Synthesis of new perfluoroalkylated 1,3,4-oxadiazoles and 1,2,4-triazoles starting from 2-(perfluoroalkyl)ethane thiols

Article abstract of DOI:10.1080/00397911.2010.494816

5-f[2-(Perfluoroalkyl)ethylthio]methylg-1,3,4-oxadiazole-2-thiones 4a, b and 4-amino-5-f[2-(perfluoroalkyl)ethylthio]methylg-4H-1,2,4-triazole-3-thiones 5a, b have been prepared from 2-(perfluoroalkyl)ethane thiols 1a, b through a multistep reaction seque

Full text of DOI:10.1080/00397911.2010.494816

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Synthesis of New Perfluoroalkylated
1,3,4-Oxadiazoles and 1,2,4-Triazoles
Starting from 2-(Perfluoroalkyl)ethane
Thiols
Ali Akremi a , Mohamed Beji a & Ahmed Baklouti a
a Faculty of Sciences of Tunis, Department of Chemistry, Laboratory
of Structural Organic Chemistry, El Manar, Tunis, Tunisia
Version of record first published: 02 May 2011.
To cite this article: Ali Akremi, Mohamed Beji & Ahmed Baklouti (2011): Synthesis of New
Perfluoroalkylated 1,3,4-Oxadiazoles and 1,2,4-Triazoles Starting from 2-(Perfluoroalkyl)ethane
Thiols, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 41:13, 1990-1998
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Synthetic Communications1, 41: 1990–1998, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.494816
SYNTHESIS OF NEW PERFLUOROALKYLATED
1,3,4-OXADIAZOLES AND 1,2,4-TRIAZOLES STARTING
FROM 2-(PERFLUOROALKYL)ETHANE THIOLS
Ali Akremi, Mohamed Beji, and Ahmed Baklouti
Faculty of Sciences of Tunis, Department of Chemistry, Laboratory of
Structural Organic Chemistry, El Manar, Tunis, Tunisia
GRAPHICAL ABSTRACT
Abstract 5-f[2-(Perfluoroalkyl)ethylthio]methylg-1,3,4-oxadiazole-2-thiones 4a, b and
4-amino-5-f[2-(perfluoroalkyl)ethylthio]methylg-4H-1,2,4-triazole-3-thiones 5a, b have
been prepared from 2-(perfluoroalkyl)ethane thiols 1a, b through a multistep reaction
sequence. Compounds 4a, b were further reacted with aryloxysulfonylisocyanates to
give the corresponding 5-f[2-(perfluoroalkyl)ethylthio]methylg-N-(aryloxysulfonyl)-2-
thioxo-1,3,4-oxadiazole-3(2H)-carboxamide 6a–d. The new products were obtained in
good to moderate yields, and their structures were established on the basis of their infrared,
NMR, and mass spectral data.
Keywords Aryloxysulfonylisocyanates; carbon disulfide; 1,3,4-oxadiazole; 2-(perfluor-
oalkyl)ethane thiols; 1,2,4-triazole
INTRODUCTION
Heterocycles containing a 1,2,4-triazole or 1,3,4-oxadiazole moiety constitute a
class of compounds that possess a wide spectrum of biological activities such as
anti-inflammatory, antiviral, antimicrobial, and antitumoral properties.[1–4] For
instance, some azole derivatives were developed as new antimicrobial agents,
such as linezolid and eperezolid, which are currently used for the treatment of
multidrug-resistant Gram-positive infections.[5–7] It was also shown that derivatiza-
tion of the carboxylate function of representative nonsteroidal anti-inflammatory
Received February 28, 2010.
Address correspondence to Ali Akremi, Faculty of Sciences of Tunis, Department of Chemistry,
Campus Universitaire, 2092 EI Manar, Tunis, Tunisia. E-mail: akrimimi@yahoo.fr
1990

PERFLUOROALKYL 1,3,4-OXADIAZOLES AND 1,2,4-TRIAZOLES
1991
drugs with less acidic azoles (viz., 1,3,4-oxadiazole, 1,2,4-triazole, etc.) resulted in an
increased anti-inflammatory activity with reduced ulcerogenicity.[8–10] 1,3,4-
Oxadiazole-containing molecules have also interesting optical properties. They have
been recently incorporated into polymers and small molecules in new optoelectronic
materials to increase external quantum efficiencies and overall device performance.[11]
On the other hand, fluorinated heterocycles are widely used in pharma-
ceuticals, agrochemicals, and new materials, and their synthesis constitutes an
increasingly valuable research area.[12–15]
Recently, we have reported the synthesis of perfluoroalkyl tertazol-5-ones[16] and
dioxalanones[17] starting from fluorinated azides and a-hydroxy acids, respectively.
Following our interest in the study of fluorine-containing compounds, we report
herein the synthesis of hybrid compounds that contain both a perfluoroalkyl group
and oxadiazole or triazole ring systems. These perfluoroalkylated oxadiazoles and tria-
zoles have been characterized by NMR, infrared (IR) and mass (MS) spectroscsopic
techniques. As for some other oxadiazole- and triazole-containing compounds, the
new fluorinated heterocycles may have important anti-inflammatory properties and
would show the effect of such hybridization on the anticipated biological properties.
RESULTS AND DISCUSSION
2-(Perfluoroalkyl)ethane thiols 1 were easily converted into 2-(perfluoroalkyl)
ethylthioacetates 2 in the presence of triethylamine and ethyl bromoacetate in
anhydrous acetone. The reaction of hydrazine hydrate with acetates 2 in refluxing
methanol afforded 2-(perfluoroalkyl)ethylthioacetohydrazide 3 in good yields
(Scheme 1). In the IR spectra of compounds 3, broad stretching bands at 3211
and 3328 cmꢀ1 were due to amine =amide, NH whereas a strong stretching band at
1
ꢁ1660 cmꢀ1 was attributed to amide carbonyl. H NMR spectra showed singlets at
ꢁ4.11 and 9.10 ppm, which were assigned to NH2 and NH groups.
Hydrazides 3 react with carbon disulfide in the presence of potassium hydrox-
ide to give the intermediate potassium dithiocarbazate salts, which on refluxing in
ethanol yield 1,3,4-oxadiazoles 4, and their treatment with hydrazine hydrate led
to formation of the corresponding 1,2,4-triazoles 5 as shown in Scheme 2. The
new products 4 and 5 were characterized by their IR, NMR, and MS spectra. The
1
1
lack of H NMR resonances observed with NH and NH2 groups in the H NMR
spectra of 4 proved that ring closure starting from 3 resulted in the formation of
an 1,3,4-oxadiazole ring. This was further confirmed by the 13C NMR data of 4,
which showed peaks at ꢁ162 and 180 ppm due to C5 and C2 of oxadiazole. Mass
spectra of 4a and 4b displayed molecular ion base peaks at m=z 479 and 579,
Scheme 1. Synthetic pathway for the preparation of 2-(perfluoroalkyl) ethylthioacetohydrazides 3a, b.

1992
A. AKREMI, M. BEJI, AND A. BAKLOUTI
Scheme 2. Synthetic pathway for the preparation of oxadiazoles 4a, b and triazoles 5a, b.
Scheme 3. Synthetic pathway for the preparation of oxadiazoles 6a–d.
respectively, which confirmed their molecular weights. The IR spectra of 5 show
1
stretching bands at about 3320 and 3115 cmꢀ1 due to NH=NH2. H NMR spectra
of this sample displayed singlets at 13.57 and 5.50 ppm, assigned to NH and NH2,
respectively, which disappeared on D2O exchange. 13C NMR spectra of 5 showed
=
signals at 168 and 149 ppm due to C S and C5 carbons of the triazole ring. Mass
spectra of 5a and 5b displayed molecular ion base peaks at m=z 507 and 607, respect-
ively, which confirmed their molecular weights.
In continuation of our research work on the reactivity of isocyanates,[18–22]
1,3,4-oxadiazoles 6 were obtained via reaction of 1,3,4-oxadiazoles 4 with aryloxy-
sulfonylisocyanate in anhydrous acetone at room temperature (see Scheme 3). The
=
N-alkylation of oxadiazoles 4 was further confirmed by the presence of a C S
stretching vibration at 1560–1575 cmꢀ1 in the IR spectra of oxadiazoles 6, together
with absorption bands in the range 3220–3230 and 1690–1700 cmꢀ1 due to NH and
1
C O, respectively. Interestingly, the H NMR spectra of products 6 show the lack of
=
NH resonance of the starting oxadiazole and the appearance of a new broad signal at
9.50 ppm, assigned to amide proton. This is in good agreement with results obtained
for unfluorinated analogs.[23]
CONCLUSION
New fluorinated oxadiazoles and triazoles were prepared from the readily
available 2-(perfluoroalkyl)ethane thiols. These compounds could present versatile

PERFLUOROALKYL 1,3,4-OXADIAZOLES AND 1,2,4-TRIAZOLES
1993
intermediates for the preparation of various oxadiazole- and triazole-containing
heterocycles. The study related to the application of these new oxadiazoles and
triazoles in biological and industrial field is ongoing.
EXPERIMENTAL
IR spectra were obtained using a Perkin-Elmer Fourier transform (FT) Pra-
gon 1000 PC. 1H, 13C, and 19F NMR spectra were recorded on a Brucker AC
300 spectrometer at 300, 75, and 282 MHz, respectively. Chemical shifts were
reported in parts per million (ppm) from external C6F6 for 19F and internal
1
tetramethylsilane (TMS) for H and 13C. The mass spectra were recorded on a
Quattro microinstrument (micromass, UK Manchester; capillary voltage:
3.2 kV; cone voltage: 25 V; source temperature: 120 ꢂC; desolvation temperature:
400 ꢂC; desolvation gaz flow: 500 L=h; neublization: 7 psi) with negative electro-
spray ionization mode. Melting points were determined using an Electrothermal
IA 9000 series II instrument and are uncorrected. 2-(Perfluoroalkyl)ethane thiols
were supplied by AtoFina and used as received. The aryloxysulfonyisocyanates
were prepared from phenols and sulfonylisocyanate chloride as previously
described.[24,25]
Synthesis of 2-(Perfluoroalkyl)ethylthioacetates (2a, b)
To a solution of 2-(perfluorohexyl)ethane thiol 1a (3.8 g, 10 mmol) and triethy-
lamine (1.2 g, 12 mmol) in 10 ml of dry acetone was added ethyl bromoacetate (2.0 g,
12 mmol). The reaction mixture was stirred at room temperature for 10 min. The
filtrate was concentrated in vacuo and the residue was distilled under reduced
pressure.
Synthesis of 2-(Perfluoroalkyl)ethylthioacetohydrazides (3a, b)
A mixture of 2-(perfluorohexyl)ethylthioacetate 2a (4.52 g, 10 mmol) and
hydrazine hydrate (1.0 g, 20 mmol) in 10 ml of methanol was heated under reflux
for 5–6 h. The reaction mixture was left overnight at room temperature. The solid
separated was collected by filtration, washed with methanol, dried, and recrystallized
from benzene.
Synthesis of 5-f[2-(Perfluoroalkyl)ethylthio]methylg-
1,3,4-oxadiazole-2-thiones (4a, b)
2-(Perfluorooctyl)ethylthioacetohydrazide 3b (1.65 g, 3 mmol) was dissolved in
a solution of potassium hydroxide (0.34 g, 6 mmol) in water (2 ml) and ethanol
(20 ml). Carbon disulfide (2.51 g, 33 mmol) was then added while stirring, and the
reaction mixture was heated under reflux for 8 h. The solvents were removed under
reduced pressure; the residue was treated with water and then filtered. The filtrate
was cooled and neutralized to pH 6 using dilute hydrochloric acid, and the separated
solid was filtered, washed with water, dried, and recrystallized from carbon
tetrachloride.

