, 2001, 11(2), 76–76
A route to ethyl α-pentafluorobenzoyl-β-oxobutanoate via its copper(II) chelate
Yanina V. Burgart, Sergei P. Kisil, Viktor I. Saloutin* and Oleg N. Chupakhin
Institute of Organic Synthesis, Urals Branch of the Russian Academy of Sciences, 620219 Ekaterinburg, Russian Federation.
Fax: +7 3432 74 5954; e-mail: saloutin@ios.uran.ru
10.1070/MC2001v011n02ABEH001399
Ethyl 2-pentafluorobenzoyl-3-oxobutanoate has been prepared by the acylation of ethyl acetoacetate with pentafluorobenzoyl
chloride via a copper(II) chelate.
The acylation of β-oxo esters by pentafluorobenzoyl chloride
is known to form 2,3-substituted 5,6,7,8-tetrafluorochromones
instead of the expected β,β'-dioxoesters.1–4
This work was supported by the State Programme for Sup-
porting Leading Scientific Schools of the Russian Federation
(grant no. 00-15-97390).
We prepared the copper chelate of ethyl 2-pentafluorobenzoyl-
3-oxobutanoate 3 using a chelation stage in the reaction of ethyl
acetoacetate 1 with pentafluorobenzoyl chloride 2. The acyla-
tion was carried out in ethanol in the presence of magnesium
ethoxide. The decomposition of chelate 3 by gaseous hydrogen
chloride gives a free ligand, ethyl 2-pentafluorobenzoyl-3-oxo-
butanoate 4. The treatment of the latter with an aqueous copper
acetate solution gives chelate 3.
References
1 N. N. Vorozhtsov, V. A. Barkhash, A. T. Prudchenko and T. I. Khomenko,
Dokl. Akad. Nauk SSSR, 1965, 164, 1046 [Dokl. Chem. (Engl. Transl.),
1965, 962].
2 N. N. Vorozhtsov, V. A. Barkhash, A. T. Prudchenko and G. S. Shchegoleva,
Zh. Obshch. Khim., 1965, 35, 1501 [J. Gen. Chem. USSR (Engl. Transl.),
1965, 35, 1503].
3 A. T. Prudchenko, V. A. Barkhash and N. N. Vorozhtsov, Izv. Akad. Nauk
SSSR, Ser. Khim., 1965, 1798 (Bull. Acad. Sci. USSR, Div. Chem. Sci.,
1965, 14, 1762).
4 R. Filler, Y. S. Rao, A. Biezais, F. N. Miller and V. D. Beacaire, J. Org.
Chem., 1970, 35, 930.
Cu0.5
O
O
Cu(OAc)2,
AcOH
Me
F
O
OEt
HCl (gas)
H
Me
OEt
3
Received: 15th November 2000; Com. 00/1725
Cu(OAc)2,
AcOH
O
O
O
New compounds and were characterised by IR (Vazeline oil), 19F
(75.3 MHz, C6F6) and 1H NMR (400 and 100 MHz) spectroscopy.
Bis(ethyl 2-pentafluorobenzoyl-3-hydroxy-2-butenoato)copper(II) 3.
(a) Ethyl acetoacetate (11.7 g, 0.09 mol) was added to a solution of
Mg(OEt)2 prepared from Mg chips (1.84 g, 0.07 mol). The reaction
mixture was stirred for 1 h at 50 °C. A solution of pentafluorobenzoyl
chloride 2 (18.4 g, 0.08 mol) in benzene (45 ml) was added. The reaction
mixture was stirred for 1 h at 20 °C and for 15 min at 50 °C. After
cooling, a solution of copper acetate (6.5 g) and acetic acid (3 g) in
40 ml of water was added. The organic layer was separated. The aqueous
layer was extracted with diethyl ether (3×30 ml). The organic layer was
dried over MgSO4. The solvent was removed in a vacuum at 20 °C. The
residue was reprecipitated from MeOH with water to give compound 3
(8.3 g, 29%); mp 162–164 °C. IR (n/cm–1): 1680 (C=O), 1630, 1580
[C=O, C=C (chelate)], 1495, 1450 (C=C), 980 (C–F). Found (%): C,
43.89; H, 2.22; F, 26.70. Calc. for C26H16F10O8Cu (%): C, 43.99; H,
2.27; F, 26.76.
