4

ISSN:2230-7346
Research Article
Available online http://WWW.JGTPS.COM
Journal of Global Trends in Pharmaceutical Sciences

Vol.1, Issue 1, pp 26-41, OctoberDecember 2011
Microwave assisted synthesis of some new 3-(4-substituted anilino)-5-(3', 4disubstituted aryl)-2-isoxazoles as potential Anthelmintic agents.
Chakka Gopinath1*, Rama Rao Nadendla2, K. Lakshmi, N. lakshmi Prasanthi, C.Vijaya
Bhaskar. M.K.Prahllad, K.B.N. Rao, R.Ramakrishna.
1
2
Hindu college of pharmacy, Guntur -522002Andhra Pradesh. India.

Chalapathi institute of pharmaceutical sciences Guntur 522034, Andhra Pradesh,India
Corresponding autor E-mail: gopinathchakka_master@yahoomail.com
ABSTRACT
56 new 3-(4-substituted anilino)-5-(3', 4-disubstituted aryl)-2-isoxazoles were synthesized by

microwave irradiation (560 w) of 3-phenyl or substituted phenyl -1- anilino or substituted
anilino -2- propene -1- ones with hydroxylamine hydrochloride and sodium acetate. The
structures of the compounds were proved by means of their I R, 1H NMR, mass spectroscope and
elemental analysis data.
Key words:- 3- phenyl or substituted phenyl -1- anilino or substituted anilino -2- propene -1ones, hydroxylamine hydrochloride, sodium acetate, Anthelmintic activity.
INTRODUCTION:
Microwave dielectric heating is widely
environmentally benign synthesis under
exploited
microwave
for
acceleration
of
organic
irradiation.
Considerable
reactions during last one decade1-16.there is
interest has been focused on the isoxazole
an increasing interest in the utility of
structure17-29, which as been known to

26
possess a broad spectrum of biological
In view of the wide range of
activities such as psychotropic effects30,
therapeutic value of isoxazole ring system
analgesics31-32,
potential
33-34
activity
antimicrobial
promoted us to plan the synthesis of a series
35
herbicidal
activity ,
of some new isoxazole derivatives by
antineoplastic activity36, , anti inflammatory
microwave
activity37,
synthesis of compounds suffered from the
CNS
activity38
and
chemotherapy39.
irradiation
the
traditional
disadvantages such as long reaction time,
The discovery of this class of drugs
low yield and inconvenience of handling
provides an outstanding case history of
where as the use of microwave irradiation
modern drugs development and also points
technology in organic synthesis lead to
out the unpredictability of biological activity
increase the purity of products, enhance the
from structural modification of a prototype
chemical yield and shorten the reaction time.
drug molecule.
EXPERMENTAL SECTION:
Melting
point
of
synthesized
synthesized compounds were elucidated by
compounds was determined by an open-end
Perkin
capillary tube method by electrically heated
Transformer-Infrared Spectrophotometer in
melting point apparatus expressed in 0C and
KBr-Pellet method. IR values are measured
was
the
in cm-1 and the results are shown below. The
compounds was checked by TLC. In all the
structures of synthesized compounds were
cases the distances traveled by the sample
elucidated by
was found to be different from that of the
AMX 400 MHz) analyzer using TMS as
parent compound spotted along with it. Thus
internal standard. The samples are dissolved
confirming the fact that the compounds
in CdCl3, DMSO and the values are
formed were entirely different from that of
measured in chemical shift in delta () ppm.
the parent compound. Rf and Rm values of
The values of the assigned structures were
title compounds were shown in Table No.-
interpreted as follows. The mass spectrum of
III-3.
the compound was recorded on MDS spiex
uncorrected.
The
purity
of
The characterization data of
Elmer
1600
series
Fourier
H FT-NMR (BRUCKER
AP12000 LC-MS mass spectrometer. Mass
the synthesized compounds were given in
spectrum
the Table No.-III-3. The structures of the
molecular ion at m/z and the results are

27
of
the
compound
showed
shown
below.
The
elements
of
the
substituent groups were observed within the
synthesized compounds were calculated by
expected chemical shift values (table No.III-
chem... office software and the data obtained
5)
from Carlo Erba- 1108 elemental analyzer
The synthesized compounds (56)
are presented in Table No.-III-4 has been
were screened for anthelmintic activity by
found to be in agreement with the molecular
using
formula of the assigned structures.
obtained from agriculture department using
IR spectra of the compounds showed N-H
standard drug. This method is effective in
stretching band at 3240. 52cm-1 in the 1H
predicting the anthelmentic activity of a
NMR spectra 3.393(NH) and the protons
wide variety of new molecules.
belonging
to
the
aromatic
ring
Peritima
posthuma
(earthworm)
and
General procedure for the synthesis of isoxazoles:

Method A (Conventional) Step 1: Synthesis of 3-phenyl or 3-substituted phenyl-1-anilino
or 1-substituted anilino-2-propene-1-ones:
To a solution of acetanilide or its derivative
TLC for the completion of reaction. Then
compounds (0.01 mole) in ethanol (25 ml),
hot reaction mixture was poured into
aldehyde (or) substituted aldehyde (0.01
crushed ice, and the separated product was
mole) was added in presence of 2% NaOH
filtered
solution. The reaction mixture was refluxed
chromatography
and
purified
by
column
for 12 hours. The reaction was monitored by

.
Step 2: Synthesis of 3-[4-substituted anilino]-5-[3`4`-disubstituted aryl]-2-isoxazole.
Isoxazoles were synthesized by refluxing
TLC for the completion of reaction. Then
Chalcones (0.01 mole) with hydroxylamine
hot reaction mixture was poured into
hydrochloride (0.00014 mole) and sodium
crushed ice, and the separated product was
acetate (0.08 mole) in ethanol, for 6 hours
filtered
and the reaction was closely monitored by
chromatography
and
purified
by
column
.
Method B (MORE) Microwave Induced Organic Reaction Enhancement Step 1:
Synthesis of 3-phenyl or substituted phenyl-1-anilino or substituted anilino-2-propene-1ones:
28
To a solution of acetanilide and its
(560W) for specified period (as ment ioned
derivative compounds (0.01 mole) in ethanol
in the Table No.-III-2). The hot reaction
(25 ml), aldehyde (or) substituted aldehyde
mixture was poured into crushed ice and the
(0.01 mole) was added in the presence of
separated product was filtered and purified
2% NaOH solution. The reaction mixture
by column chromatography.
was subjected for Microwave irradiation

Step 2: Synthesis of 3-[4-substituted anilino]-5-[3`4`-disubstituted aryl]-2-isoxazole.
By adopting the above synthetic procedure
Isoxazoles were synthesized

by
Microwave
irradiation
(560W)
of
the compounds 1-56(IIIa-IIIz, IIIaa-IIIaz,
chalcone (0.01 mole) with hydroxylamine

IIIba-IIIbd)
hydrochloride (0.00014 mole) and sodium
were
synthesized
by
conventional and microwave methods. The
acetate (0.08 mole) in ethanol, for specified

period (as mentioned in the Table No.-III-2).
physical and spectral characteristics of these
The hot reaction mixture was poured into

isoxazoles 1-56 (IIIa-IIIz, IIIaa-IIIaz, IIIba-
crushed ice, filtered and purified by column

