Synthesis, characterization and herbicidal activity of new thiazoline derivatives

Article abstract of DOI:10.1016/j.cclet.2013.01.036

A series of new thiazoline derivatives 2-alkyl(aryl) imino-4-amino-5- ethoxycarbonyl-3-phenyl-3H-thiazoline (3) and bis(2-imino-4-amino-5- ethoxycarbonyl-3-phenyl-3H-thiazoline alkylene (4) have been synthesized by reactions of intermediate 4-amino-5-ethoxycarbonyl-2-methylthio-3-phenyl-3H- thiazolinium sulphate (2) with alkylamines or arylamine in 64%-89% yields. The structures of 3 and 4 have been confirmed by ¹H NMR, EI-MS, IR spectroscopy and elemental analyses. Some compounds exhibited high or moderate herbicidal activities against the roots of rapeseed and barnyard grass at 100 mg/L.

Full text of DOI:10.1016/j.cclet.2013.01.036

Chinese Chemical Letters 24 (2013) 233–235
Contents lists available at SciVerse ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Original article
Synthesis, characterization and herbicidal activity of new thiazoline derivatives
Jian-Chao Liu a,1, Ying Liang b,1, Hong-Wu He a,
*
a College of Chemistry, Central China Normal University, Wuhan 430079, China
b Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Science, Wuhan 430064, China
A R T I C L E I N F O
A B S T R A C T
Article history:
A series of new thiazoline derivatives 2-alkyl(aryl) imino-4-amino-5-ethoxycarbonyl-3-phenyl-3H-
thiazoline (3) and bis(2-imino-4-amino-5-ethoxycarbonyl-3-phenyl-3H-thiazoline alkylene (4) have
been synthesized by reactions of intermediate 4-amino-5-ethoxycarbonyl-2-methylthio-3-phenyl-3H-
thiazolinium sulphate (2) with alkylamines or arylamine in 64%–89% yields. The structures of 3 and 4
have been confirmed by 1H NMR, EI-MS, IR spectroscopy and elemental analyses. Some compounds
exhibited high or moderate herbicidal activities against the roots of rapeseed and barnyard grass at
100 mg/L.
Received 19 November 2012
Received in revised form 13 December 2012
Accepted 6 January 2013
Available online 14 February 2013
Keywords:
Thiazoline
ß 2013 Hong-Wu He. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights
reserved.
Alkylamine
Arylamine
Herbicidal activity
1. Introduction
2. Experimental
The chemistry of 2-thiazolines, including new methodologies
for their preparation and recent applications in organic synthesis
or in the biological field, has been recently reviewed [1,2]. The 2-
iminothiazolidine ring system has gained interest for potential use
Melting points were measured on uncorrrected WRS-1B digital
apparatus. IR spectra were recorded on a Nicolet Avatar 360 FTIR
spectrometer. MS was determined on a Finnigan Trace MS 2000
spectrometer. 1H NMR spectra were recorded in CDCl3 on a Varian
Mercury 400 spectrometer and resonances are given in ppm
relative to TMS. Elemental analyses were taken on a Vario EL III
instrument. All of the solvents and materials were reagent grade
and purified before use.
as
a potent inhibitor of octopaminergic agonists [3,4], an
anthelmintic [5], an anti-inflammatory agent [6,7], a trehalase [8],
and an antimalarial agent [9]. Synthesis of the 2-iminothiazo-
line ring system generally starts from 1,3-bis-thiocarbanilides and
phenacyl bromide or the analogous reaction with
a
-chloroaliphatic
To a solution of 1 (1.40 g, 5 mmol) in CH3CN (20 mL) was added
dimethyl sulfate (0.95 g, 7.5 mmol) at room temperature. The
reaction mixture was heated to 80 8C and stirred for 3 h, then
filtered, distilled. The yellow solid was recrystallized from
anhydrous C2H5OH to give an intermediate 2 (Scheme 1).
To a solution of 2 (3.25 g, 5 mmol) in anhydrous C2H5OH
(30 mL) was added the n-propylamine (0.30 g, 5 mmol). After the
reaction mixture was stirred for 10 min, distilled water (30 mL)
was added to the reaction solution and stirred for an additional
30 min. The mixture was filtered, distilled, and the solid was
recrystallized from anhydrous C2H5OH or CH2Cl2 to give 3a (1.00 g,
65% yield). Compounds 3b–3i and 4a–4c were obtained by the
reactions of other substituted amines with intermediate 2.
ketones [10,11]. However, few 2-iminothiazoline derivatives
with bioactivity, in particular herbicidal activity, have been
reported.
Recently, we focused our attention on the synthesis of N-
heterocyclic compounds such as thienopyrimidinones, pyridopyr-
imidinones, and thiazolopyrimidinones to evaluate their biological
activities [12,13]. In this article, a series of new thiazoline
derivatives 2-alkyl(aryl)imino-4-amino-5-ethoxycarbonyl-3-phe-
nyl-3H-thiazoline (3) and bis(2-imino-4-amino-5-ethoxycarbo-
nyl-3-phenyl-3H-thiazoline alkylene (4) have been synthesized in
order to investigate their herbicidal activities.
3. Results and discussion
* Corresponding author.
The intermediate 4-amino-5-ethoxycarbonyl-2-methylthio-3-
phenyl-3H-thiazolinium sulphate (2) was prepared by the reaction
of 4-amino-2,3-dihydro-3-phenyl-2-thioxothiazole-5-carboxylate
E-mail addresses: journal@mail.ccnu.edu.cn, he1208@mail.ccnu.edu.cn
(H.-W. He).
1
Co-first authors.
1001-8417/$ – see front matter ß 2013 Hong-Wu He. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.01.036

234
J.-C. Liu et al. / Chinese Chemical Letters 24 (2013) 233–235
Ph
N+
Ph
N
Ph
N
J = 7.2 Hz, CH2CH2CH2CH3), 4.23 (q, 2H, J = 7.2 Hz, CO2CH2CH3),
NH2
NH2
NH2
Me2SO4 , 80 ºC
CH3CN
RNH
5.78 (s, 2H, NH2), 7.27–7.56 (m, 5H, Ph–H); EI-MS (70 eV, m/z)
2
MeS
R
N
S
(relative intensity %): 319 (M+, 100), 237 (72), 133 (66); IR (KBr,
2-
S
2
2 SO4
S
S
H2O
CO2Et
CO2Et
CO2Et
cmÀ1):
v3362 (N–H), 2980 (C–H), 1663 (C55O), 1607, 1529, 1268;
3
1
R
elemental anal. calcd. for C16H21N3O2S (319.4): C, 60.16; H, 6.63; N,
13.16; S, 10.04; found: C, 60.44; H, 6.55; N, 12.86; S, 10.69. 3i:
Yellow crystal; yield: 52%; mp: 156.7–158.2 8C. 1H NMR (400 MHz,
H2N (CH2)n NH2
3a: n-Pro
3b: n-Bu
3c: CH3(CH2)5
3d: PhCH2
3e: 2-ClPhCH2
3f: Ph
CDCl3): d 1.26 (t, 3H, J = 7.2 Hz, CO2CH2CH3), 2.30 (s, 3H, CH3), 4.18
Ph
NH2
N
Ph
H2N
N
(q, 2H, J = 7.2 Hz, CO2CH2CH3), 5.78 (s, 2H, NH2), 6.85–7.61 (m, 9H,
Ph–H); EI-MS (70 eV, m/z) (relative intensity %): 353 (M+, 45), 119
(100), 77 (17); IR (KBr, cmÀ1):
v3469, 3330 (N–H), 3051 (Ar–H),
3g: 4-BrPh
3h: 4-MeOPh
3i: 4-MePh
N
(CH2)n N
CO2Et
S
S
EtO2C
4
2978 (C–H), 1662 (C55O), 1524, 1524, 1272; elemental anal. calcd.
for C19H19N3O2S (353.4): C, 64.57; H, 5.42; N, 11.89; S, 9.07; found:
C, 64.91; H, 5.78; N, 11.94; S, 9.01. 4a: Yellow crystal; yield: 73%;
4a: n=2; 4b: n=3; 4c: n=6
Scheme 1. Synthesis of 3 and 4.
mp: 169.5À170.6 8C. 1H NMR (400 MHz CDCl3):
d 1.33 (t, 6H,
(1) and dimethyl sulfate in CH3CN at 80 8C. The intermediate 2 was
treated with alkylamines or arylamine at room temperature to give
2-alkyl(aryl)imino-4-amino-5-ethoxycarbonyl-3-phenyl-3H-thia-
zoline (3) in the presence of H2O in moderate yields, while 2 was
converted to bis(2-imino-4-amino-5-ethoxycarbonyl-3-phenyl-
3H-thiazoline)alkylene (4) by treating with diaminoalkanes at
room temperature.
All crude products of 3 and 4 were purified by recrystallization
from CH2Cl2 or EtOH. The structures of 3 and 4 were confirmed by
their spectroscopic data. For example, the IR spectrum of 3a
revealed absorption bands at 1662 cmÀ1 (C55O), 3363 cmÀ1 (N–H)
and 2954 cmÀ1 (C–H). The 1H NMR spectrum of 3a showed the
J = 7.2 Hz, 2CO2CH2CH3), 3.28 (s, 4H, 2CH2), 4.24 (q, 4H, J = 7.2 Hz,
2CO2CH2CH3), 5.78 (s, 4H, 2NH2), 7.27–7.52 (m, 10H, Ph-H); EI-MS
(70 eV, m/z) (relative intensity %): 553 (M+, 61), 289 (50), 275 (100),
262 (56), 230 (80); IR (KBr, cmÀ1):
v
3341 (N–H), 3069 (Ar–H), 2972
(C–H), 1674 (C55O), 1579, 1544, 1269; elemental anal. calcd. for
26H28N6O4S2 (552.7): C, 56.50; H, 5.11; N, 15.21; S, 11.60; found:
C, 56.47; H, 5.19; N, 15.43; S, 11.28. 4b: Yellow crystal; yield: 69%;
mp: 184.2–186.1 8C. 1H NMR (400 MHz, CDCl3):
1.33 (t, 6H,
C
d
J = 7.2 Hz, 2CO2CH2CH3), 1.78 (t, 2H, J = 6.8 Hz, CH2), 3.10 (t, 4H,
J = 6.4 Hz, 2CH2), 4.24 (q, 4H, J = 7.2 Hz, 2CO2CH2 CH3), 5.78 (s, 4H,
2NH2), 7.35–7.57 (m, 10H, Ph–H); EI-MS (70 eV, m/z) (relative
intensity %): 567 (M+, 100), 290 (73), 160 (46); IR (KBr, cmÀ1):
signal of N–H at
of CH3 (–CO2CH2CH3) at
0.87 and the triplet of CH2 (–CH2CH2CH3) at
signals appeared at
d
5.78, the signal of –CO2CH2– at
d
4.23, the triplet
v3319 (N–H), 3053 (Ar–H), 2979 (C–H), 1661 (C55O), 1610, 1526,
d
1.32, the triplet of CH3 (–CH2CH2CH3) at
d
1269, 1118; elemental anal. calcd. for C27H30 N6O4S2 (566.7): C,
57.22; H, 5.34; N, 14.83; S, 11.32; found: C, 57.78; H, 5.62; N, 14.29;
S, 11.27. 4c: Yellow crystal; yield: 54%; mp: 185.4–187.1 8C. 1H
d
3.07, The other
d
1.53–1.61 (m, 2H, –CH2CH2CH3) and d 7.27–
7.56 (m, 5H, Ar–H). The MS spectrum of 3a showed the molecule
ion peak at m/z 305 with 54% abundance. The structure of 3a was
also established based on the elemental analysis data.
NMR (400 MHz CDCl3): d 1.27 (s, 4H, 2CH2), 1.33 (t, 6H, J = 7.2 Hz,
2CO2CH2CH3), 1.51 (d, 4H, J = 6.4 Hz, 2CH2), 3.07 (t, 4H, J = 7.2 Hz,
2CH2), 4.24 (q, 4H, J = 7.2 Hz, 2CO2CH2CH3), 5.78 (s, 4H, 2NH2),
7.32–7.56 (m, 10H, Ph-H); EI-MS (70 eV, m/z) (relative intensity %):
609 (M+, 89), 289 (56), 277 (100), 77 (49); IR (KBr, cmÀ1):
v3354
Selected characterization data. 3a: Yellow crystal; yield: 65%;
mp: 165.5–166.4 8C. 1H NMR (400 MHz CDCl3):
d
0.87 (t, 3H,
J = 7.2 Hz, CH2CH2CH3), 1.32 (t, 3H, J = 7.2 Hz, CO2CH2CH3), 1.53–
1.61 (m, 2H, CH2CH2CH3), 3.07 (t, 2H, J = 7.2 Hz, CH2CH2CH3), 4.23
(q, 2H, J = 7.2 Hz, CO2CH2CH3), 5.78 (s, 2H, NH2), 7.27–7.56 (m, 5H,
Ph-H); EI-MS (70 eV, m/z) (relative intensity %): 305 (M+, 54), 275
(N–H), 3049(Ar–H), 2927(C–H), 1662 (C55O), 1612, 1527, 1267,
1122; elemental anal. calcd. for C30H36N6O4S2 (608.8): C, 59.19; H,
5.96; N, 13.80; S, 10.53; found: C, 59.57; H, 6.52; N, 13.79; S, 10.22.
The herbicidal activity of 3 and 4 against Brassica napus
(rapeseed) and Echinochloa crusgalli (L.) Beav (barnyard grass) has
been investigated at the dosage of 100 mg/L and 10 mg/L according
to the reported method [14] and compared with distilled water,
and 2,4-dichlorophenoxy acetic acid (2,4-D), a commercially
available herbicide. Some compounds exhibited high or moderate
herbicidal activities against the roots of rapeseed and barnyard
grass at 100 mg/L (see Table 1). For example, 3d showed higher
(52), 230 (23), 118 (100); IR (KBr, cmÀ1):
1662 (C55O), 1606, 1527, 1268; elemental anal. calcd. for
15H19N3O2S (305.4): C, 58.99; H, 6.27; N, 13.76; S, 10.50; found:
C, 58.32; H, 6.33; N, 13.53; S, 10.48. 3b: Yellow crystal; yield: 63%;
mp: 148.6–150.1 8C. 1H NMR (400 MHz CDCl3):
0.89 (t, 3H,
v3363 (N–H), 2954 (C–H),
C
d
J = 7.2 Hz, CH2CH2CH2CH3), 1.28–1.34(m, 5H, CH2CH2CH2CH3,
CO2CH2CH3), 1.50–1.54 (m, 2H, CH2CH2CH2CH3), 3.09 (t, 2H,
Table 1
Herbicidal activity of 3 and 4 (in vitro relative inhibition rate %).
Compd.
Barnyard grass
Rapeseed
Stalk
A
Root
A
Stalk
A
Root
A
B
B
B
B
3a
3b
3c
9.7
19.4
33.3
40.7
12.9
31.6
31.6
42.2
25.9
15.4
3.8
35.5
22.6
33.3
44.4
26.5
43.3
48.1
61.9
49.6
34.6
34.6
38.5
43.5
50.0
25.0
76.7
74.4
18.8
69.8
76.7
74.4
79.1
37.9
31.0
34.5
90.0
68.1
34.4
86.0
83.7
19.4
86.0
88.4
90.7
88.4
58.6
58.6
69.0
97.5
4.3
26.1
39.1
89.0
92.0
34.8
64.0
72.0
92.0
44.0
52.0
36.0
32.0
91.2
40.0
0
48.0
29.3
92.5
98.1
38.6
71.7
90.6
94.3
79.2
76.9
41.0
50.0
98.0
0
64.0
20.0
À13.0
52.0
44.0
66.0
44.0
52.0
12.0
12.0
87.5
43.4
47.2
À9.3
37.7
32.1
64.0
34.0
39.7
7.7
3d
3e
3f
3g
3h
3i
4a
4b
4c
19.2
33.3
21.8
88.8
2,4-D
A: the dosage of 10 mg/L; B: the dosage of 100 mg/L.

J.-C. Liu et al. / Chinese Chemical Letters 24 (2013) 233–235
235
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In conclusion, we have developed a facile method for the
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3-phenyl-3H-thiazoline (3) and bis(2-imino-4-amino-5-ethoxycar-
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intermediate 4-amino-5-ethoxycarbonyl-2-methylthio-3-phenyl-
3H-thiazolinium sulphate (2) with alkylamines or arylamine at
room temperature. The structures of compounds 3 and 4 have been
confirmed by 1H NMR, EI-MS, IR spectroscopy and elemental
analyses. Some target compounds possess good herbicidal activity
against the roots of Rape and Barnyard grass at 100 mg/L.
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This research was supported in part by National Basic Research
Program of China (No. 2010CB126100), the National Key Technol-
ogies R & D Program of China (No. 2011BAE06B03) and the
National Natural Science Foundation of China (No. 21172090). The
research was also supported in part by the PCSIRT (No. IRT0953).
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