Synthesis and biological activities of novel thiazole derivatives of DHPMs via the N, S-dialkylation

Article abstract of DOI:10.1080/10426500701841680

A series of novel 1-[6-aryl-1-(2-chlorothiazol-5-yl-methyl)-2-(2- chlorothiazol-5-yl -methylsulfanyl)-4-methyl-1,6-dihydropyrimidin-5-yl] carboxylates or ethanones 2 were synthesized via the N,S-dialkylation of 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) 1 us

Full text of DOI:10.1080/10426500701841680

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Synthesis and Biological
Activities of Novel Thiazole
Derivatives of DHPMs via the N,
S-dialkylation
Xiao-Fei Zhu a & De-Qing Shi a
a Key Laboratory of Pesticide & Chemical Biology of
Ministry of Education, College of Chemistry , Central
China Normal University , Wuhan, P. R. China
Published online: 28 Jul 2008.
To cite this article: Xiao-Fei Zhu & De-Qing Shi (2008) Synthesis and Biological
Activities of Novel Thiazole Derivatives of DHPMs via the N, S-dialkylation,
Phosphorus, Sulfur, and Silicon and the Related Elements, 183:8, 2020-2028, DOI:
10.1080/10426500701841680
To link to this article: http://dx.doi.org/10.1080/10426500701841680
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Phosphorus, Sulfur, and Silicon, 183:2020–2028, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701841680
Synthesis and Biological Activities of Novel Thiazole
Derivatives of DHPMs via the N, S-dialkylation
Xiao-Fei Zhu and De-Qing Shi
Key Laboratory of Pesticide & Chemical Biology of Ministry of
Education, College of Chemistry, Central China Normal University,
Wuhan, P. R. China
A series of novel 1-[6-aryl-1-(2-chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-yl -
methylsulfanyl)-4-methyl-1,6-dihydropyrimidin-5-yl]carboxylates or ethanones 2
were synthesized via the N,S-dialkylation of 3,4-dihydropyrimidin-2(1H)-ones (DH-
PMs) 1 using 2-chloro-5-(chloromethyl)thiazole as the alkylation reagent in one-pot
reaction. The structures of the target compounds were confirmed by IR, 1H NMR, EI-
MS and elemental analyses, and, in the case of 2c, by single crystal X-ray diffraction.
The preliminary bioassay indicated that the title compounds 2 possess moderate to
weak fungicidal and insecticidal activities.
Keywords 3,4-Dihydropyrimidin-2(1H)-one; biological activity; N,S-dialkylation;
substituted thiazole
INTRODUCTION
The Biginelli reaction involves an one-pot reaction between aldehyde,
1,3-dicarbonyl and urea or thiourea in the presence of an acidic
catalyst to afford 3,4-Dihydropyrimidin-2(1H)-one (DHPM). Some
DHPMs and their derivatives have attracted considerable interest
due to their significant therapeutic and pharmacological properties,
such as antiviral, antitumor, antibacterial and anti-inflammatory
properties and so on.1−3 There are some reports on the S-alkylation
of DHPMs, and the alkylation reagents are usually benzyl and allyl
halides.4,5 However, there are few reports on the N, S-dialkylation of
DHPMs in one pot reaction. Many thiazolyl containing compounds are
also known to possess a wide range of biological and pharmacological
Received 29 August 2007; accepted 28 September 2007.
The authors are grateful to the Natural Science Foundation of China (grant No.
20302002) for financial support.
Address correspondence to De-Qing Shi Key Laboratory of Pesticide & Chemical Bi-
ology of Ministry of Education, College of Chemistry, Central China Normal University,
Wuhan 430079, P. R. China. E-mail: chshidq@mail.ccnu.edu.cn
2020

Thiazole Derivatives of DHPMs via the N, S-dialkylation
2021
SCHEME 1
activities, as well as low toxicity toward mammals,6−9 and some
thiazolyl containing pesticides (such as thiamethoxam, clothianidim,
fosthiazate, etc., (Scheme 1) have been commercialized.10−13 As a
continuation of our search for new biologically active compounds.14−15
Herein, we hope to report a convenient synthesis of novel 1-[6-aryl-1-
(2-chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-yl-methylsulfanyl)-
4-methyl-1,6-dihydropyrimidin-5-yl]carboxylates or ethanones 2 via
the N, S-dialkylation of 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) 1
using 2-chloro-5-(chloromethyl)thiazole as the alkylation reagent in
one pot reaction as well as their biological activities.
RESULT AND DISCUSSION
We synthesized DHPMs according to an improved method.16 DH-
PMs reacted with 2-chloro-5(chloromethyl)thiazole to afford pure N,S-
dialkylation products in high yields and no mono S-alkylation product
was detected even in the presence of excess DHPMs (3-4 equimolecular).
It was found that different bases played a major role in the reactions,
when triethyl amine was used, the yield was very low (about 20%) in
refluxing temperature for 12 h, however, when anhydrous potassium
carbonate was used, the reaction underwent very smoothly at room
temperature and the yields were also good (Scheme 2).
All products were fully characterized by IR, 1H NMR, EIMS and el-
emental analysis. All the spectral data were in accordance with the
anticipated structures. In the 1H NMR spectra of 2, the two protons of
SCHEME 2

