N-Polyfluoro(trimethylsilyl)ethyl azole derivatives

Article abstract of DOI:10.1016/j.jfluchem.2008.01.008

A facile synthetic route to N-polyfluoro(trimethylsilyl)ethyl azole derivatives was developed starting from N-bromo(chloro)polyfluoroethyl-substituted azoles. The silanes thus obtained were reacted with various electrophiles in the presence of the fluoride ion to yield the corresponding fluorinated carbinols, ketones, carboxylic acids, and methyl dithiocarboxylates as well as N-pentafluoroethylbenzimidazole.

Full text of DOI:10.1016/j.jfluchem.2008.01.008

Available online at www.sciencedirect.com
Journal of Fluorine Chemistry 129 (2008) 301–306
www.elsevier.com/locate/fluor
N-Polyfluoro(trimethylsilyl)ethyl azole derivatives
*
Kirill I. Petko , Sergey Y. Kot, Lev M. Yagupolskii
Institute of Organic Chemistry, National Academy of Science of Ukraine, Murman’ska, str. 5, 02094 Kyiv, Ukraine
Received 27 November 2007; received in revised form 11 January 2008; accepted 17 January 2008
Available online 26 January 2008
Abstract
A facile synthetic route to N-polyfluoro(trimethylsilyl)ethyl azole derivatives was developed starting from N-bromo(chloro)polyfluoroethyl-
substituted azoles. The silanes thus obtained were reacted with various electrophiles in the presence of the fluoride ion to yield the corresponding
fluorinated carbinols, ketones, carboxylic acids, and methyl dithiocarboxylates as well as N-pentafluoroethylbenzimidazole.
# 2008 Elsevier B.V. All rights reserved.
Keywords: N-Polyfluoro(trimethylsilyl)ethylazoles; C-nucleophiles; N-Pentafluoroethylbenzimidazole
1. Introduction
[8]. Trimethylsilyl derivatives have been synthesized by
treatment of appropriate bromodifluoromethyl-substituted com-
pounds with tris(diethylamino)phosphine in methylene chloride.
A serious drawback of the method is that the target silane is
difficult to separate completely from unreacted tris(diethylami-
no)phosphine, particularly if the boiling points of the two
substances are close enough. Moreover, tris(diethylamino)pho-
sphine is a toxic reagent. The alternative route to obtain N-
difluoro(trimethylsilyl)methyl derivatives of azoles was using Al
powder in N-methylpyrrolydone [8,9].
(Trifluoromethyl)trimethylsilane obtained for the first time
by Ruppert et al. [1] is an efficient reagent in fluoroorganic
chemistry. Its chemical behaviour was thoroughly studied by
Prakash and Yudin [2]. Fluorinated silanes are similar to the
Grignard reagents in their reactivity being, at the same time,
synthetically convenient and stable to long-term storage, in
contrast to extremely labile perfluoroalkylmagnesium and -
lithium compounds.
Aza-heterocycles bearing fluorinated groups at the nitrogen
atom, although little studied as yet, have already found
agricultural applications, e.g., as herbicides (Sulfentrazone [3]
and Carfentrazone [4]). The introduction of 2-bromoperfluor-
oethyl group to the heterocycle’s nitrogen atom was done at first
on 4-dimethylaminopyridine [5]. Recently, we have synthe-
sized the N-CF2CF2Br [6] and N-CF2CFCl2 [7] substituted
azole derivatives. Substitution of a trimethylsilyl group for the
terminal halogen atom offers wide possibilities for functiona-
lization of the polyfluorinated residue bound to the nitrogen
atom of the heterocycle.
A convenient synthetic access to difluoro(trimethylsilyl)-
methyl-substituted acetylenes has been recently suggested
which implies the reaction of the corresponding bromodi-
fluoromethyl derivatives with trimethylchlorosilane and mag-
nesium [10–12]. We have taken advantage of this approach to
synthesize azoles containing a tetrafluoro(trimethylsilyl)ethyl
group at the nitrogen atom. The heterocycles under study,
including imidazole, benzimidazole, pyrazole, and 3,5-
dimethylpyrazole, have been chosen among those most
widespread in biologically active materials.
The imidazole and benzimidazole derivatives containing a
CF2SiMe3 group at the nitrogen atom were described previously
and their reactions with benzaldehyde and cyclohexanone were
reported [8]. The corresponding secondary alcohols were
obtained in the presence of tetramethylammonium fluoride
2. Results and discussion
The 2-bromotetrafluoroethyl (1a–d) and 2,2-dichlorotri-
fluoroethyl (2a–d) derivatives of the heterocycles concerned
were synthesized by the procedures previously reported by us
[6,7]; compound 1d was obtained for the first time.
