Tautomeric equilibria in solutions of 2-phenacylbenzimidazoles

Article abstract of DOI:10.1155/2019/4364207

Detailed NMR spectral analysis of DMSO-d₆ solutions of the series of substituted 2-phenacylbenzimidazoles (ketimine form, K) reveals two from three tautomeric forms. Integrals of the ¹H NMR signals are used in establishing the molar ratio of tautomers. The experimental analyses are supported by quantum-chemical calculations, which satisfactorily reproduced the experimental trends. Although the reported semiempirical quantum-chemical calculations show that enaminone E, i.e., 2-(1,3-dihydro-2H-benzo[d]imidazol-2-ylidene)-1-phenylethan-1-one, was thermodynamically most stable, the results of MP2 ab initio calculations reveal the following order of stability: Ketimine > enolimine > enaminone (substituents do not affect this sequence). ¹³C CPMAS NMR spectral data reveal that in the crystalline state the enolimine tautomer O is predominant in the p-CH₃ and p-NO₂ substituted congeners.

Full text of DOI:10.1155/2019/4364207

Hindawi
Heteroatom Chemistry
Volume 2019, Article ID 4364207, 9 pages
https://doi.org/10.1155/2019/4364207
Research Article
Tautomeric Equilibria in Solutions of 2-Phenacylbenzimidazoles
Agnieszka Skotnicka ,1 PrzemysBaw CzeleN,2 and Ryszard Gawinecki1
1Department of Chemistry, UTP University of Science and Technology, Seminaryjna 3, PL-85-326 Bydgoszcz, Poland
2Department of Physical Chemistry, Collegium Medicum, N. Copernicus University, Kurpin´skiego 5, 85-950 Bydgoszcz, Poland
Correspondence should be addressed to Agnieszka Skotnicka; askot@utp.edu.pl
Received 12 October 2018; Revised 15 December 2018; Accepted 24 December 2018; Published 3 February 2019
Academic Editor: David Barker
Copyright © 2019 Agnieszka Skotnicka et al. Tis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Detailed NMR spectral analysis of DMSO-d6 solutions of the series of substituted 2-phenacylbenzimidazoles (ketimine form, K)
reveals two from three tautomeric forms. Integrals of the 1H NMR signals are used in establishing the molar ratio of tautomers.
Te experimental analyses are supported by quantum-chemical calculations, which satisfactorily reproduced the experimental
trends. Although the reported semiempirical quantum-chemical calculations show that enaminone E, i.e., 2-(1,3-dihydro-2H-
benzo[d]imidazol-2-ylidene)-1-phenylethan-1-one, was thermodynamically most stable, the results of MP2 ab initio calculations
reveal the following order of stability: ketimine > enolimine > enaminone (substituents do not afect this sequence). 13C CPMAS
NMR spectral data reveal that in the crystalline state the enolimine tautomerO is predominant in the p-CH and p-NO substituted
3
2
congeners.
1. Introduction
compounds and 2-phenacylbenzoxazoles and 1-methyl-2-
phenacylbenzimidazoles are expected to behave similarly.
However, in drawing such conclusions one has to be very
careful: minor modifcations in the molecule may afect the
tautomeric equilibria signifcantly [1–3]. Such understanding
prompted us to see the efect of substitution of the ring
It was found recently that in chloroform solution 2-phena-
cylbenzoxazoles (K in Scheme 1, X = O) are in equilibrium
with (Z)-2-(benzo[d]oxazol-2-yl)-1-phenylethenols (enolim-
ines, O) [1]. Strong electron-donating substituents in the
benzene ring were found to stabilize the K tautomer. Te MP2
ab initio calculations supported the energetic preference of
the O (over E) form. 13C CPMAS NMR spectra proved that in
the crystalline state the ketimine tautomer K is predominant
oxygen atom in 2-phenacylbenzoxazoles and NCH group
3
in 1-methyl-2-phenacylbenzimidazoles by the NH group on
their susceptibility to proton transfer.
Tautomerism of 2-phenacylbenzimidazoles has been
already studied by the NMR methods: 2-phenacylbenzim-
idazoles (ketimines K) in DMSO-d6 solution were found
to equilibrate with 2-(1,3-dihydro-2H-benzo[d]imidazol-2-
ylidene)-1-phenylethan-1-one (enaminones) [4]. Since an
unequivocal distinguishing between enoliminesO and enam-
inones E (any of these two forms can be present in solu-
tion), based only on the simple NMR spectra, may be
difcult [1–3], ab initio calculations were performed in
the present paper in order to support or deny the earlier
conclusions [4]. Te substituent efect on tautomerism of
such derivatives is always signifcant [1–3], so the series
of substituted 2-phenacylbenzimidazoles is worth further
study.
only in the p-NMe substituted congener. On the other hand,
2
enolimine forms O were detected when the substituent had
less electron-donating character or when it had an electron-
accepting nature [1].
