Synthesis, characterization, and biological activities of novel (Z)-3-((E)-1-(alkyloxyimino)ethyl)-5-arylidene-4-hydroxypyrroline-2-one derivatives

Article abstract of DOI:10.1002/jhet.452

Twenty-four novel tetramic acid derivatives (Z)-3-((E)-1-(alkyloxyimino) ethyl)-5-arylidene-4-hydroxypyrroline-2-ones 6a-x were synthesized by the reaction of (Z)-3-acetyl-5-arylidene-4-hydroxypyrroline-2-ones 4 with O-alkyl hydroxylamines 5 under reflux conditions in good yields (77.2-92.4%). Their structures were confirmed by IR, ¹H-NMR, MS, and elemental analysis. The preliminary bioassays showed that most of the title compounds exhibited noticeable fungicidal activities against Colletotrichumorbiculare and a certain degree of fungicidal activities against Fusarium gramineaum and Rhizoctonia cerealis at a concentration of 100 μg/mL.

Full text of DOI:10.1002/jhet.452

1328
Synthesis, Characterization, and Biological Activities of Novel
(Z)-3-((E)-1-(Alkyloxyimino)ethyl)-5-arylidene-4-
hydroxypyrroline-2-one Derivatives
Vol 47
Zhao-Yong Zhu,a Xian-Feng Wang,a,b Fan-Gui Meng,a,b Qing-Bin Li,a,b
Xiao-Qian Zheng,a Sheng Qiang,c and Chun-Long Yanga,b
*
aDepartment of Applied Chemistry, College of Science, Nanjing Agricultural University,
Nanjing 210095, People’s Republic of China
bDepartment of Pesticide Science, College of Plant Protection, Key Laboratory of Monitoring and
Management of Crop Diseases and Pest Insects, Ministry of Agriculture, Nanjing Agricultural
University, Nanjing 210095, People’s Republic of China
cWeed Research Laboratory, College of Life Science, Nanjing Agricultural University,
Nanjing 210095, People’s Republic of China
*E-mail: chunlongyang@yahoo.com.cn
Received November 22, 2009
DOI 10.1002/jhet.452
Published online 23 August 2010 in Wiley Online Library (wileyonlinelibrary.com).
Twenty-four novel tetramic acid derivatives (Z)-3-((E)-1-(alkyloxyimino)ethyl)-5-arylidene-4-hydrox-
ypyrroline-2-ones 6a–x were synthesized by the reaction of (Z)-3-acetyl-5-arylidene-4-hydroxypyrroline-
2-ones 4 with O-alkyl hydroxylamines 5 under reflux conditions in good yields (77.2–92.4%). Their
structures were confirmed by IR, 1H-NMR, MS, and elemental analysis. The preliminary bioassays
showed that most of the title compounds exhibited noticeable fungicidal activities against Colletotri-
chum orbiculare and a certain degree of fungicidal activities against Fusarium gramineaum and Rhizoc-
tonia cerealis at a concentration of 100 lg/mL.
J. Heterocyclic Chem., 47, 1328 (2010).
INTRODUCTION
dine-2,4-dione derivatives and studied antitumor activ-
ities [16]. Zhu et al reported a series of 3-[(a-hydroxy-
substituted)benzylidene]pyrrolidine-2,4-dione derivatives
showing higher herbicidal activities [17].
Some hundreds of natural products containing the
ring system pyrrolidine-2,4-dione (also known as tetra-
mic acid) (Fig. 1) have been isolated from plants, fungi,
and more recently from marine sponges [1–3]. The spec-
trum of biological activities displayed by these natural
products is remarkable in its diversity [4–6]. An impor-
tant representative of the tetramic acids is tenuazonic
acid, which is a metabolite produced by some phytopa-
thogenic fungi [7]. Since its isolation in 1957 from the
culture filtrates of Alternaria tenuis [8], it has been
found possessing antitumor, antiviral, antibacterial, and
herbicidal activities [9–12]. Reutericyclin [13] is a typi-
cal 1,3-bisacyltetramic acid that is extracted from cells
and culture filtrates of Lactobacillus reuteri and found
to inhibit the growth of Salmonella and Helicobacter,
the latter being the causative agent of stomach ulcers.
The melophlins [14] are a class of N-methyl-3-acyltetr-
amic acids recently isolated from the marine sponge
Melophlus sarassinorum. Melophlin A and B displayed
cytotoxic activity against HL60 cells at 0.2 and 0.4 lg/
mL, respectively [15]. In 1971, Yuki et al synthesized a
series of 5-subsitituted-3-(1-anilinoethylidene)pyrroli-
Oxime ether derivatives have occupied an important
position in medicinal and pesticide chemistry with a
wide range of bioactivities [18]. As pesticides, they
were used as insecticides, fungicides, and herbicides.
Alloxydim [19], the first cyclohexanedione herbicide
with an oxime ether group has been commercialized.
The advantages of oxime ether derivatives, such as,
high-activity against the target, low-toxicity toward the
mammalians, and low-residue, have prompted chemists
to design and synthesize more novel oxime ether deriva-
tives [20].
In 1981, Tatsuaki et al synthesized thirteen 3-acetyl-
5-subsititutedbenzylidenetetramic acids [21], the novel
structures and infusive biological activities of which
have aroused great interest to us. Herein, we introduced
oxime ether groups into 3-acetyl-5-subsititutedbenzylide-
netetramic acids to synthesize a series of novel (Z)-3-
((E)-1-(alkyloxyimino)ethyl)-5-arylidene-4-hydroxy-pyr-
roline-2-one derivatives for the purpose of searching
C
V
2010 HeteroCorporation

November 2010
Synthesis, Characterization, and Biological Activities of Novel
(Z)-3-((E)-1-(Alkyloxyimino)ethyl)-5-arylidene-4-hydroxypyrroline-2-one Derivatives
1329
shift data for the vinyl proton signals at the region of
6.42–6.65 ppm with those of similar tetramates, the Z
configuration of the compounds could be assigned, and
this inference was consistent with crystal structure
of 6e.
In the IR spectra of the title compounds 6, there were
medium or weak absorption bands for the enolic
hydroxyl group (m OAH) at around 3300 cmꢀ1 and rela-
tively strong absorption bands for the carbonyl at around
1680 cmꢀ1. The characteristic absorption peak of oxime
ether group existed at around 1620 cmꢀ1. The main
1
characteristic of the H-NMR spectra of 6a–x was the
presence of high-frequency downfield broad singlet dH
7.53–9.72 presumably arising from the deshielded NAH
proton linked to the carbonyl group. The singlet at dH
6.21–6.49 assigned to the CAH proton of CH¼¼C and
singlet at dH 2.32–2.57 assigned to the CAH protons of
CH3C¼¼N. The signal of protons of OH group at the 4-
position in NMR spectra was not been found, and this
phenomena might be caused by the lability of these pro-
tons of compounds 4 and 6, which involved in internal
tautomerization in the enol form. Furthermore, the MS
spectra of all the compounds 6 showed the molecular
ion peak (Mþ, 3–100%), and other fragmentation ions
were consistent with their structures and could be
clearly assigned.
