Synthesis and antifungal activity of 2-(4-chlorophenylcarbamoyl)phenyl acetate

Article abstract of DOI:10.14233/ajchem.2013.14536

2-(4-Chlorophenylcarbamoyl)phenyl acetate was synthesized by the ammonolysis of 2-(chlorocarbonyl)phenyl acetate. Its structure was confirmed by IR and 1H NMR. Its antifungal activity against Sclerotinia sclerotiorum and Helminthosprium maydis has been de

Full text of DOI:10.14233/ajchem.2013.14536

Asian Journal of Chemistry; Vol. 25, No. 13 (2013), 7271-7273
http://dx.doi.org/10.14233/ajchem.2013.14536
Synthesis and Antifungal Activity of 2-(4-Chlorophenylcarbamoyl)phenyl Acetate
1,*
2
1
1
XIAORONG TANG , HUI FENG , QUAN DU and LING WANG
1School of Physics and Chemistry, Xihua University, Chengdu 610039, P.R. China
2School of Bioengineering, Xihua University, Chengdu 610039, P.R. China
*Corresponding author: Tel: +86 28 87720208; E-mail: tangxiaorong0901@163.com
(Received: 7 September 2012;
Accepted: 24 June 2013)
AJC-13688
2-(4-Chlorophenylcarbamoyl)phenyl acetate was synthesized by the ammonolysis of 2-(chlorocarbonyl)phenyl acetate. Its structure was
confirmed by IR and 1H NMR. Its antifungal activity against Sclerotinia sclerotiorum and Helminthosprium maydis has been determined
in the laboratory. Results showed that it had good antifungal activity against the above two different pathogenic fungi of plants. Its median
effective concentrations (EC50) were 28 mg L-1 and 2.3 mg L-1, respectively.
Key Words: Antifungal activity, 2-(4-Chlorophenylcarbamoyl)phenyl acetate, Synthesis.
on a Varian Unity Inova-400 instrument using deuteron-chlo-
roform as the solvent.
INTRODUCTION
Sclerotinia sclerotiorum is a harmful disease of cole1. For
a long period, benzimidazole fungicides have been mostly
used to control it. In recent years, however, it has developed
resistance to the above fungicides2-6. Moreover, its scope of
resistance continues to expand and has already included many
new fungicides7-9.
Synthesis of 2-(4-chlorophenylcarbamoyl)phenyl
acetate: The target compound was synthesized according to
the reaction shown in Fig. 1. 4-Chloroaniline (0.02 mol) and
pyridine (0.02 mol) were dissolved 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 recrys-
tallization in anhydrous ethanol.
Similarly, Helminthosprium maydis is a pathogenic fungus
of plants which has serious harm to maize. Over the past
decades, synthetic fungicides including carbendazim have
been used to prevent it. Nevertheless, the development of its
resistance to all the fungicides has reduced the efficacy of
fungicidal treatment10-16. Therefore, new fungicides are conti-
nually required.
O
O
C Cl
H
N
pyridine/CH Cl
2
+
2
H N
2
Cl
C
Cl
OCOCH
It is well-known that since aspirin (acetylsalicylic acid)
was first marketed in 1899, it has been widely used for the
treatment of pains, fever and colds17-29. Thus, in the paper,
2-(4-chlorophenylcarbamoyl)phenyl acetate was synthesized
based on aspirin. In the meantime, its antifungal activity has
been evaluated in the laboratory to find new fungicides with
high efficacy and low toxicity.
3
OCOCH
3
Fig. 1. Synthetic method of 2-(4-chlorophenylcarbamoyl)phenyl acetate
The synthesized compound (m.f. C15H12NO3Cl): white
needle crystal; yield: 40 %; m.p. 133-134 ºC; IR(KBr, νmax
cm-1): 3487, 3285, 3190, 3111, 3048, 1755, 1656, 1608, 1595,
1533, 1493, 1447, 1396, 1317, 1207, 1172, 830, 751, 701,
589;1H NMR (400 MHz, CDCl3) δ (ppm): 8.10 (s, 1H), 7.80
(d, J = 7.6 Hz, 1H), 7.49-7.55 (m, 3H), 7.30-7.36 (m, 3H),
7.14 (d, J = 8.4 Hz, 1H), 2.31 (s, 3H).
EXPERIMENTAL
Sclerotinia sclerotiorum and Helminthosprium maydis
were obtained from the Chinese Academy of Agricultural
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 spectrophotometer. 1H NMR spectra were taken
Assay of antifungal activity: The antifungal activity of
the synthesized compound against Sclerotinia sclerotiorum and
Helminthosprium maydis was determined using the plate
growth rate method30.

