Pyrimidine-2,4-diamines as antiplasmodial antifolates

Article abstract of DOI:10.24820/ARK.5550190.P011.262

Two series of substituted pyrimidine-2,4-diamines with a flexible side chain at either the 5- or 6-position of the pyrimdine ring were designed as potential inhibitors of P. falciparum dihydrofolate reductase (DHFR). The compounds were synthesised and eva

Full text of DOI:10.24820/ARK.5550190.P011.262

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Arkivoc 2020, part vi, 0-0
Reactions of 4-substituted-1-[(difluoromethyl)sulfinyl]polyfluorobenzenes
with phenolate anion
Borislav V. Koshcheev, Roman A. Bredikhin, Alexander M. Maksimov,* Vyacheslav E. Platonov and
Rodion V. Andreev
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of Russian Academy of
Sciences, 630090 Novosibirsk, Russian Federation
Email: maksimov@nioch.nsc.ru
Received 06-05-2020
Accepted 09-08-2020
Published on line 09-21-2020
Abstract
The reactions of 4-substituted-polyfluorinated-[(difluoromethyl)sulfinyl]benzenes ([4-X-C6F4S(O)CHF2 [X = H,
CF3 and C6F5S(O)]) with phenolate anion in benzene, Et2O and CH3CN have been investigated. The reactions of
the substrate (X = H, CF3) and sodium phenolate in equal amounts resulted in the formation of mixtures of the
starting compound, 2-phenoxyderivative and disubstituted products. The two-fold amount of the phenolate
afforded the 2,6-disubstituted products for X = H in MeCN and for X = CF3 in Et2O. At the same time, 4-CF3-
C6F4S(O)CHF2 in CH3CN gave a mixture of the 2,6- and 2,5-bis(phenoxy) derivatives. Quantum chemical
calculations have been performed to explain this phenomenon. For X = C6F5S(O) in MeCN, the reaction was
accompanied by sulfinyl moiety ipso-substitution.
Keywords: Polyfluoroaromatic compounds, sulfoxides, sodium phenolate, aromatic nucleophilic substitution.
DOI: https://doi.org/10.24820/ark.5550190.p011.262
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Introduction
Polyfluorinated organic compounds have found wide practical application.1 Recently, research into functional
derivatives and, in particular, sulfur-containing compounds, has been developing in the area of polyfluorinated
organic compounds.1 The reactions of sulfur-containing polyfluoroarenes with nucleophiles are being
studied.2,3,4 The sulfur atom oxidation state in such compounds can significantly affect the rate and direction
of the reaction.5
For polyfluoroaromatic compounds, nucleophilic substitution reactions are most typical.6,7 The presence
of an acceptor in the polyfluorinated ring, for example, the difluorosulfinyl group, should facilitate the
substitution of fluorine atom, which opens up wide possibilities for various transformations.
Methods for the preparation of low-fluorinated sulfoxides are presented in the literature.8,9.10 Sulfoxides
containing four or more fluorine atoms, however, are practically unknown. Meanwhile, difluoromethyl
derivatives of sulfoxides can be obtained on the basis of available polyfluorinated arene thiols11,12 by their
reaction with chlorodifluoromethane, followed by oxidation of the resulting sulfanes.
In connection with the foregoing, we have focused our attention on polyfluoroaromatic sulfoxides bearing
a difluoromethyl group since compounds of such structure have not been reported. For this reason, it was
reasonable to study the properties and transformations of such compounds.
In general, [(difluoromethyl)sulfinyl]polyfluoroarenes have two centers sensitive to nucleophilic attack –
the polyfluoroaromatic core, activated by the electron-withdrawing S(O)CHF2 group (σI = 0.51, σR = 0.07)13 -
and the sulfur atom.
Recently we have shown that [(difluoromethyl)sulfinyl]pentafluorobenzene, C6F5S(O)CHF2, readily
undergoes attack on the polyfluoroaromatic core, with substitution of the para-fluorine atom for OMe, OPh,
NHMe and SH groups under the action of the charged (NaOMe, NaOPh, KSH) or uncharged (NH2Me)
nucleophiles. The direction of substitution is consistent with the expected one.6 Surprisingly, the action of
alkali (NaOH) on C6F5S(O)CHF2 led to its decomposition, with formation of pentafluorobenzene. This result
might be attributed to the attack on the sulfur atom.14
The task of the current research was to study the transformations of para-substituted
[(difluoromethyl)sulfinyl]tetrafluorobenzenes, 4-XC6F4S(O)CHF2 [where X = H (1), CF3 (2) and S(O)C6F5 (3)] in
reactions with nucleophiles, e.g., the phenolate ion. Such substrates do not have a para-fluorine atom, are
sensitive to nucleophilic attack and, thus, new routes of reaction may be revealed. Phenolate ion is widely
used in test experiments and kinetic measurements.15 Since it was necessary for this study to avoid the
presence of water in the reaction mixture, sodium phenolate was obtained by the action of sodium hydride on
19
phenol. The reaction process was monitored by means of F NMR spectroscopy. Further confirmation of the
structures of the reaction products, if necessary, were proven by counter (alternative) syntheses.
We have shown that reactions of [(difluoromethyl)sulfinyl] benzenes (1-3) with sodium phenolate led to
the nucleophilic substitution of fluorine in the neighboring position of the [(difluoromethyl)sulfinyl] group for
phenoxide (1). The subsequent substitution reaction also occurred, however, its selectivity depended on the
electronic properties of the substituent in the polylfluoroaryl core and solvent polarity. The obtained
experimental results are also discussed using quantum-chemical calculations.
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Results and Discussion
Reactions of 3-[(difluoromethyl)sulfinyl]-1,2,4,5-tetrafluorobenzene with sodium phenolate
o
The sulfinylbenzene (1) reacted with sodium phenolate in benzene at 65 C for 8 h and gave a mixture of the
starting
compound,
3-[(difluoromethyl)sulfinyl]-1,2,5-trifluoro-4-phenoxybenzene
(4)
and
[{2-
[(difluoromethyl)sulfinyl]-4,6-difluoro-1,3-phenylene}bis(oxy)]dibenzene (5) (Scheme 1 and Table 1, entry 1).
The analogous mixture was obtained in Et2O solution after refluxing for 4 h (entry 2). The same result was
observed when the process was carried out in a polar solvent such as MeCN (entry 3). On the contrary, by
adding two equivalents of sodium phenolate, only the disubstituted derivative (5) was observed in the
reaction products (entry 4).
O
CF2H
O
CF2H
O
CF2H
F
S
S
S
PhO
OPh
OPh
F
F
F
F
PhONa
solvent
+
F
F
F
F
H
H
H
4
5
1
Scheme 1.
Table 1. Reactions of sulfinylbenzene (1) with sodium phenolate in solvents of differing polarities
PhONa
equiv.
Entry
Solvent
T, oC
Time, h NMR 19F ratio
1
2
3
4
1
1
1
2
PhH
Et2O
MeCN
MeCN
65
8
4
2
2.5
1 : 4 : 5 = 19 : 58 : 23
35 (reflux)
65
65
1 : 4 : 5 = 19 : 66 : 16
1 : 4 : 5 = 15 : 66 : 19
1 : 4 : 5 = - : - : 100
Reactions of 1-[(difluoromethyl)sulfinyl]-2,3,5,6-tetrafluoro-4-trifluoromethylbenzene with sodium
phenolate
The same set of experiments was carried out with 1-[(difluoromethyl)sulfinyl]-2,3,5,6-tetrafluoro-4-
trifluoromethylbenzene with sodium phenolate (2) (Scheme 2 and Table 2). The strong electron-withdrawing
influence of the trifluoromethyl group (σI = 0.38, σR = 0.16)13 afforded the opportunity to decrease the
temperature of the reaction for compound (2) with respect to compound (1). When compound (2) reacted
with sodium phenolate in benzene, a mixture of the starting compound, 1-[(difluoromethyl)sulfinyl]-2,3,5-
trifluoro-6-phenoxy-4-(trifluoromethyl)benzene
(6)
and
[{2-[(difluoromethyl)sulfinyl]-4,6-difluoro-5-
(trifluoromethyl)-1,3-phenylene}bis(oxy)]dibenzene (7) was formed (entry 1). The action of sodium phenolate
on compound 2 in Et2O led to the analogous distribution of the products, both at room temperature (entry 2)
or at -25oC (entry 3). So, in all cases, the formation of the monosubstituted sulfoxide (6) was accompanied
with formation of the diphenoxy-substituted product (7). When 2 moles of sodium phenolate per mole of
substrate were employed, compound (7) was the only reaction product (entry 4).
The same reaction between compound 2 and sodium phenolate in polar MeCN, however, surprisingly revealed
the formation of the isomeric [{2-[(difluoromethyl)sulfinyl]-3,6-difluoro-5-(trifluoromethyl)-1,4-
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phenylene}bis(oxy)]dibenzene (8) alongside compounds 2, 6 and 7 (entry 5). When 2 equivalents of sodium
phenolate were used, the full conversion of the sulfoxide (2) was observed with formation of compounds (7)
and (8) in the ratio 64:36 (entry 6). Thus, a polar solvent is the likely reason for the new reaction direction,
which was not observed in the case of sulfoxide (1).
O
CF2H
O
CF2H
O
CF2H
O
CF2H
F
S
S
S
S
F
OPh
PhO
OPh
OPh
F
F
F
F
PhONa
solvent
+
+
PhO
F
F
F
F
F
CF3
CF3
CF3
CF3
2
8
6
7
Scheme 2.
Table 2. Reactions of sulfinylbenzene (2) with sodium phenolate in solvents of differing polarities
PhONa
equiv.
Entry
Solvent
T, oC
Time, h NMR 19F ratio
1
2
3
4
5
6
1
1
1
2
1
2
PhH
Et2O
Et2O
Et2O
MeCN
MeCN
25
25
- 25
30
25
30
8
1
4
3
0.5
0.5
2 : 6 : 7 : 8 = 18 : 56 : 25 : -
2 : 6 : 7 : 8 = 12 : 67 : 20 : -
2 : 6 : 7 : 8 = 18 : 67 : 16 : -
2 : 6 : 7 : 8 = - : - : 100 : -
2 : 6 : 7 : 8 = 18 : 58 : 14 : 9
2 : 6 : 7 : 8 = - : - : 64 : 36
Reactions of 1-[(difluoromethyl)sulfinyl]-2,3,5,6-tetrafluoro-4-[(perfluorophenyl)sulfinyl]benzene with
sodium phenolate
We have also investigated the reaction of 1-[(difluoromethyl)sulfinyl]-2,3,5,6-tetrafluoro-4-
[(perfluorophenyl)sulfinyl]benzene (3) with sodium phenolate in PhH and MeCN solutions. Complex mixtures
of multiple components were formed in both cases. The resulting products, however, were not stable under
GC-MS analysis conditions. For these reasons, we tried to reduce S-O fragments of the obtained
sulfinylbenzenes. This would have simplified the reaction-mixture composition, since sulfane moieties were
not able to form optical isomers. A control experiment consisting of the reduction of compound 3, using AcCl16
under reflux conditions, resulted in the formation of (difluoromethyl)[2,3,5,6-tetrafluoro-4-
(perfluorophenylthio)phenyl]sulfane (9) (92% isolated yield), and demonstrated the feasibility of this approach
(Scheme 3).
F
F
F
F
F
F
F
F
AcCl, reflux
O
CF2H
S
S
S
F
S
F
CF2H
O
F
F
F
F
F
F
F
F
3
9, 92%
1:1
mixture of diastereomers
Scheme 3. Reduction of sulfoxide (3) with AcCl forming sulfane (9)
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Such a reduction procedure for non-fluorinated sulfoxides is known to demand not such severe
conditions, but the reactivity of the polyfluorinated substrates turned out to be remarkably less.16 The
electron-withdrawing character of polyfluoroaryl moiety seems to prevent the effective coordination of the
acetyl chloride and sulfinyl group.
In connection with the foregoing, the reaction mixtures were also subjected to the action of acetyl
chloride at reflux temperature. To prevent the chlorination of phenoxy groups, toluene was added to the
reaction mixture; the resulting formation of benzyl chloride was recorded using GC-MS spectrometry.
Nevertheless, even after the action of acetyl chloride, the obtained mixtures were rather complex and it was
not possible to separate them into individual compounds. For this reason, the individual compounds have
been synthesized by counter synthesis to provide us with reliable data about the products’ structures.
Therefore, the resulting mixtures were analyzed by means of GC-MS spectrometry and 19F NMR
spectroscopy for comparison with these specially prepared compounds’ spectra. The yields of the products
were calculated using 19F NMR spectroscopy with an internal quantitative standard.
Elucidation of the structures of the products obtained are supported by NMR spectra included in the
Supplementary Materials.
It was shown that solvent polarity had a remarkable effect on the predominant route of the reaction
between substrate (3) and NaOPh. Usage of the polar MeCN allowed us to substitute the para-fluorine atom,
which is a typical direction of aromatic nucleophilic substitution in polyfluoroarenes (Scheme 4).6 The reduced
product of this transformation was (difluoromethyl){2,3,5,6-tetrafluoro-4-[(2,3,5,6-tetrafluoro-4-
phenoxyphenyl)thio]phenyl}sulfane (10). (Difluoromethyl)(2,3,5,6-tetrafluoro-4-phenoxyphenyl)sulfane (11)
and bis(2,3,5,6-tetrafluoro-4-phenoxyphenyl)sulfane (12) were found in the reaction mixture in significant
amounts.
Formation of such structures obviously is a result of the ipso-attack of the nucleophile on the carbon atom
bonded with the sulfinyl group and, in fact, provides a unique reaction pattern which was not observed for
sulfoxides (1) and (2).
CF2H
OPh
S
1. PhONa (1 eq),
MeCN, reflux
2. AcCl,
PhCH3, reflux
F
F
F
F
F
F
F
F
CF2H
CF2H
F
S
S
OPh
F
F
+
F
9
F
3
+
+
+
S
S
F
F
F
F
F
F
SC6F5
OPh
F
F
PhO
F
PhO
F
10
11
12
13
NMR 19F ratio
Yield, %
29
24
31
26
16
13
18
15
6
5
Total: 83 %
Scheme 4. Composition and distribution of the products obtained in reactions of sulfoxide (3) with sodium
phenolate in polar MeCN.
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On the contrary, the action of sodium phenolate on compound (3) in non-polar benzene afforded, after
reduction, no noticeable quantities of compound (10) (Scheme 5). The main component of the product
mixture was (difluoromethyl){2,3,5-trifluoro-4-[(perfluorophenyl)thio]-6-phenoxyphenyl}sulfane (13) while
bis(phenoxy)-substituted
diphenoxyphenyl}(difluoromethyl)sulfane
compounds
(14),
{3,5-difluoro-4-[(perfluorophenyl)thio]-2,6-
{2,5-difluoro-4-[(perfluorophenyl)thio]-3,6-
and
diphenoxyphenyl}(difluoromethyl)sulfane (15), were also formed. Thus, the predominant direction of the
process, in a non-polar solvent, is nucleophilic attack on the polyfluoroaromatic ring bearing two sulfinyl
groups.
1. PhONa (1 eq),
PhH, reflux
CF2H
CF2H
2. AcCl,
PhCH3, reflux
S
S
OPh
OPh
PhO
F
F
9
13
3
+
+
+
F
F
PhO
SC6F5
SC6F5
14
15
NMR 19F ratio
Yield, %
15
12
11
9
50
40
23
19
Total: 80 %
Scheme 5. Composition and distribution of the products obtained in reactions of sulfoxide (3) with sodium
phenolate in non-polar solvent benzene.
Mechanistic rationale
The results obtained might be explained in terms of an aromatic nucleophilic substitution mechanism.
Aromatic nucleophilic substitution in polyfluoroarenes is known to proceed in a step-wise addition-elimination
process; addition of the nucleophile is usually a rate-determine stage.17,18 The regioselectivity of substitution
of fluorine in monosubstituted pentafluorobenzenes (C6F5X) is governed mainly by the other fluorine atoms
rather that the group X, with the exception of powerful electron-donating groups.6
Probably for similar reasons, the starting sulfoxide (1 or 2) and phenoxyderivative (4 or 6, respectively)
demonstrated very similar reaction capabilities. Fluorine atoms in position 2 of the starting sulfoxides are
activated by the difluoromethylsulfinyl group toward nucleophilic aromatic substitution. The fluorine atoms in
position 6 of the substituted products (4) and (6) undergo the same degree of activation, while the influence
of the phenoxy group situated in the meta position is low.
At the same time, the reaction abilities of the fluorine atoms in position 5 of products (4) and (6) vary
depending on the character of the group X. Compound (4) reacts with sodium phenolate selectively at position
6, while the fluorine atom in position 5 remains unreactive. On the contrary, sulfoxide (6) undergoes
nucleophilic substitution at positions 5 and 6 with formation of compounds (8) and (7), respectively. This
effect is obviously a result of a strong electron-withdrawing influence of the trifluoromethyl group, such that it
can stabilize the carbanion formed by addition of the phenolate-anion at position 5 of sulfoxide (6).
Investigation of reversibility formation of bisphenoxy compounds (7) and (8)
For a better comprehension of the formation process of compounds 7 and 8, it was necessary to find out if
these compounds could transform into each other under the reaction conditions. A mixture of bisphenoxy
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19
derivatives (7) and (8) (ratio 66 : 34 by F NMR) and NaF was obtained from the interaction of sulfoxide (2)
with PhONa (2 eq) after 0.5 h in MeCN. A pure sample of individual compound (7) (0.22 eq) was added to the
specified mixture, so that the ratio of compounds (7) and (8) became 72 : 28 (19F NMR). The resulting mixture
19
was kept at the reaction conditions for an additional 0.5 h and then analyzed by means of F NMR. The ratio
of 7 and 8 was not effectively changed indicating no significant reversibility of aromatic nucleophilic
substitution; the fluoride anion could not split the carbon-oxygen bond formed, and no equilibrium between
isomers (7) and (8), under the reaction conditions employed (Scheme 6).
Scheme 6. Reversibility experiment results showing no reversibility or equilibrium for arenes (7) and (8).
Quantum chemical calculations
The ratio of diphenoxy derivatives in the interaction of compounds (4) and (6) with the one equivalent of
sodium phenolate was determined by means of the quantum chemical calculations of the relative stabilities of
sigma-complexes (type A and B), which are generally considered to be on the path of the nucleophilic
substitution reaction (Scheme 7).
The results of quantum-chemistry calculations provided evidence that the probability of the reaction of
the nucleophile with the carbon atom in position 5 of sulfoxide (4) is ca. 5 kcal per mole more likely than that
in position 6, while positions 5 and 6 of the sulfoxide (6) revealed nearly the same reactivities.
Scheme 7. Formation of sigma-complexes from compounds 4 or 6 and the phenolate anion.
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As shown below in Table 3, the difference in the total energies of the resulting sigma-complexes is greater
in the case of compound 4 (X = H) than for compound 6 (Х = CF3). Independent of the solvent, in the case of X
= H, 2,6-bisphenoxy derivative (5) will form predominantly. In the case of Х = CF3, however, sigma-complexes
of types A and B turn out to be close in terms of total energy values, so we should expect the formation of
both products 7 and 8. The calculations even predict the approximately equal reaction ability of positions 5
and 6 of compound 6.
Table 3. Difference between the calculated B3LYP//6-31G(d) total energies of the corresponding sigma
complexes depending on the solvent (in the case of PCM SMD)
ΔE, kcal/mol
X
gas phase
5.32
PhH
5.53
-0.05
Et2O
5.10
-0.20
MeCN
5.09
-0.34
H
CF3
0.11
Where ΔE = E (B) - E (A).
Reactions of compounds (4) and (6) with ammonium phenolates
We tried to check this assumption by implementation of the same set of chemical transformations of
sulfinylbenzenes (4) and (6) with ammonium phenolate. Tetraalkylammonium salts are considered to display
almost pure ionic character between cation and anion species; therefore, such salts are used extensively as
phase transfer catalysts.19 We supposed that the change in the nature of the cation could affect the ratio of
the products of the reaction of compound 6 and the phenolate ion. 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)
is known to be a weakly nucleophilic base and is widely used in organic synthesis.20 Reaction of 3-
[(difluoromethyl)sulfinyl]-1,2,5-trifluoro-4-phenoxybenzene (4) with phenol in the presence of DBU expectedly
led, exclusively, to the formation of product (5) (Scheme 8). No differences in the direction of the process
were observed (Table 4: entries 1, 2).
On the contrary, the combination of DBU and phenol in the reaction with substrate (6) led to formation of
various mixtures of products (7) and (8), depending on the polarity of the solvent employed. The ratio of 7 : 8
turned out to be 72 : 28 in non-polar PhH, 64 : 36 in ether and 50 : 50 in polar MeCN (Table 4, entries 3-5). This
result provides evidence that the observed reaction of aromatic fluorine substitution with sodium phenolate
probably involves ion pairs, but not the pure phenolate anion. For this reason, the looser ion pair formed by
means of DBU displays higher reactivity.
To further verify our assumption, we synthesized benzyltriethylammonium phenolate by an exchange
reaction of sodium phenolate with excess of benzyltriethylammonium chloride (TEBAC). The excess of TEBAC
was sufficient to prevent introduction of sodium cation to the desired ammonium phenolate. When
compound (6) was subjected to the action of [NBnEt3][OPh] (1 eq.), either at room or at cold temperatures, a
complex mixture of unidentified byproducts, together with 7 and 8, was formed. For this reason, and due to
the high reactivity of this ammonium salt, further experiments were performed with a less-than-equivalent
quantity of reagent at low temperature. It was demonstrated that the reaction of compound (6) with 0.45 eq.
of [NBnEt3][OPh] in Et2O gave compounds (7) and (8) in a ratio of 28 : 13 (Table 4, entry 6), while reaction with
0.3 mole of [NBnEt3][OPh] in MeCN resulted in the formation of equal amounts of products (7) and (8)
(Table 4, entry 7). This result, in comparison with the reaction with sodium phenolate, shows that cation has
some sort of influence on the reaction ability of the phenolate anion.
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Scheme 8.
Table 4. Reaction of sulfinyl benzenes (4) and (6) with ammonium phenolates
Entry Substrate Reagent (equiv.)
Solvent
T, oC Time, h NMR 19F ratio
1
2
3
4
5
6
7
4
4
6
6
6
6
6
PhOH/DBU (1)
PhOH/DBU (1)
PhOH/DBU (1)
PhOH/DBU (1)
PhOH/DBU (1)
PhH
MeCN
PhH
Et2O
MeCN
60
60
25
25
30
-25
-30
10
2.5
4
1
0.5
1
4 : 5 = - : 100
4 : 5 = - : 100
6 : 7 : 8 = - : 72 : 28
6 : 7 : 8 = - : 64 : 36
6 : 7 : 8 = - : 50 : 50
6 : 7 : 8 = 58 : 28 : 13
6 : 7 : 8 = 72 : 14 : 14
BnEt3N+PhO- (0.45) Et2O
BnEt3N+PhO- (0.3)
MeCN
0.5
Possible mechanism for the reaction of polyfluorinated sulfinylbenzenes and sodium phenolate
We supposed that the selective formation of compound (7) in the reaction of 2 with sodium phenolate in
ether (Table 2, entry 4) might be explained by a specific interaction between the reagents in non-polar
solvents through coordination of the sodium atom with the oxygen atom of the difluoromethylsulfinyl group,
according to Scheme 9 below. Such an association would promote the attack of the carbon atom in position 6
of compound (6) by the phenolate ion, with the formation of the sigma-complex (6C). The carbon-fluorine
bond is then cleaved to give compound (7), and sodium fluoride is formed and precipitates out. The analogous
schemes as possible explanations were suggested by various researchers to describe the reactivity of
pentafluoropyridine and pentafluoronitrobenzene.21,22
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Scheme 9. Possible mechanism for the reaction of polyfluorinated sulfinylbenzene (6) and sodium phenolate
Compared to sulfinylbenzenes (1) and (2), the behavior of compound (3) in reactions with sodium
phenolate is obviously more complicated, if only because there are two polyfluoroaromatic rings and two
sulfinyl groups capable of reactions. At the same time, the solvent polarity also determines the direction of the
transformations of compound 3.
As the polarity of benzene is low, the dissociation of sodium phenolate is hardly possible. It is more likely
that sodium phenolate coordinates with the oxygen atoms of the sulfinyl groups of 3 which is analogous to the
way it is presented in Scheme 9. The difluoromethylsulfinyl group seems to be less hindered and, therefore,
preferable for coordination than the diarylsulfinyl group. For this reason, the para-position of structure 3 likely
becomes inaccessible for the phenolate ion to attack, and nucleophilic attack on the adjacent carbon atom
would, therefore, seem to be the most natural way. The substituted products thus formed are reduced by
acetyl chloride to give compounds 13, 14 and 15, respectively.
On the other hand, a polar solvent such as MeCN likely promotes the dissociation of sodium phenolate so
that the phenolate ion displaces the fluorine atom from the para-position of compound 3.
Another observed direction of the process was the attack of the phenolate ion at the carbon atom bonded
to the sulfinyl group (ipso attack). In this case, the sulfinyl group acts as a good leaving group. As a result of
this process, the C-S bond is cleaved and a C-OPh bond is formed. The products derived from compound 3 by
this method are reduced by acetyl chloride to give compounds 11 and 12, respectively. Substitution of the
sulfinyl group by the action of hydroxy anion in reactions of aromatic compounds containing strong electron
withdrawing NO2-group in the para-position, has also been previously described.23
Conclusions
Phenolate ion reacts with 4-substituted-[(difluoromethyl)sulfinyl]tetrafluorobenzenes mainly by the
mechanism of nucleophilic aromatic substitution. In the examples considered in this paper, mixtures of the
starting sulfoxide, as well as mono- and disubstituted products, were obtained. The direction of the process
depended on the structure of the substrate, the phenolate-salt cation, and the polarity of the solvent. In
nonpolar solvents such as benzene and diethyl ether, the main route of the reaction of difluoromethyl aryl
sulfoxides and sodium phenolate is substitution of the fluorine atom adjacent to the difluoromethylsulfinyl
group. This process is likely facilitated by the coordination of the sodium cation of the reagent with the oxygen
atom of the (difluoromethyl)sulfinyl group.
For compound 3 in polar MeCN, an unexpected direction of the process associated with the replacement
of the sulfoxide function with the phenoxy group was also found, apparently the result of an ipso-attack.
Experimental Section
General. The NMR spectra of reaction mixtures or individual compounds were recorded on Bruker AV-300
[300.13 (1H) MHz, 282.40 (19F) MHz, 75.47 (13C)], Bruker AV-400 [400.13 (1H) MHz, 100.61 (13C) MHz], Bruker
AV-600 [600.30 (1H) MHz, 564.84 (19F) MHz, 150.95 (13C) MHz] or Bruker DRX-500 [500.13 (1H) MHz, 125.76
19
1
13
(13C) MHz] spectrometers for solutions of samples in CCl4 : CDCl3 4:1 v/v [for F], CDCl3 [for H and C] or
CD3CN [for 1H]. NMR coupling constants (J) were measured in Hertz (Hz). IR spectra were recorded on a Bruker
Vector 22 spectrophotometer from pellets with KBr for solids and from films for liquid samples. UV spectra
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were obtained on a Hewlett Packard 8453 spectrophotometer from solutions in ethanol. The molecular mass
and elemental composition were determined from high resolution mass spectra taken on a Thermo Electron
Corporation DFS instrument (ionizing electrons energy 70 eV). GC-MS spectra were measured on a Hewlett-
Packard G1081A instrument equipped with a gas chromatograph HP 5890 Series II and a mass-selective
detector HP 5971 (EI, 70 eV), capillary column HP-5 (5% of diphenyl-, 95% dimethylsiloxane) 30 m × 0.25 mm ×
0.25 μm, carrier gas helium, flow rate 1 mL/min. Injector temperature 280 °С, ion source temperature 173 °С.
Scanning rate 1.2 scan/s in mass region 30–650 а.u.m. Analytic GLC was carried out on a Hewlett Packard 5980
chromatograph, equipped with a quartz capillary column HP-5 (stationary phase dimethyl diphenyl
polysiloxane block copolymer), 30 m × 0.52 mm × 2.6 μm, and a thermal conductivity detector.
Materials. Starting compounds were widely used commercially available products of reagent grade and were
purified in the usual manner whenever necessary prior to use. Sodium hydride was used as the commercially
available product (CAS 7646-69-7) and wasn’t purified. Solvents were purified as usual.
3-[(difluoromethyl)sulfinyl]-1,2,4,5-tetrafluorobenzene (1), (difluoromethyl)[2,3,5,6-tetrafluoro-4-(trifluoro-
methyl)phenyl]sulfane (16), (difluoromethyl)[2,3,5,6-tetrafluoro-4-(perfluorophenylthio)phenyl]sulfane (9),
were obtained according to our previous work.24
The studied (difluoromethylsulfinyl)tetrafluorobenzenes compounds (1-3) were synthesized from the
corresponding sulfanes by the action of 100% nitric acid according to our previous work.24 Compound (3) was
used as a 1 : 1 mixture of diastereomers. Characteristic features of the 19F NMR spectra of 1-3 are the
presence of diastereotopic fluorine atoms in the CF2H moiety, which showed bonding to an asymmetrical
center represented by the sulfoxide function.
Quantum chemical calculations. Calculations of the electron structures for polyfluoroaryl sulfoxides were
performed within restricted DFT theory with the B3LYP functional and 6-31G(d) basis set. All calculations were
done with the GAMESS25 package. Stationary potential energy surface points were located and their types and
interrelationships were determined by the normal vibrations analysis. The influence of polar media was taken
into account within the polarizable continuum model (PCM26,27, SMD28), using built-in parameters for benzene,
acetonitrile and diethyl ether. Molecular-orbital and molecular-structure images were constructed by
MOLDEN.29
Preparation of 4-substituted-[(difluoromethyl)sulfinyl]tetrafluorobenzenes
General procedure. Fuming nitric acid was added to the sulfane with stirring at room temperature. The
o
reaction mixture was stirred at 50 С for 3 days. The resulting solution was dissolved in 300 mL of solvent
[CHCl3 in case of sulfane (16); CH2Cl2 in case of sulfane (9)], then 300 mL H2O were added. To the resulting
mixture, Na2CO3 was added until pH 8 was obtained. The organic layer was separated, dried using MgSO4, and
the solvent was evaporated to afford the desired [(difluoromethyl)sulfinyl]tetrafluorobenzene.
1-[(Difluoromethyl)sulfinyl]-2,3,5,6-tetrafluoro-4-(trifluoromethyl)benzene (2). From the reaction of
(difluoromethyl)[2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl]sulfane (16) (39.59 g, 131.90 mmol) and fuming
nitric acid (138.53 g, 2.20 mol), compound (2) (39.43 g, purity by GLC 94 %) was obtained. The product was
distilled (1 mm Hg) and two fractions, 1) 2.08 g (bp before 113 oC, purity by GLC 93 %), and 2) 34.01 g (bp 113-
115 oC, purity by GLC 99 %), were obtained as colorless liquids with a combined yield of 85 %. When cooled to
o
room temperature, the second fraction crystallized to a colorless solid. Mp 29-30 C. IR (film, νmax, cm-1):
2991(vw) (CH), 2926(vw) (CH) 1651(w) (ArF), 1605(vw), 1487(vs) (ArF), 1421(w), 1396(vw), 1327(vs) (CF3),
1281(w), 1259(w), 1188(m), 1157(s) (CF3), 1126(s) (CF3), 1082(s) (S=O), 987(vs) (CF), 935(m), 812 (vw), 787 (w),
771 (vw), 750 (vw), 715(m), 688(w), 658(w), 571(vw), 548(w), 509(w), 482(w), 457 (vw), 419(vw). UV, λmax, nm
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Koshcheev, B.V. et al.
1
2
13
(log ε): 288 (3.62). H NMR (CDCl3, 300.13 MHz): δH 6.85 (t, JHF 55, 1H, CF2H) ppm. C NMR (100.61 MHz,
2
2
1
1
4
1
CDCl3): δC 114.8 (qt, JCF 35, JCF 12, C-(4)), 120.0 (ddt, JCF 295, JCF 287, JCF ~3.5, CF2H), 120.2 (qm, JCF 276,
CF3), 121.4 (td, 2JCF 15, 3JCF 3.5, C-(1)), 144.5 (dm, 1JCF 266, C-(3,5) or (2,6)), 145.8 (dm, 1JCF 258, C-(3,5) or (2,6))
ppm; 19F NMR [CCl4, CDCl3, 282.40 MHz]: δF -137.2 (m, 2F, F-(3,5)), -136.6 (m, 2F, F-(2,6)), -118.9 (ddt, 2JFF 268,
2JFH 55, JFF 3.4, 1F, CF2H), -116.1 (ddt, JFF 268, JFH 55, JFF 5.6, 1F, CF2H), -58.0 (t, JFF 22, 3F, CF3) ppm. Anal.
calcd for C8HF9OS, %: C 30.39; H 0.32; F 54.09; S 10.14; m/z 315.9599. Found, %: C 30.49; H 0.30; F 54.05; S
10.10; m/z 315.9608.
5
2
2
5
4
1-[(Difluoromethyl)sulfinyl]-2,3,5,6-tetrafluoro-4-[(perfluorophenyl)sulfinyl]benzene (3). From fuming nitric
acid (107.60 g, 1.71 mol) and (difluoromethyl){2,3,5,6-tetrafluoro-4-[(perfluorophenyl)thio]phenyl}sulfane 9
(24.30 g, 56.48 mmol) compound 3 (24.97 g) was obtained as mixture of diastereomeres in ratio 1:1. Yield 96
%. Colorless solid, mp 86.3 (decomp.). IR (KBr, νmax, cm-1): 2926(w) (CH), 2854(w) (CH), 1641(m) (ArF), 1498(vs)
(ArF), 1475(vs) (ArF), 1396(w), 1331(vw), 1292(m), 1275(m), 1250(s), 1109(vs) (S=O), 1022(w), 984(s) (CF),
775(w), 725(vw), 634(w), 608(w), 494(m), 447(w). UV, λmax, nm (log ε): 237 (4.52), 274 (4.26). 1H NMR (CD3CN,
2
2
600.30 MHz): δH 7.03 (t, JHF 54.1, 1H, CF2H – one of diast.). 7.04 (t, JHF 54.1, 1H, CF2H – one of diast.) ppm;
13C{19F} NMR (CD3CN, 150.95 MHz): δC (117.9, 118.0, C-(1ʼ)), 118.5 (CHF2), (121.2, 121.3, C-(1)), (127.8, 127.8,
C-(4)), 139.2 (C-(3ʼ,5ʼ)), (145.3, 145.3, C-(3,5)), (145.6, 145.6, C-(4ʼ)), (146.1, 146.1, C-(2ʼ,6ʼ)), (146.5, 146.5, C-
(2,6)) ppm; 19F NMR [ CD3CN, 564.84 MHz]: δF (-159.3, m, 4F, F-(3’,5’)), (-146.3 (tt, 3JCF 20.0, 4JCF 5.7, 1F, F-(4’) –
3
4
one of diast.), (-146.2 (tt, JCF 20.0, JCF 5.5, 1F, F-(4’) – one of diast.), (-139.4 (m, 2F, F-(2’,6’ or 3,5) – one of
diast.), (-139.2 (m, 4F, F-(2’,6’) or F-(3,5)), -138.9 (m, 2F, F-(2’,6’ or 3,5) – one of diast), (-136.5 (m, 4F, F-(2,6)), -
2
2
5
2
2
5
119.2 (ddt, JFF 262.7, JFH 54.3, JFF 6.3, 1F, CF2H - one of the diast.), -119.1 (ddt, JFF 262.5, JFH 54.3, JFF 6.6,
2
2
5
1F, CF2H - one of the diast.), -117.7 (ddt, JFF 262.7, JFH 54.1, JFF 6.1, 1F, CF2H - one of the diast.), -117.6 (ddt,
2JFF 262.5, 2JFH 54.1, 5JFF 6.1, 1F, CF2H - one of the diast.) ppm. Anal. calcd for C13HF11O2S2, %: C 33.78; H 0.22; F
45.21; S 13.87; m/z 461.9237. Found, %: C 33.99; H 0.25; F 45.15; S 13.96; m/z 461.9234.
Reactions of sulfinylbenzenes (1) and (2) with sodium phenolate
General procedure. The weighed portion of PhOH was dissolved in the appropriate volume of the dried
solvent in argon (Ar) atmosphere. Then a ca. 1M phenol solution was added to stirred ca. 1M sodium hydride
suspension and, after termination of gas evolution, the obtained suspension was added dropwise to a ca. 0.5
M solution of compound (1) or (2) with stirring in Ar atmosphere. The obtained reaction mixture was stirred at
the indicated temperature for the indicated time. At the end of the reaction the solvent was evaporated under
the reduced pressure and the residue was dissolved in CHCl3, washed with water and dried using MgSO4. Then
solution was filtered, the solvent was evaporated off under reduced pressure, and the residue was
characterized by 1H and 19F NMR spectroscopy and GC-MS.
3-[(Difluoromethyl)sulfinyl]-1,2,5-trifluoro-4-phenoxybenzene (4). From sulfoxide (1) (3.70 g, 14.91 mmol)
and PhOH (1.60 g, 17.00 mmol) in PhH, a mixture of sulfinylbenzenes (4.44 g, ratio of 1 : 4 : 5 = 19 : 58 : 23)
o
was obtained. Recrystallization from a mixture of hexane-PhH (v/v = 3:1) at -20 С gave 3.62 g of the solid.
o
o
Sublimation at 51-65 С (1 Torr) afforded 0.30 g of compound (1) and at 91-94 С (1 Torr) 2.05 g (43%) of
compound (4). White solid. Mp 70-71 C. IR (KBr, νmax, cm-1): 3061(w) (CH), 3010(w) (CH), 1605(w), 1593(w),
o
1491(vs) (ArF), 1427(m), 1362(w), 1329(vw), 1288(m), 1271(m), 1236(m), 1198(s) (CF), 1119(s) (CF), 1072(s)
(S=O), 1022(w), 935(s), 876(w), 808(w), 748(m), 710(w), 688(m), 673(w), 544(w), 486(w), 465(w), 442(w). UV,
1
2
2
λmax, nm (log ε): 291 (3.72). H NMR (CD3CN, 400.13 MHz): δH 6.97 (m, 2H, H-(2ʼ,6ʼ)), 7.06 (ddd, JHF 55.3, JHF
5
3
4
3
4
54.1, JHF 0.8, 1H, CF2H), 7.15 (tt, JHH ~7, JHH ~1, 1H, H-(4ʼ)), 7.36 (m, 2H, H-(3ʼ,5ʼ)), 7.64 (td, JHF 10, JHF 7.4,
1H, H-(1)) ppm; C NMR (CDCl3, 100.61 MHz): δC 111.9 (t, JCF 22.9, C-(6)), 115.6 (C-(2ʼ,6ʼ)), 120.3 (ddd, JCF
291, JCF 284, JCF 5, CF2H), 123.4 (dd, JCF 14, JCF 7.5, C-(3)), 124.2 (C-(4ʼ)), 130.0 (C-(3ʼ,5ʼ)), 138.5 (ddd, JCF
13
2
1
1
4
2
3
2
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14.3, 3JCF ~3.5, 4JCF ~3.5, C-(4)), 146.1 (ddd, 1JCF 257, 2JCF 14.9, 4JCF ~4, C-(2)), 147.1 (ddd, 1JCF 255, 2JCF 14, 3JCF 10,
1
3
4
19
C-(1)), 150.7 (ddd, JCF 257, JCF 8.4, JCF ~3.5, C-(5)), 157.4 (C-(1ʼ)) ppm; F NMR [CCl4, CDCl3, 282.4 MHz]: δF -
139.0 (m, 1F, F-(2)), -134.9 (ddd, 3JFF 22, 3JHF 10, 4JFF 1.5, 1F, F-(1)), -125.6 (dd, 5JFF 14.4, 3JHF 10, 1F, F-(5)), -119.9
2
2
5
2
2
5
(ddd, JFF 271, JFH 56, JFF 3.5, 1F, CF2H), -114.4 (ddd, JFF 270, JFH 54, JFF 3.8, 1F, CF2H) ppm. Anal. calcd for
C13H7F5O2S, %: C 48.45; H 2.19; F 29.48; S 9.95; m/z 322.0081. Found, %: С 48.42; H 2.22; F 29.30; S 10.03; m/z
322.0079.
Sulfoxide (5) (0.40 g, yield – 7 %) was obtained from the residue after sublimation by crystallization from
hexane-PhH (v/v 3:1).
[{2-[(Difluoromethyl)sulfinyl]-4,6-difluoro-1,3-phenylene}bis(oxy)]dibenzene (5). Sulfoxide (1) (0.344 g, 1.386
mmol) and PhOH (0.266 g, 2.826 mmol) in MeCN gave 0.485 g of the solid. Following recrystallization,
compound 5 (0.330 g, 60 %) was obtained as a white solid. Mp 113-114 oС (hexane : PhH 3:1 v/v). IR (KBr, νmax
,
cm-1): 3074(w) (CH), 3045(vw) (CH), 3018(vw) (CH), 1605(w), 1587(w), 1489(m) (ArF), 1468(vs) (ArF), 1416(w),
1348(w), 1327(vw), 1261(w), 1225(m), 1203(s), 1174(m), 1161(w), 1153(w), 1136(w), 1113(s) (S=O), 1093(m),
1068(m), 1024(w), 989(vw), 937(s), 899(w), 862(w), 804(w), 781(m), 750(m), 742(m), 729(w), 687(m), 565(vw),
1
546(w), 500(vw), 476(w), 463(vw). UV, λmax, nm (log ε): 267 (3.56), 273 (3.60), 302 (3.86). H NMR (CD3CN,
3
4
2
2
400.13 MHz): δH 7.03 (m, 4H, H-(2ʼ,2ʼʼ,6ʼ,6ʼʼ)), 7.15 (tt, JHH 7.4, JHH 0.9, 2H, H-(4ʼ,4ʼʼ)), 7.20 (dd, JHF 57, JHF
3
13
54.4, 1H, CF2H), 7.38 (m, 4H, H-(3ʼ,3ʼʼ,5ʼ,5ʼʼ)), 7.60 (t, JHF 10, 1H, H-(5)) ppm; C NMR (CDCl3, 125.76 MHz): δC
2
1
1
111.8 (t, JCF 23.4, C-(5)), 115.9 (C-(2ʼ,2ʼʼ,6ʼ,6ʼʼ)), 120.3 (dd, JCF 290, JCF 282, CF2H), 124.5 (C-(4ʼ,4ʼʼ)), 129.3 (d,
2
4
1
3
3JCF 7.2, C-(2)), 130.2 (C-(3ʼ,3ʼʼ,5ʼ,5ʼʼ)), 139.5 (dd, JCF 13, JCF 4, C-(1,3)), 151.7 (dd, JCF 257.3, JCF 9.7, C-(4,6)),
19
3
2
157.5 (C-(1ʼ,1ʼʼ)) ppm; F NMR [CCl4, CDCl3, 282.4 MHz]: δF -124.7 (d, JFH 10, 2F, F-(4,6)), -120.0 (dd, JFF 272,
2JFH 57, 1F, CF2H), -113.54 (dd, 2JFF 272, 2JFH 54.4, 1F, CF2H) ppm. Anal. calcd for C19H12F4O3S, %: C 57.58; H 3.05;
F 19.17; S 8.09; m/z 396.0438. Found, %: С 57.88; H 3.19; F 19.14; S 8.32; m/z 396.0441.
1-[(Difluoromethyl)sulfinyl]-2,3,5-trifluoro-6-phenoxy-4-(trifluoromethyl)benzene (6). From sulfoxide (2)
(4.61 g, 14.58 mmol) and PhOH (1.55 g, 16.47 mmol) in PhH, a mixture of sulfinylbenzenes (5.57 g, ratio of 2 :
6 : 7 = 18 : 56 : 25) was obtained. Recrystallization from a mixture of hexane-PhH (v/v = 3:1) followed by
o
o
cooling to -20 С gave 4.25 g of the solid. Sulfinylbenzene (2) was separated by sublimation at 71-75 С (1.0
Torr) and compound (6) (2.49 g, 39 %) was isolated by sublimation at 97-100 oС (1.0 Torr) as a white solid. Mp
69-70oC. IR (KBr, νmax, cm-1): 3068(vw) (CH), 2999(vw) (CH), 1635(w) (ArF), 1597(w), 1473(vs) (ArF), 1377(w),
1325(s) (CF3), 1279(w), 1254(w), 1192(s) (CF), 1163(s) (CF), 1153(s) (CF3), 1124(s) (CF3), 1111(s) (S=O), 1076(m),
1026(w), 985(s) (CF), 935(m), 887(vw), 822(w), 783(vw), 764(w), 746(m), 725(w), 687(m), 661(w), 498(w),
473(vw). UV, λmax, nm (log ε): 273 (3.53), 300 (3.71).
1H NMR (CD3CN, 400.13 MHz): δH 7.02 (m, 2H, H-(2ʼ,6ʼ)), 7.05 (t, 2JHF 54.1, 1H, CF2H), 7.18 (tt, 3JHH 7.4, 4JHH 0.9,
1H, H-(4ʼ)), 7.38 (m, 2H, H-(3ʼ,5ʼ)) ppm; 13C NMR (CDCl3, 100.61 MHz): δC 114.7 (qt, 2JCF 35, 2JCF 13, C-(4)), 115.7
1
1
4
1
2
(C-(2ʼ,6ʼ)), 120.3 (ddd, JCF 292, JCF 287, JCF 4, CF2H), 120.4 (q, JCF 276, CF3), 124.7 (C-(4ʼ)), 126.9 (dd, JCF 14,
3JCF ~6.5, C-(1)), 130.2 (C-(3ʼ,5ʼ)), 139.2 (ddd, 2JCF 14.5, 3JCF ~4, 4JCF ~4, C-(6)), 145.1 (dd, 1JCF 267.4, 2JCF 16, C-(2)),
1
2
3
1
19
146.7 (ddd, JCF 259, JCF 14.7, JCF ~4.5, C-(3)), 148.7 (d, JCF 267.8, C-(5)), 157.2 (C-(1ʼ)) ppm; F NMR [CCl4,
3
5
5
3
4
4
CDCl3, 282.40 MHz]: δF -137.2 (ddt, JFF 22, JFF 15, JF-CF2H ~4, 1F, F-(2)), -136.5 (dqd, JFF 22, JF-CF3 22, JFF 3.8,
4
5
4
2
2
5
1F, F-(3)), -127.1 (qdd, JF-CF3 22, JFF ~15, JFF 3.8, F-(5)), -119.4 (ddd, JFF 269.7, JFH 55.9, JFF 3.0, 1F, CF2H), -
2
2
5
114.4 (ddd, JFF 269.7, JFH 54.4, JFF 4.5, 1F, CF2H), -58.0 (t, 4JFF 22, 3F, CF3) ppm. Anal. calcd for C14H6F8O2S, %:
C 43.09; Н 1.55; F 38.95; S 8.22; m/z 389.9955. Found, %: С 43.27; H 1.62; F 39.07; S 8.42; m/z 389.9952.
Sulfoxide (7) (0.48 g, yield = 6 %) was obtained from the residue following sublimation by crystallization from
hexane.
[{2-[(difluoromethyl)sulfinyl]-4,6-difluoro-5-(trifluoromethyl)-1,3-phenylene}bis(oxy)]dibenzene
(7).
Sulfoxide (2) (1.56 g, 4.93 mmol) and PhOH (0.95 g, 10.09 mmol) in Et2O gave 2.09 g of crude product.
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o
Following recrystallization, sulfinylbenzene (7) (1.70 g, 74 %) was obtained as a white solid. Mp 110-111 C
(hexane). IR (KBr, νmax, cm-1): 3064 (vw) (CH), 3045 (vw) (CH), 3020 (vw) (CH), 1620 (w), 1605 (w) (ArF), 1595
(m), 1491 (s) (ArF), 1466 (vs) (ArF), 1371 (w), 1317 (vs) (CF3), 1252 (m), 1198 (s) (CF), 1165 (s) (CF3), 1142 (s)
(CF), 1109 (s) (S=O), 1072 (m), 1024 (w), 989 (s) (CF), 935 (m), 843 (vw), 754 (m), 723 (vw), 688 (m), 565 (w),
1
490 (w). UV, λmax, nm (log ε): 266 (3.50), 273 (3.51), 312 (3.85). H NMR (CD3CN, 300.13 MHz): δH 7.08 (m, 4H,
3
4
2
2
H-(2ʼ,2ʼʼ,6ʼ,6ʼʼ)), 7.18 (tt, JHH 7.4, JHH 1.0, 2H, H-(4ʼ,4ʼʼ)), 7.19 (dd, JHF 56, JHF 54, 1H, CF2H), 7.40 (m, 4H, H-
13
2
2
(3ʼ,3ʼʼ,5ʼ,5ʼʼ)) ppm; C NMR (CDCl3, 100.61 MHz): δC 114.8 (qt, JCF 34, JCF 13, C-(5)), 115.9 (C-(2ʼ,2ʼʼ,6ʼ,6ʼʼ)),
120.6 (q, JCF 276, CF3), 120.7 (dd, JCF 291.4, JCF 283.4, CF2H), 124.5 (C-(4ʼ,4ʼʼ)), 130.2 (C-(3ʼ,3ʼʼ,5ʼ,5ʼʼ)), 132.9
(d, JCF 7.0, C-(2)), 140.1 (dd, JCF 13.6, JCF 4.6, C-(1,3)), 149.5 (d, JCF 268.5, C-(4,6)), 157.5 (C-(1ʼ,1ʼʼ)) ppm; F
NMR [CCl4, CDCl3, 282.40 MHz]: δF -126.2 (q, 4JFF 22.7, 2F, F-(4,6)), -119.7 (dd, 2JFF 272, 2JFH 56, 1F, CF2H), -112.9
(dd, 2JFF 272, 2JFH 54, 1F, CF2H), -57.9 (t, 4JFF 22.7, 3F, CF3) ppm. Anal. calcd for C20H11F7O3S, %: C 51.73; H 2.39; F
28.61; S 6.90; m/z 464.0312. Found, %: С 51.49; H 2.46; F 28.65; S 6.96; m/z 464.0319.
1
1
1
3
2
4
1
19
[{2-[(difluoromethyl)sulfinyl]-3,6-difluoro-5-(trifluoromethyl)-1,4-phenylene}bis(oxy)]dibenzene
(8).
Sulfoxide 2 (1.79 g, 5.66 mmol) and PhOH (1.22 g, 12.96 mmol) in MeCN gave 2.09 g of solid. A mixture of
1
isomers (7) and (8) (1.57 g, 60 %) in the ratio 58 : 42 was obtained by recrystallization from hexane. H NMR
2
2
5
(CD3CN, 300.13 MHz): δH 7.02 (ddd, JHF 55, JHF 54, JHF ~1, 1H, CF2H), ~7.07 (m, 2H, H1Ph-(2,6), 7.09 (m, 2H,
H4Ph-(2,6), ~7.18 (1H, H1Ph-(4)), 7.20 (tt, 3JHH 7.4, JHH ~1.0, 1H, H4Ph-(4), ~7.40 (m, 4H, H1Ph and 4Ph-(3,5)) ppm; 13C
NMR (CDCl3, 75.47 MHz): δC 115.2 (C1Ph or 4Ph-(2,6)), 115.7 (C1Ph or 4Ph-(2,6)), 119.7 (qdd, JCF 33, JCF 10.5, JCF
~2.2, C-(5)), 120.4 (ddd, JCF 292, JCF 286, JCF ~5, CF2H), 121.2 (qm, JCF 276, CF3), 124.0 (C1Ph or 4Ph-(4)), 124.5
(C1Ph or 4Ph-(4)), 126.7 (dd, JCF 15.7, JCF 6.9, C-(2)), 130.0 (C1Ph or 4Ph-(3,5)), 130.1 (C1Ph or 4Ph-(3,5)), 138.8 (d, JCF
4
2
2
3
1
1
4
1
2
3
2
2
3
1
4
1
4
~15.5, C-(4)), 139.9 (dd, JCF ~19, JCF 4, C-(1)), 149.3 (dd, JCF 267, JCF ~2, C-(6)), 151.3 (dd, JCF 260, JCF 3.6, C-
(3)), 157.3 (d, 4JCF 1.9, C-(1’) or (1’’)), 157.4 (d, 4JCF 1.7, C-(1’) or C-(1’’)) ppm; 19F NMR [CCl4, CDCl3, 282.40 MHz]:
δF -127.6 (qd, 4JFF 27, 5JFF 15.1, 1F, F-(6)), -126.9 (dt, JFF 15.1, JFF 4.5, 1F, F-(3)), -119.7 (ddd, JFF 268.2, JFH 55,
5
5
2
2
5JFF 4.5, 1F, CF2H), -114.9 (ddd, JFF 268.2, JFH 54, JFF 4.5, 1F, CF2H), -57.9 (d, 4JFF 27, 3F, CF3) ppm. Anal. calcd
for 7 + 8 (C20H11F7O3S1), %: C 51.73; H 2.39; F 28.61; S 6.90; m/z 464.0312. Found, %: С 51.73; H 2.38; F 28.79;
S 6.80; m/z 464.0317.
2
2
5
Reduction of 1-[(difluoromethyl)sulfinyl]-2,3,5,6-tetrafluoro-4-[(perfluorophenyl)sulfinyl]benzene (3) to
(difluoromethyl)[2,3,5,6-tetrafluoro-4-([perfluorophenylthio)]phenyl)sulfane (9) by acetyl chloride. Acetyl
chloride (8.19 g, 104.33 mmol) was added to compound 3 (1.26 g, 2.73 mmol) and the resulted solution was
refluxed during 5 h. The excess of acetyl chloride was then evaporated off and the residue was dissolved in
water (30 mL) to form a precipitate, which was filtered off to give 1.08 g (92 %) of the desired sulfane (9). The
analytical characteristics of sulfane 9 correspond to literature data.Error! Bookmark not defined.
Reaction of compound (3) with sodium phenolate with subsequent reduction of the resulted mixture by
acetyl chloride. General procedure. The weighed portion of PhOH was dissolved in the appropriate volume of
the dried solvent in Ar atmosphere. Then phenol solution was added to stirred sodium hydride suspension
and, after termination of gas evolution, the obtained suspension was added dropwise to a ca. 0.5 M solution
of compound (3) with stirring in Ar atmosphere. The obtained reaction mixture was refluxed with stirring for 2
h. The solvent from the resulted mixture was evaporated, then the residue was dissolved in 50 mL CHCl3. The
solution was washed with water, and the organic layer was separated and dried using MgSO4. Then the
solvent was evaporated, and toluene and acetyl chloride were added to the crude residue. The resulting
19
solution was refluxed for 480 h to achieve, according F NMR spectroscopy, full conversion of sulfoxides to
the corresponding sulfanes. Then, the excess of acetyl chloride and toluene was evaporated. The residue thus
obtained was treated with CHCl3 (50 mL) and water (50 mL). Sodium carbonate was added to the resulting
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mixture until pH 8. The organic layer was separated, dried using MgSO4, and the solvent was evaporated off
19
under reduced pressure, and the product was analyzed by means of GC-MS and quantitative F NMR
spectroscopy with fluorobenzene (PhF) as internal standard.
In MeCN solution. Phenol (1.48 g, 15.73 mmol) in MeCN (15 mL) was treated with a suspension of NaH (0.61 g,
15.25 mmol) in MeCN (15 mL), and the resulting suspension was added to a solution of compound 3 (6.81 g,
14.73 mmol) in MeCN (30 mL), as described above, to give 7.94 g of the crude product, which was then
subjected to the action of acetyl chloride (34.05 g, 0.434 mol) in the presence of toluene (5.44 g, 59.04 mmol)
19
to afford a 7.15 g of mixture of sulfanes 9 : 10 : 11 : 12 : 13 in the ratio 29 : 31 : 16 : 18 : 6 (by F NMR),
respectively. Thus, yields of the products were 24% (9), 26% (10), 13% (11), 15% (12), and 5% (13).
In benzene solution. Phenol (1.35 g, 14.34 mmol) in PhH (15 mL) was treated with a suspension of NaH (0.57
g, 14.25 mmol) in PhH (15 mL), and the resulting suspension was added to solution of compound 3 (6.29 g,
13.61 mmol) in PhH (27 mL), as described above, to give 7.23 g of the crude product, which was then
subjected to the action of acetyl chloride (52.88 g, 0.674 mol) in the presence of toluene (5.06 g, 54.92 mmol)
19
to afford a 7.01 g sulfanes mixture of 9 : 13 : 14 : 15 in a ratio of 23 : 50 : 15 : 11 (by F NMR), respectively.
Thus, yields of the products were 19% (9), 40% (13), 12% (14), and 9% (15).
(Difluoromethyl){2,3,5,6-tetrafluoro-4-[(2,3,5,6-tetrafluoro-4-phenoxyphenyl)thio]phenyl}sulfane (10). Mp
o
68-71 С. IR (KBr, νmax, cm-1): 3064(vw) (CH), 3045(vw) (CH), 1635 (w) (ArF), 1624 (vw), 1593 (m), 1483 (vs)
(ArF), 1471 (vs) (ArF), 1437 (m), 1408 (w), 1387 (w), 1313 (m), 1296 (w), 1252 (w), 1207 (s) (CF), 1196 (m), 1169
(w), 1149 (vw), 1105 (m), 1090 (m), 1074 (m), 1059 (m), 1047 (m), 1024 (w), 980 (s) (CF), 964 (s) (CF), 868 (m),
812 (m), 781 (w), 744 (m), 723 (w), 687 (m), 631 (w), 619 (w), 588 (vw), 496 (w). UV, λmax, nm (log ε): 205
1
(4.52), 259 (4.23), 266 (4.23), 273 (4.25). H NMR (CD3CN, 300.13 MHz): δH 7.05 (m, 2H, H-(2ʼʼ,6ʼʼ)), 7.11 (t, 2JHF
3
13
55.2, 1H, CF2H), 7.17 (br.t, JHH 7.5, 1H, H-(4ʼʼ)), 7.38 (m, 2H, H-(3ʼʼ,5ʼʼ)) ppm; C NMR (CDCl3, 125.76 MHz): δC
105.5 (t, 2JCF 20.3, C-(1ʼ)), 106.8 (tt, 2JCF 21, 3JCF ~3.5, C-(1)), 115.7 (t, 2JCF 19.0, C-(4)), 116.0 (C-(2ʼʼ,6ʼʼ)), 118.3 (t,
1JCF ~280.5, CF2H), 124.4 (C-(4ʼʼ)), 130.1 (C-(3ʼʼ,5ʼʼ)), 136.2 (tt, JCF ~13, JCF ~3.5, (C-(4ʼ)), 142.0 (dm, JCF 255, C-
(2ʼ,6ʼ) or (3ʼ,5ʼ)), 146.8 (dm, JCF 252, C-(2ʼ,6ʼ) or (3ʼ,5ʼ)), 147.8 (dm, JCF ~252, (C-(2,3,5,6)), 157.1 (C-(1ʼʼ)) ppm;
19F NMR [CCl4, CDCl3, 282.40 MHz]: δF -153.2 (m, 2F, F-(3’’,5’’)), -133.4 (m, 2F, F-(2’,6’) or (3,5)), -133.2 (m, 2F,
F-(2’,6’) or (3,5)), -130.5 (m, 2F, F-(2,6)), -92.0 (dt, 2JFH 55.9, JFF 4.5, 2F, CF2H) ppm. Anal. calcd for C19H6F10OS2,
2
3
1
1
1
5
%: C 45.25; H 1.20; F 37.67; S 12.71; m/z 503.9695. Found, %: С 45.39; H 1.21; F 37.60; S 12.66; m/z 503.9691.
(Difluoromethyl)(2,3,5,6-tetrafluoro-4-phenoxyphenyl)sulfane (11). Mp 44-45. IR (KBr, νmax, cm-1): 3066 (vw)
(CH), 2974 (vw) (CH), 1637 (w) (ArF), 1591 (m), 1491 (vs) (ArF), 1456 (m), 1406 (m), 1387 (vw), 1315 (m), 1288
(w), 1209 (s) (CF), 1163 (w), 1136 (vw), 1093 (m), 1078 (s) (CF), 1049 (s) (CF), 1001 (w), 976 (s), 904 (vw), 872
(m), 835 (vw), 816 (w), 771 (w), 750 (s) (CF), 731 (m), 692 (m), 669 (vw), 656 (vw), 604 (vw), 552 (vw), 484 (w),
1
465 (w). UV, λmax, nm (log ε): 210 (4.32), 248 (3.97). H NMR (CD3CN, 300.13 MHz): δH 7.08 (m, 2H, H-(2ʼ,6ʼ)),
1
3
4
13
7.10 (t, JHF 55, 1H, CF2H), 7.19 (tt, JHH ~7, JHH 1, 1H, H-(4’)), 7.40 (m, 2H, H-(3’,5’)) ppm; C NMR (125.76
2
1
MHz, CDCl3): δC 100.4 (tm, JCF ~21, C-(1)), 116.1 (C-(2ʼ,6ʼ)), 118.5 (t, JCF 280.0, CF2H), 124.4 (C-(4’)), 130.1 (C-
(3ʼ,5ʼ)), 137.0 (tt, JCF ~13, JCF ~4, C-(4)), 142.0 (dm, JCF 253, C-(3,5)), 148.8 (ddt, JCF 250, JCF ~12, JCF ~3.7, C-
(2,6)), 157.0 (C-(1’)) ppm; F NMR [CCl4, CDCl3, 282.4 MHz]: δF -153.1 (m, 2F, F-(3,5)), -131.7 (m, 2F, F-(2,6)), -
92.5 (dt, JFH 56, JFH ~4, CF2H) ppm. Anal. calcd for C13H6F6OS, %: C 48.16; H 1.87; F 35.16; S 9.89; m/z
324.0038. Found, %: С 47.86; H 1.96; F 35.19; S 9.93; m/z 324.0034.
Bis(2,3,5,6-tetrafluoro-4-phenoxyphenyl)sulfane (12). Mp 126-129 C. IR (KBr, νmax, cm-1): 3078 (vw) (CH),
2
3
1
1
2
3
19
1
4
o
3064 (vw) (CH), 3045 (vw) (CH), 1593 (m), 1489 (vs) (ArF), 1400 (w), 1281 (vw). 1203 (s) (CF), 1169 (m), 1088
(m), 1074 (w), 1024 (vw), 978 (m), 868 (m), 744 (m), 687 (w), 496 (vw). UV, λmax, nm (log ε): 254 (4.28), 258
1
3
(4.28), 265 (4.27), 272 (4.23). H NMR (CD3CN, 300.13 MHz): δH 7.05 (m, 4H, H-(2ʼ,2ʼʼ,6ʼ,6ʼʼ)), 7.17 (t, JHH 7.4,
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13
2
2H, H-(4’,4ʼʼ)), 7.38 (m, 4H, H-(3ʼ,3ʼʼ,5ʼ,5ʼʼ)) ppm; C NMR (CDCl3, 125.76 MHz): δC 106.8 (br.t, JCF ~20, C-(1)),
115.9 (C-(2ʼ,2ʼʼ,6ʼ,6ʼʼ)), 124.3 (C-(4ʼ,4ʼʼ)), 130.0 (C-(3ʼ,3ʼʼ,5ʼ,5ʼʼ)), 135.6 (t, JCF ~13, C-(4)), 141.9 (dd, 1JCF 255, JCF
2
2
1
2
19
~15, C-(3,5)), 147.8 (dd, JCF 250, JCF ~12, C-(2,6)), 157.0 (C-(1ʼ,1ʼʼ)) ppm; F NMR [CCl4, CDCl3, 282.4 MHz]: δF -
153.3 (m, 4F, F-(3,5)), -134.0 (m, 4F, F-(2,6)) ppm. Anal. calcd for C24H10F8O2S, %: C 56.04; H 1.96; F 29.55; S
6.23; m/z 514.0268. Found, %: С 55.98; H 1.94; F 29.73; S 6.33; m/z 514.0278.
o
(Difluoromethyl){2,3,5-trifluoro-4-[(perfluorophenyl)thio]-6-phenoxyphenyl}sulfane (13). Mp 64-67 C. IR
(KBr, νmax, cm-1): 3066 (vw) (CH), 2980 (vw) (CH), 2922 (vw) (CH), 1641 (w) (ArF), 1593 (w), 1516 (s) (ArF), 1493
(vs) (ArF), 1462 (vs) (ArF), 1379 (w), 1323 (m), 1294 (vw), 1248 (m), 1207 (s) (CF), 1169 (w), 1155 (vw), 1093
(m), 1066 (m), 1049 (m), 1026 (w), 1014 (w), 970 (s) (CF), 899 (vw), 864 (m), 829 (w), 808 (w), 787 (vw), 754 (s),
1
733 (w), 692 (w), 646 (w), 494 (w). UV, λmax, nm (log ε): 208 (4.50), 211 (4.49), 215 (4.49), 275 (4.04). H NMR
(CD3CN, 400.13 MHz): δH 6.86 (m, 2H, H-(2ʼ,6ʼ)), 7.07 (td, 2JHF 56, 5JHF ~0.5, 1H, CF2H), 7.12 (tt, 3JHH ~7.5, 4JHH ~1,
1H, H-(4’)), 7.34 (m, 2H, H-(3’,5’)) ppm; C NMR (CDCl3, 125.76 MHz): δC 105.8 (tm, JCF ~21, CC6F5-(1)), 114.1
(dt, 2JCF ~16.5, 3JCF ~4.5, C-(1)), 114.3 (t, 2JCF ~20, C-(4)), 115.2 (C-(2ʼ,6ʼ)), 118.6 (td, 1JCF 280, 4JCF ~3, CF2H), 123.7
(C-(4’)), 130.0 (C-(3ʼ,5ʼ)), 138.0 (dm, 1JCF 255, CC6F5-(3,5)), 140.6 (dd, 2JCF 14, 3JCF 4, C-(6)), 142.7 (dtt, 1JCF 258, 2JCF
13
2
3
1
1
2
3
~13, JCF ~5, CC6F5-(4)), 147.5 (dm, JCF 250, CC6F5-(2,6)), 147.6 (ddd, JCF 253, JCF 16, JCF 4, C-(3 or 2)), 148.2
(ddd, JCF 252, JCF 15, JCF 4, C-(3 or 2)), 151.5 (ddd, 1JCF 254, JCF ~3, 4JCF ~3, C-(5)), 157.2 (C-(1’)) ppm; F NMR
1
2
3
3
19
3
4
[CCl4, CDCl3, 282.40 MHz]: δF -160.8 (m, 2F, FC6F5-(3,5)), -150.9 (tt, JFF ~21, JFF ~4, 1F, FC6F5-(4)), -132.9 (m, 2F,
FC6F5-(2,6)), -131.6 (ddt, 3JFF 24, 4JFF 3, 6JFF 3, 1F, F-(3)), -129.4 (ddt, 3JFF 24, JFF 12, 5JFF 5.3, 1F, F-(2)), -122.5 (dm,
5
5JFF 12, 1F, F-(5)), -92.3 (dd, JFH 57.4, JFF 5.3, 2F, CF2H) ppm. Anal. calcd for C19H6F10OS2, %: C 45.25; H 1.20; F
2
5
37.67; S 12.71; m/z 503.9695. Found, %: С 45.32; H 1.18; F 37.58; S 12.72; m/z 503.9686.
{3,5-difluoro-4-[(perfluorophenyl)thio]-2,6-diphenoxyphenyl}(difluoromethyl)sulfane (14). Mp 93 oC
(decomp.). IR (KBr, νmax, cm-1): 3070 (vw) (CH), 3045 (vw) (CH), 2924 (vw) (CH), 1637 (w) (ArF), 1591 (m), 1562
(w), 1516 (s) (ArF), 1489 (vs) (ArF), 1443 (vs) (ArF), 1377 (w), 1363 (vw), 1319 (w), 1292 (w), 1236 (w), 1200 (vs)
(CF), 1167 (m), 1092 (m), 1068 (m), 1039 (s) (CF), 1022 (w), 984 (m), 970 (s) (CF), 945 (w), 895 (vw), 862 (m),
850 (w), 829 (vw), 812 (w), 787 (vw), 754 (m), 739 (w), 698 (w), 685 (w), 648 (w), 559 (vw), 485 (w). UV, λmax
nm (log ε): 204 (4.37), 275 (3.96). H NMR (CD3CN, 400.13 MHz): δH 6.91 (m, 4H, H-(2ʼ,2ʼʼ,6ʼ,6ʼʼ)), 7.12 (t, JHH
,
1
3
2
13
7.4, 2H, H-(4ʼ,4ʼʼ)), 7.14 (t, JHF 57, 1H, CF2H), 7.35 (m, 4H, H-(3ʼ,3ʼʼ,5ʼ,5ʼʼ)) ppm; C NMR (CDCl3, 100.61 MHz):
δC 106.3 (tm, 2JCF ~21, CC6F5-(1)), 113.5 (t, 2JCF 20, C-(4)), 115.2 (C-(2ʼ,2ʼʼ,6ʼ,6ʼʼ)), 119.1 (t, 1JCF 279, CF2H), 121.8 (t,
3JCF ~2, C-(1)), 123.6 (C-(4ʼ,4ʼʼ)), 130.0 (C-(3ʼ,3ʼʼ,5ʼ,5ʼʼ)), 137.9 (dm, 1JCF 254, CC6F5-(3,5)), 140.8 (dd, 2JCF 14, JCF 4,
C-(2,6)), 142.4 (dtt, JCF 258, JCF 13.6, JCF ~5, CC6F5-(4)), 147.2 (dm, JCF 250, CC6F5-(2,6)), 152.6 (dd, JCF 254, JCF
4
1
2
3
1
1
3
19
~3.5, C-(3,5)), 157.1 (C-(1ʼ)) ppm; F NMR [CCl4, CDCl3, 282.40 MHz]: δF -161.1 (m, 2F, FC6F5-(3,5)), -151.5 (tt,
3JFF 20, JFF 3.0, 1F, FC6F5-(4)), -133.4 (m, 2F, FC6F5-(2,6)), -120.7 (t, JFF 3.0, 2F, F-(3,5)), -92.4 (d, JFH 58.2, 2F,
CF2H) ppm. Anal. calcd for C25H11F9O2S2, %: C 51.91; H 1.92; F 29.56; S 11.08; m/z 578.0051. Found, %: С 51.64;
H 1.97; F 29.39; S 11.18; m/z 578.0048.
4
6
2
{2,5-difluoro-4-[(perfluorophenyl)thio]-3,6-diphenoxyphenyl}(difluoromethyl)sulfane (15). Mp 82 oC. IR (KBr,
νmax, cm-1): 3066 (vw) (CH), 3043 (vw) (CH), 2955 (vw) (CH), 2924 (w) (CH), 2850 (vw) (CH), 1724 (vw), 1641 (w)
(ArF), 1595 (m), 1518 (s) (ArF), 1487 (vs) (ArF), 1441 (vs) (ArF), 1371 (w), 1321 (m), 1292 (w), 1234 (m), 1209 (s)
(CF), 1167 (m), 1153 (w), 1099 (m), 1070 (s) (CF), 1038 (m), 1024 (w), 972 (s) (CF), 943 (w), 891 (w), 862 (w),
839 (w), 800 (w), 752 (s), 721 (vw), 692 (w), 687 (w), 650 (w), 554 (vw), 484 (w), 426 (vw). UV, λmax, nm (log ε):
267 (4.05), 275 (4.06), 285 (4.08). 1H NMR (CD3CN, 300.13 MHz): δH 6.77 (m, 2H, H3Ph-(2,6)), 6.96 (m, 2H, H6Ph-
2
3
3
(2,6)), 7.04 (t, JHF 56, 1H, CF2H), 7.06 (t, JHH 7.4, 1H, H3Ph-(4)), 7.13 (t, JHH 7.4, 1H, H6Ph-(4)), 7.27 (m, 2H, H3Ph-
13
2
2
(3,5)), 7.37 (m, 2H, H6Ph-(3,5)). C NMR (125.76 MHz, CDCl3): δC 106.5 (tm, JCF ~20, CC6F5-(1)), 113.1 (dd, JCF
19.7, JCF ~2, C-(1)), 114.3 (C3Ph or 6Ph-(2,6)), 115.4 (C3Ph or 6Ph-(2,6)), 118.7 (td, JCF 280, JCF ~3.5, CF2H), 120.8 (d,
4JCF ~18, C-(4)), 123.6 (C3Ph or 6Ph-(4)), 123.7 (C3Ph or 6Ph-(4)), 129.8 (C3Ph or 6Ph-(3,5)), 130.0 (C3Ph or 6Ph-(3,5)), 137.8
3
1
4
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1
2
3
2
4
1
(dm, JCF 254, CC6F5-(3,5)), 139.4 (dd, JCF 16, JCF ~2.5, C(3)), 141.7 (dd, JCF 14.6, JCF ~2, C(6)), 142.1 (dtt, JCF
2
3
1
1
4
258, JCF 13.5, JCF ~5, CC6F5-(4)), 147.8 (dm, JCF 249, CC6F5-(2,6)), 151.8 (dd, JCF 252.7, JCF 3.7, C(2) or C(5)),
1
4
4
4
19
153.0 (dd, JCF 253.4, JCF 3.5, C(2) or C(5)), 156.6 (d, JCF 1.4, C3Ph or 6Ph-(1)), 157.4 (d, JCF 1.6, C3Ph or 6Ph-(1)). F
NMR [CCl4, CDCl3, 282.4 MHz]: δF -161.6 (m, 2F, F(3’,5’)), -152.6 (tt, JFF 20.4, JFF 3.0, 1F, F(4’)), -133.3 (m, 2F,
F(2’,6’)), -122.0 (d, JFF 12.8, 1F, F-(5)), -119.0 (dt, JFF 12.8, JFF 5.3, 1F, F-(2)), -92.9 (dd, JFH 58.2, JFF 5.3, 2F,
CF2H). Anal. calcd for C25H11F9O2S2, %: C 51.91; H 1.92; F 29.56; S 11.09; m/z 578.0051. Found, %: С 52.22; H
2.05; F 29.55; S 10.69; m/z 578.0049.
3
4
5
5
5
2
5
Acknowledgements
The authors thank the Multi-Access Chemical Research Center of the Siberian Branch of the Russian Academy
of Sciences for analytic measurements. The authors express deep gratitude to G.E. Salnikov for NMR studies of
compound (3). This work was supported by the Ministry of Science and Higher Education of the Russian
Federation. Authors declare no conflict of interest.
Supplementary Material
1
13
19
The Supplementary Material contains H, C and F NMR spectra data for compounds 2-8 and 10-15 are
presented in the online version of the text.
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