Synthesis and biological activities of new chiral imidazolinone derivatives

Article abstract of DOI:10.1080/10426500902717325

New optically active 2-thio-4-imidazolinones 3 with a chiral carbon at position-3 were synthesized from isothiocyanates 2, which were obtained from aza-Wittig reactions of vinyliminophosphoranes 1 with CS₂, with easily accessible chiral (S)- or (R)-amino acid methyl ester hydrochlorides. 2-Methylthio-4H-imidazolin-4-ones 4 were obtained by the S-alkylation of compounds 3 in the presence of K₂CO₃ causing partial racemization of the enantiomeric pure products. These compounds were identified by MS, IR, ¹H NMR, ¹³C NMR spectroscopy, and elemental analysis. The structures of enantiomers 3c and 3d were also confirmed by X-ray diffraction analysis. The results of preliminary bioassay indicated that compounds 4 exhibited growth inhibition of barnyard grass and cole root and stalk, and fungicidal activities against Fusarium oxysporium, Rhizoctonia solani, Gibberella zeae, Dothiorella gregaria, and Colletotrichum gossypii. Supplemental materials are available for this article. Go to the publisher′s online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Full text of DOI:10.1080/10426500902717325

This article was downloaded by: [Memorial University of Newfoundland]
On: 18 July 2014, At: 10:12
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
Synthesis and Biological Activities of
New Chiral Imidazolinone Derivatives
Xiaobo Huang a b , Dengze Wu b , Jinchang Ding c , Xichang Zhang b
Miaochang Liu b , Huayue Wu b & Weike Su a
,
a Key Laboratory of Pharmaceutical Engineering of Ministry of
Education, College of Pharmaceutical Sciences , Zhejiang University
of Technology , Hangzhou, P. R. China
b College of Chemistry and Materials Engineering , Wenzhou
University , Wenzhou, P. R. China
c Wenzhou Vocational & Technical College , Wenzhou, P. R. China
Published online: 28 Dec 2009.
To cite this article: Xiaobo Huang , Dengze Wu , Jinchang Ding , Xichang Zhang , Miaochang Liu ,
Huayue Wu & Weike Su (2009) Synthesis and Biological Activities of New Chiral Imidazolinone
Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 185:1, 117-128
To link to this article: http://dx.doi.org/10.1080/10426500902717325
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Phosphorus, Sulfur, and Silicon, 185:117–128, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902717325
SYNTHESIS AND BIOLOGICAL ACTIVITIES OF NEW
CHIRAL IMIDAZOLINONE DERIVATIVES
Xiaobo Huang,1,2 Dengze Wu,2 Jinchang Ding,3
Xichang Zhang,2 Miaochang Liu,2 Huayue Wu,2 and Weike Su1
1Key Laboratory of Pharmaceutical Engineering of Ministry of Education,
College of Pharmaceutical Sciences, Zhejiang University of Technology,
Hangzhou, P. R. China
2College of Chemistry and Materials Engineering, Wenzhou University,
Wenzhou, P. R. China
3Wenzhou Vocational & Technical College, Wenzhou, P. R. China
New optically active 2-thio-4-imidazolinones 3 with a chiral carbon at position-3 were syn-
thesized from isothiocyanates 2, which were obtained from aza-Wittig reactions of vinylim-
inophosphoranes 1 with CS2, with easily accessible chiral (S)- or (R)-amino acid methyl ester
hydrochlorides. 2-Methylthio-4H-imidazolin-4-ones 4 were obtained by the S-alkylation of
compounds 3 in the presence of K2CO3 causing partial racemization of the enantiomeric
pure products. These compounds were identified by MS, IR, 1H NMR, 13C NMR spectroscopy,
and elemental analysis. The structures of enantiomers 3c and 3d were also confirmed by
X-ray diffraction analysis. The results of preliminary bioassay indicated that compounds
4 exhibited growth inhibition of barnyard grass and cole root and stalk, and fungicidal
activities against Fusarium oxysporium, Rhizoctonia solani, Gibberella zeae, Dothiorella
gregaria, and Colletotrichum gossypii.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Aza-Wittig reaction; chiral agrochemicals; crystal structure; fungicidal activities;
herbicidal activities; imidazolinone derivatives
INTRODUCTION
Imidazolinone derivatives have received increased attention over the past two decades
due to their interesting biological activities. Some of them exhibit a broad spectrum
of pharmacological activities, such as anticonvulsive,1 antiviral,2 antitumor,3 antibacte-
rial,4 and anti-inflammatory.5 Most importantly, some imidazolinone derivatives have been
Received 31 October 2008; accepted 24 December 2008.
The authors are thankful for the financial support from National Key Technology R&D Program (Grant
No. 2007BAI34B00), the National Natural Science Foundation of China (Grant No. 20876147), and the Opening
Foundation of Zhejiang Provincial Top-Key Pharmaceutical Discipline (Grant No. 20050603, 20050610, and
20080602).
Address correspondence to Weike Su, Key Laboratory of Pharmaceutical Engineering of Ministry of Edu-
cation, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P.R. China.
E-mail: suweike@zjut.edu.cn
117

118
X. HUANG ET AL.
successfully used in crop protection. Imidazolinone herbicides, for example imazapyr,
imazapic, imazethapyr, imazamox, imazamethabenz, and imazaquin are distinguished se-
lective herbicides that act by inhibiting the enzyme acetohydroxyacid synthase (AHAS),
also known as acetolactate synthase (ALS), which is a critical enzyme for the biosynthesis of
branched-chain amino acids in plants.6 Some imidazolinones also have been found to pos-
sessfungicidal activities, forexample5-methyl-2-methylthio-5-phenyl-3-phenylamine-3,5-
dihydro-imidazolin-4-one (RPA407213) shows high fungicidal activities.7 What deserves
special mention is that the imidazolinone derivatives exhibited above as agrochemicals are
chiral compounds. For instance, the imidazolinone ring of imidazolinone herbicide has a
chiral carbon to which the methyl and isopropyl groups are attached. It has been reported
that the R-enantiomer of imazethapyr and other pyridine imidazolinones are 10-fold more
inhibitory to AHAS than the S-enantiomer.8 Many compounds used in the pharmaceutical
and agrochemical industries contain chiral centers, but they are often produced and used as
racemic mixtures. Although chiral compounds have potential advantages in terms of regu-
latory, intellectual property, and marketing benefits, limited access to chiral raw materials
and economic synthesis routes are key reasons why single isomers are less common than
they might be.9 Therefore, the development of more chiral routes is still an attractive topic
of study on agrochemicals.
In recent years, the aza-Wittig reaction of iminophosphoranes has attracted consider-
able attention due to its high potential for the synthesis of nitrogen-containing heterocycles.
This method provides one of the best procedures for the formation of carbon–nitrogen dou-
ble bonds under mild and neutral reaction conditions.10 Some imidazolinone derivatives,
such as 2-alkylthio-4H-imidazolin-4-ones, have been synthesized by this method to evaluate
their biological activities, and some of them exhibit herbicidal and fungicidal activities.11
Based on the above idea, we now report the synthesis and biological activities of a series
of new optically active imidazolinone derivatives with a chiral carbon at position-3.
RESULTS AND DISCUSSION
The synthetic pathway for 2-methylthio-4H-imidazolin-4-ones 4 is shown in
Scheme 1. The intermediate vinyliminophosphorane 1 synthesized by the method in
the literature12 reacted with CS2 to give isothiocyanates 2 via an aza-Wittig reaction.
Scheme 1

NEW CHIRAL IMIDAZOLINONE DERIVATIVES
119
Table I Synthesis of compounds 3a–m
Compound
R1
R2
R3
Yield (%)
3a
3b
3c
3d
3e
3f
3g
3h
3i
Ph
Ph
4-Cl Ph
CH3
COOCH3
CH3
COOCH3
CH3
COOCH3
CH3
COOCH3
CH2OH
CH2OH
1H-indol-3-yl
CH2COOCH3
CH2CH2COOCH3
COOCH3
CH3
COOCH3
CH3
COOCH3
CH3
COOCH3
CH3
COOCH3
COOCH3
CH3
COOCH3
COOCH3
58
57
56
55
50
61
84
81
64
67
76
78
71
4-Cl Ph
4-CH3-Ph
4-CH3 Ph
4-CH3O Ph
4-CH3O Ph
Ph
4-CH3O Ph
4-CH3O Ph
4-CH3O Ph
4-CH3O Ph
3j
3k
3l
3m
Compounds 2 reacted with easily accessible (S)- or (R)-amino acid methyl ester hy-
drochlorides in the presence of Et3N to give new single chiral 2-thio-4-imidazolinones
3 by an intramolecular cyclocondensation at room temperature in 50–84% yields
(Table I). As can be seen in Scheme 2, the reaction between isothiocyanates 2 and amino
acid methyl esters should afford intermediates 5. According to the previous reports,11,13
from these intermediates 5, the formation of two regioisomeric 2-thio-4-imidazolinones
3 and/or 6 could, in principle, take place. Pure compounds 3 were obtained separately from
Scheme 2
the reaction mixture on a silica gel column, but isomers 6 could not be isolated. Perhaps
the main cause is that compounds 3 are more stable in structure in comparison with
compounds 6. Single crystal structures of the enantiomers 3c and 3d grown from CH2Cl2
and ether (1:1, v/v) were confirmed by X-ray diffraction analysis as shown in Figures
1 and 2. Diffraction measurements were carried out on a Bruker APEX area-detector
diffractometer (graphite-monochromatized Mo-Kα radiation, λ = 0.71073 Å). The
hydrogen atoms were added according to the theoretical models. The structures were
refined by full-matrix least-squares method on F2 with anisotropic thermal parameters
for all non-hydrogen atoms. The programs for structure solution and refinement were
SHELXS-9714 and SHELXL-97,15 respectively. Crystal data are summarized in Table II.
The crystallographic data was deposited at CCDC.16 The X-ray crystal structures of 3c
and 3d indicated the compounds exist as S-configuration and R-configuration, respectively,

120
X. HUANG ET AL.
Figure 1 The molecular structure of 3c, with the atom-numbering scheme. Displacement ellipsoids are drawn at
the 50% probability level.
and they are enantiomers. The racemate of 3c and 3d was synthesized by the reaction of
racemic alanine methyl esters hydrochloride and isothiocyanate and applied to determine
the enantiomeric excess (ee) values of 3c and 3d by comparing their HPLC data. The ee
values of both these compounds were 100% determined by HPLC on Chiralcel OD-H
column.17 The results demonstrated that 3c and 3d were pure optical compounds. The
target compounds 2-methylthio-4H-imidazolin-4-ones 4 were obtained from compounds
3 by using K2CO3 as base in 67–92% yields (Table III). In view of using K2CO3 as the
base in the course of the S-alkylation reaction, the racemate of 4c and 4d was synthesized
in order to determine the optical purity of these compounds. The results showed that the
ee values of 4c and 4d were 82% and 79%, respectively,18 and indicated that the reaction
proceeds caused about 10% racemization of pure optical compounds in the presence of
K2CO3.
The biological activities in vitro of all compounds 4a–4m were investigated according
to a method reported in the literature.11b The results are summarized in Tables IV and
V (available online in the Supplemental Materials for this article). As far as different
configuration of compounds 4 was concerned, on the whole, the inhibitory activities on cole
and barnyard grass (Echinochloa crusgalli) of S-enantiomers of the target compounds were
better than those of R-enantiomers. But in view of biological activities of enantiomers, they
did not show distinguished difference, which might be caused by the partial racemization
of the target compounds under base conditions.
Figure 2 The molecular structure of 3d, with the atom-numbering scheme. Displacement ellipsoids are drawn
at the 50% probability level.

NEW CHIRAL IMIDAZOLINONE DERIVATIVES
121
Table II Crystal data and summary of data collection and structure refinement of enantiomers 3c and 3d
Entry
3c
3d
Formal
Temperature
C14H13ClN2O3S
298(2) K
C14H13ClN2O3S
298(2) K
Wavelength
0.71073
0.71073
Crystal system
Space group
Orthorhombic
P212121
Orthorhombic
P212121
a
7.0847(4) Å
6.6117(6) Å
b
6.6079(5) Å
7.0904(7) Å
c
α
30.902(2) Å
30.948(3) Å
90 o
90 o
β
90 o
90 o
90 o
90 o
γ
Volume
Z
Calculated density
Absorption coefficient
F(000)
1446.69(17) Å3
4
1450.8(2) Å3
4
1.491 Mg mm−3
0.419 mm−1
1.487 Mg mm−3
0.418 mm−1
672
672
Crystal size
θ Range for data collection
Limiting indices
0.48 × 0.19 × 0.17 mm
0.26 × 0.17 × 0.09 mm
1.32–25.26 o
2.63–25.01 o
−8 ≤ h ≤ 5, −7 ≤ k ≤ 7,
−37 ≤ l ≤ 35
7723/2609 [R (int) = 0.0201]
99.9%
Semi-empirical from equivalents
Full-matrix least-squares on F2
1.156
−7 ≤ h ≤ 7, −8 ≤ k ≤ 8,
−25 ≤ l ≤ 36
7690/2566 [R (int) = 0.0531]
99.9%
Semi-empirical from equivalents
Full-matrix least-squares on F2
1.035
Reflections collection/ unique
Completeness to θ = 25.19◦
Absorption correction
Refinement method
Goodness-of fit on F2
Final R indices [I > 2σ (I)]
Largest diff. Peak and hole
R1 = 0.0440, wR2 = 0.1151
R1 = 0.0857, wR2 = 0.2369
0.310 and −0.242 eA−3
0.542 and −0.352 eA−3
Table III Synthesis of compounds 4a–m
Compound
R1
R2
R3
Yield (%)
4a
4b
4c
4d
4e
4f
4g
4h
4i
Ph
Ph
CH3
COOCH3
CH3
COOCH3
CH3
COOCH3
CH3
COOCH3
CH2OH
CH2OH
COOCH3
CH3
COOCH3
CH3
COOCH3
CH3
COOCH3
CH3
COOCH3
COOCH3
CH3
COOCH3
COOCH3
79
92
70
83
87
67
72
72
67
68
80
90
83
4-Cl Ph
4-Cl Ph
4-CH3 Ph
4-CH3 Ph
4-CH3O Ph
4-CH3O Ph
Ph
4-CH3O Ph
4-CH3O Ph
4-CH3O Ph
4-CH3O Ph
4j
4k
4l
1H-indol-3-yl
CH2COOCH3
CH2CH2COOCH3
4m

122
X. HUANG ET AL.
CONCLUSIONS
In conclusion, we have developed an efficient synthesis of novel chiral 2-thio-4-
imidazolinones 3 via a tandem aza-Wittig reaction that utilizes easily accessible starting
material and allows mild reaction conditions with satisfactory yields. The structures of
enantiomers 3c and 3d were confirmed by X-ray diffraction analysis. Due to the use of
the base in the S-alkylation reaction of compounds 3, racemization of a small proportion
of the target 2-methylthio-4H-imidazolin-4-ones 4 was detected by HPLC. The results of
the bioassay indicated some compounds 4 exhibited not only inhibition of barnyard and
cole grass, but also fungicidal activities against Fusarium oxysporium, Rhizoctonia solani,
Gibberella zeae, Dothiorella gregaria, and Colletotrichum gossypii.
EXPERIMENTAL
The 1H NMR spectra were obtained using an Avance-300 spectrometer 300 MHz for
NMR and 75 MHz for 13C NMR and reported as parts per million (ppm) from the internal
standard TMS. IR spectra were taken on Equinox-55 Infrared spectrometer. The ee value
determination was carried out using chiral P-E Series200 HPLC with a Chiralpak OD-H
column on a Waters chromatograph with a P-E Series 200 UV/vis detector. Mass spectra
were recorded on an Agilent 1100LC/MSD Trap SL spectrometer. Elementary analyses
were taken on an Elementar Vario Micro analyzer. Optical rotations were measured with
a Rudolph Autopol IV automatic polarimeter. Melting points were determined on X4
microscopic melting apparatus (uncorrected).
General Preparation of 2-Thio-4-imidazolinones 3
To a solution of vinyliminophosphoranes 1 (5 mmol) in dry dichloromethane, excess
CS2 (50 mmol) was added, and the mixture was refluxed for 29 h under nitrogen. The
solvent was removed under pressure and ether, and petroleum ether (20 mL, 1:2, v/v)
was added to precipitate triphenylphosphine sulfide, which was removed by filtration. The
filtrate was evaporated to give isothiocyanates 2, which was used without purification. To
a solution of the crude 2 in dry CH3CN (20 mL), (S)- or (R)-amino acid methyl esters
hydrochloride (5 mmol) and Et3N (5 mmol) were added. The mixture was allowed to
reflux for 3 h and then to cool to room temperature. After evaporation, the residue was
separated by column chromatography (petroleum ether/ethyl acetate, 10:1, v/v) to afford
2-thio-4-imidazolinones 3.
(S)-2-(4-Benzylidene-5-oxo-2-thio-imidazolidin-1-yl)propanoic acid met-
hyl ester (3a). Appearance: yellow solid; mp 148–150◦C; [α]20 = –6.9 (c = 1;
D
1
(CH3)2CO); H NMR (300 MHz, CDCl3): δ 1.71 (d, 3H, J = 7.3 Hz, CH3), 3.76 (s,
3H, OCH3), 5.40 (q, 1H, J = 7.3 Hz, CH), 6.75 (s, 1H, = C H), 7.49-7.41 (m, 5H, Ar H),
8.90 (s, 1H, N H); 13C NMR (75 MHz, CDCl3): δ 14.42, 50.89, 52.81, 114.09, 126.03,
129.19, 129.50, 129.88, 132.64, 162.82, 169.53, 177.29; IR (KBr) ν/cm−1: 1269, 1440,
1642, 1726, 3414; MS: m/z = 291 (M++1); calcd. for C14H14N2O3S (%): C, 57.92; H,
4.86; N, 9.65; found (%): C, 57.89; H, 4.82; N, 9.69.
(R)-2-(4-Benzylidene-5-oxo-2-thio-imidazolidin-1-yl)propanoic acid met-
hyl ester (3b). Appearance: yellow solid; mp 147–149◦C; [α]20 = +7.2 (c = 1;
D
1
(CH3)2CO); H NMR (300 MHz, CDCl3): δ 1.70 (d, 3H, J = 7.3 Hz, CH3), 3.75 (s,
3H, OCH3), 5.40 (q, 1H, J = 7.3 Hz, CH), 6.74 (s, 1H, = C H), 7.49-7.38 (m, 5H, Ar H),

NEW CHIRAL IMIDAZOLINONE DERIVATIVES
123
9.15 (s, 1H, N H); 13C NMR (75 MHz, CDCl3): δ 14.44, 50.91, 52.80, 114.12, 126.06,
129.23, 129.55, 129.80, 132.60, 162.78, 169.49, 177.27; IR (KBr) ν/cm−1: 1267, 1443,
1640, 1725, 3410; MS: m/z = 291 (M++1); calcd. for C14H14N2O3S (%): C, 57.92; H,
4.86; N, 9.65; found (%): C, 57.88; H, 4.85; N, 9.60.
(S)-2-[4-(4-Chlorobenzylidene)-5-oxo-2-thio-imidazolidin-1-yl]propanoic
acid methyl ester (3c). Appearance: yellow solid; mp 170–172◦C; [α]20 = –4.0
D
(c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 1.71 (d, 3H, J = 7.2 Hz, CH3), 3.77 (s,
3H, OCH3), 5.40 (q, 1H, J = 7.2 Hz, CH), 6.68 (s, 1H, = C H), 7.37 (d, 2H, J = 8.6 Hz,
Ar H), 7.45 (d, 2H, J = 8.6 Hz, Ar H), 8.63 (s, 1H, N H); 13C NMR (75 MHz, CDCl3):
δ 14.41, 51.00, 52.85, 112.40, 126.29, 129.81, 130.37, 131.13, 135.89, 162.71, 169.44,
177.39; IR (KBr) ν/cm−1: 1274, 1447, 1644, 1726, 3348; MS: m/z = 324 (M+); calcd. for
C14H13ClN2O3S (%): C, 51.77; H, 4.03; N, 8.63; found (%): C, 51.66; H, 4.05; N, 8.69.
(R)-2-[4-(4-Chlorobenzylidene)-5-oxo-2-thio-imidazolidin-1-yl]propanoic
acid methyl ester (3d). Appearance: yellow solid; mp 168–170◦C; [α]20 = +3.9
D
(c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 1.71 (d, 3H, J = 7.2 Hz, CH3), 3.77 (s,
3H, OCH3), 5.40 (q, 1H, J = 7.2 Hz, CH), 6.67 (s, 1H, = C H), 7.38 (d, 2H, J = 8.6 Hz,
Ar H), 7.45 (d, 2H, J = 8.6 Hz, Ar H), 8.95 (s, 1H, N H); 13C NMR (75 MHz, CDCl3):
δ 14.36, 50.90, 52.83, 112.57, 126.16, 129.71, 130.41, 130.99, 135.80, 162.70, 169.44,
177.30; IR (KBr) ν/cm−1: 1273, 1440, 1645, 1725, 3340; MS: m/z = 324 (M+); calcd. for
C14H13ClN2O3S (%): C, 51.77; H, 4.03; N, 8.63; found (%): C, 51.70; H, 3.99; N, 8.65.
(S)-2-[4-(4-Methylbenzylidene)-5-oxo-2-thio-imidazolidin-1-yl]propanoic
acid methyl ester (3e). Appearance: yellow solid; mp 161–162◦C; [α]20 = –12.0
D
(c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 1.69 (d, 3H, J = 7.2 Hz, CH3), 2.40
(s, 3H, CH3), 3.76 (s, 3H, OCH3), 5.40 (q, 1H, J = 7.2 Hz, CH), 6.73 (s, 1H, = C H),
7.28 (d, 2H, J = 8.5 Hz, Ar H), 7.45 (d, 2H, J = 8.5 Hz, Ar H), 8.98 (s, 1H, N H); 13
C
NMR (75 MHz, CDCl3): δ 14.42, 21.51, 50.92, 52.70, 114.14, 125.74, 129.14, 130.29,
131.03, 139.72, 162.70, 169.73, 176.92; IR (KBr) ν/cm−1: 1271, 1449, 1645, 1729, 3438;
MS: m/z = 305 (M++1); calcd. for C15H16N2O3S (%): C, 59.19; H, 5.30; N, 9.20; found
(%): C, 59.23; H, 5.28; N, 9.15.
(R)-2-[4-(4-Methylbenzylidene)-5-oxo-2-thio-imidazolidin-1-yl]propanoic
acid methyl ester (3f). Appearance: yellow solid; mp 160–161◦C; [α]20 = +11.9
D
(c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 1.69 (d, 3H, J = 7.2 Hz, CH3), 2.38
(s, 3H, CH3), 3.75 (s, 3H, OCH3), 5.40 (q, 1H, J = 7.3 Hz, CH), 6.71 (s, 1H, = C H),
7.25 (d, 2H, J = 8.5 Hz, Ar H), 7.34 (d, 2H, J = 8.5 Hz, Ar H), 9.11 (s, N H, 1H); 13
C
NMR (75 MHz, CDCl3): δ 14.37, 21.48, 50.80, 52.74, 114.41, 125.26, 129.22, 129.74,
130.20, 140.52, 162.81, 169.51, 177.00; IR (KBr) ν/cm−1: 1269, 1447, 1640, 1726, 3430;
MS: m/z = 305 (M++1); calcd. for C15H16N2O3S (%): C, 59.19; H, 5.30; N, 9.20; found
(%): C, 59.16; H, 5.24; N, 9.12.
(S)-2-[4-(4-Methoxybenzylidene)-5-oxo-2-thio-imidazolidin-1-yl]propan-
oic acid methyl ester (3g). Appearance: yellow solid; mp 175–177◦C; [α]20 = –23.2
D
(c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 1.71 (d, 3H, J = 7.3 Hz, CH3), 3.76 (s,
3H, OCH3), 3.87 (s, 3H, Ar OCH3), 5.40 (q, 1H, J = 7.3 Hz, CH), 6.72 (s, 1H, = C H),
6.99 (d, 2H, J = 8.8 Hz, Ar H), 7.40 (d, 2H, J = 8.8 Hz, Ar H), 8.73 (s, N H, 1H); 13
C
NMR (75 MHz, CDCl3): δ 14.41, 50.87, 52.74, 55.48, 114.34, 115.12, 124.37, 125.21,
131.02, 161.03, 162.87, 169.55, 176.88; IR (KBr) ν/cm−1: 1263, 1463, 1646, 1723, 3437;
MS: m/z = 321 (M++1); calcd. for C15H16N2O4S (%): C, 56.24; H, 5.03; N, 8.74; found
(%): C, 56.14; H, 5.05; N, 8.79.

124
X. HUANG ET AL.
(R)-2-[4-(4-Methoxybenzylidene)-5-oxo-2-thio-imidazolidin-1-yl]propan
oic acid methyl ester (3h). Appearance: yellow solid; mp 174–176◦C; [α]20 = +22.9
(c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 1.70 (d, 3H, J = 7.3 Hz, CH3), 3.75
(s, 3H, OCH3), 3.86 (s, 3H, Ar OCH3), 5.40 (q, 1H, J = 7.3 Hz, CH), 6.71 (s, 1H, CH),
D
6.99 (d, 2H, J = 8.8 Hz, Ar H), 7.41 (d, 2H, J = 8.8 Hz, Ar H), 8.96 (s, 1H, NH); 13
C
NMR (75 MHz, CDCl3): δ 14.37, 50.79, 52.74, 55.43, 114.45, 115.03, 124.25, 125.10,
131.05, 160.96, 162.85, 169.54, 176.79; IR (KBr) ν/cm−1: 1262, 1461, 1645, 1720, 3430;
MS: m/z = 321 (M++1); calcd. for C15H16N2O4S (%): C, 56.24; H, 5.03; N, 8.74; found
(%): C, 56.20; H, 5.01; N, 8.76.
(S)-2-(4-Benzylidene-5-oxo-2-thio-imidazolidin-1-yl)-3-hydroxy-propan
oic acid methyl ester (3i). Appearance: yellow solid; mp 189–190◦C; [α]20 = +24.0
D
1
(c = 1; (CH3)2CO); H NMR (300 MHz, CDCl3): δ 3.81 (s, 3H, OCH3), 4.27-4.24
(m, 2H, CH2), 5.51 (t, 1H, J = 5.2 Hz, CH), 6.80 (s, 1H, = C H), 7.51-7.40 (m, 5H,
Ar H), 8.96 (s, N H, 1H); 13C NMR (75 MHz, CDCl3): δ 52.91, 57.96, 60.56, 114.76,
125.86, 129.18, 129.57, 130.08, 132.56, 163.80, 167.87, 177.58; IR (KBr) ν/cm−1: 1238,
1473, 1645, 1732, 3437; MS: m/z = 307 (M++1); calcd. for C14H14N2O4S (%): C, 54.89;
H, 4.61; N, 9.14; found (%): C, 54.95; H, 4.66; N, 9.09.
(S)-3-Hydroxy-2-[4-(4-methoxybenzylidene)-5-oxo-2-thio-imidazolidin-
1-yl]propanoic acid methyl ester (3j). Appearance: yellow solid; mp 220–222◦C;
[α]20 = +11.9 (c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 3.82 (s, 3H, OCH3),
D
3.89 (s, 3H, Ar OCH3), 4.33-4.26 (m, 2H, CH2), 5.53 (t, 1H, J = 5.0 Hz, CH), 6.78 (s,
1H, = C H), 7.03 (d, 2H, J = 8.8 Hz, Ar H), 7.42 (d, 2H, J = 8.8 Hz, Ar H), 8.90 (s,
1H, N H); 13C NMR (75 MHz, CDCl3): δ 52.74, 55.51, 58.12, 60.70, 115.22, 125.66,
129.67, 133.45, 135.79, 161.42, 163.27, 167.46, 177.07; IR (KBr) ν/cm−1: 1236, 1470,
1640, 1735, 3437; MS: m/z = 337 (M++1); calcd. for C15H16N2O5S (%): C, 53.56; H,
4.79; N, 8.33; found (%): C, 53.66; H, 4.73; N, 9.29.
(S)-3-(1H-Indol-3-yl)-2-[4-(4-methoxybenzylidene)-5-oxo-2-thio-imidazo
lidin-1-yl]propanoic acid methyl ester (3k). Appearance: yellow solid, mp 88–89◦C;
D
1
[α]20 = –215.9 (c = 1; (CH3)2CO); H NMR (300 MHz, CDCl3): δ 3.93-3.72 (m, 8H,
CH2 & COOCH3 & Ar OCH3), 5.71-5.66 (m, 1H, CH), 6.60 (s, 1H, = C H), 7.99-6.91
(m, 10H, Ar H & N H), 8.56 (s, 1H, N H); 13C NMR (75 MHz, CDCl3): δ 24.18, 52.79,
55.45, 55.76, 111.07, 115.01, 118.66, 119.51, 122.05, 122.99, 124.19, 125.19, 130.96,
136.08, 160.91, 163.21, 169.09, 177.18; IR (KBr) ν/cm−1: 1258, 1463, 1604, 1730, 3414;
MS: m/z = 436 (M++1); calcd. for C23H21N3O4S (%): C, 63.43; H, 4.86; N, 9.65; found
(%): C, 63.30; H, 4.90; N, 9.61.
(S)-2-[4-(4-Methoxybenzylidene)-5-oxo-2-thio-imidazolidin-1-yl]succinic
acid dimethyl ester (3l). Appearance: yellow solid; mp 48–50◦C; [α]20 = –79.6
D
(c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 3.47-3.12 (m, 2H, CH2), 3.75 (s, 3H,
OCH3), 3.84 (s, 3H, OCH3), 3.86 (s, 3H, Ar OCH3), 5.83-5.78 (m, 1H, CH), 6.72 (s, 1H, =
C H), 6.91 (d, 2H, J = 8.1 Hz, Ar H), 7.41 (d, 2H, J = 8.1 Hz, Ar H), 9.06 (s, 1H,
N H); 13C NMR (75 MHz, CDCl3): δ 33.49, 51.14, 52.15, 53.10, 55.48, 114.03, 115.06,
124.03, 125.07, 131.27, 161.12, 163.17, 168.25, 170.44, 176.61; IR (KBr) ν/cm−1: 1256,
1468, 1602, 1645, 1740, 3417; MS: m/z = 379 (M++1); calcd. for C17H18N2O6S (%): C,
53.96; H, 4.79; N, 7.40; found (%): C, 53.85; H, 4.75; N, 7.45.
(S)-2-[4-(4-Methoxybenzylidene)-5-oxo-2-thio-imidazolidin-1-yl]pentan
edioic acid dimethyl ester (3m). Appearance: yellow solid; mp 70–72◦C; [α]20
D
1
= –16.8 (c = 1; (CH3)2CO); H NMR (300 MHz, CDCl3): δ 2.70-2.17 (m, 4H, 2CH2),
3.67 (s, 3H, OCH3), 3.75 (s, 3H, OCH3), 3.87 (s, 3H, Ar OCH3), 5.41-5.36 (m, 1H,

NEW CHIRAL IMIDAZOLINONE DERIVATIVES
125
CH), 6.71 (s, 1H, = C H), 6.98 (d, 2H, J = 8.4 Hz, Ar H), 7.42 (d, 2H, J = 8.4 Hz,
Ar H), 8.98 (s, 1H, N H); 13C NMR (75 MHz, CDCl3): δ 23.85, 30.55, 51.84, 52.85,
54.33, 55.51, 114.91, 115.02, 124.06, 125.11, 131.35, 161.10, 163.34, 168.80, 172.84,
177.32; IR (KBr) ν/cm−1: 1257, 1440, 1510, 1580, 1740, 3410; MS: m/z = 393 (M++1);
calcd. for C18H20N2O6S (%): C, 55.09; H, 5.14; N, 7.14; found (%): C, 54.92; H, 5.10;
N, 7.19.
General Preparation of 2-Methylthio-4H-imidazolin-4-ones 4
A mixture of 2-thio-4-imidazolinones 3 (0.77 mol) in dry acetonitrile (20 mL), CH3I
(1.54 mmol), and solid K2CO3 (1.3 mmol) was stirred for 3 h at room temperature and
then filtered. The filtrate was concentrated under reduced pressure, and the residue was
separated by column chromatography (petroleum ether/ethyl acetate, 15:1, v/v) to afford
2-methylthio-4H-imidazolin-4-ones 4.
(S)-2-(4-Benzylidene-2-methylthio-5-oxo-4,5-dihydro-imidazol-1-yl)prop
anoic acid methyl ester (4a). Appearance: yellow solid; mp 70–71◦C; [α]20 = –10.6
D
(c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 1.69 (d, 3H, J = 7.4 Hz, CH3), 2.77
(s, 3H, SCH3), 3.76 (s, 3H, OCH3), 4.82 (q, 1H, J = 7.4 Hz, CH), 6.97 (s, 1H, = C H),
7.44-7.36 (m, 3H, Ar H), 8.15 (d, 2H, J = 8.0 Hz, Ar H); 13C NMR (75 MHz, CDCl3):
δ 13.50, 15.51, 49.96, 52.80, 124.29, 128.63, 129.87, 131.97, 134.39, 137.88, 163.88,
169.27, 169.68; IR (KBr) ν/cm−1: 1269, 1400, 1440, 1640, 1730; MS: m/z = 305 (M++1);
calcd. for C15H16N2O3S (%): C, 59.19; H, 5.30; N, 9.20; found (%): C, 59.12; H, 5.27; N,
9.27.
(R)-2-(4-Benzylidene-2-methylthio-5-oxo-4,5-dihydro-imidazol-1-yl)prop
anoic acid methyl ester (4b). Appearance: yellow solid; mp 72–74◦C; [α]20
=
D
+11.8 (c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 1.69 (d, 3H, J = 7.3 Hz, CH3),
2.77 (s, 3H, SCH3), 3.76 (s, 3H, OCH3), 4.81 (q, 1H, J = 7.3 Hz, CH), 6.97 (s, 1H, =
C H), 7.45-7.36 (m, 3H, Ar H), 8.15 (d, 2H, J = 8.0 Hz, Ar H); 13C NMR (75 MHz,
CDCl3): δ 13.56, 15.53, 49.51, 52.79, 124.31, 128.65, 129.89, 132.01, 134.40, 137.89,
163.91, 169.26, 169.66; IR (KBr) ν/cm−1: 1265, 1404, 1438, 1645, 1729; MS: m/z = 305
(M++1); calcd. for C15H16N2O3S (%): C, 59.19; H, 5.30; N, 9.20; found (%): C, 59.14;
H, 5.31; N, 9.24.
(S)-2-[4-(4-Chlorobenzylidene)-2-methylthio-5-oxo-4,5-dihydro-imidazol
-1-yl]propanoic acid methyl ester (4c). Appearance: yellow solid; p 104–106◦C;
D
1
[α]20 = –32.0 (c = 1; (CH3)2CO); H NMR (300 MHz, CDCl3): δ 1.68 (d, 3H, J =
7.3Hz, CH3), 2.78 (s, 3H, SCH3), 3.80 (s, 3H, Ar OCH3), 4.81 (q, 1H, J = 7.3 Hz, CH),
6.89 (s, 1H, = C H), 7.41 (d, 2H, J = 8.5 Hz, Ar H), 8.09 (d, 2H, J = 8.5 Hz, Ar H);
13C NMR (75 MHz, CDCl3): δ 13.52, 15.52, 51.02, 52.89, 122.43, 128.80, 133.02, 135.50,
138.14, 164.69, 169.45, 169.92; IR (KBr) ν/cm−1: 1243, 1491, 1637, 1722; MS: m/z =
339 (M++1); calcd. for C15H15ClN2O3S (%): C, 53.17; H, 4.46; N, 8.27; found (%): C,
53.13; H, 4.41; N, 8.20.
(R)-2-[4-(4-Chlorobenzylidene)-2-methylthio-5-oxo-4,5-dihydro-imidazol
-1-yl]propanoic acid methyl ester (4d). Appearance: yellow solid; mp 105–107◦C;
D
1
[α]20 = +31.1 (c = 1; (CH3)2CO); H NMR (300 MHz, CDCl3): δ 1.67 (d, 3H, J =
7.4 Hz, CH3), 2.78 (s, 3H, SCH3), 3.77 (s, 3H, Ar OCH3), 4.80 (q, 1H, J = 7.3 Hz,
CH), 6.90 (s, 1H, = C H), 7.39 (d, 2H, J = 8.5 Hz, Ar H), 8.10 (d, 2H, J = 8.4 Hz,
Ar H); 13C NMR (75 MHz, CDCl3): δ 13.57, 15.52, 49.97, 52.88, 122.75, 128.91, 133.02,
135.75, 138.13, 164.35, 169.15, 169.67; IR (KBr) ν/cm−1: 1241, 1500, 1639, 1725; MS:

126
X. HUANG ET AL.
m/z = 339 (M++1); calcd. for C15H15ClN2O3S (%): C, 53.17; H, 4.46; N, 8.27; found
(%): C, 53.21; H, 4.43; N, 8.32.
(S)-2-[4-(4-Methylbenzylidene)-2-methylthio-5-oxo-4,5-dihydro-imidazol
D
-1-yl]propanoic acid methyl ester (4e). Appearance: yellow oil; [α]20 = –39.9
(c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 1.68 (d, 3H, J = 7.2 Hz, CH3), 2.40
(s, 3H, CH3), 2.76 (s, 3H, SCH3), 3.76 (s, 3H, OCH3), 4.82 (q, 1H, J = 7.2 Hz, CH), 6.96
(s, 1H, = C H), 7.25 (d, 2H, J = 7.8 Hz, Ar H), 8.06 (d, 2H, J = 7.8 Hz, Ar H); 13
C
NMR (75 MHz, CDCl3): δ 13.46, 15.35, 21.58, 49.67, 52.78, 124.76, 129.54, 130.66,
131.76, 132.05, 140.57, 161.22, 169.19, 169.89; IR (LF) ν/cm−1: 1254, 1497, 1595, 1710;
MS: m/z = 319 (M++1); calcd. for C16H18N2O3S (%): C, 60.36; H, 5.70; N, 8.80; found
(%): C, 60.48; H, 5.74; N, 8.76.
(R)-2-[4-(4-Methylbenzylidene)-2-methylthio-5-oxo-4,5-dihydro-imidazol
D
-1-yl]propanoic acid methyl ester (4f). Appearance: yellow oil; [α]20 = +41.1
(c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 1.65 (d, 3H, J = 7.2 Hz, CH3), 2.40
(s, 3H, CH3), 2.71 (s, 3H, SCH3), 3.73 (s, 3H, OCH3), 4.84 (q, 1H, J = 7.3 Hz, CH), 6.84
(s, 1H, = C H), 7.27 (d, 2H, J = 7.8 Hz, Ar H), 8.06 (d, 2H, J = 7.8 Hz, Ar H); 13
C
NMR (75 MHz, CDCl3): δ 13.51, 15.45, 21.73, 49.89, 52.82, 124.96, 129.61, 130.82,
131.81, 132.14, 140.59, 161.02, 169.29, 169.98; IR (LF) ν/cm−1: 1253, 1490, 1589, 1715;
MS: m/z = 319 (M++1); calcd. for C16H18N2O3S (%): C, 60.36; H, 5.70; N, 8.80; found
(%): C, 60.45; H, 5.76; N, 8.75.
(S)-2-[4-(4-Methoxybenzylidene)-2-methylthio-5-oxo-4,5-dihydro-imidaz
ol-1-yl]propanoic acid methyl ester (4g). Appearance: yellow solid; mp 95–97◦C;
[α]20 = –27.9 (c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 1.64 (d, 3H, J = 7.4
D
Hz, CH3), 2.70 (s, 3H, SCH3), 3.71 (s, 3H, OCH3), 3.80 (s, 3H, Ar OCH3), 4.77 (q, 1H,
J = 7.4 Hz, CH), 6.92-6.89 (m, 3H, Ar H & = C H), 8.10 (d, 2H, J = 8.8 Hz, Ar H);
13C NMR (75 MHz, CDCl3): δ 13.46, 15.52, 49.80, 52.78, 55.29, 114.23,, 124.62, 127.27,
133.83, 136.13, 161.13, 162.10, 169.32, 169.87; IR (KBr) ν/cm−1: 1253, 1500, 1597,
1711; MS: m/z = 335 (M++1); calcd. for C16H18N2O4S (%): C, 57.47; H, 5.43; N, 8.38;
found (%): C, 57.37; H, 5.48; N, 8.35.
(R)-2-[4-(4-Methoxybenzylidene)-2-methylthio-5-oxo-4,5-dihydro-imidaz
ol-1-yl]propanoic acid methyl ester (4h). Appearance: yellow solid; mp 97–99◦C;
[α]20 = +28.8 (c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 1.64 (d, 3H, J = 7.3
D
Hz, CH3), 2.72 (s, 3H, SCH3), 3.75 (s, 3H, OCH3), 3.82 (s, 3H, Ar OCH3), 4.78 (q, 1H,
J = 7.3 Hz, CH), 6.93-6.90 (m, 3H, Ar H & = C H), 8.11 (d, 2H, J = 8.8 Hz, Ar H);
13C NMR (75 MHz, CDCl3): δ 13.45, 15.50, 49.73, 52.77, 55.27, 113.86, 114.19, 124.62,
127.21, 133.79, 136.07, 161.06, 162.10, 169.31, 169.83; IR (KBr) ν/cm−1: 1252, 1501,
1598, 1710; MS: m/z = 335 (M++1); calcd. for C16H18N2O4S (%): C, 57.47; H, 5.43; N,
8.38; found (%): C, 57.40; H, 5.40; N, 8.42.
(S)-2-(4-Benzylidene-2-methylthio-5-oxo-4,5-dihydro-imidazol-1-yl)-3-
D
hydroxypropanoic acid methyl ester (4i). Appearance: yellow oil; [α]20 = –8.0
1
(c = 1; (CH3)2CO); H NMR (300 MHz, CDCl3): δ 2.72 (s, 3H, SCH3), 3.81 (s, 3H,
OCH3), 4.24-4.22 (m, 2H, CH2), 4.64 (t, 1H, J = 5.0 Hz, CH), 6.98 (s, 1H, = C H),
7.44-7.35 (m, 3H, Ar H), 8.15 (d, 2H, J = 8.0 Hz, Ar H); 13C NMR (75 MHz, CDCl3):
13.59, 52.98, 58.11, 60.71, 125.49, 128.67, 130.18, 132.16, 134.17, 137.70, 164.03,
167.93, 170.47; IR (LF) ν/cm−1: 1258, 1497, 1633, 1738; MS: m/z = 321 (M++1);
calcd. for C15H16N2O4S (%): C, 56.24; H, 5.03; N, 8.74; found (%): C, 56.30; H, 5.05;
N, 8.70.

NEW CHIRAL IMIDAZOLINONE DERIVATIVES
127
(S)-3-Hydroxy-2-[4-(4-methoxybenzylidene)-2-methylthio-5-oxo-4,5-dih
ydro-imidazol-1-yl]propanoic acid methyl ester (4j). Appearance: yellow oil;
D
1
[α]20 = –4.0 (c = 1; (CH3)2CO); H NMR (300 MHz, CDCl3): δ 2.66 (s, 3H, SCH3),
3.74 (s, 3H, OCH3), 3.81 (s, 3H, Ar OCH3), 4.22-4.15 (m, 2H, CH2), 4.63 (t, 1H, J =
5.2 Hz, CH), 6.92-6.89 (m, 3H, Ar H & = C H), 8.08 (d, 2H, J = 8.7 Hz, Ar H); 13
C
NMR (75 MHz, CDCl3): δ 13.54, 52.89, 55.35, 58.11, 60.71, 114.28, 125.68, 127.12,
134.08, 135.99, 161.37, 162.36, 167.99, 170.48; IR (LF) ν/cm−1: 1258, 1490, 1637, 1736;
MS: m/z = 351 (M++1); calcd. for C16H18N2O5S (%): C, 54.85; H, 5.18; N, 7.99; found
(%): C, 54.92; H, 5.15; N, 7.92.
(S)-3-(1H-Indol-3-yl)-2-[4-(4-methoxybenzylidene)-2-methylthio-5-oxo-
4,5-dihydro-imidazol-1-yl]propanoic acid methyl ester (4k). Appearance: yellow
D
1
oil; [α]20 = –263.8 (c = 1; (CH3)2CO); H NMR (300 MHz, CDCl3): δ 2.58 (s, 3H,
SCH3), 3.85-3.68 (m, 8H, CH2 & Ar OCH3 & COOCH3), 4.98-4.93 (m, 1H, CH),
8.10-6.89 (m, 11H, Ar H & = C H & N H); 13C NMR (75 MHz, CDCl3): δ 13.58,
25.02, 52.84, 55.33, 55.42, 111.17, 114.25, 118.38, 119.58, 122.11, 123.03, 124.51,
127.34, 133.81, 136.22, 161.11, 162.09, 168.70, 169.33; IR (LF) ν/cm−1: 1255, 1439,
1499, 1597, 1704, 1742; MS: m/z = 450 (M++1); calcd. for C24H23N3O4S (%): C, 64.13;
H, 5.16; N, 9.35; found (%): C, 64.25; H, 5.14; N, 9.39.
(S)-2-[4-(4-Methoxybenzylidene)-2-methylthio-5-oxo-4,5-dihydro-imida
zol-1-yl]succinic acid dimethyl ester (4l). Appearance: yellow solid; mp 137–138◦C;
[α]20 = –103.9 (c = 1; (CH3)2CO); 1H NMR (300 MHz, CDCl3): δ 2.77 (s, 3H, SCH3),
D
3.42-3.35 (m, CH2, 2H), 3.71 (s, 3H, COOCH3), 3.78 (s, 3H, OCH3), 3.87 (s, 3H,
Ar OCH3), 5.14-5.09 (m, 1H, CH), 6.96-6.93 (m, 3H, Ar H & = C H), 8.12 (d, 2H, J
= 8.8 Hz, Ar H); 13C NMR (75 MHz, CDCl3): δ 13.64, 34.17, 51.40, 52.24, 53.26, 55.42,
114.36, 125.07, 127.28, 133.98, 135.85, 161.31, 162.25, 168.92, 169.54, 171.51; IR (KBr)
ν/cm−1: 1244, 1434, 1502, 1596, 1735; MS: m/z = 393 (M++1); calcd. for C18H20N2O6S
(%): C, 55.09; H, 5.14; N, 7.14; found (%): C, 55.13; H, 5.10; N, 7.11.
(S)-2-[4-(4-Methoxybenzylidene)-2-methylthio-5-oxo-4,5-dihydro-imida
D
zol-1-yl]pentanedioic acid dimethyl ester (4m). Appearance: yellow oil; [α]20
1
= –71.6 (c = 1; (CH3)2CO); H NMR (300 MHz, CDCl3): δ 2.42-2.38 (m, 4H, 2CH2)
2.75 (s, 3H, SCH3), 3.67 (s, 3H, OCH3), 3.76 (s, 3H, OCH3), 3.86 (s, 3H, Ar OCH3),
4.80-4.75 (m, 1H, CH), 6.96-6.93 (m, 3H, Ar H & = C H), 8.13 (d, 2H, J = 8.7 Hz,
Ar H); 13C NMR (75 MHz, CDCl3): δ 13.57, 24.41, 30.19, 51.76, 52.84, 53.67, 55.34,
114.29, 125.01, 127.25, 133.90, 135.93, 161.25, 162.31, 169.01, 169.63, 172.63; IR (LF)
ν/cm−1: 1257, 1440, 1501, 1599, 1739; MS: m/z = 407 (M++1); calcd. for C19H22N2O6S
(%): C, 56.15; H, 5.46; N, 6.89; found (%): C, 56.10; H, 5.43; N, 6.84.
REFERENCES
1. (a) N. B. Mehta, C. A. R. Diuguid, and F. E. Soroko, J. Med. Chem., 24, 465 (1981); (b) C.
H. Kwon, M. T. Iqbal, and J. N. D. Wurpel, J. Med. Chem., 34, 1845 (1991); (c) H. Joshi, P.
Upadhyay, D. Karia, and A. J. Baxi, Eur. J. Med. Chem., 38, 837 (2003).
2. A. A. El-Barbary, A. I. Khodair, E. B. Pedersen, and C. Nielsen, J. Med. Chem., 37, 73 (1994).
3. A. I. Khodair and P. Bertrand, Tetrahedron, 54, 4859 (1998).
4. H. Sato, M. Tsuda, K. Watanabe, and J. Kobayashi, Tetrahedron, 54, 8687 (1998).
5. B. M. Nilsson, H. M. Vargas, and U. Hacksell, J. Med. Chem., 35, 3270 (1992).
6. D. L. Shaner, P. C. Anderson, and M. A. Stidham, Plant Physiol., 76, 545 (1984).

128
X. HUANG ET AL.
7. G. Lacroix, R. Peignier, R. Pepin, J. P. Bascou, J. Perez, and C. Schmitz, US 6002016 (1999);
Chem. Abstr., 132, 35698e (2000).
8. T. E. Chin, R. B. Wong, J. L. Pont, and A. E. Karu, J. Agric. Food. Chem., 50, 3380 (2002).
9. A. Williams, Pestic. Sci., 46, 3 (1996).
10. (a) P. M. Fresneda and P. Molina, Synlett, 1 (2004); (b) P. Molina and M. J. Vilaplana, Synthesis,
1197 (1994); (c) M. W. Ding, B. Q. Fu, and L. Cheng, Synthesis, 1067 (2004); (d) M. W. Ding,
S. J. Yang, and J. Zhu, Synthesis, 75 (2004); (e) M. W. Ding, S. Z. Xu, and J. F. Zhao, J. Org.
Chem., 69, 8366 (2004).
11. (a) M. W. Ding, Y. Sun, and Z. J. Liu, Synth. Commun., 33, 1267 (2003); (b) F. L. Yang, Z. J.
Liu, X. B. Huang, and M. W. Ding, J. Heterocycl. Chem., 41, 77 (2004); (c) X. B. Huang, Z. J.
Liu, F. L. Yang, and M. W. Ding, Phosphorus, Sulfur, and Silicon, 182, 939 (2007).
12. P. Molina, A. Pastor, and M. J. Vilaplana, Tetrahedron, 49, 7769 (1993).
13. (a) W. Marckwald, M. Neumark, and R. Stelzner, Berichte, 24, 3278 (1891); (b) R. Jaksˇe, S.
Recˇnik, J. Svete, A. Golobicˇ, L. Golicˇ, and B. Stanovnik, Tetrahedron, 57, 8395 (2001); (c) J.
R. Che´rouvrier, F. Carreaux, and J. P. Bazureau, Tetrahedron Lett., 43, 3581 (2002); (d) J. R.
Che´rouvrier, F. Carreaux, and J. P. Bazureau, Tetrahedron Lett., 43, 8745 (2002).
14. G. M. Sheldrick, SHELXS-97, University of Go¨ttingen, Germany (1997).
15. G. M. Sheldrick, SHELXL-97, University of Go¨ttingen, Germany (1997).
16. Crystallographic data for the structure 3c and 3d in this article have been deposited with the
Cambridge Crystallographic Data Center as supplementary publication number CCDC 704007
and 704008, respectively. Copies of the data can be obtained free of change on application to
CCDC, 12 Union Road, Cambridge CB21EZ, U. K.; e-mail: deposit@ccdc.cam.ac.uk.
17. HPLC-separation conditions of 3c: Chiralcel OD H, 22◦C, 254 nm, 80:20 hexane:i-PrOH,
0.8 mL/min; tR = 18.6 min (S); HPLC-separation conditions of 3d: Chiralcel OD H, 22◦C, 254
nm, 80:20 hexane:i-PrOH, 0.8 mL/min; tR = 13.3 min (R).
18. HPLC-separation conditions of 4c: Chiralcel OD H, 22◦C, 254 nm, 80:20 hexane:i-PrOH,
0.8 mL/min; tR = 9.7 min (R), tR = 11.3 min (S); HPLC-separation conditions of 4d: Chiralcel
OD H, 22◦C, 254 nm, 80:20 hexane:i-PrOH, 0.8 mL/min; tR = 9.6 min (R), tR = 10.9 min (S).