Synthesis and antimicrobial activity of some novel furyl and benzimidazole substituted benzyl ethers

Article abstract of DOI:10.1002/jhet.5570440336

(Chemical Equation Presented) In this study, a series of novel furyl and benzimidazole substituted benzyl ethers were synthesized and evaluated for antibacterial and antifungal activities against S. aureus, Methicillin resistant S. aureus (MRSA), E. coli,

Full text of DOI:10.1002/jhet.5570440336

May-Jun 2007
731
Synthesis and Antimicrobial Activity of Some Novel Furyl and
Benzimidazole Substituted Benzyl Ethers
Özden Özel Güven1*, Taner Erdoꢀan1, Hakan Göker2, Sulhiye Yıldız3
1 Department of Chemistry, Faculty of Arts and Sciences, Zonguldak Karaelmas University, 67100 Zonguldak, Turkey
2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Tandoꢀan, Ankara, Turkey
3 Department of Microbiology, Faculty of Pharmacy, Ankara University, 06100 Tandoꢀan, Ankara, Turkey
Received June 21, 2006
Ar
N
O
OH
O
N
CH3
O
N
N
NaH
1) Br2
NaBH4
N
N
O
O
O
2) 1H-Benzimidazole
ArCH2X
O
In this study, a series of novel furyl and benzimidazole substituted benzyl ethers were synthesized and
evaluated for antibacterial and antifungal activities against S. aureus, Methicillin resistant S. aureus
(MRSA), E. coli, C. albicans and C. krusei. Compound 6f and 6h exhibited the most potent anti-bacterial
activity with lowest MIC values of 3.12 μg/mL against S aureus and MRSA, respectively.
J. Heterocyclic Chem., 44, 731 (2007).
INTRODUCTION
Cl
The synthesis of a new class of antibacterial and
antifungal agents against especially Gram-positive drug
resistant bacteria and some fungi are urgently need
nowadays, since these types of microorganisms are
responsible for some infections in the acute and long-term
care units in hospitals. Well known azole derivatives,
having a gem-phenyl-(1H-imidazol-1-ylmethyl) moiety
(Formula I) which is thought to be largely responsible for
imparting of antifungal activity, such as clotrimazole,
miconazole (Formula II), econazole and ketoconazole,
have been developed for clinical uses [1]. SAR studies
revealed that imidazole and phenyl rings, which are also
pharmacophoric portion of all these molecules, can be
replaced by the triazole [2,3] and furan [1], respectively.
On the other hand, recently highly potent antifungal [4]
and antibacterial [5] activities of the benzimidazoles have
been reported in our previous studies. These encouraging
results prompted us to replace phenyl and imidazole ring
of the miconazole type structure to furan and
benzimidazole, respectively, with the aim of finding new
Cl
N
N
N
O
N
Cl
Cl
I
II
agents with higher antifungal and/or antibacterial activity.
Chemistry. The synthetic pathways for preparation of the
targeted compounds listed in Table 1 is shown in Scheme
I. 1-Furan-2-yl-ethanone 1 was brominated with bromine
in dioxane-ether mixture to obtain 2-bromo-1-furan-2-yl-
ethanone 2. Dehydrohalogenation between 2 and 1H-
benzimidazole
3 led to 2-(1H-benzimidazol-1-yl)-1-
(furan-2-yl)ethanone 4. Reduction of 4 with NaBH4 gave
2-(1H-benzimidazol-1-yl)-1-(furan-2-yl)ethanol 5.