2-Bromotetrafluoroethyl derivatives react with magnesium
and trimethylchlorosilane in anhydrous THF at 30–35 8C with a
* Corresponding author. Tel.: +380 44 513 21 98; fax: +380 44 573 26 43.
E-mail address: kirpet@ukr.net (K.I. Petko).
0022-1139/$ – see front matter # 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2008.01.008

302
K.I. Petko et al. / Journal of Fluorine Chemistry 129 (2008) 301–306
Scheme 1.
significant exothermic effect (Scheme 1). The synthesis is
almost entirely free of side reactions and hence furnishes (2-
hetaryltetrafluoroethyl)trimethylsilanes 3a–d in high yields
(75–82%). Compounds 2a–d react analogously at the same
temperature with a much smaller heat release. Only one of two
chlorine atoms is substituted by the trimethylsilyl group to give
(1-chloro-2-hetaryltrifluoroethyl)trimethylsilanes 4a–d. The
yields of the target products are somewhat lower (50–60%)
due to the side reaction, viz., abstraction of two halogen atoms,
which results in the unsaturated 2-chloro-1,2-difluoroethenyl
residue at the nitrogen atom. Silanes 4a–d are easy to purify by
distillation, as they have much higher boiling points than the
side products with the unsaturated fluorinated N-substituent.
The silanes obtained were reacted with benzaldehyde in the
presence of catalytic amounts of the fluoride ion (Scheme 2). As
a source of fluoride ions, we used potassium fluoride, instead of
Scheme 2.

K.I. Petko et al. / Journal of Fluorine Chemistry 129 (2008) 301–306
303
Scheme 6.
disulfide are unstable compounds. Treatment of silane 3c with
carbon disulfide and tetramethylammonium fluoride followed
by methylation with methyl iodide at À10 to 0 8C affords the
corresponding methyl dithiocarboxylate 10 in about 35% yield
(Scheme 4). It appears as a stable red liquid distilling without
decomposition. At lower temperatures (À50 to À70 8C), the
reaction with carbon disulfide does not go to completion.
Silane 3c, when reacted with an activated halogenoarene,
such as p-iodonitrobenzene, in the presence of copper salts (as
in Ref. [13]) produces compound 12 (Scheme 5).
Scheme 3.
It was of interest to ascertain whether perfluorinated N-
substituents could result from the substitution of a fluorine atom
for the trimethylsilyl group in the silanes synthesized.
Previously we used the fluoride anion to generate a nucleophilic
N-hetaryltetrafluoroethyl anion reacting with electrophiles. To
convert the CF2CF2SiMe3 group into a C2F5 radical, it is
expedient to involve a positivated fluorine atom. We have
chosen xenon difluoride as an electrophilic fluorinating agent.
Even bearing a highly electron-acceptor polyfluorinated group
at the nitrogen atom, azoles remain reactive towards
halogenating agents, the substitution normally proceeding at
the heterocyclic ring. On the contrary, the reaction with
benzimidazole leads to N-pentafluoroethyl derivative 13,
though obtained in a low yield and mixed with side-reaction
products (Scheme 6).
Scheme 4.
tetramethylammonium fluoride suggested formerly [7]. Com-
pounds 3a–d were thus converted at room temperature into the
corresponding trimethylsilyl ethers of 2-hetaryltetrafluor-
oethyl(phenyl)carbinols 5a–d, which were hydrolyzed to the
carbinols 6a–d. By interaction of compounds 3a–d with
benzoyl fluoride in the similar conditions, 2-hetaryltetrafluoro-
ethyl(phenyl)ketones 7a–d were obtained.
Likewise, compounds 4c,d containing the CF2CFClSiMe3
moiety with an asymmetric carbon atom easily enter into this
reaction to produce an inseparable 1:1 diastereomeric mixture
of trimethylsilyl ethers of 1-chloro-2-hetaryltrifluoroethyl(phe-
nyl)carbinols 8c,d.
Silanes 3a–d and 4a–c react with carbon dioxide in glyme at
À80 to À30 8C under presence of an equimolar quantity of
tetramethylammonium fluoride (Scheme 3). (In this case,
potassium fluoride is ineffective as a catalyst, in contrast to the
reaction with benzaldehyde.) The resulting carboxylic acids,
9a–d and 10b,c, obtained in 60–65% yields appear as stable and
readily crystallizable substances which can be involved in
further conversions.
To conclude, we have obtained a number of novel synthons
derived from various azoles which contain the tetrafluoro-
(trimethylsilyl)ethyl and chlorotrifluoro(trimethylsilyl)ethyl
groups at the nitrogen atom. On this basis, synthetic routes
have been found to fluorinated heterocyclic carbinols, ketones,
carboxylic acids, and methyl dithiocarboxylates as well as to
N-pentafluoroethyl benzimidazole.
3. Experimental
3.1. General
Boiling and melting points are uncorrected. 1H NMR-
spectra were recorded in CDCl3 on a Varian VXR-300
Unlike carboxylic acids 9 and 10, their dithio analogues
produced by the reaction of silanes 3 and 4 with carbon
Scheme 5.

304
K.I. Petko et al. / Journal of Fluorine Chemistry 129 (2008) 301–306
(300 MHz) using TMS as an internal standard. 19F NMR-
spectra were recorded in CDCl3 on a Varian VXR-200
(188 MHz) using CCl3F as an internal standard. IR spectra
were recorded on UR-20 spectrophotometer. All reactions were
carried out under argon. THF and glyme were freshly distilled
from sodium benzophenone ketyl, immediately prior to use.
DMF were distilled from BaO after previous fractionalisation.
C8H12ClF3N2Si: C, 37.43; H, 4.71; Si, 10.94. Found: C,
37.51; H, 4.79; Si, 10.70.
(4b) Yield 53%; bp 103–105 8C (0.03 Torr), mp 65–66 8C;
19F NMR d À148.70 (s, 1F), À88.99 (d, 1F, J = 220 Hz),
1
À81.94 (d, 1F, J = 220 Hz). H NMR d 0.38 (s, 9H), 7.35 (m,
2H), 7.59 (m, 1H), 7.81 (m, 1H), 8.11 (s, 1H). Anal. Calcd. for
C12H14ClF3N2Si: C, 46.98; H, 4.60; Si, 9.15. Found: C, 46.85;
H, 4.55; Si, 9.09.
3.2. 1-(2-Bromotetrafluoroetyl)-3,5-dimethylpyrazole 1d
(4c) Yield 56%; bp 27–28 8C (0.5 Torr); 19F NMR d
À148.30 (s, 1F), À89.43 (d, 1F, J = 214 Hz), À87.54 (d, 1F,
J = 214 Hz). 1H NMR d 0.28 (s, 9H), 6.41 (s, 1H), 7.69 (d, 1H,
J = 1.5 Hz), 7.78 (d, 1H, J = 1.5 Hz). Anal. Calcd. for
C8H12ClF3N2Si: C, 37.43; H, 4.71; Si, 10.94. Found: C,
37.40; H, 4.56; Si, 11.00.
(4d) Yield 70%; bp 42–44 8C (0.5 Torr); 19F NMR d
À146.46 (s, 1F), À92.61 (d, 1F, J = 200 Hz), À81.94 (d, 1F,
J = 200 Hz). 1H NMR d 0.28 (s, 9H), 2.21 (s, 3H), 2.38 (s, 3H),
5.91 (s, 1H). Anal. Calcd. for C10H16ClF3N2Si: C, 42.23; H,
5.62; Si, 9.84. Found: C, 42.48; H, 5.86; Si, 9.63.
The compound was obtained by the procedure given in Ref.
[6].
Yield 82%; bp 72–74 8C (15 Torr); 19F NMR d À95.95 (s,
2F), À62.82 (s, 2F). 1H NMR d 2.21 (s, 3H), 2.35 (s, 3H), 5.95
(s, 1H). Anal. Calcd. for C7H7BrF4N2: C, 30.57; H, 2.57; Br,
29.05. Found: C, 30.85; H, 2.77; Br, 28.66.
3.3. (2-Hetaryltetrafluoroethyl)trimethylsilanes 3a–d, and
(1-chloro-2-hetaryltrifluoroethyl)trimethylsilanes 4a–d:
general procedure
3.4. Trimethylsilyl ethers of 2-
In a three-neck flask, magnesium (0.36 g, 0.015 mol) was
activated with iodine vapour in a stream of argon. After cooling
the system to room temperature, Me3SiCl (4.35 g, 0.04 mol) in
freshlydistilledTHF(10 ml)wasadded. Asolutionofcompound
1 or 2 (0.01 mol) in THF (10 ml) was slowly added through a
dropping funnel with a pressure equalizer and the mixture was
stirred with a magnetic stirrer at the temperature not above 35 8C
until an exothermic reaction occurred. After that, the stirring was
continued for 1 h at 30–35 8C. Excess trimethylchlorosilane and
a part of THF (30–40%) were removed by evaporation in vacuo.
Hexane and water were added to the residue; the organic layer
was separated, washed with water (3 Â 50 ml), and dried with
MgSO4. Hexane was evaporated on a rotary evaporator and the
residue was distilled in vacuo.
(3a) Yield 72%; bp 83–85 8C (15 Torr); 19F NMR d À127.94
(s, 2F), À91.62 (s, 2F). 1H NMR d 0.27 (s, 9H), 7.13 (m, 2H),
7.79 (s, 1H). Anal. Calcd for C8H12F4N2Si: C, 39.99; H, 5.03;
Si, 11.69. Found: C, 39.95; H, 4.97; Si, 11.66.
(3b) Yield 67%; bp 110–115 8C (0.5 Torr); 19NMR d
À126.79 (s, 2F), À91.20 (s, 2F). 1H NMR d 0.33 (s, 9H), 7.35
(m, 2H), 7.57 (m, 1H), 7.82 (m, 1H), 8.08 (s, 1H). Anal. Calcd.
for C12H14F4N2Si: C, 49.64; H, 4.86; Si, 9.67. Found: C, 49.61;
H, 4.78; Si, 9.65.
hetaryltetrafluoroethyl(phenyl)carbinols 5a–d and
diastereomeric mixture of trimethylsilyl ethers of 1-chloro-
2-hetaryltrifluoroethyl(phenyl)carbinols 8c,d: general
procedure
In an inert atmosphere, a solution of compound 3 or 4
(0.004 mol) in anhydrous THF (7 ml) was mixed with a
solution of benzaldehyde (0.48 g, 0.0045 mol) in anhydrous
THF (7 ml). KF or Me4NF (30–40 mg, 3.2 Â 10À5 to
4.3 Â 10À5 mol) were added to the stirred mixture. After
stirring for 4–5 h at room temperature, the mixture was allowed
to stand overnight. Then it was poured into water (30–40 ml)
and the product was extracted with pentane or hexane
(2 Â 25 ml). The organic extracts were washed with water
(3 Â 50 ml) and dried with MgSO4. After evaporating the
solvent, the residue was distilled in vacuo.
(5a) Yield 72%; bp 93–95 8C (0.5 Torr); 19F NMR d
À127.76 (dm, 1F, J = 280 Hz), À116.74 (d, 1F, J = 280 Hz),
1
À94.06 (d, 1F, J = 225 Hz), À91.73 (dm, 1F, J = 225 Hz). H
NMR d 0.03 (s, 9H), 5.05 (dd, 1H, J = 3 Hz), 7.10 (d, 2H,
J = 2 Hz), 7.35 (m, 5H), 7.77 (s, 1H). Anal. Calcd. for
C15H18F4N2OSi: C, 52.01; H, 5.24; Si, 8.11. Found: C, 52.18;
H, 5.15; Si, 8.23.
(3c) Yield 80%; bp 72–74 8C (20 Torr); 19F NMR d À127.88
(s, 2F), À94.99 (s, 2F). 1H NMR d 0.25 (s, 9H), 6.43 (dd, 1H,
J = 2 Hz), 7.71 (d, 1H, J = 2 Hz), 7.77 (d, 1H, J = 2 Hz). Anal.
Calcd. for C8H12F4N2Si: C, 39.99; H, 5.03; Si, 11.69. Found: C,
39.80; H, 5.15; Si, 11.70.
(5b) Yield 54%; bp 129–131 8C (0.2 Torr), mp 53–54 8C,
19F NMR d À125.47 (dm, 1F, J = 280 Hz), À114.59 (d, 1F,
J = 280 Hz), À93.65 (d, 1F, J = 225 Hz), À90.70 (dm, 1F,
1
J = 225 Hz). H NMR d 0.03 (s, 9H), 5.15 (dd, 1H, J = 3 Hz),
7.36 (m, 7H), 7.58 (d, 1H, J = 2 Hz), 7.76 (m, 1H), 8.04 (s, 1H).
Anal. Calcd. for C19H20F4N2OSi: C, 57.56; H, 5.09; Si, 7.08.
Found: C, 57.61; H, 5.14; Si, 7.15.
(3d) Yield 65%; bp 97–98 8C (15 Torr); 19F NMR d À126.10
1
(s, 2F), À92.82 (s, 2F). H NMR d 0.25 (s, 9H), 2.21 (s, 3H),
2.35 (s, 3H), 5.92 (s, 1H). Anal. Calcd. for C10H16F4N2Si: C,
44.76; H, 6.01; Si, 10.47. Found: C, 44.82; H, 5.98; Si, 10.54.
