Synthesis and Insecticidal Activity of Novel Thiazole Acrylonitrile Derivatives

Article abstract of DOI:10.1002/jhet.2961

A series of novel thiazole acrylonitrile derivatives was designed and synthesized utilizing NC-510 as a precursor. Their structures were characterized by NMR spectrometry, MS, and elemental analysis. The results of bioassay indicated that some of these ti

Full text of DOI:10.1002/jhet.2961

Month 2017
Synthesis and Insecticidal Activity of Novel Thiazole Acrylonitrile
Derivatives
Shengwen Cao,a,b,c Aiping Liu,b,c Weidong Liu,b,c Xingping Liu,b,c Yeguo Ren,b,c Hui Pei,b,c Lu Huang,b,c Xi Zheng,b,c
Mingzhi Huang,b,c and Daoxin Wu
a
*
*
aSchool of Chemistry and Biological Engineering, Changsha University of Science and Technology, Changsha 410076,
People’s Republic of China
bNational Engineering Research Center for Agrochemicals, Hunan Research Institute of Chemical Industry, Changsha
410007, People’s Republic of China
cHunan Province Key Laboratory for Agrochemicals, Changsha 410014, People’s Republic of China
*
E-mail: daoxinwu@126.com; huang-mz@163.com
Received January 25, 2017
DOI 10.1002/jhet.2961
Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel thiazole acrylonitrile derivatives was designed and synthesized utilizing NC-510 as a
precursor. Their structures were characterized by NMR spectrometry, MS, and elemental analysis. The
results of bioassay indicated that some of these title compounds exhibited 100% mortality at 50 mg/L against
Aphis fabae. In particular, the compound 11c displayed the best activity: Its LC50 value achieved 1.45 mg/L,
and its insecticidal potency is comparable with that of NC-510.
J. Heterocyclic Chem., 00, 00 (2017).
INTRODUCTION
compounds, which have been first synthesized by
Allen and Birum in 1960s [6], also have excellent
Thiazole derivative, an important class of heterocyclic
compounds, has attracted wide attention due to its
insecticidal [1], fungicidal [2], antiviral [3], herbicidal [4],
and plant-growth-regulating activities [5]. Acrylonitrile
biological
activities
including
insecticidal
and
herbicidal activities [7]. Since then, thousands of
acrylonitrile analogues with biological activity were
reported [8,9].
© 2017 Wiley Periodicals, Inc.

S. Cao, A. Liu, W. Liu, X. Liu, Y. Ren, H. Pei, L. Huang, X. Zheng, M. Huang, and D. Wu
Vol 000
In recent years, the research of thiazole acrylonitrile
compounds containing both thiazole and acrylonitrile
moiety has gained increasing popularity because of their
diverse characteristics [10], such as effective action mode,
high efficiency, low toxicity, and low residue. Thus, a
series of thiazole acrylonitrile compounds [11–15] has
been developed. Among them, NC-510 (Fig. 1) [16]
displayed excellent biological activity against Aphis fabae
and other piercing-sucking mouthparts insects and
showed no cross-resistance to currently available
insecticides [17]. These results proved that thiazolyl
acrylonitrile compounds are worth of further investigation.
Based on the aforementioned findings, we used NC-510
as a lead compound to design and to synthesize novel
pesticides (Fig. 1). In this paper, 18 unreported thiazole
acrylonitrile derivatives were designed and synthesized
by adopting analogue synthesis and sub-structure theory.
In our previous work [18], it is pointed out that a methyl
group on the 2- position of the thiazole ring was required
for the development of optimal insecticidal activity. Thus,
the goal was to optimize the R2 group. As shown in
Figure 1, moiety B was optimized by replacing the
tert-butyl with other 10 groups (A1–A10) that were
isosteres each other. Meanwhile, moiety A was optimized
as well. To search for novel analogues with unique
biological activities, a synthetic screening program was
carried out around compound 11a–11r.
RESULTS AND DISCUSSION
Synthesis. The synthetic route to the title compounds
11a–r is shown in Scheme 1. A series of novel thiazole
acrylonitrile analogues were synthesized by reacting
compound 10 with desired acid chlorides in the room
temperature in the presence of triethylamine. As shown in
Scheme 1, two methods could be used to synthesize the
key intermediate compound 3, and route 1 was adopted
because the utilization of KI improved the catalytic effect
of NaCN, and route 1 therefore has milder reaction
Figure 1. Designs strategy of target molecules. [Color figure can be viewed at wileyonlinelibrary.com]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis and Insecticidal Activity of Novel Thiazole Acrylonitrile Derivatives
Scheme 1. General synthetic route for the target compounds 11a–r.
condition, higher yield, and higher purity compared with
route 2.
fabae, and seven compounds, 11f, 11h, 11i, 11l, 11n,
11m, and 11r, have insecticidal activity with 89.61%,
83.8%, 75.4%, 87.33%, 73.5%, 87.74%, and 83.08%
mortality, respectively. In particular, with an LC50 value
of 1.45 mg/L, 11c showed an insecticidal activity slightly
Because of the presence of the C=C bond, intermediate
10 and the target molecules 11a–r have Z/E
stereoisomerism. This stereoisomerism can be rapidly
separated by column chromatography on silica gel. For
lower
to
the
reference
compound
NC-510
unambiguous
structure
elucidation,
1H
NMR
(LC50 = 0.61 mg/L).
spectroscopy was used. Taking 11a and 11b, as
examples, the resonance frequencies resulting from SCH3
group of E form and Z form are 2.058 and 2.186 ppm,
respectively, and the resonance frequencies resulting from
CH3 group of E form and Z form are 1.445 and
Structure–activity relationship. The structure–activity
relationship can be evaluated via parallel activity con-
trasting between the compounds of different substituents
against Aphis fabae at the same concentration. The
activities of the compounds 11a–r depend on the R1and
R2 moiety. The results showed that R2 has an important
effect on the activity: When R1 = CH3, and R2 = A7, the
compounds (11h and 11i) had good activities; when R2
are substituents containing sulfur atom, the compounds
(11a-11f) showed moderate activities. In general,
sequence of the substitution patterns of the R2 in
enhancement of the activity (R1 is kept as methyl) is
A2 > A4 > A8 > A7 > A1 > A3 > A5 > A6. At the
same time, E- and Z- isomers also have effect on the
activity of compounds. By comparing the activities of
compounds 11a (E form) and 11b (Z form) as well as
11h (Z form) and 11i (E form), the activity of the Z form
is slightly better than that of the E form.
1
1.550 ppm respectively in the H NMR spectrum because
of the position with C≡N group. Taking 11h and 11i as
examples, the resonance frequencies resulting from CH
group of E form and Z form are 5.120 and 5.158 ppm,
respectively, and the resonance frequencies resulting from
CH3 group of E form and Z form are 2.806 and
1
2.780 ppm respectively in the H NMR spectrum because
of the position with C ≡ N group.
Insecticidal activity. The screening date revealed that
all title compounds 11a–r had 100% mortality at
500 mg/L against Aphids. When the concentration was
decreased to 50 mg/L, the compounds 11a-11e, 11g, 11j,
11k, and 11p still exhibited 100% mortality against Aphis
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. Cao, A. Liu, W. Liu, X. Liu, Y. Ren, H. Pei, L. Huang, X. Zheng, M. Huang, and D. Wu
Vol 000
Table 1
Insecticidal activity against Aphis fabae for the target compounds.
Compound
Regression equation
Correlation
LC50 (mg/L)
Compound
Regression equation
Correlation
LC50 (mg/L)
11a
11b
11c
11d
11e
11f
Y = 4.1882 + 1.6912×
Y = 2.0768 + 6.5745×
Y = 4.7634 + 1.4590×
Y = 3.7867 + 1.7576×
Y = 4.4397 + 1.4767×
Y = 3.3186 + 2.3571×
0.9782
0.8724
0.9912
0.9971
0.9895
0.9776
3.02
2.78
1.45
4.90
2.40
5.17
11g
11h
11i
11n
Y = 3.4193 + 2.1839×
Y = 3.9704 + 2.5928×
Y = 3.9789 + 2.0924×
Y = 4.3113 + 1.7923×
Y = 5.4148 + 1.9063×
0.9872
0.9585
0.9423
0.9294
0.9977
5.29
2.49
3.08
2.42
0.61
NC-510
Further studies on the biological activity and structure–
activity relationships of this series of compounds are in
progress.
reflux for 5–6 h. The reaction mixture was cooled to
room temperature, poured into ice water, and then
extracted with ethyl acetate. The combined organic layer
was dried with anhydrous sodium sulfate and
concentrated under reduced pressure to afford the crude
product 2 as a brown liquid, 36.2 g (95.2% yield, 93.7%
purity), which was used in the following reaction without
further purification.
Synthesis of 2-(2-phenylthiazole-4-yl)-acetonitrile (3). KI
(0.83 g, 5 mmol) was added to a solution of compound 2
(20.9 g, 100 mmol) in DMF (150 mL). The mixture was
stirred at room temperature for 20 min before sodium
cyanide (5.88 g, 120 mmol) was added, and then the
mixture was stirred at room temperature for 10–12 h until
the staring materials was consumed (monitored by TLC).
The reaction mixture was poured into ice water, and
FeCl3 was added before the mixture was extracted with
ethyl acetate. The combined organic layer was dried with
anhydrous sodium sulfate and concentrated under reduced
pressure to afford the crude product 3 as a black liquid,
16.7 g (83.5% yield, 92.3% purity), which was used in
the following reaction without further purification.
CONCLUSION
In summary, a series of novel thiazole acrylonitrile
compounds were synthesized, and their insecticidal
activities were evaluated. The screening data revealed
that compounds 11a–r had good insecticidal activity, and
in particular, 11b, 11c, 11e, 11h, and 11n displayed
excellent activities. Structure–activity relationships
indicated that R2 has an important effect on the activity,
and
the
activity
order
for
R2
is
A2 > A4 > A8 > A7 > A1 > A3 > A5 > A6 (Table 1).
EXPERIMENTAL
Materials and method.
Unless otherwise noted,
reagents and solvents were used as received from
commercial suppliers. NMR spectra were obtained with a
Varian INOVA-300 spectrometer using tetramethylsilane
as internal standard and deuterochloroform (CDCl3) as
solvent. LC–MS were recorded with an Agilent 1100
series using the positive ion scan mode. Elemental
analysis data were obtained on a PE2400 II elemental
analyzer. Column chromatography was performed using a
200–300 mesh silica gel. Uncorrected melting points
were taken on a WRS-1B digital melting point apparatus.
The general synthetic schemes for compounds are
shown in Scheme 1. Reaction yields were not optimized.
Every other compound was synthesized in a manner
similar to that used for the representatives, and every new
Synthesis of ethyl 2-chloro-4,4,4-trifluoro-3-oxobutanoate
(5).
A solution of ethyl 4,4,4-trifluoro-3-oxobutanoate
(92 g, 500 mmol) in dichloromethane (100 mL) was
added dropwise to a solution of sulfonyl chloride (74.3 g,
550 mmol) in dichloromethane (30 mL) at a temperature
ranging from À5 to 0°C. The mixture was stirred at room
temperature for 10–12 h. The reaction mixture was
poured into ice water and then extracted with
dichloromethane. The combined organic layer was dried
with anhydrous sodium sulfate and concentrated under
reduced pressure to afford the crude product compound 5
as a yellow liquid,108.2 g (99.3% yield, 99.1% purity),
which was used in the following reaction without further
1
1
purification. H NMR (CDCl3, 300 MHz), δ, ppm: 1.34
compound was identified and verified by H NMR, LC–
(t, J = 6.0 Hz, 3H, CH3), 4.32 (q, J = 6.0 Hz, 2H, CH2),
4.48 (s, 1H, CH).
MS, and elemental analysis.
Synthesis of 4-chloromethyl-2-phenylthiazole (2).
1,3-
Dichloropropan-2-one (25.4 g, 200 mmol) was added
dropwise to a stirred mixture of anhydrous EtOH
(100 mL), tetrahydrofuran (THF) (50 mL), and
thiobenzamide (25.0 g, 182 mmol). After stirring at the
room temperature for 0.5 h, the mixture was heated at
Synthesis
carboxylic acid ethyl ester (6).
370 mmol) was added to a solution of compound 5
(81.0 g, 370 mmol) in anhydrous EtOH (200 mL). The
resulting mixture was heated at reflux for 8–10 h until the
of
2-amino-4-(trifluoromethyl)thiazole-5-
Thiourea (28.2 g,
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Month 2017
Synthesis and Insecticidal Activity of Novel Thiazole Acrylonitrile Derivatives
staring materials was consumed (monitored by TLC). The
reaction mixture was cooled to room temperature, poured
into ice water, and a solid was formed. The solid was
filtered and dried to afford the compound 6 as a white
Synthesis
of
3-hydroxy-3-(2-chloro-4-(trifluoromethyl)
thiazole-5-yl)-2-(2-phenylthiazole-4-yl)-acrylonitrile (10o).
t-BuOK (5.6 g, 50 mmol) was slowly added to a
solution of compound 9o (14.0 g, 50 mmol) and
compound 3 (10.0 g, 50 mmol) in THF (100 mL) at
0°C. The mixture was stirred at the room temperature
for 10–12 h. The reaction mixture was poured into ice
water and acidified with 40% hydrochloric acid to
approximity pH 2, and the product was extracted with
ethyl acetate. The combined organic layer was dried
over anhydrous sodium sulfate and concentrated under
reduced pressure to afford the compound 10o as a
brown solid, 12.3 g (59.6% yield, 97.3% purity) mp
170.0–170.4°C. 1H NMR (CDCl3, 300 MHz), δ, ppm:
7.45–7.50 (m, 3H, Ph H), 7.92–7.96 (m, 2H, Ph H), 8.28
solid, 81.8
g
(92.1% yield, 99.3% purity), mp
169.3–170.5°C. 1H NMR (CDCl3, 300 MHz), δ, ppm:
1.33 (t, J = 6.0 Hz, 3H, CH3), 4.30 (q, J = 6.0 Hz, 2H,
CH2), and 5.87 (s, 2H, NH).
Synthesis
of
2-chloro-4-(trifluoromethyl)thiazole-5-
carboxylic acid ethyl ester (7o).
Compound 6 (48.0 g,
200 mmol) was slowly added to solution of
a
hydrochloric acid (4 M, 100 mL) at À10°C, and the
mixture was stirred for 15 min before a solution of 40%
aqueous sodium nitrite was added dropwise. The mixture
was stirred at the same temperature for 2 h before stirred
at room temperature for 2 h. The resulting mixture was
poured into ice water, and a solid was formed. The solid
was filtered and dried to afford the crude product as a
brown solid, 45.6 g (88.0% yield, 93.6% purity), which
was recrystallized from petroleum ether and ethyl acetate
to afford the compound 7o (R1 = Cl) as a yellow solid,
(97.8% purity), mp 58.2–58.6°C.
(s, 1H, Thiazole H), 8.95 (s, 1H, OH).
Synthesis of 2-phenyl thiazole-3-substituted ester-
3-(substituted thiazole-5-yl) acrylonitrile (11a–r).
Compound 10o (1.03 g, 2.5 mmol), THF (30 mL), and
Et3N (0.5 g, 5 mmol) were mixed in ice bath and stirred
for 15 min. Then substituted acyl chloride (3 mmol) was
dropwise added to the mixture and stirred at room
temperature for 4 h. The reaction solution was poured
into ice water and extracted with ethyl acetate. The
organic layer was washed twice with water and dried
over anhydrous sodium sulfate, filtered, and concentrated
under reduced pressure to give the crude product, and the
residue was purified by silica-gel column chromatography
(petroleum ether + ethyl acetate =30:1 v/v) to afford
compound 11a–r as a white, yellow, or brown solid.
Synthesis
of
2-chloro-4-(trifluoromethyl)
thiazole-5-carboxylic acid (8o).
Aqueous sodium
hydroxide (0.2 M, 80 mL) was added to a solution of
compound 7o (25.9 g, 100 mmol) in anhydrous ethanol
(40 mL). The resulting mixture heated at reflux for 3–5 h
until the staring materials was consumed (monitored by
TLC). The reaction mixture was poured into ice water
and acidified with 40% hydrochloric acid to pH of
about 2, extracted with ethyl acetate. The combined
organic layer was dried with anhydrous sodium sulfate
and concentrated under reduced pressure to afford the
crude product 8o as a brown oil, 17.5 g (75.8% yield),
which was used in the following reaction without
further purification. 1H NMR (CDCl3, 300 MHz),
δ, ppm: 1.37 (t, J = 6.0 Hz, 3H, CH3), 4.38
(q, J = 6.0 Hz, 2H, CH2).
1H NMR data of compounds 11a–r. 11a:(E)-2-cyano-1-(2-
methyl-4-(trifluoromethyl)thiazol-5-yl)-2-(2-phenylthiazol-4-yl)
vinyl 2-(methylthio)propanoate.
Yield, 45.5%; yellow
1
solid; mp 109.0–110.0°C; H NMR (CDCl3, 300 MHz),
δ, ppm: 1.445 (d, J = 7.2 Hz, 3H, CH3), 2.058 (s, 3H,
CH3), 2.803 (s, 3H, CH3), 3.540 (q, J = 7.2 Hz, 1H, CH),
7.511–7.550 (m, 3H, Ph H), 7.882–7.959 (m, 2H, Ph H),
8.005 (s, 1H, Thiazole H). 13C NMR, δ: 13.38, 15.88,
19.26, 41.22, 76.57, 118.16, 122.28, 126.55, 129.03,
129.38, 130.82, 131.09, 142.71, 146.21, 149.18, 158.56,
168.53, 169.25, 170.40. LC–MS (APCI, Pos) m/z: 496
Synthesis of (2-chloro-4(-trifluoromethyl) thiazole-5-yl)(1H-
parazole-1-yl)-ketone (9o).
Sulfoxide chloride (35.4 g,
300 mmol) was dropwise added to a solution of
compound 8o (23.1 g, 100 mmol) in 1,2-
dichloroethane (120 mL), and the mixture was heated
at reflux for 5–6 h. The mixture was cooled to room
temperature, and the excess solvent and sulfoxide
chloride was removed under reduced pressure to
afford a brown liquid. Pyrazole (13.6 g, 200 mmol)
was added to the brown liquid in dichloromethane
(150 mL) and stirred for 2 h. Water was added and
extracted with dichloromethane. The combined organic
layer was dried over anhydrous sodium sulfate and
concentrated to afford the crude compound 9o as a
brown oil, 45.2 g (80.5% yield). 1H NMR (CDCl3,
300 MHz), δ, ppm: 7.80 (s, 1H, COOH).
[M
+
H]+. Elemental Anal. (%) Calcd for
C21H16F3N3O2S3: C 50.90, H 3.25, N 8.48; found C
50.80, H 3.12, N 8.17.
11b:(Z)-2-cyano-1-(2-methyl-4-(trifluoromethyl)thiazol-5-yl)-
2-(2-phenylthiazol-4-yl)vinyl 2-(methylthio)propanoate.
Yield, 32.5%; yellow solid; mp 108.6–110.1°C;1H NMR
(CDCl3, 300 MHz), δ, ppm: 1.550 (d, J = 7.2 Hz, 3H,
CH3), 2.186 (s, 3H, CH3), 2.783 (s, 3H, CH3), 3.541 (q,
J = 7.2 Hz, 1H, CH), 7.368–7.412 (m, 3H, Ph H), 7.531–
7.576 (m, 2H, Ph H), 7.609 (s, 1H, Thiazole H). 13C
NMR, δ: 14.10, 16.17, 19.14, 41.68, 76.58, 118.26,
121.44, 126.37, 128.98, 129.41, 130.80, 131.57, 145.21,
146.16, 149.23, 158.59, 168.75, 169.83,170.27. LC–MS
Journal of Heterocyclic Chemistry
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S. Cao, A. Liu, W. Liu, X. Liu, Y. Ren, H. Pei, L. Huang, X. Zheng, M. Huang, and D. Wu
Vol 000
(APCI, Pos) m/z: 496 [M + H]+. Elemental Anal. (%) Calcd
for C21H16F3N3O2S3: C 50.90, H 3.25, N 8.48; found C
50.81, H 3.34, N 8.18.
11c:(Z)-2-cyano-1-(2-methyl-4-(trifluoromethyl)thiazol-5-yl)-
7.567 (m, 3H, Ph H), 7.804 (s, 1H, Thiazole H),
7.939–7.971 (m, 2H, Ph H). LC–MS (APCI, Pos) m/z:
508 [M
H]+. Elemental Anal. (%) Calcd for
+
C22H16F3N3O4S2: C 52.07, H 3.18, N 8.28; found C
2-(2-phenylthiazol-4-yl)vinyl 2-(propylthio)propanoate.
Yield, 37.8%; yellow solid; mp 100.0–101.0°C; H NMR
51.90, H 3.75, N 7.98.
1
11h:(Z)-2-cyano-1-(2-methyl-4-(trifluoromethyl)thiazol-5-yl)-
2-(2-phenylthiazol-4-yl)vinyl cyclopentyl carbonate.
Yield,
(CDCl3, 300 MHz), δ, ppm: 0.931–1.021 (m, 3H, CH3),
1.549 (d, J = 7.2 Hz, 3H, CH3), 1.579–1.705 (m, 2H,
CH2), 2.559–2.660 (m, 2H, CH2), 2.778 (s, 3H, CH3),
3.560 (q, J = 7.5 Hz, 1H, CH), 7.366–7.428 (m, 3H, Ph
H), 7.531–7.567 (m, 2H, Ph H), 7.599 (s, 1H, Thiazole
H). 13C NMR, δ: 13.29, 16.83, 19.11, 22.43, 33.58,
40.70, 76.58, 118.26, 121.39, 126.37, 128.97, 129.41,
130.80, 131.57, 145.23, 149.23, 158.59, 168.76, 169.10,
169.29, 170.24. LC–MS (APCI, Pos) m/z: 524
29.6%; yellow solid; mp 132.0–133.0°C; 1H NMR
(CDCl3, 300 MHz), δ, ppm: 1.633–1.916 (m, 8H, 4
CH2), 2.780 (s, 3H, CH3), 5.158–5.212 (m, 1H, CH),
7.340–7.442 (m, 3H, Ph H), 7.539–7.581 (m, 2H, Ph H),
7.603 (s, 1H, Thiazole H). LC–MS (APCI, Pos) m/z: 506
[M
+
H]+. Elemental Anal. (%) Calcd for
C23H18F3N3O3S2: C 54.65, H 3.59, N 8.31; found C
53.90, H 3.52, N 8.28.
11i:(E)-2-cyano-1-(2-methyl-4-(trifluoromethyl)thiazol-5-yl)-
2-(2-phenylthiazol-4-yl)vinyl cyclopentyl carbonate.
[M
+
H]+. Elemental Anal. (%) Calcd for
Yield,
C23H20F3N3O2S3: C 52.76; H, 3.85; N, 8.03; found C
51.90, H 3.75, N 7.98.
11d:(Z)-2-cyano-1-(2-methyl-4-(trifluoromethyl)thiazol-5-yl)-
40.8%; yellow solid; mp 105.0–106.0°C; 1H NMR
(CDCl3, 300 MHz), δ, ppm: 1.564–1.868 (m, 8H, 4
CH2), 2.806 (s, 3H, CH3), 5.120–5.148 (m, 1H, CH),
7.438–7.487 (m, 3H, Ph H), 7.788 (s, 1H, Thiazole H),
7.959–7.992 (m, 2H, Ph H). LC–MS (APCI, Pos) m/z:
2-(2-phenylthiazol-4-yl)vinyl 2-(methylthio)acetate.
Yield,
41.3%; yellow solid; mp 108.0–109.0°C; 1H NMR
(CDCl3, 300 MHz), δ, ppm: 2.185 (s, 3H, CH3),
2.503 (s, 3H, CH3), 3.414 (s, 2H, CH2), 7.443–7.500
(m, 3H, Ph H), 7.591 (s, 1H, Thiazole H), 7.856–
7.909 (m, 2H, Ph H). LC–MS (APCI, Pos) m/z: 482
506 [M
+
H]+. Elemental Anal. (%) Calcd for
C23H18F3N3O3S2: C 54.65, H 3.59, N 8.31; found C
52.98, H 3.48, N 8.28.
11j:(E)-1-(2-bromo-4-(trifluoromethyl)thiazol-5-yl)-2-cyano-
2-(2-phenylthiazol-4-yl)vinyl 2-(methylthio)propanoate.
[M
+
H]+. Elemental Anal. (%) Calcd for
C20H14F3N3O2S3: C 49.89, H 2.93, N 8.73; found C
49.78; H, 2.90 N, 8.65.
1
Yield, 40.3%; yellow solid; mp 108.0–109.0°C; H NMR
(CDCl3, 300 MHz), δ, ppm: 1.457 (d, J = 6.9 Hz, 3H,
CH3), 2.215 (s, 3H, CH3), 3.347 (q, J = 7.2 Hz, 1H, CH),
7.466 (s, 1H, Thiazole H), 7.520–7.544 (m, 3H, Ph H),
7.886–7.913 (m, 2H, Ph H). LC–MS (APCI, Pos) m/z:
11e:(Z)-2-cyano-1-(2-methyl-4-(trifluoromethyl)thiazol-5-yl)-
2-(2-phenylthiazol-4-yl)vinyl 2-(ethylthio)propanoate. Yield,
46.9%; yellow solid; mp 114.0–115.0°C; 1H NMR
(CDCl3, 300 MHz), δ, ppm: 1.224 (q, J = 7.5 Hz, 3H,
CH3), 1.552 (d, J = 7.2 Hz, 3H, CH3), 2.633–2.715 (m,
2H, CH2), 2.777 (s, 3H, CH3), 3.586 (q, J = 7.2 Hz, 1H,
CH), 7.371–7.427 (m, 3H, Ph H), 7.532–7.568 (m, 2H,
Ph H), 7.599 (s, 1H, Thiazole H). LC–MS (APCI, Pos)
m/z: 510 [M + H]+. Elemental Anal. (%) Calcd for
C22H18F3N3O2S3: C 51.85, H 3.56, N 8.25; found C
51.74; H, 3.50; N, 8.14.
560 [M
+
H]+. Elemental Anal. (%) Calcd for
C20H13BrF3N3O2S3: C 42.86, H 2.34, N 7.50; found C
42.76, H 2.23, N 7.38.
11k:(E)-1-(2-chloro-4-(trifluoromethyl)thiazol-5-yl)-2-cyano-
2-(2-phenylthiazol-4-yl)vinyl
carbonate.
(tetrahydrofuran-3-yl)
Yield, 37.8%; yellow solid; mp 110.0–
1
113.0°C; H NMR (CDCl3, 300 MHz), δ, ppm: 2.053–
2.386 (m, 2H, CH2), 3.793–3.988 (m, 4H, 2 CH2),
5.268–5.298 (m, 1H, CH), 7.403–7.588 (m, 4H, Ph /
Thiazole H), 7.928–7.967 (m, 2H, Ph H). LC–MS (APCI,
Pos) m/z: 528 [M + H]+. Elemental Anal. (%) Calcd for
11f:(E)-2-cyano-1-(2-methyl-4-(trifluoromethyl)thiazol-5-yl)-
2-(2-phenylthiazol-4-yl)vinyl
propanoate.
2,2-dimethyl-3-(methylthio)
Yield, 43.2%; brown solid; mp 104.0–
1
105.0°C; H NMR (CDCl3, 300 MHz), δ, ppm: 1.308 (s,
6H, 2 CH3), 2.117 (s, 2H, CH2), 2.735 (s, 3H, CH3),
2.809 (s, 3H, CH3), 7.424–7.533 (m, 3H, Ph H), 7.820 (s,
1H, Thiazole H), 7.930–7.961 (m, 2H, Ph H). LC–MS
(APCI, Pos) m/z: 524 [M + H]+. Elemental Anal. (%)
Calcd for C23H20F3N3O2S3: C 52.76, H 3.85,N 8.03;
C21H13ClF3N3O4S2:; found C 47.78, H 2.48, N 7.96 C
47.70, H 2.43, N 7.88.
11l:(E)-1-(2-chloro-4-(trifluoromethyl)thiazol-5-yl)-2-cyano-
2-(2-phenylthiazol-4-yl)vinyl 2-(methylthio)propanoate.
1
Yield, 43.8%; yellow solid; mp 90.0–92.0°C; H NMR
(CDCl3, 300 MHz), δ, ppm: 1.560 (d, J = 7.2 Hz, 3H,
CH3), 2.195 (s, 3H, CH3), 3.518 (q, J = 6.9 Hz, 1H, CH),
7.404–7.465 (m, 3H, Ph H), 7.533–7.564 (m, 2H, Ph H),
7.704 (s, 1H, Thiazole H). LC–MS (APCI, Pos) m/z: 516
found C 51.90, H 3.75, N 7.98.
11g:(E)-2-cyano-1-(2-methyl-4-(trifluoromethyl)thiazol-5-yl)-
2-(2-phenylthiazol-4-yl)vinyl
carbonate.
107.0°C; H NMR (CDCl3, 300 MHz), δ, ppm: 2.045–
2.209 (m, 2H, CH2), 2.797 (s, 3H, CH3), 3.744–3.969
(m, 4H, 2 CH2), 5.238–5.245 (m, 1H, CH), 7.450–
(tetrahydrofuran-3-yl)
Yield, 32.7%; brown solid; mp 106.0–
1
[M
+
H]+. Elemental Anal. (%) Calcd for
C20H13ClF3N3O2S3: C 46.56, H 2.54, N 8.14; found C
45.98, H 2.47, N 7.98.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2017
Synthesis and Insecticidal Activity of Novel Thiazole Acrylonitrile Derivatives
11n:(E)-2-cyano-1-(2-methyl-4-(trifluoromethyl)thiazol-5-yl)-
C21H15BrF3N3O2S3: C 43.91, H 2.63, N 7.32; found C
43.88, H 2.69, N 7.27.
2-(2-phenylthiazol-4-yl)vinyl 3-chloro-2,2-dimethylpropanoate
.
Yield, 31.2%; yellow solid; mp 107.0–109.4°C; 1H
Biological assay. Biological assay was carried out in
the Laboratory of Biological Activities Test, Hunan
Research Institute of Chemical Industry, Changsha,
People’s Republic of China. The biological evaluation
of 11a–r was undertaken according to the mortality
rate.
NMR (CDCl3, 300 MHz), δ, ppm:1.326 (s, 6H, 2CH3),
2.797 (s, 3H, CH3), 3.609 (s, 2H, CH2), 7.425–7.497 (m,
3H, Ph H), 7.762 (s, 1H, Thiazole H), 7.900–7.941 (m,
2H, Ph H). LC–MS (APCI, Pos) m/z: 512 [M + H]+.
Elemental Anal. (%) Calcd for C22H17ClF3N3O2S2: C
51.61, H 3.35, N 8.21; found C 51.49, H 3.27, N 8.11.
11m:(Z)-2-cyano-1-(2-methyl-4-(trifluoromethyl)thiazol-5-
Target insects.
Stock colonies of Aphis fabae were
reared in a conditioned room maintained at 25 ( 5)°C, 65
yl)-2-(2-phenylthiazol-4-yl)vinyl 2-bromopropanoate. Yield,
( 5)% relative humidity and 12/12
photoperiod.
h light: dark
1
44.6%; yellow oil; H NMR (CDCl3, 300 MHz), δ, ppm:
1.844 (d, J = 7.2 Hz, 3H, CH3), 2.814 (s, 3H, CH3),
4.376 (q, J = 6.9 Hz, 1H, CH), 7.498–7.583 (m, 3H, Ph
H), 7.628 (s, 1H, Thiazole H), 7.884–7.924 (m, 2H, Ph
H). LC–MS (APCI, Pos) m/z: 528 [M + H]+. Elemental
Anal. (%) Calcd for C20H13BrF3N3O2S2:; found C 45.47,
Test methods. Test compounds were dissolved in DMF
(0.2%) and then diluted to the required test concentrations
with water containing Tween-80 (0.2%) [19].
The horse bean seedlings with Aphis fabae were
dipped in the test solutions for 5–10 s, then allowed
H 2.48, N 7.95 C 45.36, H 2.45, N 7.89.
11o:(E)-1-(2-chloro-4-(trifluoromethyl)thiazol-5-yl)-2-cyano-
to dry with filter paper, transferred to
a beaker
(100 mL) containing water (10 mL), and kept at 25°C.
Each assay contained three replications. After 24 h,
mortality was recorded. The test was run three times, and
results were averaged. The dose–response data were
analyzed by probit analysis [20], and the activities were
evaluated as LC50 values.
2-(2-phenylthiazol-4-yl)vinyl 2-(ethylthio)propanoate. Yield,
34.2%; brown oil; 1H NMR (CDCl3, 300 MHz), δ,
ppm: 1.233–1.349 (m, 3H, CH3), 1.563 (d, J = 6.9 Hz,
3H, CH3), 2.665–2.694 (q, 2H, CH2), 3.608 (q,
J = 7.2 Hz, 1H, CH), 7.522–7.563 (m, 3H, Ph H),
7.700 (s, 1H, Thiazole H), 7.889–7.921 (m, 2H, Ph H).
LC–MS (APCI, Pos) m/z: 530 [M + H]+. Elemental
Anal. (%) Calcd for C21H15ClF3N3O2S3: C 47.59, H
2.85, N 7.93; found C 47.39, H 2.82, N 7.89.
11p:(E)-1-(2-chloro-4-(trifluoromethyl)thiazol-5-yl)-2-cyano-
Acknowledgment. This work was supported by the National
Natural Science Foundation of China (No. 21572050,
21672057).
2-(2-phenylthiazol-4-yl)vinyl cyclopentyl carbonate.
Yield,
37.8%; yellow oil; 1H NMR (CDCl3, 300 MHz), δ,
ppm: 1.254–1.285 (m, 2H, CH2), 1.622–1.677 (m, 2H,
CH2), 1.779–1.896 (m, 4H, 2 CH2), 5.146–5.166 (m,
1H, CH), 7.428–7.535 (m, 3H, Ph H), 7.826 (s, 1H,
Thiazole H), 7.955–7.987 (m, 2H, Ph H). LC–MS (APCI,
Pos) m/z: 526 [M + H]+. Elemental Anal. (%) Calcd for
C22H15ClF3N3O3S2: C 50.24, H 2.87, N 7.99; found C
50.01, H 2.77, N 7.89.
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11q:(Z)-1-(2-chloro-4-(trifluoromethyl)thiazol-5-yl)-2-cyano-
2-(2-phenylthiazol-4-yl)vinyl cyclopentyl carbonate.
Yield,
27.5%; white solid; m. p. 147.0–148.9°C; 1H NMR
(CDCl3, 300 MHz), δ, ppm: 1.253–1.286 (m, 2H, CH2),
1.644–1.670 (m, 2H, CH2), 1.881–1.944 (m, 4H, 2CH2),
5.203–5.216 (m, 1H, CH), 7.401–7.430 (m, 3H, Ph H),
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11r:(E)-1-(2-bromo-4-(trifluoromethyl)thiazol-5-yl)-2-cyano-2-
(2-phenylthiazol-4-yl)vinyl 2-methyl-2-(methylthio)propanoate.
1
Yield, 39.0%; white solid; m. p. 147.0–148.9°C; H NMR
(CDCl3, 300 MHz), δ, ppm: 1.296 (s, 6H, 2CH3), 2.158 (s,
3H, CH3), 7.461 (s, 1H, Thiazole H), 7.515–7.541 (m, 3H,
Ph H), 7.881–7.907 (m, 2H, Ph H). LC–MS (APCI, Pos)
m/z: 574 [M + H]+. Elemental Anal. (%) Calcd for
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DOI 10.1002/jhet

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