Targeted compounds 6a – 6i were obtained by the
etherification of 5 with the appropriately substituted
Scheme I
N
N
H
CH2Br
O
CH3
Br2
3
O
O
N
O
1
2
Ar
O
OH
O
N
N
NaH
ArCH2X
NaBH4
N
N
N
O
O
O
4
5
6a-6i

732
Ö. Özel Güven, T. Erdoꢀan, H. Göker, S. Yıldız
Vol 44
benzyl halides in the presence of sodium hydride. In the
1H NMR spectrum of ketone 4, CH2 protons appeared as a
singlet at ꢀ 5.43. In the spectrum of alcohol 5, the methine
proton (CH-CH2) occurred as a doublet of doublets at ꢀ
5.06 (J=7.8 and 3.8 Hz) due to the adjacent diastereotopic
methylene group, and the diastereotopic methylene group
adjacent to the benzimidazole nitrogen was observed as a
doublet of doublets at ꢀ 4.40 (J=14.5, 7.8 Hz), ꢀ 4.50
(J=14.5, 3.8 Hz). In the spectrum of compound 6a, which
was typical of the benzyl ethers 6a–6i, the methine proton
(CH-CH2) occurred as a doublet of doublets at ꢀ 4.58
(J=7.6 and 4.8 Hz) due to the adjacent diastereotopic
methylene group, the protons of the methylene ether
group appeared as a pair of coupled doublets at ꢀ 4.14 and
4.42 (J=11.6 Hz), while the diastereotopic methylene
group adjacent to the benzimidazole nitrogen was
observed as a doublet of doublets at ꢀ 4.38 (J=14.4, 4.4
Hz) and 4.48 (J=14.4, 7.6 Hz).
RESULTS AND DISCUSSION
All described benzyl ethers 6a – 6i were tested in vitro
for antibacterial activity against Gram-positive
Staphylococcus
Staphylococcus
aureus, Methicillin-resistant
aureus (MRSA), Gram-negative
Escherichia coli bacteria, and for anti-fungal activity
against Candida albicans and Candida krusei by the
diffusion method [4,5]. The compounds giving a good
growth inhibition zone in this method were further tested
Table 1
Formulas and in vitro antibacterial activities as MIC (μg/mL) for 6a - 6i
Ar
O
N
N
O
No
Ar
S. aureus
ATCC25923
MRSA
ATCC43300
C. albicans
ATCC10231
C. krusei
ATCC6258
E. coli
ATCC25922
6a
6b
6c
6d
6e
12.5
12.5
12.5
6.25
12.5
25
25
25
50
25
25
50
50
50
50
50
25
NT
NT
>50
>50
NT
F
Cl
25
Br
12.5
12.5
CF3
Cl
6f
3.12
NT
12.5
NT
12.5
NT
25
50
Cl
Cl
6g
NT
NT
Cl
Cl
6h
6i
6.25
6.25
3.12
6.25
50
50
25
50
NT
NT
Cl
Cl
Cl
Ampicillin
Fluconazole
Miconazole
Ciprofloxacin
0.78
-
25
-
-
-
25
0.78
>50
-
1.56
0.19
0.39
* NT : Not tested, since no clear visible inhibition zone at the disc diffusion method

May-Jun 2007
Synthesis and Antimicrobial Activity of Some Novel Furyl
and Benzimidazole Substituted Benzyl Ethers
733
The reaction mixture was warmed to ambient temperature and
stirred for an additional 18 hours, then diluted with 20 mL of
water and extracted with chloroform. Organic extract was dried
(sodium sulfate), concentrated under reduced pressure and
residue was separated by column chromatography (silica
gel/chloroform-methanol). The ketone was obtained as
yellowish solid and recrystallized from ethyl acetate-hexane,
by the macro-broth dilution assay [6] to determine their
MIC values, which are listed in Table 1. The synthesized
compounds and reference drugs were dissolved in
DMSO-H2O (50 %), at a concentration of 400 μg/mL.
The concentration was adjusted to 100 μg/mL by fourfold
dilution with culture medium and bacterial solution at the
first tube. Data was not taken for the initial solution
because of the high DMSO concentration (12.5 %).
According to the obtained results, unexpectedly, the
antifungal activity has been found less than the
antibacterial activity of the synthesized compounds 6a –
6i . Surprisingly, some of the compounds exhibited better
activity against gram-positive bacteria S. aureus and
MRSA. It appears that halogenated benzyl substitution
enhance the antibacterial activities against S. aureus and
MRSA. This finding was also put forward by other
researchers [7]. The best results were obtained with
compounds 6f, 6i, and 6h, which have two chlorine atoms
at different positions of the phenyl ring. Interestingly,
while the same substitutions are on the C-2,6 position, 6g
has no activity. This means that the position of halogen
substitutions should be effective to modulate the activity.
