NMR investigation of hydrogen bonding and 1,3-tautomerism in 2-(2-hydroxy-5-substituted-aryl) benzimidazoles

Article abstract of DOI:10.1002/mrc.1588

The 1,3-tautomerism associated with 2-(2-hydroxy-5-substituted-aryl) benzimidazoles was studied in different solvents. The effect of hydrogen bonding involving the hydroxyl group of the 2-aryl ring on the tautomerism was investigated using NMR spectroscopy. The influence of the solvent concentration on 2-(2-hydroxy-5-chloroaryl)benzimidazole was studied in acetone-d₆ and DMSO-d₆. Copyright

Full text of DOI:10.1002/mrc.1588

MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 2005; 43: 551–556
Published online 28 April 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mrc.1588
NMR investigation of hydrogen bonding and
1,3-tautomerism in 2-(2-hydroxy-5-substituted-aryl)
benzimidazoles
V. Sridharan, S. Saravanan, S. Muthusubramanian∗ and S. Sivasubramanian
Department of Organic Chemistry, Madurai Kamaraj University, Madurai 625 021, India
Received 6 December 2004; Revised 15 February 2005; Accepted 28 February 2005
The 1,3-tautomerism associated with 2-(2-hydroxy-5-substituted-aryl)benzimidazoles was studied in
different solvents. The effect of hydrogen bonding involving the hydroxyl group of the 2-aryl ring
on the tautomerism was investigated using NMR spectroscopy. The influence of the solvent concentration
on 2-(2-hydroxy-5-chloroaryl)benzimidazole was studied in acetone-d6 and DMSO-d6. Copyright  2005
John Wiley & Sons, Ltd.
KEYWORDS: NMR; 1H NMR; 13C NMR; 2D techniques; dynamic NMR; 5-substituted 2-(2-hydroxyaryl)benzimidazoles
INTRODUCTION
RESULTS AND DISCUSSION
The chemistry1–4 of suitably substituted benzimidazoles
is very important as some benzimidazole derivatives pos-
sess anticancer,5 antiparasitic,6 antitumour,7 analgesic8 and
antipoliovirus9 activities. The 1,3-tautomerism associated
with benzimidazoles is a very popular topic and the existence
of this tautomerism has been proved by several approaches,
including NMR spectroscopy.10 This 1,3-migration is not
found when the imidazole hydrogen is replaced by other
substituents such as an alkyl group11 or under special cir-
cumstances where the hydrogen migration is affected by
inter- and/or intramolecular hydrogen bonding.
The target compounds 2 were synthesized by the lead tetraac-
etate oxidation of the imines prepared from 2-hydroxy-
5-substituted-benzaldehydes (1) with o-phenylenediamine
(Scheme 1). It has been shown that the simple benzalde-
hyde on reaction with o-phenylenediamine in a 1 : 1 molar
ratio gives the monoimine, which was then subjected to lead
tetraacetate oxidation to give benzimidazole.13 However, in
the case of 2-hydroxy-5-substituted-benzaldehydes, even in
a 1 : 1 molar ratio of o-phenylenediamine and aldehydes, the
diimine 3 and not the monoimine 4 was obtained in moderate
yield.
The treatment of o-phenylenediamine and the aldehyde
in a 1 : 2 ratio, of course, leads to the diimine 3 in very good
yield. Upon treatment of the diimine with lead tetraacetate
in acetic acid, surprisingly the target benzimidazole 2 was
obtained in good yield. Probably the initial hydrolysis of
the diimine 3 to monoimine 4 with acetic acid would have
occurred, the latter subsequently being oxidized to the target
compound 2. The imine 3 has not been separated in many
cases and the reaction product of 1 : 1 o-phenylenediamine
and aldehyde has been treated with LTA–AcOH to obtain
We have recently synthesized a set of 2-(2-hydroxy-5-
substituted-aryl)benzoxazoles12 and showed the presence of
hydrogen bonding in the compounds between the hydroxy
hydrogen and oxazole nitrogen of the benzoxazole ring. It
would be interesting to find out in analogous benzimidazoles
whether (i) the hydroxyl hydrogen of the 2-aryl group is
involved in hydrogen bonding with the imino nitrogen or
(ii) the hydroxyl oxygen is involved in hydrogen bonding
with the NH of benzimidazole or (iii) there is no hydrogen
bonding, in which case the system will have a free tautomeric
existence involving 1,3-hydrogen migration. To the best of
our knowledge, no systematic study in this respect has
been carried out on the related compounds. Hence we
planned to prepare a set of 2-(2-hydroxy-5-substituted-
aryl)benzimidazoles (2), most of which are new, and to
investigate the NMR spectra in solution to address the above
hypotheses.
