Reactions of α-fluorine-containing β-functionalized vinyl sulfides with N-nucleophiles

Article abstract of DOI:10.1023/A:1019669820268

α-Fluorine-containing β-functionalized vinyl sulfides readily react with N-nucleophiles to form α-fluorine-substituted products. The reactions with phenylhydrazines and amidines of acids are accompanied by cyclization at the functional group. Thermal cyclization of cyanotrifluoromethylketene N,S-acetals proceeds at the trifluoromethyl group to give substituted 3-cyanoquinolin-4-ones.

Full text of DOI:10.1023/A:1019669820268

1020
Russian Chemical Bulletin, International Edition, Vol. 51, No. 6, pp. 1020—1027, June, 2002
Reactions of αꢀfluorineꢀcontaining βꢀfunctionalized vinyl sulfides
with Nꢀnucleophiles
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
αꢀFluorineꢀcontaining βꢀfunctionalized vinyl sulfides readily react with Nꢀnucleophiles
to form αꢀfluorineꢀsubstituted products. The reactions with phenylhydrazines and amidines
of acids are accompanied by cyclization at the functional group. Thermal cyclization of
cyanotrifluoromethylketene N,Sꢀacetals proceeds at the trifluoromethyl group to give substiꢀ
tuted 3ꢀcyanoquinolinꢀ4ꢀones.
Key words: vinyl sulfides, substitution, Nꢀnucleophiles, cyclization.
Scheme 1
Functionalized vinyl sulfides are not only of theoꢀ
retical but also of practical interest because they can be
used as precursors of various (including heterocyclic)
compounds. Previously,1 we have developed a oneꢀstep
procedure for the synthesis of fluorineꢀcontaining vinyl
sulfides bearing functional groups at the multiple bond
due to which these compounds became accessible for
the examination of their subsequent transformations,
among them cyclization involving functional groups.
It is known that vinyl sulfides bearing the F atom at
the multiple bond readily react with Oꢀnucleophiles to
give vinyl substitution products.2,3 In particular, we have
demonstrated that the products of the reactions of
αꢀfluoroꢀα,βꢀunsaturated sulfenyl chlorides with enols
and phenols underwent intramolecular cyclization to form
substituted 1,3ꢀoxathioles.4,5 Analogous reactions with
Nꢀaryleneamines also exemplify the intramolecular
Nꢀnucleophilic vinyl substitution of the F atom.6 In the
present study, we investigated the reactions of αꢀfluoꢀ
rineꢀcontaining βꢀfunctionalized vinyl sulfides with variꢀ
ous Nꢀnucleophiles, including bifunctional nucleophiles,
and examined the possibility of their use in the synthesis
of heterocyclic compounds.
1,2
1a
1b
1c
1d
1e
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
X
Y
CF3
CF3
CF3
CF3
COOMe
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
R1
Bn
But
Bn
But
Bn
Bn
Bn
Bn
Bn
Bn
But
Bn
Bn
Bn
Bn
Bn
But
Bn
Bn
R2
—
—
—
—
—
H
Et
H
H
H
H
H
H
H
H
H
H
R3
—
—
—
—
—
H
Et
COOMe
COOMe
CN
CN
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
COOMe
CN
CN
CN
CN
CN
4ꢀC6H4Me
4ꢀC6H4OMe
4ꢀC6H4OPh
4ꢀC6H4Et
Ph
4ꢀC6H4F
4ꢀC6H4Me
4ꢀC6H4OMe
4ꢀC6H4OPh
4ꢀC6H4OMe
4ꢀC6H4Et
4ꢀC6H4COOEt
CN
COOMe
COOMe
2m
2n
COOMe
COOMe
H
H
amine serving both as the reagent and (simultaneously)
acceptor of HF. Under the aboveꢀmentioned conditions,
only vinyl sulfides containing two strong electronꢀwithꢀ
drawing groups in the β position were involved in the
reactions, whereas α,βꢀdifluoroꢀβꢀ(benzylthio)acryloꢀ
nitrile (1f) did not react with anilines even upon heating.
Sterically hindered tertꢀbutyl sulfides reacted somewhat
more slowly than their benzyl analogs. Substituents of
various electronic nature located in the para position of
aniline have no effect on the reaction rate.
Results and Discussion
Reactions with amines. In the case of activation with
strong electronꢀwithdrawing groups located in the β poꢀ
sition, the αꢀvinyl F atom in vinyl sulfides (1a—e) is
readily replaced in the reactions with ammonia, diethylꢀ
amine, and primary arylamines to form the correspondꢀ
ing ketene N,Sꢀacetals (2a—n) (Scheme 1).
The reactions were carried out at room temperature
in ethereal solutions with the use of a twofold excess of
According to the NMR data, compounds 2a—l exist
as enamines. Only the spectra of di(methoxycarboꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 938—944, June, 2002.
1066ꢀ5285/02/5106ꢀ1020 $27.00 © 2002 Plenum Publishing Corporation

Reactions of vinyl sulfides with Nꢀnucleophiles
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 6, June, 2002
1021
Scheme 3
nyl)ketene aminothioacetals 2m and 2n have signals (up
to 10%) of tautomeric imines resulting from the migraꢀ
tion of the H atom from N to C. Previously,7 it has been
noted that the initially formed alkoxycarbonyltrifluoroꢀ
methylketene aminoacetals are rather slowly rearranged
into imino esters, the rearrangement being irreversible.