None of the compounds were active against E. Coli.
1
3.45 g (51 %), mp 152-156 °C; IR: CO 1673 cm-1; H NMR
(deuteriochloroform): ꢀ 5.43 (s, 2H), 6.64 (dd, 1H, J= 3.6, 1.6
Hz), 7.25-7.35 (m, 4H), 7.70 (d, 1H, J= 1.6 Hz), 7.81 (m, 1H),
7.98 (s, 1H); 13C NMR (deuteriochloroform): ꢀ 50.4, 109.8,
113.5, 119.0, 120.7, 122.9, 123.8, 134.5, 143.5, 144.0, 147.7,
151.2, 181.1. ESI (+) m/e 227 (M+1, 100). Anal. Calcd. for
C13H10N2O2 . 0.25HOH: C, 67.67; H, 4.58; N, 12.14. Found: C,
67.42; H, 4.26; N, 12.16.
2-(1H-Benzimidazol-1-yl)-1-(furan-2-yl) ethanol (5).
A
solution of NaBH4 (6.36 mmole) in 13.5 mL ethanol was added
dropwise to an ice-cold solution of ketone (4) (6.36 mmole) in
26 mL of ethanol. After all the solution was added, the reaction
mixture was warmed to ambient temperature and stirred for an
additional 90 minutes. The solution was diluted with ether and
brine, and then extracted with ether. Organic extract was dried
(sodium sulfate) and solvent was removed under reduced
pressure. The alcohol (5) was obtained as solid 1 g (69 %), mp
1
134-136 °C; H NMR (deuteriochloroform): ꢀ 4.25 (br s, 1H),
4.37 (dd, 1H, J= 14.5, 7.8 Hz), 4.47 (dd, 1H, J= 14.5, 3.8 Hz),
5.06 (dd, 1H, J= 7.8, 3.8 Hz), 6.22-6.31 (m, 2H), 7.04-7.42 (m,
5H), 7.73 (s, 1H). 13C NMR (deuteriochloroform): ꢀ 50.3, 66.4,
107.7, 110.2, 110.8, 119.0, 123.4, 123.9, 133.3, 140.3, 142.6,
143.3, 153.5. ESI (+) m/e 229 (M+1, 100). Anal. Calcd. for
C13H12N2O2 . 0.3HOH: C, 66.83; H, 5.43; N, 11.98. Found: C,
66.89; H, 5.29; N, 11.92.
CONCLUSION
We have discovered that introduction of the
benzimidazole and furan moities to the miconazole type
structure, allowed us to obtain the desired good profile of
Gram-positive antibacterial activity against S. aureus and
MRSA. In vivo and cytotoxicity studies of the best active
compounds 6f and 6h, are necessary to fully evaluate the
potential of these compounds.
General procedure for the preparation of benzyl ethers 6a
- 6i. To a solution of alcohol 5 (0.530 mmole) in 1.2 mL DMF
was added NaH (0.663 mmole) in small fractions. The
appropriate benzyl halide (0.530 mmole) in 0.6 mL of DMF was
then added dropwise. The mixture was stirred at room
temperature for 2 hours and the excess of hydride was
decomposed with a small amount of methyl alcohol. After
evaporation to dryness under reduced pressure, the crude residue
was suspended with water and extracted with methylene
chloride. The organic layer was dried (sodium sulfate) and then
evaporated to dryness. The crude residue was purified by
chromatography on a silica-gel column using chloroform-
methanol to obtain the title compounds.