Figure 1. Some bioactive naturally occurring tetramic acids.
new potential pesticides with an excellent biological
activities. The synthetic route is shown in Scheme 1.
RESULTS AND DISCUSSION
Chemistry. The synthesis of compounds (Z)-3-acetyl-
5-arylidene-4-hydroxypyrroline-2-ones 4 involved the
condensation of 3 (1 equivalent) with substituted benzal-
dehydes (2 equivalent) in the presence of dry hydro-
chloride [21]. The dry hydrochloride as a key catalyst
was obtained by the reaction of acetyl chloride with an-
hydrous ethanol. In the 1H-NMR spectra of the com-
pounds 4a, 4c, and 4e, the protons of CH¼¼ and NH
showed the characteristic pair of signals, indicating
these compounds in deuteriochloroform solution existed
to a great extent as tautomers [22]. According to the lit-
In the crystal structure of compound 6e (Fig. 2), the
˚
bond length C(5)AN(2) [1.295(3) A] was close to the
˚
C¼¼N double bond distance (1.34 A). The bond lengths
˚
C(7)AC(9) and C(10)AC(11) were 1.354(3) A and
˚
1.338(3) A, respectively, and they were close to the
˚
C¼¼C double bond distance (1.34 A). As a result, the
benzene ring, C(10)AC(11), C(7)AC(9), C(5)AN(2),
1
˚
erature based on a comparison of the H-NMR chemical
and C(8)¼¼O(1) [1.237(2) A] formed a large conjugated
˚
system. The bond length C(8)AN(1) [1.376(2) A] was
˚
Scheme 1. General synthetic route for the target compounds 6a-x.
shorter than the normal CAN single bond (1.49 A), sug-
gesting the occurring of an electron density delocaliza-
tion. The dihedral angle between benzene ring and pyr-
roline-2-one ring [N(1), O(1), O(2), C(7), C(8), C(9),
C(10)] was 15.928(54)ꢁ. In addition, there was a weak
pꢂꢂꢂp interaction between the parallel benzene rings (the
Figure 2. Molecular structure of compound 6e.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1330
Z.-Y. Zhu, X.-F. Wang, F.-G. Meng, Q.-B. Li, X.-Q. Zheng, S. Qiang, and C.-L. Yang
Vol 47
Table 1
Antifungal activities of compounds 6a–x (100 lg/mL, inhibitory rate percent).
Inhibitory ratea (%)
Compound
R1
R2
F. gramineaum
R. cerealis
C. orbiculare
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
H
H
methyl
n-propyl
i-propyl
allyl
25.0 6 1.5
17.9 6 2.3
11.7 6 3.5
5.1 6 2.7
17.9 6 3.5
5.6 6 1.0
12.2 6 2.3
4.6 6 3.2
17.9 6 3.2
13.3 6 0.9
17.8 6 1.7
19.3 6 2.3
5.8 6 1.7
7.8 6 2.3
9.3 6 0.9
9.8 6 2.6
N.A
5.8 6 2.3
9.3 6 3.1
11.8 6 2.3
12.3 6 3.1
14.3 6 2.4
9.7 6 2.1
11.5 6 1.4
10.0 6 1.7
98.4 6 0.2
50.9 6 1.6
30.3 6 0.9
45.4 6 3.1
7.8 6 0.9
37.8 6 2.6
29.3 6 3.0
14.8 6 3.1
15.3 6 0.9
29.8 6 3.1
28.8 6 2.3
38.4 6 2.1
30.8 6 1.5
N.Ab
74.3 6 0.9
30.7 6 2.7
28.1 6 2.4
33.9 6 3.1
44.9 6 3.1
33.3 6 1.8
20.2 6 4.0
39.6 6 3.3
42.3 6 3.3
22.3 6 4.0
53.6 6 3.6
56.3 6 4.1
53.6 6 0.9
57.8 6 4.1
20.3 6 3.6
73.4 6 1.6
54.2 6 0.9
23.4 6 2.7
19.3 6 3.9
8.9 6 1.8
H
H
H
n-butyl
benzyl
n-propyl
allyl
n-butyl
benzyl
n-propyl
i-propyl
allyl
n-butyl
benzyl
n-propyl
i-propyl
allyl
H
4-OH
4-OH
4-OH
4-OH
4-OCH3
4-OCH3
4-OCH3
4-OCH3
4-OCH3
2-Cl
2-Cl
2-Cl
2-Cl
2-Cl
4-Cl
4-Cl
4-Cl
4-Cl
–
45.5 6 1.8
35.9 6 3.1
6.9 6 3.1
7.4 6 3.2
N.A
6p
6q
6r
6s
6t
6u
n-butyl
benzyl
n-propyl
i-propyl
allyl
13.0 6 1.5
17.0 6 1.8
16.5 6 2.3
16.9 6 3.7
32.4 6 1.4
42.3 6 2.8
16.1 6 3.1
99.2 6 0.1
24.0 6 3.9
39.5 6 2.7
25.0 6 1.7
49.4 6 3.0
14.5 6 3.0
95.1 6 0.3
6v
6w
6x
Tenuazonic acid
Propiconazole
n-butyl
–
–
–
a Average of three replicates.
b N.A. ¼ Not active.
Values are the mean 6 S.D. of three replicates.
˚
centroid-centroid distance was 4.36 A) to pivotally
maintain a 3D supramolecular network structure.
Furthermore, the crystal structure of compound 6e
simultaneously confirmed E configuration of 1-(alkylox-
yimino)ethyl group and Z configuration of arylidene
group, especially the enolic form at 4-position of the
title compounds.
6m, 6n, 6p, and 6q all exceeded 50%. Comparatively,
the fungicidal activities against R. oerealis were moder-
ate, but more than half of the compounds 6 were more
active than tenuazonic acid. The preliminary estimation
of structure-activity relationships indicated that the title
compounds showed more remarkable fungicidal activ-
ities against C. orbicular when R2 was saturated ali-
phatic alkyl, for example, the compound 6a (R1 was H
and R2 was CH3) gave a best activity with EC50 value
of 1.15 lg/mL (Table 2), indicating it was significant to
further modify the structure of the title compounds.
It was worthy to clarify that the herbicidal activities
of the title compounds were evaluated too. Brassica
campestris and Echinochloa crusgalli (L.) Beauv were
chosen as samples of annual dicotyledonous and mono-
cotyledonous plants. But the herbicidal activities of all
the title compounds were found to be quite weak.