2022
X.-F. Zhu and D.-Q. Shi
FIGURE 1 The structure of 2c, showing displacement ellipsoids at the 50%
probability level for non-H atoms.
the CH2S moieties displayed two doublet as the result of their differ-
ent chemical environments and coupling with each other, however, the
two protons of the CH2N moieties displayed as singlet and sometimes
appeared as two doublet. 6-Position proton of 1,6-dihydropyrimidine ex-
hibited as singlet. IR spectra of compounds 2 showed normal stretching
absorption bands, indicating the existence of C O (∼1620 cm−1), C=N
(∼1600 cm−1). The EI mass spectra of compounds 2 revealed the exis-
tence of the molecular ion peaks and anticipant fragmentation peaks,
which were in good accordance with the given structures of products.
Moreover, in order to confirm their molecular structure absolutely
and investigate its regioselectivity, a single crystal of 2c was obtained
as light yellow crystals from a dichloromethane and hexane (2:1 v/v) sol-
vent system as an example. X-ray diffraction analysis indicates that the
single crystal of 2c is monoclinic with space group P2(1)/c, cell parame-
◦
˚
ters a = 10.612 (1), b = 18.741 (1), c = 12.463 (1) A, β = 113.820 (1) , v =
3
3
−1
˚
2267.6 (2) A , z = 4, Dx = 1.492 g/cm , F (000) = 1048, µ = 0.59 mm
and final R = 0.047, wR = 0.134 for 4937 reflections (I > 2σ(I)). Figure 1
and Figure 2 show the molecular structure of compound 2c and packing
of the molecules in the unit cell, respectively. Intermolecular C-H. . . O
and C-H. . . N and C-H. . . S hydrogen bonds contribute to the stability
of the crystal structure (Figure 2 and Table 1). The dihydropyrimidine
ring is almost planer, with a mean deviation from the plane of 0.132
˚
(1) A. The dihedral angles between the dihydropyrimidine ring and the

Thiazole Derivatives of DHPMs via the N, S-dialkylation
2023
FIGURE 2 Part of the crystal packing of 2c, Hydrogen bonds are shown as
dashed lines. H atoms not involved in these interactions have been omitted.
phenyl, 1-thiazole and 2-thiazole rings are 88.5 (1), 13.6 (1) and 8.0 (1)◦,
respectively.
Compounds 2 were tested for insecticidal activities against aphides
at the concentration of 250 mg/L according to a previously reported
◦
˚
TABLE I Hydrogen-Bond Geometry (A, )
D-H. . . A
D-H
H. . . A
D. . . A
D-H. . . A
C(18)-H(18A). . . N(1)
C(14)-H(14A). . . S(2)
C(7)-H(7). . . O(1)
0.97
0.97
0.98
0.97
0.96
2.39
2.51
2.32
2.39
2.45
2.799 (3)
2.972 (2)
2.687 (3)
3.314 (3)
3.390 (3)
105
109
101
159
167
C(18)-H(18B). . . O(1)i
C(12)-H(12A). . . N(3)ii
Symmetry codes: (i) −x+1, y+1/2, −z+1/2 ; (ii) x−1, y, z.

2024
X.-F. Zhu and D.-Q. Shi
TABLE II The Insecticidal and Fungicidal Activities of Compounds
of 2a∼2i (Inhibitory Rate%)
Insecticidal
Fungicidal activity (50 mg/L)
activity
(250 mg/L) Fusarium Rhizoctonia Botrytis Gibberella Dothiorella Colletotrichum
Compd. aphides oxysporium
solani
cinereapers
zeae
gregaria
gossypii
2a
2b
2c
2d
2e
2f
2g
2h
2i
34
56
28
25
16
41
36
47
29
12
40
26
27
15
45
12
27
13
23
46
65
16
46
58
35
26
12
16
40
32
11
7
40
12
19
20
20
24
18
39
39
54
18
36
10
12
16
29
16
27
69
32
54
5
30
38
50
30
60
26
48
48
10
method.17 The result is listed in Table II, which indicated that the ti-
tle compounds 2 possess moderate to weak insecticidal activity at this
dosage.
The fungicidal activities of the target compounds 2 were tested at
a concentration of 50 mg/L. The six fungi used, Fusarium oxysporium,
Rhizoctonia solani, Botrytis cinereapers, Gibberella zeae, Dothiorella
gregaria ,Colletotrichum gossypii, belong to the group of field fungi and
were isolated from corresponding crops. The activity data were listed in
Table II. The preliminary bioassay indicated that the title compounds
2 possess moderate to weak inhibitory activities against the above six
fungi. Further structure-activity relationships are under investigation.
In conclusion,
a convenient synthesis of novel 1-[6-aryl-1-
(2-chlorothiazol-5-ylmethyl)-2-(2-chlorothiazol-5-ylmethylsulfanyl)-4-
methyl-1,6-dihydropyrimidin-5-yl]carboxylates or ethanones via the
N, S-dialkylation of 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) 1 using
2-chloro-5-(chloromethyl)thiazole as the alkylation reagent in one pot
reaction was presented. It was found that only pure N,S-dialkylation
products were formed even in the presence of excess DHPMs (3-4
equimolecular) and no mono S-alkylation product was detected. The
results of the preliminary bioassays indicated that the title compounds
2 possess moderate to weak fungicidal and insecticidal activity.
EXPERIMENTAL
Melting points were determined with a WRS-1B digital melting point
apparatus and are uncorrected. 1H NMR spectra were recorded with a
Varian Mercury PLUS400 spectrometer with TMS as the internal refer-
ence and CDCl3 as the solvent, while mass spectra were obtained with a

Thiazole Derivatives of DHPMs via the N, S-dialkylation
2025
Finnigan TRACEMS2000 spectrometer using the EI method. IR spec-
tra were measured by a Nicolet NEXUS470 spectrometer. Elemental
analyses were performed with an Elementar Vario ELXCHNSO ele-
mental analyzer. X-ray diffraction analysis was performed on a Bruker
SMART 1000 CCD diffractometer. DHPMs were synthesized according
to the reported method.16 All of the solvents and materials were reagent
grade and purified as required.
Preparation of 1-[6-Aryl-1-(2-chlorothiazol-5-ylmethyl)-2-
(2-chlorothiazol-5-ylmethylsulfanyl)-4-methyl-1,6-
dihydropyrimidin-5-yl]carboxylate or Ethanone 2—
General Procedure
A solution of DHPM 1 (2 mmol), 2-chloro-5-(chloromethyl)thiazole (0.67
g, 4 mmol), potassium carbonate powder (0.55 g, 4 mmol) and anhydrous
DMF (15 mL) was stirred vigorously at room temperature until the re-
action was complete (monitored by TLC), the solid filtered off and the
filtrate concentrated under vacuum. The residue was purified by flash
column chromatography on silica gel using ethyl acetate/petroleum
ether (1:2, v/v) as the eluent to give 2a∼2i as yellow crystals.
1-[6-(4-Chlorophenyl)-1-(2-chlorothiazol-5-yl-methyl)-2-(2-
chlorothiazol-5-yl-methylsulfanyl)-4-methyl-1,6-
dihydropyrimidin-5-yl]ethanone (2a)
Yellow crystals, yield 87%, m.p. 150–152◦C; 1H NMR (CDCl3,
400 MHz) δ: 2.32 (s, 3H, CH3), 2.48 (s, 3H, CH3), 4.41 (d, J = 15.6
Hz, 1H, SCH2), 4.56 (s, 2H, NCH2), 4.74 (d, J = 16.0 Hz, 1H, SCH2),
5.46 (s, 1H, CHAr), 7.20–7.29 (m, 4H, Ar-H), 7.42 (s, 1H, thiazole-H),
7.50 (s, 1H, thiazole-H); EI-MS (70 eV) m/z(%): 543 (M+1, 17.4), 542
(M+, 17.0), 410 (17.8), 163 (15.4), 131 (100), 96 (16.6), 76 (24.4); Anal.
calcd for C21H17Cl3N4OS3: C 46.37, H 3.15, N 10.30; found C 46.44, H
3.18, N 10.16.
1-[1-(2-Chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-yl-
methylsulfanyl)-4-methyl-6-(4-tolyl)-1,6-dihydropyrimidin-5-
yl]ethanone (2b)
Yellow crystals, yield 91%, m.p. 139–141◦C; IR (KBr): 3086 (Ar-H),
1624 (C=O), 1599 (C=N), 1494, 1409 cm−1; 1H NMR (CDCl3, 400 MHz)
δ: 2.27 (s, 3H, CH3), 2.30 (s, 3H, CH3), 2.44 (s, 3H, CH3), 4.36 (d, J= 16.0
Hz, 1H, SCH2), 4.54 (s, 2H, NCH2), 4.67 (d, J= 16.4 Hz, 1H, SCH2), 5.40
(s, 1H, CHAr), 7.10–7.18 (m, 4H, Ar-H), 7.42 (s, 1H, thiazole-H), 7.46
(s, 1H, thiazole-H); EI-MS (70 eV) m/z(%): 522 (M+, 33.0), 431 (28.4),
227 (56.6), 163 (62.3), 139 (97.3), 113 (100), 76 (98.5); Anal. calcd. for

