Novel heterocyclic compounds containing sulfur: Synthesis and insecticidal activity of (2-Chlorothiazol-5-yl)methyl 2-phenyliminothiazolidines

Article abstract of DOI:10.1080/10426500802384135

A series of new (2-chlorothiazol-5-yl)methyl 2-phenyliminothiazolidines were designed and synthesized. All new compounds were characterized by 1H NMR and, in some cases, by 13C NMR, IR, and HRMS. They are soluble in most organic solvents, which makes them

Full text of DOI:10.1080/10426500802384135

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Phosphorus, Sulfur, and Silicon
and the Related Elements
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Novel Heterocyclic Compounds
Containing Sulfur: Synthesis
and Insecticidal Activity of (2-
Chlorothiazol-5-yl)methyl 2-
Phenyliminothiazolidines
Gangyue Li a c , Shenggang Yan a , Shan Jiang a
,
Xuhong Qian b c , Qingchun Huang b & Rong Zhang c
a Electromechanics and Materials Engineering
College, Dalian Maritime University , Dalian,
People's Republic of China
b Shanghai Key Laboratory of Chemical Biology ,
Institute of Pesticides and Pharmaceuticals, East
China University of Science and Technology ,
Shanghai, People's Republic of China
c State Key Laboratory of Fine Chemicals , Dalian
University of Technology , Dalian, Liaoning Province,
People's Republic of China
Published online: 22 Jun 2009.
To cite this article: Gangyue Li , Shenggang Yan , Shan Jiang , Xuhong Qian ,
Qingchun Huang & Rong Zhang (2009) Novel Heterocyclic Compounds Containing
Sulfur: Synthesis and Insecticidal Activity of (2-Chlorothiazol-5-yl)methyl 2-
Phenyliminothiazolidines, Phosphorus, Sulfur, and Silicon and the Related Elements,
184:7, 1825-1836, DOI: 10.1080/10426500802384135
To link to this article: http://dx.doi.org/10.1080/10426500802384135
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Phosphorus, Sulfur, and Silicon, 184:1825–1836, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802384135
Novel Heterocyclic Compounds Containing Sulfur:
Synthesis and Insecticidal Activity of
(2-Chlorothiazol-5-yl)methyl 2-Phenyliminothiazolidines
Gangyue Li,1,3 Shenggang Yan,1 Shan Jiang,1 Xuhong
Qian,2,3 Qingchun Huang,2 and Rong Zhang3
1Electromechanics and Materials Engineering College, Dalian Maritime
University, Dalian, People’s Republic of China
2Shanghai Key Laboratory of Chemical Biology, Institute of Pesticides
and Pharmaceuticals, East China University of Science and Technology,
Shanghai, People’s Republic of China
3State Key Laboratory of Fine Chemicals, Dalian University of
Technology, Dalian, Liaoning Province, People’s Republic of China
A series of new (2-chlorothiazol-5-yl)methyl 2-phenyliminothiazolidines were de-
1
signed and synthesized. All new compounds were characterized by H NMR and,
13
in some cases, by C NMR, IR, and HRMS. They are soluble in most organic sol-
vents, which makes them easier to use. A preliminary bioassay showed that some of
the new compounds display insecticidal activity against third-instar larvae of Cx.
pipiens pallens at 50 mg/L and moderate insecticidal activity against A. craccivora
at 1000 mg/L.
Keywords Insecticidal activity; 2-phenyliminothiazolidine; synthesis; thiazolemethyl
INTRODUCTION
Crop protection continuously needs the discovery of novel pesticides.
The agrochemical industry has successfully developed a wide array of
pesticides with various chemical structures and modes of action.1 Due
to the emergence of resistant pests and toxicological issues associated
with certain insecticides, there is a continuing need to discover novel
chemical structures with potent activity.2
Received 15 November 2007; accepted 4 August 2008.
This project was supported by the National Key Project for Basic Research
(2003CB114400), the National Natural Science Foundation of China, and the Science
and Technology Research Project of the Education Office of Liaoning Province.
Address correspondence to Xuhong Qian, Shanghai Key Laboratory of Chemical Bi-
ology, Institute of Pesticides and Pharmaceuticals, East China University of Science and
Technology, Shanghai 200237, People’s Republic of China. E-mail: xhqian@ecust.edu.cn
1825

1826
G. Li et al.
Heterocyclic compounds play a very important role in drug design
and synthesis, owing to their unique bioactivities. Sulfur-containing
heterocyclic compounds such as 2-iminothiazolidine derivatives have
gained much interest as potent inhibitors of indolethylamine N-
methyltransferase,3,4 octopaminergicagonists,5,6 anthelmintics,7,8 di-
uretic agents,9 trehalase inhibitors,10−12 and insecticidal agents.13 It
was presumed that this class of compounds may possess good potential
with respect to agricultural bioactivities.
In the study of pharmaceuticals and agrochemicals, the introduction
of pyridine into a parent compound may improve its properties and bi-
ological activities. In fact, many pyridyl-containing compounds possess
a wide range of biological and pharmacological activities,14−17 as well
as low toxicity toward mammals. Bioisosterism is an important con-
cept in bioactive compound design. Substitution of a 2-chloro-5-pyridyl
group by a 2-chloro-5-thiazolyl group represents a successful example of
bioisosterism, such as imidacloprid.18−24 Encouraged by these reports,
we developed the idea that the replacement of the 2-chloro-5-pyridyl
with the 2-chloro-5-thiazolyl moiety in 2-phenyliminothiazolines could
improve their insecticidal activities.
Therefore, we adopted the 2-iminothiazolidine ring as pharma-
cophore and simultaneously introduced a (2-chloro-5-pyridyl)methyl
moiety and its bioisosteric 2-chloro-5-thiazole moiety into the 2-
phenyliminothiazolidine system. In our previous work, we reported
the synthesis of 2-phenyliminothiazolidines containing a pyridylmethyl
group, which showed excellent herbicidal activity.25,26 Herein we
present the synthesis of a series of (2-chlorothiazol-5-yl)methyl 2-
phenyliminothiazolidines by the replacement of the 2-chloro-5-pyridyl
with the 2-chloro-5-thiazolyl moiety in 2-phenyliminothiazolines and a
first evaluation of their insecticidal activities.
RESULTS AND DISCUSSION
Synthesis
The sulfur-containing compounds 3 were readily prepared in good
yields as shown in Scheme 1. The thioureas 2 were obtained by re-
action of the amino ethanol derivative 1 with the corresponding aryl
isothiocyanates. Cyclization of 2 with 80% sulfuric acid provided the
2-phenyliminothiazolidine derivatives 3. The overall yield of these
two steps ranged from 40% to 86%. Compounds 3 were characterized
by 1H NMR and, in some cases, by 13C NMR, IR, and HRMS. The
IR spectra of compounds 3 showed C=N and C–S stretching bands
1
at 1607–1629 cm−1 and 1221–1242 cm−1, respectively. The H NMR

New 2-Phenyliminothiazolidines
1827
N
R
N
OH
S
Cl
S
NCS
N
N
H2N
K2CO3, CH3CN
OH
HN
Cl
NH OH
Cl
S
Cl
S
R
1
2
N
N
S
N
S
1. 80 % H2SO4
2. NaOH, H2O
Cl
S
Cl
N
N
N
R
R
3
4
2 - 4
R
2 - 4
R
H
4-F
a
b
c
d
e
f
k
l
2-NO2
3-NO2
4-NO2
2,4-F2
2,6-F2
2-Cl
m
n
o
p
q
r
4-N(CH3)2
2-CH3
4-Cl
4-CH3
2,6-(CH3)2
2-CF3
4-CH3-2-NO2
4-OCH3-2-NO2
2-OCH3
g
h
i
3-CF3
s
2-F
4-OCH3
j
t
SCHEME 1 Synthesis of compounds 3.
spectra of compounds 3 showed a singlet (δ = 4.67–4.85 ppm), attributed
to the CH2 group linking to the thiazolidine ring. The two triplets at
δ = 3.11–3.24 ppm and δ = 3.47–3.63 ppm were assigned to the two
adjacent CH2 groups of the thiazolidine ring.
Insecticidal Activity
Table I displays the insecticidal activities of selected compounds 3
and 4 against third-instar larvae of Culex pipiens pallens and Aphis
craccivora. Some of the compounds exhibited high insecticidal activ-
ity against wiggler at 50 mg/L. 2-Chloro-5-thiazole is a bioisosteric
analogue of 2-chloro-5-pyridine and corresponding compounds show
similar insecticidal activity. We focused on the relationships between
the type of substituents R at the phenyl ring and the biological ac-
tivities. The compounds with a weakly electron donating or electron

