180
KOVTONYUK, KOBRINA
excess hexyne the reaction mixture was subjected to
column chromatography on silica gel. Elution with
CCl4 afforded 0.35 g (49%) of compound Vc as
viscous yellow fluid. 19F NMR spectrum (CCl4),
F, ppm: 42.1 (F1), 38.1 (F4), 2.1 (F5), 23.6
(F3). Found, %: C 64.58; H 5.08; F 20.98. M 362.
C19H18F4O2. Calculated, %: C 64.41; H 5.08;
F 21.47. M 354.
The residue was subjected to chromatography on
silica gel. Elution with CHCl3 afforded 0.33 g (85%)
of ester VIIc as viscous light-yellow fluid. H NMR
1
spectrum (CCl4), , ppm: 7.3 7.5 (C6H5), 6.3 (1H,
Ar H), 4.2 (OCH2), 3.9 (OCH3), 2.4, 1.7 1.2
(4CH2), 0.8 (2CH3). 19F NMR spectrum (CCl4),
,
F
ppm: 18.7 ( -F), 31.6 and 33.2 (F2 and F4). Found
[M]+ 394. 17562. C22H25F3O3. Calculated M
394.17556.
Propyl (5-butyl-3-methoxy-2,4-difluorophenyl)-
fluorochloroacetate (VIIa). To compound VIa pre-
pared by heating 0.46 g of dienone V with 3 ml
1-hexyne to 70 C for 20 h on removing excess
1-hexyne was added 6 ml of 1-propanol and 1 g of
freshly calcined K2CO3. The mixture was stirred for
3 h at room temperature, 50 ml of diluted hydro-
chloric acid was added, and the product was extracted
into dichloromethane (3 50 ml). The extract was
dried with calcium chloride, the solvent was
evaporated, and the residue was subjected to
chromatography on silica gel. Elution with CCl4
afforded 0.35 g of ester VIIa (50% with respect to
4-Oxo-2-phenyl-3,5,6,7-tetrafluoro-5-chlorobi-
cyclo[4.1.0]hept-2-ene-7-carbonitrile (VIII). (a) To
a solution of 0.42 g of azidodienone IIe in 10 ml of
CCl4 was added 0.4 g of phenylacetylene, and the
mixture was heated to 70 C for 8 h. The solution was
applied to a column packed with silica gel and on
successive elution with CCl4 and CHCl3 we separated
0.24 g (44%) of nitrile VIII. After two recrystalliza-
tions from hexane we obtained 0.14 g of compound
1
VIII, (VIII), mp 67 69 C. IR spectrum, , cm :
3042 w (C H), 2240 w (C N), 1722 s (C=O),
1625 m, 1447 m, 1418 m, 1331 m, 1309 m,
1249 m, 1190 m, 1162 m, 1080 m, 1023 m,
993 m, 914 m, 878 s, 835 s. Found, %:
C 53.19; H 2.07; N 4.54. [M]+ 315.00733.
C14H6ClF4NO. Calculated, %: C 53.25; H 1.90;
N 4.44. M 315.00740.
1
dienone V) as viscous light fluid. H NMR spectrum
(CCl4), , ppm: 6.9 (1H, Ar H), 3.8 (OCH2), 3.5
(OCH ), 2.2, 1.5 0.7 (4CH2), 0.5 (2CH3). 19F NMR
3
spectrum (CCl4), F, ppm: 32.2 and 33.9 (F2 and F4),
58.8 ( -F). Found [M]+ 352.10529. C16H20ClF3O3.
Calculated M 352.10500.
(b) To a solution of 0.5 g of dienone I in 10 ml of
acetonitrile was added 0.3 g of trimethylsilyl azide,
and the mixture was maintained at room temperature
for 30 min. According to 19F NMR data the resulting
mixture contained equal amounts of azidodienone IIe
and trimethylfluorosilane. To this mixture was added
0.23 g of phenylacetylene, and the resulting solution
was kept for 8 weeks with intermittent registering of
19F NMR spectra. The spectra showed that after
3 days the reaction mixture contained 67% of di-
enone IIe, 20% of cycloadduct IX, and trace
amounts of nitrile VIII. In 3 weeks these compounds
were contained in equal amounts, and in 8 weeks in
the reaction mixture was 80% of compound VIII.
Propyl (5-hydroxymethyl-3-methoxy-2,4-di-
fluorophenyl)fluorochloroacetate (VIIb). To com-
pound VIb prepared by heating 0.46 g of dienone V
with 0.23 g of propargyl alcohol in 5 ml of toluene to
115 C for 10 h on evaporating in a vacuum was
added 5 ml of 1-propanol and 2 g of freshly calcined
K2CO3. The mixture was stirred for 2 h at room
temperature, then 50 ml of diluted HCl was added,
and the product was extracted into dichloromethane
(3 50 ml). The extract was dried with calcium
chloride, the solvent was evaporated, and the residue
was subjected to chromatography on silica gel. Elu-
tion with CHCl3 afforded 0.25 g of ester VIIb (78%
with respect to dienone V). 1H NMR spectrum
(CCl4), , ppm: 7.5 (1H, Ar H), 4.6 (CH2OH), 4.2
(OCH2), 3.9 (OCH3), 3.5 (OH), 1.7 (CH2), 0.9 (CH3).
19F NMR spectrum (CCl4), F, ppm: 32.2 and 34.0
(F2 and F4), 57.3 ( -F). Found [M]+ 326.05326.
C13H14ClF3O4. Calculated M 326.05326.
REFERENCES
1. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
Kharkov: Torsing, 1998, vol. 1, 560p; vol. 2, 592 p.
2. Fluorine-Containing Molecules. Structure, Reactivity,
Synthesis and Applications, Liebman, J.F., Green-
berg, A., and Dolbier, W.R., Eds., New York: VCH
Publish. Inc., 1988.
Propyl (5-butyl-3-methoxy-2,4-difluorophenyl)-
phenylfluoroacetate (VIIc). To a solution of 0.35 g
of compound VIc in 3 ml of 1-propanol was added
1.4 g of freshly calcined K2CO3. The reaction mix-
ture was stirred for 50 h at room temperature, then
filtered, and 1-propanol was evaporated in a vacuum.
3. Organofluorine Compounds in Medicinal Chemistry
and Biomedical Applications, Filler, R., Kobaya-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 2 2002