Synthesis and activity of novel fungicide 2-(4-bromophenyl carbamoyl)phenyl acetate

Article abstract of DOI:10.14233/ajchem.2013.14355

In the present study, 2-(4-bromophenyl carbamoyl)phenyl acetate was synthesized by the ammonolysis of 2-(chloro carbonyl)phenyl acetate. Its structure was confirmed by IR and ¹H NMR. Its antifungal activity against Sclerotinia sclerotiorum and

Full text of DOI:10.14233/ajchem.2013.14355

Asian Journal of Chemistry; Vol. 25, No. 12 (2013), 6550-6552
http://dx.doi.org/10.14233/ajchem.2013.14355
Synthesis and Activity of Novel Fungicide 2-(4-Bromophenyl carbamoyl)phenyl Acetate
*
YAN ZHANG, SHAOLING CHEN, LING WANG and XIAORONG TANG
School of Physics and Chemistry, Xihua University, Chengdu 610039, P.R. China
*Corresponding author: Tel: +86 28 87720208; E-mail: tangxiaorong0901@163.com
(Received: 23 July 2012;
Accepted: 20 May 2013)
AJC-13519
In the present study, 2-(4-bromophenyl carbamoyl)phenyl acetate was synthesized by the ammonolysis of 2-(chloro carbonyl)phenyl
acetate. Its structure was confirmed by IR and 1H NMR. Its antifungal activity against Sclerotinia sclerotiorum and Botrytis cinerea has
been determined in the laboratory. The results showed that it had good antifungal activity against the two different pathogenic fungi of
plants. Its median effective concentrations (EC50) reached 8.6 mg L-1 and 1.8 mg L-1, respectively.
Key Words: Antifungal activity, 2-(4-Bromophenyl carbamoyl)phenyl acetate, Synthesis.
Synthesis of target compound: The target compound
was synthesized according to the reaction shown in Fig. 1.
4-Bromoaniline (0.02 mol) and pyridine (0.02 mol) were dissol-
ved in CH2Cl2 (15 mL). The mixture was stirred and heated to
35-45 ºC. 2-(Chlorocarbonyl) phenyl acetate (0.02 mol) with
CH2Cl2 (15 mL) was slowly added to the above mixture under
stirring until the reaction was complete. The precipitate was
filtered and washed with distilled water. The pure compound
was obtained by recrystallization in anhydrous ethanol.
INTRODUCTION
Sclerotinia sclerotiorum is a harmful disease of cole1. For
a long period, benzimidazole fungicides have been mostly used
to prevent it. In recent years, however, it has developed
resistance to these fungicides2-6. Moreover, its scope of resis-
tance continues to develop and has already included many
new fungicides7-9.
Likewise, Botrytis cinerea is a pathogenic fungus of plants
that has serious harm to vegetables and flowers. Over the past
decades, synthetic fungicides including carbendazim have been
used to prevent it. Nevertheless, the development of its resis-
tance to all the fungicides has reduced the efficacy of fungi-
cidal treatment10-16. Therefore, new fungicides are continually
necessary.
O
C Cl
OCOCH
O
H
N
pyridine/CH Cl
2
+
2
H N
2
Br
C
Br
3
OCOCH
3
Fig. 1. Synthetic method of 2-(4-bromophenyl carbamoyl)phenyl acetate
It is well-known that since aspirin (acetyl salicylic acid)
was first marketed in 1899, it has been widely used for the
treatment of pains, fever and colds17-26. Thus, 2-(4-bromophenyl
carbamoyl)phenyl acetate was synthesized on the basis of it.
In the meantime, its antifungal activity has been evaluated in
the laboratory to find novel fungicides with high efficacy and
low toxicity.
The synthesized compound (C15H12NO3Br): light yellow
needle crystal; yield: 82.0 %; m.p. 138-139 ºC; IR (KBr, νmax
,
cm-1): 3485, 3281, 3183, 3105, 3042, 1755, 1656, 1597, 1607,
1587, 1526, 1490, 1446, 1391, 1317, 1208, 1173, 826, 750,
700, 589; 1H NMR (400 MHz, CDCl3) δ (ppm): 8.15 (s, 1H),
7.77 (d, J = 7.6 Hz, 1H), 7.42-7.52 (m, 5H), 7.32 (t, J = 7.6
Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 2.30 (s, 3H).
Assay of antifungal activity: The antifungal activity of
the synthesized compound against Sclerotinia sclerotiorum and
Botrytis cinerea was determined using the plate growth rate
method27.
EXPERIMENTAL
Sclerotinia sclerotiorum and Botrytis cinerea were obtained
from the ChineseAcademy ofAgricultural Sciences. They were
preserved at 4 ºC. All chemicals and solvents were purchased
from commercial sources unless specified otherwise. IR spectra
were recorded on a Thermofisher Nicolet-6700 spectrophoto-
The synthesized compound and carbendazim (purity
90 %) were dissolved in dimethyl sulfoxide, respectively. The
two solutions were diluted into five different concentrations
with distilled water, respectively. They were added to the
sterile culture medium (PDA) at 45 ºC, mixed to homogeneity
1
meter. H NMR spectra were taken on a Varian Unity Inova-
400 instrument using deuteron-chloroform as the solvent.