The fact that this rearrangement did not take place in the
case under consideration is attributable to the electronic
effect of the S atom. The spectroscopic data also indiꢀ
cate that substituted acrylates 2a,c—f exist as the only
isomer due, apparently, to the presence of a hydrogen
bond between the amino and methoxycarbonyl groups,
whereas acrylonitriles 2g—l in which this bond cannot
occur exist as mixtures of the Е and Z isomers.
Upon heating to 150 °C, the reactions of vinyl sulꢀ
fides of interest with tertiary amines, for example, with
N,Nꢀdimethylaniline, in the absence of solvents afforded
only resinous products.
Reactions with phenylhydrazines and amidines. In spite
of the fact that functionalized fluoroolefins, in particuꢀ
lar, derivatives of perfluoromethacrylic acid,8 were exꢀ
tensively studied beginning in 1970s, examples of their
cyclization at the functional group are scarce. We found
that the reactions of compounds 1a,s,d with phenylꢀ
hydrazines were accompanied by intramolecular cyclizaꢀ
tion at the βꢀfunctional group to form the corresponding
substituted pyrazoles 3—8 (Scheme 2).
1,9,10
1g
Y
Z
—
R1
R2
—
COOMe
4ꢀMe2NC6H4
1h
1i
COOMe
COOMe
—
—
—
—
1j
COOMe
—
—
9a,10a
9b,10b
9c,10c
9d,10d
10e
CN
CN
CN
NH2
NH2
NH2
NH2
OH
Bn
But
Me
Me
Ph
Bn
CN
But
Bn
Ph
Scheme 2
COOMe
COOMe
COOMe
Me
Me
Me
10f
10g
OH
OH
But
4ꢀMe2NC6H4
10h
10i
COOMe
COOMe
OH
OH
Me
Me
10j
COOMe
OH
Me
10k
10l
COOMe
COOMe
OH
OH
Bn
Ph
Ph
4ꢀMe2NC6H4
10m
10n
COOMe
COOMe
OH
OH
Ph
Ph
R1 = PhCH2, R2 = H (4), Cl (5), F (6), CF3 (7);
R1 = But, R2 = H (8)
Undoubtedly, the aboveꢀconsidered reaction began
with the nucleophilic displacement of the vinyl F atom
although we failed to isolate intermediates. To the conꢀ
trary, heterocyclization in the reactions of vinyl sulfides 1
with Nꢀunsubstituted carbamidines occurred only upon
10o
COOMe
OH
Ph

1022
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 6, June, 2002
Kovregin et al.
Scheme 4
acted with amidines to produce the corresponding
4ꢀaminoꢀ5ꢀfluoropyrimidines 11a,b.
Cyclization of βꢀ(tertꢀbutylthio)perfluoromethacryloꢀ
nitrile with benzamidine afforded a minor product, viz.,
6ꢀtertꢀbutylthioꢀ5ꢀcyanoꢀ4ꢀfluoroꢀ
2ꢀphenylpyrimidine (12), which
was isolated by column chromaꢀ
tography and characterized by
spectroscopic data. Compound 12
was formed through cyclization inꢀ
volving the trifluoromethyl and
amino groups.
Thermal cyclization of N,Sꢀacetals. Cyclization at the
trifluoromethyl group also occurs upon heating of
(trifluoromethyl)cyanoketene N,Sꢀacetals in diphenyl oxꢀ
ide. Generally, heating of these compounds to ∼250 °C
leads to their cyclization at the nitrile group to form an
aromatic ring. Unexpectedly, the reactions of compounds
2g—j,k proceeded even at 180 °C and were accompanied
by HF evolution. Apparently, the first step involves the
migration of the proton from the N atom to the Cα
atom, dehydrofluorination of the resulting CHꢀacid, and
cyclization giving rise to an aromatic ring. Unfortunately,
attempts to isolate 4ꢀfluoroquinolines (which were preꢀ
sumably generated) in the individual form failed due to
their high hydrolytic lability. The formation of these comꢀ
pounds was evidenced by the presence of a singlet at
δ –70 in the 19F NMR spectra of the reaction mixtures.
R = Me (11a), Ph (11b)
heating. For this reason, the isolation of intermediate
products of the F atom replacement presents no probꢀ
lems as exemplified by the isolation of substituted
amidines 9a—e. Thermolysis of compounds of this type
gave rise to pyrimidines 10 (Scheme 3).
Acetamidine and benzamidine were used in the reacꢀ
tions as hydrochlorides. An aqueous solution of NaOH
was used as an acceptor of HCl and HF. Heterocyclization
at the nitrile group proceeded more difficultly than that
at the methoxycarbonyl group and was completed upon
refluxing in toluene in 4—5 h. Under analogous condiꢀ
tions, α,βꢀdifluoroꢀβꢀbenzylthioacrylonitrile (1f) also reꢀ
Scheme 5
13: R = H (a), F (b), Me (c), PhO (d)

Reactions of vinyl sulfides with Nꢀnucleophiles
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 6, June, 2002
1023
Methyl 3ꢀaminoꢀ3ꢀbenzylthioꢀ2ꢀ(trifluoromethyl)acrylate
(2a). A stream of dry ammonia (excess) was passed through
a solution of methyl 3ꢀbenzylthioꢀ3ꢀfluoroꢀ2ꢀ(trifluoromeꢀ
thyl)acrylate (1a) (2.9 g, 0.01 mol) in ether (10 mL). The
mixture was kept at 0 °C for 10 h, the residue was filtered off at
this temperature, the solvent was removed in vacuo, and the
residue was recrystallized from hexane.
Alkaline hydrolysis of the reaction products afforded the
corresponding 3ꢀcyanoquinolinꢀ4ꢀones 13a—d, which
were characterized by NMR spectroscopy (Scheme 5).
The data on the involvement of the trifluoromethyl
group in cyclization to form an aromatic ring are availꢀ
able in the literature.9 These transformations require an
additional assistance of bases. In this case, the reaction
proceeded in the absence of bases and, hence, can be
considered as the first example of thermal reactions of
this type.
Methyl
3ꢀbenzylthioꢀ3ꢀdiethylaminoꢀ2ꢀ(trifluoromeꢀ
thyl)acrylate (2b) was prepared analogously from the same ester
and diethylamine. MS, m/z: 347 [M]+.
Reactions of αꢀfluorovinyl sulfides with anilines (general proꢀ
cedure). A solution of the corresponding aniline (0.02 mol) in
ether (20 mL) was added dropwise with stirring to a solution of
vinyl sulfide (0.01 mol) in ether (10 mL). The reaction mixture
was kept at 20 °C for 25—30 h and washed with a 5—10% HCl
solution. The organic layer was separated and dried over Na2SO4.
The solvent was removed in vacuo and the residue was recrysꢀ
tallized from hexane. This procedure was used for the preparaꢀ
tion of methyl 3ꢀbenzylthioꢀ3ꢀ(4ꢀmethylphenylamino)ꢀ2ꢀ(triꢀ
fluoromethyl)acrylate (2c); methyl 3ꢀbenzylthioꢀ3ꢀ(4ꢀmethoxyꢀ
phenylamino)ꢀ2ꢀ(trifluoromethyl)acrylate (2d); methyl 3ꢀbenꢀ
zylthioꢀ3ꢀ(4ꢀphenoxyphenylamino)ꢀ2ꢀ(trifluoromethyl)acrylate
(2e); methyl 3ꢀtertꢀbutylthioꢀ3ꢀ(4ꢀethylphenylamino)ꢀ2ꢀ(triꢀ
fluoromethyl)acrylate (2f), MS, m/z: 361 [M]+; nitrile of
3ꢀbenzylthioꢀ3ꢀphenylaminoꢀ2ꢀ(trifluoromethyl)acrylic acid
(2g); nitrile of 3ꢀbenzylthioꢀ3ꢀ(4ꢀfluorophenylamino)ꢀ2ꢀ(triꢀ
fluoromethyl)acrylic acid (2h); nitrile of 3ꢀbenzylthioꢀ3ꢀ(4ꢀ
methylphenylamino)ꢀ2ꢀ(trifluoromethyl)acrylic acid (2i); niꢀ
trile of 3ꢀbenzylthioꢀ3ꢀ(4ꢀmethoxyphenylamino)ꢀ2ꢀ(trifluoroꢀ
methyl)acrylic acid (2j); nitrile of 3ꢀbenzylthioꢀ3ꢀ(4ꢀphenoxyꢀ
phenylamino)ꢀ2ꢀ(trifluoromethyl)acrylic acid (2k); nitrile of
3ꢀtertꢀbutylthioꢀ3ꢀ(4ꢀmethoxyphenylamino)ꢀ2ꢀ(trifluoroꢀ
methyl)acrylic acid (2l); methyl 3ꢀbenzylthioꢀ3ꢀ(4ꢀethylꢀ
phenylamino)ꢀ2ꢀmethoxycarbonylacrylate (2m), and methyl
3ꢀbenzylthioꢀ3ꢀ(4ꢀethoxycarbonylphenylamino)ꢀ2ꢀ(methoxyꢀ
carbonyl)acrylate (2n).
Reactions of αꢀfluorovinyl sulfides with arylhydrazines (genꢀ
eral procedure). A solution of vinyl sulfide (0.01 mol) in ether
(10 mL) was added dropwise with stirring and cooling to 10 °C
to a solution of the corresponding hydrazine (0.02 mol) in
ether (10 mL). The reaction mixture was kept at 20 °C for
15—20 h. The precipitate that formed was filtered off, the
filtrate was concentrated, and the residue was recrystallized
from alcohol. This procedure was used for the preparation of
3ꢀbenzylthioꢀ1ꢀphenylꢀ4ꢀtrifluoromethylꢀ3ꢀpyrazolꢀ5ꢀone (3);
5ꢀaminoꢀ3ꢀbenzylthioꢀ1ꢀphenylꢀ4ꢀ(trifluoromethyl)pyrazole
(4); 5ꢀaminoꢀ3ꢀbenzylthioꢀ1ꢀ(4ꢀchlorophenyl)ꢀ4ꢀ(trifluoroꢀ
methyl)pyrazole (5), MS, m/z: 383 [M]+; 5ꢀaminoꢀ3ꢀbenzylꢀ
thioꢀ1ꢀ(4ꢀfluorophenyl)ꢀ4ꢀ(trifluoromethyl)pyrazole (6); 5ꢀamiꢀ
noꢀ3ꢀbenzylthioꢀ4ꢀtrifluoromethylꢀ1ꢀ(4ꢀtrifluoromethylpheꢀ
nyl)pyrazole (7), and 5ꢀaminoꢀ3ꢀtertꢀbutylthioꢀ1ꢀphenylꢀ4ꢀ(triꢀ
fluoromethyl)pyrazole (8).
Upon heating in diphenyl oxide, cyclization of comꢀ
pounds 2m,n proceeded in a usual fashion to produce
quinolone derivatives 14a,b (Scheme 6).
Scheme 6
R = Et (14a), COOEt (14b)
Thermal cyclization of trifluoromethyl(methoxyꢀ
carbonyl)ketene N,Sꢀacetals proceeded ambiguously
(due, apparently, to competitive cyclizations at the
methoxycarbonyl and trifluoromethyl groups) and was
accompanied by substantial resinification of the reaction
mixture.