EXPERIMENTAL
Melting points were recorded on Stuart Scientific SMP 1
instrument. IR spectra were recorded on Jasco FT-IR
spectrometer, NMR spectra were recorded on Varian Mercury
400 MHz FT-NMR spectrometer (Varian Inc., Palo Alto, CA,
USA). Mass spectra were taken on a Waters ZQ micromass LC-
MS spectrometer (Waters Corporation, Milford, MA, USA) by
using ESI (+) method. Elemental analysis were performed on
LECO 932 CHNS (Leco-932, St. Joseph, MI, USA) instrument
and were within ± 0.4 % of the theoretical values.
2-(1H-Benzimidazol-1-yl)-1-(furan-2-yl)ethanone (4). Under
an argon atmosphere, bromine (38 mmole) was added dropwise
over 30 minutes period to an ice-cold solution of (1) (30 mmol)
in 18 mL of dioxane-ether (1:2). The reaction mixture was
warmed to ambient temperature and stirred for 12 hours, then
quenched with 20 mL of saturated aqueous ammonium chloride.
The organic layer was separated and extracted with ether and
then dried over anhydrous sodium sulfate. The solvent was
removed under reduced pressure and the product (2) was
obtained by column chromatography using hexane-ethyl acetate.
Then, it was dissolved in 12 mL of dioxane-ether (4:1). This
solution was added over 60 minutes to an ice-cold solution of (3)
(138 mmole) in 15 mL of methanol under argon atmosphere.
1-(2-(Benzyloxy)-2-(furan-2-yl)ethyl)-1H-benzimidazole
(6a). Yield 40 %, oily; 1H NMR (deuteriochloroform): ꢀ 4.14 (d,
1H, J= 11.6 Hz), 4.38 (dd, 1H, J= 14.4, 4.4 Hz), 4.42 (d, 1H, J=
11.6 Hz), 4.48 (dd, 1H, J= 14.4, 7.6 Hz), 4.58 (dd, 1H, J= 7.6,
4.8 Hz), 6.22 (d, 1H, J= 3.2 Hz), 6.27-6.30 (m, 1H), 6.90-6.94
(m, 2H), 7.07-7.12 (m, 3H), 7.14-7.22 (m, 3H), 7.39 (m, 1H),
7.72 (m, 1H), 7.84 (s, 1H). 13C NMR (deuteriochloroform): ꢀ
48.5, 71.1, 72.2, 109.8, 110.1, 110.8, 120.3, 122.5, 123.3, 128.0,
128.1, 128.6, 133.9, 137.1, 143.1, 143.5, 144.0, 150.7. ESI (+)
m/e 319 (M+1, 100). Anal. Calcd. for C20H18N2O2 . HOH: C,
71.41; H, 5.99; N, 8.32. Found: C, 71.55; H, 5.68; N, 8.18.
1-(2-(4-Fluorobenzyloxy)-2-(furan-2-yl)ethyl)-1H-benzimi-
1
dazole (6b). Yield 26 %, oily; H NMR (deuteriochloroform): ꢀ
4.11 (d, 1H, J= 11.6 Hz), 4.38 (d, 1H, J= 11.6 Hz), 4.43 (dd, 1H,
J= 14.2, 4.2 Hz), 4.53 (dd, 1H, J= 14.4, 8.4 Hz), 4.60 (dd, 1H, J=
8.4, 4.0 Hz), 6.26 (d, 1H, J= 3.2 Hz), 6.30-6.33 (m, 1H), 6.77 (t,
2H, J= 8.6 Hz), 6.83-6.89 (m, 2H), 7.19-7.24 (m, 3H), 7.41 (s,

734
Ö. Özel Güven, T. Erdoꢀan, H. Göker, S. Yıldız
Vol 44
1H), 7.77 (d, 1H, J= 6.8 Hz), 8.03 (s, 1H). 13C NMR
(deuteriochloroform): ꢀ 47.5, 69.2, 70.8, 108.7, 108.8, 109.5,
114.1, 114.3, 118.7, 121.8, 122.4, 128.5, 128.6, 131.5, 132.4,
140.8, 142.3, 142.4, 149.3, 160.1, 162.6. ESI (+) m/e 337 (M+1,
100). Anal. Calcd. for C20H17FN2O2 . 0.3HOH: C, 70.28; H, 5.19;
N, 8.19. Found: C, 70.13; H, 4.59; N, 8.13.
