Synthesis and antifungal activity of novel 2-benzimidazolylimino-5- arylidene-4-thiazolidinones

Article abstract of DOI:10.1002/jhet.264

(Chemical Equation Presented) A series of 5-arylidene derivatives 3a-k, as potential antifungal agents, were synthesized in good to high yields by the reaction of 2-benzimidazolylimino-4-thiazolidinone and corresponding aromatic aldehyde in a buffered med

Full text of DOI:10.1002/jhet.264

January 2010
Synthesis and Antifungal Activity of Novel
-Benzimidazolylimino-5-arylidene-4-thiazolidinones
77
2
a
Akbar Mobinikhaledi, * Naser Foroughifar, Mehdi Kalhor,
a
a
b
and Mansoureh Mirabolfathy
a
Department of Chemistry, Arak University, Arak 38156-879, Iran
b
Iranian Plant Protection Research Institute, Tehran 19395, Iran
*
E-mail: akbar_mobini@yahoo.com
Received July 8, 2009
DOI 10.1002/jhet.264
Published online 29 December 2009 in Wiley InterScience (www.interscience.wiley.com).
A series of 5-arylidene derivatives 3a-k, as potential antifungal agents, were synthesized in good to
high yields by the reaction of 2-benzimidazolylimino-4-thiazolidinone and corresponding aromatic alde-
hyde in a buffered medium. These compounds were evaluated for their antifungal activities against four
agricultural fungi, Botrytis elliptica, Fusarium graminearum, Phytophthora nicotianae, and Rhizoctonia
solani. Thereby, it was found that the compound 1 exhibits an antifungal effect against P. nicotianae
and B. elliptica, comparable with carbendazim as a standard antifungal. Our results may provide some
guidance for development of some novel benzimidazole-based antifungal lead structures.
J. Heterocyclic Chem., 47, 77 (2010).
INTRODUCTION
of these compounds was investigated against some agri-
cultural fungi.
Thiazolidin-4-ones constitute an important class of het-
erocyclic compounds because of their broad range of bio-
logical activities [1–5]. It is also well known that thiazoli-
din-4-ones have antifungal activity [6–9] and are used as a
new class of potent anti-HIV-1 agents with marked
reverse transcriptase (RT) inhibitory effects [10,11].
RESULTS AND DISCUSSION
Compound 1, N-(1H-benzimidazol-2-yl)-2-chloroacta-
mide, was synthesized from 2-amino benzimidazole
using a variation of the reported procedure [9]. The
compound 1 on heterocyclization in the presence of am-
monium thiocyanate in refluxing ethanol (96%) effi-
ciently produced compound 2 without any further purifi-
cation [5]. Compounds 3a–k were obtained by refluxing
2 with corresponding aromatic aldehydes in buffered
glacial acetic acid (Scheme 1). Compound 3k was selec-
tively obtained by the reaction of 2 with an aromatic
dialdehyde. The presence of an aldehyde group in the
phenyl ring of the product was evidently confirmed by
Benzimidazole derivatives are also of wide interest
because of their diverse biological activities, such as
anticancer, antiproliferative, antiviral, and platelet-anti-
aggregating agents [12–16]. Benzimidazoles containing
a subunit group, especially a methyl carbamate group on
position C(2) (Carbendazim), are found as potential anti-
fungal agent for plants [17]. Because of the aforemen-
tioned findings and also because of the incessant interest
in the chemistry and antimicrobial activity of benzimi-
dazoles, substantial attention should be paid to the syn-
thesis of novel benzimidazole derivatives especially ben-
zimidazolyl substituted 2-iminiothiazolidin-4-ones. In
view of these reports, we extended our research for the
synthesis of a novel class of benzimidazole substituted
1
H NMR, Ms, and infrared (IR) data. Finally, compound
4 was synthesized by refluxing 1 in the presence of
K CO in acetone. All new compounds were character-
2
3
1
13
ized using spectroscopy data (IR, H, and C NMR).
Compounds 2 and 3a–k exist as lactam forms on the
basis of the mechanism suggested by Vicini et al. [18].
