Synthesis of trifluoroalkyl- and fluoroaryl-substituted 4,5-dihydro-1H-1,2,4-triazole-5-thiones

Article abstract of DOI:10.1023/B:RUJO.0000044552.07729.40

Reactions of 4-(4-fluorophenyl)-, 4-(4-trifluoromethoxyphenyl)-, 4-(3,4-difluorophenyl)-, 4-(4-trifluoromethylphenyl)-, 4-piperidino-, and 4-(3-pyridyl)thiosemicarbazides with esters gave the corresponding 3,4-disubstituted 4,5-dihydro-1H-1,2,4-triazole-5

Full text of DOI:10.1023/B:RUJO.0000044552.07729.40

Russian Journal of Organic Chemistry, Vol. 40, No. 6, 2004, pp. 874–878. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 6, 2004,
pp. 912–916.
Original Russian Text Copyright © 2004 by Vasil’eva, Sevenard, Khomutov, Kuznetsova, Karpenko, Filyakova.
Dedicated to Full Member of the Russian Academy of Sciences
O.N. Chupakhin on his 70th Anniversary
Synthesis of Trifluoroalkyl- and Fluoroaryl-Substituted
4,5-Dihydro-1H-1,2,4-triazole-5-thiones
E. B. Vasil’eva, D. V. Sevenard, O. G. Khomutov, O. A. Kuznetsova,
N. S. Karpenko, and V. I. Filyakova
Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences,
ul. S. Kovalevskoi 20, Yekaterinburg, 620219 Russia
e-mail: cec@ios.uran.ru
Received June 5, 2003
Abstract—Reactions of 4-(4-fluorophenyl)-, 4-(4-trifluoromethoxyphenyl)-, 4-(3,4-difluorophenyl)-, 4-(4-
trifluoromethylphenyl)-, 4-piperidino-, and 4-(3-pyridyl)thiosemicarbazides with esters gave the corresponding
3,4-disubstituted 4,5-dihydro-1H-1,2,4-triazole-5-thiones and their S-alkyl derivatives. Analogous reactions
with methyl 2,2,3,3,4,4,5,5-octafluoropentanoate and 2,2,3,3,4,4,5,5-octafluoropentanenitrile afforded, respec-
tively, the acylation and addition products.
4,5-Dihydro-1H-1,2,4-triazole-5-thiones are known
to exhibit biological activity. They can be synthesized
by cyclization of 1-acyl-substituted thiosemicarbazides
[1, 2] or by direct reaction of thiosemicarbazides with
carboxylic acid esters [3]. Introduction of poly-
fluorinated substituents into various positions of the
1,2,4-triazole ring seems to be fairly promising, for
fluorine-containing compounds are characterized by
stronger biological activity as compared to non-
fluorinated analogs [4].
structure of triazole derivatives. Reactions of 2,4-di-
substituted thiosemicarbazides with trifluoroacetic
anhydride were reported to afford polyfluorinated
4,5-dihydro-1H-1,2,4-triazole-5-thiones [6]. However,
no rigorous proofs for the assumed structures were
given in these publications [5, 6].
In the present work we introduced fluorinated sub-
stituents into the 1,2,4-triazole ring by using as starting
compounds both fluoroaryl-substituted thiosemicarba-
zides and fluorine-containing electrophile. For this
purpose, we examined reactions of 4-(4-fluorophenyl)-,
4-(4-trifluoromethoxyphenyl)-, 4-(3,4-difluorophenyl)-,
4-(4-trifluoromethylphenyl)-, 4-piperidino-, and 4-(3-
pyridyl)thiosemicarbazides Ia–If with esters derived
carboxylic (IIa, IIb), hetarenecarboxylic (IIc, IId),
and fluorocarboxylic acids (IIe) (Scheme 1).
Published data on fluorine-containing 4,5-dihydro-
1H-1,2,4-triazole-5-thiones are very scanty. Vershilov
et al. [5] performed condensation of fluorine-free thio-
semicarbazides with a number of polyfluorinated acyl
fluorides and obtained a series of compounds pos-
sessing surfactant activity, which were assigned the
Scheme 1.
N
NH
N
N
MeONa/MeOH
RNH
C
S
NH NH2
+
R'COOEt
+
R'
S
R'
SMe
N
R
N
R
Ia–If
IIa–IIe
IIIa–IIIo
IVa, IVb
Ia, IIIe–IIIg, IVa, R = 4-FC6H4; Ib, IIIa–IIIc, R = 4-CF3OC6H4; Ic, IIId, R = 3,4-F2C6H3; Id, IIIh–IIIj, R = 4-CF3C6H4; Ie, IIIk–
IIIm, IVb, R = piperidino; If, IIIn, IIIo, R = 3-pyridyl; IIa, IIIa, IIIh, IIIk, R' = H; IIb, IIIb, IIId, IIIi, IIIl, IIIn, R' = Me;
IIc, IIIf, R' = 3-pyridyl; IId, IIIe, R' = 2-thienyl; IIe, IIIc, IIIg, IIIj, IIIm, IIIo, IVa, IVb, R' = CF3.
1070-4280/04/4006-0874 © 2004 MAIK “Nauka/Interperiodica”

SYNTHESIS OF TRIFLUOROALKYL- AND FLUOROARYL-SUBSTITUTED ...
875
Scheme 2.
O
MeONa
Ia
+
H(CF2)4COOMe
F
NH
C
S
NH NH
C
(CF2)4H
IIf
V
Scheme 3.
NH2
C
MeONa
Ic
+
H(CF2)4CN
F
NH
C
S
NH
N
(CF2)4H
F
VI
VII
We have found that condensation of fluoroaryl-
substituted thiosemicarbazides Ia–Id with esters IIa–
IId leads to formation of dihydro-1,2,4-triazolethiones
IIIa, IIIb, IIId–IIIf, IIIh, and IIIi containing the
corresponding fluoroaryl group in position 4 of the
heteroring. The reactions of ethyl trifluoroacetate (IIe)
with fluorine-free thiosemicarbazides Ie and If gave
1,2,4-triazole-5-thiones IIIm and IIIo in which the
fluoroalkyl group is located at C3. By condensation of
fluoroaryl-substituted thiosemicarbazides Ia–Id with
ethyl trifluoroacetate we obtained compounds IIIc,
IIIg, and IIIj having trifluoromethyl group on C3 and
fluoroaryl group on N4. In addition, we were the first
to reveal that the condensation with ethyl trifluoro-
acetate is accompanied by alkylation of the resulting
heterocycles at the sulfur atom to give 5-methyl-
sulfanyl derivatives IV. Compounds IVa and IVb were
isolated and characterized by spectral data. The
1H NMR spectra of IVa and IVb contained signals
from the substituents in positions 3 and 4 of the
triazole ring and a singlet at δ 2.75 ppm, which is
typical of SMe group.
stage of formation of primary acylation product
(Scheme 2). Presumably, the subsequent cyclization is
strongly hindered for steric reasons: attack by aryl-sub-
stituted nitrogen atom on the carbonyl group shielded
by fairly bulky polyfluoroalkyl substituent becomes
impossible. Our attempts to effect cyclization of
1-(2,2,3,3,4,4,5,5-octafluoropentanoyl)-4-(4-fluoro-
phenyl)thiosemicarbazide (V) by prolonged heating
with sodium methoxide in boiling methanol, as well as
by heating in p-xylene, resulted in tarring. We also
failed to obtain heterocyclic product by condensation
of thiosemicarbazide Ic with polyfluorinated nitrile VI
(Scheme 3). It might be expected that the cyclization
of VII should be more facile than the cyclization of
compound V. However, our numerous attempts to
effect deamination of structure VII were unsuccessful.
Thus we have demonstated the possibility of intro-
ducing fluoroaryl and fluoroalkyl groups into dihydro-
1,2,4-triazole-5-thiones, but the set of RF groups is
confined to only short trifluoromethyl substituent.
EXPERIMENTAL
Presumably, the alkylation is effected by methyl
trifluoroacetate.* The electron-acceptor trifluoromethyl
group favors formation of trifluorocarboxylate ion
which is stabilized due to the presence of sodium
cation in the reaction mixture. There are published
data on the use of fluorocarboxylic acid esters as
alkylating agents [7].
