742
M. G.Gorbunova et al.
PAPER
4-Pentafluoroethyl-2-pyrimidinol (16)
rimidinoles 16 and 17, respectively, containing C2F5 or
12 N aq HCl (1 mL) was added to a mixture of urea (0.90 g, 15
mmol), enone 3 (1.78 g, 8.2 mmol) and EtOH (5 mL) and the mix-
ture was stirred for 24 h at r.t. The solvent was evaporated and the
residue was treated with MeCN (5 mL). The precipitate was filtered
off and dried. The yield of pure compound 16 was 1.5g (85%), mp
178∞C (MeCN, decomposition).
unexpectedly CF2SO3H groups.
Compound 17 is formed as the result of fluorosulfonyl
group hydrolysis. Both pyrimidinoles are stable, colorless
crystalline compounds. The structures of compounds 16
1
and 17 were assigned by elemental analysis and H and
19F NMR data. Pyrimidinole 17 was also characterized as
its S-benzylthiuronium salt.
Anal: C6H3F5N2O (214.09): Calc C, 33.66; H, 1.41; F, 44.39.
Found: C, 33.57; H, 1.37; F, 44.32.
1H NMR (CD3OD, 200 MHZ): d = 6.90 [d, 1H, 3J(H,H) = 6.3 Hz, H5],
In summary, we have synthesized a number of useful
fluoro-containing building blocks, by the reaction of ethyl
vinyl ether with various fluorinated carboxylic acid chlo-
rides. It was shown that these available and convenient
fluorinated enones 2-6 differ insignificantly from enone
1.
8.47 [d, 1H, 3J(H,H) = 6.3 Hz, H6].
Difluoro(2-hydroxy-4-pyrimidinyl)methanesulfonic Acid (17)
12 N aq HCl (1 mL) was added to a mixture of urea (3.60 g, 60
mmol), enone 6 (12.69 g, 60 mmol) and EtOH (5 mL). The mixture
was stirred for 24 h at r.t. The solvent was evaporated and the resi-
due was treated with MeCN (5 mL). The precipitate was filtered off
and dried. The yield of pure compound 17 was 0.72g (58%), mp
270∞C (decomposition). The S-benzylthiuronium salt decomposed
at 240-250∞C.
Starting materials were of the highest commercial quality and were
used without further purification. 19F NMR chemical shifts are re-
ported in ppm, negative upfield relative to internal CFCl3; 1H NMR
and 13C NMR chemical shifts are reported in ppm, positive down-
field relative to internal TMS; spectra were recorded in CDCl3 at
200 MHz (Bruker WP-200) and 300 MHz (Varian VXR-300). GC
analyses were obtained using SE-30 (5%) column (6.3 m). Acid
chlorides of polyfluoro carboxylic acids were obtained by reaction
of the corresponding acids with PCl5 and were distilled before use.
Anal: C13H14F2N4O4S2 (392.13): Calc C, 39.82; H, 3.58; F, 9.69.
Found: C, 39.61; H, 3.55; F, 9.61.
1H NMR (CD3OD, 200 MHz): d = 7.25 [d, 1H, 3J(H,H) = 6.2 Hz, H5],
8.73 [d, 1H, 3J(H,H) = 6.2 Hz, H6].
19F NMR (CD3OD, 188.28 MHz): d = -109.6 (s).
Enones 2-6; (E)-5-Ethoxy-1,1,1,2,2-pentafluoropent-4-en-3-one
(2); Typical Procedure
Acknowledgement
We express our gratitude to Mr. Volkov N.D. (Institute of Organic
Chemistry National Academy of Sciences of Ukraine, Kiev) for
providing difluorofluorosulfoacetic acid chloride. This work was
supported by the International Association Foundation (INTAS-
UA-95-0095).
A solution of pentafluoropropionic acid chloride (18.98 g, 104
mmol) in anhyd CH2Cl2 (20 mL) was added to a mixture of ethyl vi-
nyl ether (7.59 g, 107 mmol) and pyridine (8.45 g, 107 mmol) in
CH2Cl2 (100 mL) under stirring and cooling to -10∞C. The reaction
mixture was then stirred for 20 h at 20∞C, then H2O (100 mL) was
added, the H2O phase was extracted with hexane (3 ¥ 100 mL). The
combined organic layers were dried (MgSO4) and the solvent was
evaporated. The residue was distilled under vacuum. Yields, physi-
cal constants, elemental analysis and NMR data are shown in Tables
1-3.
References
(1) Fluorine in Bioorganic Chemistry; Welch, J. T.;
Eswarakrishnan, S., Eds.; Wiley: New York, 1991.
Organofluorine Compounds in Medicinal Chemistry and
Biochemical Applications; Filler, R.; Kobayashi, J.;
Yagupolskii, L. M.; Eds.; Elsevier: Amsterdam, 1993.
(2) Percy, J. M. Top. Curr. Chem. 1997, 193, 131.
(3) Gerus, I. I.; Gorbunova, M. G.; Kukhar, V. P. J. Fluorine
Chem. 1994, 69, 195.
(4) Hojo, M.; Masuda, R.; Kokuryo, Y.; Shioda, H.; Matsuo, S.
Chem. Lett. 1976, 499.
(5) Cheburkov, Yu.; Mukhamedaliev, N.; Knunyants, I. L.
Tetrahedron 1968, 24, 341.
Enaminones 7-14; 5-Methylamino-1,1,1,2,2-pentafluoropent-4-
en-3-one (8); Typical Procedure
Na2CO3 (0.33 g, 4 mmol) was added to a mixture of methylamine
hydrochloride (0.57 g, 7 mmol) and enone 3 (1.52 g, 7 mmol) in
H2O (5 mL) under stirring at r.t. The mixture was then stirred for 2
h at 20∞C and then extracted with Et2O (3 ¥ 15 mL). The combined
ethereal phase was dried (MgSO4) and the solvent was evaporated.
The residue was distilled under vacuum or crystallized. Yields,
physical constants, elemental analysis and NMR data are shown in
the Tables 4 and 5.
(6) Hojo, M.; Masuda, R.; Sakaguchi, S.; Takagawa, H. Synthesis
1986, 1016.
(7) Wojcik, J.; Domalewski, W.; Kamienska-Trela, K.; Stefaniak,
L.;.Vdovenko, S. I.; Gerus, I. I.; Gorbunova, M. G. Magn.
Reson. Chem. 1993, 31, 808.
(8) Gerus, I. I.;.Vdovenko, S. I.; Gorbunova, M. G.; Kukhar, V. P.
Khim. Heterocycl. Soed. 1991, 502; Chem. Abstr. 1991, 115,
1832349.
4-Diethylamino-1,1-difluoro-1-fluorosulfobut-3-en-2-one (15)
Enone 6 (10.1 g, 50 mmol) was added to a solution of Et2NH (3.65
g, 50 mmol) in CH2Cl2 (20 mL) under stirring and cooling to 0-
10∞C. The mixture was stirred for 2 h at r.t. and the solvent was
evaporated. The residue was crystallized. Yields, physical con-
stants, elemental analysis, and NMR data are shown in Tables 4 and
5.
Article Identifier:
1437-210X,E;2000,0,05,0738,0742,ftx,en;H05999SS.pdf
Synthesis 2000, No. 5, 738–742 ISSN 0039-7881 © Thieme Stuttgart · New York