This mechanism is more reasonable than that one led to
2
2
-iminiothiazolidin-4-ones resulting from the reaction of
-(1H-benzimidazol-2-ylamino)-1,3-thiazol-4(5H)-one 2
with various aromatic aldehydes. The antifungal activity
V
C
2009 HeteroCorporation

7
8
A. Mobinikhaledi, N. Foroughifar, M. Kalhor, and M. Mirabolfathy
Vol 47
Scheme 1. Conditions: (a) Acetone, 2 h, reflux. (b) NH
EtOH, 8 h, reflux. (c) AcOH, AcONa, 3–10 h, reflux. (d) Acetone,
CO , 4 h, reflux.
4
SCN, 96%
Table 1
Antifungal activity studies by the agar growth medium poison
a
technique.
K
2
3
Phytophthora Botrytis Rhizoctonia Fusarium
Compound nicotianae elliptica
solani
graminearum
1
2
3
3
3
3
3
3
3
3
3
3
3
4
100
58
0
100
50
0
0
40
0
a
b
c
d
e
f
g
h
i
28
100
33
50
33
0
0
0
0
0
0
15
0
0
0
20
0
0
0
5
25
0
100
50
0
0
30
0
33
57
0
0
0
0
0
j
k
0
57
50
0
0
6
10
0
15
30
0
64
100
0
100
b
MBC
100
a
The results are reported as a percentage (%) inhibition of the fungi
growth, and the concentration of the tested compounds was 50 ppm.
the formation of an imine structure 5 as shown in
1
Scheme 2 [9]. In H NMR spectra of compounds 2 and
b
Carbendazim as a reference.
3
a–k, the resonance of two NH protons at 12.13 and
1
2.37–12.85 ppm are in support of the lactam form,
because an imine proton appears at much higher field
3f also completely inhibit the growth of B. elliptica.
Although, all of the compounds have the inhibiting
effect against B. elliptical, no Rhizoctonia solani have.
The other results are briefly mentioned in Table 1. It
may also be noticed that introduction of benzylidene
group at C-5 decreased the fungicidal activity.
1
about 9.70) [19,20]. The H NMR and IR spectroscopy
(
data (the absence signal of an OH group) is in agree-
ment with a c-lactam, confirm the 2 and 2 tautomeric
forms in the solid and liquid states (Scheme 2).
a
b
Compounds (1, 2, 3a–k, 4) were tested for fungicidal
activity against four agricultural fungi. The results (Ta-
ble 1) show that the compounds 1 and 2 have higher
antifungal activity than others and are comparable with
carbendazim. The more interesting result could be
observed in the treatment of compound 1, which could
completely inhibit the growth of Phytophthora nicotia-
nae and Botrytis elliptica isolates. Compounds 3b and
In conclusion, we have described the synthesis of 2-
benzimidazolylimino-5-arylidene-4-thiazolidinones, 3a–k
by the reaction of 2-benzimidazolylimino-4-thiazolidi-
none, 2 and corresponding aromatic aldehydes in a buf-
fered medium with good to high yields. We also evaluated
their antifungal activities against four agricultural fungi.
EXPERIMENTAL
Scheme 2
All used chemicals were prepared from Merck or Fluka
Company. Melting points were determined using an electro
thermal digital apparatus and are uncorrected. IR spectra were
performed on a Galaxy series FT IR 5000 spectrometer using
KBr discs. NMR spectra were recorded on a Bruker (300
MHz) spectrometer. Chemical shifts (ppm) were referenced to
the internal standards tetramethylsilane. Elemental analyses
were performed on a Vario EL III elemental analyzer. Reac-
tions were monitored by thin layer chromatography (TLC).
