Regioselective synthesis of 2-unsubstituted 1-aryl-4- and 1-aryl-5-acylimidazoles

Article abstract of DOI:10.1016/j.tet.2014.04.012

An efficient and simple method for the synthesis of 2-unsubstituted 1-aryl-4- and 1-aryl-5-acylimidazoles has been developed. It consists in the condensation of α-diketone monooximes with aromatic amines and formaldehyde on the presence of boron trifluori

Full text of DOI:10.1016/j.tet.2014.04.012

Accepted Manuscript
Regioselective synthesis of 2-unsubstituted 1-aryl-4- and 1-aryl-5-acylimidazoles
Vitaly S. Mityanov, Ludmila G. Kuz’mina, Valery P. Perevalov, Iosif I. Tkach
PII:
S0040-4020(14)00505-5
10.1016/j.tet.2014.04.012
TET 25462
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 11 November 2013
Revised Date: 27 March 2014
Accepted Date: 7 April 2014
Please cite this article as: Mityanov VS, Kuz’mina LG, Perevalov VP, Tkach II, Regioselective
synthesis of 2-unsubstituted 1-aryl-4- and 1-aryl-5-acylimidazoles, Tetrahedron (2014), doi: 10.1016/
j.tet.2014.04.012.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Regioselective synthesis of 2-unsubstituted 1-
aryl-4- and 1-aryl-5-acylimidazoles
Leave this area blank for abstract info.
Vitaly S. Mityanov, Ludmila G. Kuz’mina, Valery P. Perevalov and Iosif I. Tkach
a
Department of Fine Organic Synthesis and Chemistry of Dyes, D. Mendeleyev University of Chemical Technology of Russia, Miusskaya Sq., 9,
Moscow 125047, Russia
b
Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Science, Leninskii Pr., 31, Moscow 117907, Russia
BF3
O
O
O
O
O
O
NOH
O
NOH
O
H C
3
N
CH3
N
N
N
N
Ar
CH3
H C
3
CH
CH
3
3
H C
N
Ar
3
CH3
H C
3
CH3
.
Ar
Et O BF
2
3
[H]
+
ArNH2 + CH O
2
BF3
N
N
Ar
NOH
O
N
O
O
N
Ar
NOH
NOH

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Regioselective synthesis of 2-unsubstituted 1-aryl-4- and 1-aryl-5-acylimidazoles
a,
b
a
a*
Vitaly S. Mityanov , Ludmila G. Kuz’mina , Valery P. Perevalov and Iosif I. Tkach
a
Department of Fine Organic Synthesis and Chemistry of Dyes, D. Mendeleyev University of Chemical Technology of Russia, Miusskaya Sq., 9,
Moscow 125047, Russia
Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Science, Leninskii Pr., 31, Moscow 117907, Russia
b
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An efficient and simple method for the synthesis of 2-unsubstituted 1-aryl-4- and 1-aryl-5-
acylimidazoles has been developed. It consists in the condensation of α-diketone monooximes
with aromatic amines and formaldehyde on the presence of boron trifluoride etherate, leading to
the formation of stable boron trifluoride complexes of N-oxides. Further reduction of these
complexes led to the corresponding imidazoles. This method permits broad variations of
substituents in the aryl part of these compounds.
Available online
Keywords:
2
009 Elsevier Ltd. All rights reserved.
1
-Arylimidazoles
Boron trifluoride
Imidazole N-oxides
N-oxide reduction
X-ray diffraction
1
. Introduction
-Arylimidazoles have a wide range of biological activities
BF3
1
1
Me NOH
+
O
.
2-5
Et
2
O BF
3
Me
N
and great pharmacological potential. 1-Arylimidazoles without
a substituent at its position 2 are of particular importance. Several
synthetic methods for the preparation of these compounds, are
ArNH2 + CH O
2
Me
O
N
Me
Ar
6-10
known.
However, most of them apply for the preparation of
Figure 1. Synthesis of boron trifluoride complexes of 1-aryl-
only a limited number of compounds, which hinders a
comprehensive study of their properties. For this reason
developing an efficient method for 2-unsubstituted 1-
arylimidazoles synthesis is of considerable interest.
16
4
,5-dimethylimidazole N-oxides.
Aromatic amines containing different substituents, both
electron donating and withdrawing groups and aromatic amines
with bulky substituents at the ortho positions readily participate
in this reaction. This shows the prospect of using this as a
convenient and general method for the synthesis of 1-
arylimidazoles. In the present study, we investigate the viability
of this reaction for the preparation of 1-arylimidazoles containing
an acyl group at positions 4 or 5.
Our synthetic strategy consists of the preparation of 1-
arylimidazole N-oxides followed by the reduction of the N-oxide
functional group. First attempts to synthesize 2-unsubstituted 1-
11-13
arylimidazole N-oxides
involved acid-catalyzed condensation
of α-diketone monooximes either with aromatic amines and
formaldehyde or previously obtained N-arylmethylenamines, but
they failed, apparently, due to a rapid isomerization of the N-
14,15
13
oxides to the corresponding imidazol-2-ones. Other methods
2. Results and discussion
are also ineffective, since suitable starting materials often prove
to be not readily available.
It is well-known that arylation of imidazoles containing
dissimilar substituents at positions 4 and 5 leads to a mixture of
regioisomers with predominance of the less sterically hindered
We assumed that 2-unsabstituted imidazole N-oxides could be
stabilized with respect to a rearrangement to 2-imidazolones by
6,17
16
compound.
Our method makes it possible to prepare any
binding them in a complex. In our previous work we have
proved that the reaction of primary aromatic amines with
formaldehyde and butane-2,3-dione monooxime in the presence
of boron trifluoride etherate led to the formation of stable boron
trifluoride complexes of 1-aryl-4,5-dimethylimidazole N-oxides
predetermined regioisomer. The nature of substituents at
positions 4 and 5 depends on the structure of α-diketone
monooxime.
Thus, for the synthesis of 1-aryl-4-acetylimidazoles easily
18
available pentan-2,3,4-trione 3-oxime 7 can be used . Indeed, the
condensation of compound 7 with aromatic amines and
formaldehyde in the presence of boron trifluoride etherate led to
(
Fig. 1).
*
Corresponding author. Tel.: +7 499 978 8842; e-mail addresses:
mityanovvs@yandex.ru (V.M. Mityanov), iosif_tkach@mail.ru (I.I. Tkach).

2
Tetrahedron
the formation of complexes of boron trifluor
A
ide
C
w
C
it
E
h
P
1-ar
T
E
yl-4- MAch
D
NU
ro
ma
S
to
C
gr
R
ap
I
hy on silica gel led to the isolation imidazole-2-one
P
T
acetyl-5-methylimidazole N-oxides 2 in good yield.
11. Moreover, when pure compound 2c was passed through a
silica gel (eluent: chloroform-methanol) compound 11 was
obtained in nearly quantitative yield (scheme 2). At the same
time, complexes of boron trifluoride with 1-aryl-4,5-
dimethylimidazole N-oxides were smoothly isolated by
chromatography in high to moderate yields.
Boron trifluoride etherate not only stabilizes imidazole N-
oxides but also acts as an excellent acid catalyst facilitating the
reaction, so that it may proceed under mild conditions.
It is possible to use various solvents for the condensation
(chloroform, alcohols, acetic acid); the choice is mainly
determined by features of the isolation of products.
O
H
N
N
O
BF3
O
Me
O
SiO2
O
NOH
.
2c
Me
Me
Et O BF
2 3
N
Me
Me
a-e
Me
+
ArNH2 + CH O
CHCl3, MeOH
2
O
2
-PrOH, 45-50 °C
N
6a-e
7
Ar
2
MeO 11
Ar
N
Scheme 2. Transformation of boron trifluoride complex to the
imidazol-2-one
The reduction of compounds 2 proceeds facile by using
various reducing agents and results in corresponding imidazoles
.
7, Et O BF
2
3
ArNH2 + CH O
2a-c
2
N
N
2
-PrOH, 45-50 °C
Ar
Ar
6a-c
1
0a-c
1
in high yields.
Scheme 1. Synthesis of boron trifluoride complexes 2.
The use 19of the obtained 1,3,5-triarylhexahydro-1,3,5-
BF3
O
O
O
triazinanes 10 is an alternative to using a mixture of arylamines
6
Fe (dust)
N
Me
N
N
Ar
Me
and formaldehyde; compounds 10 possess a relatively high
reactivity and the greater storage stability. Also, the use of
triazinanes 10 makes it possible to minimize the amount of water
entering with formaldehyde solution. In this case, the yields of 2
are generally higher (see Table 1, entries 1-3).
AcOH, ∆
N
Me
Me
Ar
2a-e
1a-d,f
Scheme 3. Reduction of complexes 2.
Table 1. Complexes of boron trifluoride with 1-aryl-4-acetyl-
The fact that the condensation and reduction can be carried
5
-methylimidazole N-oxides 2 produced via scheme 1.
out in the same solvent (e.g., isopropyl alcohol or acetic acid)
prompted us to obtain imidazoles 1 using one-pot procedure (see
table 2).
Entry
Compound 2
Yield,
%
Table 2. 4-Acetyl-5-methyl-1-aryl-1H-imidazoles 1.
BF3
O
1
6
1
N
Yield,
1
2a
2b
2c
2
2
2
O
Entry
Compound 1
N
(80)
%
Me
Me
N
1
O
57
N
1
1a
1b
1c
2
2
2
BF3
(
(
59)
O
1
Me
4
8
Me
N
2
3
O
N
(71)
N
1
Me
Me
O
41
Me
N
2
3
32)
Me
Me
Me
BF3
O
N
1
3
3
N
1
O
N
(47)
O
27
N
MeO
Me
(46)
Me
MeO
Me
Me
N
BF3
OMe
N
O
OMe
N
O
1
N
54
O
1
4
5
2d
2e
55
4
5
1d
1f
2
2
(
45)
Me
Me
MeO
Me
MeO
Me
OMe
OMe
N
H N
2
1
BF3
O
50
O
N
N
1
(50)
O
N
83
2
Me
Me
O
N
1
Me
Method A: 1.0 equiv compound 2, 11.1 equiv iron powder, glacial acetic
acid, reflux, 2.5 h (overall yield in stepwise procedure)
Me
1
.
Method A: 1.0 equiv oxime 7, 1.1 equiv Et
2
OBF
3
, 2.0 equiv CH
2
O, 1.0
2
.
Method B: 1.0 equiv oxime 7, 1.1 equiv Et
2
OBF
6, IPA, 45-50 C, 4h. Then 15 equiv HCO
Pd/C (10%) were added and reflux for 3h (yield in one-pot procedure)
3
, 2.0 equiv CH
2
O, 1.0
◦
equiv ArNH
2
6, IPA, 45-50 C, 4h
◦
equiv ArNH
2
2
NH and 3 mol %
4
2
.
Method B: 1.0 equiv oxime 7, 1.1 equiv Et
2
OBF
3
, 1.0 equiv triazinane 10,
IPA, room temperature, 4h
4
-Acylimidazoles 3 were also obtained by using a one-pot
20
It is interesting to note that compounds 2 appeared to be less
stable than their 4,5-dimethyl analogs. Thus, the attempt to
isolate derivative 2c from the reaction by column
procedure. As it is known, oxime 8 is unstable under heating in
solvents, especially in the presence of acids. For this reason the
condensation was performed in acetic acid at room temperature

3
with an increased reaction time (20 h). The r
carried out in the conventional manner.
A
edu
C
ct
C
io
E
n
P
ste
T
p
E
w
D
as MAN
T
U
he
S
o
C
xim
R
e
I
group in these compounds is hidden the carbonyl
P
T
function. So, the reduction of compounds 5 by iron dust in
boiling acetic acid is accompanied by the hydrolysis of oxime
function and led to the formation of imidazoles 4. The isolation
of these compounds is easy and can be carried out even without
chromatography.
Table 3. The scope of 6,6-Dimethyl-1-aryl-4,5,6,7-
tetrahydro-1H-benzimidazol-4-ones 3.
NOH
.
1
) Et O BF
O
2
3
O
O
AcOH, r.t.
N
Table 5. The scope of 1-aryl-4,5,6,7-tetrahydro-1H-
benzimidazol-7-ones 4.
+
+
Me
Me
ArNH2
a,c,g
CH O
2
N
Me Me
2) Fe (dust)
Ar
6
AcOH, ∆
8
3
a,c,g
BF3
O
Fe (dust)
N
N
N
Yield,
%
AcOH, ∆
Entry
Compound 3
N
Ar
Ar
5
O
NOH
a,c,g
N
N
4a,c,g
O
1
1
2
3
3a
3c
3g
44
40
52
Yield ,
%
Entry
Compound 4
Me
Me
N
N
N
N
1
4a
4c
4g
50
O
MeO
O
Me
N
N
Me
N
N
O
2
3
45
55
MeO
O
MeOOC
N
Me
N
Me
MeOOC
21
Readily available cyclic dioxime 9 was chosen as a
precursor in the synthesis of sterically hindered 5-acylimidazoles.
In this case the condensation was carried out with two
equivalents of boron trifluoride etherate because of the potential
O
1
Yield can be increased by isolation additional amounts of product from the
filtrates.
1
In the H NMR spectra of imidazoles N-oxides 2 the signal of
proton at position 2 of the imidazole ring is found as a narrow
singlet in the 9.53-9.78 (in DMSO-d6) and 8.18-8.44 (in CDCl3)
ppm ranges. Thus, the signal of this proton in DMSO-d6 is
possibility of complexation of the BF with both N-oxide and
3
oxime groups. However, compounds 5 contain only one BF3
group.
shifted downfield to 1.2-1.4 ppm over that in CDCl , while
Table 4. The scope of boron trifluoride complexes of 1-aryl-
3
changes to the positions of other proton signals are negligible. It
should be noted that in DMSO-d6 doubling signals of all protons
is observed (see supplementary materials). In addition to the
main signal of each proton an additional signal with a close
chemical shift, but much less intense appeared. When recording
7
-hydroxyimino-4,5,6,7-tetrahydro-1H-benzimidazole 3-
oxides 5.
O
BF3
O
HON
NOH
.
Et O BF
N
2
3
spectra in CDCl this effect is not observed. For previously
+
+
3
ArNH2
CH O
2
obtained 4,5-dimethyl derivatives such an effect was also
lacking.
AcOH, r.t.
N
9
6a,c,g
Ar
NOH
The signal of the proton at the imidazole ring C-2 atom of the
compounds 5 are in the same range (9.50 - 9.62 ppm in DMSO-
d6), however, unlike compounds 2, doubling of the signals is not
observed. For imidazoles 1, 3 and 4 the proton signal at the
imidazole ring C-2 atom is a narrow singlet in the range usual for
imidazoles (7.27 - 7.78 ppm in CDCl3).
5
a,c,g
Entry
Compound 5
Yield,
%
65
5
5
5
a
O
BF3
N
N
The mass spectra of compounds 2 shows low-intensity signals
1
2
3
+
corresponding to the [M-F] cation, as well as a rather strong
HON
+
signal for the fragment with m/z = 49, corresponding to the BF
2
16
cation. Previously, on the basis of similar mass spectra we
erroneously ascribed to boron trifluoride complexes with 1-aryl-
c
68
67
O
BF3
N
4
,5-dimethylimidazole N-oxides structure of 1-aryl-3-[(
difluoroboryl)oxy]-4,5-dimethyl-1H-imidazolium fluorides.
However, as shown by single-crystal X-ray diffraction, 1-phenyl-
,5-dimethylimidazole N-oxide 12 and 1-aryl-4-acetyl-5-
N
MeO
HON
4
methylimidazole N-oxide 2b formed similar complexes with BF .
3
g
+
O
BF3
While the signal for the fragment [M-F] can be observed in
N
the mass spectra not for all compounds 2 and 5, the signal for the
N
+
MeOOC
BF2 is always present. The signal for the fragment with m/z =
+
HON
68, that would correspond to the BF
3
cation in the mass spectra
of these compounds is not detected, although in the mass spectra

4
Tetrahedron
of boron trifluoride etherate such a signa
structure of boron trifluoride complexes of imidazole N-oxides
12 and 2b) has been determined by X-ray diffraction study.
Compound 12 crystallizes as a benzene solvate of composition
2 × 1/6C H . The structure of formula units of this compound is
A
l i
C
s
C
pr
E
es
P
en
T
t.
E
T
he MA3.
D
NU
Con
SCR
clu
si
onIPT
In conclusion, we have developed a new simple and efficient
method for the synthesis of 2-unsubsituted 1-arylimidazoles. This
facilitates the synthesis of imidazole derivatives that are not
easily accessible by other methods. A wide range of arylamines
can enter in the reaction, most of starting materials being readily
available compounds. The condensation and reduction steps can
be carried out in one-pot.
(
1
6
6
shown at figure 2.
At the moment we are trying to apply our method to the
synthesis of 1,4- and 1,5-diarylimidazoles that are very
interesting compounds due to the great diversity of their
biological activity. The reactivity of complexes of 1-
arylimidazole N-oxides with boron trifluoride is under further
investigation.
4
4
. Experimental
.1. General
Chemicals were purchased from commercial sources and were
Figure 2. Structure of formula units of 12 × 1/6C H ; thermal
6
6
1
13
used without further purification. H and C NMR spectra were
recorded with Bruker AM 300 and Bruker AV 600 spectrometers
with the residual solvents as internal standards (N.D. Zelinsky
Institute of Organic Chemistry of RAS, Moscow). Mass-spectra
were recorded with a LKB-2000 mass spectrometer (N.D.
Zelinsky Institute of Organic Chemistry of RAS, Moscow). The
TLC analysis was performed with Merck Silica Gel 60 F254 pre-
coated plates. Column chromatography was performed with the
use of 63-200 mesh silica gel (Merck). IR spectra were recorded
on a Shimadzu IRAffinity-1 FTIR spectrophotometer. The
elemental analysis was performed on CHN analyzer 1108 (Carlo
Erba, Italy) (Kurnakov Institute of General and Inorganic
Chemistry of RAS, Moscow). The melting points were
determined on a Kofler hot stage and are uncorrected.
ellipsoids displacement parameters are given at the 50%
probability level.
Figure 3. Structure of compound 2b; thermal ellipsoids
displacement parameters are given at the 50% probability
level.
4
.2. General procedure for the synthesis of boron trifluoride
complexes of 4-acetyl-5-methyl-1-aryl-1H-imidazole 3-oxides
2).
(
Selected geometric parameters for molecules 12 and 2b are
listed in table 6. The corresponding values agree within
experimental errors.
Method A. A mixture of oxime 7 (2.00 g, 15.5 mmol), boron
trifluoride diethyl etherate (2.09 mL, 2.40 g, 16.9 mmol), 40%
formalin (2.13 mL, 2.33 g, 31.0 mmol) and amine 6 (15.5 mmol)
in isopropyl alcohol (20 mL) was stirred at 45-50 ºС for 4 h. The
solvent was removed under reduced pressure, and the residue was
treated with water. Resulting precipitate was filtered off, washed
with water and dried under reduced pressure over alkali to yield
the corresponding product 2. It may be crystallized from suitable
solvent if needed.
Method B. A mixture of oxime 7 (3.70 g, 28.7 mmol), boron
trifluoride diethyl etherate (3.90 mL, 4.49 g, 31.6 mmol) and
methylene(aryl)amine 10 (28.7 mmol) in isopropyl alcohol (50
mL) was stirred at room temperature for 4 h. The precipitate was
filtered off and washed with isopropyl alcohol yielding the
corresponding product 2. It may be crystallized from suitable
solvent if needed.
Table 6. Selected geometric parameters (Å, deg.) for 12 and
2
b.
Parameter
O1-N1
O1-B1
N1-C1
N1-C2
N2-C1
N2-C3
C2-C3
N1-O1-B1
12
2b
1.369(1)
1.501(2)
1.319(1)
1.379(2)
1.340(1)
1.390(1)
1.361(2)
113.26(8)
1.365(2)
1.501(3)
1.315(3)
1.387(2)
1.333(3)
1.385(2)
1.363(3)
111.8(2)
Boron atom in these compounds has tetrahedral geometry with
maximum coordination number four. Therefore, no additional
binding with the oxygen atom of the carbonyl group in the
compound 2b and further stabilizing this structure does not
occur. Furthermore, as mentioned above, boron trifluoride
complexes of 1-aryl-4-acetyl-5-methylimidazole N-oxides 2
compared with analogous complexes of 1-aryl-4,5-
dimethylimidazole N-oxides are less stable. Perhaps this is due to
a repulsion between the negatively charged boron atom and the
electron pairs of the carbonyl group.
4
.2.1 Boron trifluoride complex of 4-acetyl-5-methyl-1-
phenyl-1H-imidazole 3-oxide (2a). White powder; yield 61%
1
(
Method A), 80% (Method B); mp 169–173 ºС (toluene); H
NMR (300 MHz, DMSO-d6, 300 K): δ = 9.72 (s, 1H, H–Im);
7
.66 (s, 5H, H–Ar); 2.65 (s, 3H, CH ); 2.32 (s, 3H, CH ) ppm;
3 3
13
C NMR (75 MHz, DMSO-d6): δ = 188.9, 134.3, 133.1, 132.5,
30.9, 130.0, 129.3, 128.1, 126.8, 29.9, 10.4 ppm; MS (EI): m/z
1
+
+
+
(I, %) = 265 [M-F] (3), 216 [M-BF ] . (17), 49 [BF ] (25); IR
3
2
νmax (KBr): 3124, 3066, 1683, 1386, 1273, 1138, 1095, 920, 833,
-
1
7
65, 696, 603, 588, 517 cm ; Anal. C H BF N O (284): calcd
12 12 3 2 2
C 50.74, H 4.26, N 9.86; found C 50.70, H 4.21, N 9.90.

5
4
.2.2. Boron trifluoride complex of 4-ace
methylphenyl)-1H-imidazole 3-oxide (2b). White powder; yield
8% (Method A), 71% (Method B); mp 179–180 ºС (2-
A
tyl
C
-5
C
-m
E
et
P
hy
T
l-1
E
-(
D
4- MAch
N
lo
U
rof
S
or
C
m
R
(1
I
5
P
mL × 2). The extract was sequentially washed
T
with 10% solution of sodium hydrocarbonate (50 mL), 10%
solution of sodium chloride (50 mL) and dried over anhydrous
sodium sulfate. The solvent was removed under reduced
pressure. and the residue was purified by column
chromatography on silica gel (eluent: chloroform) to give the
corresponding product 1.
4
1
propanol); H NMR (300 MHz, DMSO-d6, 300 K): δ = 9.72 (s,
H, H–Im); 7.53 (d, J=8.07 Hz, 2H, H–Ar); 7.45 (d, J=8.79 Hz,
H, H–Ar); 2.64 (s, 3H, CH ); 2.42 (s, 3H, CH ); 2.31 (s, 3H,
1
2
3
3
1
CH ) ppm; H NMR (300 MHz, CDCl , 300 K): δ = 8.34 (s, 1H,
3
3
H–Im); 7.32 (d, J=8.07 Hz, 2H, H–Ar); 7.16 (d, J=7.35 Hz, 2H,
Method B. Mixture of oxime 7 (2.0 g; 15.5 mmol), boron
trifluoride diethyl etherate (2.09 mL, 2.40 g; 16.9 mmol), 40%
formalin (2.13 mL; 2.33 g; 31.0 mmol) and amine 6 (15.5 mmol)
in isopropyl alcohol (30 mL) was stirred at 45–50 ºС for 4 h.
Then ammonium formate (15.0 g, 240 mmol) and 10% Pd/C (0.5
g) were added. Reaction mixture was stirred under reflux for 3 h.
Then it was cooled, filtered, diluted with water (100 mL) and
extracted with chloroform (20 mL × 2). The extract was washed
with 10% solution of sodium chloride (50 mL) and dried over
anhydrous sodium sulfate. The solvent was removed under
reduced pressure. and the residue was purified by column
chromatography on silica gel (eluent: chloroform) to give the
corresponding product 1.
H–Ar); 2.68 (s, 3H, CH ); 2.37 (s, 3H, CH ); 2.33 (s, 3H, CH )
3
3
3
1
3
ppm; C NMR (75 MHz, DMSO-d6): δ = 188.9, 140.9, 134.3,
33.1, 132.5, 130.4, 129.9, 129.8, 127.9, 126.5, 29.9, 20.7, 10.4
ppm; MS (EI): m/z (I, %)=279 [M-F] (8), 230 [M-BF ] . (32), 49
BF ] (22); IR ν (KBr): 3138, 3074, 1683, 1578, 1512, 1389,
159, 925, 824, 793, 677, 633, 613, 586, 523 cm ; Anal.
1
+
+
3
+
[
1
2
max
-
1
C H BF N O (298): calcd C 52.38, H 4.73, N 9.40; found C
13
14
3
2
2
5
2.33, H 4.70, N 9.45.
4
.2.3. Boron trifluoride complex of 4-acetyl-5-methyl-1-(4-
methoxylphenyl)-1H-imidazole 3-oxide (2c). White powder; yield
1
3
3% (Method A), 47% (Method B); mp 154–157 ºС (toluene); H
NMR (300 MHz, DMSO-d6, 300 K): δ=9.63 (s, 1H, H–Im); 7.57
(
d, J=8.04 Hz, 2H, H–Ar); 7.17 (d, J=8.79 Hz, 2H, H–Ar); 3.86
4.3.1. 4-Acetyl-5-methyl-1-phenyl-1H-imidazole (1a). White
1
(s, 3H, OCH ); 2.64 (s, 3H, CH ); 2.30 (s, 3H, CH ) ppm; H
powder; yield 93% (Method A), 59% (Method B); mp 88–90 ºС
3
3
3
1
NMR (300 MHz, CDCl , 300 K): δ=8.44 (s, 1H, H–Im); 7.30 (d,
(heptane); H NMR (300 MHz, CDCl , 300 K): δ = 7.52–7.50
3
3
J=8.79 Hz, 2H, H–Ar); 7.09 (d, J=8.82 Hz, 2H, H–Ar); 3.89 (s,
(m, 4H, H–Im, H–Ar); 7.27–7.25 (m, 2H, H–Ar); 2.59 (s, 3H,
13
13
3
H, OCH ); 2.75 (s, 3H, CH ); 2.42 (s, 3H, CH ) ppm; C NMR
CH ); 2.45 (s, 3H, CH ) ppm; C NMR (75 MHz, CDCl3):
3
3
3
3
3
(
1
%
(
75 MHz, DMSO-d6): δ=188.8, 160.8, 134.6, 133.1, 132.2,
δ=195.4, 137.2, 135.4, 134.8, 134.0, 129.4, 128.8, 125.5, 27.0,
+
+.
28.2, 126.4, 125.0, 115.0, 55.7, 29.9, 10.3 ppm; MS (EI): m/z (I,
10.3 ppm; MS (EI): m/z (I, %) = 200 [M] (87), 185 [M-CH ]
3
+
+
+
)=295 [M-F] (3), 246 [M-BF ] . (39), 49 [BF ] (70); IR ν
(99); IR νmax (KBr): 3101, 3055, 1680, 1597, 1253, 1182, 1070,
3
2
max
-1
KBr): 3117, 3049, 1683, 1514, 1394, 1257, 831, 806, 660, 650,
926, 777, 702, 658, 631, 611, 565, 494 cm ; Anal. C H N O
12 12 2
-
1
6
15, 577, 529 cm ; Anal. C H BF N O (314): calcd C 49.72,
(200): calcd C 71.98, H 6.04, N 13.99; found C 71.95, H 6.01, N
14.05.
13
14
3
2
3
H 4.49, N 8.92; found C 49.68, H 4.43, N 8.90.
4
.2.4. Boron trifluoride complex of 4-acetyl-5-methyl-1-
4.3.2. 4-Acetyl-5-methyl-1-(4-methylphenyl)-1H-imidazole
(
2.4.6-trimethoxylphenyl)-1H-imidazole 3-oxide (2d). White
(1b). White powder; yield 86% (Method A), 32% (Method B);
1
powder; yield 55% (Method A); mp 200–204 ºС (toluene-
ethanol, 7:2); H NMR (300 MHz, DMSO-d6, 300 K): δ=9.53 (s,
mp 80–82 ºС (heptane); H NMR (300 MHz, CDCl , 300 K): δ =
3
1
7.45 (s, 1H, H–Im); 7.28 (d, J = 8.07 Hz, 2H, H–Ar); 7.12 (d, J =
1
H, H–Im); 6.49 (s, 2H, H–Ar); 3.89 (s, 3H, OCH ); 3.81 (s, 6H,
8.07 Hz, 2H, H–Ar); 2.59 (s, 3H, CH ); 2.41 (s, 3H, CH ); 2.39
3
3
3
1
13
OCH ); 2.64 (s, 3H, CH ); 2.16 (s, 3H, CH ) ppm; H NMR (300
(s, 3H, CH ) ppm; C NMR (75 MHz, CDCl ): δ=195.9, 139.3,
3
3
3
3
3
MHz, CDCl , 300 K): δ=8.18 (s, 1H, H–Im); 6.24 (s, 2H, H–Ar);
137.4, 135.7, 134.6, 132.5, 130.2, 125.6, 27.3, 21.0, 10.5 ppm;
3
+
+.
3
.89 (s, 3H, OCH ); 3.80 (s, 6H, OCH ); 2.79 (s, 3H, CH ); 2.27
MS (EI): m/z (I, %) = 214 [M] (68), 199 [M-CH ] (100); IR
3
3
3
3
13
(s, 3H, CH ) ppm; C NMR (75 MHz, DMSO-d6): δ=189.0,
νmax (KBr): 3107, 2920, 1694, 1548, 1255, 1175, 930, 822, 675,
3
-
1
1
3
63.5, 156.5, 136.0, 135.3, 133.8, 129.3, 128.6, 91.9, 57.0, 56.4,
660, 631, 561, 501 cm ; Anal. C H N O (214): calcd C 72.87,
13 14 2
+
0.3, 9.9 ppm; MS (EI): m/z (I, %)=355 [M-F] (3), 306 [M-
H 6.59, N 13.07; found C 72.85, H 6.52, N 13.10.
+
+
BF ] . (20), 49 [BF ] (10); IR ν (KBr): 3163, 2992, 2951,
2
3
2
max
-
1
4.3.3. 4-Acetyl-5-methyl-1-(4-methoxylphenyl)-1H-imidazole
848, 1683, 1512, 1387, 829, 746, 621, 586, 482 cm ; Anal.
(
1c). White powder; yield 82% (Method A), 46% (Method B);
C H BF N O (374): calcd C 48.16, H 4.85, N 7.49; found C
1
15
18
3
2
5
mp 82–86 ºС (heptane); H NMR (300 MHz, CDCl , 300 K): δ =
3
4
8.12, H 4.80, N 7.53.
7
.45 (s, 1H, H–Im); 7.15 (d, J=8.07 Hz, 2H, H–Ar); 6.98 (d,
4
.2.5. Boron trifluoride complex of 4-acetyl-5-methyl-1-(3-
J=8.07 Hz, 2H, H–Ar); 3.84 (s, 3H, OCH ); 2.57 (s, 3H, CH );
2.40 (s, 3H, CH ) ppm; C NMR (75 MHz, CDCl ): δ = 195.9,
3 3
3
3
13
nitrophenyl)-1H-imidazole 3-oxide (2e). Pale yellow powder;
yield 83% (Method A); mp 193–195 ºС (acetic acid); H NMR
300 MHz, DMSO-d6, 300 K): δ = 9.75 (s, 1H, H–Im); 8.65–
1
160.0, 137.3, 135.9, 134.8, 127.8, 127.2, 114.8, 55.5, 27.4, 10.5
+
+.
(
ppm; MS (EI): m/z (I, %)=230 [M] (63), 215 [M-CH ] (100);
3
7
.92 (m, 4H, H–Ar); 2.65 (s, 3H, CH3); 2.34 (s, 3H, CH3) ppm;
C NMR (75 MHz, DMSO-d6): δ = 188.8, 148.3, 134.8, 133.6,
33.4, 131.4, 126.5, 125.7, 122.8, 29.9, 10.4 ppm; MS (EI): m/z
IR νmax (KBr): 3107, 1662, 1375, 1362, 1305, 1066, 1030, 928,
13
-1
831, 673, 660, 627, 563, 513 cm ; Anal. C H N O (230): calcd
13
14
2
2
1
C 67.81, H 6.13, N 12.17; found C 67.75, H 6.10, N 12.15.
+
+
+
(
I, %) = 310 [M-F] (2), 261 [M-BF ] . (27), 49 [BF ] (26); IR
3
2
4
.3.4. 4-Acetyl-5-methyl-1-(2,4,6-trimethoxylphenyl)-1H-
νmax (KBr): 3175, 1693, 1587, 1357, 825, 810, 754, 743, 727,
6
calcd C 43.80, H 3.37, N 12.77; found C 43.77; H 3.32; N 12.99.
-
1
imidazole (1d). White powder; yield 98% (Method A), 45%
85, 646, 631, 602, 586, 527 cm ; Anal. C H BF N O (329):
1
12
11
3
3
4
(
Method B); mp 158–161 ºС (heptane); H NMR (300 MHz,
CDCl , 300 K): δ = 7.27 (s, 1H, H–Im); 6.19 (s, 2H, H–Ar); 3.85
3
4
1
.3. General procedure for the synthesis of 4-acetyl-5-methyl-
-aryl-1H-imidazoles (1).
(s, 3H, OCH ); 3.71 (s, 6H, OCH ); 2.59 (s, 3H, CH ); 2.25 (s,
3
3
3
13
3H, CH ) ppm; C NMR (75 MHz, CDCl ): δ = 195.9, 162.0,
3
3
1
56.7, 137.4, 136.9, 136.5, 105.5, 90.7, 55.9, 55.6, 27.3, 9.9 ppm;
Method A. Mixture of compound 2 (7.00 mmol) and iron
+
+
.
MS (EI): m/z (I, %)=290 [M] (54), 275 [M-CH ] (100); IR ν
3
max
powder (3.90 g, 79.6 mmol) in glacial acetic acid (30 mL) was
stirred under reflux for 2.5 h. Then it was cooled to room
temperature, poured into water (60 mL), extracted with
(
KBr): 3123, 3015, 2970, 2943, 2845, 1658, 1130, 1070, 947,
-1
9
6
26, 814, 683, 640, 474 cm ; Anal. C H N O (290): calcd C
15 18 2 4
2.06, H 6.25, N 9.65; found C 62.01, H 6.27, N 9.60.

6
Tetrahedron
4
.3.5. 4-Acetyl-5-methyl-1-(3-aminophe
A
ny
C
l)-
C
1H
E
-i
P
mi
T
da
E
zo
D
le MA4.
NU
5.
Ge
S
n
C
era
R
l
I
procedure for the synthesis of boron trifluoride
P
T
(1f). White powder; yield 60% (Method A), 50% (Method B);
complexes of 1-aryl-7-hydroxyimino-4,5,6,7-tetrahydro-1H-
benzimidazole 3-oxides (5).
1
mp 137–140 ºС (heptane); H NMR (300 MHz, CDCl , 300 K): δ
3
=
7.48 (s, 1H, H–Im); 7.27–7.21 (m, 1H, H–Ar); 6.75 (d, J=8.07
Mixture of oxime 9 (1.00 g, 6.40 mmol), boron trifluoride
diethyl etherate (1.74 mL, 2.00 g, 14.1 mmol), 40% formalin
0.44 mL, 0.48 g, 6.40 mmol) and amine 6 (6.40 mmol) in glacial
acetic acid (10 mL) was stirred at room temperature for 20 h. The
precipitate was filtered off and washed with glacial acetic acid (5
mL) and diethyl ether (5 mL) yielding corresponding product 5
as a white powder. In the case of amine 6c solvent was removed
under reduced pressure, and the residue was treated with water
yielding product 5c as an off-white powder.
Hz, 1H, H–Ar); 6.60–6.52 (m, 2H, H–Ar); 4.01 (bs, 2H, NH );
2
13
2
.59 (s, 3H, CH ); 2.45 (s, 3H, CH ) ppm; C NMR (75 MHz,
3 3
(
CDCl ): δ = 196.0, 148.1, 137.2, 135.7, 134.6, 130.2, 115.2,
3
+
1
2
3
14.8, 111.6, 27.3, 10.6 ppm; MS (EI): m/z (I, %)=215 [M] (72),
00 [M-CH3] (100); IR νmax (KBr): 3408, 3392, 3313, 3200,
103, 1662, 1610, 1379, 1366, 1286, 1230, 934, 791, 779 cm ;
+.
-
1
Anal. C H N O (215): calcd C 66.96, H 6.09, N 19.52; found C
12
13
3
6
6.92, H 6.03, N 19.50.
4
.4. General procedure for the synthesis of 6,6-dimethyl-1-
4
.5.1. Boron trifluoride complex of 1-phenyl-7-hydroxyimino-
aryl-4,5,6,7-tetrahydro-1H-benzimidazol-4-ones (3).
4
,5,6,7-tetrahydro-1H-benzimidazole 3-oxide (5a). White
powder; yield 65%; mp 232 ºС (decomp.); H NMR (300 MHz,
DMSO-d6, 300 K): δ = 11.25 (s, 1H, NOH); 9.51 (s, 1H, H–Im);
1
Mixture of oxime 8 (3.00 g, 17.7 mmol), boron trifluoride
diethyl etherate (2.41 mL, 2.77 g, 19.5 mmol), 40% formalin
(
2.44 mL, 2.66 g, 35.4 mmol) and amine 6 (17.7 mmol) in glacial
7.56 (s, 1H, H–Ar); 2.85–2.80 (m, 2H, CH
2
); 2.72–2.69 (m, 2H,
) ppm; C NMR (75 MHz, DMSO-
d6): δ = 145.2, 135.4, 134.2, 133.4, 130.1, 129.2, 126.7, 121.4,
13
acetic acid (50 mL) was stirred at room temperature for 50 hours.
Then iron powder (5.00 g, 89.3 mmol) was added and mixture
was stirred under reflux for 2.5 h. Then it was cooled to room
temperature, poured into water (150 mL), extracted with
chloroform (25 mL × 4). The extract was sequentially washed
with 10% solution of sodium hydrocarbonate (50 mL), 10%
solution of sodium chloride (50 mL) and dried over anhydrous
sodium sulfate. The solvent was removed under reduced
pressure, and the residue was purified by column
chromatography on silica gel (eluent: chloroform) to give the
corresponding imidazole product 3.
CH ); 1.96–1.91 (m, 2H, CH
2
2
+
22.3, 20.2, 18.9 ppm; MS (EI): m/z (I, %) = 243 [M-BF
] (5),
-O] (17), 49 [BF ] (47); IR νmax (KBr): 3489, 3143,
2
3
+
.
+
227 [M-BF
1494, 1155, 941, 903, 821, 770, 696, 611, 526, 486 cm ; Anal.
(311): calcd C 50.20, H 4.21, N 13.51; found C
50.15, H 4.19, N 13.55.
3
-
1
C H13BF N O
13 3 3 2
4
.5.2. Boron trifluoride complex of 1-(4-methoxyphenyl)-7-
hydroxyimino-4,5,6,7-tetrahydro-1H-benzimidazole 3-oxide (5c).
Off-white powder; yield 68%; mp 212 ºС (decomp.); H NMR
1
(
300 MHz, DMSO-d6, 300 K): δ = 11.28 (s, 1H, NOH); 9.50 (s,
1H, H–Im); 7.50 (d, J=8.07 Hz, 2H, H–Ar); 7.06 (d, J=8.79 Hz,
2H, H–Ar); 3.82 (s, 3H, OCH ); 2.81–2.82 (m, 2H, CH ); 2.69–
2.67 (m, 2H, CH ); 1.92–1.90 (m, 2H, CH ) ppm; C NMR (75
4
.4.1. 6,6-Dimethyl-1-phenyl-4,5,6,7-tetrahydro-1H-
benzimidazol-4-one (3a). White powder; yield 44%; mp 130–132
ºС; H NMR (300 MHz, CDCl , 300 K): δ = 7.68 (s, 1H, H–Im);
3
2
1
13
3
2
2
7
.53–7.47 (m, 3H, H–Ar); 7.31–7.29 (m, 2H, H–Ar); 2.67 (s, 2H,
MHz, DMSO-d6): δ = 160.1, 145.2, 134.2, 133.1, 128.0, 127.5,
121.5, 114.1, 55.6, 22.2, 20.2, 18.8 ppm; MS (EI): m/z (I, %) =
13
CH ); 2.44 (s, 2H, CH ); 1.09 (s, 6H, CH ) ppm; C NMR (75
MHz, CDCl ): δ = 191.1, 142.3, 138.7, 136.1, 135.1, 130.0,
2
2
3
+
+.
+
257 [M-BF
] (31), 241 [M-BF
-O] (15), 49 [BF
] (95); IR νmax
3
3
3
2
1
%
29.0, 124.5, 52.1, 35.8, 35.6, 28.5 ppm; MS (EI): m/z (I,
)=240 [M] (25), 225 [M-CH3] (3); IR νmax (KBr): 3045,
(KBr): 3502, 3292 (br), 3142, 3115, 1514, 1255, 900, 835, 827,
+
+.
-1
621, 600, 538 cm ; Anal. C14H15BF N O (341): calcd C 49.30,
3 3 3
2
7
6
956, 2924, 1662, 1597, 1504, 1390, 1180, 1107, 1059, 964, 777,
H 4.43, N 12.32; found C 49.25, H 4.40, N 12.35.
-1
67, 624, 521 cm ; Anal. C H N O (240): calcd C 74.97, H
15
16
2
4
.5.3. Boron trifluoride complex
of
1-(4-
.71, N 11.66; found C 74.92, H 6.65, N 11.70.
methoxycarbonylphenyl)-7-hydroxyimino-4,5,6,7-tetrahydro-1H-
4
.4.2. 6,6-Dimethyl-1-(4-methoxyphenyl)-4,5,6,7-tetrahydro-
benzimidazole 3-oxide (5g). White powder; yield 67%; mp 194–
196 ºС; H NMR (300 MHz, DMSO-d6, 300 K): δ = 11.26 (s,
1H, NOH); 9.62 (s, 1H, H–Im); 8.09 (d, J=8.04 Hz, 2H, H–Ar);
1
1
H-benzimidazol-4-one (3c). White powder; yield 40%; mp 182–
84 ºС (CCl –benzene, 1:1); H NMR (300 MHz, CDCl , 300 K):
1
1
4
3
δ = 7.64 (s, 1H, H–Im); 7.22 (d, J=8.07 Hz, 2H, H–Ar); 7.01 (d,
J=8.79 Hz, 2H, H–Ar); 3.85 (s, 3H, OCH ); 2.62 (s, 2H, CH );
2
CDCl ): δ = 191.1, 159.9, 152.5, 142.7, 138.9, 135.7, 127.8,
1
7.77 (d, J=8.79 Hz, 2H, H–Ar); 3.91 (s, 3H, COOCH
2.80 (m, 2H, CH ); 2.70–2.67 (m, 2H, CH ); 1.94–1.91 (m, 2H,
) ppm; C NMR (75 MHz, DMSO-d6): δ = 165.5, 145.1,
139.1, 134.2, 133.6, 132.9, 131.1, 130.0, 127.4, 121.4, 52.7, 22.3,
3
); 2.83–
3
2
2
2
1
3
13
.43 (s, 2H, CH ); 1.09 (s, 6H, CH ) ppm; C NMR (75 MHz,
CH
2
2
3
3
+.
25.9, 115.0, 55.6, 52.1, 35.9, 35.7, 35.4, 28.4, 28.3 ppm; MS
21.1, 20.2, 18.9 ppm; MS (EI): m/z (I, %) = 285 [M-BF
3
-O]
] (98); IR νmax (KBr): 3497, 3143, 1732, 1282, 947,
2
+
+.
+
(EI): m/z (I, %)=270 [M] (80), 255 [M-CH ] (10); IR νmax
(22), 49 [BF
901, 864, 818, 773, 696, 617, 532 cm ; Anal. C15H15BF N O
3 3 4
3
-
1
(
KBr): 3118, 2966, 2953, 1666, 1514, 1394, 1248, 1177, 1034,
-
1
9
64, 847, 667, 646, 586, 534 cm ; Anal. C H N O (270): calcd
(369): calcd C 48.81, H 4.10, N 11.38; found C 48.75, H 4.06, N
11.41.
16
18
2
2
C 71.09, H 6.71, N 10.36; found C 71.05, H 6.65, N 10.41.
4
.4.3. 6,6-Dimethyl-1-(4-methoxycarbonylphenyl)-4,5,6,7-
4.6. General procedure for the synthesis of 1-aryl-4,5,6,7-
tetrahydro-1H-benzimidazol-7-ones (4).
tetrahydro-1H-benzimidazol-4-one (3g). White powder; yield
2%; mp 132–134 ºС (CCl ); H NMR (300 MHz, CDCl , 300
K): δ = 8.22 (d, J=8.16 Hz, 2H, H–Ar);7.78 (s, 1H, H–Im); 7.42
d, J=8.07 Hz, 2H, H–Ar); 3.96 (s, 3H, COOCH ); 2.72 (s, 2H,
1
5
4
3
Mixture of compound 5 (5.00 mmol) and iron powder (1.96 g,
3
5.0 mmol) in glacial acetic acid (30 mL) was stirred under
(
3
13
reflux for 7 h. Then it was cooled to room temperature, poured
into water (100 mL), extracted with chloroform (25 mL × 2). The
extract was sequentially washed with 10% solution of sodium
hydrocarbonate (50 mL) and water (50 mL). The solvent was
removed under reduced pressure, and the residue was dissolved
in ethanol (30 mL). This solution was refluxed with activated
charcoal (2 g) for 0.5 h. Then it was filtered and concentrated
CH ); 2.48 (s, 2H, CH ); 1.13 (s, 6H, CH ) ppm; C NMR (75
2
2
3
MHz, CDCl ): δ = 191.1, 165.7, 141.9, 138.9, 138.5, 136.7,
31.5, 130.6, 124.2, 52.6, 52.1, 36.0, 35.9, 28.5 ppm; MS (EI):
m/z (I, %)=298 [M] (47), 283 [M-CH ] (1); IR νmax (KBr):
053, 2951, 1716, 1674, 1606, 1437, 1278, 1101, 964, 870, 775,
02, 629, 586, 505 cm ; Anal. C H N O (298): calcd C 68.44,
H 6.08, N 9.39; found C 68.40, H 6.05, N 9.35.
3
1
+
+
.
3
3
7
-1
17
18
2
3

7
under reduced pressure yielding chromato
corresponding product 4.
A
gr
C
ap
C
hic
E
al
P
lyTEpu
D
re MAth
N
is
U
stru
S
c
C
tur
R
e.
I
Crystallographic parameters and selected data for
P
T
structure refinement are listed in table 7.
4
.6.1. 1-Phenyl-4,5,6,7-tetrahydro-1H-benzimidazol-7-one
Table 7. Crystal data and structure refinement parameters for
compounds 12×1/6C H and 2b.
1
(
4a). White powder; yield 50%; mp 130–132 ºС; H NMR (300
MHz, CDCl , 300 K): δ = 7.76 (s, 1H, H–Im); 7.43–7.37 (m, 5H,
H–Ar); 3.00–2.97 (m, 2H, CH ); 2.56–2.52 (m, 2H, CH ); 2.22–
.18 (m, 2H, CH ) ppm; C NMR (150 MHz, CDCl ): δ = 188.2,
56.5, 141.8, 135.9, 129.2, 129.0, 125.8, 125.5, 39.2, 25.1, 23.8
ppm; MS (EI): m/z (I, %) = 212 [M] (62), 184 [M-CO] (35); IR
νmax (KBr): 3090, 3055, 2945, 1666 (br), 1068, 1011, 899, 764,
46, 692, 598, 557, 511, 430 cm ; Anal. C H N O (212): calcd
C 73.57, H 5.70, N 13.20; found C 73.55, H 5.65, N 13.24.
6
6
3
Compound
12
2b
2
2
13
2
1
2
3
empirical
formula
C H BF N O
C H BF N O
2
1
2
13
3
2
12 14
3
2
+
+.
formula
weight
269.05
298.07
183(2)
-
1
7
13 12 2
T [K]
123(2)
4
.6.2. 1-(4-Methoxyphenyl)-4,5,6,7-tetrahydro-1H-
benzimidazol-7-one (4c). White powder; yield 45%; mp 144–146
1
Crystal
system
trigonal
monoclinic
ºС; H NMR (300 MHz, CDCl , 300 K): δ = 7.66 (s, 1H, H–Im);
3
7
3
.27 (d, J=8.79 Hz, 2H, H–Ar); 6.95 (d, J=8.79 Hz, 2H, H–Ar);
.85 (s, 3H, CH ); 2.95–2.93 (m, 2H, CH ); 2.56–2.52 (m, 2H,
3
2
13
Space group
a [Å]
R-3
P2 /c
CH ); 2.21–2.17 (m, 2H, CH ) ppm; C NMR (150 MHz,
1
2
2
CDCl ): δ = 188.3, 159.7, 156.5, 141.9, 128.8, 126.6, 125.9,
3
+
24.0099(9)
24.0099(9)
11.1957(5)
-
12.1349(16)
9.9424(13)
11.8147(6)
104.568(2)
1379.6(3)
4
1
(
14.2, 55.6, 39.1, 25.1, 23.7 ppm; MS (EI): m/z (I, %) = 242 [M]
86), 214 [M-CO] (15); IR νmax (KBr): 3092, 1645 (br), 1516,
+.
b [Å]
1
390, 1253, 1223, 1032, 1016, 837, 661, 631, 590, 567, 525, 426
-
1
cm ; Anal. C H N O (242): calcd C 69.41, H 5.82, N 11.56;
14
14
2
2
c [Å]
found C 69.35, H 5.81, N 11.61.
4
.6.3. 1-(4-Methoxycarbonylphenyl)-4,5,6,7-tetrahydro-1H-
β [°]
benzimidazol-7-one (4g). White powder; yield 55%; mp 162–165
1
3]
ºС; H NMR (300 MHz, CDCl , 300 K): δ = 8.13 (d, J=8.04 Hz,
V [Å
5589.4(4)
18
3
2
3
H, H–Ar); 7.73 (s, 1H, H–Im); 7.45 (d, J=8.07 Hz, 2H, H–Ar);
.94 (s, 3H, CH ); 2.98–2.94 (m, 2H, CH ); 2.58–2.54 (m, 2H,
Z
3
2
13
CH ); 2.22–2.18 (m, 2H, CH ) ppm; C NMR (150 MHz,
2
2
-
3
CDCl ): δ = 188.2, 166.0, 157.4, 141.7, 139.5, 130.5, 130.3,
D
calc g cm
1.439
1.435
3
1
2
1
5
5
25.5, 125.1, 52.4, 39.1, 25.1, 23.6 ppm; MS (EI): m/z (I, %) =
70 [M] (83), 242 [M-CO] (26); IR νmax (KBr): 3097, 2953,
+
+
.
-1
µ [mm ]
F(000)
0.122
0.123
732 (br), 1386, 1282 (br), 1012, 897, 862, 771, 700, 613, 601,
-
1
61, 518, 434 cm ; Anal. C H N O (270): calcd C 66.66, H
2502
616
15
14
2
3
.22, N 10.36; found C 66.61, H 5.19, N 10.41.
reflections
4
.7. 4-acetyl-1-(4-methoxyphenyl)-5-methyl-1,3-dihydro-2H-
1
imidazol-2-one (11). White powder; mp 236-240 ºС; H NMR
Collected/uniq
13527/2953
224
14420/3668
246
(
300 MHz, DMSO-d6, 300 K): δ = 10.55 (s, 1H, NH); 7.24 (d,
J=8.79 Hz, 2H, H–Ar); 7.04 (d, J=8.07 Hz, 2H, H–Ar); 3.80 (s,
Number of
parameters
13
3
H, OCH ); 2.31 (s, 3H, CH ); 2.17 (s, 3H, CH ) ppm; C NMR
3 3 3
(75 MHz, DMSO-d6): δ = 186.5, 159.0, 151.8, 130.5, 129.3,
1
2
1
26.3, 118.8, 114.4, 55.4, 28.1, 11.4 ppm; MS (EI): m/z (I, %) =
2
+
+.
GOF on F
1.072
0.981
46 [M] (27), 231 [M-CH ] (3); IR ν (KBr): 3300-2900 (br),
3
max
654-1685 (br), 1170, 1070, 821, 797, 754, 619, 590, 528, 467
-
1
R / wR [I >
0.0348/0.0910
0.0559/0.1218
0.1218/0.1451
0.446 and -0.499
1
2
cm ; Anal. C H N O (246): calcd C 63.40, H 5.73, N 11.38;
found C 63.43, H 5.70, N 11.41.
13
14
2
3
2
σ(I)]
4
.8. X-ray determination. Crystals of compounds 12×1/6C H6
R / wR (all
0.0435/0.0939
6
1
2
and 2b were grown from benzene and toluene solutions
respectively. For each of compounds, a single crystal was set at a
Bruker
monochromatized Mo-K radiation, ω scan technique) under a
stream of cooled nitrogen, where crystallographic parameters and
experimental reflections were measured. Data reduction was
performed using SAINT program. The structures were solved
by direct methods and refined by least squares on F in
anisotropic approximation for non-hydrogen atoms. Positions of
H atoms were calculated geometrically. The refinement of H
atoms was carried out in isotropic approximation. In 2b, the BF3
group was found to be rotationally disordered over three
positions with near equal occupancies (0.36:0.32:0.32). Structure
data)
SMART-APEX-II
diffractometer
(graphite-
Max/min
0.202 and -
0.249
α
residuals
3
[
e/A ]
22
23
All the calculations were performed using SHELXTL-Plus software .
2
The experimental data for structures 12×1/6C H and 2b were
6 6
deposited with the Cambridge Crystallographic Data Centre
(CCDC registration numbers are 971013 and 971014,
respectively). Copies of data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2, EZ, UK
(fax: +44 (0) 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk.
1
2×1/6C H6 represents a benzene solvate, the center of the
6
benzene ring being situated at the special point at 3-fold axis. So
/6 part of the solvate molecule falls per one main molecule in
1

8
Tetrahedron
ACCEPTED MANUSCRIPT
Supplementary data
Supplementary data associated with this article can be found
in the online version, at doi:
References and notes
1
2
.
.
Pastor, I.M.; Yus, M. Curr. Chem. Biol. 2009, 1, 65.
Yamada, M.; Yura, T.; Morimoto, M.; Harada, T.; Yamada, K.;
Honma, Y.; Kinoshita, M.; Sugiura, M. J. Med. Chem. 1996, 39, 596.
Wang, L.; Woods, K.W.; Li, Q.; Barr, K. J.; McCroskey, R.W.;
3
.
Hannick, S.M.; Gherke, L.; Credo, R.B.; Hui, Y.-H.; Marsh, K.; Warner, R.;
Lee, J.Y.; Zielinski-Mozng, N.; Frost, D.; Rosenberg, S.H.; Sham, H.L. J.
Med. Chem. 2002, 45, 1697.
4
.
Romine, J.L.; Martin, S.W.; Gribkoff, V.K.; Boissard, C.G.;
Dworetzky, S.I.; Natale, J.; Li, Y.; Gao, Q.; Meanwell, N.A.; Starrett, J.E. J.
Med. Chem. 2002, 45, 2942.
5
.
Almansa, C.; Alfón, J.; de Arriba, A.F.; Cavalcanti, F.L.;
Escamilla, I.; Gómez, L.A.; Miralles, A.; Soliva, R.; Bartrolí, J.; Carceller, E.;
Merlos, M.; García-Rafanell, J. J. Med. Chem. 2003, 46, 3463.
6
.
Kiyomori, A.; Marcoux, J.-F.; Buchwald, S. L. Tetrahedron Lett.
999, 40, 2657.
Collman, J.P.; Zhong, M.; Zeng, L.; Costanzo, S. J. Org. Chem.
001, 66, 1528.
Nunami, K.-I.; Yamada, M.; Fukui, T.; Matsumoto, K. J. Org.
Chem. 1994, 59, 7635.
Katritzky, A.R.; Cheng, D.; Musgrave, R. P. Heterocycles. 1997,
1
2
7
.
8
.
9
.
4
4, 67.
0. Pawar, V.G.; De Borggraeve, W.M.; Robeyns, K.; Van Meervelt,
L.; Compernolle, F.; Hoornaert, G. Tetrahedron Lett. 2006, 47, 5451.
1
1
1. Ferguson, I.J.; Schofield, K. J. Chem. Soc., Perkin Trans. 1. 1975,
2
75.
1
1
1
1
2. Bartnic, R.; Hahn, W.E.; Mloston, G. Rocz. Chem. 1977, 51, 49.
3. Lettau, Н. Z. Chem. 1970, 10, 462.
4. Cerecetto, H.; Gerpe, A.; González, M. Synthesis. 2004, 16, 2678.
5. Alcázar, J.; Begtrup, M.; de la Hoz, A. J. Chem. Soc., Perkin
Trans. 1. 1995, 2467.
1
6. Mityanov, V.S.; Perevalov, V.P.; Tkach I.I. Chem. Heterocycl.
Compd. 2013, 48, 1793.
1
7. Collman, J.P.; Zhong, M.; Zhang, C.; Costanzo, S. J. Org. Chem.
2
001, 66, 7892.
1
1
2
2
2
8. Wolff, L. Justus Liebigs Ann. Chem. 1902, 325, 129.
9. Sprung, M.A. Chem. Rev. 1940, 26, 297.
0. Lifschitz, J. Chem. Ber. 1913, 46, 3233.
1. Treibs, A.; Kuhn, A. Chem. Ber. 1957, 90, 1691.
2. SAINT. Version 6.02. Bruker AXS Inc. Madison, Wisconsin,
USA, 2001.
2
3. SHELXTL-Plus.Version 5.10. Bruker AXS Inc. Madisonm
Wisconsin, USA, 1997.

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Supporting Information
New regiocontrolled synthesis of 2-unsubstituted 1-aryl-4- and 1-aryl-5-acylimidazoles
a
b
a
a
Vitaly S. Mityanov , Ludmila G. Kuz’mina , Valery P. Perevalov and Iosif I. Tkach
a
Department of Fine Organic Synthesis and Chemistry of Dyes, D. Mendeleyev University of Chemical Technology of Russia, Miusskaya Sq., 9,
Moscow 125047, Russia.
b
Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Science, Leninskii Pr., 31, Moscow 117907, Russia.
E-mail: iosif_tkach@mail.ru
1
13
H, C NMR, EIMS and IR spectra.

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H2O
DMSO-d6
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.95
.90
.85
.80
.75
.70
.65
.60
.55
.50
.45
.40
.35
.30
.25
.20
.15
.10
.05
0
3
00 MHz, DMSO-d6
DMSO-d6
-
BF3
O
O
+
N
1.00
CH3
N
0
0
.75
.50
CH3
0.25
0
2
a
2
.82
3.00
3
.0
2.5
Chemical Shift (ppm)
2.0
1.5
1
.02
4.88
3.00
1
8
17
16
15
14
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Chemical Shift (ppm)

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1.00
0.95
0.90
0.85
0.80
0.75
0.70
0.65
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
3
00 MHz, DMSO-d6
-
BF3
1.00
0.75
0.50
0.25
0
O
O
+
N
CH3
N
CH3
2
b
1.03
4.12
H C
3
9
.5
9.0
8.5
8.0
7.5
Chemical Shift (ppm)
DMSO-d6
1.00
0.75
0.50
0.25
0
3.00
6.29
2
.75
2.50
2.25
2.00
Chemical Shift (ppm)
1.03
4.12
6.29
18
17
16
15
14
13
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11
10
9
8
7
6
5
4
3
2
1
0
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-2
Chemical Shift (ppm)

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0
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0
0
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0
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0
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0
0
.00
.95
.90
.85
.80
.75
.70
.65
.60
.55
.50
.45
.40
.35
.30
.25
.20
.15
.10
.05
0
3
00 MHz, CDCl3
-
BF3
O
O
+
N
CH3
N
CH3
2
b
H C
3
0
.91
4.03
2.91 6.00
1
8
17
16
15
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0
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0
.00
.95
.90
.85
.80
.75
.70
.65
.60
.55
.50
.45
.40
.35
.30
.25
.20
.15
.10
.05
0
300 MHz, DMSO-d6
-
O
BF3
1
0
0
0
.00
.75
.50
.25
0
O
+
N
CH3
N
0
.97
.5
1.96 2.11
7.5 7.0
CH3
9
9.0
8.5
8.0
Chemical Shift (ppm)
2c
DMSO-d6
O
CH3
1
0
0
0
.00
.75
.50
.25
0
3
.15
2.83
3.00
4
.0
3.5
3.0
2.5
2.0
Chemical Shift (ppm)
0
.97
2.11
7
3.15
4
3.00
1
8
17
16
15
14
13
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11
10
9
8
6
5
3
2
1
0
-1
-2
Chemical Shift (ppm)

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0.95
0.90
0.85
0.80
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0.70
0.65
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
1
.00
.75
3
00 MHz, CDCl3
0
-
BF3
O
O
0.50
+
N
0.25
CH3
N
0
0
.94
2.05
2.06
7.0
CH3
8
.5
8.0
7.5
Chemical Shift (ppm)
2
c
O
CH3
1.00
0.75
0.50
0.25
0
3.20
2.97
3.00
2.5
4
.0
3.5
3.0
Chemical Shift (ppm)
0.94
2.06
7
3.20
4
3.00
18
17
16
15
14
13
12
11
10
9
8
6
5
3
2
1
0
-1
-2
Chemical Shift (ppm)

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DMSO-d6
1.00
0.95
0.90
0.85
0.80
0.75
0.70
0.65
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
3
00 MHz, DMSO-d6
-
BF3
O
1.00
0.75
O
+
N
0
.50
.25
0
CH3
O
0
N
H C
3
9
.70
2.91
2.5
3.00
2.0
CH3
O
4.5
4.0
3.5
3.0
Chemical Shift (ppm)
CH3
O
2d
CH3
0.89
2.11
9.70
4
2.913.00
18
17
16
15
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7
6
5
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2
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Chemical Shift (ppm)

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1
.00
.75
1.00
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0.90
0.85
0.80
0.75
0.70
0.65
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0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
3
00 MHz, DMSO-d6
0
-
BF3
O
0.50
O
+
N
0.25
0
CH3
0
.96
1.76
0.97 1.10
8.0
N
9.5
9.0
8.5
7.5
CH3
Chemical Shift (ppm)
O N
2
DMSO-d6
2
e
1.00
0
0
0
.75
.50
.25
0
2.60
3.00
2.25
3
.00
2.75
2.50
Chemical Shift (ppm)
0.96
1.76 1.10
8
3.00
18
17
16
15
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13
12
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10
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7
6
5
4
3
2
1
0
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Chemical Shift (ppm)

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0.95
0.90
0.85
0.80
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0.70
0.65
0.60
0.55
0.50
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0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
1
.00
0.75
3
00 MHz, CDCl3
0
.50
.25
0
O
0
N
3.73
7.5
1.90
CH3
N
8
.0
7.0
6.5
Chemical Shift (ppm)
CH3
1
a
1.00
0.75
0.50
0.25
0
3
.05 3.00
3.5
3.0
2.5
2.0
Chemical Shift (ppm)
3.69
3.05
18
17
16
15
14
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10
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8
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6
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4
3
2
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0.95
0.90
0.85
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0.70
0.65
0.60
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0.50
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0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
1
0
0
0
.00
.75
.50
.25
0
3
00 MHz, CDCl3
O
N
0
.88 2.12 2.07
CH3
8.0
7.5
7.0
6.5
Chemical Shift (ppm)
N
CH3
1
.00
.75
.50
.25
0
1
b
H C
3
0
0
0
3
.00 6.49
3.5
3.0
2.5
2.0
Chemical Shift (ppm)
2.12
6.49
18
17
16
15
14
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0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
1
.00
.75
0
3
00 MHz, CDCl3
0.50
O
0.25
N
0
0
.72
1.79
2.19
7.00
CH3
N
7
.50
7.25
6.75
Chemical Shift (ppm)
CH3
1
c
1.00
0.75
0.50
O
CH3
0.25
0
3
.11
2.82
2.5
3.00
4.0
3.5
3.0
Chemical Shift (ppm)
0.72 2.19
3.11
3.00
18
17
16
15
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0
.00
.95
.90
.85
.80
.75
.70
.65
.60
.55
.50
.45
.40
.35
.30
.25
.20
.15
.10
.05
0
0.75
0
0
.50
.25
0
300 MHz, CDCl3
1
.05
1.97
O
7
.5
7.0
6.5
6.0
N
Chemical Shift (ppm)
CH3
O
N
H C
3
CH3
O
CH3
1
.00
.75
O
1d
0
CH3
0.50
0
.25
0
2
.95 6.17
2.80
3.00
4
.0
3.5
3.0
2.5
Chemical Shift (ppm)
1
.05
1.97
6
6.17
3.00
1
8
17
16
15
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Chemical Shift (ppm)

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0.35
0.30
0.25
0.20
0.15
0.10
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0
1
0
0
.00
.75
.50
3
00 MHz, CDCl3
O
0.25
0
N
1
.09
0.98
7.25
0.89
6.75
1.82
6.50
CH3
7.50
7.00
Chemical Shift (ppm)
N
CH3
H N
2
1
f
1
0
0
.00
.75
.50
0.25
0
1
.60
3.013.00
2.5
4.0
3.5
3.0
Chemical Shift (ppm)
1.09
1.82
1.60
3.01
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
0
-1
-2
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
1.00
0.95
0.90
0.85
0.80
0.75
0.70
0.65
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
1
.00
300 MHz, CDCl3
O
0.75
0.50
N
0.25
N
0
1
.15 3.03 2.08
CH3
H C
3
8
.0
7.5
7.0
Chemical Shift (ppm)
3
a
1.00
0
0
0
.75
.50
.25
0
1
.93 1.94
6.00
1.0
2.5
2.0
1.5
Chemical Shift (ppm)
3.03
1.94
6.00
1
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
0
-1
-2
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
.00
.95
.90
.85
.80
.75
.70
.65
.60
.55
.50
.45
.40
.35
.30
.25
.20
.15
.10
.05
0
3
00 MHz, CDCl3
1.00
O
0
0
.75
.50
N
N
0.25
0
CH3
H C
3
1
.02
2.23 2.15
7.0
8
.5
8.0
7.5
6.5
3c
Chemical Shift (ppm)
O
CH3
1
0
0
0
.00
.75
.50
.25
0
3.10
2.01 1.80
6.00
3.5
3.0
2.5
2.0
1.5
1.0
Chemical Shift (ppm)
2
.23
3.10
2.01
6.00
1
1
8
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
0
-1
-2
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
1.00
0.95
0.90
0.85
0.80
0.75
0.70
0.65
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
3
00 MHz, CDCl3
1
0
0
0
.00
.75
.50
.25
0
O
N
N
CH3
2.01
1.12
2.12
7.5
H C
3
8.5
8.0
Chemical Shift (ppm)
3
g
MeOOC
1.00
0
0
0
.75
.50
.25
0
3
.14
2.03 1.95
6.00
1.0
4.0
3.5
3.0
2.5
2.0
1.5
Chemical Shift (ppm)
2
.01
2.12
3.14
2.03
6.00
1
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
0
-1
-2
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
DMSO-d6
3
00 MHz, DMSO-d6
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
.00
.95
.90
.85
.80
.75
.70
.65
.60
.55
.50
.45
.40
.35
.30
.25
.20
.15
.10
.05
0
-
BF3
O
1
0
.00
.75
+
N
0.50
0
.25
0
N
0.75
0.91
5.08
1
1
10
9
8
Chemical Shift (ppm)
HON
DMSO-d6
5a
1.00
.75
0.50
0
0
.25
0
4.00
2.45
2
.5
2.0
1.5
Chemical Shift (ppm)
0
.75
11
0.91
5.08
4.00
2.45
2
1
8
17
16
15
14
13
12
10
9
8
7
6
5
4
3
1
0
-1
-2
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
H2O DMSO-d6
3
00 MHz, DMSO-d6
1.00
0.95
0.90
0.85
0.80
0.75
0.70
0.65
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
BF3
-
O
1
0
0
0
.00
.75
.50
.25
0
+
N
N
0
.65
0.87
1.89 1.97
7
1
1
10
9
8
HON
Chemical Shift (ppm)
H2O
DMSO-d6
5c
O
CH3
1
.00
.75
.50
.25
0
0
0
0
2.90
.0
3.68
2.00
4
3.5
3.0
2.5
2.0
1.5
Chemical Shift (ppm)
0
.65
0.87
1.891.97
7
2.90
3.68
2.00
18
17
16
15
14
13
12
11
10
9
8
6
5
4
3
2
1
0
-1
-2
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
DMSO-d6
3
00 MHz, DMSO-d6
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
.00
.95
.90
.85
.80
.75
.70
.65
.60
.55
.50
.45
.40
.35
.30
.25
.20
.15
.10
.05
0
BF3
-
O
+
N
1
0
0
0
.00
.75
.50
.25
0
N
0
.73
0.80
1.871.85
8
HON
1
1
10
9
Chemical Shift (ppm)
5g
MeOOC
DMSO-d6
1
0
0
0
.00
.75
.50
.25
0
2.82
4
3.65
3.00
5
3
2
1
Chemical Shift (ppm)
0
.73
11
0.80
1.87
8
2.82
4
3.65
3.00
1
8
17
16
15
14
13
12
10
9
7
6
5
3
2
1
0
-1
-2
Chemical Shift (ppm)

ACCEPTED MANUSCRIPT
Chloroform-d
Chloroform-d
1.00
0.95
0.90
0.85
0.80
0.75
0.70
0.65
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0
3
00 MHz, CDCl3
1
0
0
0
.00
.75
.50
.25
0
N
N
1
.00
4.93
O
9.0
8.5
8.0
7.5
7.0
6.5
Chemical Shift (ppm)
4a
1
0
0
0
.00
.75
.50
.25
0
1
.89
1.97
2.5
2.00
4.0
3.5
3.0
2.0
1.5
Chemical Shift (ppm)
4.93
1.89 2.00
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
0
-1
-2
Chemical Shift (ppm)