Synthesis and structural characterization of 2-(hydroxyethoxy substituted)phenyl benzimidazoles

Article abstract of DOI:10.14233/ajchem.2015.17567

In this paper, using o-phenylendiamine, hydroxyl substituted benzaldehyde and chlorohydrin as starting materials, four 2-(hydroxyethoxy substituted)phenyl benzimidazoles were synthesized by two different routes. In route I, the hydroxyl substituted benzal

Full text of DOI:10.14233/ajchem.2015.17567

Asian Journal of Chemistry; Vol. 27, No. 5 (2015), 1719-1724
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2015.17567
Synthesis and Structural Characterization of 2-(Hydroxyethoxy Substituted)phenyl Benzimidazoles
1,2
1,2
ZHI-YUAN WANG , HAI-BIN GU1,2,*, JIA-CHENG WU1,2 and WU-YONG CHEN
1Key Laboratory of Leather Chemistry and Engineering of Ministry of Education, Sichuan University, Chengdu 610065, P.R. China
2National Engineering Laboratory for Clean Technology of Leather Manufacture, Sichuan University, Chengdu 610065, P.R. China
*Corresponding author: Fax: +86 28 85405237; Tel: +86 28 85404462; E-mail: guhaibing@scu.edu.cn
Received: 7 March 2014;
Accepted: 11 September 2014;
Published online: 20 February 2015;
AJC-16878
In this paper, using o-phenylendiamine, hydroxyl substituted benzaldehyde and chlorohydrin as starting materials, four 2-(hydroxyethoxy
substituted)phenyl benzimidazoles were synthesized by two different routes. In route I, the hydroxyl substituted benzaldehyde firstly
reacted with o-phenylendiamine to get the intermediates 2-(hydroxyl substituted)phenyl benzimidazoles which then were used to synthesize
the final products by the o-hydroxyethylation reaction with chlorohydrin. In route II, the hydroxyethoxy substituted benzaldehyde was
firstly synthesized through the o-hydroxyethylation reaction and then reacted with o-phenylendiamine. Results show that route I is
suitable only for the target compounds in which hydroxyethoxy group is located in para- and meta-position of benzimidazole in the
benzene ring. For the synthesis of 2-(o-hydroxyethoxy)phenyl benzimidazole, route II is the only choice because of its strong steric
hindrance. The structures of the four new compounds were characterized and confirmed by elemental analysis, IR, 1H NMR, 13C NMR
and single-crystal X-ray diffraction analysis.
Keywords: Benzimidazole, Hydroxyl, Hydroxyethylation, Crystal structure.
on a Shanghai Zhongguang WRS-2 melting point apparatus
and uncorrected. IR spectra (4000-400 cm-1) were recorded
on a MAGNA.IR 506 Model FT-IR spectrometer (KBr pellets).
1H NMR and 13C NMR spectra were scanned on a BrukerAvance
AVII-600 Model spectrometer using DMSO-d6 as solvent.
Chemical shifts were reported as δ (ppm) relative to TMS as
internal standard. Mass spectra were measured on a GCMS-
QP2010 Plus Model GC-MS spectrometer. Measurement of
the crystal was carried out on an Xcalibur E Model CCD X-
ray single crystal diffractometer. Elemental analyses (C, H,
N) were performed on a Carlo-Erba 1106 Model analyzer.
Synthesis of 2-(hydroxyl substituted)phenyl benzimi-
dazole intermediates (1a-1c): As the route 1 in Fig. 1, the
hydroxyl benzaldehyde derivative (36 mmol) dissolved in 50
mL of ethanol was mixed by sodium bisulfate (36 mmol) and
the mixture was stirred for 12 h at room temperature. In which
o-phenylenediamine (36 mmol) dissolved in 150 mL of DMF
was added with 140 °C in a oil bath for another 2 h of reaction.