Synthesis of N-(1H-benzimidazol-2-yl)-2-chloroactamide
(
1). A solution of 2-amino benzimidazole (4.0 g, 0.03 mole) in
ꢀ
dry acetone (40 mL) was cooled to 0–5 C. A solution of chlor-
oacetyl chloride (4.78 mL, 0.06 mole) in dry acetone (15 mL)
was slowly added to it with vigorous stirring. The reaction
mixture was refluxed for 2 h, and the solvent was removed
under reduced pressure. The residue was washed with sodium
bicarbonate (5%) and subsequently with water. The crude
product was air dried and crystallized from ethanol to give the
ꢀ
colorless crystals 1, 4.1 g (65%), mp 219–222 C; R
f
(ethyl
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2010
Synthesis and Antifungal Activity of Novel
-Benzimidazolylimino-5-arylidene-4-thiazolidinones
79
2
acetate/hexane 3:1) 0.65; IR (KBr): 3333 (NH), 3055 (CH),
966 (CH
), 1685 (C ¼¼ O), 1633, 1583 (C ¼¼ N), 1456 (C ¼¼ C)
cm ; H NMR (DMSO-d , 300 MHz): d 4.37 (s, 2H, CH ),
.09–7.13 (m, 2H, H-Ar ), 7.43–7.46 (q, 2H, H-Ar), 12.08 (s,
(KBr): 3138 (NH), 3063 (CH-Ar), 1695 (C ¼¼ O), 1618, 1581
ꢁ
1 1
2
.
(C ¼¼ N), 1469, 1350, 1251 (C ¼¼ C) cm ; H NMR (DMSO-d
6
,
ꢁ
1 1
6
2
300 MHz): d 7.15–7.63 (m, 9H, H-Ar and C ¼¼ CH-Ar), 12.40–
1
3
7
2
1
12.85 (br., s, 2H, NH); C NMR (DMSO-d , 75 MHz): d
.
6
13
H, NH); C NMR (DMSO-d , 75 MHz): d 43.9 (CH ),
112.9, 122.3, 124.1, 127.3, 127.9, 129.2, 129.7, 131.3, 132.8,
134.2, 137.2, 150.3 (C ¼¼ N), 179.2 (C ¼¼ N), 180.9 (C ¼¼ O).
6
2
14.3, 121.9, 135.7, 147.4 (C ¼¼ N), 167.7 (C ¼¼ O). Anal. Calcd.
for C
H, 3.82; N, 20.14.
9
H
8
ClN O: C, 51.56; H, 3.85; N, 20.04. Found: C, 51.45;
3
4
Anal. Calcd. for C17H11ClN OS: C, 57.55; H, 3.12; N, 15.79;
S, 9.04. Found: C, 57.33; H, 3.17; N, 15.58; S, 9.14.
2-(1H-Benzimidazol-2-ylamino)-5-(4-chlorobenzylidene)-1,
3-thiazol-4(5H)-one (3d). This compound was obtained by
Synthesis of 2-(1H-benzimidazol-2-ylamino)-1,3-thiazol-
(5H)-one (2). A solution of compound 1 (3.0 g, 0.01 mole)
4
ꢀ
and ammonium thiocyanate (1.96 g, 0.02 mole) in 50 mL of
ethanol (96%) was refluxed for 8 h and allowed to stand for
refluxing for 8 h to yield 0.16 g (52%), mp 337 C; IR (KBr):
3421, 3308 (NH), 3053 (CH-Ar), 1676 (C ¼¼ O), 1618, 1574
ꢁ
1 1
(C ¼¼ N), 1473, 1350, 1259 (C ¼¼ C) cm ; H NMR (DMSO-d ,
2
and recrystallized from dioxane/water to give light yellow
h. The precipitate was filtered, washed with aqueous ethanol,
6
300 MHz): d 7.15–7.69 (m, 9H, H-Ar. and C ¼¼ CH-Ph), 12.39
ꢀ
13
(s, 1H, NH), 12.75 (br., s, 1H, NH); C NMR (DMSO-d , 75
crystals 2 to yield 2.7 g (81%), mp 284 C; R (ethylacetate/
f
6
hexane 3:1) 0.5; IR (KBr): 3138 (NH), 3065 (CH-Ar
(
.
), 2926
ꢁ
MHz): d 112.9, 124.1, 127.6, 129.6, 129.7, 131.5, 132.1,
133.8, 134.1, 150.3 (C ¼¼ N), 179.3 (C ¼¼ N), 181.1 (C ¼¼ O).
