Full text of DOI:10.14233/ajchem.2013.15001

Asian Journal of Chemistry; Vol. 25, No. 16 (2013), 9066-9068
http://dx.doi.org/10.14233/ajchem.2013.15001
Synthesis of 2-(Phenylcarbamoyl)phenyl Acetate and Its Antifungal Activity
1
,*
2
YUQI CHEN and HUI FENG
1
2
Institute of Light Industry and Food Engineering, Guangxi University, Nanning 530004, P.R. China
School of Bioengineering, Xihua University, Chengdu 610039, P.R. China
*
Corresponding author: Tel: +86 28 87720763; E-mail: shengxiaohongb@qq.com
Received: 20 December 2012; Accepted: 16 September 2013)
(
AJC-14114
2-(Phenylcarbamoyl)phenyl acetate was synthesized by the ammonolysis of 2-(chlorocarbonyl)phenyl acetate. Its structure was confirmed
by IR and H NMR. Its antifungal activity against Rhizoctonia solani and Helminthosprium maydis has been studied. It had good antifungal
1
-1
activity against the above two different pathogenic fungi of plants. Its median effective concentrations (EC50) were 22.9 and 6.8 mg L ,
respectively.
Key Words: Antifungal activity, 2-(Phenylcarbamoyl)phenyl acetate, Synthesis.
Synthesis of target compound: The target compound
was synthesized according to the reaction shown in Fig. 1.
Aniline (0.02 mol) and pyridine (0.02 mol) were dissolved in
INTRODUCTION
Rhizoctonia solani is a harmful disease of paddy rice .
1
For a long period, benzimidazole fungicides have been mostly
used to control it. However, it has developed resistance to the
CH
5 ºC. 2-(Chlorocarbonyl)phenyl acetate (0.02 mol) with
CH Cl (15 mL) was slowly added to the above mixture under
2 2
Cl (15 mL). The mixture was stirred and heated to 35-
4
2-6
above fungicides . Moreover, its scope of resistance continues
2
2
7
-9
to expand and has already included many new fungicides .
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
stirring until the reaction was complete. The precipitate was
filtered and washed with stilled water. The pure compound
was obtained by re-crystallization in anhydrous ethanol.
O
O
H
C N
C Cl
pyridine/CH
2
Cl
2
1
0-16
+
2
H N
treatment . Therefore, new fungicides are continually
required.
OCOCH3
OCOCH
3
Fig. 1. Synthetic method of 2-(phenylcarbamoyl) phenyl acetate
It is well-known that since aspirin (acetylsalicylic acid)
was first marketed in 1899, it has been widely used for the
17-29
15 13 3
Synthesized compound (C H O N): light yellow
treatment of pains, fever and colds . Thus, in present report,
-(phenylcarbamoyl)phenyl acetate was synthesized based on
-1
powder; yield: 75.0 %; m.p. 152-153 ºC; IR(KBr, νmax, cm ):
2
3
1
5
243, 3191, 3131, 3072, 3040, 1760, 1649, 1597, 1542, 1494,
451, 1370, 1327, 1300, 1195, 1156, 1097, 758, 748, 709,
aspirin. Its antifungal activity has been evaluated to find new
fungicides with high efficacy and low toxicity.
1
96; H NMR (400 MHz, CDCl
3
) δ (ppm): 8.08 (s, 1H), 7.83
EXPERIMENTAL
(d, J = 7.6 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.49-7.53 (m,
1
H), 7.33-7.38 (m, 3H), 7.13-7.17 (m, 2H), 2.32 (s, 3H).
Assay of antifungal activity: The antifungal activity of
Rhizoctonia solani and Helminthosprium maydis 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
the synthesized compound against Rhizoctonia solani and
Helminthosprium maydis was determined using the plate
30
growth rate method .
The synthesized compound and carbendazim (purity
1
spectrophotometer. H NMR spectra were taken on a Varian
Unity Inova-400 instrument using deuteron-chloroform as the
solvent.
