Synthesis and fungicidal activities of 2-benzothiazolylthio-substituted 4H-imidazol-4-ones and 4(3H)-quinazolinones

Article abstract of DOI:10.1080/10426500490466913

4H-Imidazol-4-ones 4 or 4(3H)-quinazolinones 8 were synthesized by base catalytic reactions of 2-mercaptobenzothiazole with carbodiimides 2 or 6, respectively, which were obtained via aza-Wittig reaction of iminophosphorane 1 or 5 with aromatic isocyanates. 4 and 8 exhibited fungicidal activity.

Full text of DOI:10.1080/10426500490466913

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Phosphorus, Sulfur, and Silicon and the Related
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SYNTHESIS AND FUNGICIDAL ACTIVITIES OF 2-
BENZOTHIAZOLYLTHIO-SUBSTITUTED 4H-IMIDAZOL-4-
ONES AND 4(3H)-QUINAZOLINONES
Yang-Gen Hu a , Shang-Jun Yang a & Ming-Wu Ding a
a Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, Central China
Normal University , Wuhan, P.R. China
Published online: 16 Aug 2010.
To cite this article: Yang-Gen Hu , Shang-Jun Yang & Ming-Wu Ding (2004) SYNTHESIS AND FUNGICIDAL ACTIVITIES OF 2-
BENZOTHIAZOLYLTHIO-SUBSTITUTED 4H-IMIDAZOL-4-ONES AND 4(3H)-QUINAZOLINONES, Phosphorus, Sulfur, and Silicon and the
Related Elements, 179:10, 1933-1939, DOI: 10.1080/10426500490466913
To link to this article: http://dx.doi.org/10.1080/10426500490466913
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Phosphorus, Sulfur, and Silicon, 179:1933–1939, 2004
ꢀC
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490466913
SYNTHESIS AND FUNGICIDAL ACTIVITIES OF
2-BENZOTHIAZOLYLTHIO-SUBSTITUTED
4H-IMIDAZOL-4-ONES AND 4(3H)-QUINAZOLINONES
Yang-Gen Hu, Shang-Jun Yang, and Ming-Wu Ding
Key Laboratory of Pesticide and Chemical Biology,
Ministry of Education, Central China Normal University,
Wuhan, P.R. China
(Received December 12, 2004; accepted January 26, 2004)
4H-Imidazol-4-ones 4 or 4(3H)-quinazolinones 8 were synthesized by
base catalytic reactions of 2-mercaptobenzothiazole with carbodiimides
2 or 6, respectively, which were obtained via aza-Wittig reaction of
iminophosphorane 1 or 5 with aromatic isocyanates. 4 and 8 exhib-
ited fungicidal activity.
Keywords: 4H-Imidazol-4-ones; aza-Wittig reaction; fungicidal activi-
ties; quinazolinones; synthesis
INTRODUCTION
4H-Imidazol-4-ones and 4(3H)-quinazolinones are important heterocy-
cles having good biological and pharmaceutical activities. Some deriva-
tives of 2-alkylthioimidazolones and 2-alkylthioquinazolinones were
found to show good fungicidal or antitumor activities.1–7 Recently, we
became interested in synthesis of imidazolones and quinazolinones,
some of them having shown potential fungicidal activities.8–12 Here we
wish to report further the synthesis and fungicidal activity of some new
derivatives of 2-benzothiazolylthio-substituted 4H-imidazol-4-ones and
4(3H)-quinazolinones, which were not easily accessible by routine syn-
thetic method.
We gratefully acknowledge financial support of this work by the National Natural
Science Foundation of China (Project No. 20102001) and the National Key Project for
Basic Research (2003CB114400, 2003CB114406).
Current address of Yang-Gen Hu is Yunyang Medical College, Shiyan Hubei 442000,
P. R. China.
Address correspondence to Ming-Wu Ding, Institute of Organic Synthesis, Central
China Normal University, Wuhan, 430079, P. R. China. E-mail: ding5229@yahoo.com.cn
1933

1934
Y.-G. Hu et al.
TABLE I Preparation of 4H-imidazol-4-ones 4 and
4(3H)-quinazolinones 8
Reaction
time (h)
Compound
Ar1
Ar2
Ar
Yield (%)a
4a
4b
4c
4d
4e
4f
4g
4h
8a
8b
Ph
Ph
Ph
Ph
3
2
3
3
2
3
2
3
12
12
38
46
41
40
34
43
40
42
56
55
4-Cl-C6H4
4-CH3-C6H4
Ph
4-Cl-C6H4
4-CH3-C6H4
4-Cl-C6H4
4-CH3-C6H4
4-Cl-C6H4
4-Cl-C6H4
4-Cl-C6H4
2-Furfuryl
2-Furfuryl
Ph
4-Me-C6H4
aIsolated yields based on iminophosphosphorane used.
RESULTS AND DISCUSSION
The easily accessible vinyliminophosphorane 1 reacted with aromatic
isocyanates to give carbodiimides 2, which were allowed to react with
2-mercaptobenzothiazole in presence of catalytic solid potassium car-
bonate to give the imidazolones 4 at 50 ∼ 60◦C in moderate yields (see
Table I).
The structure of 4 has been characterized spectroscopically. For ex-
1
ample, the H NMR spectral data in 4c show the signals of CH3 at
2.29 ppm as single absorption. The chemical shift of alkenyl hydrogen is
overlapped with the signals of Ar-H (8.19–7.01). In the IR spectral data
of 4c, the strong stretching resonance peak of imidazolone C O appears
at 1723 cm−1. The stretching resonance of C C shows relatively strong
absorbtion at about 1643 cm−1 due to resonance effect. The stretching
resonance of C N shows strong absorbtion at about 1555 cm−1. The
mass spectrum of 4c shows molecule ion peak at m/z 427 with 29%
abundance.
The use of catalytic amount of solid K2CO3 gave moderate yields
of 4. The best reaction time was 2–3 h (Table I). Although the
reactivity of the carbodiimides 2 was different with respect to
substituent on the benzene ring, the reaction was carried out at
50–60◦C. The formation of 4 can be rationalized in terms of an ini-
tial nucleophilic addition of 2-mercaptobenzothiazole under potas-
sium carbonate to give the intermediates 3, which directly cyclize to
give 4.

4H-imidazol-4-ones and 4(3H)-quinazolinones
1935
The above method was also successively applied to synthesize 2-
(2-benzothiazolylthio)-4(3H)-quinazolinone 8. Iminophosphorane 5 re-
acted with aromatic isocyanates to give carbodiimides 6, which was
allowed to react with 2-mercaptobenzothiazole in the presence of solid
potassium carbonate to give 8. Moderate yields of 8 were obtained when
catalytic solid potassium carbonate was used with overnight, stirring
at 50∼60◦C (Table I). The structure of 8 has been characterized spec-
1
troscopically. For example, the H NMR spectrum data in 8a showed
the signals of 8-H in quinazolinone ring at 8.38 ppm as a double absorp-
tion and other Ar-H at 7.88–6.85 ppm as multiple absorptions. In the
IR spectral data of 8a, the strong stretching resonance peak of quina-
zolinone C O appears at 1689 cm−1. The MS spectrum of 8a shows
molecule ion peak at m/z 387 with 73% abundance. The formation of
8 can be rationalized in terms of an initial nucleophilic addition of 2-
mercaptobenzothiazole in the presence of solid potassium carbonate to
give the intermediate 7, which directly cyclized to give 8.

1936
Y.-G. Hu et al.
TABLE II The Fungicidal Activities of 4H-imidazol-4-ones 4 and
quinazolinones 8 (50 mg/l, relative inhibition %)
Fusarium Gibberella Cercospora Physalospora Pellicularia
Compound oxysporum
zeae
beticola sacc
piricola
sasakii
4a
4b
4c
4d
4e
4f
4g
4h
8a
8b
33
44
33
67
44
72
83
17
94
38
50
56
61
44
72
78
56
0
37
71
37
43
51
72
54
31
50
34
33
47
67
67
67
87
73
73
80
60
71
64
82
82
87
93
82
82
89
74
94
27
The biological activities of 4 and 8 were investigated, and the results
showed that they exhibited moderate-to-good fungicidal activities. For
example, 8a showed 94% inhibition of Fusarium oxysporum and Gib-
berella zeae in 50 mg/l (see Table II).
EXPERIMENTAL
Melting points were uncorrected. MS were measured on a Finnigan
Trace MS spectrometer. IR were recorded on a PE-983 infrared spec-
trometer as KBr pellets with absorption in cm−1. NMR were recorded
in CDCl3 on a Varian Mercury 400 or 200 spectrometer, and resonances
are given in ppm (δ) relative to TMS. Elementary analyses were taken
on a Perkin-Elmer CHN 2400 elementary analysis instrument.
Preparation of 4H-imidazol-4-ones 4
To a solution of vinyliminophosphorane 112 (5 mmol) in dry methy-
lene dichloride (15 ml) was added aromatic isocyanate (5 mmol) un-
der nitrogen at room temperature. After the reaction mixture was
standing for 3–6 h the solvent was removed 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 carbodi-
imide 2, which was used directly without further purification.
To a solution of 2 prepared above in CH3CN (30 ml) was added
2-mercaptobenzothiazole (0.84 g, 5 mmol) and catalytic solid K2CO3
(0.05 g). The reaction mixture was stirred for 2–3 h at 50–60◦C and then
filtered. The filtrate was condensed, and the residual was recrystallized

4H-imidazol-4-ones and 4(3H)-quinazolinones
1937
from methylene dichloride/petroleum ether to give 4H-imidazolin-4-
ones 4.
2-(2-benzothiazolylthio)-3-phenyl-5-phenylmethylene-
4H-imidazol-4-one (4a)
Yellow crystals, m.p. 174–176◦C, 1H NMR (CDCl3, 400 MHz) δ 8.20–
7.02 (m, 15H, Ar-H and CH); IR (cm−1), 1722, 1654, 1558, 1269; MS
(m/z, %), 413 (M+, 4), 247 (11), 191 (99), 117 (100). Elemental Anal.
Calcd. for C23H15N3OS2: C, 66.81; H, 3.66; N, 10.16. Found: C, 66.65;
H, 3.71; N, 10.14.
2-(2-benzothiazolylthio)-3-(4-chlorophenyl)-5-
phenylmethylene-4H-imidazol-4-one (4b)
Yellow crystals, m.p. 253–255◦C, 1H NMR (CDCl3, 400 MHz) δ 8.19–
7.07 (m, 14H, Ar-H and CH); IR (cm−1), 1727, 1643, 1548, 1296; MS
(m/z), 449 (23), 447 (M+, 65), 414 (38), 303 (60), 281 (80), 250 (77), 166
(92), 116 (100). Elemental Anal. Calcd. for C23H14ClN3OS2: C, 61.67;
H, 3.15; N, 9.38. Found: C, 61.71; H, 3.23; N, 9.27.
2-(2-benzothiazolylthio)-3-(4-methylphenyl)-5-
phenylmethylene-4H-imidazol-4-one (4c)
Yellow crystals, m.p. 233–235◦C, 1H NMR (CDCl3, 400 MHz) δ 8.19–
7.01 (m, 14H, Ar-H and CH), 2.29 (s, 3H, CH3); IR (cm−1), 1723, 1643,
1555, 1302; MS (m/z), 427 (M+, 29), 283 (25), 261 (90), 250 (72), 166
(41), 115 (100). Elemental Anal. Calcd. for C24H17N3OS2: C, 67.42; H,
4.01; N, 9.83. Found: C, 67.61; H, 3.95; N, 9.91.
2-(2-benzothiazolylthio)-3-phenyl-5-
(4-chlorophenylmethylene)-4H-imidazol-4-one (4d)
Yellow crystals, m.p. 224–225◦C, 1H NMR (CDCl3, 400 MHz) δ 8.15–
7.13 (m, 14H, Ar-H and CH); IR (cm−1), 1726, 1644, 1553, 1246; MS
(m/z), 449 (24), 447 (M+, 71), 414 (14), 312 (47), 281 (88), 269 (81), 165
(100), 149 (98). Elemental Anal. Calcd. for C23H14ClN3OS2: C, 61.67;
H, 3.15; N, 9.38. Found: C, 61.42; H, 3.06; N, 9.52.
2-(2-benzothiazolylthio)-3-(4-chlorophenyl)-5-
(4-chlorophenylmethylene)-4H-imidazol-4-one (4e)
Yellow crystals, m.p. 245–247◦C, 1H NMR (CDCl3, 400 MHz) δ 8.14–
7.06 (m, 13H, Ar-H and CH); IR (cm−1), 1730, 1643, 1554, 1236; MS
(m/z), 483 (29), 481 (M+, 42), 448 (14), 348 (13), 315 (51), 284 (58), 166
(100). Elemental Anal. Calcd. for C23H13Cl2N3OS2: C, 57.27; H, 2.72;
N, 8.71. Found: C, 57.04; H, 2.81; N, 8.78.

1938
Y.-G. Hu et al.
2-(2-benzothiazolylthio)-3-(4-methylphenyl)-5-
(4-chlorophenylmethylene)-4H-imidazol-4-one (4f)
Yellow crystals, m.p. 243–245◦C, 1H NMR (CDCl3, 400 MHz) δ 8.14–
7.00 (m, 13H, Ar-H and CH), 2.30 (s, 3H, CH3); IR (cm−1), 1732,
1645, 1556, 1240; MS (m/z), 463 (20), 461 (M+, 58), 428 (10), 312
(47), 295 (73), 284 (73), 165 (81), 149 (100). Elemental Anal. Calcd.
for C24H16ClN3OS2: C, 62.40; H, 3.49; N, 9.10. Found: C, 62.53; H, 3.41;
N, 9.27.
2-(2-benzothiazolylthio)-3-(4-chlorophenyl)-5-
(2-furfurylidene)-4H-imidazol-4-one (4g)
Yellow crystals, m.p. 150◦C decomposed, 1H NMR (CDCl3, 400 MHz)
δ 7.75–7.06 (m, 11H, Ar-H and CH), 6.63–6.61 (m, 1H, Furyl-4-H);
IR (cm−1), 1717, 1639, 1548, 1251; MS (m/z), 439 (18), 437 (M+, 52),
303 (52), 268 (38), 240 (61), 166 (100). Elemental Anal. Calcd. for
C21H12ClN3O2S2: C, 57.60; H, 2.76; N, 9.60. Found: C, 57.51; H, 2.94;
N, 9.44.
2-(2-benzothiazolylthio)-3-(4-methylphenyl)-5-
(2-furfurylidene)-4H-imidazol-4-one (4h)
Yellow crystals, m.p. 181◦C decomposed, 1H NMR (CDCl3, 400 MHz)
δ 7.73–7.00 (m, 11H, Ar-H and CH), 6.63–6.61 (m, 1H, Furyl-4-H),
2.29 (s, 3H, CH3); IR (cm−1), 1715, 1641, 1554, 1246; MS (m/z), 417
(M+, 53), 283 (50), 268 (38), 240 (32), 166 (100). Elemental Anal. Calcd.
for C22H15N3O2S2: C, 63.29; H, 3.62; N, 10.06. Found: C, 63.44; H, 3.72;
N, 9.93.
Preparation of 4(3H)-quinazolinones 8
To a solution of iminophosphorane 510 (2.12 g, 5 mmol) in dry methy-
lene dichloride (15 ml) was added aromatic isocyanate (5 mmol) un-
der nitrogen at room temperature. After the reaction mixture stood
for 12 h at 0–5◦C the solvent was removed under reduced pressure,
and ether/petroleum ether (1:2, 20 ml) was added to precipitate triph-
enylphosphine oxide. After filtering, the solvent was removed to give
carbodiimide 6, which was used directly without further purification.
To the solution of 6 prepared above in CH3CN (15 ml) was added
2-mercaptobenzothiazole (0.84 g, 5 mmol) and catalytic solid K2CO3
(0.05 g). The mixture was stirred for 12 h at 50–60◦C and filtered. The
filtrate was condensed and the residual was recrystallized from methy-
lene dichloride/petroleum ether to give quinazolinones 8.

4H-imidazol-4-ones and 4(3H)-quinazolinones
1939
2-(2-benzothiazolylthio)-3-phenyl-4(3H)-
quinazolinone (8a)
1
White crystals, m.p. 173–175◦C, H NMR (CDCl3, 200 MHz) δ 8.38
(d, J = 7.5 Hz, 1H, 8-H), 7.88–6.85 (m, 12H, Ar-H); IR (cm−1), 1689,
1587, 1452, 1250; MS (m/z, %), 387 (M+, 73), 310 (24), 253 (52), 221
(97), 146 (100). Elemental Anal. Calcd. for C21H13N3OS2: C, 65.10; H,
3.38; N, 10.84. Found: C, 65.26; H, 3.31; N, 10.92.
2-(2-benzothiazolylthio)-3-(4-methylphenyl)-4(3H)-
quinazolinone (8b)
1
White crystals, m.p. 182–184◦C, H NMR (CDCl3, 200 MHz) δ 8.38
(d, J = 7.5 Hz, 1H, 8-H), 7.85–6.87 (m, 11H, Ar-H), 2.15 (s, 3H, CH3);
IR (cm−1), 1680, 1589, 1452, 1255; MS (m/z, %), 401 (M+, 61), 368 (6),
252 (81), 166 (100), 118 (96). Elemental Anal. Calcd. for C22H15N3OS2:
C, 65.81; H, 3.77; N, 10.47. Found: C, 65.58; H, 3.65; N, 10.58.
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