(4a) Yield 54%; bp 37–38 8C (0.5 Torr); 19F NMR d
À149.97 (s, 1F), À90.09 (d, 1F, J = 220 Hz), À81.86 (d, 1F,
(5c) Yield 60%; mp 23–25 8C; 19F NMR d À128.60 (dm, 1F,
1
J = 280 Hz), À117.33 (d, 1F, J = 280 Hz), À94.22 (s, 2F,). H
NMR d 0.03 (s, 9H), 5.21 (dd, 1H, J = 2 Hz), 6.44 (s, 1H), 7.38
(m, 5H), 7.75 (d, 1H), 7.79 (d, 1H). Anal. Calcd. for
C15H18F4N2OSi: C, 52.01; H, 5.24; Si, 8.11. Found: C,
52.07; H, 5.32; Si, 8.05.
1
J = 220 Hz). H NMR d 0.31 (s, 9H), 7.11 (d, 1H, J = 2 Hz),
7.17 (d, 1H, J = 2 Hz), 7.78 (s, 1H). Anal. Calcd. for

K.I. Petko et al. / Journal of Fluorine Chemistry 129 (2008) 301–306
305
(5d) Yield 73%; bp 98–100 8C (0.5 Torr); 19F NMR d
3.6. 2-Hetaryltetrafluorethyl(phenyl)ketones 7a–d: general
procedure
À125.35 (dm, 1F, J = 250 Hz), À114.94 (d, 1F, J = 250 Hz),
1
À90.05 (d, 1F, J = 225 Hz), À89.14 (dd, 1F, J = 225 Hz). H
NMR d 0.01 (s, 9H), 2.25 (s, 3H), 2.35 (s, 3H), 5.51 (dd, 1H,
J = 2 Hz), 5.94 (s, 1H), 7.38 (m, 5H). Anal. Calcd. for
C17H22F4N2OSi: C, 54.53; H, 5.92; Si, 7.50. Found: C, 54.41;
H, 6.12; Si, 7.41.
In an inert atmosphere, a solution of compound 3a–d
(0.004 mol) in anhydrous THF (7 ml) was mixed with a
solution of benzoyl fluoride (0.56g, 0.0045 mol) in
anhydrous THF (7 ml). Me4NF (30–40 mg, 3.2 Â 10À5 to
4.3 Â 10À5 mol) were added to the stirred mixture. After
stirring for 4–5 h at room temperature, the mixture was allowed
to stand overnight. After evaporating the solvent in vacuo, the
residue was distilled in vacuo.
(8c) Yield 64%; bp 102–104 8C (0.5 Torr); 19F NMR d
À134.31 (m, 1F), À123.94 (m, 1F), À89.47 (dd, 2F,
1
J = 225 Hz), À87.47 (dd, 2F, J = 210 Hz). H NMR d 0.02,
0.04 (s,s, 9H), 5.35, 5.45 (d,d, 1H, J = 2 Hz), 6.50 (m, 1H), 7.41
(m, 5H), 7.82–7.90 (m, 2H). Anal. Calcd. for
C15H18ClF3N2OSi: C, 49.65; H, 5.00; Si, 7.74. Found: C,
49.53; H, 4.95; Si, 7.95.
(7a) Yield 70%; bp 108–110 8C (0.5 Torr); 19F NMR d
À114.10 (s, 2F), À92.77 (s, 2F). 1H NMR d 7.20 (s, 1H), 7.62–
7.70 (m, 3H), 7.82–7.87 (m, 1H), 8.03–8.05 (m, 2H), 8.30 (s,
1H). IR spectra: 1705 cmÀ1 (C O). Anal. Calcd. for
C12H8F4N2O: C, 52.95; H, 2.96; N, 10.29. Found: 53.12; H,
3.08; N, 10.36.
(8d) Yield 25%; bp 110–112 8C (0.1 Torr); 19F NMR d
À132.66 (m, 1F), À124.59 (m, 1F), À86.90 (dd, 1F,
J = 225 Hz), À84.75 (dd, 1F, J = 210 Hz) À84.42 (d, 1F,
J = 210 Hz), À82.34 (dd, 1F, J = 225 Hz).
(7b) Yield 72%; mp 61–62 8C; 19F NMR d À114.00 (s, 2F),
1H NMR d 0.02–0.04 (s,s, 9H), 2.26 (s, 3H), 2.35, 2.38 (s,s,
3H), 5.56, 5.63 (s,s 1H), 5.93, 5.95 (s,s 1H), 7.36–7.91 (m, 5H).
Anal. Calcd. for C17H22ClF3N2OSi: C, 52.23; H, 5.67; Si, 7.18.
Found: C, 52.30; H, 5.65; Si, 7.12.
À95.29 (s, 2F). H NMR d 7.34–7.37 (m, 2H), 7.48–7.53 (m,
1
2H), 7.61–7.64 (m, 2H), 7.80–7.83 (m, 1H), 8.02–8.05 (m, 2H),
8.18 (s, 1H). IR spectra: 1700 cmÀ1 (C O) Anal. Calcd. for
C16H10F4N2O: C, 59.63; H, 3.13; N, 8.69. Found: C, 59.52; H,
3.20; N, 8.57.
3.5. 2-Hetaryltetrafluoroethyl(phenyl)carbinols 6a–d:
general procedure
(7c) Yield 69%; bp 90–95 8C (0.5 Torr); 19F NMR d
À114.51 (s, 2F), À92.13 (s, 2F). 1H NMR d 6.45 (m, 1H), 7.47–
7.52 (m, 2H), 7.64 (m, 2H), 7.89 (m, 1H), 8.02 (m, 2H). IR
spectra: 1695 cmÀ1 (C O). Anal. Calcd. for C12H8F4N2O: C,
52.95; H, 2.96; N, 10.29. Found: C, 52.88; H, 2.98; N, 10.09.
(7d) Yield 70%; mp 62–64 8C, bp 115–117 8C (0.5 Torr);
19F NMR d À114.00 (s, 2F), À90.19 (s, 2F). 1H NMR d 1.98 (s,
3H), 2.43 (s, 3H), 5.91 (s, 1H), 7.48–7.62 (m, 3H), 7.99–8.02
(m, 2H). IR spectra: 1710 cmÀ1 (C O). Anal. Calcd. for
C14H12F4N2O: C, 56.00; H, 4.03; N, 9.33. Found: C, 56.10; H,
3.90; N, 9.60.
Compounds 5a–d (0.0035 mol) and concentrated HCl (5 ml)
were mixed in a flask. The stirred mixture was boiled for 0.5 h.
After alkalizing the solution to pH 8–9, the product was
extracted with methylene chloride (3 Â 20 ml), dried with
MgSO4, and recrystallized from hexane on cooling with liquid
nitrogen.
(6a) Yield 70%; mp 91–92 8C; 19F NMR d À129.12 (dd, 1F,
J = 280 Hz), À118.01 (d, 1F, J = 280 Hz), À94.07 (d, 2F,). 1H
NMR d 4.82 (br.s, 1H), 4.94 (dd, 1H, J = 3 Hz), 6.97 (s, 1H),
7.16 (s, 1H), 7.38–7.45 (m, 5H), 7.71 (s, 1H). Anal. Calcd. for
C12H10F4N2O: C, 52.56; H, 3.68; N, 10.22. Found: C, 52.52; H,
3.75; N, 10.31.
3.7. 2-Hetaryltetrafluoroethyl-1-carboxylic acids 9a–d and
2-hetaryl-1-chlorotrifluoroethyl-1-carboxylic acids 10b,c
(6b) Yield 72%; mp 133–134 8C; 19F NMR d À150.59 (dm,
1F, J = 280 Hz), À139.69 (dm, 1F, J = 280 Hz), À118.75 (dm,
1F, J = 225 Hz), À116.30 (dm, 1F, J = 225 Hz). 1H NMR d 4.87
(br.s, 1H), 4.95 (dd, 1H, J = 3 Hz), 7.39 (m, 8H), 7.59 (d, 1H,
J = 2 Hz), 8.08 (s, 1H). Anal. Calcd. for C16H12F4N2O: C,
59.26; H, 3.73; N, 8.64. Found: C, 59.33; H, 3.68; N, 8.74.
(6c) Yield 90%; mp 80–81 8C; 19F NMR d À130.44 (dm, 1F,
J = 280 Hz), À115.82 (dd, 1F, J = 280 Hz), À98.22 (dd, 1F,
J = 225 Hz), À93.16 (dd, 1F, J = 225 Hz). 1H NMR d 4.84 (br.s,
1H), 5.01 (dd, 1H, J = 3 Hz), 6.53 (s, 1H), 7.41–7.55 (m, 5H),
7.83 (d, 1H, J = 2 Hz), 7.91 (s, 1H, J = 2 Hz). Anal. Calcd. for
C12H10F4N2O: C, 52.56; H, 3.68; N, 10.22. Found: C, 52.72; H,
3.52; N, 10.14.
A solution of compound 3 or 4 (0.005 mol) in anhydrous
glyme (15 ml) was placed into a flask annealed in a stream of
argon. Then the system was cooled to À90 to À80 8C and
excess CO2 (2–3 g) was condensed in it after passing through
a tube filled with P2O5. Then Me4NF (0.55 g, 0.006 mol)
was poured into the stirred mixture and the stirring was
continued for 0.5 h at À35 to À40 8C and for 1 h at
room temperature. Glyme was evaporated in vacuo; ether
(30 ml) and 1% HCl (10 ml) were added to the residue. The
mixture was placed into a separating funnel and the aqueous
layer was separated. Ether was evaporated at atmospheric
pressure adding benzene to remove the dissolved water. The
residue was recrystallized from hexane with a small amount
of SiO2 added (to remove a little of unknown polymeric
material).
