TiO2-Nanoparticles Catalyzed Synthesis of New Trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles and Trifluoromethyl-1,2,4-oxadiazoles

Article abstract of DOI:10.1002/jhet.3207

Synthesis of a new series of trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles and trifluoromethyl-1,2,4-oxadiazoles have been described by utilizing the reactions between amidoximes and trifluoroacetimidoyl chlorides. Trifluoromethyl-4,5-dihydro-1,2,4-oxadia

Full text of DOI:10.1002/jhet.3207

Month 2018
TiO2-Nanoparticles Catalyzed Synthesis of New Trifluoromethyl-4,5-
dihydro-1,2,4-oxadiazoles and Trifluoromethyl-1,2,4-oxadiazoles
*
Ali Darehkordi,
Mahin Ramezani, and Fariba Rahmani
Department of Chemistry, Faculty of Science, Vali-e-Asr University of Rafsanjan, Rafsanjan 77176, Iran
*
E-mail: adarehkordi@yahoo.com; darehkordi@mail.vru.ac.ir
Received January 14, 2018
DOI 10.1002/jhet.3207
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
Synthesis of a new series of trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles and trifluoromethyl-1,2,4-
oxadiazoles have been described by utilizing the reactions between amidoximes and trifluoroacetimidoyl
chlorides. Trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles have been synthesized under mild conditions such
as Na2CO3, THF-H2O, and titanium dioxide nanoparticles as catalyst in good to excellent yields. Also,
trifluoromethyl-1,2,4-oxadiazoles have been synthesized directly from reaction of amidoximes and
trifluoroacetimidoyl chlorides in a one-pot manner in present of NaH, THF, and titanium dioxide nanoparti-
cle as catalyst.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
nanomaterials to support TiO2 has attracted much
attention because of their unique structural and electrical
properties [24].
Heterocycles containing nitrogen–oxygen atoms are very
important and attractive, because they form an important
class of natural and non-natural compounds and many of
them exhibit useful biological activities [1–4].
Oxadiazoles are the important class of heterocycles that
apply widely as drugs in pharmaceuticals [5]. Among
oxadiazoles, 1,2,4-oxadiazole derivatives have received
much attention in medicinal chemistry, for example,
prenoxdiazole, oxolamine, proxazole, and butalamine [6].
Compounds including 1,2,4-oxadiazole ring show an
extensive biological properties such as HIV integrase
inhibitors [7], antituberculostatic agents [8], and
antikinetoplastid agents [9], muscarinic agonists [10,11],
serotoninergic (5-HT3) antagonists [12], benzodiazepine
receptor agonists [13], and dopamine ligands [14].
In continuing our efforts toward the development of new
methods for the efficient synthesis of trifluoromethylated
organic compounds [25–28], in the present paper, the
reactions of trifluoroacetimidoyl chlorides and amidoximes
are reported. Aided by these compounds, we report a
high-yielding one-pot synthesis of trifluoromethyl-4,5-
dihydro-1,2,4-oxadiazoles
3 and trifluoromethyl-1,2,4-
oxadiazoles 4 by condensing trifluoroacetimidoyl chlorides
and amidoximes in a two different conditions.
Trifluoroacetimidoyl chlorides are active substrate in
nucleophilic reactions. Reaction of these compounds with
N,N-binucleophiles and N,O-binucleophiles results to
synthesis of important tifluoromethylated heterocycles
such as (trifluoromethyl)benzotriazole and (trifluoromethyl)
benzotriazine. Therefore, in these investigation, we were
interested to the synthesis of trifluoromethyl-4,5-dihydro-
1,2,4-oxadiazoles 3 from reaction of trifluoroacetimidoyl
chlorides and amidoximes in the presence of sodium
carbonate and titanium dioxide nanoparticles (TiO2-NPs)
as catalyst (Scheme 3).
In the recent years, compounds containing
trifluoromethyl group have gained
a
significant
importance due to the biological actives and using as new
materials. Today, these compounds are forehand in
developments in the pharmaceutical and agrochemical
industries [15–18].
Nowadays, metal oxide nanoparticles have drawn the
attention of scientists, because of their extensive
application in the development of new technologies in the
areas of electronics, material sciences, catalyst, and
medicine at the nanoscale [19–21]. As an efficient and
versatile catalyst, TiO2-nano-structured has been the
focus of considerable research interests in recent years.
Its small size and large specific surface area allow for
RESULTS AND DISCUSSION
The necessary amidoximes
1
were readily
synthesized according to a standard literature protocol
in one-pot way [29]. The reaction of carbonitrile with
aqueous hydroxylamine solution in ethanol under
reflux conditions provided the desired amidoximes 2
(Scheme 1).
certain
unique
and
unusual
physicochemical
properties [22,23]. In addition, the use of carbonaceous
© 2018 Wiley Periodicals, Inc.

A. Darehkordi, M. Ramezani, and F. Rahmani
Vol 000
Scheme 1. Synthesized of amidoximes.
Interestingly, during these studies, we found that
changing reaction conditions could result to synthesis of
3-(4-bromophenyl)-N-(2,5-difluorophenyl)-5-
(trifluoromethyl)-4,5-dihydro-1,2,4-oxadiazol-5-amine 3a,
which with elimination of aniline molecule afford 3-
phenyl-5-(trifluoromethyl)-1,2,4-oxadiazole 4a in good
yields so we could have different products depending on
the conditions (3a or 4a).
The optimum conditions without any catalyst were
obtained with 0.5 mmol of amidoxime (1) and 1 mmol of
trifluoroacetimidoyl chloride (2) in THF-H2O in the
presence of Na2CO3 as the base at room temperature for
20 min (entry 8 in Table 1). Alternatively, we also found
that the yield and time could be substantially improved
when the reaction was carried out in TiO2-NPs as catalyst
(entry 9 in Table 1). With the optimized conditions
The required trifluoroacetimidoyl chlorides 2 were
prepared by reaction mixture of a primary aromatic amine
and trifluoroacetic acid in carbon tetrachloride in the
presence of triethylamine and triphenylphosphine under
reflux conditions according to known literature reported
procedures [30,31], as depicted in Scheme 2.
We also expected that the reaction of amidoximes 1 and
trifluoroacetimidoyl chlorides 2 at the present of NaH,
THF, and TiO2-NPs could lead to the formation of
trifluoromethyl-1,2,4-oxadiazoles 3, but when the reaction
was carried out in these conditions (NaH as base, THF
solvent and TiO2-NPs catalyst), no appreciable amounts
established,
1,2,4-oxadiazol-5-amine
various
(trifluoromethyl)-4,5-dihydro-
(3a–d) prepared from
amidoximes 1a–d with Na2CO3 were subjected to the
reaction with trifluoroacetimidoyl chloride under mild
conditions in order to explore the scope and generality of
the reaction (Table 2). Changing the conditions (solvent
and base) CH3CN in THF instead of Na2CO3 in
THF-H2O resulted to synthesis of trifluoromethyl-
1,2,4-oxadiazoles 4a (entry 14 in Table 1) in good yields.
After the optimal reaction, conditions were established,
we continued to explore the generality of the protocol.
The outcomes were listed in Table 2.
As mentioned in Table 2, when we used NaH as the base
in THF at room temperature in the presence of TiO2-NPs
as the catalyst after 1 h, it resulted to 4a–e products, and
when we applied Na2CO3 as the base in THF-H2O at
room temperature in the presence of TiO2-NPs, catalyst at
5 min produced 3a–d products. Using TiO2-NPs in both
conditions decreased the reaction time with the higher
yield.
of
3
were obtained, only trifluoromethyl-1,2,4-
oxadiazoles 4 were detected (Scheme 3).
Subsequently, in order to obtain optimum conditions, we
investigated the reaction of amidoximes 1a and 1b with
trifluoroacetimidoyl chlorides 2a and 2b. The results are
given in Table 1. Unfortunately, the reaction of
amidoximes 1a with trifluoroacetimidoyl chloride 2a did
not produce the expected 3a or 4a, and from these
reaction, hydrolyzed product 5a was isolated (Scheme 4
and Table 1) [32–34]. In fact, compared with previous
our works [25–28], trifluoroacetimidoyl chloride could be
converted to hydrolyzed product at some condition as
main or by products.
The reaction is suggested to be proceeding via the initial
activation of imidoyl by TiO2-NPs to produce of TiO2-
imidoyl complex. Then, this activated complex is
attacked by the nucleophilic amidoxime to replace the
chlorine atom by oxygen. Subsequent attack of the –NH
anion on the imino group generates the cyclic
intermediate 3-(4-aryl)-N-(aryl)-5-(trifluoromethyl)-4,5-
Scheme 2. Synthesized of trifluoroacetimidoyl chlorides.
dihydro-1,2,4-oxadiazol-5-amine
3,
which
with
eliminating of aryl amine result to 3-(4-aryl)-5-
(trifluoromethyl)-1,2,4-oxadiazole 4 (Scheme 5).
Scheme 3. Synthesis of trifluoromethyl-1,2,4-oxadiazoles types.
CONCLUSION
In summary, we have presented a new protocol for the
synthesis of trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles
and trifluoromethyl-1,2,4-oxadiazoles using TiO2-NPs as
a catalyst. The product produced from reaction of
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Synthesis of New Trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles and
Trifluoromethyl-1,2,4-oxadiazoles
Table 1
Screening optimal conditions.
Entry
1
R1/ mmol
R2/ mmol
2,5 di F/ 1
Base
Cat (%mol)
-
Solvent
CH3CN
Conditions
r.t, 4 h
Yield (%)
0
K2CO3
2
3
4
2,5 di F/ 1
2,5 di F/ 1
2,5 di F/ 1
K2CO3
K2CO3
Na2CO3
-
-
-
CH3CN
THF
Reflux,1 h
r.t, 2 h
0
0
0
THF-DMF
50, 1 h
5
6
2,5 di F/ 1
2,5 di F/ 1
Et3N
Et3N
-
-
toluene
toluene
r.t, 5 h
0
r.t, 18 h
3a (25)
7
8
9
2,5 di F/ 1
2,5 di F/ 1
2,5 di F/ 1
Et3N
-
THF
r.t, 18 h
3a (32)
3a (67)
3a (88)
Na2CO3
Na2CO3
-
THF-H2O
THF- H2O
r.t, 20 min
r.t, 5 min
TiO2(5)
10
11
2,5 di F/ 1
3-CF3 /1
Na2CO3
NaH
TiO2(10)
-
THF-H2O
THF
r.t, 5 min
r.t, 8 h
3a (88)
4a (20)
12
3-CF3 /1
NaH
-
THF
r.t, 8 h
4a (43)
13
14
3-CF3 /1
3-CF3 /1
NaH
NaH
TiO2(5)
TiO2(5)
THF
r.t, 1 h
r.t, 1 h
4a (78)
4a (80)
CH3CN
-, The reaction proceeded in the absence of any catalyst.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Darehkordi, M. Ramezani, and F. Rahmani
Vol 000
Scheme 4. Conditions reaction for Hydrolyze 1b.
amidoximes with trifluoroacetimidoyl chlorides at the
room temperature and in the present TiO2-NPs depend
on solvent and base used. When this reaction was
carried out with Na2CO3 as the base and THF-H2O
as solvent, trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles
was synthesized in good yields, and when the reaction
occurred in THF using NaH base, resulted to
trifluoromethyl-1,2,4-oxadiazoles. In conclusion, the
chemistry developed here is very versatile and
accommodates various functional groups. Also, the
synthesized heterocycles are of potential utility as new
pharmacophores and scaffolds for drug discovery.
disappearance of substrate). After that time, the reaction
was diluted with H2O and extracted with EtOAc (3×).
The organic layer was dried (MgSO4) and residual
solvent was removed by evaporation to give the products.
3-(4-Bromophenyl)-N-(2,5-difluorophenyl)-5-
(trifluoromethyl)-4,5-dihydro-1,2,4-oxadiazol-5-amine (3a).
White solid; 92% yield, m.p. 93–95°C. IR (KBr, cmÀ1):
3464, 3354, 1711. 1H NMR (400 MHz, DMSO-d6):
δ = 8.02 (d, J = 8.4 Hz, NH), 7.85 (d, J = 8.3 Hz, 2H),
7.53 (d, J = 8.3 Hz, 2H), 7.19 (m, NH and 1H), 7.01
(ddd, J = 9.5, 6.5, 3.2 Hz, 1H), 6.90 (ddd, J = 12.1, 8.5,
3.4 Hz, 1H). 13C NMR (100 MHz, DMSO-d6):
δ = 157.54 (d, J = 253.6 Hz, C–F), 147.88 (d,
J = 253.7 Hz, C–F), 147.14, 132.66, 131.17 (2C),
129.28, 128.30 (2C), 124.96 (q, J = 266.0 Hz, C–CF3),
124.39, 115.90 (dd, J = 23.1, 9.4 Hz), 110.48 (dd,
J = 24.0, 7.5 Hz), 108.64 (dd, 25.8, 6.0 Hz), 103.24 (q,
J = 32.7 Hz, C–CF3). 19F NMR (376 MHz, DMSO-d6):
δ = À73.41 (s, 3F). Anal. Calcd. For C15H9BrF5N3O
(422.15): C, 42.68; H, 2.15; N, 9.95. Found: C, 42.33; H,
2.02; N, 9.74%.
