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Russ.Chem.Bull., Int.Ed., Vol. 51, No. 11, November, 2002
Sosnovskikh et al.
(2,2,3,3ꢀtetrafluoro)propionate and 2ꢀaminoacetophenone unꢀ
der the conditions described for the synthesis of compound 3
with the exception that the reaction mixture was boiled for 4 h.
The yield was 83%, m.p. 73—74 °C (from hexane). Found (%):
C, 43.18; H, 2.27; N, 3.59. C14H9F8NO3. Calculated (%):
C, 42.98; H, 2.32; N, 3.58. IR, ν/cm–1: 3180 (NH); 1725, 1645
(C=O); 1600, 1530 (NH, arom.). 1H NMR (400 MHz, CDCl3),
δ: 6.11 (tt, 1 H, H(CF2)2C=C, 2JH,F = 52.9 Hz, 3JH,F = 4.8 Hz);
6.23 (tt, 1 H, H(CF2)2C=O, JH,F = 52.8 Hz, JH,F = 5.4 Hz);
6.76 (s, 1 H, =CH); 7.33 (ddd, 1 H, H(5), JH(5),H(6) = 8.2 Hz,
JH(5),H(4) = 7.2 Hz, JH(5),H(3) = 1.0 Hz); 7.70 (ddd, 1 H, H(4),
JH(4),H(3) = 8.5 Hz, JH(4),H(5) = 7.2 Hz, JH(4),H(6) = 1.4 Hz); 7.91
(dd, 1 H, H(6), JH(6),H(5) = 8.2 Hz, JH(6),H(4) = 1.4 Hz); 8.70
(dd, 1 H, H(3), JH(3),H(4) = 8.5 Hz, JH(3),H(5) = 1.0 Hz); 12.16
(br.s, 1 H, NH); 14.63 (br.s, 1 H, OH).
4ꢀHydroxyꢀ2ꢀ(trifluoromethyl)quinoline hydrochloride (4a).
A mixture of EtOH (10 mL), water (1 mL), concentrated HCl
(0.7 mL), and hydrate 3 (500 mg, 1.4 mmol) was refluxed for
2 h, then all volatiles were distilled off under a reduced pressure,
and the solid residue was washed with AcOEt. The yield was
180 mg (52%). IR, ν/cm–1: 3090, 2340—2760, 1750, 1640, 1605.
Found (%): C, 49.77; H, 2.89; N, 5.81. C10H6F3NO•0.8 HCl.
Calculated (%): C, 49.57; H, 2.83; N, 5.78.
2ꢀDifluoromethylꢀ4ꢀquinolone (1b) was synthesized similarly
to quinolone 1а. The yield was 85% (from 4b), 82% (from 2b),
and 14% (from 2ꢀaminoacetophenone), m.p. 205—207 °C. IR,
ν/cm–1: 3270, 3180 (NH); 3090 (=CH); 1640, 1615 (C=O);
1570, 1515 (C=C, arom.). Found (%): C, 61.43; H, 3.65; N, 7.40.
C10H7F2NO. Calculated (%): C, 61.54; H, 3.62; N, 7.18.
2ꢀ(1,1,2,2ꢀTetrafluoroethyl)ꢀ4ꢀquinolone (1c) was syntheꢀ
sized similarly to quinolone 1а. The yield was 40% (from 2c)
and 12% (from 2ꢀaminoacetophenone), m.p. 194—196 °C. IR,
ν/cm–1: 3270, 3180 (NH); 3090 (=CH); 1645, 1615 (C=O);
1560, 1515 (C=C, arom.). Found (%): C, 54.00; H, 2.78; N, 5.68.
C11H7F4NO. Calculated (%): C, 53.89; H, 2.88; N, 5.71.
NꢀMethylꢀ2ꢀtrifluoromethylꢀ4ꢀquinolone (5). A. The ethyl
ester (CF3CO2Et) (2.6 mL, 3.1 g, 22 mmol) was added to a
solution of ButOK (0.9 g, 23.0 mmol) in ButOH (20 mL). The
resulting mixture was brought to boiling, and a solution of
2ꢀaminoacetophenone (1.0 g, 7.4 mmol) in ButOН (5 mL) was
added dropwise with stirring for 15 min. The mixture was reꢀ
fluxed for 0.5 h, and MeI (2.5 mL, 5.7 g, 40 mmol) was introꢀ
duced after cooling. The resulting mixture was stirred for 2 h at
∼20 °С and for 1 h on refluxing. Then the solvent was distilled
off on a water bath under a reduced pressure, and the residue
was treated with water (100 mL). The product was filtered off,
dried, and recrystallized from an EtOH—water (1 : 2) mixture.
The yield was 0.85 g (51%), m.p. 137—138 °C (cf. Ref. 15: m.p.
137—139 °C). IR, ν/cm–1: 1635, 1610 (C=O); 1595, 1515
(C=C, arom.).