1994
A. AKREMI, M. BEJI, AND A. BAKLOUTI
Synthesis of 4-Amino-5-f[2-(perfluoroalkyl)ethylthio]methylg-4H-
1,2,4-triazole-3-thiones (5a, b)
2-(Perfluorooctyl)ethylthioacetohydrazide 3b (1.65 g, 3 mmol) and carbon
disulfide (0.46 g, 6 mmol) were added to a solution of potassium hydroxide (0.37 g,
6.6 mmol) in absolute ethanol (30 ml), and the mixture was stirred at room tem-
perature for 16 h. Anhydrous ether was added to the resulting solution, and the
precipitated potassium dithiocarbazate salt was collected by filtration, washed with
ether, and dried under vacuum. This salt was obtained in quantitative yield and was
used in the next step without further purification.
A mixture of the potassium salt (4 g, 6 mmol), hydrazine hydrate (0.3 g,
6 mmol), and water (1 ml) was heated under reflux for 5 h. Hydrogen sulfide evolved,
the homogenous solution obtained was diluted with 50 ml water, and subsequent
acidification with dilute acetic acid gave a white precipitate, which was filtered,
washed with water, and recrystallized from hexane.
Synthesis of 5-f[2-(Perfluoroalkyl)ethylthio]methylg-N-
(aryloxysulfonyl)-2-thioxo-1,3,4-oxadiazole-3(2H)-carboxamides
(6a–c)
2,4,6-Trimethylaryloxysulfonylisocyanate (0.24 g, 1 mmol) was added to a
solution of 5-f[2-(perfluorohexyl)ethylthio]methylg-1,3,4-oxadiazole-2-thione 4a
(0.49 g, 1 mmol) in dry acetone (10 ml) while stirring. The reaction mixture was stir-
red at room temperature for 15 min, the solvent was evaporated, and the residue was
recrystallized from benzene.
Selected Data
Ethyl 2-(perfluorohexyl)ethylthioacetate (2a). Yield: 96%, colorless liquid,
ꢀ1
1
bp: 108–110 ꢂC = 15 mmHg. IR (CH3Cl, n, cm ): 1743 (C O). H NMR (CDCl3):
=
3
1.29 (t, 3H, CH3, JHH ¼ 7.20), 2.45 (m, 2H, CH2-CF2), 2.87 (t, 2H, CH2-S,
3JHH ¼ 6.93), 3.26 (s, 2H, CH2-CO), 4.22 (q, CH2-O, JHH ¼ 7.20). 13C NMR
3
2
(CDCl3): 14.1 (s, CH3-CH2-), 23.3 (s, CH2-CH2-S), 31.6 (t, CH2-CH2-S, JCF
¼
21.38), 33.7 (s, S-CH2-CO), 61.8 (s, O-CH2-CH3), 104–122 (m, C6F13), 170.1 (s,
CO). 19F NMR (CDCl3): 35.33 (m, 2 F, CF2a), 38.16 (m, 2 F, CF2b), 38.68 (m,
2 F, CF2c), 39.80 (m, 2 F, CF2d), 48.72–48.19 (m, 2 F, CF2x), 80.56 (m, 3 F, CF3).
Ethyl 2-(perfluorooctyl)ethylthioacetaꢀte1 (2b). Yield: 94%, colorless liquid,
1
bp: 165–167 ꢂC = 15 mmHg. IR (CH3Cl, n, cm ): 1749 (C O). H NMR (CDCl3):
=
3
1.26 (t, 3H, CH3, JHH ¼ 7.21), 2.47 (m, 2H, CH2-CF2), 2.88 (t, 2H, CH2-S,
3JHH ¼ 6.92), 3.25 (s, 2H, CH2-CO), 4.21 (q, 2H, CH2-O, JHH ¼ 7.21). 13C NMR
3
(CDCl3): 13.9 (s, CH3-CH2-O), 23.1 (s, CH2-CH2-S), 31.5 (t, CH2-CH2-S,
2JCF ¼ 21.40), 33.8 (s, S-CH2-CO), 61.9 (s, O-CH2-CH3), 105–122 (m, C8F17),
169.8 (s, CO). 19F NMR (CDCl3): 35.32 (m, 2 F, CF2a), 35.43 (m, 2 F, CF2b),
38.21 (m, 2 F, CF2c), 38.69 (m, 2 F, CF2d), 38.85 (m, 2 F, CF2x), 38.95 (m, 4 F,
2CF2E), 80.56 (m, 3 F, CF3).

