Chlorolysis of β-functionalized alkyl polyfluoroalkenyl sulfides

Article abstract of DOI:10.1023/A:1019673921176

Chlorolysis of β-functionalized alkyl polyfluoroalkenyl sulfides giving rise to β-functionalized polyfluoroalkenesulfenyl chlorides was examined. β-Cyano-containing sulfenyl chlorides underwent intramolecular cyclization at the nitrile group to form subst

Full text of DOI:10.1023/A:1019673921176

Russian Chemical Bulletin, International Edition, Vol. 51, No. 6, pp. 1031—1034, June, 2002
1031
Chlorolysis of βꢀfunctionalized alkyl polyfluoroalkenyl sulfides
ꢀ
A. N. Kovregin, A. Yu. Sizov, and A. F. Ermolov
Military University of Radiational, Chemical and Biological Defense,
13 Brigadirskii per., 107005 Moscow, Russian Federation.
Fax: +7 (095) 267 5107
Chlorolysis of βꢀfunctionalized alkyl polyfluoroalkenyl sulfides giving rise to βꢀfuncꢀ
tionalized polyfluoroalkenesulfenyl chlorides was examined. βꢀCyanoꢀcontaining sulfenyl
chlorides underwent intramolecular cyclization at the nitrile group to form substituted
isothiazoles.
Key words: chlorolysis, alkyl polyfluoroalkenyl sulfides, polyfluoroalkenesulfenyl chloꢀ
rides, sulfenylation.
Interest in the chemistry of fluorineꢀcontaining
sulfenyl chlorides arises primarily from their preparative
importance as convenient and sometimes unique synthons
for the insertion of polyfluoroalkylthio groups into variꢀ
ous organic compounds.1 The presence of additional
functional groups in sulfenyl chlorides makes it possible
to substantially enhance their synthetic potential, parꢀ
ticularly, for the preparation of heterocyclic compounds.
Theoretical and applied aspects of the chemistry of
α,βꢀunsaturated fluorineꢀcontaining organic derivatives
of divalent sulfur, including sulfenyl chlorides, have atꢀ
tracted growing interest in recent years.2 At the same
time, of all functionalized derivatives of polyfluoroalkeneꢀ
sulfenyl chlorides, only 1,3,3,3ꢀtetrafluoroꢀ2ꢀ(methoxyꢀ
carbonyl)propenesulfenyl chloride has been described and
investigated in sufficient detail.3—5 In the present study,
we examined the possibility of the preparation of new
representatives of sulfenyl chlorides of this type by
chlorolysis of functionalized alkyl vinyl sulfides, which
are presently readily accessible owing to a procedure
developed by us previously.6
was isolated as substituted alkylideneꢀ1,3ꢀoxathiole 5 afꢀ
ter treatment with the BF3•NEt3 complex (Scheme 1).
Scheme 1
Results and Discussion
It appeared that tertꢀbutyl 2ꢀcyanoꢀ1,3,3,3ꢀtetraꢀ
fluoropropenyl sulfide (1) is inert with respect to sulfuryl
chloride even upon refluxing. Its chlorolysis proceeds in
excess chlorine in a sealed glass tube at 20 °C. The reꢀ
sulting sulfenyl chloride 2 is thermally labile and underꢀ
goes intramolecular cyclization to form substituted
isothiazole 3 upon distillation. However, we detected
sulfenyl chloride 2 in the reactions with CHꢀacids. Thus,
its reaction with acetone gave rise to sulfide 4, whereas
the product of sufenylation of benzoylacetoacetic ester
Unlike sulfide 1, tertꢀbutyl 2ꢀcyanoꢀ1,2ꢀdifluorovinyl
sulfide (6) readily reacted with sulfuryl chloride. As a
result, the product of cyclization and simultaneous chloꢀ
rination, viz., isothiazoline 7, was isolated in 15% yield
(Scheme 2). The major portion of the reaction products
is a complex higherꢀboiling mixture, which presumably
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 948—950, June, 2002.
1066ꢀ5285/02/5106ꢀ1031 $27.00 © 2002 Plenum Publishing Corporation