The product was poured into 3 L of ice-cooled water and the
solid mass separated out was filtered, dried and crystallized
from ethanol. 2-(p-Hydroxyl)phenyl benzimidazole (1a), 2-
(m-hydroxyl)phenyl benzimidazole (1b) and 2-(3'-methoxyl-
4'-hydroxyl)phenyl benzimidazole (1c) were obtained with
melting points: 287.2-287.9 °C [278-279 °C]15, 285.0-286.2 °C
[280-282 °C]16, 225.2-226.5 °C [224.7-225.4 °C]17, respectively.
INTRODUCTION
Benzimidazole derivatives which contain two nitrogen
atoms are applied in biochemistry and pharmacology because
of their positive biological and physiological activities1-4, e.g.
antimicrobial5, anticancer6, antiviral7, insecticide8, anti-infla-
mmatory9, herbicide10, antiphlogistic, antipyretic, analgesic,
spasmolytic11.With special structure and activity, benzimidazole
derivatives have been broadly studied in recent decades12-14
.
In this article, four novel 2-(hydroxyethoxy substituted)
phenyl benzimidazoles with hydroxyl groups, which can bring
in other active groups through esterification are reported, provides
a feasible method for developing novel pharmic benzimidazole
derivatives. Based on the difference of relative position between
hydroxyethoxy and benzimidazole in target product, two syn-
thetic routes were adopted (Fig. 1) and four 2-(hydroxyethoxy-
substituted)phenyl benzimidazoles were obtained and their
structures were characterized by Mass spectra, IR, 1H NMR, 13C
NMR and elementary analysis. In order to obtain information
about the stereochemistry of the molecules and to confirm the
assigned structure, X-ray analyses were also undertaken.
EXPERIMENTAL
All materials were commercially purchased and used
without further purification. Melting points were determined

1720 Wang et al.
Asian J. Chem.
OH
X
N
N
ClCH CH OH
NH
OH
2
2
2
OCH CH OH
2
2
+
NH
CHO
2
KI NaOH/H O
N
2
I
N
H
H
X
X
2 a~c
X=H; OCH3
1 a~c
NH
NH
2
2
N
ClCH CH OH
2
2
OH
OCH CH OH
2
2
II
CHO
CHO
KI NaOH/H O
N
2
H
OCH CH OH
2
2
1 d
2 d
Fig. 1. Synthetic routes for 2-(hydroxyethoxy substituted)phenyl benzimidazoles
Synthesis of 2-(hydroxyethoxy substituted)phenyl
2946.30, 2862.03 (υCH ), 2827.39 (υCH ), 1607.30 (υC=N),
2
3
benzimidazoles (2a-2c): 2-(Hydroxyl substituted)phenyl
benzimidazole intermediate (7.5 mmol) and potassium iodide
(0.45 mmol) were dissolved in the presence of NaOH
(15 mmol) solution (15 mL). In which chlorohydrin (37.5
mmol) was added with 8-10 drops per min at 80 °C. The pH
was kept at 9 adjusted by 50 % NaOH solution for 3 h. The
product was poured into 40 mL of cold deionized water and
solid mass separated out was filtered, dried and crystallized
from ethanol.
1400.63, 1477.93, 1451.68, 1436.51 (υbenzene C=C), 1397.80
(δCH ), 1362.36, 1325.59 (υC-N), 1265.33, 1242.94 (υAr-O),
2
1087.94, 1064.13 (υC-O), 869.90, 736.66 (δAr-H). 1H NMR (400
MHz, DMSO-d6), δppm: 3.79 (q, 2H, -CH2O-), 3.91 (s, 3H,
-OCH3), 4.08 (t, 2H, -OCH2-), 4.97 (t, 1H, -OH), 7.13 (d, 1H,
Ph), 7.20 (m, 2H, Ph), 7.59 (s, 2H, Ph), 7.75 (d, 1H, Ph), 7.81
(s, 1H, Ph), 12.80 (s, 1H, -NH-). 13C NMR (400 MHz, DMSO-
d6), δppm: 55.51 (-OCH3), 59.53 (-CH2OH), 70.20 (-OCH2-),
109.90 (Ph), 112.87 (Ph), 119.27 (Ph), 121.78 (Ph), 122.74
(Ph), 149.03 (Ph), 149.69 (Ph), 151.48 (-C=N).
