Trifluoroacetylation of ethyl 2,4ꢀdioxopentanoate
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 3, March, 2007
559
25% aq. NH3 (50 mL) at 0 °C for 1 h, the precipitate that formed
was filtered off, washed with water, and dried. Recrystallization
from aq. EtOH (1 : 1) does not lead to a change in its melting
points. The yield was 3.07 g (70%), m.p. 250—252 °C (subl.).
Found (%): C, 40.61; H, 1.91; N, 6.71. C7H4F3NO3. Calcuꢀ
lated (%): C, 40.59; H, 1.95; N, 6.76. IR, ν/cm–1: 3381, 3244,
3189, 1719, 1663, 1640, 1610. 1H NMR (DMSOꢀd6), δ: 7.00 (d,
1 H, H(5), J = 2.3 Hz); 7.13 (d, 1 H, H(3), J = 2.3 Hz); 8.19,
8.37 (both s, 1 H each, NH).
is predisposed to heterocyclization into ethyl 6ꢀtrifluoroꢀ
methylcomanate.
Experimental
IR spectra were recorded on a Perkin—Elmer Spectrum
1
BXꢀII spectrometer in KBr pellets. Н NMR, 13С NMR, and
19F NMR spectra were recorded on a Bruker DRXꢀ400 specꢀ
trometer with operating frequencies of 400.1 MHz (1H),
100.6 MHz (13С), and 376.5 MHz (19F), internal standards,
Me4Si (1H, 13C) and C6F6 (19F).
4ꢀHydroxyꢀ6ꢀ(trifluoromethyl)pyridineꢀ2ꢀcarboxamide (5).
Ester 2 (3.0 g, 12.7 mmol) was gradually added to a stirred
solution of 20% aq. NH3 (15 mL). The reaction mixture was
brought to boiling temperature in an open flask, while the formed
homogeneous solution was concentrated to ~5 mL in volume.
After the reaction mixture was cooled down, the formed crystals
were filtered off and washed with water (10 mL), the filtrate was
separated and again concentrated to ~5 mL in volume. After the
mixture was cooled down, the new crop of the product was
filtered off and washed with water (10 mL) again. The procedure
with the filtrate was repeated two more times. The yield was
2.46 g (94%), colorless crystals, m.p. 202—204 °C. Recrystalliꢀ
zation from water does not lead to a change in its melting points.
Found (%): C, 40.83; H, 2.23; N, 13.74. C9H5F3N2O2. Calcuꢀ
lated (%): 40.79; H, 2.45; N, 13.59. IR, ν/cm–1: 3415, 3347,
Ethyl 4ꢀoxoꢀ6ꢀ(trifluoromethyl)ꢀ4Hꢀpyranꢀ2ꢀcarboxylate (2).
Anhydrous THF (30 mL), ButOH (0.25 mL), sodium derivative
of ethyl 2,4ꢀdioxopentanoate (1)7 (35.5 g, 0.2 mol), and
CF3CO2Et (42.6 g, 0.3 mol) were added to an alcoholic solution
of NaOEt obtained by dissolution of sodium (6.9 g, 0.3 mol) in
anhydrous EtOH (100 mL). The resulting reaction mixture was
refluxed for 12 h and then concentrated in vacuo (10—12 Torr).
The residue was thoroughly stirred with a mixture of ice (500 g)
and conc. H2SO4 (25 mL), the organic product thus obtained
was extracted with a toluene—ether (2 : 1) mixture (150 mL).
The extract was first distilled at atmospheric pressure and then
in vacuo and the fraction with b.p. 140—150 °C (10—12 Torr)
was collected. The distillate was mixed with EtOH (50 mL) and
cooled down to –25 °C, the crystallized product was filtered off,
washed with cold EtOH, and dried. The yield was 22.1 g (47%),
colorless crystals, m.p. 43—44 °C. Found (%): C, 45.64; H, 3.16.
1
3200, 1700, 1617, 1587. H NMR (DMSOꢀd6), δ: 7.34 (d, 1 H,
H(5), J = 2.2 Hz); 7.62 (d, 1 H, H(3), J = 2.2 Hz); 7.81, 7.91
(both s, 1 H each, CONH); 11.87 (s, 1 H, NH). 19F NMR
(DMSOꢀd6), δ: 95.91 (s, CF3).
C9H7F3O4. Calculated (%): C, 45.78; H, 2.99. IR, ν/cm–1
:
1
3076, 1752, 1672, 1639, 1610. H NMR (CDCl3), δ: 1.42 (t,
3 H, Me, J = 7.1 Hz); 4.46 (q, 2 H, OCH2, J = 7.1 Hz); 6.80 (d,
1 H, H(5), J = 2.3 Hz); 7.16 (d, 1 H, H(3), J = 2.3 Hz).
13С NMR (CDCl3), δ: 13.90 (Me); 63.40 (CH2); 115.93 (q,
С(5), 3JC,F = 2.6 Hz); 118.04 (q, CF3, 1JC,F = 274.2 Hz); 119.97
(C(3)); 152.88 (q, С(6), 2JC,F = 40.1 Hz); 152.90 (C(2)); 158.68
(O—C=O); 177.42 (C=O). 19F NMR (CDCl3), δ: 90.50 (s, CF3).
4ꢀOxoꢀ6ꢀ(trifluoromethyl)ꢀ4Hꢀpyranꢀ2ꢀcarboxylic acid (3).
Ester 2 (2.0 g, 8.5 mmol) was refluxed in 20% aq. HCl (20 mL)
for 2 h. Then the reaction mixture was cooled down to 0 °C, the
crystalline product was filtered off, washed with 20% aq. HCl,
and dried. The yield was 1.54 g (88%), colorless crystals, m.p.
171—172 °C. Recrystallization from water does not lead to a
change in its melting points. Found (%): C, 40.44; H, 1.16.
C7H3F3O4. Calculated (%): C, 40.40; H, 1.45. 1H NMR
(DMSOꢀd6), δ: 7.01 (d, 1 H, H(5), J = 2.3 Hz); 7.18 (d, 1 H,
H(3), J = 2.3 Hz); 11.0—17.0 (br.s, 1 H, OH).
References
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4ꢀOxoꢀ6ꢀ(trifluoromethyl)ꢀ4Hꢀpyranꢀ2ꢀcarboxamide (4).
Ester 2 (5.0 g, 21.2 mmol) was vigorously stirred with
Received November 2, 2006;
in revised form March 9, 2007