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Russ.Chem.Bull., Int.Ed., Vol. 51, No. 6, June, 2002
Kovregin et al.
Scheme 4
consists of polysulfides and intermolecular cyclization
products.
Scheme 2
Isothiazole 5 and isothiazoline 7 are colorless labile
liquids. Their structures were confirmed by 19F NMR
spectroscopy, mass spectrometry, and elemental analyꢀ
sis. Examples of intramolecular heterocyclization of
sulfenyl chlorides at the nitrile group of nonfluorinated
compounds were reported in the literature (see, for exꢀ
ample, Ref. 7).
Even in the cold, chlorolysis of 2ꢀbenzylthioꢀ
1,1ꢀdicyanoꢀ3,3,3ꢀtrifluoropropene (8) led to the
cleavage of the C—S bonds yielding sulfur dichloride
and 2ꢀchloroꢀ1,1ꢀdicyanoꢀ3,3,3ꢀtrifluoropropene (9)
(Scheme 3).
Under the conditions typical of chlorolysis of benzyl
sulfides, the reaction of methyl β,βꢀbis(benzylthio)triꢀ
fluoromethacrylate (14) with chlorine afforded a comꢀ
plex mixture inseparable by fractionation. According to
the data from GLCꢀmass spectrometry, this mixture conꢀ
tained 1,1,2ꢀtrichloroꢀ3,3,3ꢀtrifluoroꢀ2ꢀ(methoxycarboꢀ
nyl)propanesulfenyl chloride (15) (m/z: 326 [M+]). The
fact that the double bond in vinyl sulfide 14 is chloriꢀ
nated (which is untypical of such compounds) as well as
the mass spectra of other products suggest that the reacꢀ
tion involves the 1,3ꢀmigration of chlorine from the
S atom of sulfenyl chloride A (m/z: 254 [M+], two
Scheme 3
isomers) to the C atom to form thiocarbonyl comꢀ
β
pound B (m/z: 254 [M+]). Chlorination of the latter
gave rise to sulfenyl chloride 15 (Scheme 5). Chloroꢀ
tropism in the carbon—carbon—sulfur triad was exꢀ
emplified by perfluoroꢀ2ꢀmethylꢀ2ꢀpentꢀ3ꢀenesulfenyl
chloride.8
The reaction of tertꢀbutyl 1ꢀfluoroꢀ2,2ꢀdi(methoxyꢀ
carbonyl)vinyl sulfide (10) with chlorine afforded crysꢀ
talline sulfenyl chloride 11, which reacted with acetone
and indole to give the expected products 12 and 13,
respectively (Scheme 4).
Sulfenyl chloride 15 was prepared in the individual
form by the reaction performed with an excess of chloꢀ
Scheme 5

Chlorolysis of fluoroalkenyl sulfides
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 6, June, 2002
1033
then fractionated. Compound 7 was obtained in a yield of 0.7 g
(15%), b.p. 65—66 °C (50 Torr). Found (%): C, 15.97.
C3Cl3F2NS. Calculated (%): C, 15.89. 19F NMR (CDCl3):
–57.8 and –16.6 (both d, 2 CF, JF,F = 5 Hz); –32.2 and –7.5
(both d, 2 CF, JF,F = 17 Hz), the ratio of the isomers was 1 : 1.
MS, m/z: 225 [M]+.
Chlorolysis of 2ꢀbenzylthioꢀ1,1ꢀdicyanoꢀ3,3,3ꢀtrifluoroꢀ
propylene. Dry chlorine (1.4 g, 0.02 mol) was condensed with
cooling to –78 °C into a flask containing compound 8 (2.7 g,
0.01 mol). The reaction mixture was slowly heated with stirring
to 20 °C and then fractionated. As a result, SCl2 and 2ꢀchloroꢀ
1,1ꢀdicyanoꢀ3,3,3ꢀtrifluoropropylene (9) were obtained whose
physicochemical and spectroscopic characteristics correspond
to the published data.9
1ꢀFluoroꢀ2,2ꢀdi(methoxycarbonyl)ethenesulfenyl chloride
(11). An excess of dry chlorine was bubbled with stirring through
sulfide 10 (25.0 g, 0.1 mol), the temperature being maintained
at no higher than 20 °C. The reaction was accompanied by the
formation of a precipitate. After completion of the exothermic
reaction, the mixture was diluted with an equal volume of
hexane and the precipitate was filtered off. Compound 11 was
obtained in a yield of 19.0 g (83%), m.p. 34—36 °C. Found (%):
C, 31.64; H, 2.67. C6H6ClFO4S. Calculated (%): C, 31.51;
H, 2.63. 1H NMR (CDCl3): 3.80 (s, 2 OMe). 19F NMR
(CDCl3): 14.9 (s, CF).
rine in a sealed tube at 50 °C and was detected in the
reaction with diethylamine (see Scheme 5).
Experimental
The 19F NMR spectra were recorded on a Bruker ACꢀ200F
1
spectrometer (188.31 MHz). The H NMR spectra were meaꢀ
sured on a Bruker ACꢀ300SF instrument (300.13 MHz). The
chemical shifts (δ) are given relative to CF3COOH (19F, exterꢀ
nal standard) and Me4Si (1H, internal standard). The mass
spectra (EI) of the reaction products were obtained on an
HPꢀ5890 gas chromatograph equipped with an HPꢀ5972 massꢀ
selective detector; the energy of ionizing electrons was 70 eV.
The starting βꢀfunctionalized alkyl polyfluoroalkenyl sulꢀ
fides were prepared according to a procedure described previꢀ
ously.6
2ꢀCyanoꢀ1,3,3,3ꢀtetrafluoropropenesulfenyl chloride (2).
Sulfide 1 (4.55 g, 0.02 mol) was placed in a glass tube and
chlorine (2.1 g, 0.03 mol) was condensed into the tube at –78 °C.
Then the tube was sealed, slowly (3 h) heated to 20 °C, kept for
5 h, and opened. Volatile products were removed in vacuo
(50 Torr) and the remaining sulfenyl chloride 2 was used in
subsequent reactions without additional purification. 19F NMR
(CDCl3): 18.3 (m, 3 F, CF3); 33.8 (m, 1 F, CF).
3ꢀChloroꢀ5ꢀfluoroꢀ4ꢀ(trifluoromethyl)isothiazole (3). Sulfenyl
chloride 2 (4.1 g, 0.02 mol) was fractionated in vacuo (50 Torr).
Repeated distillation afforded isothiazole 3 in a yield of 2.2 g
(54%), b.p. 55—57 °C (50 Torr). Found (%): C, 23.48.
C4ClF3NS. Calculated (%): C, 23.36. 19F NMR (CDCl3): –24.4
(q, 1 F, CF, JF,F = 18 Hz); 17.3 (d, 3 F, CF3, JF,F = 18 Hz).
MS, m/z: 205 [M]+.
1ꢀ[1ꢀFluoroꢀ2,2ꢀdi(methoxycarbonyl)vinylthio]propanꢀ2ꢀone
(12) was prepared analogously to compound 4 from sulfenyl
chloride 11 and acetone. The yield was 91%, m.p. 45—47 °C.
Found (%): C, 43.33; H, 4.38. C9H11FO5S. Calculated (%):
1
C, 43.20; H, 4.40. H NMR (DMSOꢀd6): 2.25 (s, 3 H, Me);
3.78 (s, 6 H, 2 OMe); 4.07 (s, 2 H, CH2). MS, m/z: 250 [M]+.
3ꢀ[1ꢀFluoroꢀ2,2ꢀdi(methoxycarbonyl)vinylthio]indole (13).
A solution of sulfenyl chloride 11 (2.3 g, 0.01 mol) in benzene
(10 mL) was added dropwise with stirring and cooling to 10 °C
to a solution of indole (1.2 g, 0.01 mol) in benzene (20 mL),
the formation of an abundant precipitate taking place. The
reaction mixture was refluxed until evolution of HCl ceased
(6 h). Then the solvent was removed in vacuo, the product was
extracted from the residue with hot hexane, and the crystals
that formed upon cooling were filtered off. Compound 13 was
obtained in a yield of 1.6 g (53%), m.p. 74—76 °C. Found (%):
C, 54.49; H, 3.86. C14H12FNO4S. Calculated (%): C, 54.37;
H, 3.88. 1H NMR (DMSOꢀd6): 3.70 and 3.81 (both s, 3 H each,
OMe); 7.18 and 7.52 (both m, 2 H each, C6H4); 7.79 (s, 1 H,
CH); 11.80 (br.s, 1 H, NH). MS, m/z: 309 [M]+.
3ꢀ(2ꢀCyanoꢀ1,3,3,3ꢀtetrafluoropropenylthio)propanꢀ2ꢀone
(4). Acetone (2.9 g, 0.05 mol) was added with stirring to sulfenyl
chloride 2 (2.05 g, 0.01 mol). The reaction mixture became
colorless and hydrogen chloride was evolved. The mixture was
kept at 20 °C for 2 h and then fractionated. Compound 4 was
obtained in a yield of 1.2 g (53%), b.p. 91—94 °C (3 Torr).
Found (%): C, 37.07; H, 2.21. C7H5F4NOS. Calculated (%):
1
C, 37.00; H, 2.20. H NMR (DMSOꢀd6): 2.29 (s, 3 H, Me);
4.38 (s, 2 H, CH2). MS, m/z: 227 [M]+.
2ꢀ(1ꢀCyanotrifluoroethylidene)ꢀ4ꢀethoxycarbonylꢀ5ꢀphenylꢀ
1,3ꢀoxathiole (5). A mixture of sulfenyl chloride 2 (2.05 g,
0.01 mol) and ehtyl benzoylacetate (1.9 g, 0.01 mol) was kept
at 20 °C until evolution of hydrogen chloride ceased (24 h) and
then dissolved in ether (20 mL). Then the BF3•NEt3 complex
(3.4 g, 0.02 mol) was added and the reaction mixture was
stirred for 3 h. The precipitate that formed was filtered off and
the filtrate was washed with 5% HCl (2×50 mL). The organic
layer was separated and dried with Na2SO4. The solvent was
removed in vacuo and the residue was recrystallized from hexꢀ
ane. Compound 5 was obtained in a yield of 1.6 g (48%), m.p.
68—70 °C. Found (%): C, 52.90; H, 2.91. C15H10F3NO3S.
1,1,2ꢀTrichloroꢀ3,3,3ꢀtrifluoroꢀ2ꢀ(methoxycarbonyl)proꢀ
panesulfenyl chloride (15). Sulfide 14 (4.0 g, 0.01 mol) was
placed in a glass tube and chlorine (2.1 g, 0.03 mol) was conꢀ
densed into the tube at –78 °C. The tube was sealed, slowly
(3 h) warmed to 20 °C, kept for 24 h, heated at 50 °C for 2 h,
and opened. The mixture was fractionated to obtain sulfenyl
chloride 15 in a yield of 1.6 g (49%), b.p. 65—67 °C (2 Torr).
Found (%): C, 18.56; H, 1.01. C5H3Cl4F3O2S. Calculated (%):
C, 18.40; H, 0.92. 1H NMR (CDCl3): 3.83 (s, OMe). MS,
m/z: 326 [M]+.
N,NꢀDiethylꢀ[1,1,2ꢀtrichloroꢀ3,3,3ꢀtrifluoroꢀ2ꢀ(methoxyꢀ
carbonyl)propane]sulfenylamide (16). A solution of diethylamine
(1.5 g, 0.02 mol) in ether (10 mL) was added dropwise with
stirring to a solution of sulfenyl chloride 15 (3.3 g, 0.01 mol) in
ether (20 mL) at 0 °C. The reaction mixture was kept at 20 °C
for 3 h, the precipitate that formed was filtered off, and the
1
Calculated (%): C, 52.79; H, 2.93. H NMR (DMSOꢀd6): 1.31
(t, 3 H, Me, J = 7 Hz); 4.30 (q, 2 H, CH2, J = 7 Hz); 7.56 and
7.87 (both m, 3 H and 2 H, Ph). 19F (DMSOꢀd6): 24.6 and
25.9 (both s, ratio was 2 : 1, CF3). MS, m/z: 341 [M]+.
3,4,5ꢀTrichloroꢀ4,5ꢀdifluoroisothiazoline (7). Sulfuryl chloꢀ
ride (8.0 g, 0.06 mol) was added dropwise with stirring and
cooling (5—10 °C) to sulfide 6 (3.5 g, 0.02 mol). The reaction
mixture was kept at 20 °C until gas evolution ceased (3 h) and

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Kovregin et al.
filtrate was fractionated. Sulfenylamide 16 was obtained in a
yield of 1.9 g (52%), b.p. 92—94 °C (1 Torr). Found (%):
C, 29.61; H, 3.55. C9H13Cl3F3NO2S. Calculated (%): C, 29.79;
H, 3.59. H NMR (DMSOꢀd6): 1.20 (t, 6 H, 2 Me, J = 7 Hz);
3.30 and 3.45 (both sept, 2 H each, 2 CH2, J = 7 Hz); 3.96 (s,
3 H, OMe). 19F NMR (DMSOꢀd6): 12.6 (s, CF3).
4. A. N. Kovregin, A. Yu. Sizov, A. F. Ermolov, and A. F.
Kolomiets, Izv. Akad. Nauk, Ser. Khim., 2000, 1770 [Russ.
Chem. Bull., Int. Ed., 2000, 49, 1749].
5. A. N. Kovregin, A. Yu. Sizov, and A. F. Ermolov, Izv. Akad.
Nauk, Ser. Khim., 2001, 1197 [Russ. Chem. Bull., Int. Ed.,
2001, 50, 1255].
1
6. A. N. Kovregin, A. Yu. Sizov, and A. F. Ermolov, Izv. Akad.
Nauk, Ser. Khim., 2001, 1000 [Russ. Chem. Bull., Int. Ed.,
2001, 50, 1044].
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Received January 29, 2002;
in revised form March 5, 2002