2-(p-Hydroxyethoxy)phenyl benzimidazole (2a):Yield:
69.8 %. m.p.: 210.2-210.4 °C.Anal. Calcd (%) for C15H14N2O2:
C, 70.87; H, 5.51; N, 11.02. Found (%): C, 71.29; H, 6.39; N,
11.10. IR (KBr, νmax, cm-1): 3204.24 (υOH), 2926.15, 2868.24
Synthesis of o-hydroxyethoxy benzaldehyde (1d): o-
Hydroxybenzaldehyde (0.1 mol) and potassium iodide (0.006
mol) were dissolved in sodium hydroxide (0.2 mol) solution
(15 mL). In which chlorohydrin (0.5 mol) was added with
8-10 drops per min at 80 °C. The pH was kept at 9 adjusted by
50 % sodium hydroxide solution for 3 h. The product was
cooled to room temperature. The substratum was collected,
washed and dried.
Synthesis of 2-(o-hydroxyethoxy) phenyl benzimida-
zole (2d): o-Hydroxyethoxy benzaldehyde (1d, 36 mmol)
dissolved in 50 mL of ethanol was mixed by sodium bisulfate
(36 mmol) and the mixture was stirred for 12 h at room tempe-
rature. In which o-phenylenediamine (36 mmol) dissolved in
150 mL of DMF was added at 140 °C in a oil bath for another
2 h of reaction. The product was poured into 3 L of chilled
water and the solid mass separated out was filtered, dried and
crystallized from ethanol.
(υCH ), 1614.71 (υC=N), 1497.20, 1479.05, 1451.27, 1436.67
2
(υbenzene C=C), 1397.65 (δCH ), 1369.45, 1316.95 (υC-N), 1250.73
2
1
(υAr-O), 1080.29, 1058.14 (υC-O), 837.28, 743.04 (δAr-H). H
NMR (600 MHz, DMSO-d6), δppm: 3.76 (t, 2H, -CH2O-), 4.09
(t, 2H, -OCH2-), 4.94 (s, 1H, -OH), 7.12 (d, 2H, Ph), 7.18 (m,
2H, Ph), 7.56 (s, 2H, Ph), 8.10 (d, 2H, Ph), 12.75 (s, 1H, -NH-).
13C NMR (600 MHz, DMSO-d6), δppm: 60.02 (-CH2OH), 70.21
(-OCH2-), 115.35 (Ph), 122.25 (Ph), 123.08 (Ph), 128.50 (Ph),
151.85 (Ph), 160.57 (-C=N-).
2-(m-Hydroxyethoxy)phenyl benzimidazole (2b):Yield:
71.9 %. m.p.: 203.0-204.6 °C.Anal. Calcd (%) for C15H14N2O2:
C, 70.87; H, 5.51; N, 11.02. Found (%): C, 70.99; H, 5.89; N,
11.14. IR (KBr, νmax, cm-1): 3204.37 (υOH), 2926.37, 2868.49
(υCH ), 1613.89 (υC=N), 1497.38, 1479.20, 1451.68, 1436.77
2
(υbenzene C=C), 1397.66 (δCH ), 1369.60, 1316.81 (υC-N), 1251.25
Yield: 50.3 %. m.p.: 162.8-163.7 °C. Anal. Calculated
(%) for C15H14N2O2: C, 70.87; H, 5.51; N, 11.02. Found (%):
C, 71.79; H, 6.21; N, 11.24. R (KBr, νmax, cm-1): 3147.24 (υOH),
2
(υAr-O), 1080.65, 1057.93 (υC-O), 837.23, 743.24 (δAr-H). 1H NMR
(400 MHz, DMSO-d6), δppm: 3.80 (q, 2H, -CH2O-), 4.12 (t, 2H,
-OCH2-), 4.96 (t, 1H, -OH), 7.09 (d, 1H, Ph), 7.23 (m, 2H,
Ph), 7.46 (t, 1H, Ph), 7.62 (s, 2H, Ph), 7.78 (t, 2H, Ph), 12.91
(s, 1H, -NH-). 13C NMR (400 MHz, DMSO-d6), δppm: 59.56
(-CH2OH), 69.66 (-OCH2-), 111.89 (Ph), 116.42 (Ph), 118.72
(Ph), 122.09 (Ph), 130.07 (Ph), 131.42 (Ph), 135.03 (Ph),
143.88 (Ph), 151.09 (Ph), 159.06 (-C=N).
2936.66, 2879.64 (υCH ), 1621.03 (υC=N), 1530.67, 1488.67,
2
1473.44, 1445.24 (υbenzene C=C), 1403.21 (δCH ), 1369.81, 1313.68
2
(υC-N), 1244.94 (υAr-O), 1075.96, 1042.05 (υC-O), 793.36, 743.97
1
(δAr-H). H NMR (400 MHz, DMSO-d6), δppm: 3.93 (t, 2H,
-CH2O-), 4.32 (t, 2H, -OCH2-), 5.70 (s, 1H, -OH), 7.16 (t, 1H,
Ph), 7.23 (m, 2H, Ph), 7.31 (d, 1H, Ph), 7.47 (t, 1H, Ph), 7.63
(s, 2H, Ph), 8.31 (d, 1H, Ph), 12.23 (s, 1H, -NH-). 13C NMR
(400 MHz, DMSO-d6), δppm: 59.39 (-CH2OH), 71.00 (-OCH2-),
114.81 (Ph), 119.04 (Ph), 121.58 (Ph), 121.87 (Ph), 129.70
(Ph), 131.15 (Ph), 149.14 (Ph), 156.34 (-C=N).
2-(3'-Methoxyl-4'- hydroxyethoxy)phenyl benzimida-
zole (2c): Yield: 71.9 %. m.p.: 217.8-218.4 °C. Anal. Calcd
(%) for C16H16N2O3: C, 67.61; H, 5.63; N, 9.86. Found (%): C,
67.94; H, 6.11; N, 10.02. IR (KBr, νmax, cm-1): 3201.17 (υOH),

Vol. 27, No. 5 (2015)
Synthesis and Structural Characterization of 2-(Hydroxyethoxy Substituted)phenyl Benzimidazoles 1721
Determination of crystal structure : Single crystals of
1a, 2a, 2c and 2d suitable for data collection were selected
and data were collected on an Xcalibur, Eos diffractometer
equipped with a graphite-monochromatic MoKα radiation.
Details of crystal data, data collection and refinement are given
in Table-1 and 4. The structures were solved by direct methods
using SHELXS and refined by full-matrix least-squares methods
on F2 using SHELXL. All non-hydrogen atoms were refined
with anisotropic parameters. Hydrogen atoms bonded to carbon
were refined with isotropic parameters.
Fig. 2. Crystal molecular structure of 2-(p-hydroxyl)phenyl benzimidazole (1a)
RESULTS AND DISCUSSION
Meanwhile, another hydrogen bond (N2-H2...O1, 2.06 Å)
exists between O1 and the H2 of hydroxyl in another molecule.
Structural description of compound 2a, 2c and 2d:
Three target componds (2a, 2b, 2c) were synthesised by route
I. However, compond 2d can not be hydroxyethylated through
this method because of the steric hindrance at ortho-position.
Therefore, route II was adopted to synthesize 2d using o-
phenylenediamine and o-hydroxyethoxy benzaldehyde hydro-
xyethylated by o-hydroxybenzaldehyde and chlorohydrin. The
result shows that this method is viable to synthesize 2d success-
fully.
The crystal molecular structure, crystal data, structure
refinement details, selected bond lengths and angles, hydrogen
bond lengths and bond angles for 2a, 2c and 2d are shown in
Figs. 3, 4, and 5, Tables 4, 5 and 6, respectively. The crystal
molecular structure of 2a belongs to orthorhombic system,
which contains one ethanol molecule (Fig. 3). The crystal
molecular structure of 2d belongs to monoclinic system, which
All the compounds 1a, 2a, 2c and 2d were verified by IR,
Mass spectra, 1H NMR, 13C NMR and elemental analyses.