Biological activity. The results of fungicidal activ-
ities in vitro at a concentration of 100 lg/mL were
listed in Table 1. Most of the compounds 6 exhibited
notable fungicidal activities against C. orbiculare,
thereby the inhibitory rates of the compounds 6a, 6k, 6l,
Table 2
EC50 values of compounds 6a, 6n, and 6p against C. orbiculare.
Compound
Regression eq.
EC50a(lg/mL)
rb
6a
6n
6p
y ¼ 0.36423x þ 4.97749
y ¼ 0.92570x þ 3.62689
y ¼ 0.50225x þ 4.19465
1.15
30.43
40.13
0.99
0.96
0.90
CONCLUSIONS
A series of new tetramic acid derivatives containing
oxime ether group at 3-position and arylidene group at
5-position were designed and synthesized by the
a Ec50 refer to median effect concentration.
b Refer to correlative coefficient.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2010
Synthesis, Characterization, and Biological Activities of Novel
(Z)-3-((E)-1-(Alkyloxyimino)ethyl)-5-arylidene-4-hydroxypyrroline-2-one Derivatives
1331
(Z)-3-acetyl-4-hydroxy-5-(4-methoxybenzylidene)-pyrroline-
2-one (4c). Yellow powder, mp 239.3–240.1ꢁC; yield, 60.8%;
IR (KBr, cmꢀ1) m 3239, 1673, 1668, 1588, 1522, 1519, 1383,
reaction of (Z)-3-acetyl-5-arylidene-4-hydroxypyrroline-
2-ones with O-substituted hydroxylamine hydrochlor-
1
ides. The data of IR, MS, H-NMR spectra, and X-ray
1
1240, 1032, 959; H-NMR (CDCl3, 300 MHz) d: 2.58 (s, 3H,
single-crystal structure diffraction confirmed the struc-
tures of the title compounds that contained enol struc-
ture and (3E, 5Z)-configuration. The bioassay results
demonstrated that most of the title compounds, espe-
cially 6a, possessed good activity against C. orbiculare.
Further studies on structural modification are currently
underway.
COCH3), 3.87 (s, 3H, PhOCH3), 6.64, 6.66 (s, s, 1H, CH¼¼),
6.97 (d, 2H, PhH, J ¼ 6.9 Hz), 7.43 (d, 2H, PhH, J ¼ 9.3
Hz), 7.76, 8.14 (s, s, 1H, NH); Anal. Calcd for C14H13NO4: C,
64.86; H, 5.05; N, 5.40. Found: C, 64.56; H, 5.15 N, 5.48.
(Z)-3-acetyl-5-(2-chlorobenzylidene)-4-hydroxypyrroline-2-
one (4d). White powder, mp 227.5–228.9ꢁC; yield, 25.2%; IR
(KBr, cmꢀ1) m 3204, 1703, 1635, 1580, 1443, 1293, 1207,
1089, 938; 1H-NMR (CDCl3, 300 MHz) d: 2.57 (s, 3H,
COCH3), 6.89 (s, 1H, CH¼¼), 7.32–7.48 (m, 4H, PhH), 7.97,
8.38 (s, s, 1H, NH); Anal. Calcd for C13H10ClNO3: C, 59.22;
H, 3.82; N, 5.31. Found: C, 59.57; H, 3.89; N, 5.42.
EXPERIMENTAL
The melting points of the products were determined on a
WRS-1B digital melting-point apparatus and were uncorrected.
IR was recorded on a Bruker Tensor 27 FT-IR spectrometer
with KBr disk. Elemental analyses were performed on Elemen-
tar Vario-III CHN analyzer. Mass spectra were recorded on a
GC/MS-QP2010 spectrometer using direct-injection technique.
1H-NMR spectra was taken on a Mercury plus varian-300
spectrometer with TMS as the internal reference and DMSO-
d6 or CDCl3 as the solvent. X-ray diffraction was performed
with a Brucker Smart APEX II CCD diffractometer. All
reagents were analytical-reagent grade or were chemically
pure. The solvents were dried before use as needed.
Intermediate 3 was prepared according to the reported
method [23]. The intermediates 5 O-allyl, O-methyl, and O-
benzyl hydroxylamine hydrochlorides were synthesized starting
from ethyl acetate and hydroxylamine hydrochloride via a fac-
ile three-step procedure including acetylamination, etherifica-
tion, and hydrolyzation [24–26]. O-Propyl, O-isopropyl, and
O-butyl hydroxylamine hydrochlorides were synthesized start-
ing from hydroxylamine hydrochloride and phthalic anhydride
in satisfactory yield according to the method reported by Han
[27].
General procedure for the synthesis of intermediate (Z)-
3-acetyl-5-arylidene-4-hydroxy-pyrroline-2-ones (4). To the
solution of compound 3 (16 mmol) in ethanol (15 mL) added
8% HCl (18 mmol) in anhydrous ethanol and stirred until it
dissolved, after that a substituted benzaldehyde (32 mmol) was
added. The reaction mixture was refluxed for 3 h, and then
cooled to give a red precipitate, which was filtered off and
recrystallized from ethanol to afford the products 4a–e in
35.2–60.8% yields.
(Z)-3-acetyl-5-benzylidene-4-hydroxypyrroline-2-one (4a). Red
powder, mp 224.9–225.6ꢁC; yield, 36.9%; IR (KBr, cmꢀ1) m
3210, 1697, 1678, 1627, 1455, 1280, 1228, 1084, 936; 1H-
NMR (CDCl3, 300 MHz) d: 2.58 (s, 3H, COCH3), 6.67, 6.70
(s, s, 1H, CH¼¼), 7.35–7.47 (m, 5H, PhH), 8.17, 8.54 (s, s, 1H,
NH); Anal. Calcd for C13H11NO3: C, 68.11; H, 4.84; N, 6.11.
Found: C, 68.45; H, 4.92; N, 6.23.
(Z)-3-acetyl-5-(4-chlorobenzylidene)-4-hydroxy-pyrroline-2-
one (4e). White powder, mp 238.3–240.9ꢁC; yield, 40.2%; IR
(KBr, cmꢀ1) m 3185, 1705, 1624, 1586, 1493, 1420, 1247,
1089, 929; 1H-NMR (CDCl3, 300 MHz) d: 2.58 (s, 3H,
COCH3), 6.60, 6.62 (s, s, 1H, CH¼¼), 7.35–7.41 (m, 4H, PhH),
7.84, 8.11 (s, s, 1H, NH); Anal. Calcd for C13H10ClNO3: C,
59.22; H, 3.82; N, 5.31. Found: C, 59.68; H, 3.75; N, 5.23.
