis of 1,3-bis(naphthalen-2-ylmethyl)-1,3-dihydrobenzimidazol-2-one (21)
2
2

1
,3-Dihydrobenzimidazol-2-one (0.52 g, 3.88 mmol) was dissolved in acetonitrile (5 mL),
potassium hydroxide (0.32 g, 5.70 mmol) was added and the mixture was refluxed for 30 min. 2-
Bromomethyl)naphthalene (0.91 g, 4.12 mmol) was added and the mixture was refluxed
(
overnight. The reaction mixture was filtered hot to remove a white solid, presumed to be
potassium bromide. 2-(Bromomethyl)naphthalene (0.76 g, 3.44 mmol) was added to the filtrate
and refluxed overnight. The resulting precipitate was collected via vacuum filtration of the hot
reaction mixture. The solid was washed with diethyl ether (10 mL) and air-dried to yield a white
+
+
+
powder 21 (0.29 g, 18%). Mp: 147 – 150 °C. HRMS (ESI ) calcd for C29
H
22
N
2
O•Na [M+Na]
1
of m/z = 437.1630, found m/z= 437.1617. H NMR (500 MHz, DMSO- d
6
) 7.91 – 7.84 (m, 8H),
13
1
7
.50 (m, 6H), 7.16 (dd, 2H, J = 5.5, 3.1 Hz), 6.97 (dd, 2H, J = 5.5, 3.1 Hz), 5.30 (s, 4H). C{ H}
NMR (125 MHz, DMSO-d ) 153.9, 134.5, 132.7, 131.3, 128.8, 128.4, 127.6, 127.5, 126.4,
6
-
1
1
26.0, 125.9, 125.4, 121.2, 108.4, 44.1. ATR-IR (cm ): 1683 (C=O).
Crystal data for 21: C29
H
22
N
2
O, M = 414.49, monoclinic, a = 20.1385(6) Å, b = 7.0851(3)
3
Å, c = 29.7407(11) Å, α = 90°, β = 104.9380(10)°, γ = 90°,V = 4100.1(3) Å , T = 100(2) K,
space group C2/c, Z = 8, 33990 reflections measured, 4161 independent reflections (Rint
=
2
0
.0323).The final R
σ(I)). The final R
1
values were 0.0749 (I > 2σ(I)). The final wR(F ) values were 0.1904 (I >
2
2
1
values were 0.0963 (all data). The final wR(F ) values were 0.2102 (all data).
A single crystal was obtained by slow evaporation of a concentrated solution of 21 in
water/acetone/acetonitrile (1:1:1).
2
.4.21. Synthesis of 1,3-bis(naphthalen-2-ylmethyl)-1,3-dihydrobenzimidazole-2-thione (22)
-(Methylthio)benzimidazole (0.50 g, 3.04 mmol) was dissolved in acetonitrile (8 mL),
potassium hydroxide (0.26 g, 4.99 mmol) was added and the mixture was refluxed for 30 min. 2-
Bromomethyl)naphthalene (0.74 g, 3.35 mmol) was added and the mixture was refluxed
2
(
2
3

overnight. The reaction mixture was filtered hot to remove a white solid, presumed to be
potassium bromide. 2-(Bromomethyl)naphthalene (0.76 g, 3.44 mmol) was added to the filtrate
and refluxed overnight. The resulting precipitate was collected via vacuum filtration of the hot
reaction mixture. The solid was washed with diethyl ether and air-dried to yield a white solid 22
(
0.92 g, 70%). Mp: 201 – 204 °C. Anal. Calcd for C29
H
22
N
2
S: C, 80.90; H, 5.15; N, 6.51%.
) 7.91 – 7.84 (m, 8H), 7.56
1
Found: C, 80.49; H, 5.39; N, 6.40%. H NMR (500 MHz, DMSO- d
6
1
3
1
–
1
4
7.50 (m, 6H), 7.41 (m, 2H), 7.16 (m, 2H), 5.83 (s, 4H). C{ H} NMR (125 MHz, DMSO-d
6
)
70.1, 133.8, 132.6, 132.3, 131.4, 128.8, 128.3, 127.6, 127.5, 126.4 126.1, 125.3, 123.1, 110.0,
+
+
+
7.6. MS (ESI ) calcd for C29
H
22
N S•Na [M+Na] of m/z = 453.1, found m/z = 453.5. ATR-IR
2
-1
(
cm ): 1223 (C=S).
2
.4.22. Synthesis of 1,3-bis(quinolin-2-ylmethyl)benzimidazolium chloride (23).
The synthesis of 23 was previously published.[9]
2
.4.23. Synthesis of 2-methyl-1,3-bis(quinolin-2-ylmethyl)benzimidazolium chloride (24)
2
-Methyl-benzimidazole (0.50 g, 3.78 mmol) was dissolved in acetonitrile (7 mL),
potassium hydroxide (0.24 g, 4.28 mmol) was added, and the mixture was refluxed for 30 min.
-(Chloromethyl)quinoline (0.68 g, 3.83 mmol) was added, and the mixture was refluxed
2
overnight. The reaction mixture was filtered hot to remove a white solid, presumed to be
potassium chloride. 2-(Chloromethyl)quinoline (0.68 g, 3.83 mmol) was added to the filtrate
which was refluxed overnight. The resulting precipitate was collected via vacuum filtration of
the hot reaction mixture. The solid was washed with diethyl ether and air dried to yield a cream
powder 24 (0.80 g, 46%). Mp: 279 – 282 °C. Calculated for C28
H23ClN
4
•(H
2
O): C, 71.71; H,
+
+
5
.37; N, 11.95%. Found: C, 70.63; H, 5.50; N, 12.02%. HRMS (ESI ) calcd for C28
H
23
N
4
[M-
+
1
Cl] : m/z = 415.1923, found m/z = 415.1961. H NMR (500 MHz, CD
3
OD- d ) 8.42 (d, 2H, J =
4
2
4

1
3
1
8
.3 Hz), 7.96 – 7.92 (m, 4H), 7.73 – 7.58 (m, 10H), 6.21 (s, 4H), 3.12 (s, 3H). C{ H} NMR
125 MHz, CD OD-d ) 154.5, 149.0, 139.4, 133.3, 131.5, 130.0, 129.2, 128.5, 128.1, 120.8,
14.2, 51.2, 12.0.
Crystal data for the solvate of 24•4(H
(
3
4
1
2
O): C28
H23ClN
4
•4(H
2
O), M = 532.02, orthorhombic,
a = 14.5122(2) Å, b = 14.0615(2) Å, c = 24.8411(3) Å, α = 90°, β = 90°, γ = 90°,V =
3
5
069.16(12) Å , T = 100(2) K, space group Pbca, Z = 8, 29696 reflections measured, 5137
independent reflections (Rint = 0.0420).The final R
1
values were 0.0373 (I > 2σ(I)). The final
2
wR(F ) values were 0.0860 (I > 2σ(I)). The final R
1
values were 0.0497 (all data). The final
2
wR(F ) values were 0.0935 (all data). A single crystal was obtained by slow evaporation of a
concentrated solution of 24 in water/acetone (1:1).
2
.4.24. Synthesis of 5,6-dimethyl-1,3-bis(quinolin-2-ylmethyl)benzimidazolium chloride (25)
,6-Dimethyl-benzimidazole (0.41 g, 2.80 mmol) was dissolved in acetonitrile (6 mL),
potassium hydroxide (0.18 g, 3.21 mmol) was added, and the mixture was refluxed for 30 min.
-(Chloromethyl)quinoline (0.50 g, 2.81 mmol) was added, and the mixture was refluxed
5
2
overnight. The reaction mixture was filtered hot to remove a white solid, presumed to be
potassium chloride. 2-(Chloromethyl)quinoline (0.50 g, 2.81 mmol) was added to the filtrate
which was refluxed overnight. The resulting precipitate was collected via vacuum filtration of
the hot reaction mixture. The solid was washed with diethyl ether and air dried to yield a cream
powder 25 (0.80 g, 62%). Mp: 248 – 250 °C. Anal. Calcd for C29
H25ClN
4
•2(H
2
O): C, 69.52; H,
+
+
5
.83; N, 11.18% Found: C, 68.92; H, 4.91; N, 10.93%. HRMS (ESI ) calcd for C29
H
25
N
4
[M-
+
1
Cl] : m/z = 429.2079, found m/z = 429.2025. H NMR (500 MHz, DMSO-d
6
) 10.12 (s, 1H),
8
.51 (d, 2H, J = 8.3 Hz), 8.02 (d, 2H, J = 7.8 Hz), 7.82 – 7.72 (m, 8H), 7.63 (m, 2H), 6.19 (s,
2
5

1
3
1
4
1
2
H), 2.32 (s, 6H). C{ H} NMR (125 MHz, DMSO-d ) 153.9, 146.8, 143.4, 137.6, 136.4, 130.1,
6
29.9, 128.5, 128.0, 127.2, 127.0, 119.9, 113.3, 51.2, 19.9.
.4.25. Synthesis of 2-((2-(2-methoxyethoxy)ethoxy)methyl)benzimidazole (26).
Synthesized according to literature procedure.[9]
2
.4.26. Synthesis of 2-((2-(2-methoxyethoxy)ethoxy)methyl)-5,6-dimethylbenzimidazole (27)
4
,5-Dimethylbenzene-1,2-diamine (0.50 g, 3.67 mmol) was dissolved in 2-[2-(2-
Methoxyethoxy)ethoxy]acetic acid (0.68 mL, 4.41 mmol) and was refluxed overnight. The
solution was extracted in dichloromethane (2 x 32 mL). The organic layers were combined, dried
with magnesium sulfate, and the volatiles were removed under reduced pressure to a brown,
viscous oil. The oil was purified with column chromatography using a mobile phase of ethyl
acetate/hexanes (1:1) to yield a clear, orange liquid. The orange oil was dissolved in
dichloromethane (5 mL) and stirred for 1 h with sodium bicarbonate. Deionized water (10 mL)
was added to the residue, and the organic layer was extracted with dichloromethane (3 x 10 mL).
The organic layers were combined, dried with magnesium sulfate, and the volatiles were
removed under reduced pressure to yield a viscous, orange oil 27 (0.46 g, 45%). HRMS (ESI+)
+
+
+
1
calcd for C15
H
23
N
2
O
3
[M+H] of m/z = 279.1709, found [M+H] of m/z = 279.1713. H NMR
(
500 MHz, DMSO-d
6
) δ 12.18 (s, 1H), 7.33 (s, 1H), 7.30 (s, 1H), 4.67 (s, 2H), 3.63 (m, 2H),
1
3
1
3
.57 (m, 2H), 3.52 (m, 2H), 3.42 (m, 2H), 3.24 (s, 3H), 2.30 (s, 6H). C{ H} NMR (125 MHz,
) δ 150.4, 129.9, 71.3, 69.7, 66.2, 58.0, 19.8.
.4.27. Synthesis of 2-((2-(2-methoxyethoxy)ethoxy)methyl)-1,3-bis(naphthalen-2-
DMSO-d
6
2
ylmethyl)benzimidazolium bromide (28).