1828
G. Li et al.
TABLE I Insecticidal Activity Against Third-Instar Larvae of Cx.
pipiens pallens of Some Compounds 3 and 4 at 50 mg/L
R
Mortality rate (%)
3a
3f
3g
3i
3k
3l
3n
3p
3s
3t
H
2-CH3
2,6-(CH3)2
3-CF3
4-F
2,4-F,F
2-Cl
4-CH3
2-OCH3
4-OCH3
H
100
76.36
100
37.29
52.0
56.76
100
42.55
48.72
90.91
100
53.8
89.04
100
4a
4f
4g
4j
2-CH3
2,6-(CH3)2
2-F
4k
4l
4-F
97.67
81.69
61.76
59.38
79.66
55.84
77.5
2,4-F2
2,6-F2
2-Cl
4-Cl
2-OCH3
4-OCH3
4m
4n
4o
4s
4t
withdrawing group (CH3, H, Cl, F) at the phenyl ring show good bio-
logical activities. The introduction of a strongly electron withdrawing
group such as the nitro group at the phenyl ring results in a complete
loss of activity (3b–d, q, r/4b–d, q, r), while the introduction of a strong
electron donating group such as the N, N-dimethylamino group at the
phenyl ring also results in a complete loss of activity (3e/4e). Among all
compounds, 3a, g, n, and 4a, n possess significant biological activities,
and the mortality rate against third-instar larvae of Cx. pipiens pallens
reaches 100% at 50 mg/L. Further study of this aspect is underway.
Table II shows that some compounds 3 and 4 exhibit moderate insec-
ticidal activity against A. craccivora at 1000 mg/L. Selected compounds
containing the 2-chlorothiazol-5-yl unit showed insecticidal activity.
Among the compounds containing a 2-chloro-5-pyridyl moiety, only 4g
exhibited 55.7% of mortality rate against A. craccivora at 1000 mg/L.
In conclusion, we have presented the design and synthesis of novel
2-phenyliminothiazolidine derivatives containing thiazolemethyl and
pyridinemethyl moiety. A first biological assay indicated that they
possess good insecticidal activities against third-instar larvae of Cx.

New 2-Phenyliminothiazolidines
1829
TABLE II Insecticidal Activity Against A. craccivora
of Some Compounds 3 and 4 at 1000 mg/L
R
Mortality rate
3d
3f
3h
3k
3l
4-NO2
2-CH3
2-CF3
37.13
36.23
69.64
49.18
38.37
42.11
55.70
4-F
2,4-F2
2,6-F2
2,6-(CH3)2
3m
4g
pipiens pallens. It is shown that a systematic study on the structure–
activity relationships will benefit the prediction of new compounds with
better insecticidal activity. The 2-phenyliminothiazolidine framework
might be identified as a novel insecticidal lead structure.
EXPERIMENTAL
Melting points were obtained with an X-6 micro melting point ap-
paratus and are uncorrected. The IR spectra were recorded with a
Nicolet 20DXB FR-IR spectrometer using KBr pellets or films. The 1H
NMR spectra were measured with a Varian INOVA-400 spectrometer
(400 MHz) in CDCl3 with TMS as internal standard; chemical shifts are
reported in ppm. The 13C NMR spectra were measured with a Bruker
AVANCE-500 spectrometer (125 MHz) in CDCl3 using TMS as internal
standard. High-resolution mass spectra (HRMS) were obtained with a
HPLC-Q-Tof MS (Mcrio) spectrometer. Flash chromatography was per-
formed on silica gel. All the solvents were of analytical grade. All chem-
icals or reagents were purchased from standard commercial suppliers.
Synthesis of 2-[(2-Chlorothiazol-5-yl)methylamino]ethanol (1)
2-Chloro-5-(chloromethyl)thiazole (10 mmol, 1.68 g) dissolved in
100 mL of acetonitrile was added dropwise to a K2CO3 (10 mmol,
1.38 g)-containing solution of ethanolamine (10 mmol, 0.61 g) in 25
mL of acetonitrile over a period of 2 h at room temperature. The re-
sulting mixture was refluxed for 4.5 h. The solvent was evaporated in
vacuo, and the residue was purified by column chromatography on sil-
ica gel using 10% methanol/chloroform as eluent (v/v, Rf = 0.20) to give
1 as a yellowish oil in 79% yield (1.52 g). API-ES-MS (positive) m/z193.0

1830
G. Li et al.
1
([M + H]+); H NMR (400 MHz, CDCl3): δ = 2.81 (t, J = 5.0 Hz, 2H),
3.69 (t, J = 5.0 Hz, 2H), 3.98 (s, 2H), 7.37 (s, 1H).
Synthesis of 2-Phenyliminothiazolidines 3: General Procedure
To a solution of 1 (1.0 mmol, 192.7 mg) in 50 mL of ethanol, the cor-
responding phenyl isothiocyanate (1.0 mmol) was added over a period
of 10 min, and the mixture was stirred at room temperature for 30–
60 min. The solvent was evaporated in vacuo, and the residue was
washed with Et2O (3 × 10 mL) and H2O (3 × 10 mL) to afford 2, which
was used directly without further purification.
The appropriate thiourea 2 (10 mmol) was dissolved in 10 mL of
80% sulfuric acid and heated at 90◦C for 45 min. The cooled mixture
was basified with 10 M NaOH in an ice bath. The precipitated gummy
residue was extracted with CH2Cl2 (3 × 10 mL). The organic layer was
washed with brine, dried (MgSO4), and the solvent was evaporated to
give crude 3, which was purified by column chromatography on silica
gel using petroleum ether and acetone as eluents. The overall yields of
these two steps ranged from 45% to 84%.
2-(Phenylimino)-3-(2-chlorothiazol-5-yl)methylthiazolidine (3a)
Yield: 65% (201.4 mg); mp 75.3–76.2◦C; IR (KBr): vmax = 1615, 1587,
1233, 768, 699 cm−1; 1H NMR (400 MHz, CDCl3): δ = 3.16 (t, J = 6.8 Hz,
2H), 3.53 (t, J = 6.8 Hz, 2H), 4.76 (s, 2H), 6.98–7.20 (m, 2H), 7.05–
7.10 (m, 1H), 7.29–7.34 (m, 2H), 7.45 (s, 1H); 13C NMR (125 MHz,
CDCl3): δ = 26.9, 42.8, 49.8, 121.7, 123.5, 129.0, 135.0, 140.3, 151.4,
153.2, 158.5; HRMS (ESI) calcd for C13H13ClN3S2 [M + H]+ 310.0239,
found 310.0237.
2-(2-Nitrophenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3b)
Yield: 82% (291.0 mg); mp 102.8–103.8◦C; IR (KBr): vmax = 1628,
1
1601, 1517, 1228, 761 cm−1; H NMR (400 MHz, CDCl3): δ = 3.23 (t,
J = 6.8 Hz, 2H), 3.63 (t, J = 6.8 Hz, 2H), 4.79 (s, 2H), 7.07 (dd, J =
1.2 Hz, 8.2 Hz, 1H), 7.11–7.17 (m, 1H), 7.44–7.52 (m, 2H), 7.89 (dd, J =
1.2 Hz, 8.2 Hz, 1H); HRMS (ESI) calcd for C13H12ClN4O2S2 [M + H]+
355.0090, found 355.0077.
2-(3-Nitrophenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3c)
Yield: 70% (248.4 mg); mp 102.1–103.9◦C; IR (KBr): vmax = 1625,
–1
1607, 1514, 1233, 745, 690 cm
;
1H NMR (400 MHz, CDCl3): δ =

New 2-Phenyliminothiazolidines
1831
3.24 (t, J = 6.8 Hz, 2H), 3.61 (t, J = 6.8 Hz, 2H), 4.79 (s, 2H), 7.33 (d,
J = 8.4 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.48 (s, 1H), 7.82–7.85 (m,
1H), 7.90–7.96 (m, 1H); HRMS calcd for C13H12ClN4O2S2 [M + H]+
355.0090, found 355.0081.
2-(4-Nitrophenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3d)
Yield: 76% (269.7 mg); mp 140.3–141.6◦C; IR (KBr): vmax = 1620,
1581, 1499, 1240, 855 cm–1; H NMR (400 MHz, CDCl3): δ = 3.25 (t,
1
J = 7.0 Hz, 2H), 3.62 (t, J = 7.0 Hz, 2H), 4.78 (s, 2H), 6.90–7.40 (m, 2H),
7.48 (s, 1H), 8.17–8.21 (m, 2H); HRMS (ESI) calcd for C13H12ClN4O2S2
[M + H]+ 355.0090, found 355.0084.
2-(4-N,N-Dimethylaminophenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3e)
Yield: 70% (247.0 mg); oil; IR (film): vmax = 1615, 1513, 1236,
821 cm–1; 1H NMR (400 MHz, CDCl3): δ = 2.92 (s, 6H), 3.13 (t, J = 6.8
Hz, 2H), 3.47 (t, J = 6.8 Hz, 2H), 4.73 (s, 2H), 6.74 (d, J = 8.8 Hz, 2H),
6.93 (d, J = 8.8 Hz, 2H), 7.43 (s, 1H); HRMS calcd for C15H18ClN4S2
[M + H]+ 353.0661, found 353.0665.
2-(2-Methylphenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3f)
Yield: 79% (255.8 mg); mp 76.1–77.2◦C; IR (KBr): vmax = 1622, 1595,
1228, 775 cm–1; H NMR (400 MHz, CDCl3): δ = 2.21 (s, 3H), 3.15 (t,
1
J = 6.8 Hz, 2H), 3.54 (t, J = 6.8 Hz, 2H), 4.80 (s, 2H), 6.87 (d, J = 8.0 Hz,
1H), 6.99 (d, J = 7.6 Hz, 1H), 7.11–7.20 (m, 2H), 7.46 (s, 1H); HRMS
(ESI) calcd for C14H15ClN3S2 [M + H]+ 324.0396, found 324.0409.
2-(2,6-Dimethylphenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3g)
Yield: 80% (270.3 mg); mp 78.9–80.3◦C; IR (KBr): vmax = 1628, 1587,
–1
1232, 764 cm
;
1H NMR (400 MHz, CDCl3): δ = 2.15 (s, 6H), 3.12
(t, J = 7.0 Hz, 2H), 3.57 (t, J = 7.0 Hz, 2H), 4.85 (s, 2H), 6.89 (t, J =
7.6 Hz, 1H), 7.02 (d, J = 7.6 Hz, 2H), 7.49 (s, 1H); HRMS (ESI) calcd
for C15H17ClN3S2 [M + H]+ 338.0552, found 338.0557.
2-(2-Trifluoromethylphenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3h)
Yield: 80% (302.3 mg); mp 102.7–103.4◦C; IR (KBr): vmax = 1626,
1599, 1230, 762 cm–1; H NMR (400 MHz, CDCl3): δ = 3.19 (t, J =
1
7.0 Hz, 2H), 3.59 (t, J = 7.0 Hz, 2H), 4.80 (s, 2H), 7.02 (d, J = 8.0 Hz,

1832
G. Li et al.
1H), 7.12 (t, J = 7.6 Hz, 1H), 7.42–7.49 (m, 2H), 7.61 (d, J = 8.0 Hz,
1H); HRMS (ESI) calcd for C14H12ClF3N3S2 [M + H]+ 378.0113, found
378.0123.
2-(3-Trifluoromethylphenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3i)
Yield: 60% (226.7 mg); oil; IR (film): vmax = 1622, 1601, 1585, 1230,
1
799, 700 cm−1; H NMR (400 MHz, CDCl3): δ = 3.16 (t, J = 6.8 Hz,
2H), 3.53 (t, J = 6.8 Hz, 2H), 4.74 (s, 2H), 7.17 (d, J = 8.0 Hz, 1H),
7.25 (s, 1H), 7.31 (t, J = 8.0 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.45 (s,
1H); HRMS (ESI) calcd for C14H12ClF3N3S2 [M + H]+ 378.0113, found
378.0109.
2-(2-Fluorophenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3j)
Yield: 76% (249.2 mg); mp 96.2–97.0◦C; IR (KBr): vmax = 1621, 1603,
1235, 766 cm–1; H NMR (400 MHz, CDCl3): δ = 3.19 (t, J = 7.0 Hz,
1
2H), 3.58 (t, J = 7.0 Hz, 2H), 4.80 (s, 2H), 6.98–7.12 (m, 4H), 7.47 (s,
1H); HRMS (ESI) calcd for C13H12ClFN3S2 [M + H]+ 328.0144, found
328.0145.
2-(4-Fluorophenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3k)
Yield: 84% (275.4 mg); mp 91.7–92.6◦C; IR (KBr): vmax = 1613, 1502,
1223, 836 cm–1; H NMR (400 MHz, CDCl3): δ = 3.17 (t, J = 6.8 Hz,
1
2H), 3.53 (t, J = 6.8 Hz, 2H), 4.74 (s, 2H), 6.91–7.03 (m, 4H), 7.45 (s,
1H); HRMS (ESI) calcd for C13H12ClFN3S2 [M + H]+ 328.0144, found
328.0145.
2-(2,4-Difluorophenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3l)
Yield: 80% ( 276.7 mg); mp 116.8–117.3◦C; IR (KBr): vmax = 1619,
1527, 1236, 848, 806 cm−1; 1H NMR (400 MHz, CDCl3): δ = 3.20 (t, J =
7.0 Hz, 2H), 3.58 (t, J = 7.0 Hz, 2H), 4.78 (s, 2H), 6.77–6.89 (m, 2H),
6.92–7.00 (m, 1H), 7.47 (s, 1H); HRMS (ESI) calcd for C13H11ClF2N3S2
[M + H]+ 346.0051, found 346.0036.
2-(2,6-Difluorophenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3m)
Yield: 81% (280.1 mg); mp 155.1–156.0◦C; IR (KBr): vmax = 1622,
1528, 1236, 789, 743 cm–1;1H NMR (400 MHz, CDCl3): δ = 3.22 (t, J =
7.0 Hz, 2H), 3.63 (t, J = 7.0 Hz, 2H), 4.83 (s, 2H), 6.85–7.02 (m, 3H),

New 2-Phenyliminothiazolidines
1833
7.48 (s, 1H); HRMS (ESI) calcd for C13H11ClF2N3S2 [M + H]+ 346.0051,
found 346.0036.
2-(2-Chlorophenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3n)
Yield: 67% (230.7 mg); mp 100.4–101.4◦C; IR (KBr): vmax = 1619,
1584, 1230, 771 cm–1; H NMR (400 MHz, CDCl3): δ = 3.19 (t, J =
1
6.8 Hz, 2H), 3.59 (t, J = 6.8 Hz, 2H), 4.83 (s, 2H), 6.96–7.02 (m, 2H),
7.17–7.23 (m, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.49 (s, 1H), 13C NMR (125
MHz, CDCl3): δ = 26.8, 42.5, 50.1, 122.9, 124.3, 127.2, 127.3, 129.8,
135.2, 140.4, 148.4, 153.0, 159.6; HRMS (ESI) calcd for C13H12Cl2N3S2
[M + H]+ 343.9850, found 343.9862.
2-(4-Chlorophenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3o)
Yield: 70% (241.0 mg); mp 108.3–109.1◦C; IR (KBr): vmax = 1608,
1579, 1235, 836 cm–1; H NMR (400 MHz, CDCl3): δ = 3.17 (t, J =
1
7.0 Hz, 2H), 3.53 (t, J = 7.0 Hz, 2H), 4.74 (s, 2H), 6.93 (d, J = 8.8 Hz,
2H), 7.26 (d, J = 8.8 Hz, 2H), 7.45 (s, 1H); 13C NMR (125 MHz, CDCl3):
δ = 26.9, 42.7, 49.9, 123.1, 128.6, 129.0, 134.8, 140.4, 149.9, 153.2,
159.0; HRMS (ESI) calcd for C13H12Cl2FN3S2 [M + H]+ 343.9850, found
343.9863.
2-(4-Methylphenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3p)
Yield: 84% (272.0 mg); mp 65.0–65.7◦C; IR (KBr): vmax = 1621, 1602,
1505, 1231, 825 cm–1; 1H NMR (400 MHz, CDCl3): δ = 2.33 (s, 3H), 3.15
(t, J = 6.8 Hz, 2H), 3.51 (t, J = 6.8 Hz, 2H), 4.75 (s, 2H), 6.90 (d, J =
8.2 Hz, 2H), 7.12 (d, J = 8.2 Hz, 2H), 7.44 (s, 1H); HRMS (ESI) calcd
for C14H15ClN3S2 [M + H]+ 324.0396, found 324.0391.
2-(4-Methyl-2-nitrophenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3q)
Yield: 80% (295.1 mg); mp 86.8–87.7◦C; IR (KBr): vmax = 1613, 1557,
1237, 828, 794 cm–1; 1H NMR (400 MHz, CDCl3): δ = 2.38 (s, 3H), 3.21
(t, J = 7.0 Hz, 2H), 3.61 (t, J = 7.0 Hz, 2H), 4.79 (s, 2H), 6.96 (d, J =
8.4 Hz, 1H), 7.30 (dd, J = 1.2 Hz, 8.4 Hz, 1H), 7.46 (s, 1H), 7.71 (d, J =
1.2 Hz, 1H); HRMS (ESI) calcd for C14H14ClN4O2S2 [M + H]+ 369.0247,
found 369.0257.

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G. Li et al.
2-(4-Methoxy-2-nitrophenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3r)
Yield: 81% (311.7 mg); mp 112.8–113.6◦C; IR (KBr): vmax = 1607,
1561, 1225, 828, 794 cm–1; 1H NMR (400 MHz, CDCl3): δ = 3.21 (t, J =
7.0 Hz, 2H), 3.61 (t, J = 7.0 Hz, 2H), 3.85 (s, 3H), 4.79 (s, 2H), 6.99
(d, J = 8.8 Hz, 1H), 7.09 (dd, J = 2.8 Hz, 8.8 Hz, 1H), 7.43 (d, J = 2.8
Hz, 1H), 7.46 (s, 1H); HRMS (ESI) calcd for C14H14ClN4O3S2 [M + H]+
385.0196, found 385.0193.
2-(2-Methoxyphenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3s)
Yield: 45% (152.9 mg); oil; IR (film): vmax = 1622, 1586, 1247, 751
cm–1; 1H NMR (400 MHz, CDCl3): δ = 3.11 (t, J = 6.8 Hz, 2H), 3.50 (t,
J = 6.8 Hz, 2H), 3.83 (s, 3H), 4.79 (s, 2H), 6.87–6.93 (m, 3H), 7.02–7.08
(m, 1H), 7.48 (s, 1H); HRMS (ESI) calcd for C14H15ClN3OS2 [M + H]+
340.0345, found 340.0358.
2-(4-Methoxyphenyl)imino-3-(2-chlorothiazol-5-
yl)methylthiazolidine (3t)
Yield: 40% (135.9 mg); mp 78.5–79.6◦C; IR (KBr): vmax = 1619, 1502,
1229, 836 cm–1; H NMR (400 MHz, CDCl3): δ = 3.15 (t, J = 6.8 Hz,
1
2H), 3.50 (t, J = 6.8 Hz, 2H), 3.80 (s, 3H), 4.75 (s, 2H), 6.86 (d, J = 8.8
Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 7.44 (s, 1H); HRMS (ESI) calcd for
C14H15ClN3OS2 [M + H]+ 340.0345, found 340.0337.
Biological Assay
All compounds were dissolved in a mixture of DMF, emulsifier 0201
(a mixture of anionic and nonionic surfactant), and water to give a
solution of the required concentration according to the experimental
needs. The concentration of the surfactant was not higher than 0.1%.
The insecticidal bioassay tests were carried out by following the FAO
(1971) and IRAC (2004) test method.27,28
Activity Against Third-Instar Larvae of Cx. pipiens pallens
A solution of 50 mg/L was added into each well of 96 well plates.
Twenty third-instar larvae of Cx. pipiens pallens were used in each
well and kept at 24 1◦C in the thermostatic chamber for 24 h. The
mortality rates (%) of test worm were determined (Table I). The exper-
iments were conducted in three replicates for each concentration.
Activity Against A. Craccivora
A leaf-dipping method was used to evaluate the activity of the test
samples. Thirty apterous adults of A. craccivora placed on pea sprouts

New 2-Phenyliminothiazolidines
1835
were dipped into 1000 mg/L solutions for 5 s, and then excrescent solu-
tion on pea sprouts were removed. All treated samples were maintained
at 24 1◦C in the thermostatic chamber for 24 h. The mortality rates
(%) of test worm were determined (Table II). The experiments were
conducted in three replicates for each concentration.
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