952
LEBEDEV et al.
ppm: 0.83 d (6H, CH3), 2.00 m (1H, CH), 2.44 d (2H,
CH2), 7.4 br.s (NH, COOH), 19.68 (1H, COOH).
Mass spectrum, m/z: 212 [M]+ , 179 [M CH3 H2O]+,
170 [M + H C3H7]+, 165 [M 2CH3 OH]+, 152
[M C3H7 OH]+, 124 [M 2CO2]+. Found, %: C
51.04; H 5.74. C9H12N2O4. Calculated, %: C 50.94;
H 5.70.
Diethyl 2-isopropylimidazole-4,5-dicarboxylate
(VIb). mp 188 190 C. 1H NMR spectrum, , ppm:
1.26 d (6H, CH3), 1.27 t (6H, CH3), 3.10 m (1H, CH),
4.27 q (4H, OCH2), 13.10 (1H, NH). Mass spectrum:
m/z 254 [M]+ . Found, %: C 56.74; H 7.16.
C12H18N2O4. Calculated, %: C 56.68; H 7.13. Hydro-
1
chloride: mp 98 105 C. H NMR spectrum, , ppm:
1.25 d (6H, CH3), 1.28 t (6H, CH3), 3.17 m (1H, CH),
4.27 q (4H, OCH2), 7.32 t (2H, NH+2). Found, %: C
49.32; H 6.68. C12H19ClN2O4. Calculated, %: C
49.57; H 6.59.
2-(2-Pyridyl)imidazole-4,5-dicarboxylic acid
(Vd). Decomposition point 270 C. 1H NMR spectrum,
, ppm: 3.8 br.s (NH, COOH), 7.43 t (1H, Harom),
7.92 t (1H, Harom), 8.10 d (1H, Harom), 8.63 d (1H,
Harom), 19.80 (1H, COOH). Mass spectrum, m/z: 233
[M]+ , 189 [M CO2]+, 171 [M CO2 H2O]+, 145
[M 2CO2]+. Found, %: C 51.63; H 3.06. C10H7N3O4.
Calculated, %: C 51.51; H 3.03.
Diethyl 2-isobutylimidazole-4,5-dicarboxylate
1
(VIc) hydrochloride. mp 95 100 C. H NMR spec-
trum, , ppm: 0.87 d (6H, CH3), 1.29 t (6H, CH3),
2.08 m (1H, CH), 2.66 d (2H, CH2), 4.29 q (4H,
OCH2), 7.32 t (2H, NH+2). Found, %: C 51.06; H 7.04.
C13H21ClN2O4. Calculated, %: C 51.23; H 6.94.
Esterification of dicarboxylic acids Va Vd
(general procedure). Thionyl chloride, 0.2 mol, was
added dropwise to a suspension of 0.05 mol of com-
pound Va Vd in 100 ml of anhydrous ethanol or
methanol (the mixture spontaneously warmed up to
45 55 C), and the mixture was heated for 1.5 2.5 h
under reflux until it became homogeneous. The mix-
ture was then evaporated under reduced pressure, the
residue was treated with 100 150 ml of anhydrous
diethyl ether, and the precipitate of VIa VId or VIIa
hydrochloride was filtered off and dried under reduced
pressure. Yield almost quantitative. To isolate free
bases VIa VId and VIIa, the corresponding hydro-
chloride was added under vigorous stirring to a con-
centrated solution of a required amount of sodium
ethoxide or methoxide in ethanol or methanol, res-
pectively. The mixture was evaporated, and the re-
sidue was washed with water and dried under reduced
pressure. The yields of pure compounds VIa VId and
VIIa were 98 99%. Alternatively, a 12% solution of
sodium carbonate was added dropwise to an alcoholic
solution of the corresponding hydrochloride to attain
pH 4 5, maintaining the temperature below 12 C. The
mixture was evaporated by half and cooled to 5 C.
The free bases separated as difficultly crystallizable
oils; they crystallized only after treatment with cold
diethyl ether. The yields did not exceed 80%.
Diethyl 2-(2-pyridyl)imidazole-4,5-dicarboxylate
1
(VId) trihydrochloride. mp 110 116 C. H NMR
spectrum, , ppm: 1.30 t (6H, CH3), 4.28 q (4H,
OCH2), 7.36 t (4H, NH+2, NH+), 7.54 t (1H, Harom),
8.03 t (1H, Harom), 8.18 d (1H, Harom), 8.70 d (1H,
Harom). Found, %: C 41.93; H 4.70. C14H18Cl3N3O4.
Calculated, %: C 42.18; H 4.55.
Dimethyl 2-phenylimidazole-4,5-dicarboxylate
1
(VIIa). mp 204 207 C. H NMR spectrum, , ppm:
3.84 s (6H, OCH3), 7.48 m (3H, Harom), 8.08 d (2H,
Harom), 13.75 (1H, NH). Mass spectrum, m/z: 260
[M]+ . Found, %: C 59.91; H 4.68. C13H12N2O4.
Calculated, %: C 60.00; H 4.65.
Alkylation of 2-substituted imidazole-4,5-di-
carboxylic acid esters (general procedure). A mix-
ture of 0.05 mol of ester VIa or VIIa, 0.055 mol of
DBU, and 0.35 mol of bromide VIIIa in 100 ml of
acetonitrile or DMF was stirred for 27 h at the boiling
point (in acetonitrile) or for 24 h at 110 C (in DMF).
In the latter case, strong tarring occurred. The solvent
and excess dihalide VIIIa were removed under re-
duced pressure, and the residue (a viscous oil) was
1
analyzed by H NMR spectroscopy. The residue ob-
tained from the reaction mixture in acetonitrile was
subjected to chromatography on silica gel in a glass
column, 1.5 m 5 cm, using hexane benzene (4:1) as
eluent. The first fraction (Rf 0.22) contained pure
compound IXa or Xa; yield 18 and 11%, respectively.
Diethyl 2-phenylimidazole-4,5-dicarboxylate
1
(VIa). mp 200 202 C. H NMR spectrum, , ppm:
1.31 t (6H, CH3), 4.29 q (4H, OCH2), 7.48 m (3H,
Harom), 8.08 d (2H, Harom), 13.70 (1H, NH). Mass
spectrum: m/z 288 [M]+ . Found, %: C 62.39; H 5.60.
C15H16N2O4. Calculated, %: C 62.49; H 5.59. Hydro-
Diethyl 1-(2-chloroethyl)-2-phenylimidazole-4,5-
1
dicarboxylate (IXa). mp 122 125 C. H NMR spec-
1
chloride: mp 120 125 C. H NMR spectrum, , ppm:
trum, , ppm: 1.31 t (6H, CH3), 3.78 t (2H, CH2),
4.29 q (4H, OCH2), 4.58 t (2H, CH2), 7.58 m (3H,
Harom), 7.66 d (2H, Harom). Mass spectrum: m/z 350
[M]+ . Found, %: C 58.07; H 5.57. C17H19ClN2O4.
Calculated, %: C 58.21; H 5.46.
1.30 t (6H, CH3), 4.28 q (4H, OCH2), 7.34 t (2H,
NH+2), 7.57 m (3H, Harom), 8.14 d (2H, Harom). Found,
%: C 55.28; H 5.36. C15H17ClN2O4. Calculated, %:
C 55.48; H 5.28.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 5 2007