Compound 26 (1.37 g, 5.47 mmol) was dissolved in acetonitrile (20 mL), potassium
hydroxide (0.38 g, 6.77 mmol) was added, and the mixture was refluxed for 30 min. 2-
2
6

(
Bromomethyl)naphthalene (1.21 g, 5.47 mmol) was added to the flask and the mixture was
refluxed overnight. The reaction mixture was filtered hot to remove a white solid, presumed to
be potassium bromide. 2-(Bromomethyl)naphthalene (1.21 g, 5.47 mmol) was added to the
filtrate, which was refluxed overnight. The resulting precipitate was filtered hot, washed with
acetonitrile and diethyl ether, and dried in air to yield an off-white solid 28 (0.68 g, 20%). Mp:
1
6
95 – 198 °C. Anal. Calculated for C35
H
35BrN
2
O : C, 68.74; H, 5.77; N, 4.58%. Found: C,
3
+
+
+
8.46; H, 5.68; N, 4.60%. HRMS (ESI ) calculated for C35
H
35
N
2
O [M-Br] = 531.2648, found
3
1
m/z = 531.2621. H NMR (500 MHz, DMSO- d
6
) 8.00 – 7.88 (m, 10H), 7.62 (m, 3H, J = 6.1, 2.9
Hz), 7.55 (m, 5H), 6.14 (s, 4H), 5.45 (s, 2H), 3.78 (m, 2H), 3.40 (m, 2H,), 3.32 (m, 2H), 3.22 (m,
1
3
1
2
1
4
2
H), 3.09 (s, 3H). C{ H} NMR (125 MHz, DMSO-d ) 149.5, 132.6, 132.5, 131.7, 131.1, 128.6,
6
27.7, 127.6, 127.2, 126.63, 126.57, 126.4, 125.0, 114.1, 71.0, 70.5, 69.42, 69.40, 59.8, 57.9,
9.2.
.4.28. Synthesis of 2-((2-(2-methoxyethoxy)ethoxy)methyl)-3-(naphthalen-2-ylmethyl)-1-
(
quinolin-2-ylmethyl)benzimidazolium bromide (29)
Synthesized according to literature procedure[9].
2
.4.29. Synthesis of 2-((2-(2-methoxyethoxy)ethoxy)methyl)-1,3-bis(quinolin-2-
ylmethyl)benzimidazolium chloride (30)
Compound 26 (0.54 g, 2.16 mmol) was dissolved in acetonitrile (2 mL), potassium
hydroxide (0.18 g, 3.21 mmol) was added, and the mixture was refluxed for 30 min. 2-
(
Chloromethyl)quinoline (0.39 g, 2.20 mmol) was added to the flask, and the mixture was
refluxed overnight. The reaction mixture was filtered hot to remove a white solid, presumed to
be potassium chloride. 2-(Chloromethyl)quinoline (0.39 g, 2.20 mmol) was added to the filtrate,
which was refluxed overnight. The resulting precipitate was filtered hot,and washed with
2
7

acetonitrile and diethyl ether at room temperature to yield an off-white solid. The white solid was
purified by column chromatography on silica gel using a mobile phase of
methanol/dichloromethane (10:90) to yield an off-white solid 30 (0.64 g, 52%). Mp: 203 – 206
°
C. Anal. Calculated for C33
H
33ClN
4
O
3
: C, 69.65; H, 5.84; N, 9.84%. Found: C, 69.10; H, 5.82;
) 8.50 (d, 2H, J = 8.3 Hz), 8.12 (m, 2H), 8.01 (d, 2H, J
1
N, 9.84%. H NMR (500 MHz, DMSO- d
6
=
8.1 Hz), 7.76 (m, 2H), 7.68 – 7.60 (m, 8H), 6.39 (s, 4H), 5.47 (s, 2H), 3.65 (m, 2H), 3.23 –
1
3
1
3
1
5
.19 (m, 6H), 3.09 (s, 3H). C{ H} NMR (125 MHz, DMSO-d ) 153.8, 151.2, 146.7, 137.5,
6
31.5, 130.0, 128.4, 127.9, 127.2, 127.0, 126.9, 119.8, 113.7, 70.9, 70.3, 69.3, 69.2, 61.2, 57.9,
0.1.
