PAPER
Reactions of 1,1,1-Trifluoro[chloro]-4-ethoxybut-3-en-2-ones with 1,3-Dicarbonyl Compounds
767
aluminum oxide34 which have been successfully used in
other related Michael reactions, either gave poor yields,
side products, polymerization, or failed to react with our
substrate.
1-[2-Hydroxy-6-(trichloro[fluoro]methyl)pyridin-3-yl]etha-
none (6c, 7c) and 3-Acetylazet-2(1H)-one (8); General Proce-
dure
In a two necked round-bottomed flask of 50 mL b-alkoxyvinyl tri-
halomethyl ketones 1 or 2 (5.0 mmol), NaH (0.024 g, 1.0 mmol),
and anhyd THF (10 mL) was added with stirring. To this mixture
the dicarbonyl compound c (0.50 g, 5.0 mmol) in anhyd THF (10
mL) was added dropwise from an addition funnel. After stirring for
30 min at r.t., the mixture was acidified with 1M HCl until pH 3 and
extracted with CH2Cl2 (3 x 40 mL). The combined CH2Cl2 layers
were dried (MgSO4) and concentrated under vacuum to obtain 6c or
7c as brown solids which were purified by recrystallization from
CHCl3. Yield of 6c was 0.71 g (56%) and 7c was 0.59 g (58%).
The 1-[2-hydroxy-4-(trifluoromethyl)phenyl]ethanone
(5a) was obtained from the reaction of ketone 1 with
acetylacetone and sodium hydride in a molar ratio of 1:1:2
respectively, under reflux for three hours. Using these
conditions the compounds 3b, 4a,b were not converted to
the corresponding phenols.
The reaction of ketone 1 or 2 with acetylacetamide (c) and
sodium hydride in anhyd THF, carried out at room tem-
perature and equal molar ratio, resulted in a 1:1 mixture of
the cyclic compounds 1-[2-hydroxy-6-(trifluorometh-
yl)pyridin-3-yl]ethanone (7c) and 3-acetylazet-2(1H)-one
(8) or 1-[2-hydroxy-6-(trichloromethyl)pyridin-3-yl]etha-
none (6c) and 8. Compound 8 is probably formed by the
internal attack of the amidic nitrogen on the b-carbon with
the subsequent elimination of trihalomethylacetone. The
compounds 6c or 7c were obtained as pure compounds
when the reactions were carried out at room temperature
and with catalytic amounts of sodium hydride (20%).
Compound 8 was obtained together with compounds 6c or 7c when
the reaction was carried out with an equivalent amount of NaH. The
compound 8 was isolated from the compounds 6c and 7c by their
different solubility. Compounds 6c and 7c are soluble in CHCl3
while compound 8 is soluble in MeOH. After compound 8 was sep-
arated from 6c or 7c, it was recrystallized from MeOH. Yield of
pure 8 was 0.13 g (24%).
Acknowledgement
The authors thank the Conselho Nacional de Desenvolvimento
Científico
e Tecnológico (CNPq), PADCT-II/FINEP, and
Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul
(FAPERGS) for financial support.
Unless otherwise indicated all common reagents and solvents were
used as obtained from commercial suppliers without further purifi-
cation. The b-alkoxyvinyl trifluoro[chloro]methyl ketones (1a, 2a)
were prepared according to reference 11. All melting points were
determined on a Reichert Thermovar apparatus and are uncorrected.
1H and 13C NMR spectra were acquired on a Bruker DPX 400 spec-
trometer (1H at 400.13 MHz and 13C at 100.62 MHz) or on a Bruker
DPX 200 spectrometer (1H at 200.13 MHz and 13C at 50.32 MHz)
in CDCl3 (or DMSO-d6 for compound 8) using TMS as the internal
reference. IR spectra were recorded on a Bruker IFS 28 FT-IR spec-
trometer. The mass spectra were recorded on a Finnigan Mat 80A
ion trap detector connected to a Varian 3400 GC equipped with a
SE-30 fused silica capillary column, 50 m, 0.32 mm ID. Elemental
analysis was performed on a Vario EL Elementar Analysensysteme.
References
(1) Heathcock, C. H.; Oare, D. A. J. Org. Chem. 1990, 55, 157.
(2) Paganelli, S.; Schionato, A.; Botteghi, C. Tetrahedron Lett.
1991, 32, 2807.