2
3
2ꢀDifluoromethylꢀ4ꢀhydroxyquinoline hydrochloride (4b)
was synthesized similarly to salt 4а in 65% yield. IR, ν/cm–1
:
3090, 2460—2720, 1750, 1655, 1605. Found (%): C, 51.84;
H, 3.39; N, 5.94. C10H7F2NO•HCl. Calculated (%): C, 51.85;
H, 3.48; N, 6.05.
4ꢀHydroxyꢀ2ꢀ(1,1,2,2ꢀtetrafluoroethyl)quinoline hydrochloꢀ
ride (4c) was synthesized similarly to salt 4а in 35% yield. IR,
ν/cm–1: 2360—2730, 1725, 1630, 1600. Found (%): C, 46.91;
H, 2.92; N, 4.58. C11H7F4NO•HCl. Calculated (%): C, 46.91;
H, 2.86; N, 4.97.
The attempt to obtain Nꢀallylꢀ2ꢀtrifluoromethylꢀ4ꢀquinoꢀ
lone from AllI and 2ꢀaminoacetophenone under similar condiꢀ
tions produced hydrate 3 in 14% yield and a nonꢀidentified
mixture of products.
B. Diketone 2a (1.0 g, 3.1 mmol) was introduced into a
solution of ButOK (0.39 g, 10.0 mmol) in ButOH (20 mL). The
mixture was stirred at ∼20 °C until a colorless salt formed
(∼10 min), and MeI (1.9 mL, 4.26 g, 30 mmol) was added to the
suspension. The mixture was stirred for 2 h at ∼20 °С and for 1 h
on boiling. Then the solvent was distilled off on a water bath
under a reduced pressure, and the residue was treated with water
(50 mL). The product was filtered off, washed with water, dried,
and recrystallized from a toluene—hexane (1 : 1) mixture. The
yield was 0.35 g (50%), m.p. 137—138 °C.
Methylation of dilithium salt of 1,3ꢀdiketone 2а. Anhydrous
THF (20 mL), finely powdered LiH (0.40 g, 50 mmol), and
CF3CO2Et (5.0 mL, 4.3 g, 30 mmol) were placed in a roundꢀ
bottom threeꢀnecked flask equipped with a mechanical stirrer,
a reflux condenser, and a dropping funnel. A solution of
2ꢀaminoacetophenone (2.0 g, 15 mmol) in anhydrous THF
(10 mL) was added dropwise to the obtained mixture on boiling
and with stirring for 0.5 h. The mixture was refluxed for 2 h with
stirring, then MeI (5 mL, 10.4 g, 73 mmol) was added dropwise,
and the resulting mixture was refluxed for 12 h. The solvent was
distilled off to dryness on a water bath under a reduced pressure,
and the oily residue was treated with an aqueous solution of
АсОН (4.5 mL of АсОН in 100 mL of water). The oily product
that crystallized after prolonged stirring was filtered off, washed
with water, and dried, m.p. 80—85 °С. According to the 1Н NMR
spectrum, the product represented a mixture of compounds 5—8
in a ratio of 38 : 35 : 10 : 17, respectively, which, being recrysꢀ
tallized from hexane with an addition of CCl4, yielded a
mixture of quinolones 5 and 7 (was not separated further).
2ꢀTrifluoromethylꢀ4ꢀquinolone (1a). A. Anhydrous THF
(15 mL) and finely powdered LiH (0.68 g, 86 mmol) were placed
in a roundꢀbottom threeꢀnecked flask equipped with a mechaniꢀ
cal stirrer, a reflux condenser, and a dropping funnel. 2ꢀAminoꢀ
acetophenone (3.4 g, 25 mmol) and CF3CO2Et (3.6 mL, 4.3 g,
30 mmol) were added to the resulting mixture, and the reaction
mixture was refluxed for 3 h with stirring, after which the solvent
was distilled off to dryness on a water bath under a reduced
pressure. The residue was treated with an aqueous solution of
АсОН (7 mL of АсОН in 100 mL of water), and the mixture was
left for 2 days at ∼20 °С. The solidified product was filtered off,
washed with water, dried, and recrystallized from CHCl3.
The yield was 1.0 g (19%), m.p. 210—212 °C. IR, ν/cm–1
:
3260, 3160 (NH); 3090 (=CH); 1645, 1630 (C=O); 1580,
1530 (C=C, arom.). Found (%): C, 56.39; H, 2.99; N, 6.75.
C10H6F3NO. Calculated (%): C, 56.35; H, 2.84; N, 6.57.
B. Hydrochloride 4a (250 mg, 1.0 mmol) was dissolved on
heating in EtOH (3 mL), and a 25% solution of NH3 was added
dropwise to pH 8—9. The alcohol was evaporated, and the resiꢀ
due was washed with water. The yield was 200 mg (90%), m.p.
209—210 °С.
C. A mixture of EtOH (7 mL), water (0.8 mL), concentrated
HCl (0.8 mL), and hydrate 3 (300 mg, 0.87 mmol) was refluxed
for 6 h, then the solvent was evaporated, and the residue was
refluxed for 20 h in water (10 mL). The precipitate that formed
upon cooling was filtered off and dried. The yield was 120 mg
(65%), m.p. 208—210 °С.
Sosnovskikh
