Synthesis, herbicidal activity, and structure-bioactivity relationship of pyridyl-containing 2-phenyliminothiazolidines

Article abstract of DOI:10.1007/s00706-007-0696-0

A series of novel 2-phenyliminothiazolidine derivatives were designed and synthesized. All title compounds were characterized by ¹H NMR and, in some cases, by ¹³C NMR, IR, and HRMS. Their agricultural bioactivities were evaluated and some of these compounds exhibited efficient herbicidal activities against Echinochloa crusgalli, Sorghum vulgare, Digitaria sanguinalis, Eclipta prostrasta, Cucumis sativus, and Brassica campestris at 50∈μg/cm³. Analysis of the quantitative structure-activity relationship (QSAR) showed that the electronic parameter was the main factor to affect herbicidal activities.

Full text of DOI:10.1007/s00706-007-0696-0

Monatshefte f u¨ r Chemie 139, 169–178 (2008)
DOI 10.1007/s00706-007-0696-0
Printed in The Netherlands
Synthesis, Herbicidal Activity, and Structure-Bioactivity Relationship
of Pyridyl-Containing 2-Phenyliminothiazolidines
1
;3
2;3;ꢀ
1
3
3
3
Gangyue Li , Xuhong Qian
, Shenggang Yan , Jingnan Cui , Rong Zhang , and Yi Xiao
1
Electromechanics and Materials Engineering College, Dalian Maritime University, Dalian, People’s Republic of China
Shanghai Key Laboratory of Chemical Biology, Institute of Pesticides and Pharmaceuticals,
East China University of Science and Technology, Shanghai, People’s Republic of China
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Liaoning Province, Dalian,
People’s Republic of China
2
3
Received March 24, 2007; accepted (revised) April 16, 2007; published online November 16, 2007
Springer-Verlag 2007
#
Summary. A series of novel 2-phenyliminothiazolidine de-
rivatives were designed and synthesized. All title compounds
In the study of pharmaceuticals and agrochem-
icals, the introduction of pyridine into a parent com-
pound may improve the properties and biological
activities of the compounds, and many pyridyl-con-
taining compounds are also known to possess a wide
range of biological and pharmacological activities
1
were characterized by H NMR and, in some cases, by
13
C
NMR, IR, and HRMS. Their agricultural bioactivities were
evaluated and some of these compounds exhibited efficient
herbicidal activities against Echinochloa crusgalli, Sorghum
vulgare, Digitaria sanguinalis, Eclipta prostrasta, Cucumis
3
sativus, and Brassica campestris at 50ꢀg=cm . Analysis of
[
3–6], as well as low toxicity toward mammals. On
the quantitative structure-activity relationship (QSAR) showed
that the electronic parameter was the main factor to affect
herbicidal activities.
the other hand, the 2-iminothiazolidine ring system
has received much attention in biologically active
molecules, such as potent inhibitors of indoleethyl-
amine N-methyltransferase [7, 8], octopaminergic
agonists [9, 10], anthelmintics [11], diuretic agents
Keywords. 2-Phenyliminothiazolidine; Synthesis; Herbicidal
activity; QSAR.
[
12], trehalase inhibitors [13, 14], and insecticidal
Introduction
agents [15]. However, few 2-iminothiazolidine deriva-
tives with herbicidal activity were reported [16]. It was
presumed that this class of compounds probably pos-
sess high potentials on herbicidal activity. Therefore,
we adopted the 2-phenyliminothiazolidine ring as
pharmacophore and simultaneously introduced pyri-
dinemethyl into the 3-position of 2-phenyliminothia-
zolidine. The methylene group between pyridyl and
2-phenyliminothiazolidine enhanced the flexibility of
the whole molecule and further influenced the bio-
logical activities. Herein, a series of novel pyridyl-
containing 2-phenyliminothiazolidine derivatives were
conveniently synthesized, and the semiempirical
quantum chemical method and molecular modeling
Crop protection continually needs the discovery of
novel herbicides. Since the discovery of the her-
bicide 2,4-dichlorophenoxyacetic acid (2,4-D), the
agrochemical industry has successfully developed a
wide array of herbicides with various chemical struc-
tures and modes of action [1]. However, an inevi-
table problem associated with the use of herbicides
is the occurrence of herbicide resistant weeds [2].
Therefore, it is necessary to develop efficient her-
bicides with novel structures or modes of action to
overcome the resistance of weeds.
ꢀ Corresponding author. E-mail: xhqian@ecust.edu.cn

1
70
G. Li et al.
Scheme 1
were also used to study the structure-bioactivity rela-
tionship of the synthesized compounds against the
tested weeds.
aryl isothiocyanates and simply washed with Et O
2
and water without further purification. Cyclization of
3 with hydrochloric acid provided the required 2-
phenyliminothiazolidine derivatives 4. The overall
yields of these two steps ranged from 61 to 86%.
The structures of the target compounds 4 were well
Results and Discussion
1
characterized by H NMR and, in some cases, by
13
C NMR, IR, and HRMS. The IR spectra of com-
Synthesis
The intermediates 2a and 2b were synthesized by a
convenient one-pot procedure (Scheme 1). Reaction
of pyridylaldehyde with ethanolamine gave 1, which
were directly reduced to give 2a and 2b in 90–93%
yields based on the consumed pyridylaldehyde. The
intermediate 2c was prepared in refluxing acetoni-
trile in 70% yield (Scheme 2).
pounds 4 showed C¼N and C–S stretching bands
ꢁ
1
1
at 1608–1633 and 1213–1244cm . The H NMR
spectra of compounds 4 showed a singlet at ꢁ ¼
4.69–4.90ppm attributed to CH linking to the thiazo-
2
lidine ring. The two groups of triplets at ꢁ ¼ 3.09–3.24
and 3.46–3.75 ppm were due to two conjoint CH of
2
the thiazolidine ring.
The target products 4 were prepared as shown in
Scheme 3. Hydroxyeththioureas 3 were obtained by
reaction of aminoethanols 2 with the corresponding
Herbicidal Activity
In order to analyse the structure-activity relationship
of 2-phenyliminothiazilidines, compounds 4a-8 to
4a-16, 4a-1, and 4a-6 reported previously [17] are
also listed in Tables 1–3.
From the results, only compounds 4a and 4b
exhibited inhibitory activities against both dicotyle-
donous and monocotyledonous weeds, but showed
Scheme 2
Scheme 3

Pyridyl-Containing 2-Phenyliminothiazolidines
171
a
Table 1. Inhibitory activities of compounds 4 at 50 ꢀg=cm
3
Comp.
R
Growth inhibitory rates=%
D. E.
crusgalli vulgare sanguinnalis prostrasta sativus campestris
Symptoms
E.
S.
C.
B.
b
4a-1
4a-2
4a-4
H
2-NO2
4-NO2
50=50
30=20
10=20
50=10
–=–
10=10
70=30
60=10
20=10
70=80
80=80
30=20
70=80
10=20
40=30
10=10
–=–
–=–
–
D. sanguinnalis abnormality
E. crusgalli & D. sanguinnalis
albinism
4
4
4
4
a-6 2-CH3
a-7 2,6-CH ,CH
60=40
50=20
50=10
40=20
80=20
65=80
60=30
60=10
40=–
20=10
30=–
10=–
40=–
–=–
80=50
20=–
–=–
70=60
60=20
60=30
60=10
90=90
80=90
70=70
60=–
60=80
60=70
60=60
70=80
80=80
80=85
80=90
50=80
65=80
85=90
–=–
60=60
60=20
10=–
–=–
–=–
–=–
–=–
60=20
10=10
–=–
10=10
–=–
–
–
–
–
–
–
–
3
3
a-8
a-9
2-CF3
3-CF3
2-F
50=40
40=20
80=80
30=30
30=20
75=60
80=75
–=–
4a-10
4a-11
4a-12
4a-13
4a-14
4a-15
4a-16
4-F
2,4-F,F
2,6-F,F
2-Cl
4-Cl
2,6-Cl,Cl
H
D. sanguinnalis abnormality
D. sanguinnalis abnormality
E. crusgalli abnormality
40=–
20=10
–=–
50=–
60=40
20=20
–=–
90=90
60=–
–=–
20=–
–=–
–=–
4
b-1
–=–
40=30
–=–
E. crusgalli & D. sanguinnalis
albinism
4
b-6
2-CH3
b-7 2,6-CH ,CH
–=–
–=–
–=–
–=–
–=–
–=–
–=–
–=–
–=–
20=60
10=–
10=–
10=–
30=70
–=–
30=40
–=–
–=–
30=40
50=60
20=20
20=10
–=–
–=–
–=–
20=–
–=–
D. sanguinnalis albinism
–
4
4
4
3
3
b-8
b-9
2-CF3
3-CF3
2-F
–
D. sanguinnalis albinism
E. crusgalli, D. sanguinnalis
4
b-10
10=50
20=20
–=50
&
D. sanguinnalis albinism
B. campestris albinism
4
4
b-11
b-12
4-F
2,4-F,F
10=40
20=10
40=30
10=10
10=30
–=–
70=70
10=50
70=40
–=–
–=–
–=–
Albinism except for
E. prostrasta
4
4
b-14
b-16
2-Cl
4-CH3
–=10
–=–
–=–
–=–
20=10
–=–
30=30
–=–
–=–
60=50
–=20
–=–
–
–
a
b
The results of effective compounds were listed; Numerator and denominator stand for the herbicidal activity of the aerial
parts and the roots
weak inhibitory activities against S. vulgare and B.
campestris.
electron-donating group such as the N,N-dimethyl-
amino group into the phenyl ring resulted in a com-
plete loss of activity (4a-5, 4b-5).
Although we have no information about the mode
of action of these compounds, it was presumed that
their mode of action is possibly concerned with a
photoinduced process according to the symptoms of
the abnormality or albinism of some weeds and fur-
ther study of this aspect is underway.
Firstly, we investigated the influences resulting
from the structural changes of target compounds on
biological activities. From results of the bioassay we
found that their herbicidal activities descended in
the order 4a>4b>inactive 4c. This indicated that
the introduction of chlorine into the pyridine ring
led to a loss of biological activities. 3-Pyridinemethyl
derivatives 4a showed higher herbicidal activities
than the 2-pyridinemethyl derivatives 4b.
We further focused on the relationship between
the type of substituent R on phenyl ring and the bio-
logical activities. The compounds with weakly elec-
tron-donating or weakly electron-withdrawing group
Quantitative Structure-Activity Relationship
The compounds 4 showed different herbicidal ac-
tivities against different tested weeds. Results of the
multiple regression analysis between structural param-
eters and their herbicidal activity are given below
along with the statistical values (n ¼ number of com-
(CH , H, Cl, F) at the phenyl ring showed good bio-
logical activities. But the introduction of strongly
3

1
72
G. Li et al.
Table 2. Herbicidal activity of compounds 4
Comp.
R
Herbicidal activity (HA)
D. sanguinnalis E. prostrasta
E. crusgalli
S. vulgare
C. sativus
B. campestris
4
4
4
4
4
4
4
a-1
a-2
a-4
a-6
a-7
a-8
a-9
H
2.430=2.430
2.129=1.895
1.543=1.895
2.628=2.276
2.473=1.871
2.528=1.573
2.352=1.926
3.060=1.856
2.727=3.060
2.660=2.116
2.660=1.530
2.305=–
2.430=1.476
–=–
2.798=2.062
2.673=1.543
1.895=1.543
2.820=2.628
2.649=1.871
2.704=2.160
2.704=1.573
3.412=3.412
3.060=3.412
2.852=2.852
2.660=–
2.798=3.032
3.099=3.099
2.129=1.895
2.628=3.054
2.649=2.841
2.704=2.704
2.900=3.130
3.060=3.060
3.060=3.211
3.086=3.439
2.484=3.086
2.750=3.084
3.235=3.436
–=–
2.254=2.062
–=–
2.105=2.297
–=–
–=–
2.090=2.282
2.826=2.826
1.530=2.484
2.113=2.113
–=–
2.798=3.032
1.543=1.895
2.321=2.129
2.628=2.628
2.649=1.871
1.573=–
2.528=2.352
2.282=1.856
3.060=3.060
2.116=2.116
2.116=1.882
2.959=2.658
3.084=2.959
–=–
1.476=1.476
–=–
–=–
2-NO2
4-NO2
2-CH3
1.543=1.543
1.850=1.498
2.105=–
1.573=–
2.352=–
–=–
3.060=2.458
1.882=–
–=–
–=–
–=–
–=–
–=–
2,6-CH ,CH
3
3
2-CF3
3-CF3
2-F
4a-10
4a-11
4a-12
4a-13
4a-14
4a-15
4a-16
2.643=1.856
1.504=1.504
–=–
1.530=1.530
–=–
1.879=–
–=–
–=–
–=–
–=–
1.926=–
–=–
–=2.458
–=–
–=–
4-F
2,4-F,F
2,6-F,F
2-Cl
2.305=–
1.879=1.527
–=–
2.481=–
4-Cl
2.658=2.305
1.926=1.926
–=–
3.436=3.436
2.704=–
–=–
1.850=2.628
1.519=–
1.573=–
2,6-Cl,Cl
H
2-CH3
4
4
4
4
4
b-1
b-6
b-7
b-8
b-9
–=–
–=–
–=–
–=–
–=–
–=–
–=–
–=–
–=–
–=–
–=–
2.452=2.628
1.871=1.871
1.926=1.573
–=–
1.856=1.856
2.826=2.282
–=–
2,6-CH ,CH
3
3
2-CF3
3-CF3
2-F
1.573=–
4b-10
4b-11
4b-12
4b-14
4b-16
1.504=2.458
1.504=2.282
1.882=1.530
–=1.527
2.090=2.826
1.504=2.090
–=–
1.879=1.527
–=–
4-F
2.282=2.090
1.530=1.530
–=–
2,4-F,F
2-Cl
4-CH3
–=–
2.628=2.452
–=1.879
–=–
–=–
–=–
Table 3. Molecular parameters of compounds 4
Compound
Descriptor variable
3
˚
lg P
ET=a.u.
QN1
QN2
QS
QC1
QC2
V=A
4
4
4
4
4
4
4
a-1
a-2
a-4
a-6
a-7
a-8
a-9
1.27
ꢁ1.47
ꢁ1.47
1.43
1.58
1.84
1.84
0.67
0.67
0.07
0.07
1.05
1.05
0.83
1.24
1.39
1.55
1.81
1.81
0.64
0.64
0.04
1.02
1.39
ꢁ98.3806
ꢁ125.2497
ꢁ125.2588
ꢁ103.8766
ꢁ109.3730
ꢁ150.7380
ꢁ150.7461
ꢁ113.9899
ꢁ113.9925
ꢁ129.6009
ꢁ129.5989
ꢁ109.4550
ꢁ109.4575
ꢁ120.5302
ꢁ98.3831
0.0406
0.0638
0.0514
0.0379
0.0371
0.0573
0.0477
0.0468
0.0438
0.0499
0.0540
0.0468
0.0434
0.0537
0.0602
0.0624
0.0618
0.0831
0.0682
0.0671
0.0637
0.0705
0.0697
0.0597
ꢁ0.1307
ꢁ0.1960
ꢁ0.1501
ꢁ0.1230
ꢁ0.1194
ꢁ0.1595
ꢁ0.1416
ꢁ0.1320
ꢁ0.1348
ꢁ0.1358
ꢁ0.1351
ꢁ0.1349
ꢁ0.1352
ꢁ0.1415
ꢁ0.1457
ꢁ0.1406
ꢁ0.1373
ꢁ0.1774
ꢁ0.1560
ꢁ0.1461
ꢁ0.1498
ꢁ0.1499
ꢁ0.1504
ꢁ0.1439
0.0368
0.0483
0.0414
0.0367
0.0369
0.0391
0.0370
0.0330
0.0367
0.0330
0.0321
0.0357
0.0378
0.0362
0.0299
0.0303
0.0309
0.0311
0.0300
0.0263
0.0299
0.0263
0.0297
0.0297
0.0121
0.0076
0.0090
0.0130
0.0133
0.0086
0.0106
0.0113
0.0113
0.0105
0.0094
0.0112
0.0113
0.0092
ꢁ0.0167
ꢁ0.0087
ꢁ0.0075
ꢁ0.0146
ꢁ0.0171
ꢁ0.0164
ꢁ0.0175
ꢁ0.0174
ꢁ0.0116
ꢁ0.0163
ꢁ0.1664
ꢁ0.1634
ꢁ0.1617
ꢁ0.1674
ꢁ0.1672
ꢁ0.1619
ꢁ0.1634
ꢁ0.1652
ꢁ0.1647
ꢁ0.1636
ꢁ0.1616
ꢁ0.1651
ꢁ0.1651
ꢁ0.1622
ꢁ0.1654
ꢁ0.1657
ꢁ0.1656
ꢁ0.1607
ꢁ0.1623
ꢁ0.1636
ꢁ0.1637
ꢁ0.1619
ꢁ0.1633
ꢁ0.1657
790.99
820.82
850.36
812.74
855.85
834.50
870.37
793.45
799.40
801.88
800.93
812.20
834.66
850.81
794.99
821.44
863.60
840.60
873.65
797.98
803.08
806.09
819.35
848.39
4
4
4
4
4
4
4
a-10
a-11
a-12
a-13
a-14
a-15
a-16
4
4
4
4
4
b-1
b-6
b-7
b-8
b-9
ꢁ103.8785
ꢁ109.3747
ꢁ150.7414
ꢁ150.7488
ꢁ113.9926
ꢁ113.9950
ꢁ129.6039
ꢁ109.4570
ꢁ103.8835
4b-10
4b-11
4b-12
4b-14
4b-16

Pyridyl-Containing 2-Phenyliminothiazolidines
173
pounds; r ¼ correlation coefficient; s ¼ standard de-
viation; F ¼ significance index with respect to the
equation). The figures in parentheses are the confi-
dence intervals of the regression coefficient and in-
tercept. Equations (1)–(4) are significant at the
99% level on the basis of results of the statistical
F-test. The following regression model turned out
to be the best:
higher the values of QC1, the better the activity.
The lower the value of QN1 and Q , the higher
N2
the activity. Equation (3) explains that the aerial parts
activity against E. prostrasta of the tested compounds
depend on the hydrophobicity (lg P), the electronic
parameter (Q , Q ), and the spatial parameter (V).
N1
N2
The effects of the parameters on the activity des-
cended in the order Q >lg P>V>Q . The lower
N1
N2
the value of QN1 and Q , the higher the activity.
N2
2
HA ¼ 0:052 lg P ꢁ 0:285 ðlg PÞ þ 30:947 Q
C1
The higher the value of V, the better the activity.
Equation (4) explains that the roots activity against
E. prostrasta of the tested compounds depends on the
hydrophobicity (lg P) and the electronic parameter
ð0:0776Þ
ð0:0711Þ
ð6:1967Þ
ꢁ
207:662 Q ꢁ 0:027 E ꢁ 34:842
C2
T
ð72:3607Þ
ð0:0086Þ ð12:6854Þ ð1Þ
(E , Q , Q ). It was found that the effects of the
T C2 S
parameters on the activity descended in the order
n ¼ 17; r ¼ 0:914; F ¼ 11:102; s ¼ 0:231
Q >Q >E >lg P. The higher the value of Q ,
S
C2
T
S
2
HA ¼ 0:332 lg P ꢁ 0:307 ðlgPÞ ꢁ 28:572 Q
N1
the better the activity. The lower the value of E and
T
Q , the higher the activity. In addition, Eq. (1)–(4)
C2
ð0:0966Þ
ð0:0736Þ
ð16:9312Þ
imply that there is an optimum value of lg P. The
activity against other tested weeds in terms of HA
gave poor correlations and their equations were not
listed.
ꢁ
24:139 Q þ 35:196 Q þ 0:618
N2
C1
ð8:4711Þ
ð12:1392Þ
ð0:7503Þ ð2Þ
n ¼ 21; r ¼ 0:932; F ¼ 19:925; s ¼ 0:254
In conclusion, we have demonstrated that novel
2-phenyliminothiazolidine derivatives containing a
pyridinemethyl moiety presented efficient herbicidal
activities. Significant relationships were found be-
tween the parameters hydrophobicity, spatial param-
eter, and electronic parameter and the herbicidal
activity against some tested weeds. These strong
correlations imply that electronic effects may play
an important role in binding to the receptor. These
equations also imply that there are optimum values
of lg P. In general, 3-pyridinemethyl derivatives 4a
showed better herbicidal activities than 2-pyridine-
methyl derivatives 4b, as the former have more net-
charge on the C1 and S atom, and less net-charge on
N1 atom.
2
HA ¼ 0:390 lg P ꢁ 0:465 ðlg PÞ ꢁ 69:432 Q
N1
ð0:0938Þ
ð0:1135Þ
ð8:6095Þ
ꢁ
45:642 Q þ 0:007 V ꢁ 5:788
N2
ð7:4865Þ
ð0:0036Þ ð3:2449Þ
ð3Þ
n ¼ 19; r ¼ 0:917; F ¼ 13:793; s ¼ 0:214
2
HA ¼ 0:290 lg P ꢁ 0:553 ðlg PÞ ꢁ 0:028 E
T
ð0:0756Þ
ð0:0554Þ
ð0:0050Þ
ꢁ
201:451 Q þ 88:715 Q ꢁ 36:152
C2
S
ð49:4537Þ
ð12:6766Þ ð8:3703Þ ð4Þ
n ¼ 19; r ¼ 0:960; F ¼ 30:671; s ¼ 0:155
Equation (1) explains that the aerial parts activity
against E. crusgalli of the tested compounds mainly
depend on the molecular electronic properties (QC1,
Q , E ) and the hydrophobicity (lg P). It was found
Experimental
Melting points were obtained with an X-6 micro-melting point
apparatus. The infrared (IR) spectra were recorded on a Nico-
let 20DXB FT-IR spectrometer using KBr pellets or films.
C2
T
that the effects of these parameters on the activity
descended in the order Q >Q >lg P>E . The
C1
C2
T
1
The H NMR spectra were measured on a Varian INOVA-
400 spectrometer with chemical shifts reported as parts per
higher the value of Q , the better the activity. The
C1
1
million (in CDCl , TMS as internal standard). The C NMR
3
lower the values of QC2 and E , the higher the activ-
T
3
ity. Equation (2) explains that the aerial parts activ-
ity against D. sanguinnalis of the tested compounds
was mainly dependent on the electronic parame-
ter (Q , Q , Q ) and the hydrophobicity (lg P).
spectra were measured on a Bruker AVANCE-500 spectro-
meter (in CDCl , TMS as internal standard). High-resolution
mass spectra (HRMS) were obtained on an HPLC-Q-Tof MS
(Mcrio) spectrometer. Flash chromatography was performed
on silica gel. All the solvents were of analytical grade. All
chemicals or reagents were purchased from standard commer-
cial suppliers.
3
C1
N1
N2
The effects of the parameters on the activity des-
cended in the order Q >QN1>QN2>lg P. The
C1

1
74
G. Li et al.
General Synthesis Procedure for Intermediates 2a and 2b
Ethanolamine (20 mmol) and 20 mmol pyridylaldehyde in
2H), 7.25–7.31 (m, 1H), 7.34 (dd, J ¼ 4.8, 8.0Hz, 1H), 7.43 (t,
J ¼ 8.0Hz, 1H), 7.75 (d, J ¼ 8.0 Hz, 1H), 7.84 (t, J ¼ 2.0 Hz,
3
0cm methanol were stirred for 36h at room temperature.
1
H), 7.87–7.92 (m, 1H), 8.58 (dd, J ¼ 1.6, 4.8 Hz, 1H), 8.63
5
Then, 20mmol NaBH were added portionwise and the mix-
(
1
d, J ¼ 1.6 Hz, 1H) ppm; IR (KBr): ꢂꢀ ¼ 1618, 1595, 1521,
4
ꢂ
ꢁ
234, 742, 710 cm ; HRMS calculated for C H N O S
15 15 4 2
1
ture was stirred at 50 C for 4 h. Methanol was distilled off
þ
[
Mþ H ] 315.0916, found 315.0924.
under reduced pressure and the residue was purified by
column chromatography on silica gel by using dichlorometh-
ane=methanol=triethylamine as eluent to give a yellowish oil 2
2
-[(4-Nitrophenyl)imino]-3-(3-pyridylmethyl)thiazolidine
(
2a: dichloromethane=methanol=triethylamine ¼ 150=20=1,
(
Yield 72%; mp 102.6–103.1 C; H NMR (400 MHz, CDCl ):
4a-4, C H N O S)
15 14 4 2
v=v, 93% yield; 2b: dichloromethane=methanol=triethyl-
amine ¼ 150=20=1, v=v, 90% yield).
ꢂ
1
3
ꢁ
¼ 3.22 (t, J ¼ 7.0 Hz, 2H), 3.60 (t, J ¼ 7.0 Hz, 2H), 4.75
(
s, 2H), 7.02–7.08 (m, 2H), 7.32 (dd, J ¼ 4.8, 8.0 Hz, 1H),
General Synthesis Procedure for Intermediate 2c
2
1
ing (10 mmol) ethanolamine (10 mmol) solution in 25cm
acetonitrile over a period of 2 h at room temperature. The
resulting mixture was refluxed for 3–5 h. Then, the solvent
was evaporated under vacuum and the residue was puri-
fied by column chromatography on silica gel by using 10%
methanol=chloroform as eluent to give yellowish oil 2c in
7.69–7.75 (m, 1H), 8.14–8.20 (m, 2H), 8.58 (dd, J ¼ 1.2,
4
1
.8 Hz, 1H), 8.62 (d, J ¼ 1.6 Hz, 1H) ppm; IR (KBr): ꢂꢀ ¼
-Chloro-5-chloromethylpyridine (10 mmol) dissolved in
3
00 cm acetonitrile was added dropwise to a K CO -contain-
ꢁ1
621, 1578, 1492, 1233, 853 cm ; HRMS (ESI) calculated
2
3
3
þ
for C H N O S [Mþ H ] 315.0916, found 315.0911.
15 15 4 2
2-[[4-(Dimethylamino)phenyl]imino]-3-(3-pyridylmethyl)-
thiazolidine (4a-5, C H N S)
1
7 20 4
ꢂ
1
Yield 68%; mp 80.7–81.4 C; H NMR (400MHz, CDCl ):
3
ꢁ
¼ 2.91 (s, 6H), 3.11 (t, J ¼ 6.8 Hz, 2H), 3.47 (t, J ¼ 6.8 Hz,
H), 4.73 (s, 2H), 6.73 (d, J ¼ 8.8 Hz, 2H), 6.89 (d, J ¼
.8 Hz, 2H), 7.29 (dd, J ¼ 4.8, 7.6 Hz, 1H), 7.76 (d, J ¼
.6 Hz, 1H), 8.55 (dd, J ¼ 1.6, 4.8 Hz, 1H), 8.61 (d, J ¼ 1.6 Hz,
7
0% yield.
2
8
7
1
General Synthesis Procedure for the Target Compounds 4
3
To a solution of 1.0 mmol 2 in 50 cm ethanol was added
1
a 10-min period and the mixture was stirred at room tem-
perature for 30–60 min. Then, the solvent was evaporated
under vacuum and the residue was washed with diethyl
ꢁ
1
H) ppm; IR (KBr): ꢂꢀ ¼ 1619, 1512, 1239, 820 cm ; HRMS
þ
calculated for C H N S [M þ H ] 313.1487, found
17 21 4
.0 mmol of the corresponding phenyl isothiocyanate over
3
13.1497.
2-[(2,6-Dimethylphenyl)imino]-3-(3-pyridylmethyl)-
ether and H O to afford 3, which was used directly without
2
thiazolidine (4a-7, C H N S)
7 19 3
1
further purification.
The appropriate thiourea 3 (10 mmol) was dissolved in
ꢂ
1
Yield 80%; mp 74.6–76.0 C; H NMR (400 MHz, CDCl ):
3
ꢁ
2
7
¼ 2.14 (s, 6H), 3.12 (t, J ¼ 7.0 Hz, 2H), 3.56 (t, J ¼ 7.0 Hz,
H), 4.78 (s, 2H), 6.88 (t, J ¼ 7.4 Hz, 1H), 7.01 (d, J ¼
.4 Hz, 2H), 7.30 (dd, J ¼ 5.2, 7.6 Hz, 1H), 7.79 (d, J ¼
3
0cm conc. HCl and heated at 90 C for 45min. The cooled
ꢂ
1
mixture was basified with 10M NaOH in an ice bath. The
precipitated gummy residue was extracted with CH Cl . The
2
2
7.6 Hz, 1H), 8.56 (d, J ¼ 5.2 Hz, 1H), 8.65 (s, 1H) ppm;
organic layer was washed with brine, dried (MgSO ), and
4
ꢁ1
IR (KBr): ꢂꢀ ¼ 1625, 1588, 1228, 768 cm ; HRMS (ESI)
evaporated to give crude 4, which was purified by column
chromatography on silica gel by using petroleum ether and
acetone as eluents. The overall yields of these two steps ran-
ged from 61 to 86%.
þ
calculated for C H N S [M þ H ] 298.1378, found
1
7 20 3
2
98.1364.
2
-(Phenylimino)-3-(2-pyridylmethyl)thiazolidine
(
Yield 85%; mp 84.1–86.1 C; H NMR (400MHz, CDCl ):
4b-1, C H N S)
15 15 3
2
-[(2-Nitrophenyl)imino]-3-(3-pyridylmethyl)thiazolidine
ꢂ
1
3
(4a-2, C H N O S)
Yield 71%; mp 93.0–93.5 C; H NMR (400 MHz, CDCl ):
ꢁ ¼ 3.15 (t, J ¼ 7.0Hz, 2H), 3.64 (t, J ¼ 7.0 Hz, 2H), 4.85 (s,
2H), 6.96 (d, J ¼ 8.0 Hz, 2H), 7.03 (t, J ¼ 7.4 Hz, 1H), 7.20
(dd, J ¼ 5.2, 7.6 Hz, 1H), 7.23–7.31 (m, 2H), 7.45 (d, J ¼
7.8 Hz, 1H), 7.68 (ddd, J ¼ 1.6, 7.6, 7.8 Hz, 1H), 8.56 (dd,
1
5 14 4 2
ꢂ
1
3
ꢁ
¼ 3.20 (t, J ¼ 7.0 Hz, 2H), 3.59 (t, J ¼ 7.0 Hz, 2H), 4.74 (s,
H), 7.07 (dd, J ¼ 1.2, 8.2 Hz, 1H), 7.12 (ddd, J ¼ 1.2, 7.4,
.2 Hz, 1H), 7.34 (dd, J ¼ 5.0, 7.6 Hz, 1H), 7.48 (ddd, J ¼ 1.2,
.4, 8.2 Hz, 1H), 7.81–7.86 (m, 1H), 7.89 (dd, J ¼ 1.2, 8.2 Hz,
H), 8.57 (dd, J ¼ 1.2, 5.0 Hz, 1H), 8.59 (d, J ¼ 2.0 Hz, 1H)
2
8
7
1
1
3
J ¼ 1.6, 5.2 Hz, 1H) ppm; C NMR (125 MHz, CDCl ):
3
ꢁ ¼ 26.93, 50.74, 52.04, 121.94, 122.34, 122.52, 122.98,
128.80, 136.74, 149.18, 152.12, 157.33, 158.69 ppm; IR
(KBr): ꢂꢀ ¼ 1614, 1587, 1236, 761, 697 cm ; HRMS
ꢁ
1
ꢁ1
ppm; IR (KBr): ꢂꢀ ¼ 1623, 1595, 1517, 1234, 756 cm ; HRMS
þ
þ
(ESI) calculated for C H N O S [Mþ H ] 315.0916, found
(ESI) calculated for C H N S [M þ H ] 270.1065, found
15 16 3
1
5
15
4
2
3
15.0926.
270.1076.
2
-[(3-Nitrophenyl)imino]-3-(3-pyridylmethyl)thiazolidine
2-[(2-Nitrophenyl)imino]-3-(2-pyridylmethyl)thiazolidine
(4a-3, C H N O S)
Yield 75%; mp 66.5–67.5 C; H NMR (400 MHz, CDCl ):
(4b-2, C H N O S)
15 14 4 2
1
5
14
4
2
ꢂ
1
ꢂ
1
Yield 74%; mp 62.4–63.1 C; H NMR (400MHz, CDCl ):
3
3
ꢁ
¼ 3.21 (t, J ¼ 7.0 Hz, 2H), 3.59 (t, J ¼ 7.0 Hz, 2H), 4.75 (s,
ꢁ ¼ 3.22 (t, J ¼ 7.0 Hz, 2H), 3.74 (t, J ¼ 7.0 Hz, 2H), 4.84

Pyridyl-Containing 2-Phenyliminothiazolidines
175
(
s, 2H), 7.03–7.12 (m, 2H), 7.22 (dd, J ¼ 5.2, 7.4Hz, 1H),
2-[[2-(Trifluoromethyl)phenyl]imino]-3-(2-pyridylmethyl)-
thiazolidine (4b-8, C H F N S)
7
1
1
.46 (ddd, J ¼ 1.2, 7.6, 7.8 Hz, 1H), 7.54 (d, J ¼ 7.8 Hz,
H), 7.74 (ddd, J ¼ 1.6, 7.4, 7.8 Hz, 1H), 7.86 (dd, J ¼
.2, 8.0 Hz, 1H), 8.55 (dd, J ¼ 1.6, 5.2 Hz, 1H) ppm; IR
1
6 14 3 3
1
Yield 79%; oil; H NMR (400 MHz, CDCl ): ꢁ ¼ 3.10 (t,
3
J ¼ 6.8 Hz, 2H), 3.64 (t, J ¼ 6.8 Hz, 2H), 4.84 (s, 2H),
ꢁ
1
(
KBr): ꢂꢀ ¼ 1625, 1596, 1516, 1236, 757 cm ; HRMS (ESI)
6
.98–7.08 (m, 2H), 7.12–7.18 (m, 1H), 7.39 (t, J ¼ 7.6 Hz,
þ
calculated for C H N O S [M þ H ] 315.0916, found
1
5
15
4
2
1H), 7.44 (d, J ¼ 7.6 Hz, 1H), 7.55 (d, J ¼ 7.6 Hz, 1H),
3
15.0927.
7
.64 (t, J ¼ 7.6 Hz, 1H), 8.52 (d, J ¼ 4.0 Hz, 1H) ppm;
ꢁ1
IR (film): ꢂꢀ ¼ 1625, 1598, 1238, 758 cm ; HRMS (ESI)
2
-[(3-Nitrophenyl)imino]-3-(2-pyridylmethyl)thiazolidine
þ
calculated for C H F N S [M þ H ] 338.0939, found
1
6 15 3 3
(
4b-3, C H N O S)
1
338.0940.
5 14 4 2
1
Yield 78%; oil; H NMR (400 MHz, CDCl ): ꢁ ¼ 3.22 (t,
3
J ¼ 7.0 Hz, 2H), 3.72 (t, J ¼ 7.0 Hz, 2H), 4.85 (s, 2H), 7.23
2
-[[3-(Trifluoromethyl)phenyl]imino]-3-(2-pyridylmethyl)-
(
2
dd, J ¼ 5.2, 7.6 Hz, 1H), 7.25–7.31 (m, 1H), 7.37–7.43 (m,
thiazolidine (4b-9, C H F N S)
1
6 14 3 3
H), 7.71 (dd, J ¼ 7.6, 8.0 Hz, 1H), 7.80–7.88 (m, 2H), 8.58
ꢂ
1
Yield 61%; mp 42.2–43.3 C; H NMR (400MHz, CDCl ):
3
(
1
d, J ¼ 5.2 Hz, 1H) ppm; IR (film): ꢂꢀ ¼ 1622, 1596, 1521,
ꢁ
236, 744, 687 cm ; HRMS calculated for C H N O S
15 15 4 2
1
ꢁ ¼ 3.20 (t, J ¼ 7.0Hz, 2H), 3.70 (t, J ¼ 7.0 Hz, 2H), 4.85 (s,
2H), 7.13 (d, J ¼ 8.0 Hz, 1H), 7.18–7.32 (m, 3H), 7.37 (t,
J ¼ 8.0 Hz, 1H), 7.43 (d, J ¼ 8.4 Hz, 1H), 7.66–7.76 (m, 1H),
þ
[
Mþ H ] 315.0916, found 315.0918.
8
8
[
.58 (d, J ¼ 5.2 Hz, 1H) ppm; IR (KBr): ꢂꢀ ¼ 1623, 1586, 1239,
ꢁ1
16 15 3 3
2
-[(4-Nitrophenyl)imino]-3-(2-pyridylmethyl)thiazolidine
00, 702cm ; HRMS (ESI) calculated for C H F N S
(
Yield 80%; mp 72.6–73.2 C; H NMR (400 MHz, CDCl ):
4b-4, C H N O S)
15 14 4 2
þ
Mþ H ] 338.0939, found 338.0923.
ꢂ
1
3
ꢁ
¼ 3.24 (t, J ¼ 7.0 Hz, 2H), 3.75 (t, J ¼ 7.0 Hz, 2H), 4.85
(
(
2
1
s, 2H), 7.03 (d, J ¼ 8.8 Hz, 2H), 7.20–7.28 (m, 1H), 7.40
2-[(2-Fluorophenyl)imino]-3-(2-pyridylmethyl)thiazolidine
(4b-10, C15 S)
d, J ¼ 8.0 Hz, 1H), 7.65–7.74 (m, 1H), 8.16 (d, J ¼ 8.8 Hz,
H
Yield 83%; mp 46.7–47.8 C; H NMR (400MHz, CDCl ):
14FN
3
ꢂ
1
H), 8.58 (d, J ¼ 4.4Hz, 1H) ppm; IR (KBr): ꢂꢀ ¼ 1612, 1575,
3
ꢁ
þ
1
502, 1244, 852 cm
;
HRMS (ESI) calculated for
ꢁ ¼ 3.18 (t, J ¼ 7.0Hz, 2H), 3.70 (t, J ¼ 7.0 Hz, 2H), 4.88 (s,
2H), 6.95–7.09 (m, 4H), 7.21 (dd, J ¼ 5.2, 7.6 Hz, 1H), 7.52
C H N O S [Mþ H ] 315.0916, found 315.0927.
15 15 4 2
(
d, J ¼ 7.6 Hz, 1H), 7.70 (ddd, J ¼ 1.6, 7.6, 7.6 Hz, 1H), 8.55
2
-[[4-(Dimethylamino)phenyl]imino]-3-(2-pyridylmethyl)-
(dd, J ¼ 1.6, 5.2 Hz, 1H) ppm; IR (KBr): ꢂꢀ ¼ 1622, 1600,
ꢁ1
15 15 3
1
239, 754 cm ; HRMS (ESI) calculated for C H FN S
thiazolidine (4b-5, C H N S)
1
7 20 4
þ
ꢂ
1
Yield 68%; mp 65.2–66.3 C; H NMR (400 MHz, CDCl ):
[Mþ H ] 288.0971, found 288.0971.
3
ꢁ
¼ 2.91 (s, 6H), 3.14 (t, J ¼ 6.8 Hz, 2H), 3.61 (t, J ¼ 6.8 Hz,
H), 4.85 (s, 2H), 6.72 (d, J ¼ 8.6 Hz, 2H), 6.88 (d, J ¼
.6 Hz, 2H), 7.20 (dd, J ¼ 4.8, 7.6 Hz, 1H), 7.46 (d, J ¼ 8.0 Hz,
H), 7.68 (dd, J ¼ 7.6, 8.0 Hz, 1H), 8.56 (d, J ¼ 4.8Hz, 1H)
2
8
1
2
-[(4-Fluorophenyl)imino]-3-(2-pyridylmethyl)thiazolidine
(4b-11, C H FN S)
Yield 85%; mp 77.8–78.7 C; H NMR (400MHz, CDCl ):
1
5
14
3
ꢂ
1
3
ꢁ
1
ppm; IR (KBr): ꢂꢀ ¼ 1618, 1589, 1514, 1240, 827 cm
;
ꢁ
2
¼ 3.16 (t, J ¼ 7.0Hz, 2H), 3.65 (t, J ¼ 7.0 Hz, 2H), 4.83 (s,
H), 6.86–7.00 (m, 4H), 7.21 (dd, J ¼ 4.8, 7.6 Hz, 1H), 7.42
þ
HRMS calculated for C H N S [Mþ H ] 313.1487, found
1
7 21 4
3
13.1475.
(
(
1
d, J ¼ 8.0 Hz, 1H), 7.69 (ddd, J ¼ 1.6, 7.6, 8.0 Hz, 1H), 8.57
dd, J ¼ 1.6, 4.8 Hz, 1H) ppm; IR (KBr): ꢂꢀ ¼ 1614, 1589,
2
-[(2-Methylphenyl)imino]-3-(2-pyridylmethyl)thiazolidine
ꢁ1
213, 842 cm ; HRMS (ESI) calculated for C H FN S
1
5
15
3
þ
(
4b-6, C H N S)
16 17 3
[Mþ H ] 288.0971, found 288.0968.
1
Yield 70%; oil; H NMR (400 MHz, CDCl ): ꢁ ¼ 2.14 (s,
3
3
H), 3.11 (t, J ¼ 6.8 Hz, 2H), 3.65 (t, J ¼ 6.8 Hz, 2H), 4.85
2
-[(2,4-Difluorophenyl)imino]-3-(2-pyridylmethyl)-
(
7
7
s, 2H), 6.85 (d, J ¼ 7.6Hz, 1H), 6.94 (t, J ¼ 7.6 Hz, 1H),
thiazolidine (4b-12, C H F N S)
13 2 3
1
Yield 80%; mp 50.6–51.9 C; H NMR (400 MHz, CDCl ):
1
5
.06–7.21 (m, 3H), 7.44 (d, J ¼ 8.0 Hz, 1H), 7.66 (t, J ¼
.6 Hz, 1H), 8.55 (dd, J ¼ 0.8, 4.0 Hz, 1H) ppm; IR (film):
ꢂ
3
ꢁ
1
ꢁ ¼ 3.19 (t, J ¼ 7.0 Hz, 2H), 3.71 (t, J ¼ 7.0 Hz, 2H), 4.86
(s, 2H), 6.74–6.86 (m, 2H), 6.89–6.97 (m, 1H), 7.21 (dd,
J ¼ 4.8, 7.6Hz, 1H), 7.49 (d, J ¼ 8.0Hz, 1H), 7.70 (ddd,
J ¼ 1.6, 7.6, 8.0 Hz, 1H), 8.56 (dd, J ¼ 1.6, 4.8 Hz, 1H) ppm;
ꢂꢀ ¼ 1628, 1591, 1236, 761 cm ; HRMS (ESI) calculated
þ
for C H N S [Mþ H ] 284.1221, found 284.1216.
1
6 18 3
2
-[(2,6-Dimethylphenyl)imino]-3-(2-pyridylmethyl)-
ꢁ
1
IR (KBr): ꢂꢀ ¼ 1610, 1588, 1244, 846, 757cm ; HRMS (ESI)
thiazolidine (4b-7, C H N S)
1
7
19
3
þ
calculated for C H F N S [M þ H ] 306.0877, found
15 14 2 3
1
Yield 75%; oil; H NMR (400 MHz, CDCl ): ꢁ ¼ 2.10 (s, 6H),
3
3
06.0883.
3
6
.09 (t, J ¼ 6.8Hz, 2H), 3.69 (t, J ¼ 6.8 Hz, 2H), 4.86 (s, 2H),
.85 (t, J ¼ 7.6 Hz, 1H), 6.98 (d, J ¼ 7.6 Hz, 2H), 7.14–7.20
(
8
m, 1H), 7.48 (d, J ¼ 8.0 Hz, 1H), 7.66 (ddd, J ¼ 1.6, 7.6,
2-[(2,6-Difluorophenyl)imino]-3-(2-pyridylmethyl)-
.0 Hz, 1H), 8.55 (dd, J ¼ 1.6, 4.8 Hz, 1H) ppm; IR (film):
thiazolidine (4b-13, C15H
Yield 82%; mp 90.1–90.9 C; H NMR (400MHz, CDCl ):
ꢁ ¼ 3.21 (t, J ¼ 7.0 Hz, 2H), 3.74(t, J ¼ 7.0Hz, 2H), 4.90 (s,
13
ꢂ
F
2
N
1
S)
3
ꢁ
1
ꢂꢀ ¼ 1633, 1588, 1238, 764 cm ; HRMS (ESI) calculated
3
þ
for C H N S [Mþ H ] 298.1378, found 298.1382.
1
7 20 3

1
2
76
G. Li et al.
H), 6.82–6.98 (m, 3H), 7.21 (dd, J ¼ 4.8, 7.2 Hz, 1H), 7.55
1H), 7.89 (d, J ¼ 8.0 Hz, 1H), 8.36 (s, 1H) ppm; IR (KBr):
ꢁ
1
(
d, J ¼ 8.0 Hz, 1H), 7.71 (ddd, J ¼ 1.6, 7.2, 8.0 Hz, 1H), 8.55
ꢂꢀ ¼ 1624, 1599, 1517, 1230, 764 cm ; HRMS (ESI) calcu-
þ
(
dd, J ¼ 1.6, 4.8 Hz, 1H) ppm; IR (KBr): ꢂꢀ ¼ 1618, 1587,
lated for C H ClN O S [Mþ H ] 349.0526, found
1
5
14
4 2
ꢁ
þ
1
1
234, 763, 738 cm
;
HRMS (ESI) calculated for
349.0540.
C H F N S [Mþ H ] 306.0877, found 306.0887.
15 14 2 3
2
-[(3-Nitrophenyl)imino]-3-[(2-chloro-5-pyridyl)-
2
-[(2-Chlorophenyl)imino]-3-(2-pyridylmethyl)thiazolidine
methyl]thiazolidine (4c-3, C H ClN O S)
1
5
13
4 2
1
(4b-14, C H ClN S)
Yield 75%; mp 48.0–49.1 C; H NMR (400 MHz, CDCl ):
1
5
14
3
Yield 80%; oil; H NMR (400 MHz, CDCl ): ꢁ ¼ 3.22 (t,
3
ꢂ
1
3
J ¼ 6.8Hz, 2H), 3.60 (t, J ¼ 6.8Hz, 2H), 4.72 (s, 2H), 7.24–
ꢁ
2
1
¼ 3.18 (t, J ¼ 7.0 Hz, 2H), 3.72 (t, J ¼ 7.0 Hz, 2H), 4.89 (s,
H), 6.93–7.02 (m, 2H), 7.14–7.24 (m, 2H), 7.32–7.39 (m,
H), 7.61 (d, J ¼ 7.6 Hz, 1H), 7.70 (t, J ¼ 7.6 Hz, 1H), 8.56
7
1
7
.30 (m, 1H), 7.36 (d, J ¼ 8.4Hz, 1H), 7.43 (t, J ¼ 8.0, 8.0 Hz,
H), 7.74 (dd, J ¼ 2.4, 8.4Hz, 1H), 7.81 (t, J ¼ 2.0 Hz, 1H),
.84–7.91 (m, 1H), 8.41 (d, J ¼ 2.4 Hz, 1H) ppm; IR (film):
(
d, J ¼ 4.8Hz, 1H) ppm; IR (KBr): ꢂꢀ ¼ 1621, 1582, 1233,
ꢁ1
ꢂꢀ ¼ 1620, 1597, 1520, 1236, 744, 688 cm ; HRMS calcu-
ꢁ
1
7
H ] 304.0675, found 304.0672.
55 cm ; HRMS (ESI) calculated for C H ClN S [Mþ
þ
1
5
15
3
lated for C H ClN O S [Mþ H ] 349.0526, found
1
5
14
4 2
þ
3
49.0520.
2
-[(4-Chlorophenyl)imino]-3-(2-pyridylmethyl)thiazolidine
2
-[(4-Nitrophenyl)imino]-3-[(2-chloro-5-pyridyl)-
(4b-15, C H ClN S)
Yield 78%; mp 73.0–74.5 C; H NMR (400 MHz, CDCl ):
1
5
14
3
methyl]thiazolidine (4c-4, C H ClN O S)
1
5
13
4 2
ꢂ
1
3
ꢂ
1
Yield 75%; mp 117.7–118.3 C; H NMR (400 MHz, CDCl ):
3
ꢁ
(
¼ 3.17 (t, J ¼ 7.0 Hz, 2H), 3.66 (t, J ¼ 7.0 Hz, 2H), 4.83
s, 2H), 6.84–6.92 (m, 2H), 7.18–7.25 (m, 3H), 7.41 (d,
J ¼ 8.0 Hz, 1H), 7.69 (ddd, J ¼ 1.6, 7.6, 8.0 Hz, 1H), 8.57
ꢁ
2
¼ 3.23 (t, J ¼ 7.0Hz, 2H), 3.60 (t, J ¼ 7.0 Hz, 2H), 4.72 (s,
H), 7.00–7.06 (m, 2H), 7.35 (d, J ¼ 8.4 Hz, 1H), 7.71 (dd,
J ¼ 2.4, 8.4Hz, 1H), 8.14–8.20 (m, 2H), 8.40 (d, J ¼ 2.4 Hz,
1
3
(
ꢁ
dd, J ¼ 1.6, 4.4 Hz, 1H) ppm; C NMR (125 MHz, CDCl ):
ꢁ1
þ
3
1
H) ppm; IR (KBr): ꢂꢀ ¼ 1611, 1567, 1501, 1239, 854 cm
;
¼ 26.98, 50.80, 51.98, 122.40, 122.45, 123.33, 128.02,
HRMS (ESI) calculated for C H ClN O S [Mþ H ]
15
14
4 2
1
28.81, 136.77, 149.27, 150.69, 157.11, 159.14 ppm; IR
3
49.0526, found 349.0542.
ꢁ
1
(
KBr): ꢂꢀ ¼ 1613, 1580, 1238, 843 cm ; HRMS (ESI) calcu-
þ
lated for C H ClN S [Mþ H ] 304.0675, found 304.0672.
1
5
15
3
2
-[[4-(Dimethylamino)phenyl]imino]-3-[(2-chloro-5-pyridyl)-
methyl]thiazolidine (4c-5, C H ClN S)
1
7
19
4
2
-[(4-Methylphenyl)imino]-3-(2-pyridylmethyl)thiazolidine
1
Yield 68%; oil; H NMR (400 MHz, CDCl ): ꢁ ¼ 2.91 (s, 6H),
3
(4b-16, C H N S)
Yield 77%; mp 85.9–87.0 C; H NMR (400 MHz, CDCl ):
1
6 17 3
ꢂ
1
3.11 (t, J ¼ 6.8 Hz, 2H), 3.46 (t, J ¼ 6.8 Hz, 2H), 4.69 (s, 2H),
3
6
.72 (d, J ¼ 9.0 Hz, 2H), 6.87 (d, J ¼ 9.0 Hz, 2H), 7.32 (d,
ꢁ
¼ 2.31 (s, 3H), 3.14 (t, J ¼ 7.0 Hz, 2H), 3.63 (t, J ¼ 7.0 Hz,
H), 4.84 (s, 2H), 6.85 (d, J ¼ 8.4 Hz, 2H), 7.08 (d, J ¼ 8.4 Hz,
H), 7.20 (dd, J ¼ 4.8, 7.6 Hz, 1H), 7.45 (d, J ¼ 7.8 Hz, 1H),
.68 (dd, J ¼ 7.6, 7.8 Hz, 1H), 8.56 (d, J ¼ 4.8 Hz, 1H) ppm;
J ¼ 8.2Hz, 1H), 7.75 (dd, J ¼ 2.4, 8.2 Hz, 1H), 8.38 (d,
J ¼ 2.4Hz, 1H) ppm; IR (film): ꢂꢀ ¼ 1620, 1512, 1234,
2
2
7
ꢁ
1
þ
8
347.1097, found 347.1087.
22 cm ; HRMS calculated for C H ClN S [Mþ H ]
1
7
20
4
ꢁ
1
IR (KBr): ꢂꢀ ¼ 1625, 1597, 1503, 1236, 828 cm ; HRMS
þ
(
2
ESI) calculated for C H N S [Mþ H ] 284.1221, found
1
6 18 3
84.1220.
2-[(2-Methylphenyl)imino]-3-[(2-chloro-5-pyridyl)-
methyl]thiazolidine (4c-6, C H ClN S)
1
6
16
3
ꢂ
1
Yield 80%; mp 113.3–113.9 C; H NMR (400 MHz,
2
-(Phenylimino)-3-[(2-chloro-5-pyridyl)methyl]thiazolidine
CDCl ): ꢁ ¼ 2.17 (s, 3H), 3.14 (t, J ¼ 7.0 Hz, 2H), 3.53 (t,
(4c-1, C H ClN S)
Yield 81%; mp 69.0–70.0 C; H NMR (400MHz, CDCl ):
3
1
5
14
3
ꢂ
1
J ¼ 7.0 Hz, 2H), 4.72 (s, 2H), 6.83 (d, J ¼ 8.0 Hz, 1H), 6.98
3
(
1
t, J ¼ 7.6 Hz, 1H), 7.08–7.18 (m, 2H), 7.33 (d, J ¼ 8.4 Hz,
ꢁ
(
7
¼ 3.14 (t, J ¼ 6.8 Hz, 2H), 3.51 (t, J ¼ 6.8 Hz, 2H), 4.71
s, 2H), 6.95 (d, J ¼ 7.8 Hz, 2H), 7.06 (t, J ¼ 7.4 Hz, 1H),
.25–7.36 (m, 3H), 7.76 (dd, J ¼ 2.4, 8.0 Hz, 1H), 8.39 (d,
H), 7.76 (dd, J ¼ 2.4, 8.4 Hz, 1H), 8.40 (d, J ¼ 2.4 Hz, 1H)
ꢁ1
ppm; IR (KBr): ꢂꢀ ¼ 1620, 1589, 1237, 768 cm ; HRMS
þ
1
3
(
found 318.0838.
ESI) calculated for C H ClN S [M þ H ] 318.0832,
J ¼ 2.4 Hz, 1H) ppm; C NMR (125MHz, CDCl ): ꢁ ¼
16 17
3
3
2
1
1
6.80, 46.87, 50.16, 121.79, 123.25, 124.31, 128.92, 131.86,
39.06, 149.38, 150.67, 151.71, 158.72ppm; IR (KBr): ꢂꢀ ¼
ꢁ
1
615, 1590, 1238, 764, 693 cm ; HRMS (ESI) calculated
þ
2-[(2,6-Dimethylphenyl)imino]-3-[(2-chloro-5-pyridyl)-
for C H ClN S [Mþ H ] 304.0675, found 304.0672.
15
15
3
methyl]thiazolidine (4c-7, C H ClN S)
1
7
19
3
ꢂ
1
Yield 79%; mp 62.6–63.8 C; H NMR (400MHz, CDCl ):
3
2
-[(2-Nitrophenyl)imino]-3-[(2-chloro-5-pyridyl)-
ꢁ ¼ 2.12 (s, 6H), 3.12 (t, J ¼ 7.0 Hz, 2H), 3.56 (t, J ¼ 7.0 Hz,
2H), 4.75 (s, 2H), 6.88 (t, J ¼ 7.4Hz, 1H), 7.01 (d, J ¼ 7.4 Hz,
2H), 7.34 (d, J ¼ 8.4 Hz, 1H), 7.79 (dd, J ¼ 2.0, 8.4 Hz, 1H),
8.43 (d, J ¼ 2.0 Hz, 1H) ppm; IR (KBr): ꢂꢀ ¼ 1629, 1588,
methyl]thiazolidine (4c-2, C H ClN O S)
4 2
1
Yield 80%; mp 82.3–83.0 C; H NMR (400 MHz, CDCl ):
1
5
13
ꢂ
3
ꢁ
2
¼ 3.21 (t, J ¼ 7.0 Hz, 2H), 3.59 (t, J ¼ 7.0 Hz, 2H), 4.71 (s,
H), 7.05 (d, J ¼ 7.6 Hz, 1H), 7.14 (t, J ¼ 7.6 Hz, 1H), 7.38 (d,
ꢁ
1
1228, 774 cm ; HRMS (ESI) calculated for C17
H19ClN S
3
þ
J ¼ 8.0 Hz, 1H), 7.47 (t, J ¼ 8.0Hz, 1H), 7.84 (d, J ¼ 8.0 Hz,
[Mþ H ] 332.0988, found 332.0987.

Pyridyl-Containing 2-Phenyliminothiazolidines
177
2
-[[2-(Trifluoromethyl)phenyl]imino]-3-[(2-chloro-5-pyridyl)-
(s, 2H), 6.84–7.00 (m, 3H), 7.35 (d, J ¼ 8.4 Hz, 1H), 7.87
(
dd, J ¼ 2.4, 8.4 Hz, 1H), 8.39 (d, J ¼ 2.4 Hz, 1H) ppm; IR
ꢁ1
methyl]thiazolidine (4c-8, C H ClF N S)
1
1
Yield 83%; mp 87.1–88.4 C; H NMR (400 MHz, CDCl ):
6
13
3 3
ꢂ
(KBr): ꢂꢀ ¼ 1614, 1583, 1233, 750 cm ; HRMS (ESI) cal-
3
þ
culated for C H ClF N S [M þ H ] 340.0487, found
ꢁ
2
¼ 3.17 (t, J ¼ 7.0 Hz, 2H), 3.56 (t, J ¼ 7.0 Hz, 2H), 4.71 (s,
H), 7.00 (d, J ¼ 8.0 Hz, 1H), 7.10 (t, J ¼ 7.6 Hz, 1H), 7.34 (d,
15 13
2 3
3
40.0496.
J ¼ 8.4 Hz, 1H), 7.44 (t, J ¼ 7.6Hz, 1H), 7.59 (d, J ¼ 8.0 Hz,
1
H), 7.78 (dd, J ¼ 2.4, 8.4 Hz, 1H), 8.36 (d, J ¼ 2.4 Hz, 1H)
2-[(2-Chlorophenyl)imino]-3-[(2-chloro-5-pyridyl)methyl]-
ꢁ
1
ppm; IR (KBr): ꢂꢀ ¼ 1618, 1574, 1232, 761 cm ; HRMS
thiazolidine (4c-14, C H Cl N S)
1
5
13
2 3
þ
1
(
ESI) calculated for C H ClF N S [Mþ H ] 372.0549,
1
6
14
3
3
Yield 81%; oil; H NMR (400 MHz, CDCl ): ꢁ ¼ 3.16 (t,
3
found 372.0557.
J ¼ 7.0Hz, 2H), 3.56 (t, J ¼ 7.0Hz, 2H), 4.74 (s, 2H), 6.92–
7
.02 (m, 2H), 7.18 (ddd, J ¼ 1.2, 7.6, 7.6 Hz, 1H), 7.33 (d,
J ¼ 8.0Hz, 1H), 7.37 (dd, J ¼ 1.2, 7.8 Hz, 1H), 7.89 (dd,
J ¼ 2.4, 8.0 Hz, 1H), 8.42 (d, J ¼ 2.4 Hz, 1H) ppm; IR (film):
2
-[[3-(Trifluoromethyl)phenyl]imino]-3-[(2-chloro-5-pyridyl)-
methyl]thiazolidine (4c-9, C H ClF N S)
1
6
13
3 3
ꢁ
1
1
ꢂꢀ ¼ 1621, 1581, 1235, 760cm ; HRMS (ESI) calculated for
Yield 73%; H NMR (400 MHz, CDCl ): ꢁ ¼ 3.16 (t, J ¼
3
þ
C H Cl N S [Mþ H ] 338.0285, found 338.0290.
1
5
14
2 3
6
.8 Hz, 2H), 3.53 (t, J ¼ 6.8Hz, 2H), 4.69 (s, 2H), 7.12 (d,
J ¼ 7.6 Hz, 1H), 7.21 (s, 1H), 7.28 (d, J ¼ 8.4 Hz, 1H), 7.33 (d,
J ¼ 8.4 Hz, 1H), 7.38 (t, J ¼ 7.6 Hz, 1H), 7.72 (dd, J ¼ 2.0,
2-[(4-Chlorophenyl)imino]-3-[(2-chloro-5-pyridyl)methyl]-
8
1
.4 Hz, 1H), 8.39 (d, J ¼ 2.0 Hz, 1H) ppm; IR (film): ꢂꢀ ¼
thiazolidine (4c-15, C H Cl N S)
1
5
13
2 3
ꢁ
1
ꢂ
1
Yield 81%; mp 88.0–88.8 C; H NMR (400MHz, CDCl ):
623, 1602, 1585, 1236, 799, 700 cm ; HRMS (ESI) cal-
3
þ
culated for C H ClF N S [M þ H ] 372.0549, found
ꢁ ¼ 3.16 (t, J ¼ 6.8 Hz, 2H), 3.52 (t, J ¼ 6.8 Hz, 2H), 4.69
(s, 2H), 6.88 (d, J ¼ 8.6Hz, 2H), 7.24 (d, J ¼ 8.6 Hz, 2H),
1
6
14
3 3
3
72.0546.
7
.33 (d, J ¼ 8.4 Hz, 1H), 7.72 (dd, J ¼ 2.2, 8.4 Hz, 1H), 8.38
3
1
3
(
d, J ¼ 2.2 Hz, 1H) ppm; C NMR (125MHz, CDCl ):
2
-[(2-Fluorophenyl)imino]-3-[(2-chloro-5-pyridyl)methyl]-
ꢁ
131.67, 138.98, 149.39, 150.27, 150.80, 159.17 ppm; IR
¼ 26.86, 46.89, 50.23, 123.19, 124.36, 128.36, 128.95,
thiazolidine (4c-10, C H ClFN S)
3
1
Yield 82%; mp 43.2–44.6 C; H NMR (400 MHz, CDCl ):
ꢁ
1
5
13
ꢂ
3
ꢁ1
(
KBr): ꢂꢀ ¼ 1608, 1582, 1237, 835 cm ; HRMS (ESI) cal-
¼ 3.17 (t, J ¼ 7.0 Hz, 2H), 3.56 (t, J ¼ 7.0 Hz, 2H), 4.73
þ
culated for C H Cl N S [M þ H ] 338.0285, found
1
5
14
2 3
(
(
(
s, 2H), 6.94–7.10 (m, 4H), 7.34 (d, J ¼ 8.2 Hz, 1H), 7.84
3
38.0290.
dd, J ¼ 2.4, 8.2 Hz, 1H), 8.39 (d, J ¼ 2.4 Hz, 1H) ppm; IR
ꢁ
1
KBr): ꢂꢀ ¼ 1621, 1584, 1236, 767 cm ; HRMS (ESI) cal-
þ
culated for C H ClFN S [M þ H ] 322.0581, found
Biological Assay
1
5
14
3
3
22.0580.
The herbicidal activities of compounds 4 were evaluated with
a previously reported procedure [17]. Each sample was dis-
solved in DMF, and then the solution was diluted with emul-
2
-[(4-Fluorophenyl)imino]-3-[(2-chloro-5-pyridyl)methyl]-
sifier 0201 (a mixture of anionic and nonionic surfactant)
3
containing 0.1 mg=cm H O until the required concentration
thiazolidine (4c-11, C H ClFN S)
3
1
Yield 77%; mp 105.0–106.4 C; H NMR (400MHz, CDCl ):
1
5
13
ꢂ
2
3
was achieved. The biological tests were carried out in plastic
boxes. Nineteen milliliters of 0.9% thawed water agar and
ꢁ
¼ 3.15 (t, J ¼ 7.0 Hz, 2H), 3.51 (t, J ¼ 7.0 Hz, 2H), 4.69 (s,
H), 6.85–6.93 (m, 2H), 6.93–7.01 (m, 2H), 7.33 (d, J ¼
.0 Hz, 1H), 7.73 (dd, J ¼ 2.4, 8.0 Hz, 1H), 8.39 (d, J ¼ 2.4 Hz,
2
8
1
3
cm of diluted solution were added to the plastic boxes and
1
shaken. After the drug-containing agar was cool, the seeds of
Echinochloa crusgalli, Sorghum vulgare, Digitaria sanguin-
ꢁ
1
H) ppm; IR (KBr): ꢂꢀ ¼ 1618, 1587, 1235, 837 cm ; HRMS
þ
(
ESI) calculated for C H ClFN S [Mþ H ] 322.0581,
1
5
14
3
found 322.0590.
2
-[(2,4-Difluorophenyl)imino]-3-[(2-chloro-5-pyridyl)-
methyl]thiazolidine (4c-12, C H ClF N S)
1
5
12
2 3
ꢂ
1
Yield 81%; mp 96.6–98.0 C; H NMR (400 MHz, CDCl ):
3
ꢁ
2
¼ 3.18 (t, J ¼ 7.0 Hz, 2H), 3.56 (t, J ¼ 7.0 Hz, 2H), 4.72 (s,
H), 6.76–6.96 (m, 3H), 7.34 (d, J ¼ 8.4 Hz, 1H), 7.80 (dd,
J ¼ 2.4, 8.4 Hz, 1H), 8.39 (d, J ¼ 2.4 Hz, 1H) ppm; IR(KBr):
ꢁ
1
ꢂꢀ ¼ 1617, 1586, 1237, 846, 812 cm ; HRMS (ESI) cal-
þ
culated for C H ClF N S [M þ H ] 340.0487, found
1
5
13
2 3
3
40.0479.
2
-[(2,6-Difluorophenyl)imino]-3-[(2-chloro-5-pyridyl)
methyl]thiazolidine (4c-13, C H ClF N S)
1
5
13
2 3
ꢂ
1
Yield 86%; mp 85.3–85.9 C; H NMR (400 MHz, CDCl ):
Fig. 1. Demonstration of the net-charge (e.g., compound
4a-1)
3
ꢁ
¼ 3.20 (t, J ¼ 7.0 Hz, 2H), 3.60 (t, J ¼ 7.0 Hz, 2H), 4.76

1
78
G. Li et al.: Pyridyl-Containing 2-Phenyliminothiazolidines
nalis, Eclipta prostrasta, Cucumis sativus, and Brassica camp-
estris were sowed, and then the cultivations were kept at
References
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2
4 ꢃ 1 C with exposure to light of 3000 lꢄ for 7 days. The
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[
2] Heap I (accessed Sept 21, 2005) International Survey of
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HA ¼ lg½a=ð100 ꢁ aÞꢅ þ lg Mw
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(
where a indicates the growth inhibitory rates (%) and Mw
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5
[5] Wang QM, Sun HK, Cao HY, Cheng MR, Huang RQ
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Descriptor Variables
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T
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N
C
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compound were calculated, its spatial molecular conformation
was also optimized with Hyperchem to acquire its most re-
laxed conformation. All descriptor data are listed in Table 3.
In addition, the molecular shape parameters such as surface
area, angle, and length were calculated by using a molecu-
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Software based on the most optimized conformation, which
showed poor correlations with herbicidal activity and were not
listed.
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Multiple Linear Regression (MLR) Analysis
[
[
[
[
The regression analysis was done with a computer software
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minimizing the sum of squared deviations being introduced
step-by-step and the analysis being stopped when the intro-
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nificant as evidenced by F-test.
1
(
(1989) Chem Abstr 112: 198368; (1989) US patent
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17] Li GY, Qian XH, Cui JN, Huang QC, Cui DW, Zhang R,
Acknowledgements
[
This project was supported by the National Key Project for
Basic Research (2003CB114400) and the National Natural
Science Foundation of China.
Liu FY (2006) J Fluorine Chem 127: 182
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