Polyfunctional imidazoles: III?* synthesis of 1-Aryl-2,4-dihalo-1H-imidazole-5-carboxylic acids and their derivatives

Article abstract of DOI:10.1134/S1070428011080124

1-Aryl-4-chloro(2,4-dichloro)-1H-imidazole-5-carbaldehydes reacted with N-bromosuccinimide affording bromides of 1-aryl-2-bromo(2,4-dichloro)-1H- imidazole-5-carboxylic acids which were converted into the corresponding acids, esters, and amides.

Full text of DOI:10.1134/S1070428011080124

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 8, pp. 1194−1198. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © V.A. Chornous, A.N. Grozav , M.V. Vovk, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 8, pp. 1176−1180.
Polyfunctional Imidazoles: ІIІ.* Synthesis
of 1-Aryl-2,4-dihalo-1H-imidazole-5-carboxylic Acids
and Their Derivatives
V. A. Chornousa, A. N. Grozav a, and M. V. Vovkb
aBukovinskii State Medical University, Chernovtsy, 58000 Ukraine
e-mail: chornous@inbox.ru
bInstitute of Organic Chemistry, National Academy of Sciences of Ukraine, Ukraine
Received June 26, 2010
Abstract—1-Aryl-4-chloro(2,4-dichloro)-1H-imidazole-5-carbaldehydes reacted with N-bromosuccinimide
affording bromides of 1-aryl-2-bromo(2,4-dichloro)-1H-imidazole-5-carboxylic acids which were converted into
the corresponding acids, esters, and amides.
DOI: 10.1134/S1070428011080124
Imidazole-5-carboxylic acids and their derivatives are
extremely important synthetic and biological objects. For
instance, a high antihypertensive action was observed in
the 2-butyl-4-chloro-1-{[2'-(1H-1,2,3-triazol-4-yl)-1,1'-
biphenyl-4-yl]-methyl}-1H-imidazole-5-carboxylic acid,
active metabolite of Losartan [2].
The derivatives of halogenated in the ring imidazole-
5-carboxylic acids, in particular, methyl 1-methyl-2,4-di-
bromo-1H-5-imidazolecarboxylate [6], are worth special
attention. The latter ester is used in the total synthesis of
a number of imidazoquinoxaline mutagenes [7–9]. How-
ever the published procedures for preparation of this type
compounds [6] are multistage, are characterized by the
formation of side products and low yields of the target
substances (12–28%).
Esters of R-1-(1-phenylethyl)-1H-imidazole-5-car-
boxylic acid are efficient inhibitors of 11β-hydroxylase
[3], N-arylpiperazinamides of 1-(4-cyanobenzyl)
imidazole-5-carboxylic acid are prone to inhibit farnes-
yltransferase [4], and N-aryl-N-methyl(quinazolon-4-yl)
amides, NO synthase [5].
We developed a convenient procedure for the
synthesis of dihalo-substituted imidazole-5-carboxylic
acids and their derivatives underlain by the application
O
N
Br
Cl
Cl
Cl
N
N
N
HX
O
Br
C(O)Br
Br
C(O)X
CHO
N
N
N
Ar
IIа_IId
Ar
Ar
Iа_Id
IIIа_IIId, IVа_IVd,
Vа_Vc
I, II, Ar = Ph (a), 4-FC6H4 (b), 4-ClC6H4 (c), 4-MeOC6H4 (d); III, X = OH, Ar = Ph (a), 4-FC6H4 (b), 4-ClC6H4 (c),
4-MeOC6H4 (d); IV, X = OMe, Ar = Ph (a), 4-ClC6H4 (b); X = OEt, Ar = 4-FC6H4 (c); X = OPh, Ar = 4-MeOC6H4 (d); V,
Ar = 4-MeOC6H4, X = NHMe (a); Ar = 4-FC6H4, X = NHPh (b); Ar = Ph, X = N(CH2)2O(CH2)2 (c).
––––––––––––––––––––––
*
For Communication II, see [1].
1194

POLYFUNCTIONAL IMIDAZOLES: ІIІ.
1195
of available 1-aryl-4-chloro-5-formylimidazoles Ia–Id
[10]. The capability of N-bromosuccinimide to convert
aliphatic [11] and aromatic [12, 13] aldehydes into the
corresponding acyl bromides and also to brominate
the imidazole ring [6] was an important argument in
favor of the use of this reagent for the bifunctional
bromination of 5-formylimidazoles Ia–Id. The latter
treated with N-bromosuccinimide in boiling CCl4 in
the presence of the initiator of the radical bromination
(2,2'-azobisisobutyronitrile) within 7 h are converted into
bromides of 2-bromo-4-chloroimidazole-5-carboxylic
acids IIa–IId which without additional purification
were used in the preparation of the corresponding acids
IIIa–IIId, esters IVa–IVd, and amides Va–Vc obtained
in high yields.
5-carboxylic acids. It was established by an example of
aldehyde Ia that under these conditions only the oxidative
chlorination of the formyl group occurred without
involving into the reaction of the position 2 of the ring
resulting in the formation of the chloride of 1-phenyl-4-
chloroimidazole-5-carboxylic acid giving on hydrolysis
the corresponding acid VI. Therefore the preparation
of 2,4-dichloro-5-imidazolecarboxylic acids and their
derivatives was performed by the reaction of 1-aryl-2,4-
dichloro-5-imidazolecarbaldehydes VIIa–VIIc [1] with
the more available N-bromosuccinimide. The treatment of
compounds VIIa–VIIc with this reagent in boiling CCl4
in the presence of 2,2'-azobisisobutyronitrile within 0.5 h
furnished acyl bromides VIIIa–VIIIc which in their turn
were used for the preparation of acids IXa–IXc, ester X,
and amides XIa, XIb.
The use of N-chlorosuccinimide in a similar procedure
failed to provide chlorides of the 2,4-dichloroimidazole-
The composition and the structure of all compounds
Cl
Cl
Cl
N
N
N
HX
Cl
C(O)Br
Cl
C(O)X
Cl
CHO
N
N
N
Ar
Ar
Ar
IXа_IXc, X, XIа, XIb
VIIIа_VIIIc
VIIа_VIIc
VII, VIII, Ar = Ph (a), 4-FC6H4 (b), 4-MeOC6H4 (c); IX, X = OH, Ar = Ph (a), 4-FC6H4 (b), 4-MeOC6H4 (c); X, Ar =
4-FC6H4, X = OMe; XI, Ar = 4-MeOC6H4, X = HNMe (a); Ar = Ph, X = N(CH2)2O(CH2)2 (b).
obtained were confirmed by elemental analyses, IR, 1H
and 13C NMR spectra.
acid to pH 4–5, the formed precipitate was filtered off,
washed with water, dried, and crystallized from 70%
aqueous acetic acid.
EXPERIMENTAL
2-Bromo-1-phenyl-4-chloro-1H-imidazole-5-car-
boxylic acid (IIIa). Yield 80%, mp 188–189°C. IR spec-
trum, cm–1: 2510–2890 (COOH), 1715 (C=O). 1H NMR
spectrum, δ, ppm: 7.30–7.35 m (5Harom), 13.30 br.s (1H,
COOH). 13C NMR spectrum, δ, ppm: 122.89 (C5), 124.79,
127.70, 128.93, 129.55 (CAr), 135.00 (C2), 136.71 (C4),
158.12 (COOH). Found, %: C 39.67; H 2.12; N 9.55.
C10H6BrClN2O2. Calculated, %: C 39.83; H 2.01; N 9.29.
IR spectra were recorded on a spectrophotometer UR-
20 from pellets with KBr. 1H and 13C NMR spectra were
recorded on a spectrometer Bruker Advance DRX-500
(500.13, 125.75 MHz respectively), internal reference
TMS.
1-Aryl-2-bromo-4-chloro-1H-imidazole-5-carbox-
ylic acids IIIa–IIId. To a solution of 0.01 mol of aldehyde
Ia–Id in 20 ml of CCl4 was added 4.45 g (0.025 mol) of
N-bromosuccinimide, 0.16 g (0.001 mol) of 2,2'-azo-
bisisobutyronitrile, and the mixture was boiled for 7 h.
The reaction mixture was cooled, and the precipitate of
succinimide was filtered off. The filtrate was evaporated,
the residue was dissolved in 10 ml of 0.1 NaOH solution
in water-ethanol mixture (1 : 1), the solution was left
standing for 1 h, then it was diluted with water to 30 ml
and filtered. The filtrate was acidified with hydrochloric
2-Bromo-1-(4-fluorophenyl)-4-chloro-1H-
imidazole-5-carboxylic acid (IIIb). Yield 79%,
mp 190–192°C. IR spectrum, cm–1: 2580–2860 (COOH),
1
1710 (C=O). H NMR spectrum, δ, ppm: 7.37–7.54 m
(4Harom), 13.32 br.s (1H, COOH). 13C NMR spectrum, δ,
ppm: 115.82 d (CAr, 2JC–F 22.8 Hz), 122.97 (C5), 125.13,
1
130.27, 162.33 d (CAr, JC–F 251.8 Hz), 133.08 (C2),
135.07 (C4), 158.20 (COOH). Found, %: C 37.77; H 1.52;
N 8.85. C10H5CrClFN2O2. Calculated, %: C 37.59;
H 1.58; N 8.77.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

CHORNOUS et al.
1196
2-Bromo-4-chloro-1-(4-chlorophenyl)-1H-imidaz-
idazole-5-carboxylate (IVc). Yield 79%, mp 60–63°C.
1
ole-5-carboxylic acid (IIIc). Yield 81%, mp 199–201°C.
IR spectrum, cm–1: 2560–2880 (COOH), 1710 (C=O).
1H NMR spectrum, δ, ppm: 7.50 d (2Harom, J 8.2 Hz),
7.60 d (2Harom, J 8.2 Hz), 13.40 br.s (1H, COOH).
13C NMR spectrum, δ, ppm: 122.91 d (C2), 124.90,
129.03, 129.90, 134.32 (CAr), 135.13 (C2), 135.65 (C4),
158.16 (COOH). Found, %: C 35.57; H 1.62; N 8.55.
C10H5CrCl2N2O2. Calculated, %: C 35.75; H 1.50; N 8.34.
IR spectrum, cm–1: 1725 (C=O). H NMR spectrum,
δ, ppm: 1.02 t (3H, CH3, J 7.0 Hz), 4.06 q (2H, CH2,
J 7.0 Hz), 7.39–7.57 m (4Harom). Found, %: C 41.27;
H 2.52; N 7.95. C12H9CrClFN2O2. Calculated, %:
C 41.47; H 2.61; N 8.06.
Phenyl 2-bromo-1-(4-methoxyphenyl)-4-chloro-
1H-imidazole-5-carboxylate (IVd). Yield 71%,
mp 127–128°C. IR spectrum, cm-1: 1730 (C=O). 1H NMR
2-Bromo-1-(4-methoxyphenyl)-4-chloro-1H-im-
idazole-5-carboxylic acid (IIId). Yield 71%, mp 188–
190°C. IR spectrum, cm–1: 2520–2870 (COOH), 1710
(C=O). 1H NMR spectrum, δ, ppm: 3.83 s (3H, CH3O),
7.05 d (2Harom, J 8.0 Hz), 7.36 d (2Harom, J 8.0 Hz),
13.25 br.s (1H, COOH). 13C NMR spectrum, δ, ppm:
55.38 (CH3O), 114.10 (CAr), 122.96 (C5), 125.32, 129.03
(CAr), 129.35 (C2), 134.86 (C4), 158.18 (COOH), 159.73
(CAr). Found, %: C 41.67; H 2.42; N 8.65. C11H8CrCl-
N2O2. Calculated, %: C 41.87; H 2.56; N 8.88.
spectrum, δ, ppm: 3.82 s (3H, CH3O), 7.05 d (2Harom
J 9.0 Hz), 7.12 d (2Harom, J 9.0 Hz), 7.27 t (1Harom
J 8.0 Hz), 7.41 m (2Harom), 7.52 d (2Harom J 8.5 Hz).
Found, %: C 49.67; H 2.82; N 6.65. C17H12CrClN2O3.
Calculated, %: C 50.09; H 2.97; N 6.87.
,
,
1-Aryl-2-bromo-4-chloro-1H-imidazole-5-carbox-
amides Va–Vc. To a solution of 0.01 mol of aldehyde Ia,
Ib, Id in 20 ml of CCl4 was added 4.45 g (0.025 mol)
of N-bromosuccinimide, 0.16 g (0.001 mol) of 2,2'-azo-
bisisobutyronitrile, and the mixture was boiled for 7 h.
The reaction mixture was cooled, and the precipitate of
succinimide was filtered off. To the filtrate 0.025 mol of
amine was added, and the mixture was boiled for 2 h.
The solvent was evaporated, the residue was washed
with water, filtered, dried, and crystallized from 80%
aqueous ethanol.
1-Aryl-2-bromo-4-chloro-1H-imidazole-5-carbox-
ylates IVa–IVd. To a solution of 0.01 mol of aldehyde
Ia–Id in 20 ml of CCl4 was added 4.45 g (0.025 mol)
of N-bromosuccinimide, 0.16 g (0.001 mol) of 2,2'-az-
abisisobutyronitrile, and the mixture was boiled for 7 h.
The reaction mixture was cooled, and the precipitate of
succinimide was filtered off. To the filtrate 0.012 mol of
alcohol or phenol was added, and the mixture was boiled
for 2 h. The solvent was evaporated, the residue was
washed with water, filtered, dried, and crystallized from
80% aqueous ethanol.
2-Bromo-1-(4-methoxyphenyl)-4-chloro-N-meth-
yl-1H-imidazole-5-carboxamide (Va). Yield 73%,
mp 127–128°C. IR spectrum, cm–1: 3310 (NH), 1660
(C=O). 1H NMR spectrum, δ, ppm: 2.65 d (3H, CH3N,
J 4.5 Hz), 3.84 s (3H, CH3O), 7.06 d (2Harom, J 9.0 Hz),
7.29 d (2Harom, J 9.0 Hz), 8.23 m (1H, NH). 13C NMR
spectrum, δ, ppm: 25.89 (CH3N), 55.46 (CH3O), 114.26
(CAr), 121.89 (C5), 127.53, 128.78 (CAr), 127.71 (C2),
128.23 (C4), 157.50 (C=O), 159.82 (CAr). Found, %:
C 41.67; H 3.02; N 12.05. C12H11CrClN3O2. Calculated,
%: C41.83; H 3.22; N 12.19.
Methyl 2-bromo-1-phenyl-4-chloro-1H-imidazole-
5-carboxylate (IVa). Yield 76%, mp 88–89°C. IR spec-
1
trum, cm–1: 1725 (C=O). H NMR spectrum, δ, ppm:
3.64 s (3H, CH3O), 7.38 m (2Harom), 7.56 m (3Harom).
13C NMR spectrum, δ, ppm: 51.72 (CH3O), 121.90 (C5),
125.58, 127.76, 128.99, 129.71 (CAr), 135.27 (C2), 136.40
(C4), 157.27 (C=O). Found, %: C 40.97; H 2.42; N 8.55.
C11H8BrClN2O2. Calculated, %: C 41.87; H 2.56; N 8.88.
2-Bromo-1-(4-fluorophenyl)-4-chloro-N-phenyl-
1H-imidazole-5-carboxamide (Vb). Yield 75%,
Methyl 2-bromo-4-chloro-1-(4-chlorophenyl)-
mp 153–155°C. IR spectrum, cm–1: 3290 (NH), 1660
1
1H-imidazole-5-carboxylate (IVb). Yield 81%, mp
(C=O). H NMR spectrum, δ, ppm: 7.09 t (1Harom
J 7.5 Hz), 7.32 t (2Harom, J 8.0 Hz), 7.51 t (2Harom
,
,
1
142–144°C. IR spectrum, cm–1: 1725 (C=O). H NMR
spectrum, δ, ppm: 3.67 s (3H, CH3O), 7.57 d (2Harom
,
J 8.0 Hz), 7.56–7.60 m (4Harom), 10.64 s (1H, NH).
Found, %: C 48.57; H 2.52; N 10.35. C16H10CrClFN3O.
Calculated, %: C 48.70; H 2.55; N 10.65.
J 8.8 Hz), 7.61 d (2Harom, J 8.8 Hz). 13C NMR spec-
trum, δ, ppm: 51.77 (CH3O), 121.93 d (C5), 125.59,
129.05, 129.79, 134.48 (CAr), 135.28 (C2), 135.34 (C4),
157.27 (C=O). Found, %: C 37.57; H 1.92; N 7.85.
C11H7CrCl2N2O2. Calculated, %: C 37.75; H 2.02; N 8.00.
4-[(2-Bromo-1-phenyl-4-chloro-1H-imidazol-5-yl)-
carbonyl]morpholine (Vc). Yield 80%, mp 135–140°C.
IR spectrum, cm–1: 1665 (C=O). 1H NMR spectrum, δ,
ppm: 3.49–3.54 m (8H, CH2), 7.43 m (2Harom), 7.69 m
Ethyl 2-bromo-1-(4-fluorophenyl)-4-chloro-1H-im-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

POLYFUNCTIONAL IMIDAZOLES: ІIІ.
1197
(3Harom). 13C NMR spectrum, δ, ppm: 42.31 (CH2), 46.54
(CH2), 65.97 (CH2), 66.43 (CH2), 120.97 (C5), 125.56,
126.93, 127.24, 129.43 (CAr), 129.88 (C2), 134.96 (C4),
157.04 (C=O). Found, %: C 45.17; H 3.42; N 11.25.
C14H13BrClN3O2. Calculated, %: C 45.37; H 3.54;
N 11.34.
C10H6Cl2N2O2. Calculated, %: C 46.72; H 2.35; N 10.90.
2,4-Dichloro-1-(4-fluorophenyl)-1H-imidazole-
5-carboxylic acid (IXb). Yield 78%, mp 205–207°C.
IR spectrum, cm–1: 2580–2850 (COOH), 1705 (C=O).
1H NMR spectrum, δ, ppm: 7.37–7.60 m (4Harom),
13.37 br.s (1H, COOH). 13C NMR spectrum, δ, ppm:
2
1-Phenyl-4-chloro-1H-imidazole-5-carboxylic acid
(VI). To a solution of 0.01 mol of aldehyde Ia in 20 ml of
CCl4 was added 3.34 g (0.025 mol) of N-chlorosuccin-
imide, 0.16 g (0.001mol) of 2,2'-azobisisobutyronitrile,
and the mixture was boiled for 7 h. The reaction mixture
was cooled, and the precipitate of succinimide was filtered
off. The filtrate was evaporated, the residue was dissolved
in 10 ml of 0.1 NaOH solution in water-ethanol mixture
(1 : 1), the solution was left standing for 1 h, then it was
diluted with water to 30 ml and filtered. The filtrate was
acidified with hydrochloric acid to pH 4–5, the formed
precipitate was filtered off, washed with water, dried, and
crystallized from 70% aqueous acetic acid. Yield 80%,
mp 128–130°C. IR spectrum, cm–1: 2560–2910 (COOH),
115.90 d (CAr, JC–F 22.8 Hz), 122.05 (C5), 130.17,
1
134.09, 162.20 d (CAr, JC–F 251.5 Hz), 131.92 (C2),
135.02 (C4), 158.24 (COOH). Found, %: C 43.50; H 1.97;
N 10.34. C10H5Cl2FN2O2. Calculated, %: C 43.67;
H 1.83; N 10.18.
2,4-Dichloro-1-(4-methoxyphenyl)-1H-imidazole-
5-carboxylic acid (IXc). Yield 71%, mp 188–189OC.
IR spectrum, cm-1: 2580–2930 (COOH), 1710 (C=O).
1H NMR spectrum, δ, ppm: 3.84 s (3H, CH3O), 7.07 d
(2Harom, J 7.5 Hz), 7.45 d (2Harom, J 7.5 Hz), 13.24 br.s
(1H, COOH). 13C NMR spectrum, δ, ppm: 55.43 (CH3O),
114.10 (CAr), 122.08 (C5), 129.22 (CAr), 128.92 (CAr),
133.93 (C2), 135.28 (C4), 158.30 (COOH), 159.81 (CAr).
Found, %: C 46.27; H 2.72; N 9.55. C11H8Cl2N2O3. Cal-
culated, %: C 46.02; H 2.81; N 9.76.
1
1710 (C=O). H NMR spectrum, δ, ppm: 7.44–7.5 m
(5Harom), 8.04 s (1H, H2). The proton of the carboxy group
is in equilibrium with the deuteron of the heavy water
present in the DMSO-d6. 13C NMR spectrum, δ, ppm:
119.25 (C5), 126.19, 128.84, 128.89, 135.79 (CAr), 135.63
(C2), 140.48 (C4). Found, %: C 53.85; H 3.12; N 12.55.
C10H7ClN2O2. Calculated, %: C 53.95; H 3.17; N 12.58.
Methyl 2,4-dichloro-1-(4-fluorophenyl)-1H-im-
idazole-5-carboxylate (X). To a solution of 0.01 mol
of aldehyde VIIb in 10 ml of CCl4 was added 2.14 g
(0.012 mol) of N-bromosuccinimide, 0.16 g (0.001mol)
of 2,2'-azobisisobutyronitrile, and the mixture was boiled
for 0.5 h. The reaction mixture was cooled, and the pre-
cipitate of succinimide was filtered off. To the filtrate
5 ml of methanol was added, and the mixture was boiled
for 2 h. The solvent was evaporated, the residue was
washed with water, filtered, dried, and crystallized from
80% aqueous ethanol. Yield 81%, mp 103–105°C. IR
spectrum, cm–1: 1730 (C=O). 1H NMR spectrum, δ, ppm:
3.65 s (3H, CH3O), 7.40 m (2Harom), 7.60 m (2Hapom).
13C NMR spectrum, δ, ppm: 51.78 (CH3O), 116.01 d
1-Aryl-2,4-dichloro-1H-imidazole-5-carboxylic
acids IXa–IXc. To a solution of 0.01 mol of aldehyde
VIIa–VIIc in 10 ml of CCl4 was added 2.14 g (0.012 mol)
of N-bromosuccinimide, 0.16 g (0.001mol) of 2,2'-azo-
bisisobutyronitrile, and the mixture was boiled for 0.5 h.
The reaction mixture was cooled, and the precipitate of
succinimide was filtered off. The filtrate was evaporated,
the residue was dissolved in 10 ml of 0.1 NaOH solu-
tion in water-ethanol mixture (1:1), the solution was left
standing for 1 h, then it was diluted with water to 30 ml
and filtered. The filtrate was acidified with hydrochloric
acid to pH 4–5, the formed precipitate was filtered off,
washed with water, dried, and crystallized from 70%
aqueous acetic acid.
2
(CAr, JC–F 22.6 Hz), 121.10 (C5), 130.06, 131.56 (C2),
1
134.35, 162.40 d (CAr, JC–F 250.84 Hz), 135.72 (C4),
157.37 (C=O). Found, %: C 45.57; H 2.22; N 9.85.
C11H7Cl2FN2O2. Calculated, %: C 45.70; H 2.44; N 9.69.
1-Aryl-2,4-dichloro-1H-imidazole-5-carboxamides
XIa, XIb. To a solution of 0.01 mol of aldehyde VIIa,
VIIc in 10 ml of CCl4 was added 2.14 g (0.012 mol) of
N-bromosuccinimide, 0.16 g (0.001mol) of 2,2'-azobis-
isobutyronitrile, and the mixture was boiled for 0.5 h.
The reaction mixture was cooled, and the precipitate of
succinimide was filtered off. To the filtrate 0.025 mol of
amine was added, and the mixture was boiled for 2 h.
The solvent was evaporated, the residue was washed
2,4-Dichloro-1-phenyl-1H-imidazole-5-carboxylic
acid (IXa). Yield 72%, mp 212–215°C. IR spectrum,
1
cm–1: 2600–2920 (COOH), 1705 (C=O). H NMR
spectrum, δ, ppm: 7.48–7.67 m (5Harom), 13.15 br.s (1H,
COOH). 13C NMR spectrum, δ, ppm: 119.30 (C5), 126.17,
128.40, 128.90, 135.40 (CAr), 138.58 (C2), 137.65 (C4),
158.07 (COOH). Found, %: C 46.50; H 2.46; N 10.98.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011

CHORNOUS et al.
1198
Berger, M.L., Bioorg. Med. Chem. Lett., 2009, vol. 19,
with water, filtered, dried, and crystallized from 80%
p. 4284.
aqueous ethanol.
4. Dinsmore, C.J., Bergman, J.M., Wei, D.D., Zartman, C.B.,
Davide, J.P., Greenberg, I.B., Liu, D., O’Neill, T.J.,
Gibbs, J.B., Koblan, K.S., Kohl, N.E., Lobell, R.B.,
Chen, I.-W., McLoughlin, A., Ohal, T.V., Grahom, S.L.,
Hortman, G.D., and Williams, T.M., Bioorg. Med. Chem.
Lett., 2001, vol. 11, p. 537.
2,4-Dichloro-1-(4-methoxyphenyl)-N-methyl-
1H-imidazole-5-carboxamide (XIa). Yield 73%,
mp 132–134°C. IR spectrum, cm–1: 3290 (NH), 1665
(C=O). 1H NMR spectrum, δ, ppm: 2.63 d (3H, CH3N,
J 4.8 Hz), 3.84 s (3H, CH3O), 7.07 d (2Harom, J 8.0 Hz),
7.32 d (2Harom, J 8.0 Hz), 8.33 m (1H, NH). Found, %:
C 47.77; H 3.42; N 14.45. C12H11Cl2N3O2. Calculated,
%: C 48.02; H 3.69; N 14.00.
5. Bonnefous, E., Payne, J.E., Roppe, J., Zhuoug, H.,
Chen, X., Symous, K., Woug, L., Severonce, D., Walsh, J.P.,
Yazdani, N., Shiau, A.K., Noble, S., Rix, P., Rao, T.S.,
Hassiung, C.A., and Smith, N.D., J. Org. Chem., 2009,
vol. 52, p. 3047.
4-[(2,4-Dichloro-1-phenyl-1H-imidazol-5-yl)-car-
bonyl]morpholine (XIb). Yield 80%, mp 120–122°C.
IR spectrum, cm–1: 1665 (C=O). 1H NMR spectrum, δ,
ppm: 3.48–3.56 m (8H, CH2), 7.48 m (2Harom), 7.59 m
(3Harom). 13C NMR spectrum, δ, ppm: 41.96 (CH2),
46.77 (CH2), 65.86 (CH2), 66.40 (CH2), 124.97 (C5),
125.80, 126.92, 129.44, 129.83 (CAr), 131.83 (C2), 133.99
(C4), 156.90 (C=O). Found, %: C 51.37; H 3.92; N 12.75.
C14H13Cl2N3O2. Calculated, %: C 51.55; H 4.02; N 12.88.
6. O’Connell, J.F., Parguette, J., Yelle, E.W., Wang, W., and
Repoport, H., Synthesis, 1988, p. 767.
7. Kcosai, H., Shiomo, T., Sumigura, T., and Nishmura, S.,
Chem. Lett., 1987, vol. 10, p. 675.
8. Kosai, H., Yomaizumi, T., Sumigura, T., and Nishimura, S.,
Chem. Lett., 1987, vol. 10, p. 485.
9. Kosai, H., Yomaizumi, T., Wakabayashi, K., Naga, O.M.,
Sumigura, T., Yokoyama, T., Miyazava, T., and
Nishimura, S., Chem. Lett., 1980, vol. 9, p. 1391.
REFERENCES
10. Chornous, V.A., Bratenko, M.K., and Vovk, M.V., Zh. Org.
Khim., 2009, vol. 45, p. 1219.
1. Chornous, V.A., Grozav, A.M., Rusanov, E.B.,
Nesterenko, A.M., and Vovk, M.V., Zh. Org. Khim., 2011,
vol. 47, p. 699.
11. Marko, I.E. and Mekhalfia,A. and Tetrahedron Lett., 1990,
vol. 21, p. 7237.
2. Wong, P.C., Price, W.A., Chiu, A.T., Duncia, J.V.,
Corini, D.I., Wexler, R.R., Johnson, A.L., and
Timmermons, P.S., J. Pharm. Exp. Terapevtics., 1990,
vol. 255, p. 211.
12. Couture, A., Deniau, E., Woisel, P., and Grandclaudon, P.,
Synthesis., 1997, p. 1439.
13. Couture, A., Deniau, E., Grandclaudon, P., and Lebrun, S.,
Synlett., 1997, p. 1475.
3. Atucha, E., Hommerschmidt, F., Siegkort, W., and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 8 2011