We have previously shown that 1-methyl-2-phenacylben-
zimidazoles are similar in chemical properties to 2-phena-
cylbenzoxazoles [2]. Analysis of NMR spectra and the results
of the quantum-chemical calculations showed unequivocally
that 1-methyl-2-phenacylbenzimidazoles (K - form) are in
equilibrium with (Z)-2-(1-methyl-1H-benzo[d]imidazol-2-
yl)-1-phenylethen-1-ols (O - form).
Since the –N=C(–)CH CO– moiety also is present
in 2-phenacylbenzimidazoles (Scheme 1, X = NH), these
2

2
Heteroatom Chemistry
O
Ar
N
X
K
ketimines
O
H
O
H
N
Ar
Ar
N
X
X
O
E
enolimines
enaminones
X = O, NC（3 or NH
Scheme 1: Tautomeric equilibria in some selected 2-phenacyl derivatives of benzoxazole, benzimidazole, and 1-methylbenzimidazole.
R
Cl
R
O
O
R
O
O
N
N
Δ
N
N
C（3
R
NEＮ3
N
H
N
H
R
1
2a-i
O
R = p-OC（3 (a), p = C（3 (b), m-C（3 (c), H (d), p-F (e), p-Cl (f), p-Br (g), m-F (h), p-N／2 (i)
Scheme 2: Synthesis of 2-phenacylbenzimidazoles.
2. Results and Discussion
K is expected to be in equilibrium with the enolimine O, or
enaminone E tautomers.
2-Phenacylbenzimidazoles can be obtained by a variety of
methods [5–13]. Te aforementioned syntheses are char-
acterized by low yield; therefore, 2-phenacylbenzimidazoles
were prepared by treating methylbenzimidazole 1 with
benzoyl chlorides in the presence of triethylamine followed
by thermal decomposition of formed (Z)-2-(1-benzoyl-
1H-benzo[d]imidazol-2-yl)-1-phenylvinyl benzoates 2a-i
(Scheme 2) [5, 7, 11].
In order to compare 2-phenacylbenzimidazoles with
2-phenacylbenzoxazoles and 1-methyl-2-phenacylbenzim-
idazoles studied earlier [1, 2], the NMR spectra of the former
compounds should be recorded from their deuterated chlo-
roform solutions. Unfortunately, the crystals were sparingly
soluble in that solvent, so it was substituted with DMSO-d6.
Tere is a single intramolecular hydrogen bond in 2-
phenacylbenzimidazoles [2-(1H-benzo[d]imidazol-2-yl)-1-
phenylethan-1-ones] (Scheme 3). In solution, this ketimine
Due to the presence of the 2,3-dihydro-2-methylene-1H-
benzo[d]imidazole moiety in the molecules, both nitrogen
atoms in the enaminone form E are equivalent (unless they
are diferentiated by the intramolecular hydrogen bond).
For the substituents studied, presence of the enolimine O
in DMSO-d6 solution has never been reported. 1H and 13C
1
as well as H,13C HMBC NMR spectra suggest that K and
E forms are present in such solution [4]. Tere is no doubt
about the presence of the former tautomer, but unequivocal
distinguishing between enolimines and enaminones cannot
be based only on the simple NMR spectra [1–3]. It is why
the 1H,13C HMBC technique has been used earlier to prove
which of K and E is present in solution [4]. Using of the IR
spectra to identify the form present in the crystalline state E
[4] also seems unreliable.
Te chemical shifs of H10 resonances (Table 1) are
comparable to those observed for 2-phenacyl derivatives

Heteroatom Chemistry
3
H
O
12
R
14
15
17
H
O
R
16
N
N
7
13
1
8
9
N
11
6
5
2
10
18
N 3
O
H
K
4
H
O
R
N
N
H
E
Scheme 3: Tautomeric equilibria of 2-phenacylbenzimidazoles.