ŁCorrespondence to: S. Muthusubramanian, Department of
Organic Chemistry, Madurai Kamaraj University, Madurai 625 021,
India. E-mail: muthumanian2001@yahoo.com
Contract/grant sponsor: DST.
Scheme 1
Copyright  2005 John Wiley & Sons, Ltd.

552
V. Sridharan et al.
2 directly. The monoimine 4 has not been separated in any
case. The 1H NMR and 13C NMR spectral data for 2 are given
in Tables 1 and 2, respectively.
To analyse the effect of hydrogen bonding, the 2-
(2-methoxy-5-tert-butylaryl)benzimidazole 5 was also pre-
pared by treating o-phenylenediamine with 5-tert-butyl-2-
methoxybenzaldehyde, which in turn was prepared from
5-tert-butyl-2-hydroxybenzaldehyde by methylation with
dimethyl sulfate. It must be mentioned that the treatment of
O-methylated salicylaldehyde with o-phenylenediamine in a
1 : 2 ratio gives not the monoimine or diimine but a benzimi-
dazole derivative, 6a. The formation of 6a has been accounted
for by a reaction involving a hydride migration mechanism.14
Treatment of 5-tert-butyl-2-methoxybenzaldehyde with o-
phenylenediamine gives only 40% of 6b (identified by the
1H NMR spectrum of the mixture of 5 and 6b from the com-
parison of the intensity of the N-CH2 signal at υ 5.23 ppm
with that of the methoxy signals at υ 3.58, 3.78 and 4.05 ppm)
and the remaining being oxidized product 5. Formation of
Table 1. 1H NMR chemical shiftsa of benzimidazoles 2 and 5
Compound
Solvent
CDCl3
30
40
60
4,7
7.70, b
5,6
NH, OHb
9.60, b
R
2a
7.08, d,
7.43, dd,
7.56, d,
7.31, dd,
1.37, s, 9H
(8.7 Hz)
Acetone-d6 6.98, d,
(8.7 Hz)
DMSO-d6 7.00, d,
(8.7 Hz)
7.07, d,
(8.4 Hz)
Acetone-d6 6.97, d,
(8.4 Hz)
DMSO-d6 7.01, d,
(8.4Hz)
(8.7, 2.4 Hz) (2.4 Hz)
7.47, dd, 8.05, d,
(8.7, 2.4 Hz) (2.4 Hz)
7.36, dd, 7.99, d,
(8.7, 2.4 Hz) (2.4 Hz)
7.24, dd, 7.45, d,
(8.4, 2.1 Hz) (2.1 Hz)
7.27, dd, 7.99, d,
(8.4, 2.1 Hz) (2.1 Hz)
7.19, dd, 7.81, d,
(8.4, 2.1 Hz) (2.1 Hz)
7.34, dd, 7.52, d,
(8.7, 2.1 Hz) (2.1 Hz)
(6.0, 3.3 Hz) 13.00, b
7.29, dd, 12.00, b
(6.0, 3.3 Hz) (6.0, 3.3 Hz)
7.60, dd, 7.25, dd,
(6.0, 3.3 Hz) (6.0, 3.3 Hz) 13.00, b
7.65, dd,
1.36, s, 9H
1.38, s, 9H
2b
2c
CDCl3
7.63, b
7.65, b
7.60, b
7.64, b
7.30, dd,
(6.0, 3.0 Hz) 13.00, b
7.29, dd,
(6.3, 3.3 Hz)
7.24, dd,
9.70, b
1.27, d, 6H, (6.9 Hz)
2.90, sep, 1H, (6.9 Hz)
1.27, d, 6H, (6.9 Hz)
2.92, sep, 1H, (6.9 Hz)
1.26, d, 6H, (6.9 Hz)
2.89, sep, 1H, (6.9 Hz)
0.70, t, 3H, (7.5 Hz)
1.32, s, 6H,
12.70, b
(6.0, 3.0 Hz) 12.80, b
7.31, dd,
CDCl3
7.07, d,
(8.7 Hz)
—