(6d) Yield 70%; mp 55–56 8C; 19F NMR d À128.40 (dm, 1F,
J = 260 Hz), À113.95 (dd, 1F, J = 260 Hz), À94.68 (dd, 1F,
1
J = 210 Hz), À89.56 (dd, 1F, J = 210 Hz). H NMR d 2.27 (s,
(9a) Yield 55%; mp 216–217 8C; 19F NMR d À118.06 (s,
2F), À94.05 (s, 2F). 1H NMR d 7.43 (s, 1H), 7.79 (s, 1H), 8.76
(s, 1H), 11.87 (br.s, 1H). Anal. Calcd. for C6H4F4N2O2: C,
33.98; H, 1.90; N, 13.21. Found: C, 33.85; H, 1.93; N, 13.33.
3H), 2.41 (s, 3H), 4.91 (dd, 1H J = 3 Hz), 6.03 (s, 1H), 7.41 (m,
5H). Anal. Calcd for C14H14F4N2O: C, 55.63; H, 4.67; N, 9.27.
Found: C, 55.62; H, 4.58; N, 9.30.

306
K.I. Petko et al. / Journal of Fluorine Chemistry 129 (2008) 301–306
(9b) Yield 66%; mp 150–152 8C; 19F NMR d À121.66 (s,
annealed flask. After adding KF (0.002 mol) to the mixture, it
was stirred for 1 h at 100–120 8C, poured into water, extracted
with ether, and dried with MgSO4. The solvent was evaporated
and the product was isolated by column chromatography on
silica gel (with a 1:1 mixture of methylene chloride and hexane
used as an eluent). Yield 25%; mp 84–86 8C; 19F NMR d
À112.91 (s, 2F), À98.56 (s, 2F). 1H NMR d 6.44 (s, 1H), 7.66–
7.89 (m, 4H), 8.27 (d, 1H, J = 2 Hz), 8.30 (d, 1H, J = 2 Hz).
Anal. Calcd. for C11H7F4N3O2: C, 45.69; H, 2.44; N, 14.53.
Found: C, 45.58; H, 2.52; N, 14.62.
1
2F), À97.50 (s, 2F). H NMR d 7.15 (m, 2H), 7.36–7.38 (m,
1H), 7.55–7.56 (m, 1H), 7.96 (s, 1H), 11.47 (br.s, 1H). Anal.
Calcd. for C10H6F4N2O2: C, 45.82; H, 2.31; N, 10.69. Found: C,
45.69; H, 2.55; N, 10.71.
(9c) Yield 62%; mp 126–127 8C; 19F NMR d À120.08 (s,
2F), À95.60 (s, 2F). 1H NMR d 6.17 (s, 1H), 7.38 (s, 1H), 7.58
(s, 1H), 13.48 (br.s, 1H). Anal. Calcd. for C6H4F4N2O2: C,
33.98; H, 1.90; N, 13.21. Found: C, 33.99; H, 2.04; N, 13.16.
(9d) Yield 59%; mp 110–112 8C; 19F NMR d À117.69 (s,
2F), À92.85 (s, 2F). 1H NMR d 2.27 (d, 3H), 2.45 (d, 3H), 6.07
(s, 1H), 13.14 (br.s, 1H). Anal. Calcd. for C8H8F4N2O2: C,
40.01; H, 3.36; N, 11.67. Found: C, 39.80; H, 3.32; N, 11.82.
(10b) Yield 37%; mp 133–135 8C; 19F NMR d À125.50 (s,
1F), À91.06 (d, 1F, J = 220 Hz), À88.97 (d, 1F, J = 220 Hz). 1H
NMR d 7.23 (s, 1H), 7.38 (m, 1H), 7.81 (m, 2H), 8.96 (s, 1H),
13.20 (br.s, 1H). Anal. Calcd. for C10H6ClF3N2O2: C, 43.11; H,
2.17; Cl, 12.72. Found: C, 43.25; H, 2.15; Cl, 12.75.
(10c) Yield 45%; mp 113–114 8C; 19F NMR d À127.00 (s,
1F), À95.27 (d, 1F, J = 220 Hz), À91.10 (d, 1F, J = 220 Hz). 1H
NMR d 6.55 (s, 1H), 7.88 (d, 1H), 7.94 (d, 1H), 13.17 (br.s, 1H).
Anal. Calcd. for C6H4ClF3N2O2: C, 31.53; H, 1.76; Cl, 15.51.