Anal. Calcd. for C H ClN OS: C, 57.55; H, 3.12; N, 15.79;
1
CH), 1697 (C ¼¼ O), 1620, 1581 (C ¼¼ N), 1352 (C ¼¼ C) cm
;
1
H NMR (DMSO-d , 300 MHz): d 3.96 (s, 2H, CH ), 7.12–
6
2
17 11
4
7
appeared on D
.49 (m, 4H, H-Ar ), 12.13 (br., 2H, NH); the NH protons dis-
, 75 MHz): d
S, 9.04. Found: C, 57.43; H, 3.07; N, 15.78; S, 9.09.
2-(1H-Benzimidazol-2-ylamino)-5-(3-bromobenzylidene)-1,
3-thiazol-4(5H)-one (3e). This compound was obtained by
.
1
O addition; C NMR (DMSO-d
3
2
6
3
5.2 (CH
2
), 112.7, 121.8, 142.6, 152.2 (C ¼¼ N), 164.6 (C ¼¼ N),
ꢀ
1
74.7 (C ¼¼ O). Anal. Calcd. for C10
H
8
N
4
OS: C, 51.71; H, 3.47;
refluxing for 5 h to yield 0.26 g (75%), mp 306–307 C; IR
N, 24.12; S, 13.81. Found: C, 51.58; H, 3.51; N, 24.22; S,
3.80.
General procedure for the synthesis of compounds (3). A
well-stirred solution of compound 2 (0.2 g, 0.86 mmole) in 4–
(KBr): 3192 (NH), 3068 (CH-Ar), 1699 (C ¼¼ O), 1622, 1585
ꢁ
; H NMR (DMSO-d , 300
6
1 1
1
(C ¼¼ N), 1481, 1251 (C ¼¼ C) cm
MHz): d 7.16–7.88 (m, 9H, H-Ar. and C ¼¼ CH-Ar), 12.79 (br.,
13
6
s, 2H, NH); C NMR (DMSO-d , 75 MHz): d 112.8, 122.8,
6
2
mL of acetic acid was buffered with sodium acetate (0.2 g,
.58 mmole) and added the appropriate arylaldehyde (1.7
124.1, 127.2, 128.3, 129.7, 131.6, 132.1, 136.5, 137.4, 150.2,
153.1 (C ¼¼ N), 179.2 (C ¼¼ N), 180.8 (C ¼¼ O). Anal. Calcd. for
C H BrN OS: C, 51.14; H, 2.78; N, 14.03; S, 8.03. Found:
mmole). The solution was refluxed for desired time. The com-
pletion of the reaction was monitored by TLC (toluene/diox-
ane/acetic acid 18:2:1). The reaction mixture was then cooled
to room temperature to produce the precipitate. The precipitate
was filtered, abundantly washed with water, and then recrystal-
lized from dioxane or dioxane/water to give the pure crystals
17
11
4
C, 51.34; H, 2.76; N, 14.12; S, 7.99.
2-(1H-Benzimidazol-2-ylamino)-5-(4-bromobenzylidene)-1,
3-thiazol-4(5H)-one (3f). This compound was obtained by
ꢀ
refluxing for 10 h to yield 0.28 g (85%), mp 325–327 C; IR
(KBr): 3217, 3136 (NH), 3026 (CH-Ar), 1691 (C ¼¼ O), 1633,
ꢁ
1
1
(
3a–k).