(6.0, 3.0 Hz)
1.66, q, 2H, (7.5 Hz)
0.70, t, 3H, (7.5 Hz)
1.32, s, 6H,
Acetone-d6 6.99, d,
7.39, dd,
(8.7, 2.1 Hz) (2.4 Hz)
8.00, d,
7.65, dd,
(6.0, 3.3 Hz) (6.0, 3.3 Hz)
7.28, dd,
12.70, b
(8.7 Hz)
1.69, q, 2H, (7.5 Hz)
0.69, t, 3H, (7.5 Hz)
1.31, s, 6H,
DMSO-d6 7.03, d,
7.30, dd,
(8.7, 2.1 Hz) (2.1 Hz)
7.86, d,
7.60, dd,
(6.0, 3.3 Hz) (6.0, 3.0 Hz)
7.25, dd,
(8.7 Hz)
—
1.65, q, 2H, (7.5 Hz)
ortho-7.61, m
2d
CDCl3
7.21, d,
7.61, m
7.79, d,
7.85, b
7.33, dd,
9.60, b
(8.4 Hz)
(2.1 Hz)
(6.0, 3.0 Hz) 13.2, b
meta-7.46, t, (7.2 Hz)
para-7.35, tt, (7.2, 1.2 Hz)
ortho-7.65–7.72, m
meta-7.44, t, (7.5 Hz)
para-7.32, tt, (7.5, 1.2 Hz)
ortho-7.65, dd, (7.8,
1.2 Hz)
Acetone-d6 7.14, d,
7.65–7.72, m 8.36, d,
(2.4 Hz)
7.65–7.72, m 7.30, dd,
(6.0, 3.3 Hz)
12.90, b
12.50, b
(8.4 Hz)
DMSO-d6 7.13, d,
7.56, dd,
8.30, d,
(8.7, 2.1 Hz) (2.1 Hz)
7.61, dd,
7.25, dd,
(8.7 Hz)
(6.0, 3.3 Hz) (6.0, 3.3 Hz)
meta-7.42, t, (7.8 Hz)
para-7.30, tt, (7.8, 1.2 Hz)
1.72, s, 6H
7.26–7.31, 5H, m
1.56, s, 6H
7.10–7.15, 5H, m
1.61, s, 6H
7.11–7.20, m
2e
CDCl3
7.05, d,
(8.4 Hz)
7.26–7.31, m 7.40, d,
(2.1 Hz)
7.60, b
7.47, b
7.26–7.31, m
—
Acetone-d6 6.81, d,
(8.7 Hz)
DMSO-d6 6.90, d,
(8.7 Hz)
7.03, dd,
(8.7, 2.4 Hz) (2.4 Hz)
7.05, dd, 7.84, d,
(8.7, 2.4 Hz) (2.4 Hz)
7.88, d,
7.10–7.15, m 12.70, b
7.11–7.20, m
7.49, dd,
(6.0, 3.0 Hz)
Copyright  2005 John Wiley & Sons, Ltd.
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H-bonding and tautomerism in benzimidazoles
553
Table 1. (Continued)
Compound
Solvent
CDCl3
30
40
60
4,7
7.63, b
5,6
NH, OHb
9.50, b
R
2f
7.06, d,
7.21, dd,
7.42, d,
7.31, dd,
1.26, t, 3H, (7.5 Hz)
2.65, q, 2H, (7.5 Hz)
1.23, t, 3H, (7.5 Hz)
2.63, q, 2H, (7.5 Hz)
1.24, t, 3H, (7.5 Hz)
2.61, q, 2H, (7.5 Hz)
—
(8.4 Hz)
Acetone-d6 6.97, d,
(8.4 Hz)
DMSO-d6 7.00, d,
(8.4 Hz)
(8.4, 2.1 Hz) (2.1 Hz)
7.22, dd, 7.85, d,
(8.4, 2.1 Hz) (2.1 Hz)
7.14, dd, 7.78, d,
(8.4, 2.1 Hz) (2.1 Hz)
7.29, dd, 7.59, d,
(9.0, 2.4 Hz) (2.4 Hz)
(6.0, 3.0 Hz) 13.0, b
7.65, dd,
(6.0, 3.3 Hz) (6.0, 3.3 Hz)
7.59, dd, 7.23, dd,
(6.0, 3.0 Hz) (6.0, 3.0 Hz)
7.52, b(H-4) 7.35, dd,
7.28, dd,
12.20, b
12.00, b
9.60, b
2g
CDCl3
7.08, d,
(9.0 Hz)
7.78, b
(H-7)
(6.3, 3.3 Hz)
Acetone-d6 7.07, d,
(8.7 Hz)
DMSO-d6 7.01, d,
(9.0 Hz)
7.38, dd,
(8.7, 2.4 Hz) (2.4 Hz)
7.26, dd, 8.06, d,
(9.0, 2.4 Hz) (2.4 Hz)
8.06, d,
7.69, dd,
(6.0, 3.3 Hz) (6.0, 3.3 Hz)
7.54, b
(H-4)
7.33, dd,
12.90, b
13.10, b
—
—
7.28, dd,
(6.0, 2.7 Hz)
7.69, b
(H-7)
2h
CDCl3
7.03, d,
(8.7 Hz)
7.44, dd,