(3) Ballini, R.; Rinaldi, A. Tetrahedron Lett. 1994, 35, 9247.
(4) Rousseau, G.; Blanco, L.; Jouglet, B. Synlett 1991, 12, 907.
(5) Lawrence, R. M.; Perlmutter, P. Chem. Lett. 1992, 2, 305.
(6) Murahashi, S.; Mizuno, M.; Taki, H.; Naota, T. J. Am. Chem.
Soc. 1989, 111, 5954.
(7) Ito, Y.; Hamahima, H.; Sawamura, M. Tetrahedron 1994, 50,
4439.
(8) Cobayashi, S.; Hachiya, I.; Ishitani, H.; Araki, M. Synlett
1993, 7, 472.
(9) Keller, E.; Feringa, B.I. Tetrahedron Lett. 1996, 17, 1879.
(10) Boruah, A.; Baruah, M.; Prajapati, D.; Sandhu, J. Chem. Lett.
1996, 965.
(11) House, H. O.; Roelofs, W. L.; Trost, B. M. J. Org. Chem.
1966, 31, 646.
(12) Colla, A.; Clar, G.; Martins, M. A. P.; Krimmer, S.; Fischer,
P. Synthesis 1991, 483.
(13) Martins, M. A. P.; Zoch, A. N.; Flores, A. F. C.; Clar, G.;
Zanatta, N.; Bonacorso, H. G. J. Heterocycl. Chem. 1995, 32,
739.
(14) Martins, M. A. P.; Siqueira, G.; Bastos, G. P. and Zanatta, N.
J. Heterocycl. Chem. 1996, 33, 1223.
(15) Martins, M. A. P.; Freitag, R.; Flores, A. F. C.; Zanatta, N. J.
Heterocycl. Chem. 1996, 33, 1619.
(16) Braibante, M. E.; Clar, G.; Martins, M. A. P. J. Heterocycl.
Chem. 1993, 30, 1159.
(17) Martins, M. A. P.; Freitag, R.; Flores, A. F. C.; Zanatta, N. J.
Heterocycl. Chem. 1995, 32, 1491.
(18) Pachoslki, I.; Blanco, I.; Zanatta, N.; Martins, M. A. P. J.
Braz. Chem. Soc. 1992, 2, 118.
(19) Blanco, I.; Pachoslki, I.; Zanatta, N.; Martins, M. A. P. Quím.
Nova 1993, 16, 15.
(20) Zanatta, N.; Madruga, C. C.; Clerice, E.; Martins, M. A. P. J.
Heterocycl. Chem. 1995, 32, 735.
(E)-5-Acetyl[carboxyethyl]-1,1,1-trifluoro[chloro]hept-3-ene-
2,6-diones (3a,b, 4a,b); General Procedure
In a two necked round-bottomed flask of 50 mL a mixture of b-
alkoxyvinyl trihalomethyl ketones 1 or 2 (5.0 mmol), NaH (0.12 g,
5.0 mmol), and anhyd THF (10 mL) was added with stirring. To this
mixture was added the dicarbonyl compound a or b (5.0 mmol) in
anhyd THF (10 mL) dropwise from an addition funnel. After stir-
ring for 30 min at r.t., the mixture was acidified with 1 M solution
of HCl to pH 3 and the organic layer extracted with CH2Cl2 (3 x 40
mL). The combined CH2Cl2 layers were dried (MgSO4) and concen-
trated in vacuo to obtain a dark oil that was filtered through silica
gel 60 with hexane. On removal of solvent the compounds 4a and
4b crystallized and were further recrystallized from hexane. The
compounds 3a and 3b did not crystallize and were purified by col-
umn chromatography using silica gel 60 and hexane.
The 1-[2-hydroxy-4-(trifluoromethyl)phenyl]ethanone (5a) was ob-
tained when the reaction of 1 (0.84 g, 5.0 mmol), acetylacetone
(0.50 g, 5.0 mmol), and NaH (0.24 g, 10.0 mmol), was refluxed for
3 h after the addition of the reactants. The compound 5a was isolat-
ed by the same procedure adopted for the compounds 3a and 3b.
Compound 5a was obtained as a dark oil which was purified by col-
umn chromatography using silica gel and hexane as the mobile
phase. Pure 5a (0.52 g, 58% yield) was obtained.
Synthesis 1999, No. 5, 765–768 ISSN 0039-7881 © Thieme Stuttgart · New York