1
Table 1: Selected H and 13C NMR chemical shifs for 2-phenacylbenzimidazoles [2-(1H-benzo[d]imidazol-2-yl)-1-phenylethan-1-ones]
K and (Z)-2-(1H-benzo[d]imidazol-2-yl)-1-phenylethen-1-ol O (solutions in DMSO-d6, regular characters) and 13C CPMAS spectral data
a
(ꢀꢁꢂꢃꢀꢄꢅ) .
2a
2b
Comp. Taut.
R =
p-OCH
H10 b
4.66
H1 and H3
12.23
C2
137.44
C10
C11
193.89
R
39.85 c
55.71,
2a
K
3
56.06d
O
K
p-OCH
p-CH
6.06
4.64
12.39
12.25
154.34
137.58
79.58
169.62
195.08
d
3
40.03 c
21.41
3
21.65 e
154.21
154.7
136.57
80.51
77.5
168.96
177.2
195.67
e
22.4
2b
2c
O
K
p-CH
6.07
4.66
12.35
12.33
3
40.01 c
21.33,
m-CH
3
21.56 e
2c
2d
2d
2e
2e
2f
O
K
O
K
O
K
O
K
O
K
O
K
O
m-CH
H
H
p-F
p-F
p-Cl
p-Cl
p-Br
p-Br
m-F
m-F
p-NO
6.10
4.68
6.10
4.67
6.00
4.67
6.03
4.67
6.03
4.70
6.05
4.78
6.13
12.26
12.34
12.27
12.33
12.22
12.33
12.24
12.34
12.26
12.34
12.27
12.39
f
154.14
136.51
154.11
135.97
153.99
135.20
153.28
135.84
153.84
135.64
153.81
f
81.30
40.12 c
80.83
40.09 c
79.12
39.67 c
78.89
39.80
79.38
40.26 c
79.54
f
169.42
195.60
169.94
194.24
171.04
194.06
170.45
194.90
171.03
194.66
170.98
f
e
-
-
-
-
-
-
3
2f
2g
2g
2h
2h
2i
-
-
-
-
2
2i
p-NO
153.45
80.33
80.3g
76.5
171.03
2
171.1g
-
152.5
175.3
aLiterature data collected from DMSO-d6 solutions. bLiterature data: 4.6 ppm - 4.8 ppm for K and 6.0 ppm - 6.25 ppm for E [4–6, 8]. cSince this signal is
overlapped by the solvent absorptions, DEPT technique was used to determine its position in the spectrum. dDue to their comparable intensities, the signals
cannot be referred to the defnite tautomers ([K] ≈ [O], see Table 2). eTe more intense signal was assigned to the O tautomer ([K] < 50 %, see Table 2). f Due
to low amount of the K tautomer, these signals were not observed. gLiterature data [4].

4
Heteroatom Chemistry
Table 2: Content of the K form (%) (solutions in DMSO-d6).
Compound
Substituent R
[K] (%)a,b
49.2 (49.5)c; 50 [4]; 52 [5]
32.0 (33.6)c
2a
2b
2c
2d
2e
2f
2g
2h
2i
p-OCH
3
p-CH
m-CH
H
p-F
3
23.1 (24.2)c
3
21.9; 20 [4]; 21[5, 7]
21.9
p-Cl
p-Br
m-F
13.0; 12 [5]
15.3
13.0
p-NO
3.9; 2 [4]; 4 [5]; 0 [8]
2
aBased on integrals of the H10 signals (present paper). bLiterature data collected from DMSO-d6 solutions. cValues in parentheses are based on integrals of
the substituent protons (CH , 3.91 ppm for 2a (form K) and 3.87ppm for 2a (form O), 2.51 ppm for 2b (form K) and 2.37 ppm for 2b (form O), 2.51 ppm for
3
2c (form K) and 2.40 ppm for 2c (form O)).
-
／
H
２+
N
N
K
Scheme 4: Resonance structure contributing to the stabilization of the 2-phenacylbenzimidazole tautomer K by electron-donating
substituents.
of benzoxazoles [1], 1-methy-2-phenacylbenzimidazoles [2],
and their enolimine or enaminone tautomers. Tus, the
chemical shif values do not reveal whether another tautomer
in DMSO-d6 solution isO or E. One should keep in mind that
signals of the N-H protons seen at >12 ppm are comparable
to those of the hydroxyl protons in the enolimine tautomers
of 2-phenacylbenzoxazoles [1].
consequence, their proton transfer to the aza atom in these
compounds is facile.
Te dependence between pKT for 2-phenacylbenzim-
idazoles and Hammett substituent constant ꢇ [15] has the
linear character (pKT = 1.128ꢇ – 0.491, R = 0.977, Figure 1).
