Synthesis, insecticidal evaluation of novel 1,3,4-thiadiazole chrysanthemamide derivatives formed by an EDCI/HOBt condensation

Article abstract of DOI:10.3184/174751911X13230201951890

A series of novel pesticides with two components derived from a 1,3,4-thiadiazole and chrysanthemic acid were synthesised via an EDCI/HOBt condensation. These 1,3,4-thiadiazole chrysanthemamides were identified by IR, ¹H NMR and elemental analyses. Their insecticidal activity was also evaluated.

Full text of DOI:10.3184/174751911X13230201951890

JOURNAL OF CHEMICAL RESEARCH 2011
RESEARCH PAPER 703
DECEMBER, 703–706
Synthesis, insecticidal evaluation of novel 1,3,4-thiadiazole chrysanthem-
amide derivatives formed by an EDCI/HOBt condensation
Peng Yu, Jun Hu, Tao-Yu Zhou, Peng Wang and Yan-Hua Xu*
College of Environment, Nanjing University ofTechnology/ Jiangsu Key Laboratory of Industrial Water-Conservation & Emission Reduction,
Nanjing 210009, P. R. China
A series of novel pesticides with two components derived from a 1,3,4-thiadiazole and chrysanthemic acid were
1
synthesised via an EDCI/HOBt condensation. These 1,3,4-thiadiazole chrysanthemamides were identified by IR, H
NMR and elemental analyses. Their insecticidal activity was also evaluated.
Keywords: 1,3,4-thiadiazole, chrysanthemamide, insecticidal activity
1,3,4-Thiadiazole derivatives have attracted considerable
attention because of their diverse biological activity. It has
been reported that many of these of these derivatives possess a
wide spectrum of insecticidal,1,2 herbicidal3 and antimicro-
bial4–8 activity. Because of their wide spectrum of biological
activity, they have been widely used in agricultural and health
pest control. L 12159 (Fig. 1), for example, was highly effec-
tive against mosquito larvae,10 Spodoptera eridania larvae,11
and Western Sprucebudworm.12 Cyhalothrin (Fig. 1) has been
reported to effectively control the major resistant strains of
the cattle tick (Boophilus microplus) and the buffalo fly
(Haematobia irritans exigua).13
1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydro-
chloride (EDCI) is a reactive reagent for activating carboxylic
acids in amide bond formation.14–16 Under these reaction
conditions, a number of side reactions can occur, including,
racemisation of the amino acid and rearrangement of the active
O-acylisourea adduct to the N-acyl urea and guanidine forma-
tion. Additives such as 1-hydoxybenzotriazole (HOBt) have
often been added in catalytic amounts to help reduce racemisa-
tion and also to increase the rate of reaction. After the reaction
the EDCI is converted into EDU (Scheme 3) which is easily
washed out by water.
cyhalothrin were combined by an amide linkage, and a series
of novel chrysanthemamide derivatives were synthesised via
EDCI/HOBt condensation. This gave a better synthetic route-
and enabled us to investigate new structures which might have
enhanced insecticidal activity.
Results and discussion
The compounds 8a–l were synthesised by the general route as
shown in Scheme 1. The 5-aryl-1,3,4-thiadiazol-2-yl-chrysan-
themamides (8a–l) were synthesised by treatment of the
reaction of 2-amino-5-aryl-1,3,4-thiadiazoles (7a–l) with
trifluorochrysanthemic acid via an EDCI/HOBt condensation
in DMF. Compounds 7a–l were synthesised by substituted
benzoic acids (6a–l) with thiosemicarbazide in the presence of
phosphorus oxychloride.
Compounds 6g–i were synthesised in four steps. The
carboxylic acids (1g–i) were reacted with SOCl2 to afford the
acyl chlorides (2g–i), and then 2g–i combined with benzene
via a Friedel–Crafts acylation to afford 3g–i. Reduction gave
4g–i. Substituted hypnones (5g–i) were produced by the reac-
tion of 4g–i and acetic anhydride. Compounds 5g–i reacted
with sodium hypobromite to give the substituted benzoic acids
(6g–i).
In order to develop new insecticidal agents of high potency,
we have previously synthesised a series of 1,3,4-thiadiazole
chrysanthemamide derivatives using catalysis by PDCP.17
However, PDCP is caustic and requires harsh reaction condi-
tions that are hazardous while EDC/HOBT is milder and more
safer.