(8.7, 2.4 Hz) (2.4 Hz)
7.73, d,
7.51, b
(H-4)
7.76, b
(H-7)
7.64, b
(H-4)
7.75, b
(H-7)
7.34, dd,
(6.0, 3.0 Hz)
—
—
—
—
Acetone-d6 7.02, d,
7.51, dd,
(9.0, 2.4 Hz) (2.4 Hz)
8.18, d,
7.33, dd,
(6.0, 3.3 Hz)
12.50, b
(9.0 Hz)
DMSO-d6 6.96, d,
7.39, dd,
(9.0, 2.4 Hz) (2.4 Hz)
8.20, d,
7.53, b
(H-4)
7.27, dd,
(6.0, 2.7 Hz) 13.30, b
12.70, b
(9.0 Hz)
7.68, b
(H-7)
5
CDCl3
7.00, d,
(8.7 Hz)
7.45, dd,
(8.7, 2.4 Hz) (2.4 Hz)
8.62, d,
7.50, m
(H-4)
7.26, dd,
(6.0, 3.0 Hz)
10.77, b
1.38, s, 9H
4.05, s, 3H
7.84, m
(H-7)
a Chemical shifts in ppm and coupling constants (Hz) in parentheses.
b In some cases the NH and OH protons merge together or are not seen.
such an oxidized product even in the absence of the oxi-
dant is not unprecedented.15 The NMR spectral data for 5
are included along with those of 2 in the respective tables.
The assignments were made by a combination of one- and
two-dimensional NMR techniques. Most of the quaternary
carbons were assigned from the HMBC spectra, whereas the
methine carbons were assigned from the HSQC spectra.
from their coupling pattern and hence assigned. Apart from
these, a two-hydrogen doublet of doublets at υ¾7.3 ppm was
observed which was assigned to protons 5 and 6. A broad
band at υ¾7.7 ppm accounting for two hydrogens can be
assigned to protons 4 and 7. The NH/OH hydrogens appear
at υ 9.6/13.0 ppm. Although a single peak with fine coupling
for protons 5 and 6 suggests that these two hydrogens are
nearly isochronous, the distinct signals for hydrogens 4 and
7 clearly show that the 1,3-hydrogen shift is not very fast.
In other words, the exchange is slowed, probably owing to
intramolecular hydrogen bonding.
In DMSO-d6 and acetone-d6, the compounds 2 are fairly
soluble. In fact, the addition of a drop of DMSO-d6 to a
CDCl3 suspension of the compound dramatically changes the
pattern of the signals. H-60, the meta-coupled doublet, moves
downfield to a larger extent (0.5 ppm) and interestingly the
signal due to H-4 and H-7 is resolved, showing a neat doublet
of doublets, experiencing an upfield shift of 0.1 ppm (in 2a).
This clearly shows that the 4,7-hydrogens and 5,6-hydrogens
are equivalent, indicating the fast exchange of hydrogen
The compounds 2 are not very soluble in chloroform,
so only very dilute solutions of 2 in CDCl3 were prepared
and the 13C NMR spectra of these compounds could not
be measured. The 2-aryl hydrogens are identified easily
Copyright  2005 John Wiley & Sons, Ltd.