On the other hand, the 13C chemical shifs can indicate
the tautomer present in solution. C11 signals of other tau-
tomers (O or E) are located in the range of 161-171 ppm
(Table 1). Tus, the 2-phenacylbenzimidazoles K are really
in equilibrium with the O forms ((Z)-2-(1H-benzo[d]im-
idazole-2yl)-1-phenylethen-1-ols) [14].
2.2. Quantum-Chemical Calculations. Te obtained experi-
mental data seemed worthy of comparison with the results
of the respective quantum-chemical calculations. Although
semiempirical quantum-chemical calculations show that
enaminone form E of 2d is thermodynamically more stable
than ketimine form K of 2d [4], MP2 procedure is recom-
mended as the most accurate and efective ab initio method
for studying medium size molecules involving hydrogen
bonds [16]. It includes electron correlation so the calculated
and experimental data are expected to be comparable [17].
Some optimized bond lengths and dihedral angles in the
molecules of 2-phenacylbenzimidazoles and their tautomers
are presented in Table 3. Judging from the length of the
hydrogen bond, it seems to be stronger in enolimines than
in enaminones. Such an interaction is especially weak in
ketimines.
Te percent content of K form based on H10 integrals is
given in Table 2. Te accuracy of these data was supported by
the evaluation based on signal intensities of the substituent
protons and the literature data. In many cases, mainly ꢆ-
electron delocalization was found to be responsible for
tautomeric preferences but other efects, such as the strength
of the intramolecular hydrogen bond, should be taken into
account.
13C CPMAS spectra of 2b and 2i show that only one tau-
tomer is present in the solid state. Te characteristic chemical
shifs of 22.4 ppm (CH ), 77.5 ppm (C10), and 177.2 ppm (C11)
3
Te efect of the substituent on conformation of each
tautomer is negligible. Twisting of the carbonyl group with
respect to the neighbouring benzene ring in the ketimine
molecules is equal to 10-15∘ (Table 3). Te six-membered
pseudorings, including the intramolecular hydrogen bonds
in both enolimines and enaminones, are almost planar.
Te dihedral angle (Ψ) between the said benzene ring and
C10–C11–O12 moiety in these two tautomers is comparable
(ca 30∘).
for 2a and 76.5 ppm (C10) and 175.3 ppm (C11) for 2i, suggest
that it was the enolimine form O.
2.1. Substituent Efect on the Tautomeric Equilibrium. As can
be seen in Table 2, the tautomeric ratio in solutions of 2a-i
depends strongly on the substituent. Electron-acceptor sub-
stituents increase acidic character of the methylene protons
in the K forms and thus favour this tautomer (Scheme 4). In

Heteroatom Chemistry
5
2
1
0

−0,5
0,5
Figure 1: Plot of -logKT vs. Hammett substituent constants for 2a-i.
˚
Table 3: Optimized (MP2/6-311+G(d,p)) bond lengths [A] and dihedral angles [deg] for 2-phenacylbenzimidazoles and their tautomers.
Ψ
N1–H1
O12–H12
N3–H3
O12. . .H1
or
(C14–C13–C11–O12)
Ψ
Comp.
Taut.
R =
H10. . .H18
N1. . .H12
(C18–C13–C11–O12)
2a
K
p-OCH
1.01
-
-
2.70
1.74
1.82
2.69
1.74
1.82
2.82
1.73
1.82
2.22,
3.70a
12.25
3
3
3
-165.66
2a
2a
2d
2d
2d
2i
O
E
p-OCH
-
2.29
2.25
-29.75
150.23
0.99
1.01
1.03
-
1.01
1.01
-
p-OCH
-28.71
150.53
K
O
E
H
H
H
2.25,
3.70a
-15.81
162.48
-
-
2.31
-31.42
148.46
0.99
1.01
1.03
-
1.01
1.01
-
2.28
-30.93
148.00
K
O
E
p-NO
2.27,
3.71a
14.17
-164.73
2
-
-
2i
p-NO
2.26
2.26
-28.20
151.17
2
1.00
1.01
1.03
-
2i
p-NO
-29.30
149.28
2
1.01
aDistances to H18 from two distinct H10.
Although distances between H18 and methylene protons
H10 in 2-phenacylbenzoxazoles were comparable [1], these
in 2-phenacylbenzimidazoles (ketimines, K) are signifcantly
diferentiated (Table 3) because one of these methylene
hydrogens experiences steric hindrance by the aryl ring.
