Synthesis of 2,6-bis(fluoroalkyl)-2,6-dihydroxytetrahydro-2H-pyran-3,5- dicarboxylates from aldehydes and fluorinated β-oxo esters in the presence of ionic liquid-K2CO3 as catalytic system

Article abstract of DOI:10.1134/S1070428010040020

An efficient procedure has been developed for the synthesis of 4-substituted 2,6-bis(fluoroalkyl)-2,6-dihydroxytetrahydro-2H-pyran-3,5- dicarboxylates by reactions of aldehydes with fluorine-containing β-oxo esters in heterogeneous catalytic system 1-buty

Full text of DOI:10.1134/S1070428010040020

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 4, pp. 468–473. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © S.G. Zlotin, G.V. Kryshtal’, G.M. Zhdankina, A.V. Ignatenko, Ya.V. Burgart, V.I. Saloutin, O.N. Chupakhin, 2010, published in
Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 4, pp. 479–483.
Synthesis of 2,6-Bis(fluoroalkyl)-2,6-dihydroxytetrahydro-
2H-pyran-3,5-dicarboxylates from Aldehydes and Fluorinated
β-Oxo Esters in the Presence of Ionic Liquid–K2CO3
as Catalytic System
S. G. Zlotina, G. V. Kryshtal’a, G. M. Zhdankinaa, A. V. Ignatenkoa, Ya. V. Burgartb,
V. I. Saloutinb, and O. N. Chupakhinb
a Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, Leninskii pr. 47, Moscow, 119991 Russia
e-mail: zlotin@ioc.ac.ru
b Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences,
ul. S. Kovalevskoi 20, Yekaterinburg, 620219 Russia
Received May 6, 2009
Abstract—An efficient procedure has been developed for the synthesis of 4-substituted 2,6-bis(fluoroalkyl)-
2,6-dihydroxytetrahydro-2H-pyran-3,5-dicarboxylates by reactions of aldehydes with fluorine-containing
β-oxo esters in heterogeneous catalytic system 1-butyl-3-methylimidazolium tetrafluoroborate [bmim][BF4]–
K2CO3 activated by ultrasound. The system retains its catalytic activity for three reaction cycles.
DOI: 10.1134/S1070428010040020
Base-catalyzed condensation of aldehydes with
1,3-dicarbonyl compounds (Knoevenagel reaction) is
widely used to synthesize various polyfunctionalized
organic compounds [1, 2]. These reactions are usually
carried out in organic solvents (such as ethanol, tetra-
hydrofuran, benzene, or toluene) in the presence of
base catalyst [3–12]. In the recent years, examples of
Knoevenagel condensations performed in solutions
in imidazolium salts with fluorine-containing anions
[13–20] (i.e., ionic liquids [21–24]) were reported. The
use of ionic liquids made it possible to shorten the
reaction time and improve the yield [14, 17–20]. In
addition, ionic liquids as solvents can be regenerated
and used repeatedly. However, wide application of
ionic liquids is limited due to their relatively high cost
[25]. We have recently demonstrated that the amount
of ionic liquid in Michael additions of nucleophiles to
compounds possessing electron-deficient multiple
Scheme 1.
O
F3C
O
OH
OEt
Ionic liquid A–C (90 mol %)
K2CO3 (30 mol %)
CHO
O
O
F3C
HO
2
+
F3C
OEt
O2N
O
OEt
NO2
Ia
IIa
IIa
IIIa
O
F3C
Ia
+
O
OEt
IV
NO2
Ionic liquids: [bmim]BF4 (A), [HexMim]NTf2 (B), [BmPyr]NTf2 (C).
468

SYNTHESIS OF 2,6-BIS(FLUOROALKYL)-2,6-DIHYDROXYTETRAHYDRO-2H-PYRAN-...
469
Scheme 2.