General procedure for the preparation of the title com-
pounds 6a–x. To a solution of (Z)-3-acetyl-5-arylidene-4-
hydroxypyrroline-2-one 4 (1.5 mmol) and O-substituted hy-
droxylamine hydrochloride 5 (1.6 mmol) in ethanol (25 mL)
was added 0.2 mol/L NaOH (8 mL). Then, the reaction mix-
ture was refluxed for 3 h. After cooling to room temperature,
the mixture was poured into water (30 mL), and the precipitate
was filtered. The filtrate was extracted with chloroform and the
organic layer was dried over anhydrous magnesium sulfate.
The solvent was removed under reduced pressure to give a
yellow solid. Finally, the solid was collected together and
recrystallized from ethanol or ethyl acetate to give title com-
pounds 6a–x.
(Z)-5-benzylidene-4-hydroxy-3-((E)-1-(methoxyimino)ethyl)-
pyrroline-2-one (6a). Yellow powder, mp 188.5–189.1ꢁC;
yield, 90.1%; IR (KBr, cmꢀ1) m 3344, 3215, 3028, 2940, 1698,
1
1655, 1620, 1455, 1058, 903; H-NMR (CDCl3, 300 MHz) d:
2.51 (s, 3H, CH3C¼¼N), 3.93 (s, 3H, OCH3), 6.5 (s, 1H,
CH¼¼), 7.32–7.43 (m, 5H, PhH), 7.59 (s, 1H, NH); MS m/z
(%): 258(Mþ, 14), 167(26), 149(84), 81(46), 69(100), 57(94);
Anal. Calcd for C14H14N2O3: C, 65.11; H, 5.46; N, 10.85.
Found: C, 65.62; H, 5.49; N, 10.76.
(Z)-5-benzylidene-4-hydroxy-3-((E)-1-(propoxyimino)ethyl)-
pyrroline-2-one (6b). Yellow powder, mp 165.9–166.4ꢁC;
yield, 92.3%; IR (KBr, cmꢀ1) m 3332, 3211, 3029, 2967, 1687,
1615, 1566, 1450, 1384, 1245, 1050, 925; 1H-NMR (CDCl3,
300 MHz) d: 1.00 (t, 3H, CH2CH3, J ¼ 7.2 Hz), 1.71–1.83
(m, 2H, CH2CH3), 2.55 (s, 3H, CH3C¼¼N), 4.00 (t, 2H, OCH2,
J ¼ 6.3 Hz), 6.49 (s, 1H, CH¼¼), 7.30–7.43 (m, 5H, PhH),
7.74 (s, 1H, NH); MS m/z (%): 286(Mþ, 92), 228(100),
212(18), 149(16), 117(70), 82(56), 45(40); Anal. Calcd for
C16H18N2O3: C, 67.12; H, 6.34; N, 9.78. Found: C, 66.71; H,
6.43; N, 9.68.
(Z)-5-benzylidene-4-hydroxy-3-((E)-1-(isopropoxyimino)ethyl)-
pyrroline-2-one (6c). Yellow powder, mp 163.1–64.1ꢁC; yield,
87.2%; IR (KBr, cmꢀ1) m 3297, 3160, 3019, 2975, 1682, 1611,
1572, 1497, 1375, 1241, 1102, 909; 1H-NMR (CDCl3, 300
MHz) d: 1.34 (d, 6H, CH(CH3)2, J ¼ 6.3 Hz), 2.57 (s, 3H,
CH3C¼¼N), 4.22–4.30 (m, 1H, OCH), 6.49 (s, 1H, CH¼¼),
(Z)-3-acetyl-4-hydroxy-5-(4-hydroxybenzylidene)-pyrroline-
2-one (4b). Red powder, mp 262.3–263.1ꢁC; yield, 45.2%; IR
(KBr, cmꢀ1) m 3373, 3174, 1682, 1606, 1575, 1449, 1357,
1228, 1087, 930; 1H-NMR (DMSO-d6, 300 MHz) d: 2.50 (s,
3H, COCH3), 6.42 (s, 1H, CH¼¼), 6.77 (d, 2H, PhH, J ¼ 8.4
Hz), 7.49 (d, 2H, PhH, J ¼ 8.4 Hz), 9.89 (s, 1H, NH), 10.33
(s, 1H, OH); Anal. Calcd for C13H11NO4: C, 63.67; H, 4.52;
N, 5.71. Found: C, 64.01; H, 4.61; N, 5.80.
Journal of Heterocyclic Chemistry
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Z.-Y. Zhu, X.-F. Wang, F.-G. Meng, Q.-B. Li, X.-Q. Zheng, S. Qiang, and C.-L. Yang
Vol 47
7.30–7.45 (m, 5H, PhH), 7.78 (s, 1H, NH); MS m/z (%):
286(Mþ, 100), 244(28), 225(78), 172(34), 149(32), 117(60),
82(82), 58(22); Anal. Calcd for C16H18N2O3: C, 67.12; H,
6.34; N, 9.78. Found: C, 67.48; H, 6.47; N, 9.70.
3026, 2959, 1695, 1665, 1587, 1457, 1255, 1098, 913; 1H-
NMR (DMSO-d6, 300 MHz) d: 0.88 (t, 3H, CH2CH3, J ¼ 7.2
Hz), 1.31–1.44 (m, 2H, CH2CH3), 1.55–1.65 (m, 2H,
OCH2CH2), 2.35 (s, 3H, CH3C¼¼N), 4.04 (t, 2H, OCH2, J ¼
6.3 Hz), 6.21 (s, 1H, CH¼¼), 6.73 (d, 2H, PhH, J ¼ 8.4 Hz),
7.43 (d, 2H, PhH, J ¼ 7.8 Hz), 9.71 (s, 1H, NH), 9.78 (s, 1H,
OH); MS m/z (%): 316(Mþ, 3), 244(100), 227(22), 155(19),
137(25), 84(34), 55(15); Anal. Calcd for C17H20N2O4: C,
64.54; H, 6.37; N, 8.86. Found: C, 64.16; H, 6.45; N, 8.80.
(Z)-3-((E)-1-(benzyloxyimino)ethyl)-4-hydroxy-5-(4-hydrox-
ybenzylidene)-pyrroline-2-one (6j). Yellow crystal, mp 240.3–
241.9ꢁC; yield, 78.8%; IR (KBr, cmꢀ1) m 3359, 3349, 3169,
3018, 2796, 1658, 1601, 1579, 1561, 1272, 1056, 956; 1H-
NMR (DMSO-d6, 300 MHz) d: 2.32 (s, 3H, CH3C¼¼N), 5.13
(s, 2H, OCH2), 6.21 (s, 1H, CH¼¼), 6.73 (d, 2H, PhH, J ¼ 8.7
Hz), 7.33–7.45 (m, 7H, PhH), 9.71 (s, 1H, NH), 9.80 (s, 1H,
OH); MS m/z (%): 350(Mþ, 5), 244(100), 227(24), 133(17),
105(13), 84(33), 55(15); Anal. Calcd for C20H18N2O4: C,
68.56; H, 5.18; N, 8.00. Found: C, 68.92; H, 5.25; N, 8.08.