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554
V. Sridharan et al.
Table 2. 13C NMR chemical shifts (ppm) of benzimidazoles 2 and 5
Compound
Solvent
2
3a,7a
4,7
5,6
10
20
30
40
50
60
R
a
2a
Acetone-d6 153.79
DMSO-d6 152.16
Acetone-d6 153.64
DMSO-d6 152.18
Acetone-d6 155.26
DMSO-d6 152.43
Acetone-d6 153.38
—
—
—
—
—
—
—
116.00 124.16 113.03 158.08 118.26 130.32 142.89 123.52 32.20, 35.26
a
a
—
—
—
122.13 111.69 155.99 116.45 128.46 141.15 122.13 31.15, 33.88
124.16 113.41 158.39 118.52 131.41 140.55 124.34 24.88, 34.56
122.45 112.30 156.52 117.08 129.66 139.09 123.15 24.02, 33.22
a
a
a
2b
2c
a
a
117.00 124.31 114.50 159.47 118.24 130.91 142.49 124.31 11.31, 30.78, 39.26, 39.97
114.55 122.97 112.51 156.28 116.90 129.36 139.80 122.54 9.09, 28.51, 36.78, 37.37
116.00 124.35 114.16 159.85 119.22 131.39 133.16 125.37 127.66, 128.12, 130.11,
141.44
a
a
2d
a
DMSO-d6 151.71
Acetone-d6 153.66
—
114.29 122.36 112.76 157.87 117.45 129.50 131.39 124.11 126.18, 126.38, 128.31,
139.97
a
b
2e
—
115.92
—
—
113.03 158.25 118.34 132.19 142.53 124.71 31.62, 43.51, 124.21, 126.83,
127.86, 129.29, 152.06
112.58 157.07 116.91 130.46 141.43 123.60 30.77, 42.30, 122.49, 125.38,
126.51, 127.83, 151.32
b
DMSO-d6 152.76 138.00 114.54
2f
Acetone-d6 153.54 138.66 115.95 124.19 113.46 158.33 118.56 132.71 135.82 125.83 16.58, 29.02
DMSO-d6 151.99 137.08 114.38 122.40 112.25 156.39 117.01 130.93 134.22 124.55 15.53, 27.78
a
a
a
a
2g
2h
Acetone-d6 151.98
—
—
—
—
—
124.63 115.12 158.92 120.42 132.57 124.49 126.42
—
—
—
a
DMSO-d6 149.81
122.09 113.10 156.26 117.88 129.94 122.23 124.44
a
a
Acetone-d6
—
112.70 124.30c 115.74
(C-4) 125.16
119.80
—
120.85 135.43 111.42 129.35
(C-7)
DMSO-d6 150.11 140.44 110.80 121.89c 114.12 157.16 118.73 133.11 109.72 127.66
—
a
—
(C-4) 122.76
117.63
(C-7)
5
CDCl3
150.33 133.62 110.71 122.15 117.19 154.73 111.16 128.16 144.57 126.95 31.43, 34.33, 55.98
(C-3a) (C-4)
142.96 119.26 122.58
(C-7a) (C-7)
a Not seen.
b Merged with the 5-substituted cumyl group.
c Unambiguous assignment is not possible owing to poor correlation in 2D spectra.
and suggesting that the hydrogen bonding between the 2-
hydroxyl and the benzimidazole ring is not strong enough
to slow this exchange. The 13C spectra also support this
observation. The exchange seems to be so fast that in
most cases the C-3a/7a and C-4/7 carbons are not seen
at all. However, in certain substituted benzimidazoles [2a (in
acetone-d6 only), 2c, 2d, 2e, 2f and 2h], the C-4/7 carbon was
observed as a broad signal. In one compound at least (2f), all
the carbons are seen (Fig. 1).
This clearly indicates that in chloroform there exists strong
intramolecular hydrogen bonding between the methoxy oxy-
gen and the imidazole hydrogen, preventing the exchange
of protons leading to separate signals for the 4- and 7-
hydrogens and carbons. The carbons C-5 and C-6 also appear
separately even though the corresponding protons appear
together as a multiplet. The fact that there is strong hydro-
gen bonding with OMe and NH clearly suggests that similar
bonding could exist in 2 and hence it may be concluded
Ð Ð Ð
It is interesting that 2h, in both acetone-d6 and DMSO-
d6 (at the same molar concentration as for the other
compounds), shows distinctly different 13C signals for the
5,6- and 4,7-hydrogens. In the corresponding 1H NMR
spectra, two distinct broad bands are noticed for the 4-
and 7-hydrogens, though the 5- and 6-hydrogens are still
indistinguishable. Hence in this bromo compound, the
proton exchange rate seems to be slow, indicating possible
intramolecular hydrogen bonding in this case.
that N—H OH may be the preferred hydrogen bonding
Ð Ð Ð
N
in 2 rather than
H—O. The hydroxyl hydrogen may
be involved in hydrogen bonding with H-bond acceptor
solvents such as DMSO and acetone.