chromatograph.
IIIbd) were presented.
29
NH
CH3
Ar
C2H5OH, 2%NaOH
-H2O
Step - I
O
X
NH
O
CH
CH
Ar
NH
Step - II
CH
C Ar
H
Y
NH2OH. HCl,C2H5OH, CH3COOH
-H2O, -HCl
Microwave synthesis
-H2O, -HCl
NH
NH
N
NH2OH. HCl,C2H5OH
CH3COOH
Step - II
Conventional synthesis
Step - I
Microwave synthesis
Conventional synthesis
Ar
The various substituents present in the prepared isoxazoles are listed below: Table No.-III.1
S.No.
01.
02.
03.
04.
05.
06.
07.
08.
09.
10.
11.
12.
13.
14.
15.
16.
17.
18.
Comp. Code
III a
III b
III c
III d
III e
III f
III g
III h
III i
III j
III k
III l
III m
III n
III o
III p
III q
III r
X
H
H
H
H
H
H
H
OH
OH
OH
OH
OH
OH
OH
Br
Br
Br
Br
30
Y
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ar
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4(NO2)
C6H4 (NO2)
C6H4 (OCH3)
C5H4O2
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4(NO2)
C6H4 (NO2)
C6H4 (OCH3)
C5H4O2
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4(NO2)
Ar
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
III s
III t
III u
III v
III w
III x
III y
III z
III aa
IIIab
III ac
III ad
III ae
III af
III ag
III ah
III ai
III aj
III ak
III al
III am
III an
III ao
III ap
III aq
III ar
III as
III at
III au
III av
III aw
III ax
III ay
III az
III ba
III bb
III bc
III bd
Br
Br
Br
NO2
NO2
NO2
NO2
NO2
NO2
NO2
CH3
CH3
CH3
CH3
CH3
CH3
CH3
F
F
F
F
F
F
F
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
F
F
F
F
F
F
F
C6H4 (NO2)
C6H4 (OCH3)
C5H4O2
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4 (NO2)
C6H4 (NO2)
C6H4(OCH3)
C5H4O2
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4(NO2)
C6H4 (NO2)
C6H4(OCH3)
C4H3O
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4(NO2)
C6H4 (NO2)
C6H4 (OCH3)
C5H4O2
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4 (NO2)
C6H4(NO2)
C6H4 (OCH3)
C5H4O2
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4(NO2)
C6H4 (NO2)
C6H4(OCH3)
C4H3O
Comparison of microwave and conventional reactions of the title compounds Table No-III-2
S.No
01.
02.
03.
04.
05.
06.
07.
08.
09.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
Comp. code
III a
III b
III c
III d
III e
III f
III g
III h
III i
III j
III k
III l
III m
III n
III o
III p
III q
III r
III s
III t
III u
Reaction time
%Yield
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
52.6
60.1
70.5
61.4
62.6
64.6
59.5
13.43
15.0
33.9
35.8
31.44
21.00
18.4
69.6
59.2
72
56.2
58.4
56.2
49.3
Appearance
Solid(crystal),white
Solid(crystal),broen
Solid(crystal),blackishSolid(crystal), light-brown
Solid(crystal), light-orange
Solid(crystal), light-yellow
Solid(crystal),
lightSolid(amorphous), black
Solid(amorphous),
light-
Solid(crystal), dark-black
Solid(amorphous),white
Solid(amorphous),light
Solid(crystal),black
Solid(amorphous), black
31
Reaction
1.5
2.0
2.5
2.0
2.0
2.5
2.0
1.5
1.5
1.0
1.5
1.5
1.5
1.5
3.0
1.5
2.5
3.0
3.0
3.0
3.0
60.11
65.5
85.2
67.4
68.1
72.1
66.4
32.6
48.4
51.34
91.4
90.0
49.6
30.7
86.6
76.7
94
76
72
82
60
%Yield
Solid(crystal),broen
Solid(crystal),blackish-brown
Solid(crystal),light-brown
Solid(crystal),light-orange
Solid(crystal),light-yellow
Solid(crystal),light-brown
Solid(amorphous),lightSolid(crystal), dark-black
Solid(amorphous),light white
Ap
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
III v
III w
III x
III y
III z
III aa
IIIab
III ac
III ad
III ae
III af
III ag
III ah
III ai
III aj
III ak
III al
III am
III an
III ao
III ap
III aq
III ar
III as
III at
III au
III av
III aw
III ax
III ay
III az
III ba
III bb
III bc
III bd
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
360
37.5
46.2
60.6
44.2
49.1
57.2
52.6
46.2
49.2
47.9
50.1
52.2
53.9
48.7
26.7
49.8
57.7
73.5
41.6
39.7
29.8
62.0
53.7
71.5
21.4
49.8
74.9
55.6
40.8
46.5
60.4
21.4
63.6
39.2
56.4
Solid(crystal), light-white
Solid(amorphous), yellow
Solid(crystal), yellow
Solid(amorphous),pure
Solid(amorphous),lightSolid(amorphous), yellow
Solid(crystal), pure-white
Solid(amorphous),brown
Solid(amorphous)light
Solid(crystal), light black
Solid(crystal), pure white
Solid(amorphous), brown
Solid(crystal),pure white
Solid(amorphous), white
Solid(crystal), brown
Solid,(amorphous)
1.5
1.5
2.5
12.0
2.0
2.0
1.5
1.5
1.5
2.5
2.0
2.5
2.5
2.5
2.5
2.5
2.0
2.0
2.0
2.0
1.5
2.5
2.0
3.0
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.0
2.0
2.0
58.11
63.2
83.96
66.2
67.7
62.2
68.4
56.6
61.
69.3
66.8
70.1
66.1
59.2
49
61
78
95.6
58.6
50.6
44
80
64
91
34
68
98
76
60
69.5
81
37
83.7
52
70
Physical characterization of 3-(4-Substituted Anilino)-5-(3,4-Disubstituted Aryl)-2Isoxazoles Table No-III-3

S. No.
01.
02.
03.
04.
05.
06.
07.
08.
09.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
Comp.
III a
III b
III c
III d
III e
III f
III g
III h
III i
III j
III k
III l
III m
III n
III o
III p
III q
III r
III s
Mp0C
198
201
128
170
172
175
192
82.0
>220
133.0
87.0
111.0
155.0
174
79
226
129
91
117
Mol. Formula and Mol.Wt.

C15H12N2O (236)
C16H14N2O3 (282)
C17H17N3O (279)
C15H11N3O3 (282)
C15H11N3O3 (282)
C16H14N2O2 (266)
C14H13N2O3(255)
C15H12N2O2 (252.616)
C161H14N2O4 (282.292)
C17H14N3O2 (295.336)
C15H11N3O4 (297.298)
C15H11N3O4 (297.298)
C16H14N2O3 (271.248)
C14H11N2O4 (271.248)
C15H11N2OBr(315.162)
C16H13N2O3Br(361.18)
C17H16N3OBr(358.22)
C15H10N3O3Br(360.16)
C15H10N3O3Br (362)
32
Rf Value
0.680
0.672
0.580
0.499
0.501
0.702
0.696
0.590
0.499
0.692
0.689
0.699
0.598
0.594
0.612
0.596
0.482
0.613
0.624
Rm Value
-0.130
-0.311
-0.140
-0.001
0.001
-0.372
-0.360
-0.158
0.017
-0.351
-0.345
-0.366
-0.172
-0.165
-0.198
-0.169
-0.031
-0.199
-0.220
Solid(amorphous),
light
Solid(crystal), light-white
Solid(crystal), yellow
Solid(amorphous),
light
Solid(amorphous), pure white
Solid(amorphous),
lightSolid(amorphous), yellow
Solid(crystal), pure-white
Solid(amorphous),brown
Solid(amorphous), light black
Solid(amorphous),
light
Solid(amorphous)
light
Solid(crystal), light black
Solid(crystal), pure white
Solid(amorphous), brown
Solid(crystal),pure white
Solid(amorphous), white
Solid(amorphous),
light
Solid(crystal), brown
Solid,(amorphous)
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
III t
III u
III v
III w
III x
III y
III z
III aa
IIIab
III ac
III ad
III ae
III af
III ag
III ah
III ai
III aj
III ak
III al
III am
III an
III ao
III ap
III aq
III ar
III as
III at
III au
III av
III aw
III ax
III ay
III az
III ba
III bb
III bc
III bd
C16H13N2O2Br (345.18)
C14H10N2O3Br(334.14)
C15H11N3O3 (281.268)
C16H13N3O5 (327.294)
C17H16N4O3 (324.338)
C15H10N4O5 (326.27)
C15H10N4O5 (326.27)
C16H13N3O4 (311.294)
C14H10N3O5 (300.25)
C16H14N2O(250.29)
C17H16N2O3(296.31)
C18H19N3O(293.36)
C16H13N3O3 (295.294)
C16H13N3O3 (297)
C17H16N2O2 (280.31)
C15H13N2O3(269.274)
C14H10N2O3 F (273.24)
C15H11N2OF(254.25)
C16H13N2O3F (300.28)
C17H16N3OF (297.32)
C15H10N3O3F (299.26)
C15H10N3O3F N (299.26)
C16H13N2O2F (284.28)
C15H11N2OCl (270.7)
C16H13N2O3Cl (316.73)
C17H16N3OCl (314.33)
C15H10N3O3Cl (315.71)
C15H10N3O3Cl (315.71)
C16H13N2O2Cl(300.73)
C14H10N2O3Cl (289.69)
C15H10N2OClF (288.7)
C16H12N2O4ClF (350.72)
C17H15N3OClF (331.17)
C15H9N3O3ClF (333.7)
C15H9N3O3ClF (333.7)
C16H12N2O2ClF(318.73)
C13H8N2O2ClF(288.74)
149
162
203.0
203.0
123.0
173
177.0
179
191.0
199
201
128
176
171
169
186
140
142
143
90
138
140
141
162
180
120
170
176
152
166
112
116
93
108
106
112
101
0.724
0.698
0.676
0.668
0.693
0.654
0.649
0.602
0.594
0.599
0.583
0.642
0.656
0.659
0.712
0.791
0.689
0.678
0.596
0.693
0.695
0.697
0.704
0.669
0.599
0.641
0.587
0.601
0.718
0.701
0.699
0.604
0.687
0.598
0.601
0.712
0.713
-0.376
-0.364
-0.319
-0.303
-0.353
-0.276
-0.267
-0.179
-0.165
-0.174
-0.145
-0.254
-0.280
-0.286
-0.393
-0.578
-0.345
-0.324
-0.169
-0.353
-0.358
-0.362
-0.376
-0.158
-0.174
-0.251
-0.153
-0.178
-0.406
-0.370
-0.366
-0.183
-0.341
-0.172
-0.178
-0.393
-0.395
Elemental analysis of 3-(4-Substituted anilino)-5-(3,4-disubstituted aryl)-2-isoxazoles Table No-III-4
S.No
Comp.
Ar
Code
01.
02.
03.
04.
05.
06.
07.
08.
09.
10.
11.
12.
13.
14.
15.
16.
III a
III b
III c
III d
III e
III f
III g
III h
III i
III j
III k
III l
III m
III n
III o
III p
H
H
H
H
H
H
H
OH
OH
OH
OH
OH
OH
OH
Br
Br
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4(NO2)
C6H4 (NO2)
C6H4 (OCH3)
C5H4O2
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4(NO2)