Te calculated energies of diferent tautomers (Table 4)
prove the K form to be the most stable (both electron-donor
and electron-acceptor substituents follow this rule).
Te enolimine O is always less stable than ketimine
K (the more electron-accepting is the substituent, the

6
Heteroatom Chemistry
Table 4: MP2(6-311+G(d,p)) calculated relative energies [kJ⋅mol−1] of diferent tautomers.
Compound
2a
2a
2a
2d
2d
2d
2i
Tautomer
R =
p-OCH
p-OCH
p-OCH
H
Energy [kJ⋅mol−1]
0.00 a
K
O
E
3
3
3
10.06
33.94
K
O
E
0.00b
H
H
6.29
30.17
K
O
E
p-NO
p-NO
p-NO
0.00c
2
2i
2i
2.10
23.05
2
2
aAbsolute energy: -875.8329 Hartree.
bAbsolute energy: -761.5722 Hartree.
cAbsolute energy: -965.6772 Hartree.
more stable is the enolimine form). As this can be seen
in Scheme 3, the six-membered pseudoring including the
NH... O=C system in K is expected to be less aromatic
than the respective pseudorings including the NH... O=C
and OH... N moieties in E and O, respectively. Te strong
resonance assisted hydrogen bonds (RAHB), such as this
present in the molecule of the later tautomer, are well known
[18–21]. Te least stable tautomer is always E (both electron-
donor and electron-acceptor substituents follow the rule).
It is noteworthy that O seems to be really more stable
than E just because the benzene, pseudo, and imidazole
rings are aromatic in the former tautomer, while in the
enaminone that is the case for the benzene and pseudor-
ings only (Scheme 3). Tus, from this point of view, 2-
phenacylbenzimidazoles resemble 2-phenacylbenzoxazoles
[1] and 1-methyl-2-phenylbenzimidazoles [2].
from TMS) ꢈ 3.87 (3H, s, p-OCH3 (O)), 3.91 (3H, s, p-OCH3
(K)), 4.66 (2H, s, CH2CO (K)), 6.06 (1H, s, CHO (O)), 7.07
(2H, m (O)), 7.15 (2H, m, (O)), 7.21 (4H, m, (K)), 7.43 (1H,
m, (O)), 7.58 (3H, m, (O)), 7.88 (2H, m, (K)), 8.14 (2H, m,
(K)), 12.24 (1H, s, NH (K)), 12.39 (1H, s, NH (O)). 13C NMR
ꢈ 39.85, 55.71, 56.06, 79.72, 110.82, 114.21, 114.49, 114.93, 115.32,
121.80, 122.39, 127.63, 129.42, 129.96, 131.36, 132.30, 132.62,
137.44, 149.57, 154.34, 161.06, 163.95, 169,62, 193.89. Anal.
Calcd for C H N O : C, 72.16; H, 5.30; N, 10.52. Found: C,
16 14
2
2
72.21; H, 5.15, 10.18.
2-(1H-benzimidazol-2-yl)-1-(4-methylphenyl)ethan-
1-one (2b). Yellow solid; yield 0.97 g (65%); mp 192-193.5∘C
1
(lit. 195-196∘C [4]); H NMR (DMSO-d6 from TMS) ꢈ 2.37
(3H, s, p-CH3 (O)), 2.51 (3H, s, p-CH3 (K)), 4.64 (2H, s,
CH2CO (K)), 6.07 (1H, s, CHO (O)), 7.16 (3H, m (O)), 7.27
3
(2H, d, J = 7.96 Hz, (O)), 7.38 (4H, m (K)), 7.50 (1H, m
ꢀ,ꢀ
(O)), 7.57 (2H, m (K)), 7.76 (2H, m (O)), 8.00 (2H, m (K)),
12.25 (1H, s, NH (K)), 12.35 1H, s, NH (O)). 13C NMR ꢈ 21.40,
21.64, 40.03, 80.64, 110.90, 115.13, 122.37, 122.57, 125.96, 129.07,
129.47, 129.83, 130.17, 130.47, 132.30, 134.03, 134.67, 137.58,
139.87, 144.58, 149.42, 154.21, 169.45, 195.08. Anal. Calcd for
C H N O: C, 76.78; H, 5.64; N, 11.19. Found: C, 76.81; H,
3. Experimental Methods
Melting points were measured on a Boetius table and are
uncorrected. Satisfactory elemental analyses ( 0.30 % for C,
H and N) were obtained from Perkin Elmer 2400 Series II
CHNS/O.