The effect of solvent concentration on tautomerism was
studied in the case of 2-(2-hydroxy-5-chlorophenyl)benzi-
midazole (2g) with acetone-d6 and DMSO-d6. At low
concentration (0.0327 M) in acetone-d6, the 1,3-tautomerism
was fully arrested and 2g exits as a single isomer so that
the protons H-4 and H-7 appear as two different multiplets
(Fig. 2, entry 1). When the concentration of the solution is
raised, the rate of exchange of the imidazole hydrogen also
In the case of 2-(2-methoxy-5-tert-butylphenyl)benzi-
midazole (5), H-4 and H-7 appear as two different sharp sig-
nals at υ 7.50 and 7.84 ppm, respectively, at all concentrations.
Copyright  2005 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2005; 43: 551–556

H-bonding and tautomerism in benzimidazoles
555
C-5,6
C-4′
C-3′
C-6′
C-5′
C-3a,7a
C-2′
C-1′
C-4,7
C-2
160
150
140
130
120
C-5,6
110
C-4′
C-3′
C-6′
C-2′
C-5′
C-1′
C-4,7
C-2
C-3a,7a
140
160
150
130
120
110
Figure 1. 13C NMR spectra of 2-(2-hydroxy-5-ethylphenyl)-
benzimidazole (2f) in acetone-d6 (top) and in DMSO-d6
(bottom).
increases and as a result the hydrogens H-4 and H-7 appear as
broad singlets coming closer (entry 2). As the concentration
is increased further, the two broad bands merge to give a
broad singlet (entries 3 and 4) due to the fast exchange rate of
the imidazole hydrogen. In saturated solution (entry 5), both
the protons H-4 and H-7 appear as a neat doublet of doublets
with coupling constants 6.0 and 3.3 Hz, as NMR cannot
distinguish these two protons because of very fast exchange.
The same result was observed in DMSO-d6. Probably, at
lower concentration there is hydrogen bonding between
the imidazole hydrogen and the hydroxyl oxygen. If the
concentration of the solution increases, the intermolecular
hydrogen bonding between the hydroxyl groups become
dominant, accounting for the above trend.
Figure 2. Effect of solvent concentration on H-4 and H-7 in
2-(2-hydroxy-5-chlorophenyl)benzimidazole (2g) in acetone-d6.
As the concentration of the substrate is increased, not only
do H-4 and H-7 become merged, but also OH and NH in the
above cases. This clearly shows that at this concentration,
the fast tautomeric proton exchange between N-1 and N-3 is
facilitated owing to poor hydrogen bonding and also there
is an exchange between NH and OH. This could be due to a
zwitterionic form of the type shown in Fig. 3.
Figure 3. Possible zwitterionic form.
(not the hydroxyl hydrogen with the ring imino nitrogen). In
hydrogen bond acceptor solvents such as DMSO and acetone,
the hydroxyl hydrogen may have hydrogen bonding with
the solvent.
CONCLUSIONS
The tautomerism present in 2 was studied in the light
of the nature of hydrogen bonding present in 2. It was
found that in 5, the hydrogen bonding between hydrogen
of the imidazole ring and the oxygen of the methoxy
can be attributed to the arrest of the tautomerism in that
compound. This is in CDCl3, where the solvent may not
form any appreciable hydrogen bonding with NH. A similar
argument is extended to 2, in which it is suggested that the
hydrogen of the imidazole group may be involved in the
intramolecular hydrogen bonding with the hydroxyl oxygen
EXPERIMENTAL
Spectra
The 1H, 13C and related 2D NMR spectra were recorded
on a Bruker 300 MHz (UltraShield) NMR spectrometer at
room temperature. The 1H NMR spectra were measured
°
with a spectral width of 5000 Hz, a 90 flip angle and 2 s
Copyright  2005 John Wiley & Sons, Ltd.
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556
V. Sridharan et al.
Table 3. Melting-points, yields and elemental analysis data for compounds 2 and 5
Found (%)
H
Calc. (%)
H
Yield
(%)
M.p.