C6H4 (NO2)
C6H4 (OCH3)
C5H4O2
C6H5
C6H3(OH) (OCH3)
C
76.2
68.0
64.5
64.0
64.0
72.1
65.8
71.3
68.0
69.1
60.5
60.5
68.0
61.9
57.1
53.2
Found
H
5.08
4.96
6.09
3.91
3.91
5.26
4.31
4.78
4.99
5.80
3.72
3.72
4.99
4.05
3.51
3.62
33
N
11.86
9.92
15.05
14.94
14.94
10.52
10.98
11.07
9.92
14.23
14.14
14.14
9.9
10.33
8.89
7.75
O
6.77
17.02
5.73
17.08
17.08
12.03
18.82
12.6
17.0
10.83
21.5
21.5
17.0
23.5
5.07
13.28
C
73.96
66.27
63.51
62.192
63.299
70.810
63.277
68.386
66.72
68.168
60.050
60.001
67.806
60.95
56.89
51.48
H
4.978
4.795
5.972
3.713
3.821
5.106
3.445
4.855
4.353
5.638
3.643
3.647
3.982
3.746
3.421
2.963
N
10.276
9.864
14.22
12.948
12.898
10.256
10.872
10.701
9.392
12.423
13.014
13.401
9.892
9.203
8.398
6.577
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
III q
III r
III s
III t
III u
III v
III w
III x
III y
III z
III aa
IIIab
III ac
III ad
III ae
III af
III ag
III ah
III ai
III aj
III ak
III al
III am
III an
III ao
III ap
III aq
III ar
III as
III at
III au
III av
III aw
III ax
III ay
III az
III ba
III bb
III bc
III bd
Br
Br
Br
Br
Br
NO2
NO2
NO2
NO2
NO2
NO2
NO2
CH3
CH3
CH3
CH3
CH3
CH3
CH3
F
F
F
F
F
F
F
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
F
F
F
F
F
F
F
C6H4N (CH3)2
C6H4(NO2)
C6H4 (NO2)
C6H4 (OCH3)
C5H4O2
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4 (NO2)
C6H4 (NO2)
C6H4(OCH3)
C5H4O2
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4(NO2)
C6H4 (NO2)
C6H4(OCH3)
C4H3O
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4(NO2)
C6H4 (NO2)
C6H4 (OCH3)
C5H4O2
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4 (NO2)
C6H4(NO2)
C6H4 (OCH3)
C5H4O2
C6H5
C6H3(OH) (OCH3)
C6H4N (CH3)2
C6H4(NO2)
C6H4 (NO2)
C6H4(OCH3)
C4H3O
56.9
50.0
40.0
55.1
50.3
64.0
58.7
62.1
55.2
55.2
61.7
56.0
76.7
68.9
73.6
65.0
65.1
72.8
66.9
61.5
70.8
67.0
68.6
60.2
60.2
67.5
66.4
60.6
64.9
157.
157.
63.9
59.9
62.4
54.7
61.6
53.9
53.9
60.2
54.0
4.5
2.79
2.79
3.79
3.01
3.94
4.03
4.9
3.08
3.08
4.209
3.35
5.63
5.44
6.52
4.43
4.43
5.75
4.86
3.68
5.35
4.36
5.42
3.36
3.36
4.61
4.09
4.13
5.12
3.19
3.19
10.01
3.98
3.49
3.44
4.56
2.71
2.71
3.79
6.28
11.33
11.66
11.66
8.11
8.36
14.94
12.84
17.2
17.17
17.17
13.5
13.99
11.19
9.45
14.32
14.23
14.23
9.99
10.4
10.25
11.0
9.33
14.13
14.0
14.0
9.85
10.35
8.84
13.37
13.31
13.31
13.96
9.67
9.70
7.98
12.69
12.59
12.59
8.79
9.70
4.46
13.32
13.32
9.27
14.36
17.16
24.44
14.79
24.5
24.5
20.
26.6
6.39
16.9
5.45
16.25
16.25
11.41
17.82
17.
6.29
15.98
5.38
16.04
16.04
11.25
5.91
15.15
5.09
15.20
15.20
10.64
16.57
5.55
18.24
4.83
14.38
14.38
10.04
11.08
55.95
49.8
40.705
56.1
49.25
63.29
57.4
60.155
53.194
54.933
59.716
55.62
74.619
67.94
72.96
65.6
64.79
72.8
65.2
61.5
68.708
66.01
67.952
58.216
58.618
66.95
65.40
60.50
64.80
55.76
56.75
62.93
58.35
61.8
53.76
60.3
52.853
52.853
60.018
52.501
3.954
2.197
2.192
3.297
3.003
3.496
4.001
3.966
3.072
3.001
4.109
3.297
5.436
4.596
6.357
4.031
4.013
5.368
4.253
3.148
4.187
4.634
5.064
3.164
3.046
4.052
4.027
3.974
5.075
3.094
3.010
9.8
3.283
3.312
3.174
4.156
2.673
2.670
3.197
5.968
10.631
10.967
10.897
8.016
7.630
12.977
10.984
14.212
15.715
16.808
12.541
11.93
10.190
8.939
13.32
12.423
13.58
8.972
10.01
9.814
11.001
8.798
12.892
13.010
13.176
8.996
10.105
9.884
11.753
13.426
13.132
11.973
10.076
9.662
7.884
11.961
11.952
11.895
8.612
9.694
IR AND H1 NMR SPECTRAL DATA Table No-III-5