Crystal data for the solvate of 30•(H
2
O)(C
3
H
8
O): C33
H
33Cl
1
N
4
O
3
•(H
2
O)(C
3
8
H O), M =
6
9
47.19, monoclinic, a = 13.3734(5) Å, b = 12.2699(6) Å, c = 21.1045(9) Å, α = 90°, β =
3
0.419(2)°, γ = 90°,V = 3463.0(3) Å , T = 100(2) K, space group P2(1)/n, Z = 4, 29417
reflections measured, 7038 independent reflections (Rint = 0.0433).The final R
1
values were
values were
2
0
.0501 (I > 2σ(I)). The final wR(F ) values were 0.1217 (I > 2σ(I)). The final R
1
2
0
.0695 (all data). The final wR(F ) values were 0.1354 (all data). A single crystal was obtained
by slow evaporation of a concentrated solution of 30 in isopropanol.
.4.30. Synthesis of 2-((2-(2-methoxyethoxy)ethoxy)methyl)-5,6-dimethyl-1,3-bis(naphthalen-2-
2
ylmethyl)benzimidazolium bromide (31)
Compound 27 (1.00 g, 3.59 mmol) was dissolved in acetonitrile (10 mL) with potassium
hydroxide (0.24 g, 4.31 mmol) and was refluxed for 30 min. 2-(Bromomethyl)naphthalene (0.79
g, 3.59 mmol) was added and the mixture was refluxed overnight. The reaction mixture was
filtered hot to remove a white precipitate, presumed to be potassium bromide. The filtrate was
stirred with 2-(bromomethyl)naphthalene (0.79 g, 3.59 mmol) and refluxed overnight. The
2
8

volatiles were removed under reduced pressure, and the residue was washed in a mixture of
diethyl ether and acetone (4:1 v/v, 265 mL). A solid impurity was removed via a room
temperature vacuum filtration. The volatile components of the filtrate were removed under
reduced pressure and the resulting residue was purified by column chromatography on silica gel
using a mobile phase of methanol/chloroform (5:95) to yield an off white residue. The residue
was washed with diethyl ether (20 mL) at room temperature to afford a cream solid 31. (0.48 g,
2
6
7
1%). Mp: 163-166 °C. Anal. Calcd for C37
H
29BrN
2
O
3
: C, 69.48; H, 6.15; N, 4.38%. Found: C,
) δ 7.97 – 7.87 (m, 8H), 7.81 (s, 2H),
1
9.28; H, 6.12; N, 4.34%. H NMR (400 MHz, DMSO-d
6
.57 – 7.51 (m, 6H), 6.08 (s, 4H), 5.35 (s, 2H), 3.71 (m, 2H), 3.35 (m, 2H), 3.29 (m, 2H), 3.20
13
1
(
m, 2H), 3.09 (s, 3H), 2.32 (s, 6H). C{ H} NMR (125 MHz, DMSO-d
6
) δ 148.1, 137.1, 132.7,
1
5
32.5, 131.9, 129.7, 128.6, 127.8, 127.6, 126.7, 125.6, 126.1, 125.0, 71.0, 70.8, 69.40, 60.39,
+
3
+
+
7.9, 48.9, 20.0. MS (ESI+) calcd for C37
H
29
N
2
O
[M-Br] of m/z = 559.3, found [M-Br] of
m/z = 559.2.
3
. Results and Discussion
3
.1 Synthesis and Characterization
5
6
Equation 1 outlines the syntheses of the C (C ) – substituted N,N’-bis(naphthylmethyl)-
benzimidazolium salts 2-6 from commercially available benzimidazole reagents with yields
ranging from 62 to 84% with the exception of 3, which has a 19% yield. The lipophilic salts 2-5
were prepared by stirring the select benzimidazole ring (5-methoxybenzimidazole, methyl
benzimidazole-5-carboxylate, 5,6-dimethyl-benzimidazole, and dimethyl benzimidazole-5,6-
dicarboxylate) with a minimum of 1.4 molar equivalents of base and one molar equivalent of 2-
(
bromomethyl)naphthalene in acetonitrile at reflux to yield a mono-substituted intermediate.
Following the removal of a white precipitate, a second equivalent of 2-
2
9