( C)
°
Compound
Formula
—
C
N
C
N
2a
78
284–285
(282–284)16
224–225
238–239
240–241
208–209
210–211
306–307
(305–306)17
298–299
(286–288)17
258–259
—
—
—
—
—
—
2b
2c
2d
2e
2f
70
77
69
76
73
75
C16H16N2O
C18H20N2O
C19H14N2O
C22H20N2O
C15H14N2O
—
76.20
77.25
79.81
80.40
75.55
—
6.45
7.15
4.85
6.08
5.85
—
11.25
9.95
7.75
8.41
11.65
—
76.16
77.11
79.90
80.46
75.61
—
6.39
7.19
4.93
6.14
5.92
—
11.10
9.99
9.78
8.53
11.76
—
2g
2h
5
72
47
—
—
—
—
—
—
—
C18H20N2O
77.20
7.10
10.11
77.11
7.19
9.99
relaxation delay in 32 scans for ¾0.05 M solution in acetone-
d6/DMSO-d6 with TMS as internal reference. For 13C NMR
sium hydroxide. A solution of 0.01 mol (1.08 g) of o-
phenylenediamine and 0.01 mol (1.92 g) of 5-tert-butyl-2-
methoxybenzaldehyde in 50 ml of ethanol was refluxed for
2 h. After completion of the reaction, the solvent was evapo-
rated and pure 5 was obtained by the recrystallization from
light petroleum–ethyl acetate.
5: IR, 3430, 3058, 2956, 1614, 1488, 1446, 1253 cmꢀ1; MS,
m/z (intensity, %) 280 (100), 265 (14), 250 (30), 235 (74), 119
(76).
°
spectra, a pulse angle of 37.5 (5 µs), an acquisition time of
0.75 s and a repetition time of 3.72 s with a spectral width of
17 000 Hz were used. The one- and two-dimensional NMR
spectra reported in this work were recorded using Bruker
‘icon NMR’ software. IR spectra were recorded in a Jasco FT-
IR instrument in KBr pellets and mass spectra were recorded
with a Finnigan GC–MS instrument.
Acknowledgements
Compounds
The authors thank DST, New Delhi, for assistance under the IRHPA
program for the NMR facility. V.S and S.S thank CSIR, New Delhi,
for a Senior Research Fellowship and a Junior Research Fellowship,
respectively.
Analytical data are collected in Table 3. Melting-points are
uncorrected.
Preparation of 2-(2-hydroxy-5-substituted-aryl)-
benzimidazoles (2)
A
0.01 mol solution of 5-substituted-2-hydroxybenzal-
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the imine intermediate, the reaction mixture was stirred with
30 ml of acetic acid and 0.01 mol of lead tetraacetate at room
temperature for 15 min. After completion of the reaction,
the mixture was poured into water and extracted with ethyl
acetate. The pure product of 2 was obtained after evaporation
of the solvent followed by silica column chromatography and
recrystallized from light petroleum–ethyl acetate.
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2b: IR, 3457, 3261, 3056, 2960, 1598, 1504, 1390, 1253 cmꢀ1
MS, m/z (intensity, %) 252 (58), 237 (100), 236 (70), 207 (10).
2c: IR, 3415, 3251, 3058, 2964, 1594, 1504, 1388, 1257 cmꢀ1
;
;
MS, m/z (intensity, %) 280 (20), 251 (100), 236 (20), 207 (26).
2d: IR, 3467, 3303, 3050, 1606, 1486, 1390, 1278, 1253 cmꢀ1. 2e:
IR, 3438, 3266, 3058, 2967, 1596, 1498, 1384, 1267 cmꢀ1; MS,
m/z (intensity, %) 328 (4), 295 (82), 294 (100), 279 (92). 2f: IR,
3438, 3241, 3058, 2956, 1589, 1502, 1382, 1257 cmꢀ1; MS, m/z
(intensity, %) 238 (82), 223 (100), 193 (12).
Preparation of 2-(2-methoxy-5-tert-butylphenyl)-
benzimidazoles (5)
5-tert-Butyl-2-methoxybenzaldehyde was prepared from
0.02 mol (3.56 g) of 5-tert-butyl-2-hydroxybenzaldehyde,
0.03 mol (3.78 g) of dimethyl sulfate and 4 g of potas-
Copyright  2005 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2005; 43: 551–556