16 14
2
5.52; N, 11.09.
2-(1H-benzimidazol-2-yl)-1-(3-methylphenyl)ethan-1-
one (2c). Yellow solid; yield 1.11 g (70%); mp 166-171∘C (lit.
3.1. Syntheses: General Procedure. Benzoyl chloride (0.04
mole) was added in one portion to the stirred solution of 2-
methylbenzimidazole 1 (1.46 g, 0.01 mole) and triethylamine
(5.6 mL, 4.05 g, 0.04 mole) in diglyme (4 mL). Content of
the reaction vessel was heated for 1 h on the boiling water
bath. Dropwise addition of water (60 mL) to the stirred
cold reaction mixture resulted in precipitation of (Z)-2-(1H-
benzo[d]imidazol-2-yl)-1-phenylvinyl benzoates. A solution
of the crude material (0.006 mole) and morpholine (1.6 mL,
1,57 g, 0.018 mole) in methanol (9 mL) were heated under
refux with stirring for 10 min. Water (9 mL) was added to the
boiling reaction mixture, which cooled to start precipitation.
Crystallization of the collected solid from methanol afords
pure 2-phenacylbenzimidazoles 2a-i.
142-143∘C [22]); H NMR (DMSO-d6 from TMS) ꢈ 2.40
1
(3H, s, m-CH3 (O)), 2.51 (3H, s, m-CH3 (K)), 4.66 (2H, s,
CH2CO (K)), 6.66 (1H, s, CHO (O)), 7.16 (3H, m (O)), 7.26
3
(3H, d J = 7.48 Hz, (K)), 7.35 (3H, t (K)), 7.47 (3H, m
ꢀ,ꢀ
3
(O)), 7.66 (2H, m (O)), 7.89 (2H, d J = 7.36 Hz, (K)),
ꢀ,ꢀ
12.26 (1H, s, NH (O)), 12.33 (1H, s, NH (K)). 13C NMR ꢈ
21.33, 21.56, 40.10, 81.30, 110.99, 115.26, 121.83, 122.53, 123.20,
126.23, 126.50, 126.76, 128.79, 129.15, 129.24, 130.84, 132.36,
134.68, 136.57, 137.40, 138.02, 138.69, 149.37, 154.14, 169.42,
195.67. Anal. Calcd for C H N O: C, 76.78; H, 5.64; N, 11.19.
16 14
2
Found: C, 76.58; H, 5.58; N, 10.91.
2-(1H-benzimidazol-2-yl)-1-phenylethan-1-one (2d).
Light yellow solid; yield 1.22 g (87%); mp 182-183∘C (lit.
176-178 [22], 179 [6], 178-178.5 [7], 178-179∘C [4]); 1H NMR
(DMSO-d6 from TMS) ꢈ 4.68 (2H, s, CH2CO (K)), 6.10
(1H, s, CHO (O)), 7.17 (3H, m (O)), 7.42 (1H, m (O)), 7.45
2-(1H-benzimidazol-2-yl)-1-(4-methoxyphenyl)ethan-
1-one (2a). Yellow solid; yield 0.66 g (57%); mp 205-207∘C
1
(lit. 205-207 [22], 208-209∘C [4, 5]); H NMR (DMSO-d6