Vol. 25, No. 12 (2013)
Synthesis and Activity of Novel Fungicide 2-(4-Bromophenyl carbamoyl)phenyl Acetate 6551
TABLE-1
ANTIFUNGAL ACTIVITY OF 2-(4-BROMOPHENYL CARBAMOYL)PHENYL ACETATE AGAINST Sclerotinia sclerotiorum
2-(4-Bromophenyl carbamoyl)phenyl acetate
Carbendazim
Concentration (mg L-1)
Inhibition of growth∗ (%)
Regressive equation (Y = aX + b)
EC50 (mg L-1)
100
50
25
12.5
54.8
6.3
50
25
12.5
74.9
6.3
3.1
87.7
78.7
60.9
49.0
94.1
85.5
61.1
49.5
Y = 0.9837 X + 4.0811
Y = 1.2683 X + 4.3132
8.6
3.5
(95 % CL)
(5.2-11.9)
0.9741
3.443
(2.4-4.6)
0.9614
0.605
Correlative coefficient (r)
χ2
∗Based on the mean of triplicates
TABLE-2
ANTIFUNGAL ACTIVITY OF 2-(4-BROMOPHENYL CARBAMOYL)PHENYL ACETATE AGAINST Botrytis cinerea
2-(4-Bromophenyl carbamoyl)phenyl acetate
Carbendazim
12.5
Concentration (mg L-1)
Inhibition of growth∗ (%)
Regressive equation (Y = aX + b)
EC50 (mg L-1)
100
50
25
12.5
71.4
6.3
100
50
25
6.3
90.6
85.0
78.3
67.3
91.3
75.6
48.5
36.7
19.4
Y = 0.7218 X + 4.8185
Y = 1.7924 X + 2.6384
1.8
20.8
(17.6-24.3)
0.9647
(95 % CL)
(0.3-4.0)
0.9702
0.505
Correlative coefficient (r)
χ2
3.092
∗Based on the mean of triplicates
and transferred to sterile petri dishes to solidify. A mycelium
agar disc (5 mm in diameter) of the target fungi was placed in
the center of PDA plates. They were incubated at 28 ºC in the
dark until the target fungi used as controls covered the surface
of these plates. Control groups were treated with the corres-
ponding solutions without the synthesized compound or
carbendazim. The experiment for each concentration was
replicated three times. The diameter of the fungi in the cultures
was measured and the inhibition of growth was calculated
according to the formula ofAbbott. EC50 values were calculated
with the Statistics Package for the Social Sciences (SPSS)
based on probit analysis.
of the ammonolysis of 2-(chlorocarbonyl)phenyl acetate and
then its structure has been confirmed with the aid of IR and 1H
NMR.
The results of laboratory bioassay have clearly shown that
though the antifungal activity of 2-(4-bromophenylcarbamoyl)-
phenyl acetate against Sclerotinia sclerotiorum was inferior
to carbendazim, its antifungal activity against Botrytis cinerea
was superior to carbendazim. Thus, the structural modifi-
cation of aspirin was very successful. In addition, the structure
of the obtained compound is simple and its chemical synthe-
sis is easy. Therefore, on the basis of it, more derivatives may
be further synthesized so as to survey quantitative structure-
activity relationships and find novel fungicides with high
efficacy and low toxicity as well as safety to non-target organ-
isms. On the other hand, the compound is also promising in
the agricultural chemistry field because it possessed good
antifungal activity against the two different pathogenic fungi
of plants.
RESULTS AND DISCUSSION
Antifungal activity against Sclerotinia sclerotiorum:
Compared with the efficient fungicide carbendazim, the
synthesized compound was submitted to laboratorial bioassay.
The results are presented in Table-1. It had good antifungal
activity against Sclerotinia sclerotiorum. Its EC50 value was
8.6 mg L-1. The results of regressive and correlative analyses
indicated that the correlation was significant between concen-
tration and efficacy. Its correlative coefficient was 0.9741.
Chi-square test demonstrated that the results were reliable (χ2
= 3.443, df = 3, p > 0.05).
However, in order to realize the industrialization of the
compound as a fungicide, more research work needs doing.
Its antifungal spectrum needs to be determined. Its mode of
action and its safety to humans and non-target organisms also
need to be further investigated.
ACKNOWLEDGEMENTS
Antifungal activity against Botrytis cinerea: As shown
in Table-2, using the efficient fungicide carbendazim as the
comparative standard, the synthesized compound was subjec-
ted to laboratorial bioassay. Its EC50 value reached 1.8 mg L-1.
The results of regressive and correlative analyses revealed that
the correlation was significant between concentration and
efficacy. The correlative coefficient was 0.9702. As for the
results of Sclerotinia sclerotiorum, chi-square test also showed
that the results were reliable (χ2 = 0.505, df = 3, p > 0.05).
The target compound [2-(4-bromophenylcarbamoyl)
phenyl acetate] has been successfully synthesized by means
This project was supported by the Scientific Research
Fund of Sichuan Provincial Education Department (No.
12233450), the Key Scientific Research Fund of Xihua
University (No. Z0913307) and the Organic Chemistry Key
Discipline of Xihua University.
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