The NMR spectra were recorded on Tesla BS-567A
1
(80 MHz for H and 75 MHz for 19F) and Bruker
1
DRX-400 (400MHz for H and 100 MHz for 19F)
spectrometers using tetramethylsilane as reference
1
(for H). The IR spectra were measured on Specord
75-IR and Perkin–Elmer Spectrum I instruments from
samples dispersed in mineral oil. The mass spectra
(electron impact, 70 eV) were obtained on a MAT
INCOS50 spectrometer with direct sample asdmission
into the ion source.
We failed to obtain 1,2,4-triazole-5-thiones having
longer polyfluoroalkyl substituents. The reaction of
thiosemicarbazide Ia with methyl 2,2,3,3,4,4,5,5-octa-
fluoropentanoate (IIf) as electrophile stopped at the
Thiosemicarbazides Ia–If were synthesized by the
procedure reported in [8].
* In the reactions with ethyl trifluoroacetate, the corresponding
methyl ester is formed as a result of transesterification with the
solvent (methanol).
4-(4-Fluorophenyl)thiosemicarbazide (Ia). Yield
65%, colorless crystals, mp 180–181°C (from water).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004

VASIL’EVA et al.
876
1H NMR spectrum (DMSO-d6), δ, ppm: 4.7 br.s (2H,
NH2), 7.09–7.60 m (4H, C6H4), 9.13 s (2H, 2NH).
Found, %: C 45.40; H 4.37; F 10.24. C7H8FN3S. Cal-
culated, %: C 45.40; H 4.40; F 10.26.
solution was heated for 5 min at the boiling point and
filtered. After cooling, the precipitate was filtered off,
reprecipitated from DMF with water, and recrystallized
from hexane. We thus isolated compounds IV. The
filtrate was cooled and acidified with concentrated
hydrochloric acid to pH 2–3. The precipitate of com-
pound III was filtered off and recrystallized from
appropriate solvent.
4-(4-Trifluoromethoxyphenyl)thiosemicarbazide
(Ib). Yield 60%, colorless crystals, mp 124–125°C
(from toluene). 1H NMR spectrum (DMSO-d6), δ, ppm:
4.8 br.s (2H, NH2), 7.28–7.84 m (4H, C6H4), 9.25 s
(2H, 2NH). Found, %: C 38.12; H 2.90; F 22.67;
N 16.67. C8H8F3N3OS. Calculated, %: C 38.25; H 3.21;
F 22.69; N 16.73.
4-(4-Trifluoromethoxyphenyl)-4,5-dihydro-1H-
1,2,4-triazole-5-thione (IIIa). Yield 60%, colorless
crystals, mp 178–179°C (from toluene). IR spectrum,
1
ν, cm–1: 3060, 3100, 2740 (N–H). H NMR spectrum
4-(3,4-Difluorophenyl)thiosemicarbazide (Ic).
(DMSO-d6), δ, ppm: 7.58–7.85 m (4H, C6H4), 8.74 s
(1H, HC=N), 14.0 br.s (1H, NH). Found, %: C 41.09;
H 2.61; F 21.68; N15.99. C9H7F3N3OS. Calculated, %:
C 41.22; H 2.69; F 21.73; N 16.02.
Yield 65%, colorless crystals, mp 173–174°C (from
1
ethanol). H NMR spectrum (DMSO-d6), δ, ppm:
3.3 br.s (1H, NH), 5.3 br.s (2H, NH2), 7.18–8.04 m
(3H, C6H3), 9.2 br.s (1H, NH). Found, %: C 41.45;
H 3.50; F 18.70. C7H7F2N3S. Calculated, %: C 41.37;
H 3.47; F 18.70.
3-Methyl-4-(4-trifluoromethoxyphenyl)-4,5-di-
hydro-1H-1,2,4-triazole-5-thione (IIIb). Yield 55%,
light yellow crystals, mp 110–111°C (from toluene).
IR spectrum, ν, cm–1: 3060, 3100, 2740 (N–H).
1H NMR spectrum (CDCl3), δ, ppm: 2.22 s (3H, CH3),
7.26–7.52 m (4H, C6H4), 11.9 br.s (1H, NH). Found,
%: C 43.59; H 3.01; F 20.50; N 15.24. C10H8F3N3OS.
Calculated, %: C 43.64; H 2.93; F 20.71; N 15.27.
4-(4-Trifluoromethylphenyl)thiosemicarbazide
(Id). Yield 68%, colorless crystals, mp 162–163°C
1
(from ethanol). H NMR spectrum (DMSO-d6), δ,
ppm: 5.2 br.s (2H, NH2), 7.60–7.98 m (4H, C6H4),
9.40 s (2H, 2NH). Found, %: C 40.85; H 3.43;
F 24.23; N 17.86. C7H7F2N3S. Calculated, %: C 40.70;
H 3.38; F 24.23; N 17.81.
4-(4-Trifluoromethoxyphenyl)-3-trifluoro-
methyl-4,5-dihydro-1H-1,2,4-triazole-5-thione (IIIc).
Yield 58%, light yellow crystals, mp 163–164°C (from
toluene). IR spectrum, ν, cm–1: 3060, 3100, 2740
4-Piperidinothiosemicarbazide (Ie). Yield 65%,
colorless crystals, mp 170–171°C (from ethanol).
1H NMR spectrum (DMSO-d6), δ, ppm: 0.92–1.14 m
(2H, CH2), 2.29–2.49 m (4H, 2CH2), 2.68–2.89 m (4H,
2CH2), 4.7 br.s (2H, NH2), 8.66 s (2H, 2NH). Found,
%: C 41.63; H 7.80; N 32.25; S 18.36. C6H14N4S. Cal-
culated, %: C 41.35; H 8.10; N 32.15; S 18.40.
1
(N–H). H NMR spectrum (CDCl3), δ, ppm: 7.37–
7.98 m (4H, C6H4), 11.5 br.s (1H, NH). Found, %:
C 36.50; H 1.50; F 34.51; N 12.69. C10H5F6N3OS.
Calculated, %: C 36.48; H 1.53; F 34.62; N 12.76.
4-(3,4-Difluorophenyl)-3-methyl-4,5-dihydro-
1H-1,2,4-triazole-5-thione (IIId). Yield 66%, color-
less crystals, mp 228–230°C (from o-xylene). IR spec-
4-(3-Pyridyl)thiosemicarbazide (If). Yield 70%,
colorless crystals, mp 177–178°C (from ethanol).
1H NMR spectrum (DMSO-d6), δ, ppm: 5.2 br.s (2H,
NH2), 6.88–8.70 m (4H, C5H4N), 9.32 s (2H, 2NH).
Found, %: C 42.75; H 4.61; N 33.01. C6H8N4S. Calcu-
lated, %: C 42.84; H 4.79; N 33.31.
1
trum, ν, cm–1: 3050, 3100, 2750 (N–H). H NMR
spectrum (DMSO-d6), δ, ppm: 2.12 s (3H, CH3), 7.26–
7.84 m (3H, C6H3), 13.7 br.s (1H, NH). Found, %:
C 47.75; H 2.91; F 17.00; N 18.49; S 14.07.
C9H7F2N3S. Calculated, %: C 47.57; H 3.11; F 16.72;
N 18.49; S 14.11.
General procedure for the synthesis of com-
pounds IIIa–IIIo, IVa, and IVb. Carboxylic acid
ester IIa–IIe, 0.03 mol, was added to a solution of
0.02 mol of sodium methoxide in 10 ml of anhydrous
methanol. The mixture was heated to the boiling point,
a solution of 0.01 mol of thiosemicarbazide Ia–If in
5 ml of anhydrous methanol was added dropwise over
a period of 1 h, and the mixture was heated for 15 h
under reflux. The solvent was removed under reduced
pressure, the residue was dissolved in 10 ml of boiling
water, a small amount of charcoal was added, and the
4-(4-Fluorophenyl)-3-(2-thienyl)-4,5-dihydro-
1H-1,2,4-triazole-5-thione (IIIe). Yield 63%, color-
less crystals, mp 218–220°C (from toluene). IR spec-
1
trum, ν, cm–1: 3060, 3100, 2740 (N–H). H NMR
spectrum (CDCl3), δ, ppm: 7.23–8.18 m (7H, C6H4,
C4H3S), 11.3 br.s (1H, NH). Found, %: C 52.23;
H 2.46; N 15.16; S 23.27. C12H7FN3S2. Calculated, %:
C 52.16; H 2.55; N 15.21; S 23.20.
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SYNTHESIS OF TRIFLUOROALKYL- AND FLUOROARYL-SUBSTITUTED ...
877
(acetone-d6), δ, ppm: 1.47–1.74 m and 3.46–3.48 m
(10H, C5H10N), 8.23 s (1H, HC=N), 12.2 br.s (1H,
NH). Found, %: C 45.25; H 6.40; N 30.25. C7H12N4S.
Calculated, %: C 45.63; H 6.56; N 30.41.
4-(4-Fluorophenyl)-3-(3-pyridyl)-4,5-dihydro-
1H-1,2,4-triazole-5-thione (IIIf). Yield 41%, color-
less crystals, mp 255–256°C (from hexane–chloro-
form, 1:10). IR spectrum, ν, cm–1: 3060, 3100, 2740
1
(N–H). H NMR spectrum (DMSO-d6–CCl4), δ, ppm:
3-Methyl-4-piperidino-4,5-dihydro-1H-1,2,4-
triazole-5-thione (IIIl). Yield 70%, colorless crystals,
mp 180–181°C (from hexane–chloroform, 1:10). IR
7.27–8.53 m (8H, C5H4N, C6H4), 14.1 br.s (1H, NH).
Found, %: C 57.25; H 3.17; F 6.88; N 20.49.
C13H9FN4S. Calculated, %: C 57.34; H 3.33; F 6.97;
N 20.58.
1
spectrum, ν, cm–1: 3060, 3100, 2740 (N–H). H NMR
spectrum (CDCl3), δ, ppm: 2.29 s (3H, CH3); 1.32–
1.38 m, 1.57–1.81 m, 2.91–2.93 m (10H, C5H10N);
10.9 br.s (1H, NH). Found, %: C 48.54; H 6.99;
N 28.19; S 16.08. C8H14N4S. Calculated, %: C 48.46;
H 7.12; N 28.26; S 16.17.
4-(4-Fluorophenyl)-3-trifluoromethyl-4,5-di-
hydro-1H-1,2,4-triazole-5-thione (IIIg). Yield 22%,
colorless crystals, mp 160–161°C (from water). IR
1
spectrum, ν, cm–1: 3090, 3100, 2750 (N–H). H NMR
spectrum (CDCl3), δ, ppm: 7.26–7.35 m (4H, C6H4),
12.6 br.s (1H, NH). 19F NMR spectrum (CDCl3), δF,
ppm: 53.61 s (1F), 98.30 s (3F, CF3). Mass spectrum,
m/z (Irel, %): 263 (100) [M]+, 154 (2.39), 136 (8.00), 69
(6.83). Found, %: C 40.98; H 1.62; F 28.92; N 15.86.
C9H5F4N3S. Calculated, %: C 41.08; H 1.92; F 28.88;
N 15.97.
4-Piperidino-3-trifluoromethyl-4,5-dihydro-1H-
1,2,4-triazole-5-thione (IIIm). Yield 60%, colorless
crystals, mp 178–180°C (from o-xylene). IR spectrum,
1
ν, cm–1: 3060, 3100, 2740 (N–H). H NMR spectrum
(CDCl3), δ, ppm: 1.18–1.25 m, 1.65–1.77 m, 3.13–
3.15 m (10H, C5H10N); 9.7 br.s (1H, NH). Found, %:
C 38.15; H 4.32; N 22.09; S 12.61. C8H11F3N4S.
Calculated, %: C 38.09; H 4.40; N 22.21; S 12.71.
4-(4-Trifluoromethylphenyl)-4,5-dihydro-1H-
1,2,4-triazole-5-thione (IIIh). Yield 43%, colorless
crystals, mp 185–186°C (from hexane–chloroform,
1:10). IR spectrum, ν, cm–1: 3060, 3100, 2740 (N–H).
1H NMR spectrum (CDCl3), δ, ppm: 7.78–7.85 m
(4H, C6H4), 7.98 s (1H, HC=N), 11.8 br.s (1H, NH).
19F NMR spectrum (CDCl3), δF, ppm: 98.94 s (3F,
CF3). Found, %: C 43.95; H 2.39; F 22.75; N 16.86.
C9H6F3N3S. Calculated, %: C 44.08; H 2.47; F 23.24;
N 17.14.
3-Methyl-4-(3-pyridyl)-4,5-dihydro-1H-1,2,4-
triazole-5-thione (IIIn). Yield 56%, colorless crystals,
mp 254–255°C (from hexane–chloroform, 1:10). IR
1
spectrum, ν, cm–1: 3060, 3100, 2740 (N–H). H NMR
spectrum (CDCl3), δ, ppm: 2.22 s (3H, CH3), 7.26–
7.52 m (4H, C5H4N), 11.9 br.s (1H, NH). Found, %:
C 49.84; H 4.10; N 29.21; S 16.61. C8H8N4S. Calcu-
lated, %: C 49.98; H 4.19; N 29.14; S 16.68.
4-(3-Pyridyl)-3-trifluoromethyl-4,5-dihydro-1H-
1,2,4-triazole-5-thione (IIIo). Yield 67%, colorless
crystals, mp 226–228°C (from toluene). IR spectrum,
3-Methyl-4-(4-trifluoromethylphenyl)-4,5-di-
hydro-1H-1,2,4-triazole-5-thione (IIIi). Yield 40%,
colorless crystals, mp 186–187°C (from o-xylene). IR
1
ν, cm–1: 3060, 3100, 2740 (NH). H NMR spectrum
1
spectrum, ν, cm–1: 3060, 3100, 2740 (N–H). H NMR
(CDCl3), δ, ppm: 7.36–8.25 m (4H, C5H4N), 11.5 br.s
(1H, NH). Found, %: C 38.91; H 1.92; F 22.99;
N 22.58. C8H5F3N4S. Calculated, %: C 39.03; H 2.05;
F 23.15; N 22.76.
spectrum (DMSO-d6–CCl4), δ, ppm: 2.17 s (3H, CH3),
7.56–7.99 m (4H, C6H4), 13.6 br.s (1H, NH). Found,
%: C 46.39; H 2.97; F 22.05; N 16.26. C10H8F3N3S.
Calculated, %: C 46.33; H 3.11; F 21.98; N 16.21.
4-(4-Fluorophenyl)-5-methylsulfanyl-3-trifluoro-
methyl-1,2,4-triazole (IVa). Yield 32%, colorless
crystals, mp 148–149°C (from hexane). IR spectrum,
ν, cm–1: 1460 (C=N); 1188, 1170, 1148 (CF). 1H NMR
spectrum (CDCl3), δ, ppm: 2.74 s (3H, CH3), 6.81–
7.33 m (4H, C6H4). Found, %: C 43.18; H 2.45;
N 15.05. C10H7F4N3S. Calculated, %: C 43.32; H 2.54;
N 15.16.
3-Trifluoromethyl-4-(4-trifluoromethylphenyl)-
4,5-dihydro-1H-1,2,4-triazole-5-thione (IIIj). Yield
71%, colorless crystals, mp 173–174°C (from toluene).
IR spectrum, ν, cm–1: 3060, 3100, 2740 (N–H).
1H NMR spectrum (CDCl3), δ, ppm: 7.56–7.99 m (4H,
C6H4), 11.1 br.s (1H, NH). Found, %: C 38.40; H 1.55;
F 36.28; N 13.42; S 10.19. C10H5F6N3S. Calculated, %:
C 38.35; H 1.61; F 36.39; N 13.36; S 10.24.
4-Piperidino-4,5-dihydro-1H-1,2,4-triazole-5-
thione (IIIk). Yield 84%, colorless crystals, mp 192–
193°C (from hexane–chloroform, 1:10). IR spectrum,
5-Methylsulfanyl-4-piperidino-3-trifluoro-
methyl-1,2,4-triazole (IVb). Yield 68%, gray crystals,
mp 84–85°C (from hexane). IR spectrum, ν, cm–1:
1
1
ν, cm–1: 3060, 3100, 2740 (N–H). H NMR spectrum
1466 (C=N); 1179, 1149 (CF). H NMR spectrum
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004

VASIL’EVA et al.
878
(CDCl3), δ, ppm: 1.16–1.24 m, 1.66–1.75 m, 3.11–
3.16 m (10H, C5H10N); 2.75 s (3H, CH3). Found, %:
C 40.48; H 4.83; F 21.31; N 20.96. C9H13F3N4S.
Calculated, %: C 40.60; H 4.92; F 21.40; N 21.04.
(1H, NH), 10.6 br.s (1H, NH). Found, %: C 33.75;
H 1.84; N 13.39; S 7.26. C12H8F10N4S. Calculated, %:
C 33.50; H 1.87; N 13.02; S 7.45.
REFERENCES
4-(4-Fluorophenyl)-1-(2,2,3,3,4,4,5,5-octafluoro-
pentanoyl)thiosemicarbazide (V). Yield 57%, color-
less crystals, mp 108–109°C (from hexane–toluene,
4 :1). IR spectrum, ν, cm–1: 1690 (CONH), 3250
1. Silberg, A. and Cosma, N., Acad. Rep. Populare Romine,
Filiala Cluj, Studii cercetari chim., 1959, vol. 10, p. 151;
Chem. Abstr., 1960, vol. 54, no. 8794f.
1
(N–H). H NMR spectrum (acetone-d6), δ, ppm:
2
3
2. Mndzhoyan, A.L., Afrikyan, V.G., and Dokhikyan, A.A.,
6.78 t.t [1H, (CF2)4H, JHF = 51.2, JHF = 5.6 Hz],
7.04–7.59 m (4H, C6H4), 9.25 s (1H, NH), 9.52 s
(1H, NH), 10.6 br.s (1H, NH). Found, %: C 35.11;
H 2.06; N 10.15. C12H8F9N3OS. Calculated, %:
C 34.88; H 1.95; N 10.17.
Izv. Akad. Nauk Arm. SSR, 1957, vol. 10, p. 357.
3. Pesson, M., Polmanns, G., and Dupin, S., C. R. Acad.
Sci., 1959, vol. 248, p. 1677.
4. Kobayashi, E., Kumagane, I., and Taguti, T., Novoe v
tekhnologii soedinenii ftora (New Technologies in
Fluorine Chemistry), Ishikawa, N., Ed., Moscow: Mir,
1984, p. 500.
1-(1-Amino-2,2,3,3,4,4,5,5-octafluoropentyli-
dene)-4-(3,4-difluorophenyl)thiosemicarbazide
(VII). 2,2,3,3,4,4,5,5-Octafluoropentanenitrile (VI),
1.2 g (5.3 mmol), was added to a solution of 0.25 g
(1.2 mmol) of thiosemicarbazide Ic in 15 ml of anhy-
drous methanol, and the mixture was left to stand for
48 h. The solvent was distilled off, and the residue was
recrystallized from heptane. Yield 0.17 g (33%), color-
less crystals, mp 104–105°C. IR spectrum, ν, cm–1:
5. Vershilov, S.V., Popova, L.M., Mungalov, V.E., and Rya-
binin, N.A., Zh. Prikl. Khim., 1994, vol. 67, p. 1124.
6. Kondo, K., Kono, H., Simmons, K.K., Dixson, J.A.,
Halling, B.P., Plummer, E.L., Plummer, M.J., and
Tymonko, J.M., US Patent no. 5108486; Chem. Abstr.,
1992, vol. 117, p. 331.
7. Krolevets, A.A., Itogi Nauki Tekh., Ser. Org. Khim., 1985,
3318, 3355, 3430 (NH). 1H NMR spectrum (CDCl3), δ,
vol. 6, p. 36.
2
ppm: 5.89 s (2H, NH2), 6.05 t.t [1H, (CF2)4H, JHF
=
8. Kazakov, V.Ya. and Postovskii, I.Ya., Dokl. Akad. Nauk
SSSR, 1960, vol. 134, p. 824.
3
52.1, JHF = 5.40 Hz], 7.11–7.66 m (3H, C6H3), 9.10 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004