Heteroatom Chemistry
7
(2H, m (O)), 7.49 (1H, m (K)), 7.57 (5H, m (K)), 7.68 (1H, m
(K)), 7.86 (2H, m (O)), 8. 09 (2H, m (K)), 12.27 (1H, s, NH
(O)), 12.34 (1H, s, NH (K)). 13C NMR ꢈ 40.12, 80.83, 110.95,
115.06, 121.86, 122.51, 126.01, 128.88, 128.94, 129.28, 130.17,
132.25, 134.08, 136.51, 137.23, 137.63, 149.31, 154.11, 169.94,
195.60. Anal. Calcd for C H N O: C, 74.22; H, 5.13; N,
(O)), 7.41 (1H, s (O)), 7.59 (1H, s (O)), 8.11 (2H, m (O)), 8.30
(2H, m (O)), 12.39 (1H, s NH (O)).13C NMR ꢈ 80.32, 111.06,
114.25, 122.99, 124.07, 131.75, 134.89, 145.06, 148.25, 153.45,
171.03. Anal. Calcd for C H N O : C, 71.87; H, 4.90; N,
15 11
3
3
10.85. Found: C, 71.77; H, 5.10; N, 10.94.
15 12
2
10.18. Found: C, 74.35; H, 4.97; N, 10.23.
1
3.2. NMR Spectral Analysis. Te H and 13C NMR spectra
2-(1H-benzimidazol-2-yl)-1-(4-fuorophenyl)ethan-1-
one (2e). Brownish solid; yield 0.74 g (59%); mp 196-200∘C
(lit. 204-205∘C [22]; 1H NMR (DMSO-d6 from TMS) ꢈ 4.67
(2H, s, CH2CO (K)), 6.67 (1H, s, CHO (O)), 7.17 (3H, m
(O)), 7.28 (2H, m (O)), 7.38 (1H, m (O)), 7.43 (2H, m (K)),
7. 55 (4H, m (K)), 7.91 (2H, m (O)), 8.18 (2H, m (K)), 12.22
(1H, s, NH (O)), 12.33 (1H, s, NH (K)). 13C NMR ꢈ 40.09,
79.12, 110.82, 114.43, 115.54, 115.76, 116.22, 116.44, 121.91, 122.61,
128.42, 128.51, 131.97, 132.07, 133.23, 133.26, 134.92, 134.95,
135.97, 149.20, 153.99, 162.26, 164.47, 164.71, 166.98, 171.04,
194.24. Anal. Calcd for C H FN O: C, 73.26; H, 4.99; N,
were recorded for diluted DMSO-d6 solution at 298 K on a
Bruker Ascend 400 MHz spectrometer. Te chemical shifs
are referenced to the signal of internal TMS at ꢈ=0.00 ppm.
1
1
Te H, 13C and PFG H,13C HMQC and HMBC spectra
were recorded on a Bruker Avance DRX 500 spectrometer
equipped with an inverse detection probehead and z-gradient
accessory working at 500.13 MHz and 125.77 MHz, respec-
tively. Te number of data points in PFG H,13C HMQC
1
and HMBC measurements were 1024 (f ) x 256 (f ). Tis
2
1
15 11
2
matrix was zero flled to 2048 x 512 and apodized by a
10.05. Found: C, 73.04; H, 5.16; N, 10.02.
shifed sine bell window function along both axes prior to
FT.
2-(1H-benzimidazol-2-yl)-1-(4-chlorophenyl)ethan-1-
one (2f). Yellow solid; yield 1.05 g (68%); mp 232-234∘C (lit.
Te solid state 13C CPMAS NMR spectra were recorded
on a Bruker Avance 400 FT NMR spectrometer using the
samples packed in 4.0 mm o.d. zirconia rotors. Te samples
were spun at 10 KHz rate and >1000 transients were accumu-
lated. Te FIDs are apodized by 10 Hz exponential window
before FT. Te shifs are referenced to the C=O signal of
glycine standard at ꢈ=176.03 ppm.
1
226-228∘C [4, 5]; H NMR (DMSO-d6 from TMS) ꢈ 4.67
(2H, s, CH2CO (K)), 6.03 (1H, s, CHO (O)), 7.14 (3H, m
(K)), 7.19 (2H, m (O)), 7.48 (4H, m, (O)), 7.63 (3H, d, 3J
=
ꢀ,ꢀ
8.40 Hz, (K)), 7.68 (2H, d, 3J = 8.40 Hz, (O)), 8.40 (2H, d,
ꢀ,ꢀ
3J = 8.40 Hz, (K)), 12.24 (1H, s, NH (O)), 12.33 (1H, s, NH
ꢀ,ꢀ
(K)). 13C NMR ꢈ 39.67, 78.89, 110.33, 113.91, 121.33, 122.12,
127.42, 128.28, 128.84, 130.31, 131.38, 134.16, 134.58, 135.20,
136.78, 138.51, 148.54, 153.28, 170.45, 194.06. Anal. Calcd for
C H ClN O: C, 72.41; H, 4.93; N, 9.93. Found: C, 72.46; H,
3.3. Quantum-Chemical Calculations. Geometries for the
isolated molecules (vacuum) of the tautomers were optimized
using the second order Mo¨ller-Plesset method (MP2) [23,
24]. Computations were carried out utilizing the split-valence
triple-zeta basis sets 6-311+G(d,p) [25]. All calculations were
realized with use of Gaussian 09 package [26].
15 11
2
4.88; N, 9.86.