2026
X.-F. Zhu and D.-Q. Shi
C22H20Cl2N4OS3: C 50.47, H 3.85, N 10.70; found: C 50.29, H 3.73,
N 10.54.
1-[1-(2-Chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-yl-
methylsulfanyl)-4-methyl-6-phenyl-1,6-dihydropyrimidin-5-
yl]ethanone (2c)
Yellow crystals, yield 87%, m.p. 150–152◦C; 1H NMR (CDCl3,
400 MHz) δ: 2.27 (s, 3H, CH3), 2.32 (s, 3H, CH3), 4.37 (d, J = 16.4
Hz, 1H, SCH2), 4.53 (s, 2H, NCH2), 4.69 (d, J = 16 Hz, 1H, SCH2), 5.46
(s, 1H, CHAr), 7.27–7.31 (m, 5H, Ar-H), 7.41 (s, 1H, thiazole-H), 7.47
(s, 1H, thiazole-H); Anal. Calcd for C21H18Cl2N4OS3: C 49.50, H 3.56,
N 11.0; found: C 49.37, H 3.60, N 11.23.
1-[1-(2-chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-yl-
methylsulfanyl)-6-(4-methoxyphenyl)-4-methyl-1,6-
dihydropyrimidin-5-yl]ethanone (2d)
Yellow crystals, yield 90%, m.p. 129–131◦C; IR (KBr): 3081 (Ar-H),
1623 (C=O), 1064 (C=N), 1495, 1460 cm−1; 1H NMR (CDCl3, 400 MHz)
δ: 2.25 (s, 3H, CH3), 2.46 (s, 3H, CH3), 3.77 (s, 3H, OCH3), 4.43 (d, J =
15.6 Hz, 1H, SCH2), 4.52 (s, 2H, NCH2), 4.70 (d, J= 15.2 Hz, 1H, SCH2),
5.38 (s, 1H, CHAr), 6.81–7.27 (m, 4H, Ar-H), 7.42 (s, 1H, thiazole-H),
7.47 (s, 1H, thiazole-H); Anal. calcd for C22H20Cl2N4O2S3: C 48.98, H
3.74, N 10.38; found: C 49.06, H 3.61, N 10.25.
1-[1-(2-Chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-yl-
methylsulfanyl)-4-methyl-6-(thiophen-2-yl)-1,6-
dihydropyrimidin-5-yl]ethanone (2e)
Yellow crystals, yield 80%, m.p. 109–110◦C; 1H NMR (CDCl3,
400 MHz) δ: 2.36 (s, 3H, CH3), 2.46 (s, 3H, CH3), 4.53 (d, J = 16.8
Hz, 1H, SCH2), 4.59 (s, 2H, NCH2), 4.79 (d, J = 16.4 Hz, 1H, SCH2),
5.76 (s, 1H, CHAr), 6.88-6.92 (m, 1H, Thiophene-H), 7.21 (d, J =
14.6 Hz, 2H, Thiophene-H), 7.46 (s, 2H, thiazole-H); Anal. calcd. for
C19H16Cl2N4OS4: C 44.27, H 3.13, N 10.87; found: C 44.14, H 3.01, N
10.69.
1-[1-(2-Chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-yl-
methylsulfanyl)-4-methyl-6-(4-nitrophenyl)-1,6-
dihydropyrimidin-5-yl]ethanone (2f)
Yellow crystals, yield 63%, m.p. 206–208◦C; 1H NMR (CDCl3,
400 MHz) δ: 2.37 (s, 3H, CH3), 2.47 (s, 3H, CH3), 4.37 (d, J = 16 Hz,
1H, SCH2), 4.55 (d, J = 10.8 Hz, 1H, NCH2), 4.63 (d, J = 10.4 Hz, 1H,
NCH2), 4.75 (d, J = 16.4 Hz, 1H, SCH2), 5.63 (s, 1H, CHAr), 7.42–7.50
(m, 4H, Ar-H), 8.14 (s, 1H, thiazole-H), 8.16 (s, 1H, thiaole-H); Anal.

Thiazole Derivatives of DHPMs via the N, S-dialkylation
2027
calcd. for C21H17Cl2N5O3S3: C 45.49, H 3.09, N 12.63; found: C 45.67,
H 3.15, N 12.78.
Ethyl 1-[1-(2-Chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-
yl-methylsulfanyl)-4-methyl-6-(4-tolyl)-1,6-dihydropyrimidin-
5-yl]carboxylate (2g)
Yellow crystals, yield 75%, m.p. 148–149◦C; IR (KBr): 3091 (Ar-H),
1664 (C=O), 1602, 1558 (C=N), 1500, 1422 cm−1;1H NMR (CDCl3,
400 MHz) δ: 1.17 (t, J = 8 Hz, 3H, CH3), 2.33 (s, 3H, CH3), 2.44 (s,
3H, CH3), 3.98–4.02 (m, 2H, OCH2), 4.30 (d, J = 15.6 Hz, 1H, SCH2),
4.34 (d, J = 10.0 Hz, 1H, NCH2), 4.49 (d, J = 10.4 Hz, 1H, NCH2),
4.66 (d, J = 16.0 Hz, 1H, SCH2), 5.25 (s, 1H, CHAr), 7.11–7.27 (m, 4H,
Ar-H), 7.41 (s, 1H, thiazole-H), 7.45 (s, 1H, thiaole-H); Anal. calcd. for
C23H22Cl2N4O2S3: C 49.90, H 4.01, N 10.02; found: C 60.81, H 4.07, N
9.83.
Ethyl 1-[1-(2-Chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-
yl-methylsulfanyl)-4-methyl-6-phenyl-1,6-dihydropyrimidin-5-
yl]carboxylate (2h).
Yellow crystals, yield 75%, m.p. 136–138◦C; IR (KBr): 3084 (Ar-H),
1
1660 (C=O), 1598, 1558 (C=N), 1501, 1444 cm−1; H NMR (CDCl3,
400 MHz) δ: 1.17 (t, J = 7.6 Hz, 3H, CH3), 2.44 (s, 3H, CH3), 3.98–4.04
(m, 2H, OCH2), 4.31 (d, J = 16.4 Hz, 1H, SCH2), 4.45 (d, J = 10.0 Hz,
1H, NCH2), 4.53 (d, J = 10.8 Hz, 1H, NCH2), 4.69 (d, J = 14.8 Hz,
1H, SCH2), 5.30 (s, 1H, CHAr), 7.27–7.34 (m, 5H, Ar-H), 7.40 (s, 1H,
thiazole-H), 7.43 (s, 1H, thiaole-H); EI-MS (70 eV) m/z(%): 538 (M+, 94),
462 (71.4), 404 (98.7), 275 (68.3), 168 (98.6), 113 (100), 87 (98.7); Anal.
calcd. for C22H20Cl2N4O2S3: C 48.98, H 3.74, N 10.38; found: C 48.80,
H 3.55, N 10.41.
Ethyl 1-[1-(2-Chlorothiazol-5-yl-methyl)-2-(2-chlorothiazol-5-
yl-methylsulfanyl)-6-(4-methoxyphenyl)-4-methyl-1,6-
dihydropyrimidin-5-yl]carboxylate (2i)
Yellow crystals, yield 80%, m.p. 118–119◦C; 1H NMR (CDCl3,
400 MHz) δ: 1.18 (t, J = 8 Hz, 3H, CH3), 2.44 (s, 3H, CH3), 3.79 (s,
3H, OCH3), 3.98–4.06 (m, 2H, OCH2), 4.36 (d, J = 15.6 Hz, 1H, SCH2),
4.48 (d, J = 10.0 Hz, 1H, NCH2), 4.50 (d, J = 10.8 Hz, 1H, NCH2), 4.86
(d, J = 16.0 Hz, 1H, SCH2), 5.22 (s, 1H, CHAr), 6.82–7.27 (m, 4H, Ar-H),
7.41 (s, 1H, thiazole-H), 7.45 (s, 1H, thiaole-H); EI-MS (70 eV) m/z(%):
568 (M+, 14.1), 523 (12.7), 330 (19.5), 158 (22.5), 132 (100), 87 (13.1);
Anal. calcd. for C23H22Cl2N4O3S3: C 48.50, H 3.89, N 9.84; found: C
48.71; H 4.02, N 9.78.

2028
X.-F. Zhu and D.-Q. Shi
Fungicidal Activity Testing
The fungicidal activity measurement method was adapted from the
one described by Molina.18 The synthesized target compounds were
dissolved in 0.5–1.0 mL of DMF to the concentration of 500 mg/L. The
solutions (1 mL) were mixed rapidly with thawed potato glucose agar
culture medium (9 mL) under 50◦C. The mixtures were poured into
Petri dishes. After the dished were cooled, the solidified plates were
incubated with 4 mm mycelium disk, inverted, and incubated at 28◦C
for 48 h. Water was used as the blank control. Three replicates of each
test were carried out. The mycelial elongation radius (mm) of fungi
settlements was measured after 48 h of culture. The growth inhibitory
rates were calculated with the following equation: I = [(C − T)/C] ×
100%. Here, I is the growth inhibitory rate (%), and T is the treatment
group fungi settlement radius (mm). The results are listed in Table II.
REFERENCES
[1] C. O. Kappe, Tetrahedron 49, 6937 (1993).
[2] C. O. Kappe, Acc. Chem. Res., 33, 879 (2000).
[3] C. O. Kappe, Eur. J. Med. Chem., 35, 1043 (2000).
[4] M. M. Ghorab, S. M. Abdel-Gawad, and M. S. A. El-Gaby, Farmaco, 55, 249 (2000).
[5] K. Rana, B. Kaur, and B. Kumar, Indian J. of Chem., 43B (7), 1553 (2004).
[6] M. C. Liu, T. S. Lin, J. G. Cory, A. H. Cory, and A. C. Sartorelli, J. Med. Chem., 39,
2586–2593 (1996).
[7] B. L. Finkelstein, M. A. Martz, C. Strock, J. Pestic. Sci., 50, 319–323 (1997).
[8] G. Y. Li X. H. Qian, J. N. Cui, Q. C. Huang, R. Zhang, and H. Guan, J. Agric. Food
Chem., 54, 125–129 (2006).
[9] Y. W. Jo, W. B. Im, J. K. Rhee, M. J. Shim, W. B. Kim, and E. C. Choi, Bioorg. Med.
Chem., 12, 5909–5915 (2004).
[10] C. D. S. Tomlin, The Pesticide Manual (British Crop Production Council, Hampshire,
2000) 12th ed., pp. 355–1008.
[11] S. Zhang, A. Phadke, C. Liu, X. Wang, J. Quinn, D. Chen, V. Gadhachanda, S. Li, M.
Deshpande, Thiazole compounds and Methods of Use, WO 2 006 122 011, (2006).
[12] C. L. Liu, L. Li, and Z. M. Li, Bioorg. Med. Chem., 12, 2825 (2004).
[13] (a) R. P. Alexander, P. Aujla, M. J. Batchelor, D. C. Brookings, G. M. Buckley, K. V. L.
Crepy, C. L. Kulisha, J. P. Turner, Fused Thiazole Derivatives as Kinase Inhibitors,
WO 2 006 114 606, (2006).
(b) Li, G.; Qian, X.; Cui, J.; Huang, Q.; Zhang, R.; Liu, F. J. Fluorine Chem. 2006,
127, 182.
[14] Z. G. Luo and D. Q. Shi, J. Heterocycl. Chem., 43, 1021–1026 (2006).
[15] X. B. Chen, D. Q. Shi, and X. F. Zhu, Chin. J. Chem. 25, 1854–1858 (2007).
[16] G. Sabitha, G. S. K. K. Reddy, C. S. Reddy, and J. S. Yadav, Synlett., 858–860 (2003).
[17] K. Kiriyama, S. Kagabu, and K. Nishimura, J. Pestic. Sci., 29, 43 (2004).
[18] J. Molina-Torres, C. J. Salazar-Cabrera, C. Armenta-Salinas, and E. Ramirez-
Chavez, J. Agric. Food Chem., 52, 4700–4704 (2004).