OR1 R2
OR1
Ionic liquid (90 mol %)
K2CO3 (30 mol %)
65°C, ultrasound
O
O
O
O
2
+
R2CHO
OH
HO
RF
RF
OR1
O
RF
IIIa–IIIm
Ia–Ie
IIa–IIh
I, R1 = Et, RF = CF3 (a), H(CF2)2 (c), C4F9 (e); R1 = Me, RF = C3F7 (b), H(CF2)4 (d); II, R2 = 4-O2NC6H4 (a), Ph (b), 4-MeOCO-
C6H4 (c), 4-ClC6H4 (d), 4-MeOC6H4 (e), 3-thienyl (f), pyridin-3-yl (g), Et (h); III, RF = CF3, R1 = Et, R2 = 4-O2NC6H4 (a), Ph (b),
4-MeOCOC6H4 (c), 4-ClC6H4 (d), 4-MeOC6H4 (e), 3-thienyl (f), pyridin-3-yl (g), Et (h); RF = C3F7, R1 = Me, R2 = 4-O2NC6H4 (i),
4-ClC6H4 (j); RF = H(CF2)2, R1 = Et, R2 = 4-O2NC6H4 (k); RF = H(CF2)4, R1 = Me, R2 = 4-O2NC6H4 (l); RF = C4F9, R1 = Me,
R2 = 4-O2NC6H4 (m).
bonds may be considerably reduced (to 30–90 mol %)
by carrying out these reactions in the presence of
a solid base [26, 27]. In such systems ionic liquid
simultaneously acts as solvent (which reduces the
viscosity of the reaction medium) and phase-transfer
catalyst.
detected (compound IV was formed in nonpolar
organic solvent, such as benzene or toluene) [29]. The
best yield of IIIa was obtained when the reaction was
carried out at 65°C under ultrasonic activation using
1-butyl-3-methylimidazolium tetrafluoroborate
[bmim][BF4] (A, 90 mol %; see table, run no. 3). Pre-
sumably, ultrasound increases dispersity of the solid
base thus enhancing phase transfer of the reactants and
product. The reaction rate and the yield of compound
IIIa were lower in the absence of ultrasound, as well
as in the presence of a smaller amount of ionic liquid
(0–30 mol %; see table, run nos. 1, 2, 4). The yield
also decreased upon lowering the temperature to 40°C
(see table, run no. 5).
In the present work we were the first to perform
reactions of aldehydes with fluorinated 1,3-dicarbonyl
compounds in the system ionic liquid–solid base. The
products, 4-substituted 2,6-bis(fluoroalkyl)-2,6-dihy-
droxytetrahydro-2H-pyran-3,5-dicarboxylates [28–31],
attract interest as analogs of known compounds
exhibiting antitumor activity [31]. We initially studied
the condensation of ethyl 4,4,4-trifluoro-3-oxobuta-
noate (Ia) with 4-nitrobenzaldehyde (IIa) as model
process. Compounds Ia and IIa reacted with each
other in the presence of K2CO3 (30 mol %) and ionic
liquid (30–90 mol %) to give tetrahydropyran deriva-
tive IIIa (Scheme 1), regardless of the reactant ratio.
Even traces of 1:1 condensation product IV were not
The described reaction also occurred in the pres-
ence of other ionic liquids (90 mol %), including
1-hexyl-3-methylimidazolium bis(trifluoromethylsul-
fonyl)imide [HexMim][NTf2] (B) and 1-butyl-3-
methylpyrrolidinium bis(trifluoromethylsulfonyl)imide
[BmPyr][NTf2] (C), but in these cases complete con-
Condensation of ethyl 3,3,3-trifluoro-3-oxobutanoate (Ia) with 4-nitrobenzaldehyde (IIa) in heterogeneous systems ionic
liquid–K2CO3
Run no.
Iionic liquid (mol %)
Reaction time, h (65°C)
Ultrasound
Yield of IIIa, % (number of cycles)
1
2
–
07
07
07
12
35
15
22
+
+
+
–
40
A (30)
A (90)
A (90)
A (90)
B (90)
C (90)
58
3
81 (1), 80 (2), 80 (3)a
b4b
c5c
6
60
58d
+
+
+
80
7
78 (1), 82 (2), 82 (3)a
a
b
c
d
A fresh portion of K2CO3 (30 mol %) was added.
The reactin mixture was stirred using a magnetic stirrer.
The reaction was carried out at 40°C; reactant ratio Ia–IIa 1:1.
Calculated on the reacted compound IIa.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

ZLOTIN et al.
470
version of the initial reactants was achieved in a longer
time, 15 and 22 h, respectively, against 7 h in the reac-
tion with [bmim][BF4] (A).
procedure described in [32], and ionic liquids A–C
were prepared as reported in [33–35]. The progress of
reactions was monitored by thin-layer chromatography
using Silufol plates (eluent benzene−ethyl acetate, 9:1;
development with UV irradiation or by treatment with
iodine vapor). The products were purified by column
chromatography on silica gel (0.060–0.200 mm; Acros
Organics). A 1.6-l Reltec 1/100 TH ultrasonic bath
(operating frequency 47 kHz) was used for ultrasonic
Taking into account that the catalytic system
[bmim][BF4] (90 mol %)–K2CO3 (30 mol %) ensured
the best results in the condensation of ethyl 4,4,4-tri-
fluoro-3-oxobutanoate (Ia) with 4-nitrobenzaldehyde
(IIa), it was used to synthesize other 4-substituted
2,6-bis(fluoroalkyl)-2,6-dihydroxytetrahydro-2H-pyr-
an-3,5-dicarboxylates IIIb–IIIm. Under these condi-
tions we performed condensations of fluorinated β-oxo
esters Ia–Ie having different polyfluoroalkyl groups
with a series of aldehydes IIa–IIh, including aromatic
aldehydes with electron-donating and electron-with-
drawing substituents in the aromatic ring, aldehydes
of the thiophene (IIf) and pyridine series (IIg), and
propanal (IIh) (Scheme 2).
1
activation. The H NMR spectra were recorded on
a Bruker AM-300 spectrometer at 300.13 MHz; the
13C NMR spectra were measured on a Bruker Avance-
300 instrument at 75 MHz; and the 19F NMR spectra
were obtained on a Bruker AC-200 spectrometer at
188.31 MHz. The IR spectra were measured in KBr on
a Specord M-82 spectrometer. The elemental com-
positions were determined on a Perkin–Elmer 2400
analyzer.
In all cases, the corresponding condensation prod-
ucts IIIa–IIIm were isolated in fairly high yields (71–
88%), and the yields of previously reported com-
pounds IIIb [28, 29], IIIe [28], IIIg [31], and IIIh
[28] considerably exceeded those obtained in organic
solvents. The catalytic system ionic liquid–K2CO3 is
advantageous due to its easy regeneration. When the
reaction was complete, compounds III were extracted
into an organic solvent (benzene or diethyl ether), new
portions of the reactants were added to the remaining
mixture of ionic liquid and base, and the second reac-
tion cycle was characterized by the same efficiency.
The yield of the product was somewhat lower in the
third cycle, but in increased again when an additional
amount of the base was added to the system (see table,
run nos. 3, 7).
4-Substituted 2,6-bis(fluoroalkyl)-2,6-dihydroxy-
tetrahydro-2H-pyran-3,5-dicarboxylates IIIa–IIIm
(general procedure). A mixture of 2.0 mmol of β-oxo
ester Ia–Ie, 1.0 mmol of aldehyde IIa–IIh, 0.9 mmol
of 1-butyl-3-methylimidazolium tetrafluoroborate, and
0.3 mmol of potassium carbonate was heated for 5–
20 h at 65°C in an ultrasonic bath until the initial com-
pounds disappeared (TLC). The mixture was cooled
and extracted in succession with benzene (2×5 ml) and
diethyl ether (2×5 ml). The extracts were combined,
washed with water (3×25 ml), and dried over MgSO4,
the solvent was reduced under reduced pressure (40°C,
40 mm), and the residue was purified by column chro-
matography on silica gel using in succession hexane,
hexane−benzene (1:1), and benzene as eluents.
Diethyl 2,6-dihydroxy-4-(4-nitrophenyl)-2,6-
bis(trifluoromethyl)tetrahydro-2H-pyran-3,5-dicar-
boxylate (IIIa). Reaction time 7 h. Yield 81%,
mp 141–143°C. IR spectrum, ν, cm–1: 3420 (OH),
Thus we have proposed a procedure for the syn-
thesis of 4-substituted 2,6-bis(fluoroalkyl)-2,6-dihy-
droxytetrahydro-2H-pyran-3,5-dicarboxylates from the
corresponding aldehydes and fluorinated β-keto esters
in heterogeneous catalytic system ionic liquid–K2CO3,
which conforms to “green chemistry” requirements.
The proposed procedure is advantageous due to high
yields of the target products, experimental simplicity,
and minimal consumption of ionic liquid, and no
organic solvent is necessary.