EXPERIMENTAL SECTION
General information. Melting points were determined
using a Melt-Tem II melting point apparatus and are
uncorrected. IR spectra were recorded on Matson-1000
FT-IR spectrometer. All of the NMR spectra were
recorded on a Bruker model DRX-400 AVANCE (1H:
400, 13C: 100, F: 376 MHz) NMR spectrometer.
N-(2,5-difluorophenyl)-3-(4-fluorophenyl)-5-
(trifluoromethyl)-4,5-dihydro-1,2,4-oxadiazol-5-amine (3b).
1
Chemical shifts of H and 13C NMR are reported in parts
per million (ppm) downfield from an internal TMS
(trimethylsilane) reference in DMSO-d6 or CDCl3 as a
solvent and 19F NMR are reported in ppm from CFCl3 as
an internal standard in DMSO-d6 or CDCl3 as solvent.
Coupling constants (J) are reported in Hertz (Hz), and
spin multiplicities are presented by the following
symbols: s (singlet), br s (broad singlet), d (doublet), t
(triplet), q (quartet), m (multiplet). Element analyses
White solid; 90% yield, m.p. 84–86°C. IR (KBr, cmÀ1):
3503, 3362, 1732. 1H NMR (400 MHz, DMSO-d6):
δ = 8.10–8.12 (m, NH and 1H), 6.82–7.76 (m, NH and
4H), 6.49 (m, 1H), 6.24(m, 1H). 13C NMR (100 MHz,
DMSO-d6): δ = 163.33(d, J = 251.8 Hz, C–F), 159.03
(d, J = 251.8 Hz, C–F), 153.11 (d, J = 251.9 Hz, C–F),
149.98, 130.11, 128.85, 128.73, 126.32, 123.80 (q,
J = 268.1 Hz, C–CF3), 116.82 (dd, J = 20.0, 7.6 Hz),
115.36, 115.07, 110.38 (dd, J = 24.0, 7.5 Hz), 108.71
(dd, J = 20.0, 7.6 Hz), 102.45 (q, J = 26.7 Hz, C–CF3).
19F NMR (376 MHz, DMSO-d6): δ = À69.60 (s, 3F),
À109.62 (m, 1F), À118.98 (m, 1F), À130.78 (m, 1F).
Anal. Calcd. For C15H9F6N3O (361.25): C, 49.87; H,
2.51; N, 11.63. Found: C, 49.84; H, 2.46; N, 11.59%.
(CHN) were performed with
EuroEA3000 CHNSO analyzer.
a
EUROVECTOR
General procedure for the synthesis of compounds 3a–d.
To a stirred solution of the corresponding amidoxime 1a–f
(0.5 mmol), Na2CO3(0.6 mmol) and titanium dioxide (5%
mmol) as catalyst in THF, H2O 1:1 (5 mL) was added
mixture of acetimidoyl chloride 2a–e (1 mmol) in 5 ml
THF and the resulting solution was stirred for 5 min. The
mixture was stirred until substrate was consumed (the
progress of the reaction was monitored by TLC for
3-(2-Bromophenyl)-N-(2,5-difluorophenyl)-5-
(trifluoromethyl)-4,5-dihydro-1,2,4-oxadiazol-5-amine (3c).
Cream solid; 88% yield, m.p. 92–95°C. IR (KBr, cmÀ1):
3480, 3334, 1685. 1H NMR (400 MHz, DMSO-d6):
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Synthesis of New Trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles and
Trifluoromethyl-1,2,4-oxadiazoles
Table 2
One-pot synthesis of trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles and trifluoromethyl-1,2,4-oxadiazoles in the presence of TiO2-NPs.
Entry
1
R1
R2
Base/ solvent
NaH/THF
Products
Time
1 h
Yield (%)
88
2
3
Na2CO3/THF-H2O
Na2CO3/THF-H2O
5 min
5 min
92
90
4
5
Na2CO3/THF-H2O
5 min
88
90
NaH/THF
1 h
6
7
NaH/THF
NaH/THF
1 h
1 h
85
80
8
9
Na2CO3/THF-H2O
5 min
87
89
NaH/THF
1 h
Journal of Heterocyclic Chemistry
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A. Darehkordi, M. Ramezani, and F. Rahmani
Vol 000
Scheme 5. Proposed mechanism for synthesis of trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles and trifluoromethyl-1,2,4-oxadiazoles.
δ = 7.92 (m, NH and 1H), 7.69–7.55 (m, 3H), 6.97 (ddd,
J = 11.1, 8.9, 5.2 Hz, 1H), 6.52 (ddd, J = 10.5, 7.3,
3.1 Hz, 1H), 6.25 (tt, J = 8.6, 3.2 Hz, 1H). 13C NMR
159.74, 127.07 (2C), 123.93, 115.71 (q, J = 267.3 Hz,
C–CF3), 113.50(2C), 55.04. 19F NMR (376 MHz,
DMSO-d6): δ = À77.46 (s, 3F). Anal. Calcd. For
C10H7F3N2O2 (244.17): C, 49.19; H, 2.89; N, 11.47.
Found: C, 48.91; H, 2.88; N, 11.44%.
(100 MHz, DMSO-d6):
δ = 167.95, 158.76 (d,
J = 236.1 Hz), 146.85 (d, J = 230.8 Hz), 134.29, 133.54,
132.31 (2C), 128.32, 125.63, 125.19 (q, J = 268.7 Hz,
C–CF3), 121.25, 115.35 (dd, J = 20.9, 10.9 Hz), 105.40
(q, J = 26.2 Hz, C–CF3), 101.91 (dd, J = 27.2, 4.9 Hz),
100.85 (dd, J = 24.5, 7.1 Hz). 19F NMR (376 MHz,
DMSO-d6): δ = À73.45 (s, 3F). Anal. Calcd. For
C15H9BrF5N3O (422.15): C, 42.68; H, 2.15; N, 9.95.
Found: C, 42.21; H, 1.83; N, 9.54%.
3-(4-Fluorophenyl)-5-(trifluoromethyl)-1,2,4-oxadiazole
(4b). The product was purified by Plate Chromatography
(n-hexane/EtOAc, 4:1) to give product as cream solid; 90%
1
yield. m.p. 190°C dec. H NMR (400 MHz, DMSO- d6):
δ = 7.87–7.78 (m, 2H), 7.28–7.18 (m, 2H).13C NMR
(100 MHz, DMSO-d6): δ = 174.15 (q, J = 31.5 Hz,
C–CF3), 167.03, 163.01 (d, J = 245.2 Hz, C–F), 128.32,
128.24, 124.98, 115.71, 115.50, 116.33 (q, J = 286.3 Hz,
C–CF3). 19F NMR (376 MHz, DMSO-d6): δ = À73.58
(s, 3F), À112.72 (m, 1F). Anal. Calcd. For C9H4F4N2O
(232.14): C, 46.57; H, 1.74; N, 12.07. Found: C, 46.56;
H, 1.77; N, 12.12%.
3-(4-Chlorophenyl)-N-(2,4-dimethylphenyl)-5-
(trifluoromethyl)-4,5-dihydro-1,2,4-oxadiazol-5-amine (3d).
White solid; 87% yield, m.p. 124–130°C. 1H NMR
(400 MHz, CDCl3) δ = 7.75–7.53 (m, 4H), 6.93–6.86 (m,
2H), 6.80 (s, 1H, NH), 6.76 (dd, J = 7.8, 1.9 Hz, 1H),
2.32 (s, 3H, CH3), 2.24 (s, 3H, CH3). 13C NMR
(100 MHz, CDCl3) δ = 150.00, 141.09, 136.29, 133.21,
131.00, 130.88, 128.96 (2C), 128.44 (2C), 127.51,
124.68, 122.73 (q, J = 268.4 Hz, C–CF3), 120.86, 102.45
(q, J = 26.7 Hz, C–CF3), 20.84 (CH3), 17.62 (CH3). 19F
NMR (376 MHz, CDCl3): δ = À73.42 (s, 3F). Anal.
Calcd. For C17H15ClF3N3O (369.77): C, 55.22; H, 4.09;
N, 11.36. Found: C, 55.18; H, 3.96; N, 11.08%.
3-(4-Bromophenyl)-5-(trifluoromethyl)-1,2,4-oxadiazole
(4c). The product was purified by Plate Chromatography
(n-hexane/EtOAc, 3:1) to give product as yellow solid;
85% yield. m.p. 230–235°C. 1H NMR (400 MHz,
DMSO-d6): δ = 8.17 (d, J = 8.7 Hz, 2H), 7.44 (m, 2H).
13C NMR (100 MHz, DMSO-d6): δ = 143.13, 140.05 (q,
J = 32.2 Hz, C–CF3), 126.86, 125.33, 125.01(2C),
121.29(2C), 117.55 (q, J = 288.2 Hz, C–CF3).19F NMR
(376 MHz, DMSO-d6): δ = À73.47(s, 3F).
General procedure for the synthesis of compounds 4a–e.
To the stirred solution of the amidoximes 1a–f (0.5 mmol),
NaH (2 mmol) and titanium dioxide (5% mmol) as catalyst
in THF (10 ml) was added mixture of acetimidoyl
chlorides 2a–e (1 mmol) in 5 ml THF and the resulting
solution was stirred for 1 h. The mixture was stirred at
room temperature appropriate time and then filtered.
After removing the solvent under reduced pressure, the
crude product was purified by preparative thin-layer
chromatography on silica gel [eluent: n-hexane/EtOAC]
to give the products.
3-(4-Nitrophenyl)-5-(trifluoromethyl)-1,2,4-oxadiazole
(4d). The product was purified by Plate Chromatography
(n-hexane/EtOAc, 4:1) to give product as cream solid; 80%
yield. m.p. 56–60°C. IR (KBr, cmÀ1): 3103, 1607, 1544.
1H NMR (400 MHz, DMSO-d6): δ = 8.48–8.43 (m, 2H),
8.38–8.31 (m, 2H). 13C NMR (100 MHz, DMSO-d6):
δ = 177.00 (q, J = 32.3 Hz, C–CF3), 167.13, 149.70,
130.15 (2C), 128.88 (2C), 124.67, 115.63 (q,
J = 267.5 Hz, C–CF3). 19F NMR (376 MHz, DMSO-d6):
δ = À72.36 (s, 3F). Anal. Calcd. For C9H4F3N3O3
(259.14): C, 41.71; H, 1.56; N, 16.22. Found: C, 41.64;
H, 1.42; N, 16.66%.
3-(4-Methoxyphenyl)-5-(trifluoromethyl)-1,2,4-oxadiazole
(4a). The product was purified by Plate Chromatography
(n-hexane/EtOAc, 6:1) to give product as a yellow oil;
3-(4-Chlorophenyl)-5-(trifluoromethyl)-1,2,4-oxadiazole
(4e). The product was purified by Plate Chromatography
1
88%yeild. IR (neat, cmÀ1): 3020, 2959, 1718, 1678. H
NMR (400 MHz, DMSO-d6): δ = 7.75–7.66 (m, 2H),
7.06–6.79 (m, 2H), 3.77 (s, 3H). 13C NMR (100 MHz,
DMSO-d6): δ = 173.69 (q, J = 32.4 Hz, C–CF3), 167.04,
(n-hexane/EtOAc, 4:1) to give product as white solid; 89%
1
yield. m.p. 256–260°C. H NMR (400 MHz, DMSO-d6)
δ = 7.81–7.76 (m, 2H), 7.47–7.43 (m, 2H). 13C NMR
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Synthesis of New Trifluoromethyl-4,5-dihydro-1,2,4-oxadiazoles and
Trifluoromethyl-1,2,4-oxadiazoles
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(100 MHz, DMSO-d6) δ = 174.95 (q, J = 39.4 Hz, C–CF3),
173.30, 128.26 (2C), 127.35 (2C), 126.31, 116.13 (q,
J = 267.6 Hz, C–CF3). 19F NMR (376 MHz, DMSO-d6):
δ = À73.46 (s, 3F). Anal. Calcd. For C9H4ClF3N2O
(248.59): C, 43.48; H, 1.62; N, 11.27. Found: C, 43.38;
H, 1.80; N, 11.20%.
Acknowledgments. We gratefully acknowledge the Vail-e-Asr
University of Rafsanjan Faculty Research Grant for financial
support.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet