A new method for the synthesis of fluorinated vinyl sulfides and ketene dithioacetals

Article abstract of DOI:10.1023/A:1011325520421

A new method was developed for the synthesis of fluorine-containing functionally substituted vinyl sulfides and ketene dithioacetals from the corresponding derivatives of α-trifluoromethyl-substituted CH-acids and thiols in the presence of BF₃

Full text of DOI:10.1023/A:1011325520421

1044
Russian Chemical Bulletin, International Edition, Vol. 50, No. 6, pp. 1044—1046, June, 2001
A new method for the synthesis of fluorinated vinyl sulfides
and ketene dithioacetals
A. N. Kovregin, A. Yu. Sizov,« and A. F. Ermolov
Military University of Radiational, Chemical and Biological Defense,
13 Brigadirskiy per., 107005 Moscow, Russian Federation.
Fax: +7 (095) 267 5107
A new method was developed for the synthesis of fluorine-containing functionally
substituted vinyl sulfides and ketene dithioacetals from the corresponding derivatives of
α-trifluoromethyl-substituted CH-acids and thiols in the presence of BF3•NEt3.
Key words: CH-acids, thiols, fluorinated vinyl sulfides, fluorinated ketene dithioacetals,
dehydrofluorination, BF3•NEt3.
Scheme 1
One of the main methods for the synthesis of fluori-
nated vinyl sulfides involves the reactions of thiols with
fluoroalkenes followed by dihydrofluorination of the
addition products.1 Vinyl sulfides and ketene dithioacetals
are formed in one stage by the reactions of fluoroalkenes
with sodium thiolates, the direction of the reaction
depending on the order in which the reagents are added
and on the reagent ratio.2 However, the starting
fluoroalkenes, in particular, functionally substituted com-
pounds, are difficultly accessible compounds, which is
an essential limitation of these procedures.
We found that the reactions of thiols with derivatives
of some α-trifluoromethyl-containing CH-acids in the
presence of 2 equiv. of the BF3•NEt3 complex afforded
vinyl sulfides 1 in one step in preparative yields
(Scheme 1). In some cases, fluorine-containing ketenes 2
are formed as the major products or by-products (Table 1).
Functionally substituted fluorine-containing CH-ac-
ids, such as methyl ester and nitrile of 2-hydro-
hexafluoroisobutyric acid, dimethyl (trifluoromethyl)ma-
lonate, and 2-hydrotetrafluoropropiononitrile, enter into
this reaction. The reaction conditions are determined by
X
2 BF3•NEt3
+
F3C CH
RSH
Y
X
Y
X
Y
+
RS CF
C
(RS)2C C
1
2
the strength of the CH-acid. Thus the reactions with
derivatives of hexafluoroisobutyric and (trifluoro-
methyl)malonic acids occurred at 50 °C, the reaction
with tetrafluoroproiononitrile, which is a weaker
CH-acid, required heating to 90—100 °C, whereas me-
thyl 2-hydrotetrafluoropropionate (the weakest CH-acid
studied) did not give the target products even on heating
in a sealed tube at 150 °C.
Apparently, the first stage of the reaction (Scheme 2)
involves dehydrofluorination of the CH-acid to form
Scheme 2
Table 1. Products of the reactions of CH-acids with RSH
BF3•NEt3
RSH + BF3•NEt3
Com-
pound
X
Y
R
1 : 2
CF3 CHXY
CF2 CXY
–NEt3HBF4
1à, 2à
1b, 2b
1c
1d, 2d*
1e, 2e
1f, 2f
1g
CF3
CF3
CF3
COOMe
CF3
CF3
CF3
F
COOMe
COOMe
COOMe
COOMe
CN
CN
CN
CN
CN
PhCH2
CH2COOMe
But
PhCH2
PhCH2
CH2COOMe
But
3
2
1
0
1
3
2
0
4
0
9
1
1
4
7
3
1
1
1
1
NEt3H RS CF CXY + BF3
F
–NEt3HBF4
RSH + BF3•NEt3
1h, 2h
1i
1j, 2j
PhCH2
But
Me
1
F
F
CN
* Compound 2d was not isolated in individual form because it
decomposed on fractionation; its formation was detected based
on the data from GLC-mass spectrometry (m/z 388 [M]+).
NEt3H (RS)2C CXY + BF3
F
2
–NEt3HBF4
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1000—1002, June, 2001.
1066-5285/01/5006-1044 $25.00 © 2001 Plenum Publishing Corporation

Vinyl sulfides and ketene dithioacetals
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 6, June, 2001
1045
the corresponding fluoroalkene. The latter is immedi-
ately attacked by the anion generated under the action
of BF3•NEt3 on a thiol. The intermediate thus formed
is stabilized by β-elimination of the fluoride ion, which
is irreversibly incorporated into triethylammonium
tetrafluoroborate. It is this fact that is responsible for
the absence of the addition products. Products 2 are
formed analogously.
Mixtures of products 1 and 2 can readily be sepa-
rated by fractionation or crystallization. The proportion
of disubstitution products depends on the reaction con-
ditions (the yield increases under more drastic condi-
tions) and on the structure of the initial thiol. Thus the
reaction of tetrafluoropropiononitrile with methanethiol
afforded ketene dimethyl dithioacetal 2j as the major
product, whereas even no traces of the corresponding
ketene dithioacetal were detected among the products of
the reaction with sterically hindered ButSH. Previously,3
the role of steric effects in the reactions of fluoroalkenes
with secondary amines has been noted.
The composition of the reaction products depends
essentially on the reagent ratio. Thus the introduction of
the third equivalent of BF3•NEt3 and the second equiva-
lent of the thiol makes it possible to direct the synthesis
toward double substitution products. In particular, bi-
functional thiols, such as 1,2-ethanedithiol and mer-
captoethanol, gave exclusively ethylene (di)thioacetals 3
(Scheme 3).
Table 2. Yields, properties, spectral characteristics, and the data from elemental analysis of compounds 1—3
Com- Yield B.p./°C
Found
Calculated
Molecular
formula
1H NMR (DMSO-d6), δ
MS
(EI, 70eV),
m/z, [M]+
(%)
H
pound (%)
(Torr)
[m.p./°C]
C
1à
1b
52
43
112—114
(3)
103—104
(3)
48.76
48.98
34.95
34.78
3.43
3.40
2.92
2.90
C12H10F4O2S
C8H8F4O4S
7.75 (m, 5 H, Ph); 4.34 and 4.28 (both s,
2 H each, ÑÍ2, ratio 1 : 9); 3.79 (s, 3 H, Me)
4.02 and 3.97 (both s, 2 H, ÑÍ2, ratio 1 : 7);
3.84 and 3.82 (both s, 3 H, Me, ratio 1 : 7);
3.68 (s, 3 Í, Me)
294
276
1c4
1d
1e
1f
71
66
63
52
73
18
73
9
55—57
(3)
160—165
(3)
86—88
(3)
78—79
(3)
70—72
(12)
76—78
(3)
57—60
(15)
45—47
(15)
41.40
41.54
54.80
54.93
50.71
50.57
34.80
34.57
42.37
42.29
56.92
56.87
47.65
47.46
35.29
35.56
57.34
57.29
36.52
36.46
59.27
59.18
36.63
36.47
64.91
64.76
36.68
36.81
34.52
34.43
34.20
34.12
37.36
37.27
36.92
36.84
4.58
4.62
4.57
4.58
2.63
2.68
2.04
2.06
4.00
3.96
3.33
3.32
5.05
5.08
2.27
2.22
4.23
4.27
3.61
3.59
3.85
3.84
3.08
3.04
4.40
4.44
3.71
3.68
2.90
2.87
1.87
1.90
2.50
2.48
3.06
3.07
C9H12F4O2S
C13H13FO4S
C11H7F4NS
C7H5F4NO2S
C8H9F4NS
3.83 and 3.81 (both s, 3 Í, Me, ratio 1 : 4);
1.53 (s, 9 Í, Âut)
7.30 (m, 5 H, Ph); 4.27 (s, 2 Í, ÑÍ2);
3.74 (s, 3 Í, Må); 3.70 (s, 3 H, Må)
7.30 (m, 5 Í, Ph); 5.50 (s, 2 Í, ÑÍ2)
260
284
261
243
227
211
177
135
398
362
365
329
315
163
244
211
161
228
4.11 (s, 2 Í, ÑÍ2); 3.78 (s, 3 Í, Må)
1.67 (s, But)
1g
1h
1i
C10H7F2NS
C7H9F2NS
7.35 (m, 5 Í, Ph); 4.32 and 4.27 (both s,
2 H each, ÑÍ2, ratio 1 : 1)
1.50 (s, But)
1j
C4H3F2NS
2.58 and 2.57 (both s, Må, ratio 3 : 1)
2a
2b
2e
2f
34
46
24
32
59
69
82
76
72
75
185—190
(3)
160—163
(3)
C19H17F3O2S2
C11H13F3O6S2
C18H14F3NS2
7.30 (m, 10 Í, 2 Ph); 4.26 and 4.18 (both s,
2 H each, 2 ÑÍ2); 3.68 (s, 3 Í, Må)
3.86 (s, 2 Í, ÑÍ2); 3.83 (s, 3 Í, Må);
3.77 (s, 2 Í, ÑÍ2); 3.69 (s, 6 Í, 2 Må)
7.35 (m, 10 Í, 2 Ph); 4.46 and 4.42 (both s,
2 H each, 2 ÑÍ2)
[53—54]
145—147
(3)
177—180
(3)
109—111
(9)
[51—52]
C10H10F3NO4S2 4.07 and 4.04 (both s, 2 H each, 2 ÑÍ2);
3.75 and 3.74 (both s, 3 H each, 2 Må)
2h
2j
C17H14FNS2
C5H6FNS2
C7H7F3O2S2
C6H4F3NS2
C5H4FNS2
C7H7O3F3S
7.30 (m, 10 Í, 2 Ph); 4.25 and 4.08 (both s,
2 H each, 2 ÑÍ2)
2.55 and 2.48 (both s, 3 H each, 2 Må)
3a
3b
3c
3d
3.75 (s, 3 Í, Må); 3.57 and 3.46 (both m,
2 H each, 2 ÑÍ2)
3.86 and 3.74 (both m, 2 H each, 2 ÑÍ2)
[55—56]
[56—57]
[30—31]
3.68 (m, 2 ÑÍ2)
4.75 (t, 2 Í, ÑÍ2Î, J = 8 Hz); 3.73 (s,
3 Í, Må); 3.32 (t, 2 Í, ÑÍ2S, J = 8 Hz)

1046
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 6, June, 2001
Kovregin et al.
Scheme 3
3-Benzylthio-3-fluoro-2-trifluoromethylacrylonitrile (1å),
19F NMR (CD3CN), δ: E-isomer, 22.5 (q, 1 F, CF,
J = 18.0 Hz); 19.7 (m, 3 F, CF3); Z-isomer, 24.0 (q, 1 F, CF,
X
X
Y
J = 10.9 Hz); 19.7 (m, 3 F, CF3); E/Z = 4 : 1. Methyl
S
Z
3 BF3•NEt3
–1
(2-cyanotetrafluoroprop-1-enyl)thioacetate (1f), IR, ν/cm
:
+
F3C CH
HSCH2CH2ZH
C
2235 and 2230 (CN); 1710 (C=O); 1590 (C=C). 3-tert-Bu-
Y
–1
tylthio-3-fluoro-2-trifluoromethylacrylonitrile (1g), IR, ν/cm
:
2241 and 2223 (CN); 1592 (C=C). 3-Benzylthio-2,3-difluoro-
acrylonitrile (1h), 19F NMR (DMSO-d6), δ: E-isomer, –4.4
and –50.7 (both d, 1 F each, CF, J = 12 Hz); Z-isomer, –30.2
and –76.6 (both d, 1 F each, CF, J = 144 Hz), Z/E = 1 : 1.
3-tert-Butylthio-2,3-difluoroacrylonitrile (1i), IR, ν/cm–1: 2225
(CN); 1595 (C=C). 2,3-Difluoro-3-methylthioacrylonitrile (1j),
19F NMR (DMSO-d6), δ: E-isomer, –4.6 and –50.3 (both d,
1 F each, CF, J = 12 Hz); Z-isomer, –30.5 and –75.2
(both d, 1 F each, CF, J = 144 Hz), Z/E = 1 : 1. Methyl
3,3-bis(benzylthio)-2-trifluoromethylacrylate (2a), 19F NMR
(DMSO-d6), δ: 24.5 (s, CF3). Methyl 3,3-bis(methoxy-
carbonylmethylthio)-2-trifluoromethylacrylate (2b), 19F NMR
(DMSO-d6), δ: 24.1 (s, CF3). Bis(benzylthio)-2-trifluoro-
methylacrylonitrile (2å), 19F NMR (DMSO-d6), δ: 26.5 (s, CF3).