Structural description of compound 1a: In the synthesis
route I, three 2-(hydroxyl) phenyl benzimidazole intermediates
(1a, 1b, 1c) were synthesised by using hydroxyl benzaldehyde
derivatives and o-phenylenediamine. The crystal of 2-(p-
hydroxyl)phenyl benzimidazole (1a) was obtained. The crystal
molecular structure, crystal data, structure refinement details,
selected bond lengths and angles, hydrogen bond lengths and
bond angles for 1a are shown in Fig. 2, Tables 1, 2 and 3,
respectively. Double-bond N1-C7 (1.3265(17)Å) is shorter
than single-bond N2-C7 (1.3597(18)Å). The bond angle of
C7-N2-C2 (108.28(12)°) is larger than that of C1-N1-C7, which
is in accordance with the literature15. The bond angle on N1
atom sp2 hybridized is condensed to 105.64(12)°. In addition,
there is a strong hydrogen bond between N1 and the H1 of
hydroxyl in another 1a molecule, O1-H1...N1 (1.83 Å).
TABLE-1
CRYSTAL DATA AND STRUCTURE REFINEMENT DETAILS FOR 2-( p -HYDROXYL)PHENYL BENZIMIDAZOLE (1a)
Empirical formula
Temperature (K)
Space group
C13H10N2O
293.15
P21/n
90.00, 90.606(4), 90.00
4, 1.303
28.00 × 0.32 × 0.25
Formula weight
Crystal system
a/Å, b/Å, c/Å
Volume/Å3
210.23
Monoclinic
7.1685(3), 15.2342(6), 9.8163(4)
1071.94(7)
0.085, 440.0
6.28 to 52.74°
4935
2054/0/146
α/°, β/°, γ/°
Z, ρcalc (mg mm-3)
µ/mm-1, F(000)
Crystal size (mm3)
Index ranges
2θ Range for data collection
Reflections collected
Data/restraints/parameters
Absorption correction
Refinement method
-8 ≤ h ≤ 8, -19 ≤ k ≤ 19, -12 ≤ l ≤ 9
2054 (0.0180)
1541
1.0 and 0.99519
1.044
R1 = 0.0592, wR2 = 0.1097
Independent reflections (Rint)
Observed reflections
Max. and Min. transmission
Goodness-of-fit on F2
Final R indexes [all data]
Multi-scan
Full-matrix least-squares on F2
R1 = 0.0414, wR2 = 0.0981
0.12/-0.21
Final R indexes [I>2σ (I)]
Largest diff. peak/hole/e Å-3
TABLE-2
SELECTED BOND LENGTHS (Å) AND ANGLES (°) FOR 2-(p-HYDROXYL)PHENYL BENZIMIDAZOLE (1a)
Bond
O1-C11
N1-C1
Angle
Dist.
1.3619(18)
1.392(2)
Bond
N2-C2
N1-C7
Angle
Dist.
1.3783(19)
1.3265(17)
Bond
N2-C7
C7-C8
Angle
Dist.
1.3597(18)
1.457(2)
(°)
(°)
(°)
C7-N1-C1
C7-N2-C2
105.64(12)
108.28(12)
N1-C7-N2
N1-C7-C8
111.35(13)
124.41(13)
O1-C11-C10
O1-C11-C12
118.03(13)
123.07(13)
TABLE-3
HYDROGEN BOND LENGTHS (Å) AND BOND ANGLES (°) FOR 2-(p-HYDROXYL)PHENYL BENZIMIDAZOLE (1a)
D-H ... A
O1-H1...N11
N2-H2...O12
D-H(Å)
0.82
0.86
H…A(Å)
1.83
2.06
D…A(Å)
2.6493(16)
2.8528(15)
<(DHA)(°)
174.0
153.7
Symmetry code: 1-1/2 + X, 3/2-Y, -1/2 + Z; 2-1/2 + X, 3/2-Y, 1/2 + Z

1722 Wang et al.
Asian J. Chem.
TABLE-4
CRYSTAL DATA AND STRUCTURE REFINEMENT DETAILS FOR
2-(HYDROXYETHOXY SUBSTITUTED)PHENYL BENZIMIDAZOLES
Compound
Compound 2a
C17H19N2O3
299.34
Compound 2d
C15H14N2O2
254.28
Compound 2c
C16H16N2O3
284.31
Empirical formula
Formula weight (g/mol)
Temperature (K), Wavelength
(Å)
Crystal system, Space group
a/Å, b/Å, c/Å
143(1), 0.7107
293.15, 0.7107
143.00(10), 0.7107
Monoclinic, P21/c
14.0226(8), 7.2522(4), 14.7512(7)
90.00, 112.440(7), 90.00
1386.53(13)
4, 1.362, 600.0
0.095
0.30 × 0.25 × 0.20
5.98 to 52.74
Orthorhombic, Pbca
9.0642(3), 17.2613(5) , 20.0602(6) 14.8860(5), 12.0542(4), 14.9127(5)
90.00, 90.00, 90.00
3138.62(17)
8, 1.267, 1272.0
0.088
Monoclinic, P21/n
90.00, 104.267(4), 90.00
2593.39(15)
8, 1.303, 1072.0
0.088
0.30 × 0.25 × 0.20
6.58 to 50
α/(°), β/(°), γ/(°)
V/Å3
Z, ρcalc (mg/m3), F(000)
µ(mm-1)
Crystal size (mm3)
2θ range for data collection (°)
Index ranges
0.30 × 0.25 × 0.20
6.06 to 50
-7 ≤ h ≤ 10, -19 ≤ k ≤ 20, -23 ≤ l ≤ 13 -17 ≤ h ≤ 17, -14 ≤ k ≤ 14, -16 ≤ l ≤ 17 -17 ≤ h ≤ 17, -8 ≤ k ≤ 9, -18 ≤ l ≤ 18
7943
Reflections collected
19848
6037
Independent reflections (Rint) 2761 (0.0238)
4551 (0.0258)
3362
2822 (0.0232)
2175
Observed reflections
2218
Absorption correction
Multi-scan
Multi-scan
Multi-scan
Max. and Min. transmission
Refinement method
1.0 and 0.99084
Full-matrix least-squares on F2
2761/0/206
1.0 and 0.87622
Full-matrix least-squares on F2
4551/0/356
1.0 and 0.93478
Full-matrix least-squares on F2
2822/0/199
Data/restraints/parameters
Goodness-of-fit on F2
1.060
1.050
1.033
R1 = 0.0604, wR2 = 0.1506
R1 = 0.0753, wR2 = 0.1621
0.82/-0.89
R1 = 0.0422, wR2 = 0.0965
R1 = 0.0635, wR2 = 0.1084
0.34/-0.24
R1 = 0.0459, wR2 = 0.0959
R1 = 0.0646, wR2 = 0.1081
0.19/-0.27
Final R indices [I > 2σ(I)]
Final R indexes (all data)
Largest diff. peak/hole/e Å-3
TABLE-5
SELECTED BOND LENGTHS (Å) AND ANGLES (°)
FOR 2-(HYDROXYETHOXY SUBSTITUTED)PHENYL BENZIMIDAZOLES
Compound 2a
Bond
O1-C11
N1-C1
N2-C7
Angle
Dist.
Bond
O1-C14
N1-C7
-
Dist.
1.436(3)
1.325(3)
-
Bond
O2-C15
N2-C2
-
Dist.
1.423(3)
1.381(3)
-
1.366(3)
1.387(3)
1.364(3)
Angle
Angle
(°)
(°)
(°)
C11-O1-C14
O1-C14-C15
C7-N1-C1
117.9(2)
107.8(2)
105.3(2)
130.1(2)
O1-C11-C10
O2-C15-C14
C7-N2-C2
115.1(2)
112.0(2)
107.1(2)
105.5(2)
O1-C11-C12
N1-C7-N2
N1-C1-C2
N2-C2-C3
125.1(2)
112.5(2)
109.7(2)
132.2(2)
N1-C1-C6
N2-C2-C1
Compound 2d
Bond
O1-C9
O3-C24
N1-C1
N2-C7
N2-C17
Angle
Dist.
Bond
O1-C14
O3-C29
N1-C7
N3-C16
N2-C22
Angle
Dist.
Bond
O2-C15
O4-C30
N2-C6
N3-C22
-
Dist.
1.410(2)
1.412(2)
1.392(2)
1.361(2)
-
1.362(2)
1.366(2)
1.377(2)
1.323(2)
1.389(2)
1.435(2)
1.424(2)
1.364(2)
1.375(2)
1.327(2)
Angle
(°)
(°)
(°)
C9-O1-C14
C24-O3-C29
C7-N1-C1
119.58(15)
119.58(14)
108.01(15)
107.90(15)
O1-C9-C8
O3-C24-C23
C7-N2-C6
116.14(15)
115.86(15)
105.41(14)
105.14(14)
O1-C9-C10
O3-C24-C25
N2-C7-N1
123.75(17)
123.32(15)
111.58(15)
111.86(15)
C22-N3-C16
C22-N4-C17
N4-C22-N3
Compound 2c
Bond
O1-C10
O2-C15
N1-C7
Angle
Dist.
Bond
O1-C14
O3-C16
N2-C2
Angle
Dist.
Bond
O2-C11
N1-C1
N2-C7
Angle
Dist.
1.3648(19)
1.433(2)
1.327(2)
1.423(2)
1.426(2)
1.384(2)
1.3651(19)
1.396(2)
1.363(2)
(°)
(°)
(°)
C10-O1-C14
O2-C11-C10
C7-N1-C1
117.67(13)
115.10(14)
105.02(14)
130.33(16)
C11-O2-C15
O2-C11-C12
C7-N2-C2
117.67(13)
125.60(15)
107.23(15)
105.40(14)
O3-C16-C15
N1-C7-N2
N1-C1-C2
N2-C2-C3
111.88(14)
112.71(15)
109.63(15)
132.04(17)
N1-C1-C6
N2-C2-C1

Vol. 27, No. 5 (2015)
D-H ... A
Synthesis and Structural Characterization of 2-(Hydroxyethoxy Substituted)phenyl Benzimidazoles 1723
TABLE-6
HYDROGEN BOND LENGTHS (Å) AND BOND ANGLES (°) FOR
2-(HYDROXYETHOXY SUBSTITUTED)PHENYL BENZIMIDAZOLES
D-H(Å)
H…A(Å)
D…A(Å)
<(DHA)(°)
Compound 2a
1.851
O2-H2…O31
O3-H3A…N12
N2-H2A…O23
0.840
0.840
0.876
2.679
2.741
2.781
168.17
169.35
172.29
1.911
1.910
Compound 2d
1.985
O4-H4…N21
N3-H3…O3
N3-H3…O4
N1-H1…O1
N1H1…O2
O2H2…N42
0.820
0.844
0.844
0.889
0.889
0.913
2.790
2.666
3.181
2.678
3.124
2.774
166.86
114.47
167.23
115.86
163.63
158.01
2.204
2.353
2.168
2.261
1.906
Compound 2c
1.925
O3-H3…N11
N2-H2…O31
0.898
0.922
2.786
2.850
159.92
167.80
1.943
Symmetry code: (#1for 2a)1[-x + 2, y-1/2, -z + 3/2], 2[x-1/2, y, -z + 3/2], 3[-x + 3/2, y + 1/2, z]; (#1 for 2d)1 [ -x + 3/2, y-1/2, -z + 1/2],
2[ -x + 2, -y + 1, -z ]; (#1 for 2c) 1[-x + 1, y-1/2, -z + 1/2]
contains two 2d molecules (Fig. 4). Moreover, the crystal
molecular structure of 2c belongs to monoclinic system. In
these three crystals, the planes between benzimidazole ring
and the substituted benzene ring are not co-plane and the
intersection angles are 19.73°(2a), 20.04°(2d), 13.02°(2c),
respectively.
Fig. 5. Crystal molecular structure of 2-(3'-methoxyl-4'-hydroxyethoxy)-
phenyl benzimidazole (2c)
There are a large mount of hydrogen bonds in the three
crystal molecular structures, especially in 2d as shown in
Table-6. In the crystal molecular structure of 2a, hydrogen
bonds exist between the O3 atom of ethanol and the H2 atom
in hydroxyl of 2a (O2-H2...O3, 1.851 Å), between the H3 atom
Fig. 3. Crystal molecular structure of 2-(p-hydroxyethoxy)phenyl
benzimidazole (2a)
of ethanol and the N1 atom in imidazole ring (O3-H3A...N1,
1.911Å) and between the O2 atom in hydroxyl of 2a and the
H2 atom in the N2 atom of another 2a (N2-H2A...O2, 1.910Å).
As two 2a molecules exist in the 2a crystal molecular structure,
a large quantity of hydrogen bonds happen on the two nitrogen
atoms of imizole ring and the oxygen atom of hydroxyl.
Meanwile, the hydrogen bonds in the crystal molecular
structure of 2c mainly appear on the two nitrogen atoms of
imizole ring and the oxygen atom of hydroxyl, too.
1
Spectra analysis: Analogical IR, H NMR, 13C NMR
spectra data results are presented for the four 2-(hydroxyethoxy
substituted)phenyl benzimidazoles synthesized by two diffe-
rent routes. The spectral data of 2-(m-hydroxyethoxy)phenyl
benzimidazoles (2b) are illustrated below. The stretching
vibration peak of OH appears at 3204.37 cm-1. The stretching
vibration peaks of two -CH2- come out at 2926.37 and 2868.49
cm-1. The existence of meta-disubstituted benzene are indicated
by the four peaks at 1497.38, 1479.20, 1451.68 and 1436.77
cm-1 of benzene carbon skeleton stretching vibration peaks
Fig. 4. Crystal molecular structure of 2-(o-hydroxyethoxy)phenyl
and the peaks at 837.23 and 743.24 cm-1. The structure of
benzimidazole (2d)

1724 Wang et al.
Asian J. Chem.
aromatic oxide is proved by the presence of aryloxy bond
stretching vibration peak at 1251.25 cm-1 and the peaks at
1080.65 and 1057.93 cm-1 of C-O bond.
ACKNOWLEDGEMENTS
The project is financially supported by the National Science
Foundation of China (No. 21106088) and the Ph. D. Programs
Foundation of Ministry of Education of China (No. 2011018-
1120079).
From the 1H NMR chemical shift data of 2b, the resonance
peaks of two H protons (-CH2O-) appear at 3.80 ppm and the
resonance peaks of two H protons (-OCH2-) come out at 4.12
ppm. Meanwhile, the resonance peaks of H proton (-OH) are
found at 4.96 ppm. A multiple resonance peaks at 7.09-7.78
ppm present the H protons in the two benzenes of 2b. In
addition, a single resonance peak at 12.91 ppm shows the H
proton of N-H. In the 13C NMR chemical shifts of 2b, we can
find that the carbon atom resonance peaks of -CH2OH, -OCH2-
and C=N appear at 59.56, 69.66 and 159.06 ppm, respectively.
Moreover, the carbon atom resonance peaks of benzene
skeleton are found at 111.89-151.09 ppm. All of the spectra
data above support the results of the four target products.
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In this pater, two routes were adopted to synthesize four
2-(hydroxyethoxy substituted)phenyl benzimidazoles. In route
I, the hydroxyl substituted benzaldehyde firstly reacted with
o-phenylendiamine to gain the intermediates -2-(hydroxyl
substituted)phenyl benzimidazoles which then were used to
synthesize the final products through the o-hydroxyethylation
reaction with chlorohydrin. This synthesis route is suitable
only for the target compounds in which hydroxyethoxy group
is located in para- and meta-position of benzimidazole in the
benzene ring. As to the ortho-substituted phenyl benzimi-
dazole, route II is viable, that is the hydroxyethoxy substituted
benzaldehyde is firstly synthesized by the o-hydroxyethylation
reaction and then reacts with o-phenylendiamine, which can
avoid the steric hindrance. The structures of the four new com-
pounds were characterized and proved by elemental analysis
1
(EA), IR, Mass spectra, H NMR, 13C NMR and the single-
crystal X-ray diffraction analysis.