PERFLUOROALKYL 1,3,4-OXADIAZOLES AND 1,2,4-TRIAZOLES
1995
2-(Perfluorohexyl)ethylthioacetohydrazide (3a). Yield: 90%, white solid,
ꢀ1
1
mp: 58 ꢂC. IR (KBr, n, cm ): 3328 (NH), 3211 (NH2), 1660 (C O). H NMR
=
3
(acetone-d6): 2.44 (m, 2H, CH2-CF2), 2.89 (t, 2H, CH2-S, JHH ¼ 6.89), 3.28 (s,
2H, CH2-CO), 4.11 (br, 2H, NH2), 9.10 (br, 1H, NH-CO). 13C NMR (acetone-d6):
23.7 (s, CH2-CH2-S), 31.2 (t, CH2-CH2-S,2JCF ¼ 21.45), 34.1 (s, S-CH2-CO), 105–122
(m, C6F13), 173.8 (s, CO). 19F NMR (acetone-d6): 35.35 (m, 2 F, CF2a), 38.14 (m,
2 F, CF2b), 38.65 (m, 2 F, CF2c), 39.82 (m, 2 F, CF2d), 48.70–48.17 (m, 2 F, CF2x),
80.57 (m, 3 F, CF3). MS: m=z ¼ 451 (M ꢀ H)ꢀ.
2-(Perfluorooctyl)ethylthioacetohydrazide (3b). Yield: 93%, white solid,
ꢀ1
1
mp: 111 ꢂC. IR (KBr, n, cm ): 3327 (NH), 3210 (NH2), 1663 (C O). H NMR
=
3
(acetone-d6): 2.52 (m, 2H, CH2-CF2), 2.91 (t, 2H, CH2-S, JHH ¼ 6.90), 3.24 (s,
2H, CH2-CO), 4.09 (br, 2H, NH2), 9.11 (br, 1H, NH-CO). 13C NMR (acetone-d6):
24.6 (s, CH2-CH2-S), 30.6 (t, CH2-CH2-S,2JCF ¼ 21.43), 32.9 (s, S-CH2-CO), 105–122
(m, C8F17), 172.9 (s, CO). 19F NMR (acetone-d6): 35.33 (m, 2 F, CF2a), 35.45 (m,
2 F, CF2b), 38.24 (m, 2 F, CF2c), 38.71 (m, 2 F, CF2d), 38.88 (m, 2 F, CF2x), 38.96
(m, 4 F, 2CF2E), 80.58 (m, 3 F, CF3). MS: m=z ¼ 551 (M ꢀ H)ꢀ.
5-f[2-(Perfluorohexyl)ethylthio]methylg-1,3,ꢀ41-oxadiazole-2-thione (4a).
Yield: 54%, white solid, mp: 93 ꢂC. IR (KBr, n, cm ): 3347 (NH), 1629 (C N),
=
1567 (C S), and 1123 (¼ C-O-C ¼). 1H NMR (DMSO-d6): 2.49 (m, 2H, CH2-
=
3
CF2), 2.82 (t, 2H, CH2-CH2-S, JHH ¼ 6.92), 3.85 [s, 2H, CH2-C(O)(N)], 14.4 (br,
NH). 13C NMR (DMSO-d6): 22.1 (s, CH2-CH2-S), 24.3 [s, CH2-C(O) ¼ N], 30.4
2
(t, CH2-CH2-S, JCF ¼ 21.63), 107–122 (m, C6F13), 161.8 [s, CH2-C(O) ¼ N], 177.9
(s, C S). 19F NMR (DMSO-d6): 35.33 (m, 2 F, CF2a), 38.16 (m, 2 F, CF2b), 38.64
=
(m, 2 F, CF2c), 39.83 (m, 2 F, CF2d), 48.71–48.19 (m, 2 F, CF2x), 80.54 (m, 3 F,
CF3). MS: m=z ¼ 479 (M ꢀ H)ꢀ, MS2(m=z¼479): m=z ¼ 147 (M-H-CH2 ¼ CH-C6F13)ꢀ
AR ¼ 100%.
5-f[2-(Perfluorooctyl)ethylthio]methylg-1,3,4-oxadiazole-2-thione (4b).
ꢀ1
Yield: 61%, white solid, mp: 110 ꢂC. IR (KBr, n, cm ): 3345 (NH), 1622 (C N),
=
1565 (C S) and 1128 (¼ C-O-C ¼). 1H NMR (DMSO-d6): 2.51 (m, 2H, CH2-
=
3
CF2), 2.85 (t, 2H, CH2-CH2-S, JHH ¼ 6.93), 3.86 [s, 2H, CH2-C(O)(N)], 14.5 (br,
NH). 13C NMR (DMSO-d6): 23.4 (s, CH2-CH2-S), 25.8 [s, CH2-C(O) ¼ N], 32.3
2
(t, CH2-CH2-S, JCF ¼ 21.65), 108–122 (m, C8F17), 162.2 [s, CH2-C(O) ¼ N], 179.8
(s, C S). 19F NMR (DMSO-d6): 35.34 (m, 2 F, CF2a), 35.46 (m, 2 F, CF2b), 38.28
=
(m, 2 F, CF2c), 38.71 (m, 2 F, CF2d), 38.88 (m, 2 F, CF2x), 38.90 (m, 4 F, 2CF2E),
80.56 (m, 3 F, CF3). MS: m=z ¼ 579 (M ꢀ H)ꢀ, MS2(m=z¼579): m=z ¼ 147 (M-H-
CH2 ¼ CH-C8F17)ꢀ AR ¼ 100%.
4-Amino-5-f[2-(perfluorohexyl)ethylthio]methylg-4H-1,2,4-triazole-3-
thione (5a). Yield: 49%, white solid, mp: 90 ꢂC. IR (KBr, n, cmꢀ1): 3320 (NH),
1
3115 (NH2), 1570 (C S), and 1621 (C N). H NMR (DMSO-d6): 2.63 (m, 2H,
=
=
3
CH2-CF2), 2.98 (t, 2H, CH2-CH2-S, JHH ¼ 6.92), 3.38 [s, 2H, CH2-C(N)(N)], 5.50
(br, NH2), 13.57 (br, NH). 13C NMR (DMSO-d6): 24.4 (s, CH2-CH2-S), 32.5 (t,
2
CH2-CH2-S, JCF ¼ 21.55), 33.7 (s, CH2-C(N) ¼ N), 111–122 (m, C6F13), 149.0 [s,
CH2-C(N) ¼ N], 167.8 (s, C S). 19F NMR (DMSO-d6): 35.36 (m, 2 F, CF2a),
=
38.14 (m, 2 F, CF2b), 38.66 (m, 2 F, CF2c), 39.88 (m, 2 F, CF2d), 48.67–48.15

1996
A. AKREMI, M. BEJI, AND A. BAKLOUTI
(m, 2 F, CF2x), 80.55 (m, 3 F, CF3). MS: m=z ¼ 507 (M ꢀ H)ꢀ, MS2(m=z¼507)
m=z ¼ 161 (M-H-CH2 ¼ CH-C6F13)ꢀ AR ¼ 100%.
:
4-Amino-5-f[2-(perfluorooctyl)ethylthio]methylg-4H-1,2,4-triazole-3-
thione (5b). Yield: 57%, white solid, mp: 113 ꢁC. IR (KBr, n, cmꢀ1): 3219 (NH),
1
3113 (NH2), 1571 (C S) and 1623 (C N). H NMR (DMSO-d6): 2.61 (m, 2H,
=
=
3
CH2-CF2), 2.97 (t, 2H, CH2-CH2-S, JHH ¼ 6.91), 3.36 [s, 2H, CH2-C(N)(N)], 5.52
(br, NH2), 13.58 (br, NH). 13C NMR (DMSO-d6): 24.5 (s, CH2-CH2-S), 32.6 (t,
2
CH2-CH2-S, JCF ¼ 21.54), 33.7 [s, CH2-C(N) ¼ N], 110–122 (m, C8F17), 149.1 [s,
CH2-C(N) ¼ N], 167.9 (s, C S). 19F NMR (DMSO-d6): 35.31 (m, 2 F, CF2a),
=
35.44 (m, 2 F, CF2b), 38.27 (m, 2 F, CF2c), 38.73 (m, 2 F, CF2d), 38.89 (m, 2 F,
CF2x), 38.92 (m, 4 F, 2CF2E), 80.52 (m, 3 F, CF3). MS: m=z ¼ 607 (M ꢀ H)ꢀ,
MS2(m=z¼607): m=z ¼ 161 (M-H-CH2 ¼ CH-C8F17)ꢀ AR ¼ 100%.
5-f[2-(Perfluorohexyl)ethylthio]methylg-N-(2,4,6-trimethylphenyloxy-
sulfonyl)-2-thioxo-1,3,4-oxadꢀia1zole-3(2H)-carboxamide (6a). Yield: 91%, white
solid, mp: 96 ꢁC. IR (KBr, n, cm ): 3221 (NH), 1698 (C O), 1563 (C S), 1399, 1174
(SO2 sym., asym. stretching), and 1123 (¼ C-O-C ¼). 1H NMR (DMSO-d6): 2.10 (s,
3H, CH3arom), 2.19 (s, 6H, 2CH3arom), 2.65 (m, 2H, CH2-CF2), 2.97 (t, 2H, CH2-
=
=
3
CH2-S, JHH ¼ 6.90), 3.36 (s, 2H, CH2-CH2-S-CH2), 6.94 (s, 2H, Harom), 9.21 (br,
1H, NH-CO). 13C NMR (DMSO-d6): 23.4 (s, CH2-CH2-S), 25.8 (s, S-CH2-CO)
2
32.6 (t, CH2-CH2-S, JCF ¼ 21.63), 107–122 (m, C6F13), 129–144 (Carom), 148.4 (s,
CO), 160.2 [s, CH2-C(O) ¼ N], 176.8 (s, C S). 19F NMR (DMSO-d6): 35.36 (m,
=
2 F, CF2a), 38.19 (m, 2 F, CF2b), 38.67 (m, 2 F, CF2c), 39.84 (m, 2 F, CF2d),
48.73–48.21 (m, 2 F, CF2x), 80.61 (m, 3 F, CF3). MS: m=z ¼ 762 (M-H þ CH3CN)ꢀ,
MS2(m=z¼762): m=z ¼ 197 [HS-CO-NH-SO3 þ CH3CN]ꢀ AR ¼ 100%.
5-f[2-(Perfluorohexyl)ethylthio]methylg-N-(2,4,6-trichlorophenyloxy-
sulfonyl)-2-thioxo-1,3,4-oxadiazole-3(ꢀ21H)-carboxamide (6b). Yield: 88%,
white solid, mp: 117 ꢁC. IR (KBr, n, cm ): 3229 (NH), 1691 (C O), 1575 (C S),
1409, 1178 (SO2 sym., asym. stretching), and 1125 (¼ C-O-C ¼). 1H NMR
=
=
3
(DMSO-d6): 2.63 (m, 2H, CH2-CF2), 2.91 (t, 2H, CH2-CH2-S, JHH ¼ 6.89), 3.35
(s, 2H, CH2-CH2-S-CH2), 7.49 (s, 2H, Harom), 9.50 (br, 1H, NH-CO). 13C NMR
(DMSO-d6): 24.4 (s, CH2-CH2-S), 27.1 (s, S-CH2-CO), 33.9 (t, CH2-CH2-S,
2JCF ¼ 21.64), 105–122 (m, C6F13), 125–149 (Carom), 149.8 (s, CO), 160.9 [s, CH2-
C(O) ¼ N], 177.0 (s, C S). 19F NMR (DMSO-d6): 35.38 (m, 2 F, CF2a), 38.22 (m,
=
2 F, CF2b), 38.68 (m, 2 F, CF2c), 39.85 (m, 2 F, CF2d), 48.75–48.22 (m, 2 F, CF2x),
80.63 (m, 3 F, CF3). MS: m=z ¼ 836 (M ꢀ H þ CH3CN)ꢀ, MS2(m=z¼836): m=z ¼ 197
[HS-CO-NH-SO3 þ CH3CN]ꢀ AR ¼ 100%.
5-f[2-(Perfluorooctyl)ethylthio]methylg-N-(2,4,6-trimethylphenyloxy-
sulfonyl)-2-thioxo-1,3,4-oxadiazole-3(2H)-carboxamide (6c). Yield: 89%, white
ꢀ1
solid, mp: 124 ꢁC. IR (KBr, n, cm ) 3220 (NH), 1697 (C O), 1561 (C S), 1400,
=
1
=
1175 (SO2 sym., asym. stretching), and 1121 (¼ C-O-C ¼). H NMR (DMSO-d6):
2.11 (s, 3H, CH3arom), 2.20 (s, 6H, 2CH3arom), 2.64 (m, 2H, CH2-CF2), 3.01 (t,
3
2H, CH2-CH2-S, JHH ¼ 6.91), 3.35 (s, 2H, CH2-CH2-S-CH2), 6.97 (s, 2H, Harom),
9.25 (br, 1H, NH-CO). 13C NMR (DMSO-d6): 23.3 (s, CH2-CH2-S), 25.7 (s,
S-CH2-CO) 32.5 (t, CH2-CH2-S, 2JCF ¼ 21.64), 105–122 (m, C8F17), 129–144 (Carom),
148.5 (s, CO), 159.9 [s, CH2-C(O) ¼ N], 178.1 (s, C S). 19F NMR (DMSO-d6): 35.32
=

PERFLUOROALKYL 1,3,4-OXADIAZOLES AND 1,2,4-TRIAZOLES
1997
(m, 2 F, CF2a), 35.44 (m, 2 F, CF2b), 38.25 (m, 2 F, CF2c), 38.68 (m, 2 F, CF2d), 38.86
(m, 2 F, CF2x), 38.89 (m, 4 F, 2CF2E), 80.55 (m, 3 F, CF3). MS: m=z ¼ 862 (M-H þ
CH3CN)ꢀ, MS2(m=z¼862): m=z ¼ 197 [HS-CO-NH-SO3 þCH3CN]ꢀ AR ¼ 100%.
5-f[2-(Perfluorooctyl)ethylthio]methylg-N-(2,4,6-trichlorophenyloxysul-
fonyl)-2-thioxo-1,3,4-oxadiazoleꢀ-31(2H)-carboxamide (6d). Yield: 84%, white
solid, mp: 101 ꢂC. IR (KBr, n, cm ): 3230 (NH), 1693 (C O), 1574 (C S), 1408,
=
=
1
1177 (SO2 sym., asym. stretching) and 1119 (¼ C-O-C¼). H NMR (DMSO-d6):
3
2.65 (m, 2H, CH2-CF2), 2.92 (t, 2H, CH2-CH2-S, JHH ¼ 6.92), 3.36 (s, 2H, CH2-
CH2-S-CH2), 7.48 (s, 2H, Harom), 9.54 (br, 1H, NH-CO). 13C NMR (DMSO-d6):
2
24.6 (s, CH2-CH2-S), 26.9 [s, CH2-C(O)¼N], 33.8 (t, CH2-CH2-S, JCF ¼ 21.63),
105–122 (m, C8F17), 125–149 (Carom), 149.9 (s, CO), 159.8 [s, CH2-C(O) ¼ N],
177.5 (s, C S). 19F NMR (DMSO-d6): 35.33 (m, 2 F, CF2a), 35.43 (m, 2 F, CF2b),
=
38.26 (m, 2 F, CF2c), 38.69 (m, 2 F, CF2d), 38.86 (m, 2 F, CF2x), 38.90 (m, 4 F,
2CF2E), 80.56 (m, 3 F, CF3). MS: m=z ¼ 936 (M-H þ CH3CN)ꢀ, MS2(m=z¼936)
:
m=z ¼ 197 [HS-CO-NH-SO3 þ CH3CN]ꢀ AR ¼ 100%.
ACKNOWLEDGMENTS
We are grateful to the Tunisian Ministry of High Education and Scientific
Research and Technology for financial support (LR99ES14) of this research and
to Dr. M. A. Sanhoury, MRSC of the Department of Chemistry, Faculty of Sciences
of Tunis, for technical assistance and helpful discussions.
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