1609 (C ¼¼ N), 1487, 1350, 1257 (C ¼¼ C) cm
;
H NMR
2
5H)-one (3a). This compound was obtained by refluxing for
-(1H-Benzimidazol-2-ylamino)-5-benzylidene-1,3-thiazol-4
(DMSO-d
6
, 300 MHz): d 7.02–7.95 (m, 9H, H-Ar and C ¼¼ CH-
1
Ar), 12.40 (s, 1H, NH), 12.78 (br., s, 1H, NH); C NMR
3
(
ꢀ
7
h to yield 0.26 g (96%), mp 326–327 C; IR (KBr): 3138
(DMSO-d , 75 MHz): d 112.9, 123.0, 124.1, 127.7, 129.7,
6
(
NH), 3067 (CH-Ar), 1697 (C ¼¼ O), 1618, 1581 (C ¼¼ N), 1454,
131.7, 132.3, 132.5, 134.2, 150.3 (C ¼¼ N), 179.3 (C ¼¼ N), 181.0
ꢁ
1 1
1
7
1
1
(
C
352, 1253 (C ¼¼ C) cm ; H NMR (DMSO-d
6
, 300 MHz): d
(C ¼¼ O). Anal. Calcd. for C17
4
H11BrN OS: C, 51.14; H, 2.78; N,
.14–7.71 (m, 10H, H-Ar and C ¼¼ CH-Ph), 12.38 (s, 1H, NH),
14.03; S, 8.03. Found: C, 50.91; H, 2.75; N, 14.02; S, 8.05.
2-(1H-Benzimidazol-2-ylamino)-5-(3-nitrobenzylidene)-1,3-
thiazol-4(5H)-one (3g). This compound was obtained by
1
3
2.75 (s, 1H, NH); C NMR (DMSO-d , 75 MHz): d 112.9,
6
21.8, 124.1, 129.1, 129.6, 129.9, 130.5, 133.8, 134.1, 150.3
ꢀ
C ¼¼ N), 179.3 (C ¼¼ N), 181.2 (C ¼¼ O). Anal. Calcd. for
OS: C, 63.73; H, 3.78; N, 17.49; S, 10.01. Found: C,
4.01; H, 3.81; N, 17.39; S, 10.00.
-(1H-Benzimidazol-2-ylamino)-5-(2-chlorobenzylidene)-1,
refluxing for 3 h to yield 0.28 g (90%), mp 333 C; IR (KBr):
3138 (NH), 3068 (CH-Ar), 1716 (C ¼¼ O), 1655, 1620 (C ¼¼ N),
17
H
12
N
4
ꢁ
1
1
6
1531, 1352 (NO2), 1464, 1265 (C ¼¼ C) cm
;
H NMR
2
(DMSO-d , 300 MHz): d 7.17–8.55 (m, 9H, H-Ar and C ¼¼ CH-
6
1
3
3
refluxing for 6 h to yield 0.16 g (52%), mp 304 C; IR (KBr):
3
1
-thiazol-4(5H)-one (3b). This compound was obtained by
ꢀ
Ar), 12.43 (s, 1H, NH), 12.85 (br., s, 1H, NH); C NMR
(DMSO-d , 75 MHz): d 112.9, 123.8, 124.2, 126.4, 129.7,
131.0, 134.0, 135.7, 136.7, 148.6, 150.1, 172.5 (C ¼¼ N), 178.9
S: C,
6
151 (NH), 3063 (CH-Ar), 1695 (C ¼¼ O), 1622, 1589 (C ¼¼ N),
ꢁ
6
1
;
1
471, 1352, 1255 (C ¼¼ C) cm
H NMR (DMSO-d
, 300
(C ¼¼ N), 180.8 (C ¼¼ O). Anal. Calcd. for C17
11 5 3
H N O
MHz): d 7.15–7.68 (m, 8H, H-Ar), 7.87 (s, 1H, C ¼¼ CH-Ar),
55.88; H, 3.03; N, 19.17; S, 8.78. Found: C, 55.80; H, 3.05;
N, 19.19; S, 8.75.
1
3
1
d
1
(
5
2.42 (s, 1H, NH), 12.92 (br., s, 1H, NH); C-NMR (DMSO-
(CD SO, 75 MHz): 112.9, 123.8, 124.2, 128.4, 129.0,
29.7, 130.6, 131.1, 131.9, 132.9, 134.6, 150.1 (C ¼¼ N), 179.3
6
3
)
2
2-(1H-Benzimidazol-2-ylamino)-5-(4-nitrobenzylidene)-1,3-
thiazol-4(5H)-one (3h). This compound was obtained by
ꢀ
C ¼¼ N), 180.7 (C ¼¼ O). Anal. Calcd. for C H ClN OS: C,
refluxing for 10 h to yield 0.30 g (96%), mp 353 C; IR (KBr):
3148 (NH), 3076 (CH-Ar), 1705 (C ¼¼ O), 1631, 1599 (C ¼¼ N),
1
7
11
4
7.55; H, 3.12; N, 15.79; S, 9.04. Found: C, 57.79; H, 3.16;
ꢁ
1 1
N, 15.88; S, 9.13.