90 %) were dissolved in dimethyl sulfoxide, respectively. The
two solutions were diluted into five different concentrations

Vol. 25, No. 16 (2013)
Synthesis of 2-(Phenylcarbamoyl)phenyl Acetate and Its Antifungal Activity 9067
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 (SPSS)
based on probit analysis.
The target compound 2-(phenylcarbamoyl) phenyl acetate
has been successfully synthesized by means of the ammonolysis
of 2-(chlorocarbonyl) phenyl acetate and then its structure has
1
been confirmed with the aid of IR and H NMR.
The results of laboratory bioassay have apparently shown
that though the antifungal activity of 2-(phenylcarbamoyl)
phenyl acetate against Rhizoctonia solani was inferior to
carbendazim, its antifungal activity against Helminthosprium
maydis was superior to carbendazim. Therefore, 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 quantitative 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.
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.
RESULTS AND DISCUSSION
Antifungal activity against Rhizoctonia solani: Compared
with the efficient fungicide carbendazim, the synthesized com-
pound was submitted to laboratorial bioassay. The results are
presented in Table-1. It had good antifungal activity against
-1
Rhizoctonia solani. Its EC50 value was 22.9 mg L . The results
of regressive and correlative analyses indicated that the corre-
lation was significant between concentration and efficacy. Its
correlative coefficient was 0.9635. Chi-square test demon-
ACKNOWLEDGEMENTS
2
strated that the results were reliable (χ = 2.913, df = 3, p >
0
.05).
Antifungal activity against Helminthosprium maydis:
This project was supported by the Science and Technology
Support Program of Sichuan Province (2009PZ0055).
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 6.8
REFERENCES
1
.
X.J. Chen, M.J. Cao, Y. Wang, Y.H. Tong and J.Y. Xu, Chin. J. Oil Crop
Sci., 31, 503 (2009).
-
1
mg L . The results of regressive and correlative analyses
revealed that the correlation was significant between concen-
tration and efficacy. The correlative coefficient was 0.9776.
As for the results of Rhizoctonia solani, chi-square test also
2
3
4
.
.
.
Y.L. Pan, Z.Y. Wang and H.Z. Wu, J. Jiangsu Agric., 13, 32 (1997).
Z.Q. Shi, M.G. Zhou and Z.Y. Ye, J. Jiangsu Agric., 16, 212 (2000).
W. Li, W. Li, Y.-J. Zhou and H.G. Chen, Chin. J. Oil Crop Sci., 29, 63
(
2007).
5. K.Y. Liu and F.X. Chen, Anhui Agric. Sci., 35, 756 (2007).
R.E. Beever and H.M.R. Brien, Agric. Res., 26, 391 (1983).
2
showed that the results were reliable (χ = 4.241, df = 3, p >
0
6
.
.05).
TABLE-1
ANTIFUNGAL ACTIVITY OF 2-(PHENYLCARBAMOYL) PHENYL ACETATE AGAINST Rhizoctonia solani
2
-(Phenylcarbamoyl)phenyl acetate
Carbendazim
-
1
Concentration (mg L )
100
50
25
12.5
28.7
6.3
12.5
96.5
6.3
3.1
1.6
0.8
Inhibition of growth* (%)
Regressive equation (Y = aX + b)
88.7
73.3
48.4
20.5
91.7
73.4
59.8
52.4
Y = 1.7449X + 2.6267
Y = 1.4684X + 5.0660
-1
EC50 (mg L )
95 % Cl)
22.9
(19.5-26.9)
0.9635
0.9
(
(0.6-1.2)
0.9585
4.508
Correlative coefficient (r)
2
χ
2.913
*Based on the mean of triplicates.
TABLE-2
ANTIFUNGAL ACTIVITY OF 2-(PHENYLCARBAMOYL) PHENYL ACETATE AGAINST Helminthosprium maydis
2
-(Phenylcarbamoyl)phenyl acetate
Carbendazim
-
1
Concentration (mg L )
100
50
25
12.5
57.2
6.3
100
50
25
12.5
41.5
6.3
Inhibition of growth* (%)
Regressive equation (Y = aX + b)
92.5
84.1
68.0
54.2
87.5
70.8
57.5
35.5
Y = 1.1037X + 4.0798
Y = 1.2373X + 3.5189
-1
EC50 (mg L )
95 % Cl)
6.8
15.7
(12.1-19.6)
0.9808
(
(4.1-9.5)
0.9776
4.241
Correlative coefficient (r)
2
χ
2.862
*Based on the mean of triplicates.

9
068 Chen et al.
Asian J. Chem.
7
8
9
1
.
D.G. Hutton, Australasian Plant Pathol., 17, 34 (1988).
Y.X. Qi, F.X. Chen and K.J. Ding, Pesticides, 8, 567 (2006).
FAO, FAO Plant Protect. Bull., 30, 30 (1982).
18. D.W. Gilroy, Prostag. Leukotr. Ess., 73, 203 (2005).
.
.
19. C. Millikan and N. Futrell, J. Stroke Cerebrovasc Dis., 5, 248 (1995).
20. J.R. Vane, R.J. Flower and R.M. Botting, Stroke, 21, 12 (1990).
21. M.L. Dyken, H.J.M. Barnett, J.D. Easton, W.S. Fields, V. Fuster, V.
Hachinski, J.W. Norris and D.G. Sherman, Stroke, 23, 1395 (1992).
22. H. Tohgi, S. Konno, K. Tamura, B. Kimura and K. Kawano, Stroke, 23,
1400 (1992).
0. A. Have, R. Van Berloo, P. Lindhout and J.A.L. Van Kan, Eur. J. Plant
Pathol., 113, 153 (2007).
1
1
1
1
1
1
1
1. S.I. Ignatova, N.S. Gorshkova and T.A. Tereshonkova, Acta Physiol.
Plant, 22, 326 (2000).
2. H. Egashira, A. Kuwashima, H. Ishiguro, K. Fukushima, T. Kaya and
S. Imanishi, Acta Physiol. Plant, 22, 324 (2000).
3. R.L. Guimaraes, R.T. Chetelat and H.U. Stotz, Eur. J. Plant Pathol.,
23. R.H. Ackerman and K.L. Newman, Ann. Neurol., 28, 224 (1990).
24. C.M. Helgason, K.L. Tortorice, S.R. Winkler, D.W. Penney, J.J. Schuler,
T.J. McClelland and L.D. Brace, Stroke, 24, 345 (1993).
1
10, 13 (2004).
25. W.K. Hass, J.D. Easton, H.P.Adams Jr, W. Pryse-Phillips, B.A. Molony,
S. Anderson and B. Kamm, N. Engl. J. Med., 321, 501 (1989).
26. D.M. McCarthy, Best Pract. Res. Clin. Gastroenterol., 26, 101 (2012).
27. R. Eccles, Int. Pharm. J., 6, 7 (1995).
4. R. Finkers, P. van de Berg, R. van Berloo, A. Have, A.W. van Heusden,
J.A.L. van Kan and P. Lindhout, Theor. Appl. Genet., 114, 585 (2007).
5. Richard Finkers, A.W. van Heusden, F. Meijer-Dekens, J.A.L. van Kan,
P. Maris and P. Lindhout , Theor. Appl. Genet., 114, 1071 (2007).
6. R. Finkers, Y.L. Bai, P. van de Berg, R. van Berloo, A. Have, J.A.L.
van Kan, P. Lindhout andA.W. van Heusden, Euphytica, 159, 83 (2008).
7. X. Wang, Med. Hypotheses, 50, 239 (1998).
28. C. Lampl, M. Voelker and H.C. Diener, J. Neurol., 254, 705 (2007).
29. J.A. Forbes, I.A. Edquist, F.G. Smith, M.K. Schwartz and W.T. Beaver,
Pharmacotherapy, 11, 64 (1991).
30. W. Huang and G.F. Yang, Bioorg. Med. Chem., 14, 8280 (2006).