(Z)-4-hydroxy-5-(4-methoxybenzylidene)-3-((E)-1-(propoxyimi-
no)ethyl)-pyrroline-2-one (6k). Yellow powder, mp 174.0–
175.7ꢁC; yield, 86.8%; IR (KBr, cmꢀ1) m 3321, 3216, 2964,
2874, 1680, 1602, 1514, 1249, 1117, 1054, 1037, 928; 1H-
NMR (CDCl3, 300 MHz) d: 0.99 (t, 3H, CH2CH3, J ¼ 7.5
Hz), 1.71–1.80 (m, 2H, CH2CH3), 2.53 (s, 3H, CH3C¼¼N),
3.84 (s, 3H, PhOCH3), 4.00 (t, 2H, OCH2, J ¼ 7.2 Hz), 6.46
(s, 1H, CH¼¼), 6.93 (d, 2H, PhH, J ¼ 8.7 Hz), 7.36 (d, 2H,
PhH, J ¼ 8.7 Hz), 7.53 (s, 1H, NH). MS m/z (%): 316(Mþ, 6),
258(100), 202(22), 179(19), 137(25), 83(34), 45(15); Anal.
Calcd for C17H20N2O4: C, 64.54; H, 6.37; N, 8.86. Found: C,
64.89; H, 6.45; N, 8.94.
(Z)-4-hydroxy-3-((E)-1-(isopropoxyimino)ethyl)-5-(4-methoxy-
benzylidene)-pyrroline-2-one (6l). Yellow powder, mp 206.8–
208.0ꢁC; yield, 91.0%; IR (KBr, cmꢀ1) m 3320, 3207, 2979,
2835, 1687, 1602, 1517, 1253, 1187, 1115, 1036, 980; 1H-
NMR (CDCl3, 300 MHz) d:1.34 (d, 6H, CH(CH3)2, J ¼ 6.0
Hz), 2.55 (s, 3H, CH3C¼¼N), 3.84 (s, 3H, PhOCH3), 4.24–4.28
(m, 1H, OCH), 6.47 (s, 1H, CH¼¼), 6.93 (d, 2H, PhH, J ¼ 8.7
Hz), 7.36 (d, 2H, PhH, J ¼ 8.1 Hz), 7.56 (s, 1H, NH). MS m/z
(%): 316(Mþ, 5), 279(16), 202(36), 167(35), 149(100), 69(53),
57(56), 45(66); Anal. Calcd for C17H20N2O4: C, 64.54; H,
6.37; N, 8.86. Found: C, 64.82; H, 6.31; N, 8.77.
(Z)-3-((E)-1-(allyloxyimino)ethyl)-4-hydroxy-5-(4-methoxy-
benzylidene)-pyrroline-2-one (6m). Yellow powder, mp
168.7–169.7ꢁC; yield, 90.0%; IR (KBr, cmꢀ1) m 3323, 3202,
2981, 2835, 1677, 1602, 1568, 1514, 1255, 1183, 1037, 931;
1H-NMR (CDCl3, 300 MHz) d: 2.51 (s, 3H, CH3C¼¼N), 3.85
(s, 3H, PhOCH3), 4.55 (d, 2H, OCH2, J ¼ 6.0 Hz), 5.40–5.47
(m, 2H, CH¼¼CH2), 5.95–6.06 (m, 1H, CH¼¼CH2), 6.51 (s,
1H, CH¼¼C), 6.94 (d, 2H, PhH, J ¼ 9.0 Hz), 7.36 (d, 2H,
PhH, J ¼ 8.7 Hz), 7.69 (s, 1H, NH). MS m/z (%): 314(Mþ, 7),
258(100), 241(19), 148(20), 132(24), 83(18), 45(21); Anal.
Calcd for C17H18N2O4: C, 64.96; H, 5.77; N, 8.91. Found: C,
64.51; H, 5.72; N, 8.98.
(Z)-3-((E)-1-(allyloxyimino)ethyl)-5-benzylidene-4-hydroxy-
pyrroline-2-one (6d). Red powder, mp 170.2–171.3ꢁC; yield,
85.3%; IR (KBr, cmꢀ1) m 3328, 3218, 3030, 2936, 1681, 1621,
1564, 1452, 1269, 1088, 1005, 936; 1H-NMR (CDCl3, 300
MHz) d: 2.52 (s, 3H, CH3C¼¼N), 4.54 (d, 2H, OCH2, J ¼ 6.3
Hz), 5.40–5.48 (m, 2H, CH¼¼CH2), 5.95–6.08 (m, 1H,
CH¼¼CH2), 6.49 (s, 1H, CH¼¼C), 7.31–7.42 (m, 5H, PhH),
7.56 (s, 1H, NH); MS m/z (%): 284(Mþ, 24), 267(10),
213(18), 167(28), 149(100), 81(66), 69(68), 57(36); Anal.
Calcd for C16H16N2O3: C, 67.59; H, 5.67; N, 9.85. Found: C,
67.14; H, 5.72; N, 9.80.
(Z)-5-benzylidene-3-((E)-1-(butoxyimino)ethyl)-4-hydroxy-
pyrroline-2-one (6e). Yellow crystal, mp 158.9–159.5ꢁC;
yield, 82.3%; IR (KBr, cmꢀ1) m 3328, 3215, 3028, 2957, 2874,
1679, 1655, 1624, 1451, 1367, 1092, 1048, 973; 1H-NMR
(CDCl3, 300 MHz) d: 0.97 (t, 3H, CH2CH3, J ¼ 7.2 Hz),
1.41–1.54 (m, 2H, CH2CH3), 1.69–1.78 (m, 2H, OCH2CH2),
2.56 (s, 3H, CH3C¼¼N), 4.05 (t, 2H, OCH2, J ¼ 6.3 Hz), 6.50
(s, 1H, CH¼¼), 7.33–7.48 (m, 5H, PhH), 7.98 (s, 1H, NH); MS
m/z (%): 300(Mþ, 82), 228(100), 210(22), 172(20), 117(64),
90(48), 82(42), 45(46); Anal. Calcd for C17H20N2O3: C, 67.98;
H, 6.71; N, 9.33. Found: C, 68.25; H, 6.60; N, 9.43.
(Z)-5-benzylidene-3-((E)-1-(benzyloxyimino)ethyl)-4-hydroxy-
pyrroline-2-one (6f). Yellow powder, mp 201.7–202.5ꢁC;
yield, 90.5%; IR (KBr, cmꢀ1) m 3349, 3207, 3008, 2932, 1698,
1657, 1622, 1455, 1367, 1096, 995; 1H-NMR (CDCl3, 300
MHz) d: 2.45 (s, 3H, CH3C¼¼N), 5.07 (s, 2H, OCH2), 6.50 (s,
1H, CH¼¼), 7.30–7.42 (m, 10H, 2PhH), 7.50 (s, 1H, NH); MS
m/z (%): 334(Mþ, 18), 228(74), 210(14), 117(20), 115(26),
91(100), 77(22), 45(34); Anal. Calcd for C20H18N2O3: C,
71.84; H, 5.43; N, 8.38. Found: C, 72.19; H, 5.49; N, 8.30.
(Z)-3-((E)-1-(propoxyimino)ethyl)-4-hydroxy-5-(4-hydroxyben-
zylidene)-pyrroline-one (6g). Yellow powder, mp 225.2–
226.5ꢁC; yield, 80.0%; IR (KBr, cmꢀ1) m 3378, 3346, 3156,
1
2967, 1661, 1601, 1580, 1513, 1233, 1148, 1067, 935; H-NMR
(DMSO-d6, 300 MHz) d: 0.90 (t, 3H, CH2CH3, J ¼ 7.2 Hz),
1.57–1.69 (m, 2H, CH2CH3), 2.35 (s, 3H, CH3C¼¼N), 4.00 (t,
2H, OCH2, J ¼ 6.3 Hz), 6.21 (s, 1H, CH¼¼), 6.73 (d, 2H, PhH, J
¼ 8.4 Hz), 7.43 (d, 2H, PhH, J ¼ 8.1 Hz), 9.71 (s, 1H, NH),
9.78 (s, 1H, OH); MS m/z (%): 302(Mþ, 4), 244(100), 227(22),
133(22), 84(38), 55(20); Anal. Calcd for C16H18N2O4: C, 63.56;
H, 6.00; N, 9.27. Found: C, 63.37; H, 6.08; N, 9.20.
(Z)-3-((E)-1-(allyloxyimino)ethyl)-4-hydroxy-5-(4-hydroxyben-
zylidene)-pyrroline-2-one (6h). Red powder, mp 231.2–
232.4ꢁC; yield, 83.3%; IR (KBr, cmꢀ1) m 3363, 3348, 3159,
2982, 1662, 1598, 1513, 1274, 1234, 1152, 1065, 958; 1H-
NMR (DMSO-d6, 300 MHz) d: 2.33 (s, 3H, CH3C¼¼N), 4.60
(d, 2H, OCH2, J ¼ 5.7 Hz), 5.28–5.40 (m, 2H, CH¼¼CH2),
5.93–6.07 (m, 1H, CH¼¼CH2), 6.24 (s, 1H, CH¼¼C), 6.74 (d,
2H, PhH, J ¼ 8.4 Hz), 7.44 (d, 2H, PhH, J ¼ 8.1 Hz), 9.72 (s,
1H, NH), 9.81 (s, 1H, OH); MS m/z (%): 300(Mþ, 4), 271(14),
244(100), 226(22), 137(24), 84(52), 57(88); Anal. Calcd for
C16H16N2O4: C, 63.99; H, 5.37; N, 9.33. Found: C, 63.55; H,
5.29; N, 9.40.
(Z)-3-((E)-1-(butoxyimino)ethyl)-4-hydroxy-5-(4-methoxybenzy-
lidene)-pyrroline-2-one (6n). Yellow powder, mp 166.3–
167.0ꢁC; yield, 87.6%; IR (KBr, cmꢀ1) m 3319, 3186, 2956,
1685, 1604, 1514, 1253, 1176, 1067, 956; 1H-NMR (CDCl3,
300 MHz) d: 0.95 (t, 3H, CH2CH3, J ¼ 7.5 Hz), 1.39–1.52
(m, 2H, CH2CH3), 1.67–1.76 (m, 2H, OCH2CH2), 2.52 (s, 3H,
CH3C¼¼N), 3.84 (s, 3H, PhOCH3), 4.04 (t, 2H, OCH2, J ¼
(Z)-3-((E)-1-(butoxyimino)ethyl)-4-hydroxy-5-(4-hydroxyben-
zylidene)-pyrroline-2-one (6i). Yellow powder, mp 210.2–
211.2ꢁC; yield, 85.5%; IR (KBr, cmꢀ1) m 3386, 3351, 3189,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2010
Synthesis, Characterization, and Biological Activities of Novel
(Z)-3-((E)-1-(Alkyloxyimino)ethyl)-5-arylidene-4-hydroxypyrroline-2-one Derivatives
1333
6.6 Hz), 6.45 (s, 1H, CH¼¼), 6.92 (d, 2H, PhH, J ¼ 8.4 Hz),
7.37 (d, 2H, PhH, J ¼ 8.7 Hz), 7.66 (s, 1H, NH). MS m/z (%):
330(Mþ, 5), 258(100), 202(25), 147(24), 132(37), 83(24),
45(19); Anal. Calcd for C18H22N2O4: C, 65.44; H, 6.71; N,
8.48. Found: C, 65.94; H, 6.76; N, 8.40.
205.5ꢁC; yield, 91.3%; IR (KBr, cmꢀ1) m 3331, 3236, 3029,
2930, 1698, 1620, 1565, 1442, 1369, 1095, 1041, 995; 1H-
NMR (CDCl3, 300 MHz) d: 2.42 (s, 3H, CH3C¼¼N), 5.08 (s,
2H, OCH2), 6.67 (s, 1H, CH¼¼), 7.21–7.50 (m, 9H, PhH), 7.56
(s, 1H, NH); MS m/z (%): 368(Mþ, 2), 308(14), 153(100),
127(65), 98(74), 63(25), 50(11); Anal. Calcd for
C20H17ClN2O3: C, 65.13; H, 4.65; N, 7.60. Found: C, 65.54;
H, 4.72; N, 7.52.
(Z)-5-(4-chlorobenzylidene)-4-hydroxy-3-((E)-1-(propoxyi-
mino)ethyl)-pyrroline-2-one (6u). Yellow powder, mp 222.2–
223.8ꢁC; yield, 89.5%; IR (KBr, cmꢀ1) m 3336, 3208, 3024,
2968, 1685, 1656, 1617, 1433, 1385, 1275, 1093, 1010, 968;
1H-NMR (CDCl3, 300 MHz) d: 1.00 (t, 3H, CH2CH3, J ¼ 7.8
Hz), 1.74–1.81 (m, 2H, CH2CH3), 2.56 (s, 3H, CH3C¼¼N),
4.00 (t, 2H, OCH2, J ¼ 6.6 Hz), 6.44 (s, 1H, CH¼¼), 7.32–
7.40 (m, 4H, PhH), 7.47 (s, 1H, NH); MS m/z (%): 320(Mþ,
4), 262(100), 206(19), 152(30), 116(15), 89(32), 58(23),
45(26); Anal. Calcd for C16H17ClN2O3: C, 59.91; H, 5.34; N,
8.73. Found: C, 60.14; H, 5.42; N, 8.66.
(Z)-3-((E)-1-(benzyloxyimino)ethyl)-4-hydroxy-5-(4-methox-
ybenzylidene)-pyrroline-2-one (6o). Yellow powder, mp 205.8–
206.7ꢁC; yield, 77.2%; IR (KBr, cmꢀ1) m 3322, 3212, 2924,
1
2837, 1692, 1618, 1601, 1513, 1252, 1180, 1036, 990; H-NMR
(CDCl3, 300 MHz) d: 2.43 (s, 3H, CH3C¼¼N), 3.84 (s, 3H,
PhOCH3), 5.08 (s, 2H, OCH2), 6.40 (s, 1H, CH¼¼), 6.92 (d, 2H,
PhH, J ¼ 9.0 Hz), 7.34–7.40 (m, 7H, PhH), 7.56 (s, 1H, NH);
MS m/z (%): 364(Mþ, 4), 258(100), 243(22), 147(13), 132(14),
83(23), 45(18); Anal. Calcd for C21H20N2O4: C, 69.22; H, 5.53;
N, 7.69. Found: C, 69.58; H, 5.42; N, 7.60.
(Z)-5-(2-chlorobenzylidene)-4-hydroxy-3-((E)-1-(propoxyi-
mino)ethyl)-pyrroline-2-one (6p). Yellow powder, mp 164.7–
165.9ꢁC; yield, 82.3%; IR (KBr, cmꢀ1) m 3336, 3222, 2965,
2874, 1695, 1654, 1620, 1442, 1369, 1244, 1091, 989; 1H-
NMR (CDCl3, 300 MHz) d: 1.00 (t, 3H, CH2CH3, J ¼ 7.2
Hz), 1.74–1.81 (m, 2H, CH2CH3), 2.55 (s, 3H, CH3C¼¼N),
4.00 (t, 2H OCH2, J ¼ 6.6 Hz,), 6.72 (s, 1H, CH¼¼), 7.23–
7.47 (m, 4H, PhH), 7.60 (s, 1H, NH); MS m/z (%): 320(Mþ,
3), 285(31), 227(100), 210(73), 115(17), 83(16), 55(19); Anal.
Calcd for C16H17ClN2O3: C, 59.91; H, 5.34; N, 8.73. Found:
C, 61.23; H, 5.39; N, 8.83.
(Z)-5-(2-chlorobenzylidene)-4-hydroxy-3-((E)-1-(isopropoxyi-
mino)ethyl)-pyrroline-2-one (6q). Yellow powder, mp 187.7–
189.2ꢁC; yield, 85.7%; IR (KBr, cmꢀ1) m 3340, 3224, 2977,
2944, 1683, 1618, 1442, 1396, 1246, 1087, 1041, 985; 1H-
NMR (CDCl3, 300 MHz) d: 1.35 (d, 6H, CH(CH3)2, J ¼ 6.0
Hz), 2.56 (s, 3H, CH3C¼¼N), 4.22–4.31 (m, 1H, OCH), 6.72
(s, 1H, CH¼¼), 7.22–7.46 (m, 4H, PhH), 7.56 (s, 1H, NH); MS
m/z (%): 320(Mþ, 5), 285(100), 243(32), 227(43), 198(34),
89(46), 45(20); Anal. Calcd for C16H17ClN2O3: C, 59.91; H,
5.34; N, 8.73. Found: C, 61.35; H, 5.45; N, 8.78.
(Z)-3-((E)-1-(allyloxyimino)ethyl)-5-(2-chlorobenzylidene)-
4-hydroxy-pyrroline-2-one (6r). Yellow powder, mp 194.1–
196.5ꢁC; yield, 86.0%; IR (KBr, cmꢀ1) m 3331, 3195, 3027,
2911, 1705, 1660, 1623, 1440, 1347, 1249, 1097, 1044, 993;
1H-NMR (CDCl3, 300 MHz) d: 2.51 (s, 3H, CH3C¼¼N), 4.54
(d, 2H, OCH2, J ¼ 6.9 Hz), 5.41–5.48 (m, 2H, CH¼¼CH2),
5.95–6.08 (m, 1H, CH¼¼CH2), 6.71 (s, 1H, CH¼¼C), 7.22–7.48
(m, 4H, PhH), 7.76 (s, 1H, NH); MS m/z (%): 318(Mþ, 7),
283(27), 227(100), 210(68), 115(10), 89(15), 45(19); Anal.
Calcd for C16H15ClN2O3: C, 60.29; H, 4.74; N, 8.79. Found:
C, 60.01; H, 4.82; N, 8.64.
(Z)-5-(4-chlorobenzylidene)-4-hydroxy-3-((E)-1-(isopropox-
yimino)ethyl)-pyrroline-2-one (6v). Yellow powder, mp 231.3–
233.6ꢁC; yield, 81.2%; IR (KBr, cmꢀ1) m 3331, 3194, 3030,
1
2978, 1674, 1655, 1618, 1430, 1368, 1154, 1090, 985; H-NMR
(CDCl3, 300 MHz) d:1.34 (d, 6H, CH(CH3)2, J ¼ 6.3 Hz), 2.57
(s, 3H, CH3C¼¼N), 4.21–4.30 (m, 1H, OCH), 6.42 (s, 1H,
CH¼¼), 7.34–7.41 (m, 4H, PhH), 8.16 (s, 1H, NH); MS m/z (%):
320(Mþ, 10), 262(100), 206(48), 151(42), 129(32), 89(48),
58(63), 45(60); Anal. Calcd for C16H17ClN2O3: C, 59.91; H,
5.34; N, 8.73. Found: C, 59.47; H, 5.27; N, 8.61.
(Z)-3-((E)-1-(allyloxyimino)ethyl)-5-(4-chlorobenzylidene)-
4-hydroxy-pyrroline-2-one (6w). Yellow powder, mp 209.2–
209.9ꢁC; yield, 80.2%; IR (KBr, cmꢀ1) m 3327, 3205, 3028,
2919, 1694, 1655, 1619, 1430, 1365, 1266, 1092, 1010, 993;
1H-NMR (CDCl3, 300 MHz) d: 2.51 (s, 3H, CH3C¼¼N), 4.54
(d, 2H, OCH2, J ¼ 6.9 Hz), 5.41–5.47 (m, 2H, CH¼¼CH2),
5.95–6.08 (m, 1H, CH¼¼CH2), 6.41 (s, 1H, CH¼¼C), 7.34–7.41
(m, 4H, PhH), 8.05 (s, 1H, NH); MS m/z (%): 318(Mþ, 3),
262(100), 210(10), 152(25), 116(15), 83(32), 55(19), 45(31);
Anal. Calcd for C16H15ClN2O3: C, 60.29; H, 4.74; N, 8.79.
Found: C, 60.02; H, 4.70; N, 8.87.
(Z)-3-((E)-1-(butoxyimino)ethyl)-5-(4-chlorobenzylidene)-4-
hydroxy-pyrroline-2-one (6x). Yellow crystal, mp 203.3–
207.2ꢁC; yield, 92.4%; IR (KBr, cmꢀ1) m 3294, 3201, 3019,
1
2957, 1708, 1679, 1617, 1431, 1367, 1276, 1092, 1010, 974; H-
NMR (CDCl3, 300 MHz) d: 0.96 (t, 3H, CH2CH3, J ¼ 7.5 Hz),
1.40–1.52 (m, 2H, CH2CH3), 1.68–1.77 (m, 2H, OCH2CH2), 2.55
(s, 3H, CH3C¼¼N), 4.04 (t, 2H, OCH2, J ¼ 6.9 Hz), 6.44 (s, 1H,
CH¼¼), 7.33–7.40 (m, 4H, PhH), 7.70 (s, 1H, NH); MS m/z (%):
334(Mþ, 6), 262(100), 206(42), 152(45), 113(28), 84(59), 57(46),
45(88); Anal. Calcd for C17H19ClN2O3: C, 60.99; H, 5.72; N,
8.37. Found: C, 60.55; H, 5.79; N, 8.52.
Crystal structure determination. The single crystal of 6e
was selected and glued on the tip of a glass fiber. Both cell
dimensions and intensities were measured on a Bruker Smart
APEX CCD diffractometer with graphite monochromated Mo
(Z)-3-((E)-1-(butoxyimino)ethyl)-5-(2-chlorobenzylidene)-4-
hydroxy-pyrroline-2-one (6s). Yellow powder, mp 165.7–
166.9ꢁC; yield, 88.7%; IR (KBr, cmꢀ1) m 3285, 3200, 2958,
2872, 1685, 1652, 1624, 1441, 1369, 1246, 1049, 976; 1H-
NMR (CDCl3, 300 MHz) d: 0.96 (t, 3H, CH2CH3, J ¼ 7.2
Hz), 1.40–1.52 (m, 2H, CH2CH3), 1.67–1.77 (m, 2H,
OCH2CH2), 2.50 (s, 3H, CH3C¼¼N), 4.05 (t, 2H, OCH2, J ¼
7.5 Hz), 6.69 (s, 1H, CH¼¼), 7.21–7.50 (m, 4H, PhH), 7.57 (s,
1H, NH); MS m/z (%): 334(Mþ, 5), 299(25), 227(100),
210(88), 114(13), 89(17), 45(22); Anal. Calcd for
C17H19ClN2O3: C, 60.99; H, 5.72; N, 8.37. Found: C, 61.30;
H, 5.81; N, 8.42.
˚
Ka radiation (k ¼ 0.71073 A) at 296(2) K. ymax ¼ 25.99;
6205 measured reflections; 3113 independent reflections (Rint
¼ 0.0385) of which 2421 had I > 2d (I). Data was corrected
for Lorentz and polarization effects and absorption (Tmin
0.9781, Tmax ¼ 0.9831). Crystal structure was solved by direct
¼
(Z)-3-((E)-1-(benzyloxyimino)ethyl)-5-(2-chlorobenzylidene)-4-
hydroxy-pyrroline-2-one (6t). Yellow crystal, mp 205.0–
methods using the SHELXS-97 program [28]. All nonhydrogen
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1334
Z.-Y. Zhu, X.-F. Wang, F.-G. Meng, Q.-B. Li, X.-Q. Zheng, S. Qiang, and C.-L. Yang
Vol 47
[3] Satan, U.; Wada, S. I.; Matsunagas, S.; Watabe, S.; Vanso-
est, R. W. M.; Fusetanin, N. J Org Chem 1999, 64, 2331.
[4] Hopmann, C.; Kurz, M.; Bronstrup, M.; Wink, J.; LeBeller,
D. Tetrahedron Lett 2002, 43, 435.
atoms were refined anisotropically. The CAH hydrogen atoms
were positioned geometrically and refined using a riding
model. The hydrogen atoms linked to nitrogen and oxygen
were located from the difference Fourier map and were set as
isotropic. Full-matrix least squares refinement based on F2
[5] Aoki, S.; Higuchi, K.; Ye, Y.; Satari, R.; Kobayashi, M.
Tetrahedron 2000, 56, 1833.
2
using the weight of 1/[r2(Fo ) þ (0.1206P)2 þ 0.0717P] gave
[6] Ohta, E.; Ohta, S.; Ikegami, S. Tetrahedron 2001, 57, 4699.
[7] Motta, S. D.; Soares, L. M. V. Food Chem 2000, 71, 111.
[8] Rosett, B. T.; Sankhala, R. H.; Stickings, C. E.; Taylor, M.
E. U.; Thomas, R. Biochem J 1957, 67, 390.
final values of R ¼ 0.0575, xR ¼ 0.1770, and GOF(F) ¼
1.044. The maximum and minimum difference peaks and holes
were 0.352 and –0.381 e Aꢀ3, respectively.
˚
The crystallographic data have been deposited with Cam-
bridge crystallographic data center, CCDC No. 734371. Copies
of this information can be obtained free of charge from the
Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK
(fax: þ44 1223 336 033; or E-mail: deposit@ccdc.cam.ac.uk).
Fungicidal assay. Inhibition effects of the title compounds
6a–x on phytopathogenic fungi (Fusarium gramineaum, Colleto-
trichum orbiculare, and Rhizoctonia cerealis) were tested using a
radial growth inhibition technique according to literature [29].
Each compound was diluted with 0.5 mL DMF and added to
potato sucrose agar medium (PSA), respectively to obtain a con-
centration of 100 lg/mL immediately before pouring into the pe-
tri dishes. Each concentration was tested in triplicate. Parallel
controls were maintained with 0.5 mL DMF mixed with PSA
medium. The discs of mycelial felt (0.5 cm diameter) of fungi
were transferred aseptically to the center of Petri dishes. The
treatments were incubated at 25ꢁC in the dark. The diameter of
the mycelium was measured after the fungal growth in the con-
trol treatments had covered two-thirds of the Petri dishes. The
growth inhibition rates were calculated with the following equa-
tion: I ¼ [(C ꢀ T)/C] ꢃ 100%. Here, I was the growth inhibition
rate (%), C was the control settlement radius (mm), and T was
the treatment group fungi settlement radius (mm).
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the National High Technology Research and Development Pro-
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and Technology Development Foundation of Nanjing Agricultural
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet