Synthesis and fungicidal activities of 4H-imidazolin-4-ones containing sulfur substituent

Article abstract of DOI:10.1080/10426500211728

4H-Imidazolin-4-ones 3 and 4 were synthesized respectively by base catalytic reactions of 4-methylthiophenol or phenthiol with carbodiimides 2, which were obtained via aza-Wittig reaction of iminophosphorane 1 with aromatic isocyanates. 3 and 4 exhibited

Full text of DOI:10.1080/10426500211728

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Phosphorus, Sulfur, and Silicon and the Related
Elements
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Synthesis and Fungicidal Activities of 4H-Imidazolin-4-
ones Containing Sulfur Substituent
Ming-Wu Ding a , Gui-Ping Zeng a & Zhao-Jie Liu a
a Central China Normal University , Wuhan, China
Published online: 27 Oct 2010.
To cite this article: Ming-Wu Ding , Gui-Ping Zeng & Zhao-Jie Liu (2002) Synthesis and Fungicidal Activities of 4H-Imidazolin-4-
ones Containing Sulfur Substituent, Phosphorus, Sulfur, and Silicon and the Related Elements, 177:5, 1315-1321, DOI:
10.1080/10426500211728
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Phosphorus, Sulfur and Silicon, 2002, Vol. 177:1315–1321
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DOI: 10.1080/10426500290092596
SYNTHESIS AND FUNGICIDAL ACTIVITIES OF
4H-IMIDAZOLIN-4-ONES CONTAINING SULFUR
SUBSTITUENT
Ming-Wu Ding, Gui-Ping Zeng, and Zhao-Jie Liu
Institute of Organic Synthesis, Central China Normal
University, Wuhan, China
(Received October 22, 2001; accepted December 10, 2001)
4H-Imidazolin-4-ones 3 and 4 were synthesized respectively by base cat-
alytic reactions of 4-methylthiophenol or phenthiol with carbodiimides
2, which were obtained via aza-Wittig reaction of iminophosphorane 1
with aromatic isocyanates. 3 and 4 exhibited good fungicidal activity
against Pellicularia sasakii.
Keywords: Aza-Wittig reaction; fungicidal activities; 4H-Imidazolin-4-
ones; synthesis
INTRODUCTION
4H-Imidazolin-4-ones are important heterocycles having fungicidal ac-
tivities, especial some 2-alkylthioimidazolinones.1–3 Since a new mito-
chondrial respiratory inhibitor 1 (RPA407213) was found to show high
fungicidal activities, many other 2-methylthioimidazolinones were syn-
thesized to evaluated their fungicidal activities.4–7 Recently, we are
interested in the synthesis of biologically active imidazolinones via tan-
dem aza-Wittig reaction.8–10 Here we wish to report further the synthe-
sis and fungicidal activity of some new 4H-imidazolin-4-one derivatives
containing sulfur substituent.
We gratefully acknowledge financial support of this work by the Natural Science
Foundation of China (Project No. 20102001).
Address correspondence to Zhao-Jie Liu, Institute of Organic Synthesis, Central
China Normal University, Wuhan 430 079, P.R. China. E-mail: ding5229@yahoo.com
1315

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M.-W. Ding et al.
RESULTS AND DISCUSSION
The easily accessible vinyliminophosphorane 1 reacted with aromatic
isocyanates to give carbodiimides 2, which were allowed to react with
4-methylthiophenol in presence of catalytic solid potassium carbon-
ate to give the imidazolinones 3 at room temperature. Imidazolinones
4 was also obtained in good yields when phenthiol was used. Since
the direct reaction of carbodiimide 2 with 4-methylthiophenol or phen-
thiol will take place at high temperature which will result in complex
mixture,11 the presence of solid potassium carbonate is necessary for
the reaction to occur at room temperature. However, when butylthiol
was utilized in presence or absence of K2CO3(s) or NaOH(s), no 2-butyl-
thioimidazolinone 5 was obtained (see Table I.)
The structure of 3 and 4 has been characterized spectroscopically. For
1
example, the H NMR spectral data in 3b show the signals of SCH3
and CH3 at 2.48 ppm and 2.39 ppm as single absorption respectively.
The chemical shift of alkenyl hydrogen is 7.05 with single absorption.
In the IR spectral data of 3b, the strong stretching resonance peak of
imidazolinone C O appears at 1720 cm 1. The stretching resonance of
C C shows relatively strong absorbtion at about 1648 cm 1 due to reso-
nance effect. The stretching resonance of C N shows strong absorbtion

Imidazolinones
1317
TABLE I Preparation of 4H-Imidazolin-4-ones 3 and 4
Compound
Ar
Reaction time (hr)
Yield (%)a
3a
3b
3c
3d
4a
4b
4c
4d
5a
Ph
7
8
6
77
82
87
89
78
76
75
74
0
4-Me Ph
4-Cl Ph
3-Cl Ph
Ph
4-Me Ph
4-Cl Ph
3-Cl Ph
Ph
6
12
12
10
10
6
aIsolated yields based on iminophosphosphorane used.
1
at about 1560 cm 1. The strong absorbtion at about 1290 cm is prob-
ably due to the stretching resonance of C O C. The MS spectrum of
3b shows strong molecule ion peak at m/z 400 with 100% abundance.
Rearrangement occurs in the MS condition and the split of 3b can be
described as follows.
The use of catalytic amount of solid K2CO3 gave good yields of 3 or
4. The best reaction time was approximately 6–12 h (Table I). Although
the reactivity of the carbodiimides 2 was different with respect to sub-
stituent on the benzene ring, the reaction was carried out smoothly at
room temperature. The formation of 3 or 4 can be rationalized in terms
of an initial nucleophilic addition of 4-methylthiophenol or phenthiol
under potassium carbonate to give the intermediates 6 which directly
cyclize to give 3 or 4. When methylene dichloride was used as solvent

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M.-W. Ding et al.
in some cases, the intermediates 6 were isolated and characterized by
1H NMR and MS.
The biological activity of 3 and 4 was investigated and the results
showed that they exhibited fungicidal activities, especially against
Pellicularia sasakii. For example, 3c showed 95% inhibition of Pellicu-
laria sasakii in 50 mg/L (see Table II).
EXPERIMENTAL
Melting points were uncorrected. MS were measured on a HP5988A
spectrometer. IR were recorded on a Shimadzu IR-408 infrared spec-
trometer. NMR were taken on a Varian XL-200 spectrometer. Elemen-
tary analysis were taken on a CHN 2400 elementary analysis instru-
ment.
Preparation of Vinyliminophosphorane 1
Vinyliminophosphorane 1 was prepared by the Staudinger reaction of
vinyl azide and triphenyl phosphine according to the literature report.12
m.p. 148–150 C (Lit.12 m.p. 149 C).
Preparation of 4H-Imidazolin-4-ones 3
To a solution of vinyliminophosphorane 1 (2.25 g, 5 mmol) in dry methy-
lene dichloride (15 mL) was added aromatic isocyanate (5 mmol) under
nitrogen at room temperature. After the reaction mixture was stand
TABLE II The Fungicidal Activities of 4H-Imidazolin-4-ones 3
and 4 (50 mg/L, relative inhibition %)
Compound
3a 3b 3c 3d
4a
4b
4c
4d
Pellicularia sasaki
Rhizoctonia solani
Botryosphaeria berengeriana
92
26
26
74
26
0
87
7
0
86
0
26
87
0
33
4
0
26
95
0
0
91
0
0

Imidazolinones
1319
for 3–6 h, the solvent was removed off under reduced pressure and
ether/petroleum ether (1:2, 20 mL) was added to precipitate triph-
enylphosphine oxide. Filtered, the solvent was removed to give car-
bodiimide 2, which was used directly without further purification.
To a solution of 2 prepared above in CH3CN (30 mL) was added
4-methylthiophenol (0.70 g, 5 mmol) and catalytic solid K2CO3 (0.05 g).
The reaction mixture was stirred for 6–8 h and filtered; the filtrate was
condensed and the residual was recrystallized from methylene dichlo-
ride/petroleum ether to give 4H-imidazolin-4-ones 3.
2-(4-Methylthiophenoxy)-3-pheny-5-phenylmethylene-4H-
imidazolin-4-one (3a)
1
Light yellow crystals, m.p. 138–140 C, H NMR (CDCl3, 200 MHz)
7.96–7.20 (m, 14H, Ar H), 7.06 (s, 1H, CH), 2.48 (s, 3H, SCH3); IR
(cm 1), 1721, 1650, 1562, 1280; MS (m/z), 386 (M+, 100%), 239 (51%),
224 (9%), 116 (44%). Elemental Anal. Calcd. for C23H18N2O2S: C, 71.48;
H, 4.69; N, 7.25. Found: C, 71.34; H, 4.84; N, 7.37.
2-(4-Methylthiophenoxy)-3-(4-methylpheny)-5-
phenylmethylene-4H-imidazolin-4-one (3b)
Light yellow crystals, m.p. 146–148 C, 1H NMR (CDCl3, 200 MHz)
7.98–7.18 (m, 13H, Ar H), 7.05 (s, 1H, CH), 2.48 (s, 3H, SCH3), 2.39 (s,
3H, CH3); IR (cm 1), 1720, 1650, 1560, 1290; MS (m/z), 400 (M+, 100%),
386 (7%), 239 (43%), 224 (7%), 116 (39%). Elemental Anal. Calcd. for
C24H20N2O2S: C, 71.98; H, 5.03; N, 6.99. Found: C, 71.73; H, 5.26; N,
6.74.
2-(4-Methylthiophenoxy)-3-(4-chloropheny)-5-
phenylmethylene-4H-imidazolin-4-one (3c)
1
Light yellow crystals, m.p. 154–156 C, H NMR (CDCl3, 200 MHz)
7.98–7.20 (m, 13H, Ar H), 7.06 (s, 1H, CH), 2.50 (s, 3H, SCH3); IR
(cm 1), 1728, 1650, 1568, 1292; MS (m/z), 420 (M+, 100%), 239 (48%),
224 (8%), 116 (44%). Elemental Anal. Calcd. for C23H17CLN2O2S: C,
65.63; H, 4.07; N, 6.66. Found: C, 65.37; H, 3.93; N, 6.83.
2-(4-Methylthiophenoxy)-3-(3-chloropheny)-5-
phenylmethylene-4H-imidazolin-4-one (3d)
Light yellow crystals, m.p. 88–90 C, 1H NMR (CDCl3, 200 MHz)
7.98–7.18 (m, 13H, Ar H), 7.07 (s, 1H, CH), 2.50 (s, 3H, SCH3); IR
(cm 1), 1726, 1650, 1565, 1290; MS (m/z), 420 (M+, 100%), 239 (57%),
224 (10%), 116 (52%). Elemental Anal. Calcd. for C23H17ClN2O2S: C,
65.63; H, 4.07; N, 6.66. Found: C, 65.51; H, 4.25; N, 6.47.

1320
M.-W. Ding et al.
Preparation of 4H-Imidazolin-4-ones 4
To a solution of 2 prepared above in CH3CN (30 mL) was added phen-
thiol (0.55 g, 5 mmol) and catalytic solid K2CO3 (0.05 g). The reac-
tion mixture was stirred for 10–12 h and filtered; the filtrate was
condensed and the residual was recrystallized from methylene dichlo-
ride/petroleum ether to give 4H-imidazolin-4-ones 4.
2-Phenylthio-3-pheny-5-phenylmethylene-4H-
imidazolin-4-one (4a)
Yellow crystals, m.p. 152–154 C, 1H NMR (CDCl3, 200 MHz) 7.94–
7.20 (m, 15H, Ar H), 6.96 (s, 1H, CH); IR (cm 1), 1712, 1628, 1490,
1210; MS (m/z), 356 (M+, 100%), 247 (32%), 212 (40%), 109 (63%). Ele-
mental Anal. Calcd. for C22H16N2OS: C, 74.13; H, 4.52; N, 7.86. Found:
C, 74.27; H, 4.36; N, 7.93.
2-Phenylthio-3-(4-methylpheny)-5-phenylmethylene-4H-
imidazolin-4-one (4b)
Yellow crystals, m.p. 108–110 C, 1H NMR (CDCl3, 200 MHz) 7.92–
7.18 (m, 14H, Ar H), 6.93 (s, 1H, CH), 2.40 (s, 3H, CH3); IR (cm 1),
1710, 1630, 1485, 1210; MS (m/z), 370 (M+, 100%), 261 (57%), 226 (34%),
116 (40%). Elemental Anal. Calcd. for C23H18N2OS: C, 74.57; H, 4.90;
N, 7.56. Found: C, 74.43; H, 4.81; N, 7.59.
2-Phenylthio-3-(4-chloropheny)-5-phenylmethylene-4H-
imidazolin-4-one (4c)
Yellow crystals, m.p. 194–196 C, 1H NMR (CDCl3, 200 MHz) 7.92–
7.18 (m, 14H, Ar H), 6.94 (s, 1H, CH); IR (cm 1), 1720, 1630, 1490,
1205; MS (m/z), 390 (M+, 100%), 281 (38%), 246 (30%), 109 (49%). El-
emental Anal. Calcd. for C22H15ClN2OS: C, 67.60; H, 3.87; N, 7.17.
Found: C, 67.84; H, 3.81; N, 7.23.
2-Phenylthio-3-(3-chloropheny)-5-phenylmethylene-4H-
imidazolin-4-one (4d)
Yellow crystals, m.p. 154–156 C, 1H NMR (CDCl3, 200 MHz) 7.94–
7.18 (m, 14H, Ar H), 6.94 (s, 1H, CH); IR (cm 1), 1720, 1628, 1492,
1208; MS (m/z), 390 (M+, 100%), 281 (21%), 246 (31%), 109 (55%). El-
emental Anal. Calcd. for C22H15ClN2OS: C, 67.60; H, 3.87; N, 7.17.
Found: C, 67.33; H, 3.93; N, 7.05.

Imidazolinones
1321
REFERENCES
[1] B. L. Pilkington, S. E. Russell, A. J. Whittle, W. R. Mound, M. D. Turnbull, A. M.
Kozakiewicz, and W. G. Whittingham, Brit. UK Pat. Appl. (GB) 2329180 (1999).
[2] G. Emeric, J. Hutt, and J. Perez, PCT Int. Appl. (WO) 9602538 (1996).
[3] J. P. Bascou, A. Gadras, J. Perez, G. Emeric, G. Lacroix, and C. Veyrat, Eur. Pat.
Appl. (EP) 668270 (1995).
[4] B. L. Pilkington, S. E. Russell, A. J. Whittle, W. R. Mound, M. D. Turnbull, A. M.
Kozakiewicz, D. J. Hughes, and W. G. Whittingham, Brit. UK Pat. Appl. (GB)
2327676 (1999).
[5] J. A. Bruhn, M. C. Crompton, and S. R. Foor, PCT Int. Appl. (WO) 9833382 (1998).
[6] J. P. Bascou, G. Lacroix, A. Gadras, and J. Perez, Eur. Pat. Appl. (EP) 629616 (1994).
[7] G. Lacroix, R. Peignier, and R. Pepin, Eur. Pat. Appl. (EP) 551048 (1993).
[8] M. W. Ding, Z. F. Xu, and T. J. Wu, Synth. Commun., 29, 1171 (1999).
[9] M. W. Ding, H. Y. Tu, and Z. J. Liu, Synth. Commun., 27, 3657 (1997).
[10] M. W. Ding, H. Y. Tu, Z. J. Liu, and N. B. Zhuang, Chem. J. Chinese Universities, 18,
572 (1998).
[11] M. Mikolajczyk and P. Pielbasinski, Tetrahedron, 37, 233 (1981).
[12] P. Molina, A. Pastor, and M. J. Vilaplana, Tetrahedron, 49, 7769 (1993).