1
1718 (C=O), 1190–1168 (C–F). H NMR spectrum
(CDCl3), δ, ppm: 0.87 t (6H, CH3, J = 7.2 Hz), 3.27 d
(2H, 3-H, 5-H, J = 12.04 Hz), 3.9 q (4H, OCH2, J =
7.2 Hz), 4.13 t (1H, 4-H, J = 12.04 Hz), 5.63 s (2H,
OH), 7.3 d (2H, o-H, J = 8.7 Hz), 8.25 d (2H, m-H,
J = 8.7 Hz). 13C NMR spectrum (CDCl3), δC, ppm:
13.5 (CH3), 39.9 (C4), 48.0 (C3, C5), 62.6 (OCH2), 94.9
(C2, C6), 123.2 (CF3), 124.01 (Cm), 129.7 (Co), 142.5
(Ci), 148.1 (Cp), 166.9 (C=O). 19F NMR spectrum
(CDCl3): δF − 85.17 ppm, s (CF3). Found, %: C 44.15;
H 3.75; F 21.80; N 2.64. C19H19F6NO9. Calculated, %:
C 43.92; H 3.69; F 21.96; N 2.70.
EXPERIMENTAL
Initial aldehydes IIa–IIh and potassium carbonate
were commercial products (Acros Organics) which
were used without additional purification. Fluorinated
β-oxo esters Ia–Ie were synthesized according to the
Diethyl 2,6-dihydroxy-4-phenyl-2,6-bis(trifluoro-
methyl)tetrahydro-2H-pyran-3,5-dicarboxylate
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

SYNTHESIS OF 2,6-BIS(FLUOROALKYL)-2,6-DIHYDROXYTETRAHYDRO-2H-PYRAN-...
471
(IIIb). Reaction time 8 h. Yield 74%, mp 118–119°C;
published data [28, 29]: yield 43% in the system
EtOH−KF at 78°C, mp 116–118.5°C.
2.84 Hz), 7.32 d.d (1H, 4′-H, J = 2.84, 4.82 Hz).
13C NMR spectrum (CDCl3), δ, ppm: 13.4 (CH3), 35.5
(C4), 48.3 (C3, C5), 62.4 (OCH2), 94.0 (C2, C6), 121.4
(CF3); 124.5, 126.1, 126.8, 135.5 (C4H3S); 170.8
Diethyl 2,6-dihydroxy-4-(4-methoxycarbonyl-
phenyl)-2,6-bis(trifluoromethyl)tetrahydro-2H-
pyran-3,5-dicarboxylate (IIIc). Reaction time 12 h.
Yield 88%, mp 165–167°C. IR spectrum, ν, cm–1: 3472
19
(C=O). F NMR spectrum (CDCl3): δF −85.42 ppm, s
(CF3). Found, %: C 42.65; H 3.89; F 23.61; S 6.53.
C17H18F6SO7. Calculated, %: C 42.51; H 3.78; F 23.73;
S 6.67.
1
(OH), 1720 (C=O), 1212–1188 (C–F). H NMR spec-
trum (DMSO-d6), δ, ppm: 0.75 t (6H, CH3, J =
6.62 Hz), 3.46 d (2H, 3-H, 5-H, J = 12.02 Hz), 3.5–
3.7 m (4H, OCH2), 3.87 s (3H, OCH3), 4.2 t (1H, 4-H,
J = 12.02 Hz), 7.57 br.s (2H, o-H), 7.87 d (2H, m-H,
Diethyl 2,6-dihydroxy-4-(pyridin-3-yl)-2,6-bis-
(trifluoromethyl)tetrahydro-2H-pyran-3,5-dicar-
boxylate (IIIg). Reaction time 5 h. Yield 85%,
mp 126–128°C; published data [31]: yield 20% in the
system EtOH−piperidine at 20°C, mp 126–127°C.
13
J = 8.1 Hz), 8.11 br.s (2H, OH). C NMR spectrum
(DMSO-d6), δC, ppm: 13.4 (CH3), 37.9 (C4), 49.1
(OCH3), 52.1 (C3, C5), 60.2 (OCH2), 94.4 (C2, C6),
119.9 (CF3), 123.7 (Cm), 128.9 (Ci), 129.7 (Co), 142.6
(Cp), 166.9 (C=O). 19F NMR spectrum (DMSO-d6):
δF −81.95 ppm, s (CF3). Found, %: C 47.49; H 4.21;
F 21.30. C21H22F6O9. Calculated, %: C 47.38; H 4.17;
F 21.41.
