Synthesis and Biological Activities of 2-Alkylthio-5-furylmethylidene 4H-imidazolin-4-ones

Article abstract of DOI:10.1002/jhet.5570410112

Novel 2-alkylthio-5-furylmethylidene-4H-imidazolin-4-ones 4 have been synthesized via tandem aza-Wittig reaction. The structures were determined by ir, nmr, mass spectroscopy, and elemental analysis. They were screened for fungicidal activities against Fu

Full text of DOI:10.1002/jhet.5570410112

Synthesis and Biological Activities of 2-Alkylthio-5-furylmethylidene-
Jan-Feb 2004
77
4H-imidazolin-4-ones
*
Feng-Ling Yang, Zhao-Jie Liu , Xiao-Bo Huang and Ming-Wu Ding
Institute of Organic Synthesis, Central China Normal University,
Wuhan, 430079, P.R. China
Received September 23, 2003
Novel 2-alkylthio-5-furylmethylidene-4H-imidazolin-4-ones 4 have been synthesized via tandem aza-
Wittig reaction. The structures were determined by ir, nmr, mass spectroscopy, and elemental analysis. They
were screened for fungicidal activities against Fusarium oxysporium, B o t ryosphaeria berengeriana and
Rhizoctonia solani, and growth inhibition of Barnyard grass and Cole root and stalk. A few of them possess
significant biological activities.
J. Heterocyclic Chem., 41, 77 (2004).
many other 2-methylthio-imidazolinone derivatives have
been synthesized to evaluate their fungicidal activities [6-
10]. Most of those reported are 5,5-dialkyl-substituted
2-methylthio-imidazolinones synthesized from the corre-
sponding amino acetic acid [7,9]. However, 2-alkylthio-5-
furylmethylidene-imidazolinones can not be synthesized
via the general method because of the unstable starting
material, vinyl amino acetic acid. As part of our current
studies on the synthesis of the biologically active imida-
Introduction.
4H-Imidazolin-4-ones derivatives are found to possess
significant biological activities such as fungicidal and her-
bicidal activities. They are highly important heterocycles,
and have been one of the most successfully used in
research and development of agrochemicals [1-5]. Since a
novel mitochondrial respiratory inhibitor, 5-methyl-2-
methylthio-5-phenyl-3-phenylamino-3,5-dihydro-imida-
zolin-4-one, was found to show high fungicidal activity,
Table 1
Synthesis of Compounds 2, 3a - k and 4a – t
'
R X
No.
R
Reaction Conditions [a]
Yield [b] ( % )
2
/
/
/
/
/
/
/
/
/
/
/
/
/
75 °C / 29 h
r.t. / 0.5 h
r.t. / 0.5 h
r.t. / 1.5 h
r.t. / 1 h
r.t. / 0.5 h
r.t. / 2 h
r.t. / 3 h
r.t. / 2 h
r.t. / 2 h
r.t. / 3 h
r.t. / 3 h
40 °C / 3 h
60 °C / 5 h
r.t. / 1 h
50 °C / 5 h
60 °C / 5 h
r.t. / 3 h
60 °C / 3 h
r.t. / 3 h
60 °C / 3 h
r.t. / 3 h
r.t. / 3 h
46
51
47
57
90
64
49
60
56
58
46
61
48
54
69
30
47
78
76
64
81
62
87
93
81
75
51
59
81
61
89
73
3a
3b
3c
3d
3e
3f
3g
3h
3i
Prn
Bun
Thenyl
4-Morpholinoethylene
2-Pyridylmethylene
3-Pyridylmethylene
2-F-Benzyl
3-F-Benzyl
4-F-Benzyl
3j
2-Cl-Benzyl
3-Cl-Benzyl
Prn
3k
4a
4b
4c
4d
4e
4f
4g
4h
4i
Prn Br
Prn
ClCH2COOEt
MeI
Bun
Thenyl
Thenyl
Bun Br
ClCH2COOEt
MeI
ClCH2COOEt
MeI
ClCH(Me)COOEt
MeI
MeI
ClCH2COOEt
MeI
ClCH2COOEt
MeI
ClCH2COOEt
MeI
ClCH2COOEt
MeI
ClCH2COOEt
4-Morpholinoethylene
4-Morpholinoethylene
2-Pyridylmethylene
2-Pyridylmethylene
3-Pyridylmethylene
2-F-Benzyl
2-F-Benzyl
3-F-Benzyl
3-F-Benzyl
4-F-Benzyl
4-F-Benzyl
4j
4k
4l
60 °C / 5 h
r.t. / 3 h
60 °C / 4 h
r.t. / 1 h
60 °C / 3 h
r.t. / 3 h
60 °C / 5 h
r.t. / 1 h
60 °C / 2 h
4m
4n
4o
4p
4q
4r
4s
4t
2-Cl-Benzyl
2-Cl-Benzyl
3-Cl-Benzyl
3-Cl-Benzyl
[a] r.t.: room temperature; h: hour; [b] Isolated yields of 2 based on 1 used; Isolated yields of 3 based on 2 used; Isolated yields of 4 based on 3 used.