Found: C, 31.72; H, 1.68; Cl, 15.33.
3.10. 1-Pentafluoroetylbezimidazole 13
Xenon difluoride (1.86 g, 0.011 mol) was suspended in
anhydrous methylene chloride (20 ml) at À30 8C in an inert
dry atmosphere and compound 3b (2.9 g, 0.01 mol) was slowly
added to it. Gradual heating of the reaction mixture up to À5 8C
resulted in an exothermic reaction with the release of xenon.
The stirred mixture was cooled so that the temperature was not
above 20 8C. The reaction flask was equipped with a reflux
condenser and methylene chloride was evaporated in vacuo.
The residue was fractioned and the most volatile product was
collected. Yield 15%; bp 78–80 8C (20 Torr); 19F NMR d
À98.98 (s, 2F), À85.22 (s, 3F). 1H NMR d 7.35 (m, 2H), 7.56
(m, 1H), 7.79 (m, 1H), 8.10 (s, 1H). Anal. Calcd. for
C9H5F5N2: C, 45.78; H, 2.13; N, 11.86. Found: C, 45.71; H,
2.24; N, 11.78.
3.8. 2-(1-Pyrazolyl)tetrafluoroethyl-1-
methylditiocarboxylate 11
In a flask annealed in a stream of argon, compound 3c
(0.96 g, 0.004 mol) and CS2 (0.6 g, 0.008 mol) were mixed in
anhydrous glyme (15 ml). The mixture was cooled to À20 8C
and Me4NF (0.46 g, 0.005 mol) was added in a stream of argon.
After stirring at À10 to À15 8C for 5 min, CH3I (0.5 ml, 1.1 g,
0.008 mol) was added, followed by stirring for another 0.5 h at
room temperature and evaporating glyme. The residue was
treated with water (20 ml) and the product was extracted with
pentane (2 Â 20 ml). The pentane solution was washed with
water (3 Â 20 ml) and dried with MgSO4. Pentane was
evaporated and the residue was distilled in vacuo. Yield
35%; bp 96–98 8C (10 Torr); 19F NMR d À104.87 (s, 2F),
À96.32 (s, 2F). 1H NMR d 2.18 (s, 3H), 6.42 (m, 1H), 7.65 (d,
1H J = 2 Hz), 7.75 (d, 1H, J = 2 Hz). Anal. Calcd. for
C7H6F4N2S2: C, 32.56; H, 2.34; S, 24.83. Found: C, 32.36;
H, 2.32; S, 24.58.
References
[1] I. Ruppert, K. Schlich, W. Volbach, Tetrahedron Lett. 25 (1984) 2195–
2198.
[2] G.K. Surya Prakash, A.K. Yudin, Chem. Rev. 97 (1997) 757–786.
[3] J. Becker, Inventory of Industrial Fluoro-biochemicals, Eyrolles, Paris,
1996.
[4] F.E. Dayan, S.O. Duke, J.D. Weete, G. Hancock, Pestic. Sci. 51 (1999)
65–73.
[5] A. Kolomeitsev, R.-M. Schoth, E. Lork, G.V. Roschenthaler, J. Chem. Soc.
Chem. Commun. (1996) 335–336.
[6] K.I. Petko, T.M. Sokolenko, A.V. Bezdudny, L.M. Yagupolskii, J. Fluorine
Chem. 126 (2005) 1342–1346.
[7] K.I. Petko, L.M. Yagupolskii, Synth. Commun. 14 (2006) 1368–1372.
[8] G. Bissky, G.V. Roschenthaler, E. Lork, J. Barten, M. Medebielle, V.I.
Staninets, A. Kolomeitsev, J. Fluorine Chem. 109 (2001) 173–181.
[9] G. Bissky, V.I. Staninets, A. Kolomeitsev, G.V. Roschenthaler, Synlett
(2001) 374–378.
[10] G.B. Hammond, J. Fluorine Chem. 127 (2006) 476–488.
[11] M. Mae, J.A. Hong, K. Uneyama, G.B. Hammond, Tetrahedron Lett. 46
(2005) 1787–1789.
3.9. 1-(1-Pyrazolyl)-2-(4-nitrophenyl)tetrafluoroethane 12
4-Iodonitrobenzene (0.47 g, 0.0019 mol), CuI (0.48 g,
0.0025 mol), and a solution of compound 3c (0.48 g,
0.002 mol) in anhydrous DMF (2 ml) were mixed in an
[12] H.E. Hurst, M. Mae, J.A. Hong, G.B. Hammond, J. Fluorine Chem. 127
(2006) 126–132.
[13] H. Urata, T. Fuchicami, Tetrahedron Lett. 32 (1991) 91–94.