Insecticidal activities
The preliminary insecticidal activity of compounds 8a–l
against Plutella xylostella, Aphis craccivora (Pea aphids)
and Tetranychus cinnabarinus were measured. All bioassays
were performed on representative test organisms reared in the
laboratory. The bioassay was repeated at 25 1 °C according
To solve the resistance problem, and to find new bioactive
compounds with low toxicity, the effective parts of L1215 and
Fig.1 Design strategy of the target compounds.
* Correspondent. E-mail: yhxu2008@163.com

704 JOURNAL OF CHEMICAL RESEARCH 2011
Scheme 1 General synthetic route for substituted benzoic acid 6g–i.
Scheme 2 General synthetic route for the target compounds 8a–l.
Elementer Vario EL III elementary analysis instrument. 1H NMR
to statistical requirements. All compounds were dissolved
in acetone and diluted with water containing Tween 80
(500 mg L−1) to obtain a serial concentrations of 400.0 mg L−1
for bioassays. The numbers of live and dead insects were
counted after 72 h. Each treatment was performed three times.
For comparative purposes, the commercial insecticide aver-
mectin was tested under the same conditions. The results are
listed in Table 2.
spectra were obtained in CDCl3 or DMSO-d6, and were recorded on a
Bruker DRX500 spectrometer and resonance were given in ppm (δ)
relative to TMS, and peak multiplicity is reported as s (singlet), d
(doublet), t (triplet), q (quartet), m (multiplet), or b (broad). IR spectra
in KBr were recorded on a Perkin-Elmer PE-683 IR spectrometer.
Preparation of 2; general procedure
SOCl2 (0.45mol) was added dropwise to carboxylic acids (1g–i)
(0.25 mol) were added in an ice bath. The reaction mixture was heated
to reflux and stirred for 2 h. After cooling, the remaining SOCl2 was
evaporated under reduced pressure to afford compound 2.
Experimental
Unless otherwise noted, all reagents and solvents were used as
received. Reactions were monitored by TLC with visualisation by UV
light. Melting points were recorded on an X-4 binocular microscope
melting point apparatus (Beijing Tech Instruments Co., Beijing,
China) and were corrected. Elemental analyses were performed on an
Preparation of 3; general procedure
To a mixture of benzene (0.28 mol) and aluminium trichloride
(0.11 mol) was added 2 (0.1 mol) dropwise in the ice bath. The reac-
tion mixture was heated to reflux and stirred for 3 h. After completion

JOURNAL OF CHEMICAL RESEARCH 2011 705
Table 1 Physical constants of products 7a–l
Compd
Ar
Recrystallisation solvent
Yield
/%
M.p.
/°C
M.p.(lit.)
/°C
7a
7b
7c
7d
7e
7f
7g
7h
7i
2-Chlorophenyl
3-Chlorophenyl
2-Nitrophenyl
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Acetone
Ethanol
Methanol
Ethanol
Ethanol
Ethanol
Acetone
73.2
78.4
76.2
75.9
70.5
82.1
68.9
65.2
72.3
82.5
74.6
79.3
180–181
223–224
239–240
248–250
216–218
185–186
141–142
191–194
187–191
171–173
222–224
228–230
182–184 18
226 19
232–234 20
3-Nitrophenyl
–
3,5-Dinitrophenyl
2,6-Difluorophenyl
4-Octylphenyl
212–214 21
–
–
4-Dodecylphenyl
4-Phenoxyphenyl
3,5-Dimethylphenyl
Pyridine-3-yl
–
–
7j
7k
7l
170–173 18
230–232 18
225 22
Pyridine-4-yl
Table 2 The insecticidal activities of the title compounds 8a–l
Preparation of 5-aryl-1,3,4-thiadiazol-2-amines 7a–l: general
procedure
Comp.
Concen-
tration
(ppm)
Insecticidal targeta
A mixture of substituted benzoic acid I (0.1 mol) and thiosemicarba-
zide (0.1 mol) was treated with POCl3 (0.3 mol) dropwise at 0–5 °C
and maintained at this temperature for 30 minutes. The reaction
mixture was heated until reflux and stirred for 4 h. After cooling,
50 mL water was added to the reaction mixture. The pH of the
reaction solution was adjusted to the range of 8–9 with the solution of
50% NaOH. The crude product precipitated, filtered, washed with
water, dried, and recrystallised from ethanol to afford compounds
7a–l as listed in Table 1.