1-(2-(4-Chlorobenzyloxy)-2-(furan-2-yl)ethyl)-1H-benz-
imidazole (6c). Yield 36 %, oily; 1H NMR (deuterio-
chloroform): ꢀ 4.29 (d, 1H, J= 12.8 Hz), 4.40 (d, 1H, J= 12.8
Hz), 4.43 (dd, 1H, J= 14.4, 4.4 Hz), 4.55 (dd, 1H, J= 14.4, 8.4
Hz), 4.64 (dd, 1H, J= 8.4, 4.4 Hz), 6.29 (d, 1H, J= 3.2 Hz), 6.30-
6.33 (m, 1H), 6.86 (d, 1H, J= 8.0 Hz), 6.93 (dd, 1H, J= 8.2, 1.8
Hz), 7.17-7.26 (m, 5H), 7.42 (s, 1H), 7.74 (dd, 1H, J= 6.2, 1.4
Hz), 7.85 (s, 1H). 13C NMR (deuteriochloroform): ꢀ 48.5, 70.3,
72.2, 109.6, 110.1, 110.8, 120.6, 122.4, 123.2, 128.7, 129.2,
133.8, 133.9, 135.6, 143.6, 143.7, 144.1, 150.6. ESI (+) m/e 353
(M+1, 100), 355 (M+2+1, 33). Anal. Calcd. for C20H17ClN2O2 .
0.25HOH: C, 67.23; H, 4.94; N, 7.83. Found: C, 67.13; H, 5.38;
N, 7.61.
Hz), 4.70 (d, 1H, J= 10.8 Hz), 4.74-4.78 (m, 1H), 6.32 (dd, 1H,
J= 2.8, 2.0 Hz), 6.37 (d, 1H, J= 2.8 Hz), 7.01 (dd, 1H, J= 9.0, 7.0
Hz), 7.10 (d, 2H, J= 8.4 Hz), 7.19-7.27 (m, 3H), 7.42 (s, 1H),
7.73 (d, 1H, J= 6.4 Hz), 8.05 (s, 1H). 13C NMR (deuterio-
chloroform): ꢀ 47.7, 64.8, 72.1, 108.7, 108.8, 109.6, 118.3,
122.1, 122.6, 127.3, 129.2, 131.3, 132.0, 135.5, 139.5, 141.9,
142.4, 149.2. ESI (+) m/e 387 (M+1, 100), 389 (M+2+1, 65),
391 (M+4+1, 11). Anal. Calcd. for C20H16Cl2N2O2: C, 62.03; H,
4.16; N, 7.23. Found: C, 61.8; H, 4.13; N, 7.22.
1-(2-(2,5-Dichlorobenzyloxy)-2-(furan-2-yl)ethyl)-1H-benz-
1
imidazole (6h). Yield 48 %, mp 89-92 °C; H NMR (deuterio-
chloroform): ꢀ 4.38 (d, 1H, J= 12.8 Hz), 4.45 (d, 1H, J= 13.2
Hz), 4.68 (dd, 1H, J= 14.4, 4.0 Hz), 4.76 (dd, 1H, J= 14.4, 7.6
Hz), 4.88 (dd, 1H, J= 7.6, 4.4 Hz), 6.37-6.43 (m, 2H), 7.10-7.2
(m, 3H), 7.35-7.39 (m, 2H), 7.44-7.51 (m, 2H), 7.85-7.91 (m,
1H), 8.49 (s, 1H). 13C NMR (deuteriochloroform): ꢀ 48.3, 67.9,
73.8, 109.6, 110.4, 110.8, 120.7, 122.4, 123.2, 128.9, 129.0,
130.4, 130.9, 133.0, 134.0, 136.9, 143.7, 143.9, 150.2. ESI (+)
m/e 387 (M+1, 100), 389 (M+2+1, 66), 391 (M+4+1, 12). Anal.