2-(1H-benzimidazol-2-yl)-1-(4-bromophenyl)ethan-
1-one (2g). Yellow solid; yield 1.48 g (82%); mp 193-195∘C
(lit. 238-240 [22], 244-246∘C [4]); 1H NMR (DMSO-d6 from
TMS) ꢈ 4.67 (2H, s, CH2CO (K)), 6.03 (1H, s, CHO (O)),
7. 17 (2H, m (O)), 7.37 (3H, s (K)), 7.56 (3H, s (K)), 7.66 (3H,
m (O)), 7.80 (3H, m (O)), 8.01(2H, m (K)), 12.26 (1H, s NH
(O)), 12.34 (1H, s, NH (K)). 13C NMR ꢈ 39.80,79.38, 110.89,
111.49, 114.45, 121.47, 122.30, 122.54, 122.80, 123.49, 128.23,
130.97, 131.77, 132.37, 133.13, 135.50, 135.84, 137.67, 149.06,
153.84, 171.03, 194.90. Anal. Calcd for C H BrN O: C,
4. Conclusions
In DMSO-d6 solution, 2-phenacylbenzimidazoles (ketimine
tautomeric form, K) are in equilibrium with (Z)-2-(1H-
benzo[d]imidazol-2-yl)-1-phenylethen-1-ol (enolimine form,
O). 2-(1H-benzo[d]imidazol-2(3H)-ylidene-1-phenyletha-
nones (enaminones E) were not detected (our fndings are
diferent from those reported earlier by other authors [4]).
Te molar ratio of diferent forms in solution (based on
15 11
2
70.19; H, 4.78; N, 9.63. Found: C, 68.99; H, 4.83; N, 9.47.
2-(1H-benzimidazol-2-yl)-1-(3-fuorophenyl)ethan-1-
one (2h). Yellow solid; yield 1.32 g (77%); mp 211-213∘C; 1H
NMR (DMSO-d6 from TMS) ꢈ 4.70 (2H, s, CH2CO (K)),
6.05 (1H, s, CHO (O)), 7.17 (2H, m (O)), 7.19 (3H, m (K)),
7. 28 (1H, m (O)), 7.38 (1H, m (O)), 7.49 (3H, m (K)), 7.51 (1H,
m (O)), 7.57 (1H, m (O)), 7.61 (1H, m (O)), 7.64 (2H, m (K)),
7. 70 (1H, m (O)), 12.27 (1H, s, NH (O)), 12.34 (1H, s, NH
(K)). 13C NMR ꢈ 40.26, 79.54, 110.94, 112.63, 112.85, 114.38,
115.33, 115.55, 116.66, 116.87, 120.89, 121.10, 122.18, 122.72,
125.17, 130.79, 131.49, 131.93, 135.64, 141.34, 149.02, 153.81,
161.63, 164.05, 170.98, 194.66. Anal. Calcd for C H FN O:
1
the integrals of H NMR signals) depends on substituent.
Electron-acceptor substituents increase the acidic character
of the methylene protons in the ketimine forms K. In
consequence, the transfer of such a proton to the carbonyl
oxygen is very easy in these compounds. Te calculated
energies of diferent tautomers prove the ketimine form K
including the OH... N hydrogen bond to be the most stable
(both electron-donor and electron-acceptor substituents
follow this rule). Te enolimine tautomers O are always less
stable than ketimines K. Te most labile tautomer is always
enaminone E. Enolimine tautomers O were detected by solid
state 13C CPMAS NMR.
15 11
2
C, 73.26; H, 4.99; N, 10.05. Found: C, 73.37; H, 5.11; N, 10.22.
2-(1H-benzimidazol-2-yl)-1-(4-nitrophenyl)ethan-
1-one (2i). Orange solid; yield 1.7 g (95%); mp 159-161
(lit. 165-166 [8], 270-272 [22], 295-297∘C [4, 5]); H NMR
1
(DMSO-d6 from TMS) ꢈ 6.13 (1H, s, CHO (O)), 7.20 (2H, m

8
Heteroatom Chemistry
Data Availability
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Conflicts of Interest
[13] M. S. Frasinyuk, N. V. Grobulenko, and V. P. Khilya, “Chemistry
of the heteroanalogs of isofavones. 20. Benzimidazole analogs
of isofavones,” Chemistry of Heterocyclic Compounds, vol. 33,
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Te authors declare that they have no conficts of interest.
Acknowledgments
[14] R. A. More O’Ferrall and B. A. Murray, “1H and 13C NMR
spectra of ꢉ-heterocyclic ketones and assignment of keto, enol
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Tis research was supported in part by PL-Grid Infrastruc-
ture.
Supplementary Materials
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