Synthesis and fungicidal activity of 2-(3-fluorophenylcarbamoyl)phenyl acetate

Article abstract of DOI:10.14233/ajchem.2013.14056

In the present study, 2-(3-Fluorophenylcarbamoyl)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 Cochliobolus

Full text of DOI:10.14233/ajchem.2013.14056

Asian Journal of Chemistry; Vol. 25, No. 8 (2013), 4541-4543
http://dx.doi.org/10.14233/ajchem.2013.14056
Synthesis and Fungicidal Activity of 2-(3-Fluorophenylcarbamoyl)phenyl acetate
*
HUI FENG, CHIXIANG ZHANG, JIA LIU, PENGCHENG TANG, YUANMOU TANG, XIAORONG TANG and SHIRONG JIAO
School of Bioengineering, Xihua University, Chengdu 610039, P.R. China
*Corresponding author: Tel: +86 13882002899; E-mail: huif2010@163.com
(Received: 12 May 2012;
Accepted: 15 February 2013)
AJC-13007
In the present study, 2-(3-Fluorophenylcarbamoyl)phenyl acetate was synthesized by the ammonolysis of 2-(chlorocarbonyl)phenyl
1
acetate. Its structure was confirmed by IR and H NMR. Its antifungal activity against Sclerotinia sclerotiorum and Cochliobolus
heterostrophus Drechsler has been determined. The results showed that it had good antifungal activity against the two different pathogenic
fungi of plants. Its median effective concentrations (EC50) reached 8.3 and 0.9 mg L-1, respectively.
Key Words: Synthesis, Antifungal activity, 2-(3-Fluorophenylcarbamoyl)phenyl acetate.
Nicolet-6700 spectrophotometer. 1H NMR spectra were taken
on a Varian Unity Inova-400 instrument using deuteron-
INTRODUCTION
Sclerotinia sclerotiorum is an important disease of cole1.
In recent years by the cultivation, management condition,
chloroform as the solvent.
Synthesis of target compound: The target compound
variety resistance and climate factors, Sclerotinia sclerotiorum
damage happened already quite common. For a long period,
was synthesized according to the route shown in Fig. 1 and
their yield was not optimized. 3-Fluoro aniline or its deri-
benzimidazole fungicides have been mostly used to control it.
vatives (30 mmol) and pyridine (30 mmol) were dissolved in
CH2Cl2 (10 mL). The mixture was stirred and heated to 30 ºC.
However, in recent years, it has developed resistance to them2-6.
Similarly, Cochliobolus heterostrophus Drechsler is a
2-(Chlorocarbonyl)phenyl acetate (30 mmol) were dissolved
in CH2Cl2 (10 mL) and was slowly to the mixture under stirring
pathogenic fungus of corn, It caused great harmfulness and
strong infectivity. Corn under production and quality decline
3-5 h until the reaction was complete. The precipitate was
filtered and washed with distilled water. The pure compound
are mainly caused by it7-9.
Over the past decades, synthetic fungicides including
was obtained by re-crystallization in anhydrous ethanol.
carbendazim have been used to control it. Nevertheless, the
development of its resistance to all these fungicides has
O
reduced the efficacy of fungicidal treatment10-16. Thus, new
fungicides are continually necessary.
C
Cl
NH2
O
C
OCOCH3
Salicylic acid is a natural compound existing in many
plants. It can help plants to disease resistance17-25. Its structure
is simple and its chemical synthesis is easy. Therefore, 2-(3-
fluorophenylcarbamoyl)phenyl acetate was synthesized based
on it. Meanwhile, its antifungal activity has been evaluated in
the laboratory to find novel fungicides with high effect and
low toxicity.
p yridine/CH Cl
2
NH
2
F
F
OCOCH 3
Fig. 1. Synthetic method of 2-(3-fluorophenylcarbamoyl) phenylacetate
The synthesized compound 2-(3-fluorophenylcarbamoyl)-
phenyl acetate: white crystal, yield: 20 %, m.p. 116-117 ºC;
IR (KBr, νmax, cm-1): 3296, 3261, 3187, 3077, 1770, 1743,
1666, 1593, 1537, 1484, 1450, 1368, 1316, 1227, 1162, 1135,
785, 775, 751, 696, 680, 583; 1H NMR (400 MHz, CDCl3) δ
(ppm): 2.32 (s, 3H), 7.13 (t, J = 8.4 Hz, 2H),7.26 (t, J = 8.0
Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H),
7.51 (t, J = 7.2 Hz, 1H), 7.74 (s, 1H), 7.79 (d, J = 8.0 Hz, 1H),
8.14 (s, 1H).
EXPERIMENTAL
Sclerotinia sclerotiorum and Cochliobolus heterostrophus
Drechsler were obtained from the Chinese Academy of Agri-
cultural 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