Calcd. for C20H16Cl2N2O2 . 0.5HOH: C, 60.61; H, 4.32; N, 7.10.
Found: C, 60.86; H, 4.10; N, 7.15 .
1-(2-(4-Bromobenzyloxy)-2-(furan-2-yl)ethyl)-1H-benzimi-
1
dazole (6d). Yield 34 %, oily; H NMR (deuteriochloroform): ꢀ
4.09 (d, 1H, J= 12 Hz), 4.35 (d, 1H, J= 12 Hz), 4.39 (dd, 1H, J=
14.8, 4.0 Hz), 4.51 (dd, 1H, J= 14.8, 8.4 Hz), 4.57 (dd, 1H, J=
8.4, 3.6 Hz), 6.24 (d, 1H, J= 3.6 Hz), 6.32 (dd, 1H, J= 3.4, 1.8
Hz), 6.76 (d, 2H, J= 8.8 Hz), 7.17-7.25 (m, 5H), 7.41-7.43 (m,
1H), 7.75 (d, 1H, J= 7.6 Hz), 7.84 (s, 1H). 13C NMR
(deuteriochloroform): ꢀ 48.5, 70.3, 72.2, 109.7, 110.1, 110.8,
120.5, 122.0, 122.6, 123.3, 129.6, 131.7, 133.9, 136.1, 143.5,
143.6, 144.1, 150.6. ESI (+) m/e 397 (M+1, 100), 399 (M+2+1,
100). Anal. Calcd. for C20H17BrN2O2 . 0.25HOH: C, 59.78; H,
4.39; N, 6.97. Found: C, 59.52; H, 4.18; N, 6.77.
1-(2-(3,4-Dichlorobenzyloxy)-2-(furan-2-yl)ethyl)-1H-benz-
imidazole (6i). Yield 40 %, oily; 1H NMR (deuteriochloroform):
ꢀ 4.17 (d, 1H, J= 12.4 Hz), 4.39 (d, 1H, J= 12.8 Hz), 4.48 (dd,
1H, J= 14.0, 4.4 Hz), 4.59 (dd, 1H, J= 14.0, 8.4 Hz), 4.65 (dd,
1H, J= 8.4, 4.4 Hz), 6.32 (d, 1H, J= 3.6 Hz), 6.38-6.46 (m, 1H),
6.74 (dd, 1H, J= 8.0, 1.6 Hz), 7.11 (d, 1H, J = 1.6), 7.18 (d, 1H,
J= 8.0 Hz), 7.26-7.31 (m, 3H), 7.49 (s, 1H), 7.82 (d, 1H, J= 8.0
Hz), 7.88 (s, 1H). 13C NMR (deuteriochloroform): ꢀ 48.4, 69.7,
72.7, 109.7, 110.2, 110.8, 120.6, 122.5, 123.3, 126.9, 129.6,
130.6, 131.9, 132.6, 133.9, 137.4, 143.5, 143.6, 143.9, 150.4.
ESI (+) m/e 387 (M+1, 100), 389 (M+2+1, 61), 391 (M+4+1,
10). Anal. Calcd. for C20H16Cl2N2O2: C, 60.61; H, 4.32; N, 7.07.
Found: C, 60.28; H, 4.35; N, 7.01.
1-(2-(4-(Trifluoromethyl)benzyloxy)-2-(furan-2-yl)ethyl)-
1
1H-benzimidazole (6e). Yield 42 %, oily; H NMR (deuterio-
chloroform): ꢀ 4.22 (d, 1H, J= 12.4 Hz), 4.40-4.46 (m, 2H),
4.50-4.60 (m, 2H), 6.27 (d, 1H, J= 2.8 Hz), 6.32-6.33 (m, 1H),
7.04 (d, 2H, J= 8.0 Hz), 7.16-7.28 (m, 3H), 7.32 (d, 2H, J= 8.4
Hz), 7.42 (m, 1H), 7.75 (d, 1H, J= 8.0 Hz), 7.86 (s, 1H). 13C
NMR (deuteriochloroform): ꢀ 48.5, 70.3, 72.5, 109.6, 110.2,
110.8, 120.5, 122.6, 123.3, 125.4, 125.5, 127.8, [129.7, 130.0,
130.3, 130.6], 133.9, 141.1, 143.5, 143.7, 144.1, 150.4. ESI (+)
m/e 387 (M+1, 100). Anal. Calcd. for C21H17F3N2O2 . 0.5HOH:
C, 63.79; H, 4.58; N, 7.09. Found: C, 63.63; H, 4.33; N, 7.10.