-(1H-Benzimidazol-2-ylamino)-5-(3-chlorobenzylidene)-1,
3
refluxing for 4 h to yield 0.26 g (85%), mp 320–322 C; IR
1512, 1342 (NO ) cm ; H NMR (DMSO-d , 300 MHz): d
2
6
2
-thiazol-4(5H)-one (3c). This compound was obtained by
7.16–8.32 (m, 9H, H-Ar and C ¼¼ CH-Ar), 12.42 (s, 1H, NH),
6
1
3
12.92 (s, 1H, NH); C NMR (DMSO-d
124.1, 124.5, 126.2, 129.6, 130.6, 135.6, 141.4, 146.9, 150.1
, 75 MHz): d 112.9,
ꢀ
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

8
0
A. Mobinikhaledi, N. Foroughifar, M. Kalhor, and M. Mirabolfathy
Vol 47
(
C ¼¼ N), 178.9 (C ¼¼ N), 180.7 (C ¼¼ O). Anal. Calcd. for
S: C, 55.88; H, 3.03; N, 19.17; S, 8.78. Found: C,
6.07; H, 3.02; N, 19.20; S, 8.80.
-(1H-Benzimidazol-2-ylamino)-5-(4-methylbenzylidene)-1,
using the agar growth medium poison technique [8]. The me-
dium was potato dextrose agar, and the concentration of the
tested compounds was 50 ppm. After 5 days incubation at
17 11 5 3
C H N O
5
ꢀ
2
25 C, the growth diameter of treatments was measured, and
3
refluxing for 9 h to yield 0.15 g (52%), mp 331 C; IR (KBr):
-thiazol-4(5H)-one (3i). This compound was obtained by
ꢀ
the percentage inhibition of growth for each compound was
determined based on the negative control growth of each fun-
gal species under the same incubation conditions. Carbendazim
as a reference was included to compare with compounds (1, 2,
3a–k, and 4). All tests were performed in triplicate and the av-
erage results, as a percentage (%) inhibition of growth, are
shown in Table 1.
3
1
217, 3144 (NH), 3043 (CH-Ar), 2943 (Me), 1685 (C ¼¼ O),
ꢁ
1
1
620, 1533 (C ¼¼ N), 1444, 1273 (C ¼¼ C) cm
;
H NMR
(
DMSO-d , 300 MHz): d 2.35 (s, 1H, CH ), 7.15–7.67 (m, 9H,
6 3
H-Ar and C ¼¼ CH-Ar), 12.37 (s, 1H, NH), 12.70 (br., s, 1H,
1
3
NH); C NMR (DMSO-d
18.5, 121.8, 124.1, 150.4, 129.8, 130.6, 131.8, 139.7, 157.4
C ¼¼ N), 179.5 (C ¼¼ N), 181.2 (C ¼¼ O). Anal. Calcd. for
C H N OS: C, 64.65; H, 4.22; N, 16.75; S, 9.59. Found: C,
6 3
, 75 MHz): d 21.5 (CH ), 112.8,
1
(
Acknowledgment. We thank the Chemistry Department of Arak
University for providing of financial supports and the Department
of Plant Diseases of Iranian Plant Protection Research Institute
for the evaluating of biological activities.
1
8 14 4
6
4.93; H, 4.23; N, 16.78; S, 9.56.
-(1H-Benzimidazol-2-ylamino)-5-(3-methoxybenzylidene)-
2
,3-thiazol-4(5H)-one (3j). This compound was obtained by
1
refluxing for 5 h to yield 0.24 g (80%), mp 271–272 C; IR
ꢀ
(
(
1
3
1
KBr): 3200, 3148 (NH), 3045 (CH-Ar), 2960 (Me), 1695
1
REFERENCES AND NOTES
ꢁ
C ¼¼ O), 1640, 1620 (C ¼¼ N), 1533, 1448, 1352 (C ¼¼ C) cm
;
1
273, 1228 (OMe); H NMR (DMSO-d
6
, 300 MHz): d 3.81 (s,
[1] Gaikwad, N. J.; Tirpude, R. N. Indian Drugs 1994, 31, 593.
[2] Diurno, M. V.; Mazzoni, O.; Piscopo, E.; Calignano, A.;
Giordano, F.; Bolognese, A. J Med Chem 1992, 35, 2910.
H, OMe), 6.98–7.68 (m, 9H, H-Ar and C ¼¼ CH-Ar), 12.39 (s,
1
H, NH), 12.74 (br., s, 1H, NH); C NMR (DMSO-d , 75
3
6
[3] Kouznetsov, V.; Rodrıguez, W.; Stashenko, E.; Ochoa, C.;
´
Vega, C.; Rol o´ n, M.; Pereira, D. M.; Escario, J. A.; Barrio, A. G. J
Heterocycl Chem 2004, 41, 995.
MHz): d 55.6 (OMe), 112.8, 115.4, 116.2, 122.3, 124.1, 129.7,
1
29.0, 129.7, 130.8, 131.3, 150.3, 160.0 (C ¼¼ N), 179.5 (C ¼¼ N),
1
81.1 (C ¼¼ O). Anal. Calcd. for C18 S: C, 61.70; H, 4.03;
14 4 2
H N O
[
4] Ramla, M. M.; Omar, A. M.; Tokudo, H.; El-Diwoni, I. H.
Bioorg Med Chem 2007, 15, 6489.
5] Vicini, P.; Geronikaki, A.; Incerti, M.; Zani, F.; Dearden,
J.; Hewitt, M. Bioorg Med Chem 2008, 16, 3714.
N, 15.99; S, 9.15. Found: C, 62.02; H, 4.00; N, 15.87; S, 9.10.
-{[2-(1H-Benzimidazol-2-ylamino)-4-oxo-1,3-thiazol-5(4H)-
ylidene]methyl} benzaldehyde (3k). This compound was
4
[
obtained by refluxing for 3 h to yield 0.27 g (90%). mp 339–
[
[
6] Lakhan, R.; Singh, O. P. J Ind Chem Soc 1984, 61, 784.
7] Bhargava, P. N.; Prakash, S.; Lakhan, R. Ind J Chem 1981,
ꢀ
3
2
1
7
1
1
41 C; IR (KBr): 3452, 3221 (NH), 3065 (CH-Ar), 2785,
885 (CH, aldehyde), 1691 (C ¼¼ O), 1622, 1589 (C ¼¼ N), 1481,
2
5
0B, 927.
ꢁ
1 1
350, 1261 (C ¼¼ C) cm ; H NMR (DMSO-d , 300 MHz): d
6
[
[
8] Lokhan, R. Agric Biol Chem 1982, 46, 557.
9] Hui-ling, L.; Zongcheng, L.; Thorleif, A. Molecules 2000,
.17–8.02 (m, 9H, H-Ar and C ¼¼ CH-Ar), 10.03 (s, 1H, CHO),
þ
2.85–12.94 (br., s, 2H, NH); MS (m/z, %): 348 (M , 100),
59 (92), 133 (15), 105 (12), 89 (24). Anal. Calcd. for
, 1055.
10] Barreca, M. L.; Balzarini, J.; chimirri, A.; De-clercq, E.;
[
C H N O S: C, 62.06; H, 3.47; N, 16.08; S, 9.20. Found: C,
12
18
4
2
De-luca, L.; Holtje, H. D.; Holtje, M.; Monforte, A. M.; Monforte, P.;
Pannecouque, C.; Rao, A.; Zappala, M. J Med Chem 2002, 45, 5410.
[11] Rao, A.; Balzarini, J.; Carbone, A.; chimirri, A.; De-clercq,
E.; Monforte, A. M.; Monforte, P.; Ponnecouque, C.; Zappala, M. Il
Farmaco 2004, 59, 33.
6
2.37; H, 3.45; N, 16.17; S, 9.17.
Synthesis of 1H-imidazo[1,2-a]benzimidazol-2(3H)-one
(4). To a well-stirred solution of compound 1 (0.4 g, 2 mmole)
in dry acetone (30 mL), K CO (0.32 g, 2 mmole) was added.
2
3
The reaction mixture was refluxed for 4 h. The result solid
was filtered, and water (5 mL) was added to the filtration to
give compound 4, which then filtered and washed with water
[12] (a) Desai, G. K.; Desai, R. K. J Saudi Chem Soc 2006, 9,
631; (b) Desai, G. K.; Desai, R. K. J Sulfur Chem 2006, 27, 315; (c)
Desai, G. K.; Desai, R. K. Bioorg Med Chem 2006, 14, 8271.
[13] Andrzejewska, M.; Mulia, L. Y.; Rivera, R. C.; Tapia, A.;
Vilpo, L.; Kazimierezuk, Z. Eur J Med Chem 2002, 37, 973.
[14] Ottana, R.; Carotti, S.; Maccari, R.; Landini, I.; Chiricosta,
G.; Cacigli, B.; Vigorita, G. M.; Mini, E. Bioorg Med Chem Lett
ꢀ
and air dried to yield 0.16 g (50 %); mp 216–219 C; IR
(
2
KBr): 3358 (NH), 3051 (CH-Ar), 2991, 2930 (CH ), 1666
ꢁ
1
1
; H
(
C ¼¼ O), 1585, 1527 (C ¼¼ N), 1448, 1336 (C ¼¼ C) cm
NMR (DMSO-d , 300 MHz): d 4.90 (s, 2H, CH ), 7.10–7.42
6
2
2005, 15, 3930.
(
m, 4H, H-Ar), 12.51 (br. s, 1H, NH); The NH proton disap-
1
3
[15] Tonelli, M.; Paglietti, G.; Boido, V.; Marongiu, F.; Maron-
2 6
peared on D O addition; C NMR (DMSO-d , 75 MHz): d
giu, E.; Colla, P. L.; Loddo, R. Chem Biodiv 2008, 5, 2386.
16] Vazzana, I.; Terranova, E.; Tasso, B.; Tonelli, M.; Piana,
A.; Gastaldi, S.; Sparatore, F. Chem Biodiv 2008, 5, 714.
17] Clemons, G. P.; Sisler, H. D. Pestic Biochem Physiol 1971,
, 32.
18] Vicini, P.; Geronikaki, A.; Anastasia, K.; Incerti, M.; Zani,
F. Bioorg Med Chem 2006, 14, 3859.
19] Ottana, R.; Maccari, R.; Barreca, M. L.; Bruno, G.;
4
2
7.6 (CH ), 110.6, 112.3, 121.8, 123.1, 129.4, 130.4, 147.6,
[
1
75.2 (C ¼¼ O). Anal. Calcd. for C H N O: C, 62.42; H, 4.07;
9
7 3
N, 24.27. Found: C, 62.22; H, 4.08; N, 24.32.
Antifungal assays. Fungicidal activity of compounds (1, 2,
[
1
3
a–k, and 4) were tested against four phytopathogenic fungal
[
isolates, including B. elliptica, Fusarium graminearum, P. nic-
otianae, and R. solani, provided by Department of Plant dis-
eases of Iranian Plant Protection Research Institute in vitro.
Two negative controls: one with DMSO, the solvent of all
tested compounds (no antifungal activity has been noted) and
the other as untreated potato dextrose agar petri dishes used
[
Rotondo, A.; Rossi, A.; Chiricosta, G.; Paola, R. D.; Sautebin, L.;
Cuzzocrea, S.; Vigorita, M. G. Bioorg Med Chem 2005, 13, 4243.
[20] Bacchi, A.; Careelli, M.; Pelizzi, G.; Vicini, P. Arch Pharm
1995, 328, 217.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet