Synthesis of β-functionalized ethyl polyfluoroaryl sulfides, sulfoxides, and sulfones underlain by pentafluorobenzoic acid

Article abstract of DOI:10.1134/S1070428009110104

The reaction of pentafluorobenzoic acid with 2-mercaptoethanol followed by modification of the reaction product by oxidationm halohydroxylation and (or) decarboxylation led to the formation of β-halo- and β-oxyethyl polyfluoroaryl sulfides, sulfoxides, an

Full text of DOI:10.1134/S1070428009110104

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 11, pp. 1637−1643. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © V.V. Litvak, A.S. Kondrat’ev, V.D. Shteimgarts, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 11,
pp. 1648−1653.
Synthesis of β-Functionalized Ethyl Polyfluoroaryl Sulfides,
Sulfoxides, and Sulfones Underlain by Pentafluorobenzoic Acid
V. V. Litvak†a, A. S. Kondrat’evb,c and V. D. Shteimgartsb,d
aInstitute of Biochemistry and Fundamental Medicine, Siberian Division,
Russian Academy of Sciences, Novosibirsk, Russia
bVorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division,
Russian Academy of Sciences, Novosibirsk, 630090 Russia
e-mail: shtein@nioch.nsc.ru
cNovosibirsk State Pedagogical University, Novosibirsk, Russia
dNovosibirsk State University, Novosibirsk, Russia
Received October 3, 2008
Abstract—The reaction of pentafluorobenzoic acid with 2-mercaptoethanol followed by modification of the
reaction product by oxidationm halohydroxylation and (or) decarboxylation led to the formation of β-halo- and
β-oxyethyl polyfluoroaryl sulfides, sulfoxides, and sulfones, initial compounds for the synthesis of fluorine-
containing 2,3-dihydro-1,4-benzothiazines, 2,3-dihydro-1,4-benzoxathiynes, and 2,3-dihydro-1,4-benzodithiynes
and also of their S-oxides and S-dioxides based on intramolecular nucleophilic sybstitution.
DOI: 10.1134/S1070428009110104
saturated ethers [14], by Diels–Alder heteroreaction of
o-thioquinone with vinyl compounds [22], or by intra-
molecular alkoxydechlorination of S-(2'-hydroxyethyl)-2-
chlorothiophenol derivatives [23]. The syntheses of 2,3-
dihydro-1,4-benzodithiynes involve the reactions of benzo-
pentathiepines with unsaturated compounds [24], cyclo-
hexanone or cyclohexenone with 1,2-ethanedithiol in the
presence of 1,1'-(ethane-1,2-diyl)dipyridinium bistri-
bromide [25], and also intramolecular cyclization of
2-phenylsulfanylethylthiosulfonates or the reactions of
dithiopyrocatechol derivatives with 1,2-dibromoethane
[26].
Among the sulfur-containing benzoheterocycles
physiologically active compounds were found of a wide
range of action [1]. From this viewpoint 2,3-dihydro-1,4-
benzothiazines, 2,3-dihydro-1,4-benzoxathiynes, and 2,3-
dihydro-1,4-benzodithiynes and also their S-oxides and
S-dioxides are especially interesting [2–5]. The intro-
duction of fluorine into a heterocyclic compound may
significantly affect the character and power of its bio-
logical action [6–10]. Besides the presence in the benzene
fragment of the benzoheterocycle of several fluorine
atoms provides a possibility of a repeated modification
of the compound by a nucleophilic substitution [11–13].
This information underlies the interest to fluorinated
derivatives of the mentioned heterocyclic systems.
Thus the introducing into the sulfur-containing ring of
the second heteroatom is due to its presence in the initial
compound, but the methods of building up the heterocyclic
fragment underlain by its character are not general. In
their turn the syntheses of compounds contain-ing sulfur
in the oxidized state (sulfoxide or sulfone) are performed
commonly by the oxidation of the sulfide unit of the already
formed heterocycle [2, 3, 5, 23]. This fact provides certain
limitations for the preparation by this procedure of
compounds containing easily oxidizable groups. Besides
it is impossible to prepare derivatives substituted in the
The synthesis of 2,3-dihydro-1,4-benzothiazine is
commonly based on the application as initial compounds
of the 2-aminothiophenol [1, 14–16] or of a o-halo-
substituted nitroarene [3, 17–19]. Other ways to 2,3-di-
hydro-1,4-benzothiazine derivatives were also described
[15, 16, 20]. 2,3-Dihydro-1,4-benzoxathiynes are prepared
by the reductive cyclization of o-oxyarylthioketones [5,
21], by the addition of o-mercaptophenol to α,β-un-
† Deceased.
1637

LITVAK et al.
1638
Scheme 1.
X
F
X
X
F
F
F
F
F
F
F
F
F
F
_HF
F
Y
YH
OnS
OnS
n = 0, 1, 2; YH = OH, NH2, NHR, SH
benzene ring requiring the presence in the precursor of a
substituent whose nature is incompatible with the
synthesis conditions.
presence of a carboxy group that at least does not hamper
the introduction of the β-functionalized ethylsulfide into
the para-position with respect to it by the nucleophilic
substitution of a fluorine atom and the subsequent
cyclization furnishes wide opportunities for further
functionalization of the synthesized heterocyclic
compound both at the carboxy group and by the
nucleophilic substitution of fluorine atoms. The attractive
feature of this function is also the easy opportunity of its
removal from the polyfluoroaromatic ring by decarboxyla-
tion giving a place for a wide range of modifications by
means of electrophilic substitution of the hydrogen.
With respect to the synthesis of polyfluoro-2,3-dihydro-
1,4-benzothiazines, -oxathiynes and -dithiynes, and also
of the corresponding S-oxides and S-dioxides it seemed
possible to overcome the above-mentioned difficulties
using a common approach to all cases based on the
presence in the initial compound of several fluorine atoms.
This approach makes it possible to use as the general
basic compound an available polyfluoroarene, and as the
method of building up on this compound of the heterocycle,
the introducing by the nucleophilic substitution of the
fluorine an ethylsulfide moiety containing a functional
group in the β-position either directly playing the role of
the reaction site for the final nucleophilic cyclization or
easily converted into it (Scheme 1). If the sulfide sulfur
required oxidation then depending on the structure of the
heterocycle precursor it can be carried out either before
cyclization or in the cyclic sulfide. Therewith the presence
of a sulfur-containing group in the ortho-position to the
fluorine substituted at the cyclization in any case favors
the intramolecular cyclization.
As the first step to the performance of the above
defined procedure with respect to the synthesis of the
building blocks for the sulfur-containing polyfluoro-
benzoheterocycles we studied in this research the reac-
tions of the pentafluorobenzoic acid with 2-mercapto-
ethanol. The choice of this compound is stipulated by
the fact that after the substitution of the first fluorine
atom by the β-hydroxyethylthiol group the hydroxy group
of the latter may be used in the final heterocyclization in
two ways (cf. [29]): both as a nucleophilic site and for
introducing other nucleophilic groups by successive
replacement of the hydroxyl by halogen atom any further
by (alkyl)amino or mercapto group. Therewith the
primarily introduced sulfide sulfur atom may if required
be oxidized with retaining either the hydroxy group or
the opportunity of its replacement. This approach allows
the application of the same bifunctional reagent for the
synthesis of sulfur-containing heterocycles differing by
the nature of the second heteroatom and the state of
sulfur oxidation.
Some examples of this approach were described in
the literature, for instance, the synthesis of the derivative
of bis(5,8-vinylsulfanyl)-6-fluoro-2,3-dihydro-1,4-
benzothiazine by the reaction of bis(1,4-vinylsulfanyl)tetra-
fluorobenzene with 2-aminoethanethiol [27].Amosova et
al for the preparation of di- and tetraoxides of the
fluorinated benzo-di-1,4-thiazines used the addition to the
vinyl group of 1,4-bis(vinylsulfinyl- and -sulfonyl)-
tetrafluorobenzenes followed by the nucleophilic
cyclization [28].
The reaction of pentafluorobenzoic acid with
2-mercaptoethanol cleanly provided 4-(2-hydroxyethyl-
sulfanyl)-2,3,5,6-tetrafluorobenzoic acid (I) (Scheme 2).
The conversion of acid I into other compounds being
potential precursors of heterocycles may be performed
The suitable type of the underlying compound for
putting this synthetic scheme into operation are
polyfluoroarenecarboxylic acids. This choice beside the
accessibility of these compounds is supported by the
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SYNTHESIS OF β-FUNCTIONALIZED ETHYL POLYFLUOROARYL SULFIDES
1639
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LITVAK et al.
1640
by modification of three functional groups present in the
molecule: carboxy, hydroxy, and sulfide moieties. In the
present study we performed the oxidation of sulfur,
halodehydroxylation, and decarboxylation. It turned out
that in the former two cases depending on the reaction
conditions different degree of modification was attained.
sulfides IX and III respectively.
The composition and structure of all compounds obtain-
ed was proved by elemental analysis and 1Hand 19F NMR
1
spectra. In the H NMR spectra of compounds I, III,
VII–XI, XIII, and XIV in the region δ 3.0–4.5 ppm
two signals of methylene groups appear in the form of
triplets. In the spectra of compounds II, IV–VI, and XII
the analogous signals have a more complex structure. In
the spectra of sulfoxides IV–VI, XII this pattern is
evidently caused by the nonequivalence of the geminal
protons due to the asymmetry of the sulfur atom. In the
spectrum of compound II the proton signals of ethylene
bridge are overlapped and appear as a common multiplet.
For instance, a cautious oxidation of sulfide I, and also
of 4-(2-bromomethylsulfanyl)-2,3,5,6-tetrafluoro-benzoic
acid (II) and 2,3,5,6-tetrafluoro(2-chloroethylsulfanyl)-
benzene (III) with a stoichiometric amount of hydrogen
peroxide in water or AcOH gave the corresponding
compounds containing a sulfoxide moiety: 4-(2-hydroxy-
ethylsulfinyl)- and 4-(2-bromoethylsulfinyl)-2,3,5,6-
tetrafluorobenzoic acids (IV, V), and also 2,3,5,6-
tetrafluoro(2-chloroethylsulfinyl)benzene (VI). Vigorous
oxidation of sulfides I and II with a 5-fold amount of
hydrogen peroxide in trifluoroacetic acid gave sulfones:
4-(2-hydroxyethylsulfonyl)- and 4-(2-bromoethyl-
sulfonyl)-2,3,5,6-tetrafluorobenzoic acids (VII, VIII).
1
In the H NMR spectra of all tetrafluorobenzene
derivatives the characteristic signal of the proton of the
aromatic ring at δ ~7–7.5 ppm regularly shifts downfield
in going from sulfides III and XI to sulfoxides VI and
XII and further to sulfones XIV and XIII. The protons
of the alcohol hydroxy groups appear at δ ~2–3.5 ppm.
In the spectra of acids I and IV in the region δ 6–10 ppm
the averaged signal of two hydroxy groups is observed.
This signal was not found in the spectrum of compound
VII due to its complete broadening. In the spectra of
bromine-containing acis the intensity and chemical shifts
of the broadened signals of hydroxy protons are
somewhat distorted apparently due to the water or ethanol
impurity in the deuterated solvents used in the registering
of the spectra. In the 19F NMR spectra two multiplets in
the region δ 20–30 ppm typical of 1,4-di-substituted
tetrafluorophenyl fragment are present.
By treating compound I with hydrobromic acid we
succeeded in clean replacement of the alcohol hydroxyl
by bromine to obtain acid II. In reactions of compounds
I and VII with phosphorus pentachloride both hydroxy
groups were replaced by chlorine to give acid chlorides
of 4-(2-chloroethylsulfanyl)- and 4-(2-chloroethylsul-
fonyl)-2,3,5,6-tetrafluorobenzoic acids (IX, X) respec-
tively. The building blocks containing acyl chloride groups,
on the one hand, may be easily converted into versatile
other functional groups, and on the other hand, provide
a possibility of additional fusion of heterocycle and going
over to tricyclic structures, also interesting for the
synthesis of potential biologically active substances. The
possibility of heterocyclization of polyfluorobenzoic acids
chlorides was demonstrated in [30,31].
EXPERIMENTAL
1H and 19F NMR spectra wee registered on
spectrometers Bruker WP-200SY (frequency 200.13
(1H), 188.28 MHz (19F)] and Bruker AV-300 [frequency
300.13 (1H), 282 MHz (19F)], internal references
hexamethyldisiloxane (δH 0.0 ppm) and C6F6 (δF 0.0 ppm).
4-(2-Hydroxyethylsulfanyl)-2,3,5,6-tetrafluoro-
benzoic acid (I). To a dispersion of 6.83 g (0.032 mol)
of pentafluorobenzoic acid in 30 ml of water was added
at stiring 2.77 g (0.035 mol) of 2-mercaptoethanol and
7.16 g (0.071 mol) of triethylamine. The mixture was left
overnight, then acidified to pH 0, the separated precipitate
was filtered off, washed with a little cold water, and
recrystallized from water. Yield 7.24 g (83%), mp 144–
145°C. 1H NMR spectrum [CDCl3, (CD3)2SO], δ, ppm:
3.08 t [2H, S(CH2)2O , J 6.2 Hz], 3.67 t [2H, S(CH2)2O,
J 6.2 Hz], 6.86 br.s (2H, COOH + CH2OH). 19F NMR
By easy decarboxylation at short boiling in a mixture
acetonitrile–triethylamine acids I, IV, and VII were
converted into analogous derivatives of tetrafluoro-
benzene: (2-hydroxyethylsulfanyl)-, (2-hydroxyethyl-
sulfinyl)-, and (2-hydroxyethylsulfonyl)-2,3,5,6-tetra-
fluorobenzenes (XI–XIII). By treating with thionyl
chloride compounds XI and XIII were readily converted
into sulfide III and 2,3,5,6-tetrafluoro(2-chloroethyl-
sulfonyl)benzene (XIV) respectively. Sulfide XI was also
obtained by the reaction of pentafluorobenzene with
2-mercaptoethanol. Same as with pentafluorobenzoic acid,
this reaction proceeded regioselectively. We failed to
convert sulfoxides IV and XII into sulfoxides XV and VI
by treating with phosphorus pentachloride or thionyl
chloride: according to 1H and 19F NMR spectra formed
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 11 2009

SYNTHESIS OF β-FUNCTIONALIZED ETHYL POLYFLUOROARYL SULFIDES
1641
spectrum, δ, ppm.: 24.6 m (2F), 28.4 m (2F). Found, %:
C 40.11; H 2.33; F 28.57; S 12.20. C9H6F4O3S.
Calculated, %: C 40.00; H 2.22; F 28.15; S 11.85.
heated for 6 h at 55°C, then the reaction mixture was
diluted with 1.5-fold volume of water and was heated to
boiling. The precipitate separated on cooling was filtered
off and dried on the filter. Yield 0.31 g (63%), mp 89–
4-(2-Bromoethylsulfanyl)-2,3,5,6-tetrafluoro-
benzoic acid (II). A mixture of 0.54 g(2 mmol) of
compound I and 5 ml of concn. HBr was stirred for 5 h
at 90°C. Then the reaction mixture was cooled to room
temperature, the precipitate was filtered off, dried on the
filter, and recrystallized from a mixture benzene–hexane,
1
91°C. H NMR spectrum [CDCl3, (CD3)2SO], δ, ppm:
3.48–3.57 m [1H, SO(CH2)2Br], 3.65–3.83 m [2H,
SO(CH2)2Br], 3.94–4.02 m [1H, SO(CH2)2Br], 6.82 br.s
(OH). 19F NMR spectrum, δ, ppm: 23.0 m (2F), 24.8 m
(2F). Found, %: C 30.21; H 1.92; Br 23.34; F 21.75; S
9.47. C9H5BrF4O3S. Calculated, %: C 31.03; H 1.44; Br
22.99; F 21.84; S 9.2.
1
1:2. Yield 0.55 g (83%), mp 118–120°C. H NMR
spectrum [CDCl3, (CD3)2SO], δ, ppm: 3.21 br.s (OH),
3.38 m [4H, S(CH2)2Br]. 19F NMR spectrum, δ, ppm:
24.6 m (2F), 29.3 m (2F). Found, %: C 32.49; H 1.72; Br
24.46; F 24.14; S 9.03. C9H5BrF4O2S. Calculated, %:
C 32.53; H 1.51; Br 23.8; F 22.9; S 9.64.
2,3,5,6-Tetrafluoro(2-chloroethylsulfinyl)-
benzene (VI). Amixture of 0.39 g (1.6 mmol) of sulfide
III and a solution of 0.13 g (1.8 mmol) of 50% hydrogen
peroxide in 0.7 ml of glacial acetic acid was heated for
7 h at 55°C. Then the reaction mixture was diluted with
1.5-fold volume of water and was heated to boiling. On
cooling 0.3 g (73%) of compound VI was filtered off, mp
2,3,5,6-Tetrafluoro(2-chloroethylsulfanyl)-
benzene (III). A mixture of 0.74 g (3.3 mmol) of
compound XI, 3 ml of chloroform, and 0.64 g (5.4 mmol)
of thionyl chloide was heated at reflux for 2 h. Then the
reaction mixture was evaporated in a vacuum, the dry
residue was washed with water and dried on the filter to
obtain 0.77 g (97%) of compound III with the content of
1
50–52°C. H NMR spectrum (CDCl3), δ, ppm: 3.35–
3.47 m [1H, SO(CH2)2Cl], 3.83–4.04 m [3H,
SO2(CH2)2Cl], 7.25 m (1H, C6F4H). 19F NMR spectrum,
δ, ppm: 22.47 m (2F), 26.53 m (2F). Found, %: C 36.84;
H 1.93; F 29.2; S 12.58. C8H5ClF4OS. Calculated, %:
C 36.9; H 1.92; F 29.92; S 12.32.
1
the main substance ~95% (by the data of H and 19F
NMR spectra). The analytical sample was prepared by
sublimation in a vacuum at 100–110°C (3 mm Hg). mp
4-(2-Hydroxyethylsulfonyl)-2,3,5,6-tetrafluoro-
benzoic acid (VII). In 2 ml of boiling trifluoroacetic acid
was dissolved 2.4 g (9 mmol) of sulfide I. To the hot
solution was added dropwise at stirring 3.02 g (44 mmol)
of 50% hydrogen peroxide. After keeping at room
temperature for 24 h the reaction mixture was cooled to
–10°C, the precipitate was filtered off and recrystallized
from a mixture chloroform–acetonitrile, 3:1. Yield 2.14 g
1
39–40°C. H NMR spectrum (CDCl3), δ, ppm: 3.17 t
[2H, S(CH2)2Cl, J 7.7 Hz], 3.55 t [2H, S(CH2)2Cl,
J 7.7 Hz], 7.03 m (1H, C6F4H). 19F NMR spectrum, δ, ppm:
24.3 m (2F), 28.6 m (2F). Found, %: Cl 14.52; F 31.08;
S 13.09. C8H5ClF4S. Calculated, %: Cl 14.18; F 31.09;
S 13.26.
4-(2-Hydroxyethylsulfinyl)-2,3,5,6-tetra-
fluorobenzoic acid (IV). A mixture of 0.99 g (4 mmol)
of sulfide I and 4.35 g (4 mmol) of 3% hydrogen peroxide
was heated for 12 h at 85°C, the reaction mixture was
evaporated in a vacuum, the residue was recrystallized
from a mixture chloroform–acetone, 3:1. Yield 0.72 g
1
(79%), mp 178–180°C. H NMR spectrum [CDCl3,
(CD3)2SO], δ, ppm: 3.52 t [2H, SO2(CH2)2O, J 5.3 Hz],
3.99 t [2H, SO2(CH2)2O, J 5.3 Hz]. 19F NMR spectrum,
δ, ppm: 24.1 m (2F), 25.5 m (2F). Found, %: C 35.70;
H 2.16; F 24.47; S 10.50. C9H6F4O5S. Calculated, %:
C 35.76; H 1.98; F 25.17; S 10.59.
1
(68%), mp 143–145°C. H NMR spectrum [CDCl3,
(CD3)2SO], δ, ppm: 3.31–3.40 m [1H, SO(CH2)2O], 3.59–
3.66 m [1H, SO(CH2)2O], 3.90–3.97 m [1H,
SO(CH2)2O], 4.02–4.10 m [1H, SO(CH2)2O], 6.79 br.s
(2H, COOH + CH2OH) 19F NMR spectrum, δ, ppm:
22.8 m (2F), 24.1 m (2F). Found, %: C 37.58; H 2.07;
F 26.52; S 11.12. C9H6F4O4S. Calculated, %: C 37.76;
H 2.09; F 26.57; S 11.19.
4-(2-Bromoethylsulfonyl)-2,3,5,6-tetrafluoro-
benzoic acid (VIII). In 0.7 ml of boiling trifluoroacetic
acid was dissolved 0.25 g (0.8 mmol) of sulfide II. To
the hot solution was added dropwise at stirring 0.26 g
(3.8 mmol) of 50% hydrogen peroxide. After keeping for
24 h the precipitate was filtered off, the mother liquor
was diluted with water, and the precipitate was filtered
off. The combined precipitate was dried in air and
recrystallized from a mixture benzene–hexane, 1:1. Yield
4-(2-Bromoethylsulfinyl)-2,3,5,6-tetrafluoro-
benzoic acid (V). A mixture of 0.48 g (1.5 mmol) of
sulfide II and a solution of 0.12 g (1.7 mmol) of 50%
hydrogen peroxide in 0.5 ml of glacial acetic acid was
1
0.19 g (69%), mp a53–a55°C. H NMR spectrum
[CDCl3, (CD3)2SO], δ, ppm: 3.63 t [2H, SO2(CH2)2Br,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 11 2009

LITVAK et al.
1642
J 7.3 Hz], 3.82 t [2H, SO2(CH2)2Br, J 7.3 Hz], 8.82 br.s
(OH). 19F NMR spectrum, δ, ppm: 25.6 m (2F), 26.4 m
(2F). Found, %: C 30.21; H 1.85; F 19.78; S 9.47.
C9H5BrF4O4S. Calculated, %: C 29.67; H 1.37; F 20.9;
S 8.8.
in the preceding experiment from 0.074 g (0.26 mmol) of
acid IV and 0.245 g (2.4 mmol) of triethylamine in 1 ml
of acetonitrile after evaporating the reaction mixture in
a vacuum was recrystallized from the mixture chloro-
form–hexane–tetrachloromethane, 1:1:1. Yield 0.047 g
1
(75%), mp 81–83°C. H NMR spectrum (CDCl3), δ,
4-(2-Chloroethylsulfanyl)-2,3,5,6-tetra-
fluorobenzoic acid chloride (IX). 0.47 g (1.7 mmol)
of compound I was mixed with 0.73 g (3.5 mmol) of
phosphorus pentachloride.After 5 min started a vigorous
reaction, and on its completion a homogeneous solution
formed of yellow color. The phosphorus oxychloride was
distilled off in a vacuum to obtain 0.51 g (96%) of oily
acyl chloride IX containing over 95% of the main sub-
ppm: 3.26–3.35 m [1H, SO(CH2)2O], 3.53 br.s (1H,
CH2OH), 3.67–3.74 m [1H, SO(CH2)2O], 4.03–4.10 m
[1H, SO(CH2)2O], 4.15–4.23 m [1H, SO(CH2)2O],
7.24 m (1H, C6F4H). 19F NMR spectrum, δ, ppm:
22.3 m (2F), 26.1 m (2F). Found, %: C 39.57; H 2.34;
F 31.14; S 12.87. C8H6F4O2S. Calculated, %: C 39.67;
H 2.48; F 31.40; S 13.22.
1
stance (by the data of H and 19F NMR spectra). The
(2-Hydroxyethylsulfonyl)-2,3,5,6-tetrafluoro-
benzene (XIII). Similarly to the procedure described
for compound XII from 0.41 g (1.3 mmol) of acid VII
and 0.73 g (7.2 mmol) of triethylamine in 2 ml of
acetonitrile we obtained 0.24 g (70%) of compound XIII,
mp63–64°C (benzene–hexane, 1:2). 1H NMR spectrum
(CDCl3), δ, ppm: 2.25 br.s (1H, CH2OH), 3.55 t [2H,
SO2(CH2)2O, J 5.3 Hz], 4.11 t [2H, SO2(CH2)2O,
J 5.3 Hz], 7.33 m (1H, C6F4H). 19F NMR spectrum, δ,
ppm: 25.1 m (2F), 27.0 m (2F). Found, %: C 37.35;
H 2.51; F 29.69; S 12.4. C8H6F4O3S. Calculated, %:
C 37.21; H 2.33; F 29.46; S 12.4.
analytical sample was prepared by sublimation in
1
a vacuum at 140–150°C (3 mm Hg). H NMR spectrum
(CDCl3), δ, ppm: 3.31 t [2H, S(CH2)2Cl, J 7.3 Hz],
3.61 t [2H, S(CH2)2Cl, J 7.3 Hz]. 19F NMR spectrum, δ,
ppm: 23.8 m (2F), 30.1 m (2F). Found, %: C 36.09;
H 1.47; Cl 23.18; F 24.57; S 10.31. C9H4Cl2F4OS.
Calculated, %: C 35.18; H 1.3; Cl 23.13; F 24.76; S 10.42.
4-(2-Chloroethylsulfonyl)-2,3,5,6-tetrafluoro-
benzoic acid chloride (X). Similarly to the procedure
described for compound IX from 0.089 g (0.3 mmol) of
sulfone VII and 0.123 g (0.6 mmol) of phosphorus
pentachloride we obtained 0.051 g (51%) of acyl chloride
X, mp 65–67°C (benzene–hexane, 1:5). 1H NMR spec-
trum (CDCl3), δ, ppm: 3.76 t [2H, SO2(CH2)2Cl,
J 6.4 Hz], 3.91 t [2H, SO2(CH2)2Cl, J 6.4 Hz]. 19F NMR
spectrum, δ, ppm: 26.4 m (2F), 28.4 m (2F). Found, %:
C 3a.25; H 1.19; F 24.48; S 9.36. C9H4Cl2F4O3S.
Calculated, %: C 31.86; H 1.18; F 22.42; S 9.44.
2,3,5,6-Tetrafluoro(2-chloroethylsulfonyl)-
benzene (XIV). A mixture of 0.95 g (3.7 mmol) of
sulfone XIII, 5 ml of chloroform, and 1.32 g (11 mmol)
of thionyl chloride was heated at reflux for 3 h. Then the
reaction mixture was evaporated to dryness, and the
residue was recrystallized from aqueous acetic acid. Yield
1
0.5 g (49%), mp 63–66°C. H NMR spectrum (CDCl3),
δ, ppm: 3.73 t [2H, SO2(CH2)2Cl, J 6.6 Hz], 3.88 t [2H,
SO2(CH2)2Cl, J 6.6 Hz], 7.37 m (1H, C6F4H). 19F NMR
spectrum, δ, ppm: 25.5 m (2F), 27.4 m (2F). Found, %: C
35.33; H 1.54; F 26.9; S 11.82. C8H5ClF4O2S. Calculated,
%: C 34.72; H 1.81; F 27.49; S 11.57.
(2-Hydroxyethylsulfanyl)-2,3,5,6-tetrafluoro-
benzene (XI). A mixture of 0.17 g (0.63 mol) of acid I,
2 ml of acetonitrile, and 0.46 g (4.3 mmol) of triethylamine
was heated at reflux for 1.5 h. Acetonitrile and triethyl-
amine were evaporated in a vacuum to obtain 0.13 g
(95%) of compound XI containing over 95% of the main
The study was carried out under a financial support
from the Russian Foundation for Basic Research (grant
no. 09-03-00248).
1
substance (by the data of H and 19F NMR spectra).
The analytical sample was prepared by sublimation in
a vacuum at 115–125°C (3 mm Hg), mp 25–26°C.
1H NMR spectrum (CDCl3), δ, ppm: 2.16 br.s (aH,
CH2OH), 3.04 t [2H, S(CH2)2O, J 5.8 Hz], 3.65 t [2H,
S(CH2)2O, J 5.8 Hz], 7.01 m (aH, C6F4H). 19F NMR
spectrum, δ, ppm: 24.0 m (2F), 28.3 m (2F). Found, %:
C 42.82; H 2.65; F 33.51; S 14.23. C8H6F4OS. Calculated,
%: C 42.48; H 2.65; F 33.63; S 14.16.
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