Diethyl 4-ethyl-2,6-dihydroxy-2,6-bis(trifluoro-
methyl)tetrahydro-2H-pyran-3,5-dicarboxylate
(IIIh). Reaction time 6 h. Yield 80%, mp 123–125°C;
published data [28]: yield 62% in the system EtOH−KF
at 78°C; mp 125–127.5°C.
Dimethyl 2,6-bis(heptafluoropropyl)-2,6-dihy-
droxy-4-(4-nitrophenyl)tetrahydro-2H-pyran-3,5-
dicarboxylate (IIIi). Reaction time 7 h. Yield 80%,
mp 148–150°C. IR spectrum, ν, cm–1: 3400 (OH),
Diethyl 4-(4-chlorophenyl)-2,6-dihydroxy-2,6-
bis(trifluoromethyl)tetrahydro-2H-pyran-3,5-dicar-
boxylate (IIId). Reaction time 7 h. Yield 79%,
mp 124–125.5°C. IR spectrum, ν, cm–1: 3340 (OH),
1
1724 (C=O), 1236–1128 (C–F). H NMR spectrum
(CDCl3), δ, ppm: 3.42 m (8H, OCH3, 3-H, 5-H), 4.12 t
(1H, 4-H, J = 12.0 Hz), 5.92 s (2H, OH), 7.48 d (2H,
o-H, J = 8.1 Hz), 8.25 d (2H, m-H, J = 8.1 Hz).
13C NMR spectrum (CDCl3), δC, ppm: 40.1 (C4), 47.1
(C3, C5), 53.3 (OCH3), 98.0 (C2, C6), 109–122.9 m
(CF2CF2CF3), 124.5 (Cm), 129.5 (Co), 142.1 (Ci), 148.3
(Cp), 170.3 (C=O). 19F NMR spectrum (CDCl3), δF,
ppm: −80.91 s (6F, CF3), −119.82 and −122.55 (4F,
CF2, AB system, JAB = 278.0 Hz), −123.72 s (4F,
CF2CF3). Found, %: C 36.63; H 2.28; F 38.33; N 2.11.
C21H15F14NO9. Calculated, %: C 36.48; H 2.19;
F 38.47; N 2.03.
1
1712 (C=O), 1112–1084 (C–F). H NMR spectrum
(CDCl3), δ, ppm: 0.87 t (6H, CH3, J = 7.12 Hz), 3.19 d
(2H, 3-H, 5-H, J = 12.3 Hz), 3.88 q (4H, OCH2, J =
7.12 Hz), 3.90 t (1H, 4-H, J = 12.3 Hz), 5.71 br.s (2H,
OH), 7.25 d (2H, o-H, J = 8.36 Hz), 7.35 d (2H, m-H,
13
J = 8.36 Hz). C NMR spectrum (CDCl3), δC, ppm:
13.4 (CH3), 39.6 (C4), 48.5 (C3, C5), 62.5 (OCH2), 94.9
(C2, C6), 121.4 (CF3), 129.2 (Cm), 129.8 (Co), 133.4
(Ci), 134.8 (Cp, 170.4 (C=O). 19F NMR spectrum
(CDCl3): δF −85.32 ppm, s (CF3). Found, %: C 45.01;
H 3.82; Cl 7.05; F 22.28. C19H19ClF6O7. Calculated,
%: C 44.85; H 3.76; Cl 6.97; F 22.40.
Dimethyl 4-(4-chlorophenyl)-2,6-bis(hepta-
fluoropropyl)-2,6-dihydroxytetrahydro-2H-pyran-
3,5-dicarboxylate (IIIj). Reaction time 12 h. Yield
71%, mp 127–129°C. IR spectrum, ν, cm–1: 3360
Diethyl 2,6-dihydroxy-4-(4-methoxyphenyl)-2,6-
bis(trifluoromethyl)tetrahydro-2H-pyran-3,5-dicar-
boxylate (IIIe). Reaction time 20 h. Yield 70%,
mp 97–98°C; published data [28]: yield 38% in the
system EtOH−KF at 78°C, mp 95–96°C.
1
(OH), 1715 (C=O), 1250–1118 (C–F). H NMR spec-
trum (CDCl3), δ, ppm: 3.30 d (2H, 3-H, 5-H, J =
12.2 Hz), 3.41 s (6H, OCH3), 3.90 t (1H, 4-H, J =
12.2 Hz), 5.97 s (2H, OH), 7.18 d (2H, o-H, J =
7.4 Hz), 7.33 d (2H, m-H, J = 7.4 Hz). 13C NMR spec-
trum (CDCl3), δC, ppm: 39.8 (C4), 47.4 (C3, C5), 53.1
(OCH3), 97.9 (C2, C6), 102.2–122.5 m (CF2CF2CF3),
129.2 (Cm), 129.3 (Co), 133.0 (Ci), 134.9 (Cp), 171.3
(C=O). 19F NMR spectrum (CDCl3), δF, ppm: −80.94 t
(6F, CF3, J = 10.0 Hz), −120.22 and −122.38 (4F, CF2,
AB system, JAB = 283.0 Hz), −123.74 m (4F, CF2CF3).
Diethyl 2,6-dihydroxy-4-(3-thienyl)-2,6-bis(tri-
fluoromethyl)tetrahydro-2H-pyran-3,5-dicarbox-
ylate (IIIf). Reaction time 6 h. Yield 78%, mp 108–
109°C. IR spectrum, ν, cm–1: 3370 (OH), 1710 (C=O),
1
1220–1020 (C–F). H NMR spectrum (CDCl3), δ,
ppm: 0.91 t (6H, CH3, J = 7.09 Hz), 3.17 d (2H, 3-H,
5-H, J = 12.22 Hz), 3.96 q (4H, OCH2, J = 7.09 Hz),
4.02 t (1H, 4-H, J = 12.22 Hz), 5.77 br.s (2H, OH),
3
7.02 d (1H, 5′-H, J = 4.82 Hz), 7.16 d (1H, 2′-H, J =
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 4 2010

ZLOTIN et al.
472
Found, %: C 37.12; H 2.29; Cl 5.37; F 39.19.
C21H15ClF14O7. Calculated, %: C 37.05; H 2.22;
Cl 5.31; F 39.07.
δC, ppm: 40.3 (C4), 47.5 (C3, C5), 53.4 (OCH3), 98.3
(C2, C6), 124–129 m (CF2CF2CF2CF3), 124.1 (Cm),
128.9 (Co), 142.1 (Ci), 148.3 (Cp), 170.8 (C=O).
19F NMR spectrum (DMSO-d6), δF, ppm: −79.55 t
(6F, CF3, J = 9.9 Hz), −117.3 and −119.8 (4F, α-CF2,
AB system, JAB = 282.6 Hz), −119.2 m (4F, β-CF2),
−125.24 m (4F, γ-CF2). Found, %: C 35.07; H 1.99;
F 43.05; N 1.89. C23H15F18NO9. Calculated, %:
C 34.91; H 1.91; F 43.21; N 1.77.
Diethyl 2,6-dihydroxy-4-(4-nitrophenyl)-2,6-bis-
(1,1,2,2-tetrafluoroethyl)tetrahydro-2H-pyran-3,5-
dicarboxylate (IIIk). Reaction time 18 h. Yield 75%,
mp 137–139°C. IR spectrum, ν, cm–1: 3364 (OH),
1
1704 (C=O), 1220–1016 (C–F). H NMR spectrum
(CDCl3), δ, ppm: 0.85 t (6H, CH3, J = 7.2 Hz), 3.36 d
(2H, 3-H, 5-H, J = 12.3 Hz), 3.88 q (4H, OCH2, J =
7.2 Hz), 4.02 t (1H, 4-H, J = 12.3 Hz), 5.98 s (2H,
OH), 6.15 t.t (2H, CHF2, J = 6.3, 52.6 Hz), 7.50 d (2H,
o-H, J = 8.8 Hz), 8.23 d (2H, m-H, J = 8.8 Hz).
13C NMR spectrum (CDCl3), δC, ppm: 13.3 (CH3),
40.0 (C4), 45.5 (C3, C5), 62.5 (OCH2), 96.4 (C2, C6),
108.0 (CF2), 113.0 (CHF2), 123.9 (Cm), 129.7 (Co),
142.2 (Ci), 148.0 (Cp), 170.8 (C=O). 19F NMR spec-
trum (CDCl3), δF, ppm: −130.7 d (4F, CF2, J =
274.6 Hz), −135.2 and −137.6 (4F, CHF2, AB system,
JAB = 304.8, JFH = 52.6 Hz). Found, %: C 43.37;
H 3.70; F 26.11; N 2.34. C21H21F8NO9. Calculated, %:
C 43.24; H 3.63; F 26.05; N 2.40.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 06-03-32603).
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vol. 22, p. 1704.
Dimethyl 2,6-dihydroxy-4-(4-nitrophenyl)-2,6-
bis(1,1,2,2,3,3,4,4-octafluorobutyl)tetrahydro-2H-
pyran-3,5-dicarboxylate (IIIl). Reaction time 12 h.
Yield 86%, mp 129–130.5°C. IR spectrum, ν, cm–1:
4. Gnanadickam, C., Ann. Chim., 1962, vol. 7, p. 826.
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1
3440 (OH), 1716 (C=O), 1220–1092 (C–F). H NMR
spectrum (DMSO-d6), δ, ppm: 3.24 s (6H, OCH3),
3.60 d (2H, 3-H, 5-H, J = 11.92 Hz), 4.33 t (1H, 4-H,
J = 11.92 Hz), 7.0 t (2H, CHF2, J = 50.3 Hz), 7.72 br.s
(2H, o-H), 7.93 s (2H, OH), 8.20 d (2H, m-H, J =
7.97 Hz). 13C NMR spectrum (DMSO-d6), δC, ppm:
40.5 (C4), 47.5 (C3, C5), 53.3 (OCH3), 98.2 (C2, C6),
124.1 (Cm), 124.17–122.28 m (CF2CF2CF2), 128.9
(Co), 129.5 (CHF2), 142.1 (Ci), 148.3 (Cp), 170.8
(C=O). 19F NMR spectrum (DMSO-d6), δF, ppm:
7. Niwas, S., Kumar, S., and Bhaduri, A.P., Indian J.
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10. Loeller, J.R., Tetrahedron Lett., 1989, vol. 30, p. 1457.
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Vater, W., Arzneim.-Forsch., 1981, vol. 31, p. 407.
−117.3 and −120.0 (4F, α-CF2, AB system, JAB
=
12. Gein, V.L., Gein, N.V., Voronina, E.V., and Kriven’-
282.8 Hz), −120.06 m (4F, β-CF2), −128.96 m (4F,
γ-CF2), −137.30 d (4F, CHF2, J = 50.1 Hz). Found, %:
C 36.73; H 2.35; F 40.11; N 1.93. C23H17F16NO9. Cal-
culated, %: C 36.57; H 2.27; F 40.24; N 1.85.
ko, A.P., Khim.-Farm. Zh., 2002, vol. 36, p. 23.
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Dimethyl 2,6-dihydroxy-4-(4-nitrophenyl)-2,6-
bis(nonafluorobutyl)tetrahydro-2H-pyran-3,5-di-
carboxylate (IIIm). Reaction time 9 h. Yield 85%,
mp 118–120°C. IR spectrum, ν, cm–1: 3420 (OH),
no. 4, p. 555.
15. Morrison, D.W., Forbes, D.C., and Davis, J.H., Tetra-
hedron Lett., 2001, vol. 42, p. 6053.
16. Formentin, P., Garcia, H., and Leyva, A., J. Mol. Catal.
A: Chem., 2004, vol. 214, p. 137.
1
1728 (C=O), 1236–1104 (C–F). H NMR spectrum
(DMSO-d6), δ, ppm: 3.25 s (6H, OCH3), 3.69 d (2H,
3-H, 5-H, J = 11.77 Hz), 4.36 t (1H, 4-H, J =
11.77 Hz), 7.75 br.s (2H, o-H), 8.07 s (2H, OH), 8.20 d
(2H, m-H, J = 8.6 Hz). 13C NMR spectrum (DMSO-d6),
17. Hangarge, R.V. and Shingare, M.S., Mendeleev
Commun., 2003, no. 2, p. 79.
18. Hangarge, R.V., Jarikote, D.V., and Shingare, M.S.,
Green Chem., 2002, vol. 4, p. 266.
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SYNTHESIS OF 2,6-BIS(FLUOROALKYL)-2,6-DIHYDROXYTETRAHYDRO-2H-PYRAN-...
473
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