3
4
†
H
O
O
1
Mg(OEt)2
Cl
∆
,
Me
OEt
F
DMSO
O
4
F
∆
2
O
O
OEt
HCl
F
O
Me
5
Two groups of signals appeared in the 1H and 19F NMR
spectra of β,β'-dioxoester 4 obtained in CDCl3 solutions.† The
resonance signal of a methine proton of the keto form is absent
(b) To a solution of ester 4 (0.26 g, 0.8 mmol) in methanol (5 ml), a
solution of copper acetate (0.3 g, 1.6 mmol) in water (10 ml) was added.
The resulting precipitate was filtered off and dried at 100 °C to give
chelate 3 (0.26 g, 91%).
1
from the H NMR spectrum. At the same time, two downfield
signals at 17.44 and 14.65 ppm corresponding to two enol
hydroxyl protons are observed. Thus, β,β'-dioxoester 4 exists in
a CDCl3 solution as a mixture of two enol tautomers in the
ratio ~4:1.
Ethyl 2-pentafluorobenzoyl-3-oxobutanoate 4. Dry gaseous hydrogen
chloride was passed through a solution of chelate 3 (0.3 g, 0.845 mmol)
in anhydrous diethyl ether (50 ml). The resulting precipitate was filtered
off. Diethyl ether was removed in a vacuum at 20 °C to give compound 4
(0.27 g, 99%) as an oil. 1H NMR (CDCl3, a mixture of two tautomers in
the ratio 4:1) d: 1.12, 1.39 (t, 3H, OCH2Me, J 7.1 Hz), 2.57, 2.47 (s, 3H,
Me), 4.10, 4.40 (q, 2H, OCH2Me, J 7.1 Hz), 17.44, 14.65 (br. s, 1H,
OH). 19F NMR (CDCl3, a mixture of two tautomers in the ratio 4:1) d:
20.21, 18.42 (2F, m), 9.95 (1F, m), 1.11, –2.93 (2F, m). IR (n/cm–1):
2930 (OH), 1710 (C=O), 1650, 1570 [C=O, C=C (enol)]; 1520, 1500
(C=C), 985 (C–F). Found (%): C, 47.93; H, 2.73; F, 29.15. Calc. for
C13H9F5O4 (%): C, 48.16; H, 2.80; F, 29.30.
3-Ethoxycarbonyl-2-methyl-5,6,7,8-tetrafluoro-4H-1,4-dihydrobenzo-
pyran-4-one 5. (a) Compound 4 (6.48 g, 0.02 mol) was heated at 100–
110 °C for 1 h. The resulting solid was recrystallised from CCl4–hexane
(1:2) to give product 5 (5.6 g, 92%); mp 91–92 °C. The physico-chemical
properties were identical to published data.1 (b) A solution of chelate 3
(0.5 g, 1.41 mmol) in DMSO (12 ml) was heated at 80 °C for 3 h and
allowed to stand at 20 °C for 24 h. A mixture of concentrated HCl
(12 ml) and water (12 ml) was added. The mixture was extracted with
diethyl ether (3×15 ml). The extracts were washed with water and dried
with MgSO4. The solvent was removed in a vacuum. The residue was
recrystallised from CCl4–hexane (1:2) to give product 5 (0.2 g, 47%).
The isolation of β,β'-dioxoester 4 was considered impossible1–4
because of its instability and ready intramolecular cyclization
into 3-ethoxycarbonyl-2-methyl-5,6,7,8-tetrafluorochromone 5.
In fact, β,β'-dioxoester 4 was readily converted into chromone
5 upon heating in the absence of solvents or in DMSO. Chro-
mone 5 was also obtained when chelate 3 was heated in DMSO.
The cyclization proceeds through the intramolecular substitution
for an ortho-fluorine atom in the pentafluorophenyl substituent.
We found that, in contrast to the reports on the impossibility
of the isolation of α-pentafluorobenzoyl-β-dicarbonyl compounds
in the reactions of β-oxo esters and β-diketones with penta-
fluorobenzoyl chloride, these compounds can be obtained using
interchelate stabilization. This method blocks the formation of
chromone structures, which occur under usual reaction condi-
tions. Thus, we developed a simple procedure for the synthesis
of β,β'-tricarbonyl compounds containing ortho-fluorine atoms
in a benzoyl substituent. These compounds may be of interest
as novel building blocks for the synthesis of fluoroheterocycles.
– 76 –
Burgart