COMPO
UND
IBr(KBr,cm-1)
HNMR CDCl3(ppm)9
1.IIIa
3240.52(N-H str); 1650.0(CH=CH str); 1361.79(C-NO2 str); 732.97(Ar-CH str);
3.397 (N-H); 7.953(Ar-CH);6.709(CH=CH);
2.IIIb
3286.81(N-H str); 1660.55(CH=CH str); 1365.65(C-NO2 str); 748.41(Ar-CH

str); 3259.81(OH);
3.140(N-H); 6.705(CH=CH);10.062(OH);
7.953(ArH)3.462(N-CH3);
3.IIIc
3286.81(N-H str); 1650.0(CH=CH str); 1365.65(C=H str); 732.97(Ar-CH str);
3.397(NH); 6.705(CH-CH); 7.953(ArH);2.943(N-CH3);
4.IIId
3.397(NH);7.953(ArH);6.709CH=CH);
5.IIIe
3.397(NH);7.953(ArH);6.709CH=CH);
6.IIIf
3286.81(N-H str); 1650.0 (CH=CH str); 1365.65(C-NO2 str); 732.97(Ar-CH str);
3.397(NH); 6.709(CH=CH); .953(ArH);3.462(OCH3);
7.IIIg
3286.81(N-H str); 1650.0 (CH=CH str); 1365.65(C-NO2 str); 732.97(Ar-CH str);
3.397(NH); 6.709(CH=CH); 7.953(ArH);
8.IIIh

str);3259.81(OH);
3.140(NH); 6.705(CH=CH); 7.953(ArH);10.062(OH);
34
9.IIIi

str);3259.81(OH);
3.140(NH); 6.705(CH=CH);
7.953(ArH);10.062(OH);3.462(N-CH3);
10.IIIj

3259.81(OH);
3.397(NH); 6.705(CH=CH); 7.953(ArH);2.943(N-CH3);

10.062(OH);
11.IIIk
3.397(NH); 6.705(CH=CH); 7.953(ArH);10.062(OH);
12.IIIl
3.397(NH); 6.705(CH=CH); 7.953(ArH);10.062(OH);
13.IIIm

str); 3259.81(N-H str);
3.140(NH); 6.705(CH=CH); 7.953(ArH); 3.462(N-CH3);
14.IIIn

str); 3259.81(N-H str);
3.140(NH); 6.705(CH-ArOH); 7.953(ArH); 10.062(OH);
15.IIIo

str);
3.140(NH); 6.705(CH=CH); 7.953(ArH);
16.IIIp

str); 3259.81(OH);
3.140(NH); 6.705(CH=C); 7.953(ArH); 3.462(N-CH3);

10.062(OH);
17.IIIq

str);
3.397(NH); 6.705(CH=CH); 7.953(ArH); 2.943(N-CH3)
18.IIIr

1346.36(NO2);
3.397(NH); 6.705(CH=CH); 7.953(ArH);
19.IIIs

1346.36(NO2);
3.397(NH); 6.705(CH=CH); 7.953(ArH);
20.IIIt
3.397(NH); 6.709(CH=CH); 7.953(ArH); 3.462(OCH3);
21.IIIu
3.397(NH); 6.709(CH=CH); 7.953(ArH); 3.462(OCH3);
22.IIIv

1346.36(NO2);
3.397(NH); 6.705(CH=CH); 7.953(ArH);
23.IIIw

1346.36(NO2); 3259.81(OH);
3.397(NH); 6.705(CH=CH); 7.953(ArH);

10.062(OH); 3.462(OCH3);
24.IIIx

1346.36(NO2); 3259.81(OH);
3.397 (NH); 6.705(CH-ArOH); 7.953(ArH);2.943(NCH3);
25.IIIy

1346.36(NO2);
3.397(NH); 6.705(CH=CH); 7.953(ArH);
26.IIIz

1346.36(NO2);
3.397(NH); 6.705(CH=CH); 7.953(ArH);
27.IIIaa

1346.36(NO2);
3.397(NH); 6.709(CH=CH); 7.953(ArH); 3.462(OCH3);
28.IIIab

1346.36(NO2);
3.397 (NH); 7.9533(Ar-H) ;6.709(C=C);
29.IIIac
3.397(N-H); 6.709(CH=CH); 7.953 (Ar-H); 2.002(NCH3)10.062;
30.IIIad

3259.81(-OH);
3.397(NH); 6.709(CH=CH); 7.953(ArH);2.002(N-CH3);

10.062(-OH);
31.IIIae
3240.52(N-H);1650.0(CH=CH); 361.79(C=N);732.97(Ar-CH );1346.36(C-NO2)
3.397(NH); 6.709(CH=CH); 7.953(ArH); 2.002(CCH3);

2.943(-N-CH3);
32.IIIaf

3259.81(-OH);
3.397(NH); 6.709(C=C); 7.953(ArH);2.002(N-CH3);
33.IIIag
3.397(NH); 6.709(C=C); 7.953(ArH);2.002(N-CH3);
35
3259.81(-OH);
34.IIIah
3240.52(N-H str); 1650.0(CH=CH str); 1361.79(C=N); 732.97(Ar-CH str);
3.397(NH); 6.709(C=C); 7.953(ArH);2.002(CH3);

3.462(OCH3);
35.IIIai
3.397(NH); 6.709(CH=CH); 7.953(ArH);2.002(CH3);
36.IIIaj
3240.52(N-H str); 1650.0(CH=CH str); 1365.65(C=Nstr); 732.97(Ar-CH str);
3.397(NH); 6.709(CH=CH); 7.953(ArH);
37.IIIak
3286.81(N-H str); 1660.55(CH=CH str); 1365.65(C=Nstr); 748.41(Ar-CH str);

3259.81(-OH);
3.140(NH); 6.705(CH=CH); 7.953(ArH);3.462(O-CH3);

10.062(-OH);
38.IIIal
3286.81(N-H str); 1650.0(CH=CH str); 1365.65(C=N str); 732.97(Ar-CH str);
3.397(NH); 6.709(CH=CH); 7.953(ArH);2.002(N-CH3);
39.IIIam
3.397(NH); 6.709(CH-ArOH); 7.953(ArH);
40.IIIan
3.397(NH); 6.709(CH=CH); 7.953(ArH);
41.IIIao
3.397(NH); 6.709(CH=CH); 7.953(ArH); 3.462(-OCH3);
42.IIIap
3.397(NH); 6.709(CH=CH); 7.953(ArH);
43.IIIaq
3286.81 (N-H str); 1650.0(CH=CH str); 1365.65(C=N); 732.97(Ar-CH str);
3.397(NH); 6.709(CH=CH); 7.953(ArH); 3.462(-OCH3);
44.IIIar
3.397(NH); 6.709(CH=CH); 7.953(ArH); 3.462(-OCH3);

10.062(-OH);
45.IIIas
3286.81(N-H str); 1650.0(CH=CH str); 1365.65(C=N str); 732.97(Ar-CH

str);3259.81(OH)
3.397(NH); 6.709(CH=CH); 7.953(ArH);

3.462(OCH3);
46.IIIat

1346.97(C-NO2);
3.397(NH); 6.709(CH=CH); 7.953(ArH);
47.IIIau

1346.97(C-NO2);
3.397(NH); 6.709(CH=CH); 7.953(ArH);
48.IIIav
3286.81 (N-H str); 1650.0(CH=CH str); 1365.65(C-NO2 str); 732.97(Ar-CH str);
3.397(NH); 6.709(CH=CH); 7.953(ArH); 3.462(OCH3);
49.IIIaw
3.397(NH); 6.709(CH=CH); 7.953(ArH);
50.IIIax
3.397(NH); 6.709(CH=CH); 7.953(ArH);
51.IIIay
3.397(NH); 6.709(CH=CH); 7.953(ArH);
52.IIIaz
3240.52(N-H str); 1650.0(CH=CH str); 136179(C=N str); 732.97(Ar-CH str);
3.397(NH); 6.709(CH=CH); 7.953(ArH); 2.943(N-CH3);
53.IIIba

str); 1346.36(NO2);
3.140(NH); 6.709(CH=CH); 7.953(ArH);
54.IIIbb

1346.36(NO2);
3.397(NH); 6.709(CH=CH); 7.953(ArH);
55.IIIbc
3286.89(NH);1660.59(CH=CH); 1365.65(C=N)748.41(Ar-CH);
3.140(NH); 6.705(CH=CH); 7.953(ArH); 3.462(OCH3);
56..IIIbd
3240.52(NH); 1650.0(CH=CH); 1361.79(C=N); 732.97(Ar-H)
3.397(NH); 6.709(CH=CH); 7.953(ArH);
Anthelmintic Activity of Isoxazoles:

Helminthic
infections
are
now
being
world suffers from worm infection of one or
recognized as cause of much chronic ill
the other.
health and sluggishness amongst the tropical

people. More than half of population in the
36
All the newly synthesized compounds 57-
with the intestine roundworm parasites of
112 (IIIa-IIIz, IIIaa-IIIaz, IIIba-IIIbd) have
human being according to method described
tested for anthelmintic activity due to its
in detail by kailashraj and kurupa40-42.
anatomical and physiological resemblance

Experimental / Methodology:
Peritima posthuma(earthworm) obtained
the worms didnt revive even in normal
from agriculture department, Guntur of
saline. Death was concluded or ascertained
nearly equal size (91.5cm)was selected for
when worms lost their motility even by
present study. The synthesized compounds
external stimuli which stimulates and induce
were prepared in 3% tween-80 in normal
movement in the earthworm if alive and
saline or 1% DMF
in normal saline to
followed by fading away of their body
obtain 1mg/ml concentration which was
colour. The activity was compared with the
taken in each Petri dish (4inches).The
standard
movement of earthworms were observed for
mebendazole, and albendazole under the
the time taken to paralysis and death of
same condition. The time taken for complete
individual worms lost up to the 1hr of the
paralysis and death are reported in Table
test period. Paralysis was said to occur when
No-III-6
anthelminitic
substances
Anthelmintic Activity of Isoxazoles

S.No
Compound
code
Paralytic
Lethal
Paralytic
Lethal
(sec)
(sec)
Compound
(sec)
(sec)
S.NO
III h
230.42
660.33
20
III ao
161.98
541.236
III i
180.52
750.691
21
III ap
131.36
451.200
III j
250.35
690.632
22
III aq
180.29
690.632
III l
170.25
730.891
23
III ar
190.75
490.43
III n
130.50
800.121
24
III as
100.62
980.44
III p
130.014
901.32
25
III at
160.36
660.51
III q
201.05
76+0.53
26
III av
150.45
340.62
III r
130.014
601.0
27
III aw
120.39
350.32
III t
201.05
901.32
28
III ax
270.98
701.23
10
III v
230.36
660.321
29
III ay
170.56
731.400
37
i.e.
11
III w
180.33
751.631
30
III az
151.25
421.00
12
III x
250..22
691.22
31
III ba
141.95
501.6321
13
III z
170.144
731.20
32
III bb
140.95
481.023
14
IIIab
130.014
801.22
33
III bc
150.16
481.023
15
III ae
201.05
51+0.65
34
III bd
180.99
400.23
16
III aj
140.25
640.66
Albendazole
130.014
340.233
17
III ak
160.19
400.21
Mebendazole
90.1
280.11
III al
131.56
510.05
Controle
(3%Tween -80
in Norma
Saline)
18
19
III an
201.25
600.821
RESULTS AND DISCUSSION:

In the present investigation 56 newer
method in 1.5 6 min, while conventional
isoxazole compounds were synthesized by
method required 5-12 hrs. reflux.
conventional and microwave techniques.
results (Table) also indicated that in
The products produced by both methods
conventional method the yield was lower as
were
characterized
HNMR,
compared
spectral
demonstrating the effect of microwave
analysis and compared. The experimental
irradiation is not purely thermal irradiation
results of present investigation indicated that
but facilitates the polarization of the
all
molecule under irradiation causing rapid
elemental
newer
synthesized
analysis
by
IR,
and
Mass
The
isoxazole
by
compounds
microwave
were
irradiation
to
microwave
irradiation,
reaction to occur.
Acknowledgments
The author thanks to sri Y.V. Anjaneyulu president of
Guntur (dt), Andhra Pradesh, india. For providing
chalapathi educational society, Guntur 522034,
facilities to carryout research work, author also
Andhra Pradesh, india. Sri C. Gangi reddy, Chairman,
thankful to Dr. G. Achaiah, principal, University
Annamacharya educational trust, Rajampet, Kadapa
College
(dt) Andhra Pradesh, india. Sri M. Shesagiri Rao,
University, Warangal for his help in QSAR studies, the
President, Bapatla educational society, Bapatla,
author is thankful to MTCC institute of Microbial
38
of
pharmaceutical
sciences,
Kakatiya
technology, Chandigarh, for supplying different microbial
Satyanarayana, secretary and correspondent, Hindu
strains. Author also thankful to Dr. Mannava Radha
college of Pharmacy, Guntur 522002.
Krishna
moorthy,
Chairman
and
Godavarthy
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Available online http://WWW.JGTPS.COM

Journal of Global Trends in Pharmaceutical Sciences

Hindu college of pharmacy, Guntur -522002Andhra Pradesh. India.

56 new 3-(4-substituted anilino)-5-(3', 4-disubstituted aryl)-2-isoxazoles were synthesized by

environmentally benign synthesis under

reactions during last one decade1-16.there is

interest has been focused on the isoxazole

an increasing interest in the utility of

structure17-29, which as been known to

possess a broad spectrum of biological

In view of the wide range of

activities such as psychotropic effects30,

therapeutic value of isoxazole ring system

promoted us to plan the synthesis of a series

of some new isoxazole derivatives by

antineoplastic activity36, , anti inflammatory

synthesis of compounds suffered from the

disadvantages such as long reaction time,

The discovery of this class of drugs

low yield and inconvenience of handling

provides an outstanding case history of

where as the use of microwave irradiation

modern drugs development and also points

technology in organic synthesis lead to

out the unpredictability of biological activity

increase the purity of products, enhance the

from structural modification of a prototype

chemical yield and shorten the reaction time.

synthesized compounds were elucidated by

compounds was determined by an open-end

capillary tube method by electrically heated

melting point apparatus expressed in 0C and

KBr-Pellet method. IR values are measured

in cm-1 and the results are shown below. The

compounds was checked by TLC. In all the

structures of synthesized compounds were

cases the distances traveled by the sample

was found to be different from that of the

AMX 400 MHz) analyzer using TMS as

parent compound spotted along with it. Thus

internal standard. The samples are dissolved

confirming the fact that the compounds

in CdCl3, DMSO and the values are

formed were entirely different from that of

measured in chemical shift in delta () ppm.

the parent compound. Rf and Rm values of

The values of the assigned structures were

title compounds were shown in Table No.-

interpreted as follows. The mass spectrum of

the compound was recorded on MDS spiex

The characterization data of

AP12000 LC-MS mass spectrometer. Mass

the synthesized compounds were given in

the Table No.-III-3. The structures of the

molecular ion at m/z and the results are

substituent groups were observed within the

synthesized compounds were calculated by

expected chemical shift values (table No.III-

chem... office software and the data obtained

from Carlo Erba- 1108 elemental analyzer

The synthesized compounds (56)

are presented in Table No.-III-4 has been