The aboveꢀconsidered approaches to the preparation
of heteroaromatic derivatives bearing sulfurꢀcontaining
fragments in the side chain are of interest as applied to
the synthesis of biologically active compounds.
Experimental
The 19F NMR spectra were recorded on a Bruker ACꢀ200F
spectrometer (188.31 MHz). The 1H 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 course of the reactions and the purities of the resulting
compounds were monitored by TLC on Merck 60Fꢀ254 plates
in an acetone—CCl4 system.
The starting vinyl sulfides 1 were synthesized according to
a procedure reported previously.1
The yields, physicochemical properties, spectroscopic charꢀ
acteristics, and data from elemental analysis for the resulting
compounds are given in Table 1.
Reactions of αꢀfluorovinyl sulfides with amidines (general
procedure). A 40% aqueous solution of NaOH (0.02 mol) was
added portionwise with vigorous stirring to a suspension of the
corresponding αꢀfluorovinyl sulfide (0.01 mol) and the correꢀ
sponding amidine hydrochloride (0.01 mol) in benzene (20 mL).
The reaction mixture was kept at ∼20 °C for 30 min and then
hexane (10 mL) was added. The precipitate that formed was
filtered off, washed on a filter with water and hexane, and
dried in air. This procedure was used for the preparation of

1024
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 6, June, 2002
Kovregin et al.
Table 1. Yields, physicochemical properties, spectroscopic characteristics, and data from elemental analysis for the compounds
synthesized
Comꢀ Yield M.p. Found
pound (%) /°С Calculated
Molecular
formula
NMR (δ, J/Hz)*
(%)
19F
1Н
С
Н
2a
55 103—105 51.77 4.35 С12H12F3NO2S 21.2 (s, CF3)
51.61 4.30
3.75 (s, 3 H, ОМе); 4.25 (s, 2 H, СH2);
7.40 (m, 5 H, Ph);
5.70, 9.50 (both br.s, 1 H each, NH2)
1.19 (m, 6 H, 2 Ме); 3.59 (m, 7 H, 2 СH2 and ОМе);
4.06 (s, 2 H, СH2); 7.29 (m, 5 H, Ph)
2.30 (s, 3 H, Ме); 3.72 (s, 3 H, ОМе);
4.31 (s, 2 H, CH2); 4.81 (br.s, 1 H, NH); 6.60,
7.16 (both d, 2 H each, J = 8); 7.29 (m, 5 H, Ph)
3.76 (s, 6 H, 2 OМе); 4.30 (s, 2 H, CH2); 4.83
(br.s, 1 H, NH); 6.78 (m, 4 H); 7.32 (m, 5 H)
3.75 (s, 3 H, 2 OМе); 4.31 (s, 2 H, CH2);
4.98 (br.s, 1 H, NH); 6.70—7.40 (m, 14 H)
1.58 (s, 9 H, But); 2.28 (t, 3 H, Ме, J = 7.0);
2.65 (q, 2 H, СH2, J = 7.0); 3.81 (s, 3 H, OMe);
4.69 (br.s, 1 H, NH); 6.65, 7.18
2b
2с
53 34—36 55.39 5.75 C16H20F3NO2S 24.5, 20.9 (both s,
55.33 5.76
85 60—62 59.88 4.71 C19H18F3NO2S
59.84 4.72
СF3, 5 : 1)
—
2d
2e
2f
80 52—54 57.49 4.50 C19H18F3NO3S
57.43 4.53
62 50—52 62.78 4.38 C24H20F3NO3S
62.75 4.36
—
—
60 38—40 56.56 6.10 C17H22F3NO2S 19.3 (s, CF3)
56.51 6.09
(both d, 2 H each, J = 8)
2g
2h
85 68—70 61.13 3.91
61.08 3.89
C17H13F3N2S
—
3.86, 3.96 (both s, 2 H, CH2, 1 : 1);
7.14—7.28 (m, 10 H, 2 Ph); 9.51, 9.98
(both br.s, 1 H, NH, 1 : 1)
84 104—106 57.99 3.38
57.95 3.41
C17H12F4N2S –33.9, –33.5 (both 3.90, 4.03 (both s, 2 H, CH2, 3 : 4);
s, 1 F, CF, 4 : 3);
27.1, 32.5 (both s,
3 F, CF3, 3 : 4)
—
7.06 (m, 4 H);
7.22 (m, 5 H); 9.57, 9.90
(both br.s, 1 H, NH, 3 : 4)
2i
85 69—71 62.12 4.29
62.07 4.31
C18H15F3N2S
2.36 (s, 3 H, Me); 3.90, 4.02 (both s,
2 H, CH2, 1 : 1); 7.00 (m, 2 H); 7.21 (m, 7 H);
9.63, 9.94 (both br.s, 1 H, NH, 1 : 1)
3.73 (s, 3 H, OMe); 3.87, 3.96 (both s, 2 H,
CH2, 3 : 4); 7.09 (m, 2 H); 7.37 (m, 2 H);
9.50, 9.78 (both br.s, 1 H, NH, 3 : 4)
3.92, 4.03 (both s, 2 H, CH2, 3 : 4); 6.96 (m, 4 H);
7.09 (m, 3 H); 7.27 (m, 7 H); 9.57, 9.90
(both br.s, 1 H, NH, 3 : 4)
1.30, 1.41 (both s, 9 H, But, 1 : 1); 3.79 (s, 3 H,
OMe); 6.89 (m, 2 H); 7.13 (m, 2 H);
7.27 (m, 2 H); 9.52 (br.s, 1 H, NH)
1.29 (m, 3 H, Ме); 2.69 (m, 2 H, СH2);
3.68 (m, 8 H, 2 ОМе and СH2); 7.20 (m, 9 H);
4.14, 10.30 (both s, 1 H, CH : NH = 1 : 9)
Enamine: 1.36 (t, 3 H, Ме, J = 7.0); 3.59 (s,
6 H, 2 OMe); 3.80 (s, 2 H, СH2); 4.30 (q,
2 H, СH2, J = 7.0); 7.21 (m, 7 H); 7.91 (m,
2 H); 9.89 (s, 1 H, NH); imine: 1.33 (m, 3 H,
Ме); 3.68 (s, 2 H, СH2); 3.71 (s, 6 H, 2 OMe);
4.27 (s, 1 H, СH); 4.29 (m, 2 H, СH2);
7.20 (m, 7 H); 7.92 (m, 2 H)
2j
71 75—77 59.27 4.10 C18H15F3N2OS
59.34 4.12
—
—
2k
2l
60 93—95 64.87 3.97 C23H17F3N2OS
64.79 3.99
67 65—67 54.63 5.16 C15H17F3N2OS
54.55 5.15
2m
2n
71 63—65 65.54 5.95
65.45 5.97
C21H23NO4S
C22H23NO6S
—
—
73 69—71 61.70 5.33
61.54 5.36
3
4
5
41 155—157 58.37 3.69 C17H13F3N2OS
58.29 3.71
—
—
—
3.80 (s, 2 H, CH2); 6.92 (m, 2 H); 7.21 (m, 5 H);
7.41 (m, 3 H); 10.95 (br.s, 1 H, NH)
4.25 (s, 2 H, CH2); 7.25 (m, 3 H);
7.40 (m, 3 H); 7.52 (m, 4 H)
4.25 (s, 2 H, CH2); 7.25 (m, 3 H); 7.38 (m, 2 H);
7.50 (m, 4 H)
44 68—70 58.40 3.97
58.45 4.01
C17H14F3N3S
53 140—142 53.27 3.36 C17H13ClF3N3S
53.19 3.39
(to be continued)

Reactions of vinyl sulfides with Nꢀnucleophiles
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 6, June, 2002
1025
Table 1 (continued)
Comꢀ Yield M.p. Found
pound (%) /°С Calculated
Molecular
formula
NMR (δ, J/Hz)*
(%)
19F
1Н
С
Н
6
57 74—76 55.67 3.55
55.59 3.54
63 68—70 51.88 3.15
51.80 3.12
59 82—84 53.40 5.07
53.33 5.08
C17H13F4N3S –30.9 (s, 1 F, CF); 4.27 (s, 2 H, CH2); 5.90 (br.s, 2 H, NH2);
28.9 (s, 3 F, CF3)
C18H13F6N3S 21.7 (s, CF3);
28.8 (s, CF3)
7.30 (m, 7 H); 7.55 (m, 2 H)
7
4.27 (s, 2 H, CH2); 5.89 (br.s, 2 H, NH2);
7.27 (m, 3 H); 7.40 (m, 2 H); 7.81 (m, 4 H)
1.45 (s, 9 H, But); 5.51 (br.s, 2 H, NH2);
7.44 (m, 1 H); 7.52 (m, 4 H)
8
C14H16F3N3S
—
9a
68 86—88 52.27 3.99
52.17 4.01
C13H12F3N3S
—
1.79, 1.89 (both s, 3 H, СH3, 1 : 2);
3.98, 4.09 (both s, 2 H, СH2, 1 : 2);
7.30 (m, 7 H, 5 CH + NH2)
9b
9c
9d
9e
74 132—134 47.42 5.70
47.31 5.73
77 124—126 59.91 3.90
59.83 3.88
69 116—118 55.13 4.87
55.05 4.89
65 80—82 57.97 4.28 C19H17F3N2O2S
57.89 4.31
C11H16F3N3S
C18H14F3N3S
—
—
1.47 (s, 9 H, But); 1.93, 1.99 (both s, 3 H,
Me, 5 : 2); 7.25 (br.s, 2 H, NH2)
3.93, 4.08 (both s, 2 H, СH2, 5 : 1);
7.24 (m, 5 H); 7.48 (m, 3 H); 7.91 (m, 2 H)
C15H16F3N3S 25.6, 28.1 (both s, 1.42, 1.47 (both s, 9 H, But, 4 : 1);
CF3, 1 : 4)
—
7.49 (m, 5 H, 3 CH + NH2); 7.90 (m, 2 H)
3.58 (s, 3 H, OMe); 3.80 (s, 2 H, CH2);
7.07 (br.s, 2 H, NH2); 7.24 (m, 5 H);
7.45 (m, 3 H); 7.91 (m, 2 H)
10a
10b
10c
10d
10e
10f
70 93—95 52.25 4.00
52.17 4.01
72 98—100 45.37 5.24
45.28 5.28
77 78—80 60.01 3.94
59.83 3.89
51 101—103 55.16 4.85
55.05 4.89
64 208—210 52.11 3.64 C13H11F3N2OS 26.3 (s, CF3)
52.00 3.67
66 83—85 45.20 4.84 C10H13F3N2OS
45.11 4.89
C12H12F3N3S 26.7 (s, CF3)
2.40 (s, 3 H, Me); 4.40 (s, 2 H, CH2); 6.58
(br.s, 2 H, NH2); 7.25 (m, 3 H); 7.37 (m, 2 H)
1.58 (s, 9 H, But); 2.35 (s, 3 H, Me);
7.25 (br.s, 2 H, NH2)
4.60 (s, 2 H, CH2); 6.75 (br.s, 2 H, NH2);
7.25 (m, 3 H); 7.43 (m, 5 H); 8.34 (m, 2 H)
1.68 (s, 9 H, But); 7.20 (br.s, 2 H, NH2);
7.55 (m, 3 H); 8.31 (m, 2 H)
2.38 (s, 3 H, Me); 4.45 (s, 2 H, CH2);
7.30 (m, 3 H); 7.40 (m, 2 H)
1.67 (s, 9 H, But); 2.25 (s, 3 H, Me);
12.90 (br.s, 1 H, OH)
C10H14F3N3S
C18H14F3N3S
—
C15H16F3N3S 28.1 (s, CF3)
—
10g
69 247—249 51.16 4.24 C14H14F3N3OS
—
2.08 (s, 3 H, Me); 3.00 (s, 6 H, 2 NCH3);
6.67 (m, 2 H);
(with
51.06 4.26
decomp.)
7.22 (m, 2 H)
10h
71 243—245 45.79 3.44 C11H10F3N3OS
—
2.10 (s, 3 H, Me); 3.52 (s, 3 H, NCH3);
6.10 (m, 1 H); 6.40 (m, 1 H); 7.10 (m, 1 H);
12.95 (br.s, 1 H, OH)
(with
45.67 3.46
decomp.)
10i
10j
10k
10l
55 273—275 51.77 3.10 C14H10F3N3OS 26.9 (s, CF3)
51.69 3.08
1.90 (s, 3 H, Me); 7.10 (m, 2 H); 7.40 (m, 2 H);
7.65 (m, 1 H); 11.57 (br.s, 1 H, NH)
2.20 (s, 3 H, Me); 2.30 (s, 3 H, Me); 3.30 (s,
3 H, NCH3); 7.32 (m, 3 H); 7.50 (m, 2 H)
4.59 (s, 2 H, CH2); 7.30 (m, 3 H); 7.40 (m, 2 H);
7.55 (m, 2 H); 7.64 (m, 1 H); 8.18 (m, 2 H)
3.05 (s, 6 H, 2 NCH3); 6.78 (m, 2 H);
7.30 (m, 4 H); 7.51 (m, 1 H); 7.79 (d, 2 H, J = 9)
58 308—310 51.63 3.76 C17H15F3N4O2S
51.52 3.79
65 260—262 59.74 3.58 C18H13F3N2OS
59.67 3.59
—
—
—
53 278—280 58.39 4.07 C19H16F3N3OS
(with
58.31 4.09
decomp.)
10m
59 252—254 54.81 3.44 C16H12F3N3OS 26.2 (s, CF3)
54.70 3.42
3.57 (s, 3 H, NCH3); 6.20 (m, 1 H); 6.43 (m, 1 H);
7.12 (s, 1 H); 7.38 (m, 2 H); 7.54 (m, 1 H);
7.80 (m, 2 H)
10n
10o
47 286—288 59.03 3.11 C19H12F3N3OS
58.91 3.10
51 332—334 57.74 3.69 C22H17F3N4O2S
57.64 3.71
—
—
7.15 (m, 4 H); 7.40 (m, 4 H); 7.55 (m, 1 H);
7.74 (s, 1 H); 11.65 (br.s, 1 H, NH)
2.33 (s, 3 H, Me); 3.30 (s, 3 H, NCH3);
7.35 (m, 5 H); 7.55 (m, 3 H); 7.93 (d, 2 H, J = 9)
(to be continued)

1026
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 6, June, 2002
Kovregin et al.
Table 1 (continued)
Comꢀ Yield M.p. Found
Molecular
formula
NMR (δ, J/Hz)*
(%)
pound (%)
/°С
Calculated
19F
1Н
С
Н
11a
11b
12
48 91—93 57.90 4.84
57.83 4.82
49 111—113 65.68 4.47
65.59 4.50
15 174—176 62.85 4.87
62.72 4.88
69 256—258 69.96 4.09
69.86 4.11
65 268—270 65.94 3.57
65.81 3.55
72 270—272 70.70 4.55
70.59 4.58
C12H12FN3S
C17H14FN3S
C15H14FN3S
C17H12N2OS
–75.2 (s, CF)
2.37 (s, 3 H, Me); 4.39 (s, 2 H, CH2); 6.40
(br.s, 2 H, NH2); 7.23 (m, 3 H); 7.36 (m, 2 H)
4.58 (s, 2 H, CH2); 6.85 (br.s, 2 H, NH2);
7.27 (m, 3 H); 7.41 (m, 5 H); 8.29 (m, 2 H)
1.26 (s, 9 H, But); 7.67 (m, 3 H);
—
–65.6 (s, CF)
—
8.36 (m, 2 H)
13a
13b
13c
4.69 (s, 2 H, CH2); 7.34 (m, 6 H); 7.78 (m, 2 H);
8.07 (m, 1 H); 12.52 (br.s, 1 H, NH)
4.65 (s, 2 H, CH2); 7.37 (m, 5 H); 7.70 (m, 2 H);
7.81 (m, 1 H); 12.58 (br.s, 1 H, NH)
2.40 (s, 3 H, Me); 4.64 (s, 2 H, CH2);
7.29 (m, 5 H); 7.63 (m, 2 H); 7.88 (m, 1 H);
12.46 (br.s, 1 H, NH)
C17H11FN2OS –33.2 (s, CF)
C18H14N2OS
—
13d
14a
64 285—287 71.97 4.14
71.88 4.17
52 224—226 68.11 5.34
67.99 5.38
C23H16N2O2S
C20H19NO3S
—
—
4.67 (s, 2 H, CH2); 7.09 (m, 2 H); 7.38 (m, 10 H);
7.80 (m, 1 H); 12.56 (br.s, 1 H, NH)
1.25 (t, 3 H, Me, J = 7); 2.76 (q, 2 H, CH2,
J = 7); 3.75 (s, 3 H, OMe); 4.48 (s, 2 H, CH2);
7.29 (m, 5 H); 7.60 (m, 2 H); 7.88 (m, 1 H);
11.82 (br.s, 1 H, NH)
14b
47 246—248 63.53 4.81
63.48 4.79
C21H19NO5S
—
1.35 (t, 3 H, Me, J = 7); 3.75 (s, 3 H, OMe);
4.37 (q, 2 H, CH2, J = 7); 4.53 (s, 2 H, CH2);
7.30 (m, 5 H); 7.79 (m, 1 H); 8.22 (m, 1 H);
8.64 (m, 1 H); 12.19 (br.s, 1 H, NH)
* The spectra of all compounds were recorded in DMSOꢀd6, except for compound 2a (in CDCl3).
Nꢀ(1ꢀbenzylthioꢀ2ꢀcyanoꢀ2ꢀtrifluoromethylvinyl)acetamidine
(9a), MS, m/z: 299 [M]+; Nꢀ(1ꢀtertꢀbutylthioꢀ2ꢀcyanoꢀ2ꢀ
trifluoromethylvinyl)acetamidine (9b); Nꢀ(1ꢀbenzylthioꢀ2ꢀ
cyanoꢀ2ꢀtrifluoromethylvinyl)benzamidine (9c), MS, m/z:
361 [M]+; Nꢀ(1ꢀtertꢀbutylthioꢀ2ꢀcyanoꢀ2ꢀtrifluoromethylꢀ
vinyl)benzamidine (9d), and Nꢀ(1ꢀbenzylthioꢀ2ꢀmethoxyꢀ
carbonylꢀ2ꢀtrifluoromethylvinyl)benzamidine (9e).
4ꢀAminoꢀ6ꢀbenzylthioꢀ2ꢀmethylꢀ5ꢀ(trifluoromethyl)pyrimiꢀ
dine (10a). A solution of amidine 9a (1 g) in toluene (10 mL)
was refluxed for 5 h and then cooled to 20 °C. The crystals that
precipitated were filtered off. Compound 10a was obtained in a
yield of 0.7 g, MS, m/z: 299 [M]+.
4ꢀAminoꢀ6ꢀtertꢀbutylthioꢀ2ꢀmethylꢀ5ꢀ(trifluoromeꢀ
thyl)pyrimidine (10b) and 4ꢀaminoꢀ6ꢀbenzylthioꢀ2ꢀphenylꢀ5ꢀ
(trifluoromethyl)pyrimidine (10c) were prepared analogously.
4ꢀAminoꢀ6ꢀtertꢀbutylthioꢀ2ꢀphenylꢀ5ꢀ(trifluoromethyl)pyriꢀ
midine (10d) and 6ꢀtertꢀbutylthioꢀ5ꢀcyanoꢀ4ꢀfluoroꢀ2ꢀphenylꢀ
pyrimidine (12). A solution of amidine 9d (1 g) in toluene (10 mL)
was refluxed for 5 h, the solvent was removed in vacuo, and the
residue was chromatographed on a column with silica gel (150 g)
using a 1 : 2 ethyl acetate—hexane mixture as the eluent. Pyriꢀ
midine 10d was obtained in a yield of 0.51 g, MS, m/z:
327 [M]+. Pyrimidine 12 was obtained in a yield of 0.15 g, MS,
m/z: 287 [M]+.
Synthesis of 4ꢀhydroxypyrimidines (general procedure).
A 40% aqueous solution of NaOH (0.02 mol) was added
portionwise with vigorous stirring to a suspension of the correꢀ
sponding methyl acrylate (0.01 mol) and the corresponding
amidine hydrochloride (0.01 mol) in benzene (20 mL). The
reaction mixture was kept at ∼20 °C for 30 min, refluxed for
1 h, and cooled to 20 °C. The precipitate that formed was
filtered off, washed on a filter with water and benzene, and
dried in air. This procedure was used for the preparation of
6ꢀbenzylthioꢀ4ꢀhydroxyꢀ2ꢀmethylꢀ5ꢀ(trifluoromethyl)pyrimiꢀ
dine (10e); 6ꢀtertꢀbutylthioꢀ4ꢀhydroxyꢀ2ꢀmethylꢀ5ꢀ(trifluoroꢀ
methyl)pyrimidine (10f); 6ꢀ(4ꢀdimethylaminophenylthio)ꢀ4ꢀ
hydroxyꢀ2ꢀmethylꢀ5ꢀ(trifluoromethyl)pyrimidine (10g); 4ꢀhydrꢀ
oxyꢀ2ꢀmethylꢀ6ꢀ[2ꢀ(Nꢀmethyl)pyrrolylthio]ꢀ5ꢀ(trifluoromeꢀ
thyl)pyrimidine (10h); 4ꢀhydroxyꢀ6ꢀ(3ꢀindolylthio)ꢀ2ꢀmethylꢀ
5ꢀ(trifluoromethyl)pyrimidine (10i); 4ꢀhydroxyꢀ6ꢀ[4ꢀ(2,3ꢀdiꢀ
methylꢀ5ꢀoxoꢀ1ꢀphenyl)pyrazolylthio]ꢀ2ꢀmethylꢀ5ꢀ(trifluoroꢀ
methyl)pyrimidine (10j); 6ꢀbenzylthioꢀ4ꢀhydroxyꢀ2ꢀphenylꢀ5ꢀ
(trifluoromethyl)pyrimidine (10k); 4ꢀhydroxyꢀ6ꢀ(4ꢀdimethylꢀ
aminophenylthio)ꢀ2ꢀphenylꢀ5ꢀ(trifluoromethyl)pyrimidine
(10l); 4ꢀhydroxyꢀ6ꢀ[2ꢀ(Nꢀmethyl)pyrrolylthio]ꢀ2ꢀphenylꢀ5ꢀ
(trifluoromethyl)pyrimidine (10m); 4ꢀhydroxyꢀ6ꢀ(3ꢀindolylꢀ
thio)ꢀ2ꢀphenylꢀ5ꢀ(trifluoromethyl)pyrimidine (10n), and
6ꢀ[4ꢀ(2,3ꢀdimethylꢀ5ꢀoxoꢀ1ꢀphenyl)pyrazolylthio]ꢀ4ꢀhydroxyꢀ
2ꢀphenylꢀ5ꢀ(trifluoromethyl)pyrimidine (10o).
4ꢀAminoꢀ6ꢀbenzylthioꢀ5ꢀfluoroꢀ2ꢀmethylpyrimidine (11a). A
solution of NaOH (0.8 g, 0.02 mol) in water (1.2 mL) was
added with vigorous stirring to a suspension of 2ꢀbenzylthioꢀ
1,2ꢀdifluoroacrylonitrile (1f) (2.1 g, 0.01 mol) and acetamidine
hydrochloride (0.95 g, 0.01 mol) in toluene (20 mL). The reacꢀ
tion mixture was kept at 20 °C for 30 min, refluxed for 5 h, and
cooled. The residue was filtered off and recrystallized from
benzene. Pyrimidine 11a was obtained in a yield of 1.2 g, MS,
m/z: 249 [M]+.

Reactions of vinyl sulfides with Nꢀnucleophiles
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 6, June, 2002
1027
4ꢀAminoꢀ6ꢀbenzylthioꢀ5ꢀfluoroꢀ2ꢀphenylpyrimidine (11b)
was prepared analogously from benzamidine hydrochloride.
2ꢀBenzylthioꢀ3ꢀcyanoquinolinꢀ4ꢀone (13a). A solution of
acrylonitrile 2g (1 g) in diphenyl oxide (5 mL) was heated at
180 °C for 30 min. The reacton was accompanied by gas evoluꢀ
tion. The mixture was cooled to 50 °C and the precipitate that
formed was filtered off, washed on a filter with benzene, and
dissolved in a 10% aqueous solution of NaOH. The crystals
that formed after neutralization with a solution of HCl were
filtered off and dried in air. Quinolinꢀ4ꢀone (13a) was obtained
in a yield of 0.6 g.
2ꢀBenzylthioꢀ3ꢀcyanoꢀ6ꢀfluoroquinolinꢀ4ꢀone (13b), MS,
m/z: 310 [M]+; 2ꢀbenzylthioꢀ3ꢀcyanoꢀ6ꢀmethylquinolinꢀ4ꢀone
(13c), and 2ꢀbenzylthioꢀ3ꢀcyanoꢀ6ꢀphenoxyquinolinꢀ4ꢀone
(13d) were synthesized analogously.
2ꢀBenzylthioꢀ6ꢀethylꢀ3ꢀ(methoxycarbonyl)quinolinꢀ4ꢀone
(14a). A solution of diether 2m (1 g) in diphenyl oxide (5 mL)
was heated at 220 °C for 30 min. The reaction was accompaꢀ
nied by precipitation. The mixture was cooled to 50 °C. The
precipitate was filtered off and washed on a filter with benzene
and hexane. Quinolinоne 14a was obtained in a yield of 0.48 g.
2ꢀBenzylthioꢀ6ꢀethoxycarbonylꢀ3ꢀ(methoxycarbonyl)quinoꢀ
linꢀ4ꢀone (14b) was prepared analogously from diether 2n.
2. S. R. Sterlin, V. M. Izmailov, V. L. Isaev, A. A. Shal´, R. N.
Sterlin, B. L. Dyatkin, and I. L. Knunyants, Zh. Vsesoyuz.
Khim. Obshch. im. D. I. Mendeleeva, 1973, 18, 710 [Mendeleev
Chem. J., 1973, 18 (Engl. Transl.)].
3. Yu. G. Shermolovich, P. P. Kornuta, E. I. Slyusarenko, and
V. M. Timoshenko, Zh. Org. Khim., 1997, 33, 348 [Russ.
J. Org. Chem., 1997, 33 (Engl. Transl.)].
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].
6. A. N. Kovregin, A. Yu. Sizov, and A. F. Ermolov, Izv. Akad.
Nauk, Ser. Khim., 2001, 1568 [Russ. Chem. Bull., Int. Ed.,
2001, 50, 1645].
7. E. G. TerꢀGabrielyan, E. P. Lur´e, Yu. V. Zeifman, and
N. P. Gambaryan, Izv. Akad. Nauk SSSR, Ser. Khim., 1975,
1380 [Bull. Acad. Sci. USSR, Div. Chem. Sci., 1975, 24, 1645
(Engl. Transl.)].
8. E. M. Rokhlin, E. G. Abduganiev, and U. Utebaev, Usp.
Khim., 1976, 45, 1176 [Russ. Chem. Rev., 1976, 45 (Engl.
Transl.)].
9. K. W. Chi, G. G. Furin, I. Yu. Bagryanskaya, and Yu. V.
Gatilov, J. Fluor. Chem., 1999, 94, 37.
References
1. 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].
Received January 29, 2002;
in revised form March 5, 2002