3,3-Bis(methoxycarbonylmethylthio)-2-trifluoromethylacryl-
onitrile (2f), 19F NMR (DMSO-d6), δ: 26.7 (s, CF3).
3,3-Bis(benzylthio)-2-fluoroacrylonitrile (2h), 19F NMR
(DMSO-d6), δ: –20.5 (s, CF). 2-Fluoro-3,3-bis(methyl-
thio)acrylonitrile (2j), IR, ν/cm–1: 2225 (CN); 1600 (C=C).
Reactions of CH-acids with bifunctional thiols. The reac-
tions were carried out with the use of 3 equiv. of the BF3•NEt3
complex as described above. After removal of the solvent, the
compounds were recrystallized from hexane. This proce-
dure was used for the preparation of 2-(1-methoxycarbo-
nyl)trifluoroethylidene-1,3-dithiolane (3a); 2-(1-cyano)tri-
fluoroethylidene-1,3-dithiolane (3b); 2-(cyano)fluoromethyl-
idene-1,3-dithiolane (3c), IR, ν/cm–1: 2218 (CN), 1599 (C=C);
and 2-(1-methoxycarbonyl)trifloroethylidene-1,3-oxathio-
lane (3d).
3a—d
a
b
c
d
Õ
CF3
COOMe
S
CF3
CN
S
F
CN
S
CF3
COOMe
O
Y
Z
Thus, this type of reactions is a convenient one-
stage procedure for the synthesis of fluorine-containing
vinyl sulfides and ketene dithioacetals containing func-
tional groups at the double bond based on the use of
readily accessible fluorine-containing CH-acids.
Experimental
The 19F NMR spectra were recorded on a Bruker AC-200F
spectrometer operating at 188.31 MHz. The H NMR spectra
1
were measured on a Bruker AC-300SF instrument operating at
300.13 MHz. The chemical shifts (δ) are given relative to
CF3COOH (19F, the external standard) and Me4Si (1H, the
internal standard). The IR spectra were recorded on a
Perkin—Elmer 1720X instrument. The ratios of the reaction
products were determined by GLC on an HÐ5890 instrument
equipped with an HÐ-5972 mass-selective detector. The yields,
properties, spectral characteristics, and the data from elemental
analysis of the resulting compounds are given in Table 2.
Reactions of CH-acids with thiols (general procedure). A
mixture of a CH-acid (0.1 mol), a thiol (0.1 mol), and
the BF3•NEt3 complex (0.21 mol) was heated in a flask
equipped with a reflux condenser to 50 °C (the reactions of
2-hydrotetrafluoropropiononitrile were carried out in sealed
glass tubes at 100 °C). The beginning of the reaction was
evidenced by the appearance of traces of a white fume above
the reaction mixture and substantial heat evolution. Once the
reaction started, heating was terminated, and the reaction
mixture was cooled with cold water, which was accompanied by
formation of an abundant precipitate. The mixture was washed
with water and 5% HCl. The reaction products were extracted
with ether, dried with Na2SO4, and fractionated.
Methyl 3-benzylthio-3-fluoro-2-trifluoromethylacrylate (1a),
19F NMR (DMSO-d6), δ: E-isomer, 20.4 (d, 3 F, CF3,
J = 22.0 Hz); 15.3 (q, 1 F, CF, J = 22.0 Hz); Z-isomer, 21.2
(d, 3 F, CF3, J = 13.5 Hz); 17.1 (q, 1 F, CF, J = 13.5 Hz),
E/Z = 9 : 1. Methyl 3-fluoro-3-(methoxycarbonylmethyl)thio-
2-trifluoromethylacrylate (1b), IR, ν/cm–1: 1740, 1730 (C=O);
1600 (C=C). Methyl 3-tert-butylthio-3-fluoro-2-trifluoromethyl-
acrylate (1c) (cf. lit.4) Dimethyl benzylthio(fluoro)methyl-
idenemalonate (1d), 19F NMR (DMSO-d6), δ: 17.3 (s, CF).
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Received January 9, 2001;
in revised form March 12, 2001