78
F.-L. Yang, Z.-J. Liu, X.-B. Huang and M.-W. Ding
Vol. 41
Scheme 1
disulfide in refuxing dichloromethane for 29 hours at 75
°C under inert and anhydrous conditions, to obtain
3-furan-2-yl-2-isothiocyanato acrylic acid ethyl ester 2.
Cyclocondensation of the intermediate 2 in situ with
RNH at room temperature in 0.5 - 3 hours yielded
2
directly 5-furylmethylidene-2-thio-4-imidazolidinones 3.
Scheme
2
zolinone derivatives via tandem aza-Wittig reaction [11-
16], we now report the synthesis and biological activities
of some novel 2-alkylthio-5-furylmethylidene-imidazoli-
nones (4a - t) from the stable vinyliminophosphorane 1.
Results and Discussion.
The synthetic route (Scheme 1) involved the aza-Wittig
reaction of the vinyliminophosphorane 1 with carbon

Jan-Feb 2004
Synthesis and Biological Activities
79
Table 2 (continued)
Table 3
-1
IR (KBr, ν/cm ), and EI-MS Data of Compounds 3a – k, and 2
No.
ν
;
ν
;
ν
;
ν
;
ν
C=S
m/z (abundance, %)
N-H
C=O
C=C
C=C (in ring)
+
3a
3b
3c
3d
3e
3f
3g
3h
3i
3234; 1724;
3293; 1735;
3289; 1715;
3235; 1730;
3242; 1731;
3120; 1716;
3253; 1740;
3292; 1737;
3236; 1727;
3230; 1726;
3308; 1736;
1650;
1652;
1647;
1650;
1655;
1649;
1650;
1651;
1653;
1648;
1650;
1486, 1458, 1434, 1405;
1485, 1455, 1442, 1403;
1484, 1448, 1424, 1395;
1485, 1453, 1447, 1407;
1484, 1452, 1438, 1396;
1498, 1466, 1431,1399;
1485, 1455, 1435, 1402;
1484, 1449, 1433, 1399;
1485, 1453, 1431, 1395;
1483, 1447, 1436, 1395;
1483, 1447, 1432, 1394;
1117
1129
1125
1115
1140
1143
1138
1139
1160
1149
1137
236(M , 38); 194(23); 107(100)
+
250(M , 44); 217(78); 107(100)
+
290(M , 64); 257(45); 97(100)
+
307(M , 11); 274(27); 100(100)
+
285(M , 90); 252(75); 107(100)
+
285(M , 90); 252(70); 107(100)
+
302(M , 70); 269(11); 109(100)
+
302(M , 82); 269(17); 109(100)
+
302(M , 81); 269(12); 109(100)
+
+
3j
3k
2
320(M +1,31); 318(M -1,18); 107(100)
+
+
320(M +1,35); 318(M -1,93); 107(100)
+
2021(N=C=S); 1719(C=O); 1623(C=C); 1263(C=S)
223(M ,100); 108(26); 45(39)
In the presence of K CO (s), the S-alkylation reaction of
241 °C range. Reaction conditions and yields data are
given in Table 1.
2
3
3 with R'X (X = Cl, Br, I) provided 2-alkylthio-5-furyl-
methylidene-4 H-imidazolin-4-ones 4 in satisfactory
yields. When X was I or Br, the S-alkylation reaction could
be carried out smoothly in 1 - 3 hours at room temperature;
When X was Cl, reaction time was for 3 - 5 hours at 40 –
60 °C to accomplish the S-alkylation reaction. The pres-
ence of K CO (s), 3:K CO (s) = 1:6-10 mole ratio, was
The structures of all compounds 2, 3a - k and 4a - t were
established on the basis of elemental analysis and spectral
data. Physical properties and elemental analysis data of
compounds 2, 3a - k and 4a - t are presented in Table 2.
The difference between found value and calculated value
of elemental analysis of all compounds 2, 3a - k and 4a - t
was under 0.5 %.
The ir spectral data of the reaction products 2, 3a - k and
4a - t are given in Table 3 and Table 4, and are in agreement
with the corresponding structures [17]. The ir spectral data
of compounds 2 showed absorption bands at 2021 cm-1 due
to N=C=S group, at 1719 cm-1 due to C=O group, at 1623
2
3
2
3
necessary for the S-alkylation reaction to take place in
short time and at lower temperature. Thin layer chro-
matography was employed to follow the progress of the
above reactions.