1-(2-(2,4-Dichlorobenzyloxy)-2-(furan-2-yl)ethyl)-1H-benz-
imidazole (6f). Yield 45 %, oily; 1H NMR (deuteriochloroform):
ꢀ 4.1 (d, 1H, J= 11.6 Hz), 4.36 (d, 1H, J= 11.6 Hz), 4.38 (dd,
1H, J= 14.0, 4.0 Hz), 4.5 (dd, 1H, J= 14.0, 8.4 Hz), 4.56 (dd, 1H,
J= 8.4, 4.0 Hz), 6.24 (d, 1H, J= 2.8 Hz), 6.30-6.32 (m, 1H), 6.81
(d, 2H, J= 8.0 Hz), 7.03 (d, 2H, J= 8.0 Hz), 7.17-7.21 (m, 2H),
7.41 (s, 1H), 7.74 (d, 1H, J= 7.6 Hz), 7.82 (s, 1H). 13C NMR
(deuteriochloroform): ꢀ 48.5, 70.3, 72.3, 109.7, 110.1, 110.8,
120.5, 122.5, 123.3, 128.7, 129.3, 133.9, 134.0, 135.6, 143.6,
144.1, 150.7. ESI (+) m/e 387 (M+1, 100), 389 (M+2+1, 59),
391 (M+4+1, 9.5). Anal. Calcd. for C20H16Cl2N2O2 . 0.75HOH:
C, 59.94; H, 4.40; N, 6.99. Found: C, 59.93; H, 4.12; N, 6.93.
1-(2-(2,6-Dichlorobenzyloxy)-2-(furan-2-yl)ethyl)-1H-
benzimidazole (6g). Yield 49 %, mp 79-80 °C; 1H NMR
(deuteriochloroform): ꢀ 4.40-4.54 (m, 2H), 4.52 (d, 1H, J= 10.8
Acknowledgement. This work was supported by Zonguldak
Karaelmas University Research Fund (Project No: 2004-13-02-
16). Central Lab. of Pharmacy Faculty of Ankara University
provided support for acquisition of the NMR, Mass
spectrometer, and elemental analyzer used in this work.
REFERENCES
[1] Bennett, G. A.; Mullen, G. B.; Mitchell, J. T.; Jones, W. E.;
Allen, S. D.; Kinsolving, C. R.; Georgiev, V. Eur. J. Med. Chem. 1989,
24, 579.
[2] Rossello, A.; Bertini, S.; Lapucci, A.; Macchia, M.;
Martinelli, A.; Rapposelli, S.; Herreros, E.; Macchia, B. J. Med. Chem.
2002, 45, 4903.
[3] Wahbi, Y.; Caujolle, R.; Tournaire, C.; Payard, M.; Linas, M.
D.; Seguela, J. P. Eur. J. Med. Chem. 1995, 30, 955.
[4] Göker, H.; Kus, C.; Boykin, D.W.; Yildiz, S.; Altanlar, N.
Bioorg. Med. Chem. 2002, 10, 2589.
[5] Özden, S.; Karataꢁ, H.; Yildiz, S.; Göker, H. Arch. Pharm.
2004, 337, 556.
[6] Göker, H.; Özden, S.; Yildiz, S.; Boykin, D. W. Eur. J. Med.
Chem. 2005, 40, 1062.
[7] Vlaovic, D.; Brunet, J. C.; Balaz, J.; Juranic, I.; Djokovic, D.;
Mackenzei, K. Biosci. Biotechnol. Biochem. 1992, 56, 199.