7272 Tang et al.
Asian J. Chem.
TABLE-1
ANTIFUNGAL ACTIVITY OF 2-(4-CHLOROPHENYLCARBAMOYL)PHENYL ACETATE AGAINST Sclerotinia sclerotiorum
2-(4-Chlorophenylcarbamoyl)phenyl acetate
Carbendazim
12.5
−
1
Concentration (mg L )
100
50
25
12.5
17.1
6.3
6.3
50
25
6.3
3.1
Inhibition of growth∗ (%)
93.7
79.0
37.2
94.1
85.5
74.9
61.1
49.5
Regressive equation (Y = aX + b)
−
Y = 2.6821X + 1.1201
Y = 1.2683X + 4.3132
1
EC50 (mg L )
28.0
(24.9-31.5)
0.9507
3.5
(95% CL)
(2.4-4.6)
0.9614
0.605
Correlative coefficient (r)
χ2
4.416
∗Based on the mean of triplicates
TABLE-2
ANTIFUNGAL ACTIVITY OF 2-(4-CHLOROPHENYLCARBAMOYL)PHENYL ACETATE AGAINST Helminthosprium maydis
2-(4-Chlorophenylcarbamoyl)phenyl acetate
Carbendazim
−
1
Concentration (mg L )
100
50
25
12.5
70.8
6.3
100
50
25
12.5
41.5
6.3
35.5
Inhibition of growth∗ (%)
91.6
85.1
78.8
65.6
87.5
70.8
57.5
Regressive equation (Y = aX + b)
−
Y = 0.7948X + 4.7185
Y = 1.2373X + 3.5189
1
EC50 (mg L )
2.3
15.7
(12.1-19.6)
0.9808
(95% CL)
(0.5-4.5)
0.9698
0.472
Correlative coefficient (r)
χ2
2.862
∗Based on the mean of triplicates
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 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 of Abbott. EC50 values were calcu-
lated with the statistics package for the social sciences based
on probit analysis.
Antifungal activity against Helminthosprium maydis:
As shown in Table-2, using the efficient fungicide carbendazim
as the comparative standard, the synthesized compound was
subjected to laboratorial bioassay. Its EC50 value reached 2.3
mg L-1. The results of regressive and correlative analyses
revealed that the correlation was significant between concen-
tration and efficacy. The correlative coefficient was 0.9698.
As for the results of Sclerotinia sclerotiorum, chi-square test
also showed that the results were reliable (χ2 = 0.472, df = 3,
p > 0.05).
Conclusion
The results of laboratory bioassay have apparently shown
that though the antifungal activity of 2-(4-chlorophenyl-
carbamoyl)phenyl acetate against Sclerotinia sclerotiorum
was inferior to carbendazim, its antifungal activity against
Helminthosprium maydis was superior to carbendazim. There-
fore, the structural modification of aspirin was very successful.
In addition, the structure of the obtained compound is simple
and its chemical synthesis is easy. Thus, based on it, more
derivatives may be further synthesized so as to survey quanti-
tative structure-activity relationships and find new fungicides
with high efficacy and low toxicity as well as safety to non-
target organisms. On the other hand, the compound is also
promising in the agricultural chemistry field because it had
good antifungal activity against the two different pathogenic
fungi of plants.
RESULTS AND DISCUSSION
The target compound [2-(4-chlorophenylcarbamoyl)-
phenyl acetate] has been successfully synthesized by means
of the ammonolysis of 2-(chlorocarbonyl)phenyl acetate and
1
then its structure has been confirmed by IR and H NMR
spectra.
Antifungal activity against Sclerotinia sclerotiorum:
Compared with the efficient fungicide carbendazim, the synthe-
sized 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 28 mg L-1.
The results of regressive and correlative analyses indicated
that the correlation was significant between concentration and
efficacy. Its correlative coefficient was 0.9507. Chi-square test
demonstrated that the results were reliable (χ2 = 4.416, df = 3,
p > 0.05).
ACKNOWLEDGEMENTS
This project was supported by the Scientific Research
Fund of Sichuan Provincial Education Department (No.
09ZA113), the Key Scientific Research Fund of Xihua
University (No. Z0913302) and the Organic Chemistry Key
Discipline of Xihua University.

Vol. 25, No. 13 (2013)
Synthesis of 2-(4-Chlorophenylcarbamoyl)phenyl Acetate and Its Antifungal Activity 7273
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