5-(3-Nitrophenyl)-1,3,4-thiadiazol-2-amine (7d): IR (KBr) ν: 3420,
3108, 1623, 1506, 1342, 1270, 1131 cm−1. Anal. Calcd for C8H6N4O2S:
C, 43.24; H, 2.72; N, 25.21. Found: C, 43.19; H, 2.73; N, 25.13%.
5-(2,6-Difluorophenyl)-1,3,4-thiadiazol-2-amine (7f): IR (KBr) ν:
3279, 3109, 1633, 1513, 1312, 1275, 1181,Anal. Calcd for C8H5F2N3S:
C, 45.07; H, 2.36; N, 19.71. Found: C, 45.01; H, 2.42; N, 19.59%.
5-(4-Octylphenyl)-1,3,4-thiadiazol-2-amine (7g): IR (KBr) ν: 3269,
3101, 2921, 2850, 1620, 1510, 1265, 1135 cm-1. Anal. Calcd for
C16H23N3S: C, 66.39; H, 8.01; N, 14.52. Found: C, 66.49; H, 8.03; N,
14.72%.
5-(4-Dodecylphenyl)-1,3,4-thiadiazol-2-amine (7h): IR (KBr) ν:
3272, 3161, 2921, 2850, 1683, 1558, 1303, 1145. Anal. Calcd for
C20H31N3S: C, 69.52; H, 9.04; N, 12.16. Found: C, 69.63; H, 9.08; N,
12.26%.
5-(4-Phenoxyphenyl)-1,3,4-thiadiazol-2-amine (7i): IR (KBr) ν:
3265, 3101, 1620, 1558, 1265, 1134, 981 cm-1. Anal. Calcd for
C14H11N3OS: C, 62.43; H, 4.12; N, 15.60. Found: C, 63.21; H, 3.93;
N, 15.82%.
Plutella
Aphis
Tetranychus
xylostella craccivora cinnabarinus
(Pea aphids)
8a
400
400
400
400
400
400
400
400
400
400
400
400
400
–
–
+
+
–
–
8b
8c
–
+
–
8d
+
+
–
8e
–
+
+
8f
–
+
+
8g
–
–
–
8h
–
+
+
8i
–
–
+
8j
–
+
–
8k
–
–
–
8l
–
+
++
+++
Avermectins
+++
+++
a Activity is expressed in four categories: (–) < 50%, (+) 51 –70%,
(++) 71 –90%, (+++) > 90%.
of the reaction, the mixture was poured into ice water. The pH was
adjusted to 5–6 with concentrated hydrochloric acid. It was then
extracted with benzene (3×30 mL) and washed by 10% sodium bicar-
bonate and pure water until the pH reached 7. The benzene layer was
dried over anhydrous MgSO4 and distilled under reduced pressure to
afford yellow liquid 3.
Preparation of 1,3,4-thiadiazole chrysanthemamides 8a–l; general
procedure
Preparation of 4; general procedure
Hydrazine hydrate (0.38 mol) was added to a mixture of 3 (0.11 mol)
and diglycol at room temperature. The mixture was heated to reflux
and stirred for 2.5 h. Refluxing was continued for a further 4 h after
adding potassium hydroxide (25.5 g). At the end of the reaction, the
mixture was extracted, washed to neutral, dried and distilled under
reduced pressure to afford 4.
A solution of 7a–l (2.5 mmol) and trifluorochrysanthemic acid
(2.3 mmol) in DMF (40 mL) was treated with EDCI (2.5 mmol)
and HOBt (2.5 mmol). The mixture was stirred overnight at room
temperature, monitored by TLC. After the reaction was complete, the
mixture was poured into water. The crude precipitate was filtered and
washed with water to obtain the crude product. The crude products
were recrystallised from ethanol to give compounds 8a–l.
Preparation of 5; general procedure
3-(2-Chloro-3,3,3-trifluoroprop-1-en-1-yl)-N-(5-(2-chlorophenyl)-
1,3,4-thiadiazol-2-yl)-2,2-dimethylcyclopropanecarboxamide (8a):
Yield 85.2%; m.p. 201–203 °C. 1H NMR (500 MHz, CDCl3) δ (ppm):
1.37 (s, 6H, CH3), 2.29 (t, 1H, CH), 2.40 (d, 1H, CH), 7.11 (d, 1H,
C=CH), 7.38–8.16 (m, 4H, Ph), 12.68 (s, 1H, NH). IR (KBr) ν: 3244,
3157, 3080, 2958, 2898, 1681, 1652, 1560, 1299, 1276, 1134, 1118,
781cm−1. Anal. Calcd for C17H14Cl2F3N3OS: C, 46.80; H, 3.23; N,
9.63. Found: C, 46.78; H, 3.33; N, 9.62%.
3-(2-Chloro-3,3,3-trifluoroprop-1-en-1-yl)-N-(5-(3-chlorophenyl)-
1,3,4-thiadiazol-2-yl)-2,2-dimethylcyclopropanecarboxamide (8b):
Yield 83.1%; m.p. 209–211 °C. 1H NMR (500 MHz, CDCl3) δ (ppm):
1.35 (s, 6H, CH3), 2.28 (t, 1H, CH), 2.42 (d, 1H, CH), 7.10 (d, 1H,
C=CH), 7.42–7.97 (m, 4H, Ph), 12.79 (s, 1H, NH). IR (KBr) ν: 3251,
3161, 3080, 2960, 2866, 1683, 1652, 1568, 1303, 1272, 1145, 1116,
784 cm−1. Anal. Calcd for C17H14Cl2F3N3OS: C, 46.80; H, 3.23; N,
9.63. Found: C, 45.97; H, 3.27; N, 9.66%.
Acetic anhydride (0.04 mol) was added dropwise to a mixture of
4 (0.04 mol) and anhydrous CS2 (20 mL) was added at room tempera-
ture and the mixture was subsequently stirred at 50 °C. After comple-
tion of the reaction, the mixture was poured into ice water (100 mL)
and concentrated hydrochloric acid (20 mL) was added. It was then
extracted with benzene (3×30 mL) and washed by 10% sodium bicar-
bonate and pure water until the pH reached 7. The organic phase was
dried over anhydrous MgSO4 and distilled under reduced pressure to
afford yellow oily liquid 5.
Preparation of 6; general procedure
5 (0.04 mol) was added dropwise to a mixture of sodium hypobromite
(75 mL) and tetrahydrofuran (70 mL) was added at 0–5 °C. After 1 h
ice-bath reaction, the mixture was heated until reflux and stirred for
2 h. The mixture was separated and the aqueous phase was acidified
and filtered to obtain the crude product. The crude product was recrys-
tallised from toluene to give compound 6 (6g, m.p. 95–96 ºC, 6h, m.
p. 90–91 ºC (lit.23 93–95 ºC) and 6i, m.p. 167–169 ºC). Registry CAS
No.: 6g 3575-31-3, 6h 21021-55-6, 6i 2215-77-2.
3-(2-Chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethyl-N-(5-
(2-nitrophenyl)-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamide (8c):
Yield 79.1%; m.p. 235–237 °C. 1H NMR (500 MHz, CDCl3) δ (ppm):

706 JOURNAL OF CHEMICAL RESEARCH 2011
1.36 (s, 6H, CH3), 2.48 (t, 1H, CH), 2.62 (d, 1H, CH), 7.09 (d, 1H,
C=CH), 7.64–7.91 (m, 4H, Ph), 13.89 (s, 1H, NH). IR (KBr) ν: 3244,
3155, 3078, 2908, 2740, 1699, 1652, 1558, 1544, 1299, 1141, 1120,
771 cm−1. Anal. Calcd for C17H14ClF3N4O3S: C, 45.70; H, 3.16; N,
12.54. Found: C, 45.73; H, 3.12; N, 12.58%.
3-(2-Chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethyl-N-(5-
(3-nitrophenyl)-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamide (8d):
Yield 78.3%; m.p. 216–218 °C. 1H NMR (500 MHz, CDCl3) δ (ppm):
1.37 (s, 6H, CH3), 2.49 (t, 1H, CH), 2.63 (d, 1H, CH), 7.08 (d, 1H,
C=CH), 7.64–7.71 (m, 4H, Ph), 13.89 (s, 1H, NH). IR (KBr) ν: 3452,
3149, 3031, 2958, 2866, 1695, 1652, 1556, 1529, 1299, 1147, 1116,
727 cm−1. Anal. Calcd for C17H14ClF3N4O3S: C, 45.70; H, 3.16; N,
12.54. Found: C, 45.89; H, 3.22; N, 12.64%.
3-(2-Chloro-3,3,3-trifluoroprop-1-en-1-yl)-N-(5-(3,5-dinitrophenyl)-
1,3,4-thiadiazol-2-yl)-2,2-dimethylcyclopropanecarboxamide (8e):
Yield 77.6%; m.p. 232–234 °C. 1H NMR (500 MHz, CDCl3) δ (ppm):
1.39 (s, 6H, CH3), 2.33 (t, 1H, CH), 2.44 (d, 1H, CH), 7.10 (d, 1H,
C=CH), 9.03–9.11 (m, 3H, Ph), 13.07 (s, 1H, NH). IR (KBr) ν: 3458,
3097, 3008, 2962, 2885, 1683, 1654, 1548, 1508, 1296, 1139, 1116,
730 cm−1. Anal. Calcd for C17H13ClF3N5O5S: C, 41.51; H, 2.66; N,
14.24. Found: C, 41.58; H, 2.64; N, 14.29%.
3-(2-Chloro-3,3,3-trifluoroprop-1-en-1-yl)-N-(5-(2,6-difluorophenyl)-
1,3,4-thiadiazol-2-yl)-2,2-dimethylcyclopropanecarboxamide (8f):
Yield 87.3%; m.p. 226–228 °C. 1H NMR (500 MHz, CDCl3) δ (ppm):
1.37 (s, 6H, CH3), 2.33 (t, 1H, CH), 2.48 (d, 1H, CH), 7.07–7.12 (m,
3H, Ph), 7.42 (d, 1H, C=CH), 12.96 (s, 1H, NH). IR (KBr) ν: 3149,
3083, 2968, 2896, 1683, 1654, 1558, 1298, 1276, 1143, 1118, 781
cm−1. Anal. Calcd for C17H13ClF5N3OS: C, 46.64; H, 2.99; N, 9.60.
Found: C, 46.36; H, 2.92; N, 9.52%.
83.1%; m.p. 240–242 °C. 1H NMR (500 MHz, CDCl3) δ (ppm): 1.47
(s, 6H, CH3), 2.41 (t, 1H, CH), 2.52 (d, 1H, CH), 7.22 (d, 1H, C=CH),
7.77–8.82 (m, 4H, Ph), 13.01 (s, 1H, NH). IR (KBr) ν: 3452, 3155,
3082, 2966, 2896, 1683, 1652, 1568, 1303, 1143, 1118, 823 cm−1.
Anal. Calcd for C16H14ClF3N4OS: C, 47.71; H, 3.50; N, 13.91. Found:
C, 47.73; H, 3.59; N, 13.90%.
Biological assay
The results indicated that most of the title compounds showed low
activity against Plutella xylostella while exhibiting moderate activity
against Aphis craccivora (Pea aphids). Compounds 8e, 8f, 8h, 8i and
8l also showed moderate activities against Tetranychus cinnabarinus.
The results showed that compounds containing electron withdrawing
groups especially, –NO2, –F group, would enhance the insecticidal
activity against Aphis craccivora (Pea aphids). It is worth mentioning
that compound 8h exhibited better activity than 8g might be better
absorbed because of its higher lipophilicity.
Analysis of the results reveals that a change in the HLB value
of molecule by modifying the substitutent on the phenyl from an
electron-donating group to electron-withdrawing group can enhance
the biological activity. Other heterocyclic compounds might be
introduced instead of the substituted phenyl groups.
We thank Dr Wei Jia of Jiangsu Yangnong Chemical Co., LTD
for support with the bioassays. Generous financial support
of this work came from the National High Technology
Research and Development (863 Program) of China (No.
2007AA06A402), Key Projects in the National Science and
Technology Pillar Program (No. 2006BAC02A15), Key Proj-
ects in the National Water pollution control and management
Pillar Program (No. 2008ZX07101-003), 2011 Key projects
of Natural Science of Jiangsu Province-owned colleges
(No.11KJA610001).
3-(2-Chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethyl-N-(5-
(4-octylphenyl)-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamide (8g):
Yield 68.6%; m.p. 203–209 °C. 1H NMR (500 MHz, CDCl3) δ (ppm):
0.88 (t, 3H, CH3), 1.31 (s, 3H, CH3), 1.50 (m, 10H, CH3), 1.62 (s, 3H,
CH3), 1.64 (m, 2H, CH2) 2.45 (d, 1H, CH), 2.63 (t, 2H, CH2), 2.91 (d,
1H, CH), 7.17 (d, 1H, C=CH), 7.29–7.79 (m, 4H, Ph), 14.13 (s, 1H,
NH). IR (KBr) ν: 3244, 3151, 3064, 2958, 2854, 1683, 1652, 1564,
1299, 1137, 950, 727 cm−1.Anal. Calcd for C25H31ClF3N3OS: C, 58.41;
H, 6.08; N, 8.17. Found: C, 58.49; H, 6.03; N, 8.19%.
Received 9 November 2011; accepted 22 November 2011
Paper 1100970 doi: 10.3184/174751911X13230201951890
Published online: 27 December 2011
3-(2-Chloro-3,3,3-trifluoroprop-1-en-1-yl)-N-(5-(4-dodecylphe-
nyl)-1,3,4-thiadiazol-2-yl)-2,2-dimethylcyclopropanecarboxamide
(8h): Yield 66.4%; m.p. 216–217 °C. H NMR (500 MHz, CDCl3)
1
References
δ (ppm): 0.87 (t, 3H, CH3), 1.25 (m, 18H, CH2), 1.31 (s, 3H, CH3),
1.49 (s, 3H, CH3), 1.64 (m, 2H, CH2), 2.41 (t, 1H, CH), 2.63 (m, 2H,
CH2), 2.90 (t, 1H, CH), 7.16 (d, 1H, C=CH), 7.27–7.81 (m, 4H, Ph),
14.09 (s, 1H, NH). IR (KBr) ν: 3244, 3163, 3080, 2958, 2852, 1683,
1652, 1573, 1303, 1145, 952, 729 cm−1. Anal. Calcd for
C29H39ClF3N3OS: C, 61.09; H, 6.89; N, 7.37. Found: C, 61.03; H,
6.84; N, 7.39%.
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4
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6
3-(2-Chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethyl-N-(5-(4-
phenoxyphenyl)-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamide (8i):
Yield 76.2%; m.p. 204–206 °C. 1H NMR (500 MHz, CDCl3) δ (ppm):
1.25 (s, 3H, CH3), 1.47 (s, 3H, CH3), 2.43 (t, 1H, CH), 2.87 (d, 1H,
CH), 7.15 (d, 1H, C=CH), 7.05–7.86 (m, 9H, Ph), 14.04 (s, 1H, NH).
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1145, 1053, 954, 752 cm−1. Anal. Calcd for C23H19ClF3N3O2S: C,
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nyl)-1,3,4-thiadiazol-2-yl)-2,2-dimethylcyclopropanecarboxamide
7
8
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(8j): Yield 83.1%; m.p. 229–230 °C. H NMR (500 MHz, CDCl3)
δ (ppm): 1.42 (s, 6H, CH3), 2.28 (t, 1H, CH), 2.58 (d, 1H, CH), 3.88
(s, 6H, CH3), 6.69 (d, 1H, C=CH), 7.12–7.67 (m, 3H, Ph), 12.66 (s,
1H, NH). IR (KBr) ν: 3452, 3164, 3083, 2958, 2854, 1676, 1654,
1569, 1303, 1176, 1134, 1118, 779 cm−1. Anal. Calcd for
C19H19ClF3N3O3S: C, 49.41; H, 4.15; N, 9.10. Found: C, 49.32; H,
4.12; N, 9.05%.
3-(2-Chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethyl-N-(5-
(pyridin-3-yl)-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamide (8k):
Yield 81.2%; m.p. 238–239 °C. 1H NMR (500 MHz, DMSO-d6)
δ (ppm): 1.31 (s, 6H, CH3), 2.23 (t, 1H, CH), 2.58 (d, 1H, CH), 7.10
(d, 1H, C=CH), 7.27–8.25 (m, 4H, Ph), 12.79 (s, 1H, NH). IR (KBr)
ν: 3452, 3159, 3080, 2960, 2871, 1683, 1652, 1569, 1305, 1143, 1120,
705 cm−1. Anal. Calcd for C16H14ClF3N4OS: C, 47.71; H, 3.50; N,
13.91. Found: C, 47.79; H, 3.49; N, 13.94%.
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3-(2-Chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethyl-N-(5-(pyridin-
4-yl)-1,3,4-thiadiazol-2-yl)cyclopropanecarboxamide (8l): Yield
23 F.K. Kirchner, J.H. Bailey and C.J. Cavallito, J. Am. Chem. Soc., 1949, 71,
1210.

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