All of the compounds 2, 3a - k and 4a - t were readily
soluble in polar organic solvents and melt within the 42 –

80
F.-L. Yang, Z.-J. Liu, X.-B. Huang and M.-W. Ding
Vol. 41
Table 4
-1
IR (KBr, ν/cm ) , and EI-MS Data of Compounds 4a – t
No.
ν
;
ν
;
ν
;
ν
C=N & C=C (in ring)
m/z (abundance, %)
CO Et
2
C=O
C=C
+
4a
4b
4c
4d
4e
4f
4g
4h
4i
1700;
1708;
1702;
1696;
1712;
1708;
1704;
1707;
1714;
1710;
1702;
1709;
1705;
1708;
1707;
1709;
1702;
1713;
1706;
1707;
1638;
1639;
1638;
1634;
1642;
1633;
1642;
1632;
1640;
1634;
1626;
1632;
1636;
1642;
1634;
1631;
1632;
1632;
1633;
1642;
1488, 1468
1491, 1466
1492, 1468
1487, 1465
1493, 1468
1493, 1469,1433
1494, 1474, 1461
1590, 1568, 1488, 1466, 1419
1592, 1568, 1494, 1469, 1421
1577, 1556, 1491, 1463, 1418
1556, 1490, 1462, 1427
1582, 1489, 1468, 1453
1615, 1590, 1551, 1469
1592, 1493, 1470, 1448
1599, 1554, 1492, 1465
1558, 1512, 1487, 1467
1551, 1491, 1463, 1422
1554, 1492, 1463, 1444
1598, 1578, 1493, 1465
1571, 1494, 1468, 1437
278(M , 86); 236(90); 107(100)
+
1729;
322(M , 100); 236(63); 107(70)
+
264(M , 100); 236(17); 107(52)
+
346(M , 40); 290(40); 97(100)
+
1731;
1735;
1736;
376(M , 67); 289(28); 97(100)
+
321(M , 12); 274(65); 100(100)
+
393(M , 7); 274(68); 100(100)
+
299(M , 36); 252(100); 106(22)
+
385(M , 90); 252(100); 106(50)
+
4j
4k
4l
299(M , 85); 252(60); 92(100)
+
316(M , 75); 283(6); 109(100)
+
1729;
1740;
1741;
1730;
1738;
388(M , 66); 315(65); 109(100)
+
4m
4n
4o
4p
4q
4r
4s
4t
316(M , 99); 283(39); 109(100)
+
388(M , 87); 315(58); 109(100)
+
316(M , 82); 283(5); 109(100)
+
388(M , 47); 315(20); 109(100)
+
333(M , 32); 297(86); 125(100)
+
405(M , 7); 369(57); 125(100)
+
333(M , 25); 332(100); 125(87)
+
405(M , 37); 331(65); 125(100)
Table 5
1
H NMR Data of Compounds 2, 3a - k and 4a - t
1
No.
H NMR (δ/ppm, 300MHz, CDCl )
3
2
7.64 - 6.47(m, 3H, Furyl-H); 7.72(s, 1H, =CH); 4.39 - 4.32(q, 2H, OC H CH , J=6.9 Hz); 1.42 - 1.37(t, 3H, OCH CH , J = 6.9 Hz).
2 3 2 3
3a
9.24(bs, 1H, NH); 7.61 - 6.48(m, 3H, Furyl-H); 6.68(s, 1H, =CH); 3.88 - 3.63(t, 2H, NCH , J = 7.4 Hz); 1.81 - 1.69(m, 2H,
NCH CH ); 0.99 - 0.94(t, 3H, CH , J = 7.8 Hz).
2
2
9.23(bs, 1H, NH); 7.60 - 6.47(m, 3H, Furyl-H); 6.68(s, 1H, =CH); 3.91 - 3.86(t, 2H, NCH , J = 7.3 Hz); 1.72 - 1.65(m, 2H,
2
3
3b
2
NCH CH ); 1.42 - 1.34(m, 2H, CH CH ); 0.98 - 0.93(t, 3H, CH , J = 7.3 Hz).
2
9.30(bs, 1H, NH); 7.60 - 6.47(m, 3H, Furyl-H); 7.26 - 6.93(m, 3H, Thiophen-yl-H); 6.68(s, 1H, =CH); 5.03(m, 2H, NCH ).
2
2
3
3
3c
2
3d
9.25(bs, 1H, NH); 7.60 - 6.47(m, 3H, Furyl-H); 6.68(s, 1H, =CH); 4.04 - 4.01(m, 2H, NCH , J = 5.9 Hz); 3.65 - 3.61(m, 4H,
2
CH OCH ); 2.69(s, 2H, CH N(CH ) ); 2.54(s, 4H, CH N( C H ) ).
2
9.37(bs, 1H, NH); 8.52 - 7.13(m, 4H, Pyridyl-H); 7.60 - 6.53(m, 3H, Furyl-H); 6.69(s, 1H, =CH); 5.24(s, 2H, NCH ).
2
2
2 2 2 2
2
3e
3f
3g
3h
3i
2
9.38(bs, 1H, NH); 8.74 - 7.21(m, 4H, Pyridyl-H); 7.61 - 6.50(m, 3H, Furyl-H); 6.70(s, 1H, =CH); 5.09(s, 2H, NCH ).
9.36(bs, 1H, NH); 7.61 - 6.51(m, 3H, Furyl-H); 7.25 - 7.00(m, 4H, Ar-H); 6.70(s, 1H, =CH); 5.17 (s, 2H, NCH ).
2
2
9.33(bs, 1H, NH); 7.60 - 6.49(m, 3H, Furyl-H); 7.26 - 6.91(m, 4H, Ar-H); 6.68(s, 1H, =CH); 5.06 (s, 2H, NCH ).
2
9.26(bs, 1H, NH); 7.60 - 6.48(m, 3H, Furyl-H); 7.49 - 6.94(m, 4H, Ar-H); 6.68(s, 1H, =CH); 5.31 (s, 2H, NCH ).
2
3j
9.44(bs, 1H, NH); 7.62 -6.54(m, 3H, Furyl-H); 7.37 - 6.99(m, 4H, Ar-H); 6.71(s, 1H, =CH); 5.21 (s, 2H, NCH ).
2
3k
4a
9.29(bs, 1H, NH); 7.60 - 6.49(m, 3H, Furyl-H); 7.43 - 7.21(m, 4H, Ar-H); 6.69(s, 1H, =CH); 5.04 (s, 2H, NCH ).
2
7.53 - 6.54(m, 3H, Furyl-H); 6.86(s, 1H, =CH); 3.55 - 3.50(t, 2H, NCH , J = 7.5 Hz); 3.35 - 3.30 (t, 2H, SCH , J = 7.2 Hz);
2
1.91 - 1.81(m, 2H, NCH CH ); 1.75 - 1.61(m, 2H, SCH CH ); 1.12 – 1.07(t, 3H, NCH CH CH , J = 7.2 Hz); 0.95 - 0.91(t, 3H,
2
2
2
2
2
2
2
3
SCH CH CH , J = 7.2 Hz).
2
7.53 - 6.54(m, 3H, Furyl-H); 6.89(s, 1H, =CH); 4.26 - 4.19(q, 2H, OCH , J = 7.2 Hz); 4.07(s, 2H, SCH ); 3.58 - 3.53(t, 2H, NCH ,
2
3
4b
2 2 2
J = 7.4 Hz); 1.74 - 1.64(q, 2H, NCH CH , J = 7.4 Hz); 1.31-1.26 (t, 3H, OCH CH , J = 7.2 Hz); 0.97 - 0.92(t, 3H, NCH CH CH ,
2
2
2
3
2
2
3
J = 7.4 Hz).
7.54 - 6.54(m, 3H, Furyl-H); 6.87(s, 1H, =CH); 3.60 - 3.55(t, 2H, NCH , J = 7.4 Hz); 2.72(s, 3H, SCH ); 1.68 - 1.58(m, 2H,
4c
4d
4e
4f
2
3
NCH CH ); 1.40 - 1.30(m, 2H, CH CH ); 0.96 - 0.91(t, 3H, CH CH , J = 7.4 Hz).
2
2
2
3
7.57 - 6.56(m, 3H, Furyl-H); 7.26 - 6.93(m, 3H, Thiophen-yl-H); 6.94(s, 1H, =CH); 4.93(s, 2H, N-CH ); 3.42 - 3.73(t, 2H, SCH ,
2
3
2
J = 6.9 Hz); 1.89 - 1.80(m, 2H, SCH CH ); 1.59 - 1.47(m, 2H, SCH CH CH CH ); 1.03 - 0.98(t, 3H, CH CH , J = 7.4 Hz).
2
2
2
2
2
2
3
2
3
7.53 - 6.54(m, 3H, Furyl-H); 7.23 - 6.91(m, 3H, Thiophen-yl-H); 6.93(s, 1H, =CH); 4.93(s, 2H, NCH ); 4.25 - 4.18(q, 2H, OCH ,
2
2
J = 7.2 Hz); 4.04(s, 2H, SCH ); 1.30 - 1.25(t, 3H, OCH CH , J = 7.2 Hz).
2
7.55 - 6.53(m, 3H, Furyl-H); 6.87(s,1H, =CH); 3.72 - 3.64(m, 6H, NCH and CH OCH ); 2.73(s, 3H, SCH ); 2.60 - 2.56(m, 2H,
2
3
2
2
2
3
NCH CH ); 2.52 - 2.46(m, 4H, N(CH ) ).
