Synthesis and herbicidal activity of 4-benzylidene-2-phenyl oxazol-5(4H)-one derivatives using l-proline as catalyst

Article abstract of DOI:10.14233/ajchem.2018.21251

A simple, efficient and environmentally benign method for the synthesis of 4-benzylidene-2-phenyl oxazol-5(4H)-one derivatives by the reaction of aromatic aldehydes and hippuric acid using acetic anhydride as dehydrating agent and L-proline as catalyst ha

Full text of DOI:10.14233/ajchem.2018.21251

Asian Journal of Chemistry; Vol. 30, No. 8 (2018), 1717-1722
A
SIAN
J
OURNAL OF HEMISTRY
C
https://doi.org/10.14233/ajchem.2018.21251
Synthesis and Herbicidal Activity of 4-Benzylidene-2-phenyl
oxazol-5(4H)-one Derivatives using L-Proline as Catalyst
*
S. BHANDARI and V. KASANA
Department of Chemistry, Govind Ballabh Pant University of Agriculture & Technology, Pantnagar-263 145, India
*Corresponding author: Fax: +91 5944 233473, E-mail: sunitabhandari77@gmail.com
Received: 25 January 2018;
Accepted: 13 March 2018;
Published online: 30 June 2018;
AJC-18962
A simple, efficient and environmentally benign method for the synthesis of 4-benzylidene-2-phenyl oxazol-5(4H)-one derivatives by the
reaction of aromatic aldehydes and hippuric acid using acetic anhydride as dehydrating agent and L-proline as catalyst has been developed.
L-proline acts as a highly efficient organocatalyst .It is thermally stable and can withstand harsh reaction conditions besides being easily
available and environmentally non-hazardous. The structures of synthesized compounds were evaluated by FT-IR and 1H-NMR spectroscopy.
The present method is superior to the existing methods as it takes less reaction time, involves easy work up and affords products in
excellent yield. The preliminary bioassay of synthesized compounds indicated that most of the compounds exhibited good seed germination
inhibition activity against radish seed (Raphanus sativus).
Keywords: L-Proline, Organocatalyst, Oxazolone, Green method.
of 3,4,5-trisubtituted oxazolone remains challenging to the
chemists. For the synthesis of oxazolone by the condensation of
aldehyde, hippuric acid and dehydrating agent acetic anhydride
various catalysts such as include Na2CO3 [24], POCl3 [25], carbodi-
imides [26], polyphosphoric acid [27], Al2O3 [28], Bi(OAc)3
[29], silica-supported heteropolyacids [30,31], Yb(OTf)3 [32],
Ca(OAc)2 [33], supported KF [34], Fe2O3 [35], ZnO [36] and
Al2O3-H3BO3 [37] have been used.Although these methods have
some merits, but most of them still require high temperature,
expensive and toxic reagents, hazardous transition metal catalysts.
Nowadays, strategy towards for developing the hetero-
cyclic compound is favoured which is particularly important
for the drug promoted molecules for biological screeing. Recently,
organocatalysis emerged as an area of research for efficient
and environmentally benign synthesis. In view of the above
perception, the development of environmentally benign and
green method for high selectivity and high yield is desirable.
Herein, we report a concise and efficient method for the synthesis
of oxazolone derivatives using L-proline as organocatalyst via
aldol condensation reaction (Scheme-I). L-proline is easily
available and inexpensive catalyst [38].
INTRODUCTION
During recent years, diversity oriented synthesis of small
molecule libraries has become increasingly important to the
development of new pharmaceuticals [1]. The first report on
the synthesis of oxazolones using condensation of benzalde-
hyde with N-acetylglycine in the presence of sodium acetate
as a basic catalyst and acetic anhydride as dehydrating agent
was reported by Erlenmeyer [2]. Oxazolones are attractive building
blocks in organic synthesis [3]. These are very promising inter-
mediates for the preparation of amino acids [4], heterocyclic
compounds [5], biosensors or coupling and photosensitive devices
[6]. These compounds are biologically important as antimicro-
bials [7,8], antitumor [9], antioxidants [10], anti-inflammatory
[11], anti-HIV [12,13] and tyrosinase inhibiting [14], antidia-
betic [15], etc.
Recently, several methods for oxazolones synthesis such
as cyclization [16], transition metal catalyzed synthesis [17-20],
photocyclization [21], solid-phase synthesis [22] and cross-
coupling of bromoalkyne with secondary tert-butyloxycarba-
mate [3] have been reported. Most of the methods used metal
catalysts, in which separation is crucial because of residual
toxicity of metals in the target compound. In past few years,
promising methods for oxazolone synthesis were developed
by Hashima et al. [23] and Gagosz et al. [3] wherein they reported
the 3,5- disubtituted oxazolone via Au-catalyzed transforma-
tion of N-alkynyl ter-butyloxycarbamate.Yet, still now synthesis
Herein, we report the protocol which offers several merits
over other existing synthetic methods in many ways such as
use of thermally stable and inexpensive catalyst, high yield
(85-95%), short reaction times and easy workup. To the best
of our knowledge, L-proline is being used as catalyst first time
for the synthesis of oxazolones.

1718 Bhandari et al.
Asian J. Chem.
O
O
N
O
Ar
HO
L-Proline (10 mol%)
reflux (20-40 min)
N
H
Ac2O
+
+
Ar
H
H
O
O
1a-i
1a:Ar=H
1b:Ar= 3-OMe-C H4
2
Yield= 85-95 %
1d:Ar= 3-Br-C H4
1e:Ar= 4-Me-C6H4
1f:Ar= Furfural
1g:Ar= 3-Cl-C6H4
1h:Ar= 4-N(CH3)2C6H4
1i:Ar= 4-OH-3,4-(MeO)-C H4
6
3 a-i
6
1c:Ar= 2,3-Cl-C H3
6
6
Scheme-I: Synthesis of oxazolone derivatives
58.56; H, 3.07; N, 4.27. Found: C, 59.03; H, 3.02; N, 4.16.
FT-IR (νmax, cm-1): 1790 (C=O), 1660 (C=N), 1595 (C=C),
1224 (C-O) lactone , 980, 870, 775, 672; 1H NMR (400 MHz,
CDCl3): δ 2.35 (s, 3H, -CH3), 7.10 (s, 1H, =CH), 7.50-8.01 (m,
5H, ArH), 8.13-8.15 (dd, 2H, ArH), 8.38-8.44 (dd, 2H, ArH).
4-(4-Methylbenzylidene)-2-phenyloxazol-5(4H)-one
(3e): Yellow solid; Yield: 94 %; m.p.: 144-146 ºC, lit. m.p.:
145-146 ºC [33]; Anal calcd. (%) for C17H13NO2: C, 77.55; H,
EXPERIMENTAL
All chemicals were obtained from Hi-Media, SDS and used
as received. FT-IR spectra were recorded on Bruker model-
alpha spectrophotometer using KBr disc technique. The H
1
NMR spectra were recorded on Spectrometer JNM-ECS400
MHz instruments. Chemical data for protons are reported in
parts per million (ppm) downfield from tetramethylsilane as
reference to residual proton in NMR spectrophotometer using
CDCl3 (7.26 ppm) as solvent.
Hippuric acid (2 mmol, 0.358 g), benzaldehyde (2 mmol,
0.212 g), acetic anhydride (0.6 mL) and L-proline (10 mol %,
0.023 g) as catalyst were taken in a round bottom flask and
stirred at 80 ºC. The completion of reaction was monitored by
TLC (5 % ethyl acetate:hexane).After completion of reaction,
the mixture was cooled to room temperature. Solid mass obtained
was filtered and washed with water. The crude product was recry-
stallized from ethanol to afford the pure product. The identity
and purity of the products are confirmed by IR, 1H NMR spectro-
scopic analysis and melting point.
4.98; N, 5.32. Found: C, 76.93; H, 5.23; N, 4.87. FTIR (νmax
,
cm-1): 1800 (C=O), 1660 (C=N), 1590 (C=C), 1220 (C-O) lactone;
1H NMR (400 MHz, CDCl3): δ 2.47 (s, 3H, -CH3), 7.31 (s, 1H,
=CH), 7.56-7.58 (m, 2H, ArH), 7.33 (d, 2H, ArH), 8.13 (dd,
1H, ArH), 8.22 (d, 2H, ArH), 8.24 (dd, 2H, ArH).
4-[(Furan-2-yl)methylene]-2-phenyloxazol-5(4H)-one
(3f): Light yellw solid;Yield: 88 %; m.p.: 171-173 ºC, lit. m.p.:
171 ºC [39];Anal calcd. (%) for C14H9NO3: C, 70.29; H, 3.79;
N, 5.86. Found: C, 71.02; H, 3.42; N, 5.20. FTIR (νmax, cm-1):
1790 (C=O), 1660 (C=N), 1640 (C=N), 1520 (C=C), 1210
1
(C-O) lactone; H NMR (400 MHz, CDCl3): δ 6.69 (1H, s,
=CH), 7.21-7.60 (m, 5H, ArH), 7.71 (dd, 1H, ArH), 8.18 (d,
1H, ArH), 8.20 (d, 1H, ArH).
4-Benzylidene-2-phenyloxazol-5(4H)-one (3a): Light
yellow crystalline solid; Yield: 92 %; m.p.: 165-167 ºC, lit.
m.p.:167-168 ºC [28];Anal calcd. (%) for C16H11NO2: C, 77.10;
4-(3-Chlorobenzylidene)-2-phenyloxazol-5(4H)-one
(3g):Yellow crystalline solid;Yield: 90 %; m.p.: 176-178 ºC;
Anal calcd. (%) for C16H10NO2Cl: C, 67.74; H, 3.55; N, 4.94.
Found: C, 68.04; H, 3.17; N, 4.23. FTIR(νmax, cm-1): 1787 (C=O),
1651 (C=N), 1554 (C=C), 1158 (C-O) lactone; 1H NMR (400
MHz, CDCl3): δ 7.22 (1H, =CH), 7.28-7.31 (m, 3H, ArH), 7.54
(t, 2H,ArH), 7.59-7.63 (m, 1H,ArH), 8.11 (d, 2H,ArH), 8.18-
8.20 (d, 2H, ArH).
4-[4-(Dimethylamino)benzylidene]-2-phenyloxazol-
5(4H)-one (3h): Red needle crystal; Yield: 96 %; m.p.: 213-
215 ºC, lit. m.p.: 215 ºC [40]; Anal calcd. (%) for C18H16N2O2:
C, 73.95; H, 5.52; N, 9.58. Found: C, 72.15; H, 4.96; N, 10.03.
FTIR (νmax, cm-1): > 3612, 2875, 1827, 1643, 1523, 1368, 1157,
809, 687, 1755 (C=O), 1643 (C=N), 1597 (C=C), 1191 (C-O)
lactone; 1H NMR (400 MHz, CDCl3): δ 3.10 (s, 6H, (CH3)2),
6.72-6.75 (m, 2H, ArH), 7.21 (s, 1H, =CH), 7.48-7.55 (m,3H,
ArH), 8.03-8.23 (m, 4H, ArH).
H, 4.45; N, 5.62. Found: C, 77.20; H, 4.48; N, 5.30. FTIR (νmax
,
cm-1): 1790 (C=O), 1650 (C=N), 1550 (C=C), 1150 (C-O) lactone;
1H NMR (400 MHz, CDCl3): δ 7.29 (1H, =CH), 8.25-8.22 (m,
4H, ArH), 8.21-7.57 (m, 3H, ArH), 7.52-7.50 (m, 3H, ArH).
4-(3-Methoxybenzylidene)-2-phenyloxazol-5(4H)-one
(3b): Pale yellow solid; Yield: 91 %; m.p.: 101-103 ºC, lit.
m.p.: 99-102 ºC [28];Anal calcd. (%) for C17H13NO3: C, 73.11;
H, 4.69; N, 5.02. Found: C, 72.89; H, 4.73; N, 5.10. FTIR (νmax
,
cm-1): 1775 (C=O), 1660 (C=N), 1590 (C=C), 1225 (C-N), 1155
(C-O) lactone; 1H NMR (400 MHz, CDCl3):δ3.95 (3H, s, -OCH3),
7.25 (1H, s, =CH), 7.29-7.59 (m, 5H,ArH), 7.65 (t, 1H, ArH),
8.18 (d, 1H, ArH), 8.20 (d, 1H, ArH), 8.22 (s, 1H, ArH).
4-(2,3-Dichlorobenzylidene)-2-phenyloxazol-5(4H)-
one (3c): Light yellow solid; Yield: 86 %; m.p.: 170-173 ºC;
Anal calcd. (%) for C16H9NO2Cl2: C, 60.40; H, 2.85; N, 4.40.
Found: C, 61.10; H, 2.40; N, 4.80. FTIR (νmax, cm-1): 1790 (C=O),
1654 (C=N), 1554 (C=C), 1450, 1320, 1160 (C-O) lactone; 1H
NMR (400 MHz, CDCl3): δ 7.29 (1H, s, =CH), 7.38-7.67 (m,
5H, ArH), 8.20 (1H, dd, ArH), 8.22 (1H, d, ArH), 8.86 (1H, d,
ArH).
4-(4-Hydroxy-3,5-dimethoxybenzylidene)-2-phenyl-
oxazol-5(4H)-one (3i):Yellow solid;Yield: 94 %; m.p.: 216-
218 ºC, lit. m.p.: 217-219 ºC [20];Anal calcd. (%) for C18H15NO5:
C, 66.46; H, 4.65; N, 4.31. Found: C, 67.03; H, 4.88; N, 4.93.
FTIR (νmax, cm-1): 3565 (O-H), 1767 (C=O), 1651 (C=N), 1594
1
4-(3-Bromobenzylidene)-2-phenyloxazol-5(4H)-one
(3d): Light yellow solid; Yield: 89 %; m. p.: 146-148 ºC, lit.
m.p.: 148-149 ºC [20]; Anal calcd. (%) for C16H10NO2Br: C,
(C=C), 1222 (C-O) lactone; H NMR (400 MHz, CDCl3): δ
7.18 (s, 1H, =CH), 6.72 (s, 1H, O-H), 7.44-7.64 (m, 5H, ArH),
7.80-7.88 (m, 1H, ArH), 8.13 (d, 1H, ArH).

Vol. 30, No. 8 (2018)
Synthesis and Herbicidal Activity of 4-Benzylidene-2-phenyl oxazol-5(4H)-one Derivatives 1719
TABLE-2
RESULTS AND DISCUSSION
For the optimization of amount of catalyst, the model
EFFECT OF TEMPERATURE ON THE MODEL REACTION
Entry
Temp. (°C)
Time (min)
Yielda (%)
reaction using reactants benzaldehyde (1a), hippuric acid (2)
and acetic anhydride was carried out at 80 ºC using different
amounts of catalyst (Table-1, entries 1-3). In starting 15 mol%
catalyst was loaded, it took 20 min to complete the reaction
and afforded 92 % yield. The reaction was carried out with 10
mol % amount of catalyst, took 20 min and afforded 92 %
yield. Further decreasing the amount of catalyst to 5 mol%
decreased the yield to 65% by taking a time of 50 min. Thus,10
mol % amount of catalyst was used for carrying out the reaction
for other substrates.
1
2
3
4
Room temperature
300
80
20
70
80
92
92
60
80
90
20
aIsolated yield of products
In order to test the substrate scope of aldehydes, the reaction
was carried out with different aromatic aldehydes having
o-, m- and p-directing substituents on benzene ring.Aldehydes
bearing various functional groups, such as -OMe, -F, -Br, -OH,
-Cl, N(CH3)2, -CH3, produced the corresponding oxazolones
(3a-i). Aromatic aldehydes having o- and p-directing substi-
tuents gave slightly higher yield in comparison to the comp-
ounds having m-directing substituents (Table-3, entries 1-9).
The substituents on the aromatic aldehydes were found to have
a minimal electronic effects.
A plausible mechanism of reaction catalyzed by L-proline
is shown in Scheme-II. The complexA formed by interaction
of acetic anhydride and L-proline initially activates the carboxyl
group of hippuric acid to give compex B which cyclizes to give
intermediate (C). Formation of intermediate (C) has been supp-
orted by earlier workers [41,42]. L-proline abstracts hydrogen
ion from intermediate (C) to convert it to nucleophile (D).
Nucleophile (D) attacks on catalyst activated carbonyl carbon of
aldehyde. Finally removal of water molecule gives the product (E).
Herbicidal activity of synthesized compounds: The pre-
emergence herbicidal activity of synthesized oxazolone deriv-
atives was evaluated against radish seeds (Raphanus sativus).
TABLE-1
EFFECT OF CATALYST LOADING ON THE MODEL REACTION
Entry
Catalyst
Time (min)
Yielda (%)
1
2
3
15
10
5
20
20
50
92
92
65
aIsolated yield of products
In order to optimize the temperature, the model reaction
was carried out at different temperatures (Table-2, entries 1-4).
Initially, the reaction was carried out at ambient temperature
it took 5 h to complete the reaction affording 70 % yield. By
carrying out reaction at 80 ºC, there was significant decrease
in time. The reaction completed within 20 min affording 92 %
yield. Further increase in temperature to 90 ºC did neither impro-
ved yield nor decreased the time. Thus, we selected 80 ºC for carry-
ing out the reaction.
CH3
O
NH
O
O
O O
HO
H3C
O
O
N
Ph
H3C O CH3
H
OH
O
H
O
A
O
-CH3COOH
N
O
NH
Ph
O
OH
B
O
CH3
cat.
O
Ph
-H2O
O
HO
H
O
Ph
H
O
O
H
Ph
E
cat.
Ph
O
N
N
O
H
N
D
H
Ph
-H2O
H
H
N
O
H
OH
N
C
Ph
Ph
O
O
E
Scheme-II: Plausible mechanism for synthesis of oxazolone derivatives using L-proline as catalyst

1720 Bhandari et al.
Asian J. Chem.
TABLE-3
TABLE-4
SYNTHESIS OF 4-ARYLIDENE-2-PHENYL-5(4H)-
MEAN PERCENT GERMINATION INHIBITION
VALUES OF SYNTHESIZED COMPOUNDS
OXAZOLONES DERIVATIVESa 3(a-i)
Timeb
(min)
Compd. code
0.005 M
40.0
40.0
30.0
40.0
36.7
40.0
30.0
46.7
30.0
56.7
15.2
0.01 M
70.0
66.7
63.3
63.3
46.7
70.0
60.0
56.7
56.7
66.7
20.4
0.02 M
86.7
86.7
80.0
76.7
56.7
83.3
76.7
70.0
76.7
80.0
15.6
CD at 5%
21.0
27.4
17.6
24.0
NS
17.6
17.6
17.6
22.1
9.4
Entry
Aldehyde
Products
Yieldc (%)
3a
3b
3c
3d
3e
3f
3g
3h
3i
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
3a
3b
3c
3d
3e
3f
3g
3h
3i
18
22
12
25
16
23
17
18
40
92
91
86
89
94
88
90
96
94
aReaction conditions: aldehyde (1a, 2 mmol), hippuric acid (2, 2
mmol), acetic anhydride (0.6 mL) and L-proline (10 mol %), 80 °C.
bReaction progress by TLC.
Stand. (Butachlor)
CD at 5%
CD = Critical difference
–
cIsolated yield of products.
The mean per cent shoot length inhibition values of synthe-
sized compounds along with standard are presented in Table-5.
The results revealed that with increase in concentration from
0.005 M to 0.01 M and then to 0.02 M, there is significant increase
in activity for all the compounds except compounds 3e and 3h
for which the data are not statistically significant. Comparison
of the shoot inhibition values of the compounds with standard at
concentration 0.005 M indicates that all the compounds exhibit
significantly lower activity in comparison to standard (75.2 %).
At concentration 0.01 M, all the compounds exhibit significantly
lower activity in comparison to standard (83.6 %) while at
concentration 0.02 M for all compounds except compound 3e
(83.7 %) and compound 3h (85.2%) again significant activity at
par with standard (94.4%) is observed.
The herbicide butachlor was taken as standard. Each of the
compound was first dissolved in minimum amount of ethanol,
two drops of 1 % Tween 20 were added to the solution and made
up with distilled water to prepare a stock solution of concen-
tration 500 mg/L. Then by serial dilution with distilled water,
solutions of concentration 0.02, 0.01 and 0.005 M were prepared.
Three replicates were used for each treatment. Prior to putting
the seeds in Petri-dish for germination, the seed of radish
(Raphanus sativus) were sterilized in 1% sodium hypochlorite
solution for 30 min. Ten seeds of raddish were taken in each
petri dish containing a piece of filter paper and 7 mL solution
of each test solution. Distilled water was used as control. The
petri dishes were closed by parafilm to prevent the loss of mois-
ture. The petri dishes were kept in incubator at 25 2 ºC for
germination. The seed germination was assessed by taking obser-
vations after 120 h of incubation. The number of seeds germi-
nated were counted. Shoot and rooth lengths were also measured.
The germination inhibition, root length inhibition and shoot
lengthinhibition were subjected to analysis of variance (ANOVA)
by STPR3 software and critical differences (CDs) at p > 0.05 were
calculated.
The mean percent germination inhibition values of synthe-
sized compounds and standard (butachlor) with their CD values
are presented inTable-4, which clearly indicates that with increase
in concentration from 0.005 M to 0.01 M for all the compounds
including standard except compounds 3b and 3i, there is signi-
ficant increase in activity while with increase in concentration
from 0.01 M to 0.02 M there is no significant increase in activity
for the compounds except compounds 3d, 3e and 3h. Though
for standard significant increase in activity is observed. So,
concentration 0.01 M may be taken to get limiting activity for
the compounds mentioned previously. Comparison of activity
of compounds at 0.005 M concentration with standard revealed
that only the compound 3h exhibited activity (46.7 %) at par
with standard (56.7 %).At concentration 0.01 M all the comp-
ounds exhibited significant activity at par with standard (66.7
%). At concentration 0.02 M also all the compounds except
compound 3e (56.7%), significant activity at par with standard
(80 %). It may be inferred that all the compounds exhibit signi-
ficant activity at par with standard at concentration 0.01 M and
this concentration may be taken as basal concentration for
achieving limiting activity.
TABLE-5
MEAN PERCENT SHOOT LENGTH INHIBITION
VALUES OF SYNTHESIZED COMPOUNDS
Compd. code
0.005 M
51.5
57.0
54.2
60.5
54.7
58.7
57.0
54.5
58.4
75.2
10.7
0.01 M
68.1
70.3
72.9
74.5
67.2
74.2
70.1
60.6
71.6
83.6
6.8
0.02 M
95.2
95.1
96.7
100
83.7
95.6
93.9
85.2
96.3
94.4
4.3
CD at 5%
2.1
3a
3b
3c
3d
3e
3f
3g
3h
3i
2.7
1.8
2.4
NS
1.8
1.8
NS
2.2
Stand. (Butachlor)
CD at 5 %
0.9
–
The anomaly of getting higher activity at lower concen-
tration and vice versa may be explained by keeping in view
the fact that some compounds may exhibit plant growth regul-
atory activity depending upon the dose [43].
The mean percent root length inhibition values of synthe-
sized compounds including standard are presented in Table-6.
The results indicates that with increase in concentration from
0.005 to 0.01 M and then to 0.02 M, there is significance increase
in concentration for all the compounds including standard.
Comparison of activity of synthesized compounds with standard
at 0.005 M concentration revealed that all the compounds except
compound 3d (76.1%) exhibit significantly lower activity in
comparison to standard (73.7 %). At concentration 0.01 M, the

Vol. 30, No. 8 (2018)
Synthesis and Herbicidal Activity of 4-Benzylidene-2-phenyl oxazol-5(4H)-one Derivatives 1721
7. N.D. Argade, B.K. Kalrale and C.H. Gill, E-J. Chem., 5, 120 (2008);
TABLE-6
https://doi.org/10.1155/2008/265131.
MEAN PERCENT ROOT LENGTH INHIBITION
VALUES OF SYNTHESIZED COMPOUNDS
8. M. Tandon, D.L. Coffen, P. Gallant, D. Keith and M.A.Ashwell, Bioorg.
Med. Chem. Lett., 14, 1909 (2004);
https://doi.org/10.1016/j.bmcl.2004.01.094.
9. F.M. Perron-Sierra, A. Pierré, M. Burbridge and N. Guilbaud, Bioorg.
Med. Chem. Lett., 12, 1463 (2002);
https://doi.org/10.1016/S0960-894X(02)00197-X.
10. M. Parveen, A. Ali, S. Ahmed, A.M. Malla, M. Alam, P.S. Pereira Silva,
M.R. Silva and D.-U. Lee, Spectrochim. Acta A Mol. Biomol. Spectrosc.,
104, 538 (2013);
Compd. code
0.005 M
55.7
42.7
63.7
76.1
44.9
46.9
43
0.01 M
83.2
68.6
83.9
85.3
55.6
67
0.02 M
96.7
97.0
93.6
94.9
61.2
86.1
83.1
93.6
85.5
94.9
5.0
CD at 5%
4.3
3a
3b
3c
3d
3e
3f
3g
3h
3i
4.9
7.9
1.3
3.9
6.6
1.4
3.0
1.2
https://doi.org/10.1016/j.saa.2012.11.054.
65.2
68
11. U. Salgin-Göksen, N. Gökhan-Kelekçi, Ö. Göktas, Y. Köysal, E. Kilic,
S. Isik, G. Aktay and M. Özalp, Bioorg. Med. Chem., 15, 5738 (2007);
https://doi.org/10.1016/j.bmc.2007.06.006.
12. M. Witvrouw, C. Pannecouque, E. De Clercq, E. Fernández-Alvarez and
J.L. Marco, Arch. Pharm., 332, 163 (1999);
48.3
65.7
73.7
3.1
74.7
81.9
2.0
Stand. (Butachlor)
CD at 5 %
0.6
–
https://doi.org/10.1002/(SICI)1521-4184(19995)332:5<163::AID-
ARDP163>3.0.CO;2-2.
compounds 3a (83.2 %), 3c (83.9 %) and 3d (85.3 %) exhibit
activity at par with standard (81.9 %) while the remaining comp-
ounds exhibit significantly lower activity in comparison to the
standard. At concentration 0.02 M, the compounds 3a (96.7 %),
3b (97.0 %), 3c (93.6 %), 3d (94.9 %) and 3h (93.6 %) exhibit
activity at par with standard (94.9 %) while compounds 3e
(61.2%), 3f (86.1%), 3g (83.1 %) and 3i (85.5 %) exhibit activity
significantly lower in comparison to the standard.
13. I.L. Pinto, A. West, C.M. Debouck, A.G. DiLella, J.G. Gorniak, K.C.
O’Donnell, D.J. O’Shannessy, A. Patel and R.L. Jarvest, Bioorg. Med.
Chem. Lett., 6, 2467 (1996);
https://doi.org/10.1016/0960-894X(96)00456-8.
14. K.M. Khan, U.R. Mughal, M.T.H. Khan, Zia-Ullah, S. Perveen and M.
Iqbal Choudhary, Bioorg. Med. Chem., 14, 6027 (2006);
https://doi.org/10.1016/j.bmc.2006.05.014.
15. G. Mariappan, B.P. Saha, S. Datta, D. Kumar and K.P. Haldar, J. Chem.
Sci., 123, 335 (2011);
https://doi.org/10.1007/s12039-011-0079-2.
In conclusion, pre-emergence seed germination inhibition
studies clearly indicate that most of the compounds are at par
with standard butachlor in activity. So, these compounds may
be developed as potential herbicides. Moreover, with variation
in concentration, shoot growth is not inhibited with increase in
concentration which indicates plant growth regulatory activitiy
present in compounds. Though, it needs further research to ascer-
tain plant growth regulatory activity of these compounds.
16. G. Ozturk, S. Alp and Y. Ergun, Tetrahedron Lett., 48, 7347 (2007);
https://doi.org/10.1016/j.tetlet.2007.08.018.
17. D.I. Chai, L. Hoffmeister and M. Lautens, Org. Lett., 13, 106 (2011);
https://doi.org/10.1021/ol102634c.
18. Z. Lu, X. Xu, Z. Yang, L. Kong and G. Zhu, Tetrahedron Lett., 53, 3433
(2012);
https://doi.org/10.1016/j.tetlet.2012.04.074.
19. A.M. Tikdari, S. Fozooni and H. Hamidian, Molecules, 13, 3246 (2008);
https://doi.org/10.3390/molecules13123246.
20. M. Rostami,A.R. Khosropour,V. Mirkhani, I. Mohammadpoor-Baltork,
M. Moghadam and S. Tangestaninejad, Chimie, 14, 869 (2011);
https://doi.org/10.1016/j.crci.2011.02.003.
Conclusion
A novel and eco-freiendly approach for the synthesis of
4-benzylidene-2-phenyloxazol-5(4H)-one derivatives in excellent
yield using L-proline as convenient and inexpensive organo-
catalyst is reported. The preliminary bioassay showed that most
of the synthesized compounds had good to excellent seed germi-
nation inhibition activity against radish seed (Raphanus sativus).
21. D. Roiban, E. Serrano, T. Soler, I. Grosu, C. Cativiela and E.P. Urriolabeitia,
Chem. Commun., 4681 (2009);
https://doi.org/10.1039/b907647f.
22. M. Yamashita, S.-H. Lee, G. Koch, J. Zimmermann, B. Clapham and
K.D. Janda, Tetrahedron Lett., 46, 5495 (2005);
https://doi.org/10.1016/j.tetlet.2005.06.061.
23. A.S.K. Hashmi, R. Salathé and W. Frey, Synlett, 1763 (2007);
https://doi.org/10.1055/s-2007-982562.
24. V. Taile, K. Hatzade, P. Gaidhane and V. Ingle, Turk. J. Chem., 33, 295
(2009).
ACKNOWLEDGEMENTS
25. R. Khosropour, M.M. Khodaei and S.J.H. Jomor, J. Heterocycl. Chem.,
45, 683 (2008);
https://doi.org/10.1002/jhet.5570450308.
26. F.M.F. Chen, K. Kuroda and N.L. Benoiton, Synthesis, 230 (1979);
https://doi.org/10.1055/s-1979-28634.
The authors are grateful to Department of Chemistry,
Govind Ballabh Pant University ofAgriculture & Technology,
Pantnagar, India for support.
27. Y.J. Rao, Org. Chem., 41, 722 (1976);
REFERENCES
https://doi.org/10.1021/jo00866a037.
28. P.A. Conway, K. Devine and F. Paradisi, Tetrahedron, 65, 2935 (2009);
https://doi.org/10.1016/j.tet.2009.02.011.
29. K.A. Monk, D. Sarapa and R.S. Mohan, Synth. Commun., 30, 3167 (2000);
https://doi.org/10.1080/00397910008086926.
30. G. Romanelli, J.C. Autino, P. Vazquez, L. Pizzio, M. Blanco and C.
Caceres, Appl. Catal. A, 352, 208 (2009);
1. S.L. Schreiber, Science, 287, 1964 (2000);
https://doi.org/10.1126/science.287.5460.1964.
2. E.E. Jun, Ann. Chem., 275, 1 (1893);
https://doi.org/10.1002/jlac.18932750102.
3. F.M. Istrate, A.K. Buzas, I.D. Jurberg, Y. Odabachian and F. Gagosz, Org.
Lett., 10, 925 (2008);
https://doi.org/10.1021/ol703077g.
4. F.M. Bautista, J.M. Campelo, A. Garcia, D. Luna and J.M. Marinas, Amino
Acids, 2, 87 (1992);
https://doi.org/10.1007/BF00806078.
5. M.I. Ismail, Can. J. Chem., 69, 1886 (1991);
https://doi.org/10.1139/v91-273.
6. B.S. Park, C.M. Oh, K.H. Chun and J.O. Lee, Tetrahedron Lett., 39, 9711
(1998);
https://doi.org/10.1016/j.apcata.2008.10.003.
31. B.S.G. Taki,V. Mirkhani, I.M. Baltork, M. Moghadam, S. Tangestaninejad,
M. Rostami and A.R. Khosropour, J. Inorg. Organomet. Polym., 23, 758
(2013);
https://doi.org/10.1007/s10904-012-9810-9.
32. C. Yu, B. Zhou, W. Su and Z. Xu, Synth. Commun., 36, 3447 (2006);
https://doi.org/10.1080/00397910600941521.
33. S. Paul, P. Nanda, R. Gupta and A. Loupy, Tetrahedron Lett., 45, 425
(2004);
https://doi.org/10.1016/S0040-4039(98)02232-1.
https://doi.org/10.1016/j.tetlet.2003.10.125.

1722 Bhandari et al.
Asian J. Chem.
34. F.M. Bautista, J.M. Campelo, A. Garcia, D. Luna, J.M. Marinas and A.
Romero, J. Chem. Soc., Perkin Trans. 2, 227 (2002);
https://doi.org/10.1039/b109413k.
35. S.J. Ahmadi, S. Sadjadi and M. Hosseinpour, Ultrason. Sonochem.,
20, 408 (2013);
39. E.M. Beccalli, F. Clerici and M.L. Gelmi, Tetrahedron, 55, 781 (1999);
https://doi.org/10.1016/S0040-4020(98)01070-9.
40. M. Parveen, F. Ahmad, A.M. Malla, S. Azaz, M.R. Silva and P.S.P. Silva,
RSC Adv., 5, 52330 (2015);
https://doi.org/10.1039/C5RA09290F.
https://doi.org/10.1016/j.ultsonch.2012.07.008.
36. M.A. Pasha, V.P. Jayashankara, K.N. Venugopala and K.G. Rao, J.
Pharmacol. Toxicol., 2, 264 (2007);
https://doi.org/10.3923/jpt.2007.264.270.
37. J. Kashyap,A.B. Chetry and P.J. Das, Synth. Commun., 28, 4187 (1998);
https://doi.org/10.1080/00397919809458699.
41. T. Cleary, J. Brice, N. Kennedy and F. Chavez, Tetrahedron Lett., 51,
625 (2010);
https://doi.org/10.1016/j.tetlet.2009.11.081.
42. S. Paul, P. Nanda, R. Gupta and A. Loupy, Tetrahedron Lett., 43, 4261
(2002);
https://doi.org/10.1016/S0040-4039(02)00732-3.
43. S.C. Fang and J.S. Butts, Plant Physiol., 29, 365 (1954);
https://doi.org/10.1104/pp.29.4.365.
38. S. Tanimori,Y. Kobayashi,Y. Iesaki,Y. Ozaki and M. Kirihata, Org. Biomol.
Chem., 10, 1381 (2012);
https://doi.org/10.1039/C1OB05875D.