4542 Feng et al.
Asian J. Chem.
Assay of antifungal activity: The antifungal activity of
was subjected to laboratorial bioassay using the efficient
fungicide carbendazim as the comparative standard. Its EC50
value reached 0.9 mg L-1. The results of regressive and corre-
lative analysis revealed that the correlation was very significant
between concentration and efficacy. The correlative coefficient
was 0.9594. As for the results of Cochliobolus heterostrophus
Drechsler, chi square test also showed that the results were
reliable (χ2 = 0.448, df = 3, p > 0.05).
the synthesized compound against Sclerotinia sclerotiorum and
Cochliobolus heterostrophus Drechsler was determined using
the plate growth rate method26.
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 the controls covered the
surface of these plates. Control groups were treated with the
corresponding 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 Abbott, s formula. EC50 values were calculated
with the Statistics Package for the Social Sciences (SPSS)
based on probit analysis.
The target compound (2-(3-fluorophenylcarbamoyl)-
phenyl acetate) has been successfully synthesized by means
of the ammonolysis of 2-(chlorocarbonyl)phenyl acetate and
its structure has also been confirmed with the aid of IR and 1H
NMR.
The results of laboratory bioassay have clearly demons-
trated the antifungal activity of 2-(3-fluorophenylcarbamoyl)-
phenyl acetate against Sclerotinia sclerotiorum and Cochliobolus
heterostrophus Drechsler although its antifungal activity was
inferior to the comparative standard. Therefore, on the basis
of it, more derivatives may be further synthesized to survey
quantitative structure-activity relationships and find novel
fungicides with high effect and low toxicity as well as safety
to non-target organisms. Meanwhile, these results suggested
that the design and synthesis of the compound may be condu-
cive to the antifungal activity of analogues of salicylic acid
The compound is also promising in the agricultural chemistry
field because its antifungal activity against the two different
pathogenic fungi of plants was close to the efficient fungicide
carbendazim.
RESULTS AND DISCUSSION
Antifungal activity against Sclerotinia sclerotiorum:
The synthesized compound was submitted to laboratorial
bioassay compared with the efficient fungicide carbendazim.
The results are presented in Table-1. It had good antifungal
activity against Sclerotinia sclerotiorum. Its EC50 value was
8.3 mg L-1. The results of regressive and correlative analysis
indicated that the correlation was significant between concen-
tration and efficacy. Its correlative coefficient was 0.9643. Chi
square test demonstrated that the results were reliable (χ2 =
2.736, df = 3, p > 0.05).
However, in order to realize the industrialization of the
compound as a fungicide there is large amounts of research
work to be done. 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.
Antifungal activity against Cochliobolus heterostrophus
Drechsler: As shown in Table-2, the synthesized compound
TABLE-1
ANTIFUNGAL ACTIVITY OF 2-(3-FLUOROPHENYLCARBAMOYL)PHENYL ACETATE AGAINST Sclerotinia sclerotiorum
2-(3-Flurophenylcarbamoyl)phenyl acetate
Carbendazim
12.5
Concentration (mg L-1)
Inhibition of growth* (%)
Regressive equation (Y = aX + b)
EC50 (mg L-1)
25
12.5
61.4
6.3
1.6
0.9
50
25
6.3
3.1
91.1
36.9
15.7
5.13
94.1
85.5
74.9
61.1
49.5
Y = 2.4054X + 2.7838
Y = 1.2683X + 4.3132
8.3
(7.4-9.5)
0.9643
3.5
(2.3-4.6)
0.9614
(95 % CL)
Correlative coefficient (r)
χ2
2.736
0.605
*Based on the mean of triplicates.
TABLE-2
ANTIFUNGAL ACTIVITY OF 2-(3-FLUOROPHENYLCARBAMOYL)PHENYL
ACETATE AGAINST Cochliobolus heterostrophus Drechsler
2-(3-Flurophenylcarbamoyl)phenyl acetate
Carbendazim
Concentration (mg L-1)
Inhibition of growth* (%)
Regressive equation (Y = aX + b)
EC50 (mg L-1)
100
90.1
50
83.5
25
80.2
12.5
74.4
6.3
70.1
100
87.5
50
70.8
25
57.5
12.5
41.5
6.3
35.5
Y = 0.5972X + 4.9787
Y = 1.2373X + 3.518
15.7
0.9
(95 % CL)
Correlative coefficient (r)
(3.4-6.6)
0.9594
(12.1-19.6)
0.9808
χ2
0.448
2.862
*Based on the mean of triplicates.

Vol. 25, No. 8 (2013)
ACKNOWLEDGEMENTS
Synthesis and Fungicidal Activity of 2-(3-Fluorophenylcarbamoyl)phenyl acetate 4543
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