2 2
2
7.54 - 6.55(m, 3H, Furyl-H); 6.89(s, 1H, =CH); 4.26 - 4.20(q, 2H, OC H CH , J = 6.9 Hz); 4.07(s, 2H, SCH ); 3.71 - 3.67(m, 6H, NCH
2
4g
2 3 2 2
and CH OCH ); 2.61 - 2.57(t, 2H, NCH CH , J= 6.2 Hz); 2.52 - 2.47(m, 4H, N(CH ) ); 1.32 - 1.27(t, 3H, OCH CH , J = 6.9 Hz).
2 2
2
2
2
2
8.54 - 7.15(m, 4H, Pyridyl-H); 7.55 - 6.55(m, 3H, Furyl-H); 6.95(s, 1H, =CH); 4.92(s, 2H, NCH ); 2.68(s, 3H, SCH ).
2
3
4h
4i
2 3
8.53 - 7.17(m, 4H, Pyridyl-H); 7.53 - 6.55(m, 3H, Furyl-H); 6.94(s, 1H, =CH); 4.96 - 4.82(m, 2H, NCH ); 4.61 - 4.54(q, 1H, SCH,
2
J = 7.2 Hz); 4.28 - 4.10(m, 2H, OCH ); 1.68 - 1.65(d, 3H, SCH (M e), J = 6.9 Hz); 1.27 – 1.20(m, 3H, OCH CH ).
2
8.59 - 7.20(m, 4H, Pyridyl-H); 7.55 - 6.55(m, 3H, Furyl-H); 6.93(s, 1H, =CH); 4.77(s, 2H, NCH ); 2.69(s, 3H, SCH ).
2
3
4j
2 3

Jan-Feb 2004
Synthesis and Biological Activities
81
Table 5 (continued)
1
No.
H NMR (δ/ppm, 300MHz, CDCl )
3
4k
4l
7.55 - 6.55(m, 3H, Furyl-H); 7.31 - 7.03(m, 4H, Ar-H); 6.94(s, 1H, =CH); 4.85(s, 2H, NCH ); 2.66 (s, 3H, SCH ).
2 3
7.54 - 6.55(m, 3H, Furyl-H); 7.30 - 7.01(m, 4H, Ar-H); 6.95(s, 1H, =CH); 4.86(s, 2H, NCH ); 4.24 - 4.16(q, 2H, OC H CH , J = 7.2 Hz);
2
2
3
4.00 (s, 2H, SCH ); 1.29 - 1.24(t, 3H, OCH CH , J = 7.2 Hz).
2
2
4m 7.54 - 6.54(m, 3H, Furyl-H); 7.26 - 6.94(m, 4H, Ar-H); 6.93(s, 1H, =CH); 4.73(s, 2H, NCH ); 2.66 (s, 3H, SCH ).
3
2
3
4n
7.55 - 6.56(m, 3H, Furyl-H); 7.29 - 6.98(m , 4H, Ar-H); 6.96(s, 1H, =CH); 4.77(s, 2H, NCH ); 4.25 - 4.18(q, 2H, OC H CH , J = 6.9 Hz);
2 2 3
4.02(s, 2H, SCH ); 1.29 - 1.25(t, 3H, OCH CH , J = 6.9 Hz).
2
7.54 - 6.54(m, 3H, Furyl-H); 7.30 - 6.95(m, 4H, Ar-H); 6.92(s, 1H, =CH); 4.71(s, 2H, NCH ); 2.67 (s, 3H, SCH ).
2
3
4o
4p
2 3
7.54 - 6.55(m, 3H, Furyl-H); 7.31 - 6.96(m, 4H, Ar-H); 6.94(s, 1H, =CH); 4.74(s, 2H, NCH ); 4.24 - 4.17(q, 2H, OC H CH , J = 7.2 Hz);
2
2
3
4.03(s, 2H, SCH ); 1.29 - 1.25(t, 3H, OCH CH , J = 7.1 Hz ).
2
7.56 - 6.56(m, 3H, Furyl-H); 7.34 - 7.01(m, 4H, Ar-H); 6.97(s, 1H, =CH); 4.91(s, 2H, NCH ); 2.66 (s, 3H, SCH ).
2
3
4q
4r
2 3
7.55 - 6.57(m, 3H, Furyl-H); 7.37 - 7.04(m, 4H, Ar-H); 6.97(s, 1H, =CH); 4.92(s, 2H, NCH ); 4.24 - 4.16(q, 2H, OC H CH , J = 7.2 Hz);
3
2
2
4.00(s, 2H, SCH ); 1.29 - 1.24(t, 3H, OCH CH , J = 7.2 Hz).
2
7.55 - 6.55(m, 3H, Furyl-H); 7.31 -7.10(m, 4H, Ar-H); 6.94(s, 1H, =CH); 4.72(s, 2H, NCH ); 2.68 (s, 3H, SCH ).
2
3
4s
4t
2 3
7.55 - 6.56(m, 3H, Furyl-H); 7.27 - 7.17(m, 4H, Ar-H); 6.95(s, 1H, =CH); 4.75(s, 2H, NCH ); 4.24 - 4.18(q, 2H, OC H CH , J = 6.8 Hz);
2
2
3
4.02(s, 2H, SCH ); 1.29 - 1.25(t, 3H, OCH CH , J = 6.8 Hz).
2
2
3
Table 6
13
C NMR Data of Compounds 4e and 4g
13
No.
C NMR (CDCl , δ / ppm , 300MHz)
3
4e
4g
166.05(COOEt); 165.37( C=O); 159.04(N=C-S); 148.68, 142.83, 110.95, 110.42(4 Carbons, Furyl); 135.03(CH=C); 132.88, 124.56,
123.79, 115.48(4 Carbons, Thiophen-yl); 125.22(CH=C); 59.84 (OCH ); 36.72 (NCH ); 30.72 (SCH ); 11.73 (OCH CH ).
169.20(COOEt); 169.04( C=O); 162.58(N=C-S); 151.31, 145.28, 113.46, 112.51 (4 Carbons, Furyl); 135.84(CH=C); 117.80(CH=C);
2
2
2
2
3
67.10(2 Carbons, CH OCH ); 62.39(OCH ); 56.70(CH N(CH ) ); 53.88(2 Carbons, CH N(CH ) ); 38.263(O=C-NCH );
2
2
2
2
2 2 2 2 2
2
33.27(SCH ); 14.31(OCH CH )
2
2
3
Table 7
The Fungicidal Activity of Compounds 4a – t
(50 µg/mL, Relative Inhibition %)
No.
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
Fusarium oxysporium
Botryosphaeria berengeriana
Rhizoctonia solani
53.8
33.3
25.0
23.1
33.3
50.0
42.3
26.7
55.3
53.8
33.3
62.5
13.0
0
20.0
13.0
40.0
50.0
13.0
6.7
25.0
13.0
0
12.5
33.3
41.6
28.6
21.7
0
25.0
No.
4k
4l
4m
4n
4o
4p
4q
4r
4s
4t
Fusarium oxysporium
Botryosphaeria berengeriana
Rhizoctonia solani
22.2
62.5
48.6
44.4
62.5
57.1
61.1
50.0
42.8
55.6
68.7
37.1
61.1
50.0
42.8
11.7
0
25.0
5.6
50.0
60.0
88.9
62.5
65.7
61.1
50.0
42.8
55.6
75.0
37.1
cm-1 due to C=C group, at 1263 cm-1 due to C=S group.
The ir spectral data of compounds 3a - k showed absorp-
tion bands in the 3308 - 3120 cm-1 range due to N-H group,
in the 1740 - 1715 cm-1 range due to C=O group, in the
1655 - 1647 cm-1 range due to C=C group on the side chain
of imidazolinone, and in the 1160 - 1115 cm-1 range due to
the C=S group. The ir spectral data of compounds 4a - t
was also sound. For example, the ir spectral data of 4n
showed a strong absorption bands for the C=O group on the
side chain COOEt at 1740 cm-1, a strong absorption bands
for C=O group in the imidazolinone framework at 1708
cm-1. The resonance absorption bands of the Aryl and furyl
framework are observed at 1493, 1470, and 1448 cm-1. In
addition to the two relatively strong absorption bands at
1642 and at 1592 cm-1, which can be assigned to the C=C
group on the side chain of imidazolinone and C=N group in
the imidazolinone framework, respectively.
The H nmr spectra of compounds 3a - k exhibited a
1
broad singlet signal in the δ 9.23 - 9.44 range accounting
for the proton of N-H, a sharp singlet signal in the δ 6.68 -
6.69 range accounting for the alkenyl hydrogen on the
side chain of imidazolinone, multiple signals in the δ 7.62
- 6.47 range accounting for 3 hydrogens of furyl group,
multiple signals in the δ 7.49 - 6.91 range accounting for 4
hydrogens of aryl group, in the δ 8.52 - 7.13 range with
multiple signals for the 4 hydrogens of pyridyl group, and
multiple signals in the δ 7.26 - 6.93 range accounting for
the 3 hydrogens of thiophenyl group. The 1H nmr spectra
of compounds 4a - t are explained with compound 4n as
an example, which exhibited multiple signals in the δ 7.55

82
F.-L. Yang, Z.-J. Liu, X.-B. Huang and M.-W. Ding
Vol. 41
Table 8
exhibited herbicidal and fungicidal activities (see Table 7
and Table 8). Especially, in 50 µg/mL, 4r showed 88.9 %
inhibition of Fusarium oxysporium. In 100 µg/mL, 4p
showed 94.8 % inhibition of Cole root, 89.7 % inhibition
of Cole stalk, and 96.0 % inhibition of Barnyard grass
root. Compounds 4c and 4r showed 86.5 % and 89.9 %
inhibition of Barnyard grass root in 100 µg/mL, respec-
tively. To some extent, compounds 4s and 4t showed
promotion growth of Barnyard grass stalk and Cole stalk,
respectively.
The Herbicidal Activity of Compounds 4a - t
(Relative Inhibition %) [d]
Cole
Barnyard grass
No.
100 µg/ m
L10 µg/mL
(Root/Stalk)
100 µg / mL
10 µg / m L
(Root/Stalk)
(Root/Stalk)
(Root/Stalk)
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
18.2 / 50.0
17.2 / 37.0
76.1 / 49.1
36.4 / 40.7
69.8 / 6.7
55.2 / 26.7
79.3 / 28.9
49.1 / 4.4
49.5 / 22.8
62.9 / 31.1
52.2 / -7.7
26.1 / 15.4
24.3 / 0
35.6 / 2.6
28.7 / 10.3
94.8 / 89.7
56.5 / 12.8
77.4 / 41.0
29.6 / 2.6
23.5 / -17.9
99.2 / 98.0
17.2 / 33.3
15.2 / 33.3
32.7 / 24.6
30.3 / 31.5
25.0 / 0
25.0 / 8.9
44.8 / 24.4
34.5 / 0
24.8 / 10.5
44.8 / 26.7
27.8 / -7.7
24.3 / 5.1
19.1 / 0
-6.0 / 47.2
6.0 / 63.9
86.5 / 59.5
4.0 / 44.4
70.0 / 9.1
55.0 / 22.7
57.5 / 13.6
72.5 / 9.1
67.6 / 37.8
65.0 / 13.6
75.5 / 5.3
40.8 / 36.8
69.4 / -10.5
77.6 / 5.3
71.4 / 26.3
96.0 / 77.1
75.5 / 5.3
89.9 / 0
-14.0 / 44.4
6.0 / 44.4
45.9 / 37.8
4.0 / 41.7
37.5 / 13.6
15.0 / 18.2
50.0 / 13.6
52.5 / 9.1
35.1 / 32.4
65.0 / 10.9
71.4 / 5.3
40.8 / -10.5
36.7 / -10.5
48.9 / -5.3
55.1 / -5.3
68.0 / 25.0
16.3 / -15.8
73.5 / 0
EXPERIMENTAL
Chemistry.
Melting points were determined on an X melting-point appa-
4
ratus, and are not corrected; Elemental analyses were taken on a
PE-2400-CHN elemental analysis instrument. The ir spectra
were recorded on a Perkin-Elmer-1600 FT Infrared spectrometer
in KBr pellets (ν in cm-1). The 1H and 13C nmr were measured in
9.6 / 0
18.3 / -5.1
35.4 / 39.7
26.1 / 10.3
33.9 / 25.6
17.4 / 0
CDCl on a Varian XL-300 spectrometer with TMS as an internal
3
standard (δ in ppm). The Mass spectra were recorded on a
Finnigen TRACE GC-MS spectrometer at an ionization potential
70 eV. Thin layer chromatography was employed to follow the
progress of all synthetic reactions.
77.6 / -15.8
46.9 / 21.0
99.9 / 65.8
48.9 / -31.6
42.8 / 0
98.4 / 66.6
4t
2,4-D
17.4 / -20.5
97.9 / 96.7
The vinyliminophosphorane 1 was prepared according to the
literature report [18].
[d] positive: growth inhibition; minus: promotion growth; 0 % = no effect,
100 % = complete killing. 2,4-D: (2,4-dichloro-phenoxy)-acetic acid.
General Procedure for the Preparation of 2.
A solution of 2.21 g, 5 mmoles vinyliminophosphorane 1 in 20
mL dry dichloromethane and 3.5 g, 50 mmoles carbon disulfide
was refluxed for 29 hours under stirring and the protection of a
nitrogen atmosphere, and then allowed to cool to room tempera-
ture. The solvent and excess carbon disulfide was removed in
v a c u o. The residue was dissolved completely in 15 mL
dichloromethane, and a 30 mL mixture of ether and petroleum
ether (1:2, volume ratio) was added to precipitate the triph-
enylphosphine sulfide. The solution was filtered, and the filtrate
was condensed in vacuo keeping the temperature < 40 °C, and the
residual was recrystallized from a 20 mL mixture of ether and
petroleum ether (1:3, volume ratio) to yield 3-furan-2-yl-2-isoth-
iocyanato acrylic acid ethyl ester 2.
- 6.56 range accounting for the 3 hydrogens of furyl group,
multiple signals in the δ 7.29 - 6.94 range accounting for
the 4 hydrogens of aryl group. The chemical shift of the
alkenyl hydrogen on the side chain of imidazolinone was
observed at δ 6.96 with a single signal, δ 4.77 and δ 4.02
with a single signal accounting for the 2 hydrogens of
NCH2 and SCH2, respectively. Four signals with J = 6.9
Hz in the range δ 4.25 - 4.18 for the 2 hydrogens of
OC H 2CH 3 group, three signals with J = 6.9 Hz in the
range δ 1.29 - 1.25 for the 3 hydrogens of OCH2C H 3
group (see Table 5).
The 13C nmr spectra for compounds 4e and 4g were con-
General Procedure for the Synthesis of 2-Thio-4-imidazol-
idinones 3.
sistent with the assigned structures (see Table 6).
The EI-mass spectra of most of compounds 2, 3a - k
and 4a - t except 3j and 3k exhibited strong molecule ion
peaks (see Table 3 and Table 4). Compounds 3j and 3k
showed fragment ion peaks corresponding to [M+1]+ at
m/z 320 and [M-1]+ at m/z 318, respectively, instead of
the molecular ion peak of M+ at m/z 319. The major
fragmentation pathways are explained with that of com-
pound 4n as an example, which showed a strong molec-
ular ion peak M+ with m/z 388 and 87 % relative abun-
dance. The fragmentation pathways of 4n are rational-
ized in Scheme 2.
To a solution of 2 prepared above in 20 mL dry dichloro-
methane was added RNH (if R = Pr or Bu, 5 mmoles; if R =
2
Benzyl-typed alkyl, 3 mmoles). The mixture was stirred for 0.5 -
3 hours at room temperature and filtered, the solvent and excess
RNH in the filtrate was evaporated in vacuo. The residual was
2
recrystallized from a 20 mL mixture of dry dichloromethane and
petroleum ether (1:3, volume ratio) to obtain 3.
General Procedure for the Synthesis of 2-Alkylthio-4H- i m i d a-
zolin-4-ones 4.
A mixture of 3 mmoles 3 in 10 mL dry acetonitrile, 3.5 - 5
mmoles R'X, and 3.33 g, 24 mmoles K CO (s) was stirred for 1 - 5
2
3
The biological activities of all compounds 4a - t were
investigated and the results of bioassay showed that they
hours at room temperature or 40 - 60 °C, and was allowed to stand
in order to precipitate the solid potassium carbonate completely.

Jan-Feb 2004
Synthesis and Biological Activities
83
The mixture was filtered, the filtrate was condensed, and the resid-
ual was recrystallized from a 20 mL mixture of dry
dichloromethane and petroleum ether (1:4, volume ratio) to yield 4.
Address correspondence to Prof. Zhao-Jie Liu, Institute of
O rganic Synthesis, Central China Normal University, Wuhan,
430079, P. R. China. E-mail: yfling2000cn@yahoo.com.cn
Biological Testing.
REFERENCES AND NOTES
The newly synthesized compounds 4a-t were tested for fungici-
dal activities against specified microorganisms such as Fusarium
oxysporium, Botryosphaeria berengeriana and Rhizoctonia
solani, using 400 µg/mL (w/v) solutions in sterile acetone, respec-
tively. The concentration of each tested compound was made 50
µg/mL with sterile acetone, emulsifier and distilled water. A 50
µg/mL solution of the tested compound was poured aseptically in
a well of 5 mm diameter made by a borer in a seeded agar
medium, respectively. The distilled water was used as a compari-
son compound. After pipetting the same volume in wells of all
tested microorganisms, respectively, pathogen test plates were
incubated at 37 °C for 24 hours, fungal test plates and the compar-
ison plate were incubated at 25 °C for 48 hours. The activities
were expressed as inhibition rate (inhibition zones in diameter,
mm, as clear areas) in comparison with distilled water.
Herbicidal testing of the newly synthesized compounds 4a-t
was carried out in a plant growth room, temperature 23±1 °C,
RH 60±5 %, light intensity 10 klux, photoperiod 8 hours.
Twenty seeds of each one of weed species including Barnyard
grass (Echinochloa cru s g a l l i) and Cole (Brassica campestris
Var. Oleifera) were chosen for testing. Seedlings were grown in
the test plate of 9 cm diameter containing two pieces of filter
paper and 9 mL solution of the tested compound (10 and 100
µg/mL, respectively). Distilled water and (2,4-dichlorophenoxy)-
acetic acid (2,4-D) were used as comparison compounds. The
herbicidal activity was assessed as the inhibiton rate in compari-
son with the distilled water and (2,4-dichlorophenoxy)acetic
acid 8 days after treatment. The herbicidal rating score based on
visual observation, range from 0 % to 100 %; 0 % = no eff e c t ,
100 % = complete killing.
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The authors gratefully acknowlege financial support of this
work by the Natural Science Foundation of China (Grant No.
20102001) and the funded Project of youth cadreman teacher in
the Universities of Henan Province (Grant No. 2003100260).