REACTION OF ETHYL 3-(1-ADAMANTYL)-3-OXOPROPANOATE
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However, compounds II–IV reacted with hydrazine
hydrochloride in ethanol (under “milder” conditions)
to give pyrazoles V–VII (Scheme 2). In this case, the
reaction involved only ketone carbonyl groups in the
substrate, whereas the ester group remained intact.
Ethyl 3-(1-adamantyl)-5-(4-fluorophenyl)-1H-
pyrazole-4-carboxylate (V). Hydrazine hydrochlo-
ride, 0.04 g (0.39 mmol), was added to a solution of
0.12 g (0.32 mmol) of compound II in 5 ml of ethanol,
the mixture was stirred for 16 h at room temperature
and heated for 3 h at 80°C, and the precipitate was
filtered off and recrystallized from ethanol. Yield
0.09 g (80%), colorless crystals, mp 176–178°C. IR
spectrum, ν, cm–1: 3240 (N−H), 2908, 2851 (C−HAd),
1713 (C=O), 1608 (C–Carom), 840, 813 (δC–Harom).
1H NMR spectrum, δ, ppm: 1.00 t (3H, CH3), 1.71–
2.12 m (15H, Ad), 3.99 q (2H, OCH2), 7.14 d (2H,
Ethyl 3-(1-adamantyl)-2-(4-fluorobenzoyl)-3-
oxopropanoate (II). A mixture of 2.00 g (8 mmol) of
ester I [9] and 0.18 g (8 mmol) of metallic sodium in
30 ml of anhydrous diethyl ether was stirred for 24 h at
room temperature, 1.27 g (8 mmol) of 4-fluorobenzoyl
chloride was added over a period of 2 h, and the mix-
ture was heated for 2 h under reflux, cooled, poured
into water, and acidified with 2% sulfuric acid. The
organic phase was separated and dried over sodium
sulfate, the solvent was distilled off, and the residue
was recrystallized from petroleum ether (bp 40–60°C).
Yield 1.87 g (63%), colorless crystals, mp 126–128°C.
IR spectrum, ν, cm–1: 2908, 2854 (C−HAd), 1744
(C=O, ester), 1705, 1682 (C=O, ketone), 1597
Harom), 8.22 d (2H, Harom), 10.05 br.s (1H, NH). Found,
%: C 71.89; H 6.92; N 7.56. C22H25FN2O2. Calculated,
%: C 71.74; H 6.79; N 7.61.
Compounds VI and VII were synthesized in a simi-
lar way.
Ethyl 3-(1-adamantyl)-5-(2,3,4,5-tetrafluoro-
phenyl)-1H-pyrazole-4-carboxylate (VI) was synthe-
sized from 0.12 g (0.28 mmol) of compound III and
0.04 g (0.39 mmol) of hydrazine hydrochloride. Yield
0.08 g (71%), colorless crystals, mp 301°C. IR spec-
trum, ν, cm–1: 3234 (N−H), 2908, 2851 (C−HAd), 1710
(C=O), 1604 (C–Carom), 837 (δC–Harom). 1H NMR spec-
trum, δ, ppm: 1.17 t (3H, CH3), 1.79–2.23 m (15H,
Ad), 4.15 q (2H, OCH2), 8.10 q (1H, Harom), 9.88 br.s
(1H, NH). Found, %: C 62.64; H 5.34; N 6.98.
C22H22F4N2O2. Calculated, %: C 62.56; H 5.21; N 6.64.
1
(C–Carom), 852, 821 (δC–Harom). H NMR spectrum, δ,
ppm: 1.09 t (3H, CH3), 1.49–1.92 m (15H, Ad), 4.04 q
(2H, OCH2), 6.42 s (1H, CH), 7.34 d (2H, Harom),
7.98 d (2H, Harom). Found, %: C 70.85; H 6.54.
C22H25FO4. Calculated, %: C 70.97; H 6.72.
Compounds III and IV were synthesized in a simi-
lar way.
Ethyl 3-(1-adamantyl)-3-oxo-2-(2,3,4,5-tetra-
fluorobenzoyl)propanoate (III) was synthesized from
2.00 g (8 mmol) of ester I and 1.70 g (8 mmol) of
2,3,4,5-tetrafluorobenzoyl chloride. Yield 2.66 g
(78%), colorless crystals, mp 266–268°C. IR spectrum,
ν, cm–1: 2908, 2854 (C−HAd), 1740 (C=O, ester), 1686,
1647 (C=O, ketone), 1593 (C–Carom), 806, 787, 763
Ethyl 3-(1-adamantyl-5-(2-chloro-4-fluorophen-
yl)-1H-pyrazole-4-carboxylate (VII) was synthesized
from 0.12 g (0.30 mmol) of compound IV and 0.04 g
(0.39 mmol) of hydrazine hydrochloride. Yield 0.075 g
(63%), colorless crystals, mp 210–211°C. IR spectrum,
ν, cm–1: 3230 (N−H), 2908, 2851 (C−HAd), 1710
(C=O), 1604 (C–Carom), 842, 810 (δC–Harom). 1H NMR
spectrum, δ, ppm: 1.05 t (3H, CH3), 1.85–2.10 m (15H,
Ad), 4.07 q (2H, OCH2), 7.87 m and 8.22 m (3H,
1
(δC–Harom). H NMR spectrum, δ, ppm: 0.90 t (3H,
CH3), 1.26–2.18 m (15H, Ad), 4.22 q (2H, OCH2),
5.73 s (1H, CH), 7.35 q (1H, Harom). Found, %:
C 61.99; H 5.36. C22H22F4O4. Calculated, %: C 61.97;
H 5.16.
H
arom), 10.10 br.s (1H, NH). Found, %: C 65.78;
H 5.23; N 6.94. C22H24ClFN2O2. Calculated, %:
C 65.51; H 5.46; N 6.95.
Ethyl 3-(1-adamantyl)-2-(2-chloro-4-fluoroben-
zoyl)-3-oxopropanoate (IV) was synthesized from
2.00 g (8 mmol) of ester I and 1.54 g (8 mmol) of
2-chloro-4-fluorobenzoyl chloride. Yield 1.66 g (51%),
colorless crystals, mp 179–180°C. IR spectrum, ν,
cm–1: 2908, 2854 (C−HAd), 1732 (C=O, ester), 1697
(C=O, ketone), 1596 (C–Carom), 914, 872 (δC–Harom).
1H NMR spectrum, δ, ppm: 1.19 t (3H, CH3), 1.63–
1.96 m (15H, Ad), 4.13 q (2H, OCH2), 5.79 s (1H,
CH), 7.27 m (2H, Harom), 7.70 m (1H, Harom). Found,
%: C 65.27; H 6.05. C22H24O4ClF. Calculated, %:
C 65.02; H 5.91.
The IR spectra were measured in KBr on
a Shimadzu FTIR-8400S spectrometer. The 1H NMR
spectra were recorded on a Bruker AM 300 instrument
at 300 MHz using DMSO-d6 as solvent and tetra-
methylsilane as internal reference. The elemental com-
positions were determined on a Thermo Finnigan Flash
1112 NCH analyzer. The purity of the products was
checked by TLC (Silufol) and GLC.
This study was performed under financial support
by the Ministry of Education and Science of the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 6 2010