Synthesis, characterization and antimicrobial activity of some disubstituted 1,3,4-oxadiazoles carrying 2-(aryloxymethyl)phenyl moiety

Article abstract of DOI:10.1016/j.ejmech.2010.06.027

Disubstituted 1,3,4-oxadaiazoles (4a-z, 4a′-f′), Mannich bases (6a-p) and S-alkylated derivatives (7a-t) have been synthesized from 2-(aryloxymethyl)benzoic acids (1a-d) through a multi-step reaction sequence. The structures of new compounds were established on the basis of their elemental analyses, IR, ¹H NMR, ¹³C NMR and mass spectral data. All the synthesized compounds were screened for their in vitro antibacterial and antifungal activity and some of them exhibited good activity.

Full text of DOI:10.1016/j.ejmech.2010.06.027

European Journal of Medicinal Chemistry 45 (2010) 4708e4719
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Synthesis, characterization and antimicrobial activity of some disubstituted
1,3,4-oxadiazoles carrying 2-(aryloxymethyl)phenyl moiety
,
,
c
Channamata Shankara Naveena a b, Poojary Boja a , Nalilu Sucheta Kumari
*
a Department of Chemistry, Mangalore University, Mangalagangothri-575199, Karnataka, India
b SeQuent Scientific Limited, New Mangalore-575011, Karnataka, India
c Department of Biochemistry, K.S. Hegde Medical Academy, Deralakatte-574162, Karnataka, India
a r t i c l e i n f o
a b s t r a c t
Disubstituted 1,3,4-oxadaiazoles (4aez, 4a0ef0), Mannich bases (6aep) and S-alkylated derivatives (7aet)
have been synthesized from 2-(aryloxymethyl)benzoic acids (1aed) through a multi-step reaction
sequence. The structures of new compounds were established on the basis of their elemental analyses, IR,
1H NMR, 13C NMR and mass spectral data. All the synthesized compounds were screened for their in vitro
antibacterial and antifungal activity and some of them exhibited good activity.
Article history:
Received 31 January 2010
Received in revised form
14 June 2010
Accepted 16 June 2010
Available online 23 June 2010
Ó 2010 Published by Elsevier Masson SAS.
Keywords:
1,3,4-Oxadaiazoles
Antibacterial activity
Antifungal activity
1,3,4-Oxadiazol-2-thiones
2-(Aryloxymethyl) phenyl moiety
1. Introduction
2. Results and discussion
1,3,4-Oxadiazoles constitute an important family of heterocyclic
compounds as they have attracted significant interest in medicinal
chemistry, pesticide chemistry and polymer science. Since many of
1,3,4-oxadiazoles display a remarkable biological activity, their
syntheses and transformations have been received particular
interest for a long time. The 1,3,4-oxadiazoles have been found to
exhibit diverse biological activities such as antimicrobial [1], anti-
HIV[1], antitubercular [2], antimalarial [3], analgesic [4], antiin-
flammatory [5], anticonvulsant [6], hypoglycemic [7] and other
biological properties such as genotoxic [8] and lipid peroxidation
inhibitory activities [9]. 5-Substituted-1,3,4-oxadiazole-2-thiones
possess CNS depressant [10], pesticidal [11,12], tyrosinase inhibi-
tion [13] property. We therefore are interested in exploring the
biological activity of such molecules through structural modifica-
tions. In view of these observations, we hereby report syntheses,
characterization and antimicrobial activity of some disubstituted
oxadiazoles (Fig. 1).
2.1. Chemistry
The target compounds (4aez), (4a0ef0), (6aep) and (7aet) were
synthesized as illustrated in Scheme 1. Acid hydrazides (3aed)
derived from 2-(aryloxymethyl)benzoic acids (1aed) were cyclized
withsubstitutedbenzoicacids inpresenceofphosphorusoxychloride
to afford 2,5-disubstituted-1,3,4-oxadiazole derivatives (4aez) and
(4a0ef0). The reaction of the above acid hydrazides (3aed) with
carbon disulphide under basic conditions yielded 1,3,4-oxadiazol-2-
thiones (5aed), which underwent N-aminomethylation reaction on
treating with formaldehyde and primary/secondary amines to afford
the compounds (6aep). Further, the alkylation of 5aed yielded
regioselectively S-alkylated products (7aet). All the compounds were
characterized by analytical and spectroscopic (IR, 1H NMR, 13C NMR
and Mass) data. The characterization data of the newly synthesized
compounds are given in Tables 1, 2 and 3.
In the IR spectrum of compound 4a, absorption bands seen at
3072 cmꢀ1 were assigned to aromatic CeH stretch. Another band at
2962 cmꢀ1 was due to the presence of CH3 group stretching vibra-
tions. The absorption bands due to C]N was observed at 1680 cmꢀ1
.
The 1H NMR spectrum of compound 4a, showed sharp singlet at
2.29 for its CH3 protons. The two hydrogen atoms of the aryloxy-
methylene group were appeared as a singlet at 5.62. The 3,4-
d
* Corresponding author. Tel.: þ91 824 2287262; fax: þ91 824 2287367.
E-mail address: bojapoojary@gmail.com (P. Boja).
d
0223-5234/$ e see front matter Ó 2010 Published by Elsevier Masson SAS.
doi:10.1016/j.ejmech.2010.06.027

C.S. Naveena et al. / European Journal of Medicinal Chemistry 45 (2010) 4708e4719
4709
R2
R3
C
N
N
C
N
N
N
N
N
N
R1
S
O
S
B
SH
O
O
O
B
C
B
B
R
O
R
R
R
O
O
O
A
A
A
A
(7)
(6)
(5)
(4)
Fig. 1. General structures of substituted 1,3,4-oxadiazoles.
aromatic protons ring B (Fig. 1) appeared as two distinct triplets at
8.08 (J ¼ 7.05 Hz) and 8.11 (J ¼ 7.60 Hz), where as 2,5-aromatic
protons resonated as two doublets at 8.18
(J ¼ 7.60 Hz). Similarly, the 3,6-aromatic protons of ring A resonated
as two distinct doublets at
d
6.90 and
d
7.02 with J ¼ 7.3 Hz and
d
d
J ¼ 8.1 Hz respectively. The 4,5-ring A protons resonated as a multi-
d
7.85 (J ¼ 7.05 Hz) and
d
plet in the region, 7.17e7.21. The remaining five aromatic protons of
d
ring C appeared as a complex multiplet in the region d 7.51e7.64.
CO2 C2 H5
CO-NH-NH2
CO2 H
R
R
(1)
(3)
(2)
R
O
O
O
Ar-CO2H/POCl3
CS2/K2CO3
N
N
N
N
SH
Ar
O
O
R
(5)
R
O
(4)
O
10/20 amines,CH2O
R''-Cl/NaOH
R'
N
N
N
N
S
S
O
O
R''
R
R
O
O
(7)
(6)
R= 2-CH3, 3-CH3, 4-CH3 and 4-Cl.
Ar = C6H5, 2-Cl-nicotinyl, 3,5-(CH3)2-C6H3, 2-F-C6H4,4-Cl-C6H4, 3,4,5-(OCH3)3-C6H2, 5-quinolinyl, 3-Br-
C6H4
R'
.
N
O
-NH-C6H3-2-Cl-5-CH3,-NH-C6H4-3-CF3, -NH-C6H3-2-COCF3-4-Cl
=
,
″
R = C H5, C6H5CH2, 2,4-Cl2 -C6H3CH2, 4-Cl-C6H5CH2, 3-CH3C6H4CH2.
2
Scheme 1. Synthesis of 2,5-disubstituted-1,3,4-oxadiazoles carrying 2-(aryloxymethyl)phenyl moiety.

4710
C.S. Naveena et al. / European Journal of Medicinal Chemistry 45 (2010) 4708e4719
Table 1
Characterization data of 2-(aryloxymethyl)-5-phenyl-1,3,4-oxadiazoles (4aez) and (4a0ef0).
Compd.
R
Ar
Mol.formula (Mol. wt)
m.p. ꢁC
Analysis (%) Found (calculated)
C
H
N
4a
4b
4c
4d
4e
4f
o-CH3
m-CH3
p-CH3
p-Cl
C6H5
C22H18N2O2
(342.39)
C22H18N2O2
(342.39)
C22H18N2O2
(342.39)
C21H15ClN2O2
(362.29)
C24H22N2O2
(370.44)
C24H22N2O2
(370.44)
C24H22N2O2
(370.44)
C23H19ClN2O2
(390.86)
C25H24N2O5
(432.46)
C25H24N2O5
(432.46)
C25H24N2O5
(432.46)
C24H21ClN2O5
(452.88)
C22H17FN2O2
(360.38)
C22H17FN2O2
(360.38)
C22H17FN2O2
(360.38)
C21H14ClFN2O2
(360.38)
C22H17ClN2O2
(376.83)
C22H17ClN2O2
(376.83)
C22H17ClN2O2
(376.83)
C21H14Cl2N2O2
(397.25)
C26H20N2O2
(392.44)
C26H20N2O2
(392.44)
C26H20N2O2
(392.44)
90e92
66.23
(66.08)
77.17
(77.08)
77.32
(77.08)
69.52
(69.42)
77.81
(77.69)
77.28
(77.69)
77.83
(77.69)
70.62
(70.69)
69.43
(70.09)
69.86
(70.09)
69.30
(70.09)
63.65
(63.48)
73.32
(73.49)
72.92
(73.49)
73.32
(73.49)
66.24
(66.49)
70.12
(70.1)
70.10
(70.12)
70.12
(70.10)
63.49
(66.49)
79.59
(79.45)
79.22
(79.45)
79.40
(79.45)
72.73
(72.45)
62.72
(62.55)
62.23
(62.55)
62.70
(62.55)
57.10
(57.02)
66.76
(66.46)
66.12
(66.46)
66.40
(66.46)
60.32
5.56
(5.53)
5.30
(5.83)
5.37
(5.23)
4.17
(4.17)
5.99
(5.17)
5.22
(5.17)
5.41
(5.70)
4.90
(4.17)
5.59
(5.37)
5.23
(5.37)
5.10
(5.37)
4.67
(4.44)
4.75
(4.67)
4.53
(4.67)
4.75
(4.67)
3.71
(3.67)
4.55
(4.45)
4.30
(4.45)
4.55
(4.45)
3.55
(3.67)
5.14
(5.05)
4.85
(5.05)
5.12
(5.05)
4.15
(4.05)
4.07
(4.05)
3.90
(4.05)
4.02
(4.05)
3.19
(3.05)
4.27
(4.73)
4.28
(4.73)
4.53
(4.73)
3.29
8.58
(8.28)
8.18
(8.11)
8.41
(8.21)
7.72
(7.62)
7.56
(7.62)
7.45
(7.62)
7.56
(7.62)
7.17
(7.62)
6.48
(6.42)
6.31
(6.42)
6.40
(6.42)
6.19
(6.12)
7.77
(7.62)
7.20
(7.62)
7.60
(7.62)
7.36
(7.22)
7.43
(7.22)
7.10
(7.22)
7.43
(7.22)
7.05
(7.22)
7.14
(7.12)
7.05
(7.12)
6.86
(7.12)
6.79
(6.62)
6.65
(6.52)
6.40
(6.52)
6.20
(6.52)
6.34
(6.12)
11.12
(10.95)
10.68
(10.95)
11.10
(10.95)
10.55
(10.45)
C6H5
142e144
102
C6H5
C6H5
158e160
136e140
78e80
o-CH3
m-CH3
p-CH3
p-Cl
3,5(CH3)2C6H3
3,5(CH3)2C6H3
3,5(CH3)2C6H3
3,5(CH3)2C6H3
3,4,5-(OCH3)3C6H2
3,4,5-(OCH3)3C6H2
3,4,5-(OCH3)3C6H2
3,4,5-(OCH3)3C6H2
2-FeC6H4
4g
4h
4i
112e114
126e128
126e128
100e102
106e108
98e100
o-CH3
m-CH3
p-CH3
p-Cl
4j
4k
4l
4m
4n
4o
4p
4q
4r
o-CH3
m-CH3
p-CH3
p-Cl
140e146
130e132
134e136
156e160
196e198
176e178
180e182
168e170
198e200
178e182
168e170
174e178
154e156
106e108
124e126
158e162
136e138
102e104
168e170
128e130
2-FeC6H4
2-FeC6H4
2-FeC6H4
o-CH3
m-CH3
p-CH3
p-Cl
4-CleC6H4
4-CleC6H4
4s
4-CleC6H4
4t
4-CleC6H4
4u
4v
4w
4x
4y
4z
4a0
4b0
4c0
4d0
4e0
4f0
o-CH3
m-CH3
p-CH3
p-Cl
5-Quinolinyl
5-Quinolinyl
5-Quinolinyl
5-Quinolinyl
3-BreC6H4
C25H17 ClN2O2
(412.86)
C22H17BrN2O2
(421.28)
C22H17BrN2O2
(421.28)
C22H17BrN2O2
(421.28)
C21H14BrClN2O2
(441.71)
C21H16ClN3O2
(377.82)
C21H16ClN3O2
(377.82)
C21H16ClN3O2
(377.82)
o-CH3
m-CH3
p-CH3
p-Cl
3-BreC6H4
3-BreC6H4
3-BreC6H4
o-CH3
m-CH3
p-CH3
p-Cl
2-chloronicotinyl
2-chloronicotinyl
2-chloronicotinyl
2-chloronicotinyl
C20H13Cl2N3O2
(398.24)
(60.46)
(3.18)
Further, 13C NMR spectrum of 4a manifested signals at
67.74 due to eCH3 and eOCH2 respectively, peaks at
163.85 were due to C2 and C5 of oxadiazole moiety, while peaks at
111.13, 120.24, 120.48, 123.26, 126.32, 126.52, 127.23, 127.26, 128.21,
128.68, 130.26, 131.23, 131.39, 137.53 and 156.18 were due to other
aromatic carbon atoms. The peaks at 16.51, 67.74, 111.13, 120.48,
d
16.51 and
123.26,127.23,127.26,130.26,131.23,131.39,128.68 and 128.21, were
observed in DEPT experiment. The other peaks at 163.51, 163.85,
156.18, 137.53, 126.32, 126.52 and 120.24 due to quaternary carbon
atoms were disappeared on DEPT experimentation. Further, FAB MS
spectrum showed the molecular ion peak at m/z 342 which corre-
sponds to its molecular formula, C22H18N2O2.
d
163.51 and
d
d
d

C.S. Naveena et al. / European Journal of Medicinal Chemistry 45 (2010) 4708e4719
4711
Table 2
Characterization data of Mannich bases (6aep).
Compd.
R
R0
Mol. formula (Mol. wt)
m.p. ꢁ
C
Analysis (%) Found (calculated)
C
H
N
C21H23N3O3S
(397.48)
63.45
(63.41)
5.84
(5.86)
10.58
(10.26)
6a
6b
6c
6d
o-CH3
m-CH3
p-CH3
p-Cl
124e126
158e160
152e154
129
C21H23N3O3S
(397.48)
63.22
(63.41)
5.62
(5.86)
10.10
(10.26)
C21H23N3O3S
(397.48)
63.18
(63.41)
5.42
(5.86)
10.13
(10.26)
C20H20ClN3O3S
(417.9)
57.58
(57.61)
4.82
(4.86)
10.05
(10.06)
6e
6f
o-CH3
m-CH3
p-CH3
p-Cl
3-CF3C6H3NH
C24H20F3N3O2S
(471.49)
C24H20F3N3O2S
(471.49)
C24H20F3N3O2S
(471.49)
C23H17ClF3N3O2S
(491.91)
C25H19ClF3N3O3S
(533.95)
C25H19ClF3N3O3S
(533.95)
C25H19ClF3N3O3S
(533.95)
C24H16Cl2F3N3O2S
(554.36)
C24H22ClN3O2S
(451.96)
C24H22ClN3O2S
(451.96)
C24H22ClN3O2S
(451.96)
C23H19Cl2N3O2S
(472.38)
126e128
98e100
61.14
(61.61)
59.95
(61.21)
60.23
(60.61)
56.16
(56.11)
56.24
(56.12)
56.24
(56.12)
56.10
(56.12)
52.00
(61.61)
63.78
(63.54)
63.22
(63.54)
63.28
(63.54)
58.48
4.28
(4.26)
4.12
(4.26)
3.92
(4.06)
3.48
(3.26)
3.59
(3.16)
3.59
(3.16)
3.42
(3.16)
2.91
(4.26)
4.91
(4.75)
4.52
(4.75)
4.42
(4.75)
4.05
8.91
(8.26)
8.90
(8.26)
8.11
(8.26)
8.54
(8.36)
7.87
(7.54)
7.87
(7.54)
7.80
(7.54)
7.58
(8.26)
9.30
(9.11)
9.10
(9.11)
9.12
(9.11)
8.90
(8.71)
3-CF3C6H3 NH
6g
6h
6i
3-CF3C6H3 NH
130e132
136e138
120e122
118e120
88e90
3-CF3C6H3 NH
o-CH3
m-CH3
p-CH3
p-Cl
NHeC6H3e2-COCF3e4-Cl
NHeC6H3e2-COCF3e4-Cl
NHeC6H3e2-COCF3e4-Cl
NHeC6H3e2-COCF3e4-Cl
NHeC6H3e2-Cle5-CH3
NHeC6H3e2-Cle5-CH3
NHeC6H3e2-Cle5-CH3
NHeC6H3e2-Cle5-CH3
6j
6k
6l
128e130
136e140
138e142
124e126
110e112
6m
6n
6o
6p
o-CH3
m-CH3
p-CH3
p-Cl
(58.32)
(3.96)
The structure of oxadiazole 5a was also confirmed by its spec-
troscopic data. The IR spectrum showed a weak SH stretching
absorption at 2592 cmꢀ1. The absorption bands due to C]N was
m/z 331, which was assigned to a fragment produced by the loss of
morpholino radical from the molecular ion.
IR spectrum of compound 7o showed absorption bands at 3051
and 2981 cmꢀ1 for its aromatic and aliphatic CeH stretching vibra-
tions. The C]N and CeO moieties showed their characteristic
absorption bands at 1670 and 1270 cmꢀ1 respectively. The charac-
teristic CeCl stretching vibrationwas observed at 750 cmꢀ1. The sharp
observed at 1681 cmꢀ1. A broad downfield signal observed at
d
11.8
in the 1H NMR spectrum was assigned to NH/SH tautomeric proton.
In 13C NMR spectrum, eC]S carbon appeared at
177.13 in addi-
d
tion to other characteristic signals of remaining carbon atoms. The
FAB mass spectrum showed a protonated molecular ion peak at m/z
299 in agreement with its molecular formula, C16H14N2O2S.
In the IR spectrum of compound 6d, the aromatic CeH
stretching vibration was observed at 3047 cmꢀ1. The absorption
band due to CH2 group of morpholine moiety was seen at 2916/
2850 cmꢀ1. The C]N and C]S moieties showed their characteristic
absorption bands at 1681 and 1356 cmꢀ1 respectively. The 1H NMR
singlet at
protons. Another sharp singlet observed at
protons was assigned to SeCH2 protons. The OeCH2 protons reso-
nated as a sharp singlet at 5.54. The three aromatic protons of ring A
resonated as a multiplet in the region, 6.79e6.87. Another proton of
ring A was also appeared as a multiplet in the region 7.17e7.21. The
protons of ring B resonated as two multiplets in the region 7.55e7.58
and 7.86e7.94 respectively integrating for two protons each. Two
d
2.35 in the 1H NMR spectrum was assigned for ring A-CH3
4.48 integrating for two
d
d
d
d
d
spectrum showed a sharp singlet at
d 5.02 for NeCH2eN protons.
Eight protons of morpholine moiety resonated as two triplets at
distinct characteristic doublets centered at d 7.33 and 7.42 with
d
2.75 and
d
3.62 with J ¼ 6.80 Hz. In 13C NMR spectrum, the signals
J ¼ 7.5Hz were observed for ring C protons. Further,13C NMR spectrum
observed at
d
67.91 and 70.12 were assigned to C2, C6 and C3, C5 of
manifested signals at d 21.12, 35.49 and 67.49 due to eCH3, eSCH2e
morpholine ring respectively. The signal due to aryloxymethylene
carbon appeared at 68.23. The aryloxymethine carbon atom
resonated at , 156.69, while other aromatic carbon atoms appeared
at 115.47, 119.51, 125.68, 128.17, 128.43, 128.61, 129.00, 131.97 and
135.64. Further, the structure of 6d was also confirmed by recording
its mass spectrum, which showed a molecular ion peak at m/z 417.
The observed molecular mass is in agreement with the assigned
molecular formula, C20H20N3O3SCl. The base peak was observed at
and eOCH2e carbon atoms. The aryloxymethine carbon atom reso-
nated at 158.06, while the peaks at 111.38, 115.25, 119.96, 121.50,
d
d
d
d
127.20, 127.31, 127.97, 128.55, 128.81, 130.06, 131.21, 133.63, 133.73,
137.18 and 139.16 were due to other aromatic carbon atoms. The
signals observed at 163.12 and 164.74 were attributed to C3 and C5 of
oxadiazole ring respectively. The mass spectrum of this compound
showed molecular ion peak m/z 388 in consistent with its molecular
formula, C23H20N2O2S.
d

4712
C.S. Naveena et al. / European Journal of Medicinal Chemistry 45 (2010) 4708e4719
Table 3
Characterization data of 2-thioalkyl/aralkyl-5-(2-[aryloxymethyl])-1,3,4-oxadiazoles (7aet).
Compd.
R
R00
Mol. formula (Mol. wt)
m.p. ꢁ
C
Analysis (%) Found (calculated)
C
H
N
7a
7b
7c
7d
7e
7f
o-CH3
m-CH3
p-CH3
p-Cl
C2H5
C18H18N2O2S
(326.416)
C18H18N2O2S
(326.416)
C18H18N2O2S
(326.416)
C17H15ClN2O2S
(346.83)
C23H20N2O2S
(388.48)
C23H20N2O2S
(388.48)
C23H20N2O2S
(388.48)
C22H18ClN2O2S
(409.91)
C23H18Cl2N2O2S
(457.37)
C23H18Cl2N2O2S
(457.37)
C23H18Cl2N2O2S
(457.37)
C22H15Cl3N2O2S
(477.79)
C23H19ClN2O2S
(422.92)
C23H19ClN2O2S
(422.92)
C23H19ClN2O2S
(422.92)
C22H16Cl2N2O2S
(443.34)
78e80
100e102
80e82
66.23
(66.08)
59.58
(66.08)
66.00
(66.08)
58.87
(58.61)
71.10
(71.09)
70.50
(70.95)
69.84
(71.19)
64.46
(64.08)
60.40
(60.32)
60.11
(60.32)
60.40
(60.32)
55.30
(55.15)
65.32
(65.12)
64.88
(65.12)
65.30
(65.12)
59.60
5.56
(5.83)
5.62
(5.83)
5.29
(5.83)
4.36
(4.26)
5.19
(5.13)
4.92
(5.03)
4.96
(5.13)
4.43
(4.23)
3.97
(3.81)
3.65
(3.81)
3.97
(3.81)
3.16
(3.21)
4.53
(4.68)
4.42
(4.68)
4.40
(4.68)
3.64
8.58
(8.21)
8.32
(8.21)
8.10
(8.21)
8.08
(8.26)
7.21
(7.10)
7.11
(7.12)
7.20
(7.05)
6.83
(6.61)
6.12
(6.11)
5.96
(6.11)
6.12
(6.11)
5.86
(5.92)
6.62
(6.44)
6.23
(6.44)
6.62
(6.44)
6.32
C2H5
C2H5
C2H5
106e108
108e112
76e78
o-CH3
m-CH3
p-CH3
p-Cl
C6H5CH2
C6H5CH2
7g
7h
7i
C6H5CH2
116e118
102e104
118e120
94e102
108e110
100e102
128e130
114e116
96e98
C6H5CH2
o-CH3
m-CH3
p-CH3
p-Cl
2,4-Cl2C6H3CH2
2,4-Cl2C6H3CH2
2,4-Cl2 C6H3CH2
2,4-Cl2C6H3CH2
4-CleC6H5CH2
4-CleC6H5CH2
4-Cl-C6H5CH2
4-CleC6H5CH2
3-CH3C6H4CH2
3-CH3C6H4CH2
3-CH3C6H4CH2
3-CH3C6H4CH2
7j
7k
7l
7m
7n
7o
7p
7q
7r
7s
7t
o-CH3
m-CH3
p-CH3
p-Cl
98e104
82e84
(60.12)
71.61
(71.46)
71.23
(71.46)
71.16
(71.46)
65.32
(3.61)
5.51
(5.65)
5.22
(5.65)
5.81
(5.65)
4.53
(6.18)
6.96
(6.58)
6.18
(6.58)
6.90
(6.58)
6.62
o-CH3
m-CH3
p-CH3
p-Cl
C24H22N2O2S
(402.51)
C24H22N2O2S
(402.51)
C24H22N2O2S
(402.51)
C23H19ClN2O2S
(422.93)
88e90
108e110
118e121
(65.21)
(4.32)
(6.48)
2.2. Antimicrobial studies
(6 kV, 10 mA)FAB gas, at 70 eV. Elemental analyses were carried out
using Flash EA 1112 Series, CHNSO Analyzer (Thermo). The progress
of the reaction was monitored by thin layer chromatography (TLC)
on pre-coated silica gel G plates.
All the newly synthesized oxadiazoles were screened for their in
vitro antibacterial and antifungal activity. For antibacterial studies
microorganisms employed were Staphylococcus aureus, Bacillus sub-
tilis, Escherichia coli and Pseudomonas aeruginosa. For antifungal
screening, Penicillium Marneffei and Aspergillus flavus strains were
used. Both microbial studies were assessed by Minimum Inhibitory
Concentration (MIC) by serial dilution method [14]. For this, the
compound whose MIC has to be determined was dissolved in serially
diluted DMF. Then a standard drop of the culture prepared for the
assay is added to each of the dilutions, and incubated for 16e18 h at
37 ꢁC. MIC is the highest dilution of the compound, which shows clear
fluid with no development of turbidity. The antibacterial and anti-
fungal activity data are presented in Tables 4 and 5.
3.1. General procedure for the preparation of 2-(aryloxymethyl)
benzoic acids [15] (1aed)
Phthalide (15.0 g, 112 mmol), substituted phenols (23.6 g,
214 mmol) and sodium methoxide (47.6 g, 220 mmol) were sus-
pended in 150 ml of n-butanol and stirred at 140 ꢁC for 15 h. The
reaction mixture was cooled, 400 ml of water was added and the
mixturewasacidified to pH 4 at 20ꢁC withconcentrated hydrochloric
acid. The productobtained wasfiltered, washed withwaterand dried.
The crude product was recrystallized from methanol/water.
1a. Colourless solid (75%); mp 150e152 ꢁC; IR (KBr,
3450 (OeH), 3056 (AreH), 2941 (CeH), 1694 (C]O), 1245 (CeO);
1H NMR (400 MHz, CDCl3,
ppm): 2.21 (s, 3H, Ring A-CH3), 5.46 (s,
n
cmꢀ1):
3. Experimental protocols
d
Melting points were determined by the open capillary method
and are uncorrected. The IR spectra (in KBr pellets) were recorded
on a Shimadzu FT-IR 4100 type A spectrophotometer. 1H NMR and
13C spectra were recorded on a Varian 400 MHz NMR spectrometer/
PerkineElmer EM300 MHz spectrometer using TMS as an internal
standard. The FAB mass spectra were recorded on a JEOL SX 102/
DA-6000 spectrophotometer/Data system using Argon/Xenon
2H, eOCH2), 6.71e6.79 (m, 3H, Ring A-H), 7.107 (t, 1H, Ring A-H),
7.27e7.36 (d, 1H, Ring B-H, J ¼ 8.8 Hz),7.45e7.51 (d, 1H, Ring B-H,
J ¼ 8.9 Hz), 7.84e7.89 (t, 1H, Ring B-H), 8.06e8.18 (t, 1H, Ring B-H).
1b. Colourless solid (74%); mp 146e148 ꢁC; IR (KBr,
n
cmꢀ1):
3445 (OeH), 3058 (AreH), 2992 (CeH), 1689 (C]O), 1255 (CeO).
1c. Colourless solid (78%); mp 126e128 ꢁC; IR (KBr, cmꢀ1): 3455
(OeH), 3078 (AreH), 2970 (CeH), 1685 (C]O), 1256 (CeO); 1H NMR
n

C.S. Naveena et al. / European Journal of Medicinal Chemistry 45 (2010) 4708e4719
4713
Table 4
Antibacterial activity data oxadiazoles (4aez), (4a0ef0), (6aep) and (7aet).
Compound
MIC in
m
g/mL and Zone of inhibitiona (in mm)
S. aureus
E. coli
P. aeruginosa
K. pneumoniae
4a
4b
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4c
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4d
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
25 (<10)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
25 (<10)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
25 (<10)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
25 (<10)
4q
4r
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4s
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4t
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4u
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4v
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4w
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4x
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4y
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4z
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4a0
4b0
4c0
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
25 (<10)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
25 (<10)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
25 (<10)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
25 (<10)
4d0
4e0
4f׳
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
25 (<10)
25 (<10)
25 (<10)
25 (<10)
6k
25 (<10)
25 (<10)
25 (<10)
25 (<10)
6l
25 (<10)
25 (<10)
25 (<10)
25 (<10)
6m
25 (<10)
25 (<10)
25 (<10)
25 (<10)
6n
25 (<10)
25 (<10)
25 (<10)
25 (<10)
6o
25 (<10)
25 (<10)
25 (<10)
25 (<10)
6p
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7a
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7b
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7c
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7d
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7e
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7f
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7g
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7h
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7i
7j
7k
7l
7m
7n
7o
7p
7q
7r
7s
7t
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (30e40)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (23e27)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (25e33)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
1.56 (22e30)
Standard (Ciprofloxacin)
a
Values shown in within the parentheses represent zone of inhibition.

4714
C.S. Naveena et al. / European Journal of Medicinal Chemistry 45 (2010) 4708e4719
Table 5
Antifungal activity data of oxadiazoles (4aez), (4a0ef0), (6aep) and (7aet).
Compound
MIC in m
g/mL and Zone of inhibitiona (in mm)
P. marneffei
T. mentagrophytes
A. flavus
25 (<10)
25 (<10)
25 (<10)
A. fumigatus
4a
4b
4c
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4d
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
25 (<10)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
25 (<10)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
25 (<10)
6.25 (16e20)
6.25 (16e20)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
25 (<10)
4q
4r
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4s
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4t
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4u
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4v
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4w
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4x
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4y
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4z
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4a׳
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4b׳
25 (<10)
25 (<10)
25 (<10)
25 (<10)
4c׳
4d׳
4e׳
4f׳
6a
6b
6c
6d
6e
6f
6g
6h
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
25 (<10)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
25 (<10)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
25 (<10)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
25 (<10)
6i
6j
25 (<10)
25 (<10)
25 (<10)
25 (<10)
6k
25 (<10)
25 (<10)
25 (<10)
25 (<10)
6l
25 (<10)
25 (<10)
25 (<10)
25 (<10)
6m
25 (<10)
25 (<10)
25 (<10)
25 (<10)
6n
25 (<10)
25 (<10)
25 (<10)
25 (<10)
6o
25 (<10)
25 (<10)
25 (<10)
25 (<10)
6p
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7a
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7b
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7c
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7d
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7e
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7f
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7g
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7h
25 (<10)
25 (<10)
25 (<10)
25 (<10)
7i
7j
7k
7l
7m
7n
7o
7p
7q
7r
7s
7t
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (20e27)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
3.125 (27e33)
6.25 (16e20)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
3.125 (25e30)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
6.25 (16e20)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
12.5 (11e15)
6.25 (16e20)
6.25 (16e20)
12.5 (11e15)
12.5 (11e15)
6.25 (25e30)
Standard (Ciclopiroxolamine)
a
Values shown in within the parentheses represent zone of inhibition.

C.S. Naveena et al. / European Journal of Medicinal Chemistry 45 (2010) 4708e4719
4715
(400MHz,CDCl3,
d
ppm):2.38(s, 3H, RingA-CH3), 5.36(s, 2H, eOCH2),
5.26 (s, 2H, eOCH2), 6.76e6.80 (m, 4H, Ring A-H), 7.48e7.52 (m, 4H,
6.75 (d, 2H, Ring A-H, J ¼ 8.9 Hz), 6.85 (d, 2H, Ring A-H, J ¼ 8.9 Hz),
Ring B-H), 7.48 (br s, 1H, NH).
7.07e7.50 (m, 2H, Ring B-H), 7.65e8.18 (m, 2H, Ring B-H).
3c. Colourless solid (90%); mp 112e114 ꢁC; IR (KBr, cmꢀ1): 3288
n
1d. Colourless solid (80%); mp 167e169 ꢁC; IR (KBr,
n
cmꢀ1):
(NH2/NH), 3020 (AreH), 1646 (C]O), 1250 (CeO); 1H NMR
(300 MHz, CDCl3, ppm): 2.12 (s, 3H, AreCH3), 4.11 (s, 2H, eNH2),
3440 (OeH), 3096 (AreH), 2988 (CeH), 1694 (C]O), 1236 (CeO),
d
748 (CeCl); 1H NMR (300 MHz, CDCl3,
d
ppm): 5.53 (s, 2H, eOCH2),
5.34 (s, 2H, eOCH2), 6.33e7.37 (d, 2H, Ring A-H, J ¼ 7.2 Hz),
6.90e6.94 (d, 2H, Ring A-H, J ¼ 7.2 Hz), 7.48e7.58 (m, 4H, Ring B-H),
7.55 (br s, 1H, NH).
6.93 (d, 2H, Ring A-H, J ¼ 8.9 Hz), 7.26 (d, 2H, Ring A-H, J ¼ 8.9 Hz),
7.44 (t, 1H, Ring B-H, J ¼ 7.5 Hz), 7.63 (t, 1H, Ring B-H, J ¼ 7.5 Hz),
7.77 (d, 1H, Ring B-H, J ¼ 7.2 Hz), 8.18 (d, 1H, Ring B-H, J ¼ 7.2 Hz).
3d. Colourless solid (92%); mp 122e125 ꢁC; IR (KBr,
n
cmꢀ1):
3291 (NH2/NH), 3014 (AreH), 1638 (C]O), 1256 (CeO), 746 (CeCl);
1H NMR (400 MHz, CDCl3,
d
ppm):4.07(s, 2H, eNH2), 5.22 (s, 2H,
3.2. General procedure for the preparation of ethyl
2-(aryloxymethyl) benzoates (2aed)
eOCH2), 6.92 (d, 2H, Ring A-H, J ¼ 7.2 Hz), 6.25 (d, 2H, Ring A-H,
J ¼ 7.2 Hz), 7.59e7.48 (m, 4H, Ring B-H), 7.40 (br s, 1H, NH).
The above esters were prepared by refluxing 2-(aryloxymethyl)
benzoic acids (1aed) in excess absolute ethanol in the presence of
few drops of conc. sulfuric acid as per the general method
employed for the esterification [16]. The resulting esters have been
judged to be pure by TLC.
3.4. General procedure for the of synthesis of 2-(aryloxymethyl)-5-
phenyl-1,3,4-oxadiazoles (4aez, 4a0-f0)
A mixture of acid hydrazides (3aed) (1 mmol), substituted
benzoic acids (1 mmol) and phosphorus oxychloride (2.5 mmol)
was refluxed at 100e110 ꢁC for 6 h. The excess solvent was distilled
off under reduced pressure and the residue was quenched with ice
cold water. The solid separated was filtered, washed and dried. The
crude product was purified by recrystallization from a suitable
solvent to afford above oxadiazoles in 65e75% yield (Table 1).
2a. Colourless solid (82%); mp 54e56 ꢁC; IR (KBr, cmꢀ1): 3072
n
(AreH), 2980 (CeH), 1716 (C]O), 1247 (CeO); 1H NMR (400 MHz,
CDCl3, d ppm): 1.39 (t, 3H, eCH3 ester, J ¼ 7.2 Hz), 2.36 (s, 3H, Ring
A-CH3), 4.36 (q, 2H, eCH2 ester, J ¼ 7.2 Hz), 5.51 (s, 2H, eOCH2),
6.80e6.87 (m, 3H, Ring A-H), 7.17 (t, 1H, Ring A-H, J ¼ 7.8 Hz), 7.39
(d, 1H, Ring B-H, J ¼ 8.7 Hz), 7.58 (d, 1H, Ring B-H, J ¼ 7.8 Hz), 7.81 (t,
1H, Ring B-H, J ¼ 7.5 Hz), 8.06 (t, 1H, Ring B-H, J ¼ 7.5 Hz).
4b. IR (KBr,
n
cmꢀ1): 3085 (AreH), 2962 (CeH), 1674 (C]N),
ppm): 2.36 (s,
1245(CeO), 1082 (CeO); 1H NMR (300 MHz, CDCl3,
d
2b. Colourless solid (85%); mp 68e70 ꢁC; IR (KBr, cmꢀ1): 3082
n
3H, Ring A-CH3), 5.58 (s, 2H, eOCH2), 6.75e7.11 (m, 4H, Ring A-H),
7.35e7.64 (m, 5H, Ring C-H), 7.75 (d, 1H, Ring B-H, J ¼ 7.8 Hz),
8.01e8.18 (t, 1H, Ring B-H, J ¼ 7.5 Hz), 8.22e8.32(t, 1H, Ring B-H,
J ¼ 7.5 Hz), 8.41e8.53 (d, 1H, Ring B-H, J ¼ 7.8 Hz); MS (VG, 70 eV):
m/z 342 (Mþ) consistent with the molecular formula, C22H18N2O2.
(AreH), 2972 (CeH), 1715 (C]O), 1264 (CeO); 1H NMR (400 MHz,
CDCl3,
d
ppm): 1.42 (t, 3H, eCH3 ester, J ¼ 7.2 Hz), 2.42 (s, 3H, Ring
A-CH3), 4.42 (q, 2H, eCH2 ester, J ¼ 7.2 Hz), 5.58 (s, 2H, eOCH2),
6.86e7.17 (m, 4H, Ring A-H), 7.23e7.52 (m, 2H, Ring B-H), 7.67 (d,
1H, Ring B-H, J ¼ 7.8 Hz), 7.90 (d, 1H, Ring B-H).
4c. IR (KBr, n
cmꢀ1): 3098 (AreH), 2975 (CeH),1662 (C]N),1249
2c. Colourless solid (87%); mp 52e54 ꢁC; IR (KBr,
n
cmꢀ1): 3094
(CeO), 1112 (CeO); MS (VG, 70 eV): m/z 342 (Mþ, 6%) consistent
(AreH), 2975 (CeH), 1712 (C]O), 1231 (CeO); 1H NMR (400 MHz,
CDCl3,
with the molecular formula, C22H18N2O2.
d
ppm): 1.32 (t, 3H, eCH3 ester, J ¼ 7.2 Hz), 2.32 (s, 3H, Ring A-
4d. IR (KBr,
n
cmꢀ1): 3070 (AreH), 2970 (CeH), 728 (CeCl), 1660
CH3), 4.46 (q, 2H, eCH2 ester, J ¼ 7.2 Hz), 5.56 (s, 2H, eOCH2), 6.74 (d,
2H, RingA-H, J¼ 7.5Hz), 7.05e7.12(d, 2H, RingA-H, J ¼ 7.5Hz), 7.39(d,
1H, Ring B-H, J ¼ 8.7 Hz), 7.49 (d,1H, Ring B-H, J ¼ 7.8 Hz), 7.78 (t, 1H,
Ring B-H, J ¼ 7.5 Hz), 8.12e8.18 (t, 1H, Ring B-H, J ¼ 7.5 Hz).
(C]N), 1252 (CeO), 1120 (CeO); 1H NMR (400 MHz, CDCl3,
d
ppm):
5.63 (s, 2H, eOCH2), 7.00 (d, 2H, Ring A-H, J ¼ 7.2 Hz), 7.26 (d, 2H,
Ring A-H, J ¼ 7.2 Hz), 7.51e7.64 (m, 5H, Ring C-H), 7.85 (d, 1H, Ring
B-H, J ¼ 7.8 Hz), 8.09 (t, 1H, Ring B-H, J ¼ 7.5 Hz), 8.12 (t, 1H, Ring B-
H, J ¼ 7.5 Hz), 8.18 (d, 1H, Ring B-H, J ¼ 7.2 Hz); 13C NMR (100 MHz,
2d. Colourless solid (89%); mp 60e62 ꢁC; IR (KBr, cmꢀ1): 3092
n
(AreH), 3004 (CeH), 1708 (C]O), 1284 (CeO), 748 (CeCl); 1H NMR
(400 MHz, CDCl3,
CDCl3,
d ppm): 67.82, 111.13, 120.24, 120.48, 123.26, 126.32, 126.52,
d
ppm):1.42 (t, 3H, eCH3 ester, J ¼ 7.2 Hz), 4.52 (q,
127.23, 127.26, 128.21, 128.68, 130.26, 131.23, 131.39, 137.53 and
156.18; DEPT: 111.62, 120.73, 127.02, 127.75, 128.70, 129.17, 130.76,
131.72, 131.89; CH2 d ¼ 68.23; MS (VG, 70 eV): m/z 363 (Mþ þ 1, 5%)
consistent with the molecular formula, C21H15ClN2O2.
2H, eCH2 ester, J ¼ 7.2 Hz), 5.62 (s, 2H, eOCH2), 6.67 (d, 2H, Ring A-
H, J ¼ 8.9 Hz), 7.11e7.21 (d, 2H, Ring A-H, J ¼ 8.9 Hz), 7.33e7.62 (m,
2H, Ring B-H), 7.68e7.76 (d, 1H, Ring B-H, J ¼ 7.8 Hz), 7.88e7.96 (d,
1H, Ring B-H, J ¼ 7.8 Hz).
4e. IR (KBr,
n
cmꢀ1): 3040 (AreH), 2970 (CeH), 1675 (C]N),
1253 (CeO), 1112 (CeO); 1H NMR (300 MHz, CDCl3,
d
ppm):2.30 (s,
3.3. General procedure for the preparation of 2-(aryloxymethyl)
benzoylhydrazide [17] (3aed)
3H, Ring A-CH3), 2.42 (s, 6H, Ring C-(CH3)2), 5.62 (s, 2H, eOCH2),
6.88e6.98 (d, 2H, Ring A-H, J ¼ 7.6 Hz), 7.04 (s, 1H, Ring C-H),
7.16e7.2 (d, 2H, Ring A-H, J ¼ 7.6 Hz), 7.64e7.74 (s, 2H, Ring C-H),
7.44e7.52 (t, 1H, Ring B-H, J ¼ 7.5 Hz), 7.52e7.62 (t, 1H, Ring B-H,
J ¼ 7.5 Hz), 7.82e7.90 (d, 1H, Ring B-H, J ¼ 7.8 Hz), 8.12e8.20 (d, 1H,
Ring B-H, J ¼ 7.8 Hz); MS (VG, 70 eV): m/z 370 (Mþ, 6%) consistent
with the molecular formula, C24H22N2O2.
A
mixture of ethyl 2-(aryloxymethyl)benzoates (2aed)
(0.1 mol), hydrazine hydrate (0.15 mol) and 20 ml of n-propanol
was refluxed on an oil bath for 10 h. The excess solvent was then
distilled off under reduced pressure and the concentrated solution
was quenched to ice cold water. The solid separated was filtered,
washed and dried. The crude product was purified by recrystalli-
zation from ethanol.
4f. IR (KBr,
n
cmꢀ1): 3048 (AreH), 1674 (C]N), 1271 (CeO), 1094
ppm):2.33 (s, 3H, Ring A-CH3),
(CeO); 1H NMR (300 MHz, CDCl3,
d
2.48 (s, 6H, Ring C-(CH3)2), 5.48 (s, 2H, eOCH2), 6.72e6.81 (s, 2H,
Ring C-H), 7.02e7.09 (s, 1H, Ring C-H), 7.11e7.68 (m, 4H, Ring A-H),
7.32e7.41 (t, 1H, Ring B-H, J ¼ 7.6 Hz), 7.42e7.58 (t, 1H, Ring B-H,
J ¼ 7.6 Hz), 7.64e7.78 (d, 1H, Ring B-H, J ¼ 7.8 Hz), 8.02e8.12 (d, 1H,
Ring B-H, J ¼ 7.8 Hz); MS (VG,70 eV): m/z 370 (Mþ) consistent with
the molecular formula, C24H22N2O2.
3a. Colourless solid (89%); mp 118e120 ꢁC; IR (KBr,
3286 (NH2/NH), 3012 (AreH), 1644 (C]O), 1252 (CeO); 1H NMR
(400 MHz, CDCl3, ppm): 2.30 (s, 3H, Ring A-CH3), 4.18 (s, 2H,
n
cmꢀ1):
d
eNH2), 5.31 (s, 2H, eOCH2), 6.93 (m, 3H, Ring A-H), 6.36 (t, 1H, Ring
A-H, J ¼ 7.8 Hz), 7.48e7.56 (m, 4H, Ring B-H), 7.48 (br s, 1H, NH).
3b. Colourless solid (92%); mp 108e110 ꢁC; IR (KBr,
n
cmꢀ1):
4h. IR (KBr,
1250 (CeO), 1118 (CeO); 1H NMR (400 MHz, CDCl3,
6H, Ring C-(CH3)2), 5.61 (s, 2H, eOCH2), 6.96e7.00 (m, 3H, Ring C-
n
cmꢀ1): 3046 (AreH), 2972 (CeH), 1670 (C]N),
ppm):2.40 (s,
3292 (NH2/NH), 3016 (AreH), 1638 (C]O), 1256 (CeO); 1H NMR
(300 MHz, CDCl3, ppm): 2.36 (s, 3H, AreCH3), 4.16(s, 2H, eNH2),
d
d

4716
C.S. Naveena et al. / European Journal of Medicinal Chemistry 45 (2010) 4708e4719
H), 7.22 (d, 2H, Ring A-H, J ¼ 7.4 Hz), 7.26 (d, 2H, Ring A-H,
J ¼ 7.4 Hz), 7.70e7.81 (m, 2H, Ring B-H), 7.83e7.85 (t, 1H, Ring B-H,
J ¼ 7.5 Hz), 8.16e8.18 (t, 1H, Ring B-H, J ¼ 7.5 Hz).
4u. IR (KBr,
n
cmꢀ1): 3056 (AreH), 2960 (CeH), 1655 (C]N), 1248
ppm):2.24 (s, 3H, Ring
(CeO), 1116 (CeO); 1H NMR (400 MHz, CDCl3,
d
A-CH3), 5.63 (s, 2H, eOCH2), 6.89 (t, 1H, Ring A-H, J ¼ 7.3 Hz), 7.03 (d,
1H, Ring A-H, J ¼ 8.1 Hz), 7.13 (d, 1H, Ring A-H, J ¼ 7.1 Hz), 7.19 (t, 1H,
Ring A-H, J ¼ 7.7 Hz), 7.58 (t,1H, Ring B-H, J ¼ 7.6 Hz), 7.69 (t, 1H, Ring
C-H, J ¼ 7.5 Hz), 7.94 (d,1H, Ring B-H, J ¼ 7.7 Hz), 8.02 (d, 2H, Ring B-H,
J ¼ 7.2 Hz), 8.25 (d,1H, Ring C-H, J ¼ 7.7 Hz), 8.32 (d, 1H, Ring C-H,
J ¼ 7.4 Hz), 9.01 (d, 1H, Ring C-H, J ¼ 8.6 Hz), 9.14 (d, 1H, Ring C-H,
J ¼ 4.3 Hz),10.50 (d,1H, Ring C-H, J ¼ 8.4 Hz); MS (VG, 70 eV): m/z 409
(Mþ, 11%) consistent with the molecular formula, C26H23N3O2.
4i. IR (KBr, n
cmꢀ1): 3146 (AreH), 2952 (CeH), 1665 (C]N), 1270
(CeO), 1112 (CeO); 1H NMR (300 MHz, CDCl3,
d ppm):1.55 (s, 3H, Ring
A-CH3), 3.94 (s, 9H, Ring C-(OCH3)3), 5.56 (s, 2H, eOCH2), 7.23e7.26
(m, 4H, Ring A-H), 7.34 (s, 2H, Ring C-H), 7.52 (t, 1H, Ring B-H,
J ¼ 7.3 Hz), 7.61 (t, 1H, Ring B-H, J ¼ 7.3 Hz), 7.86 (d, 1H, Ring B-H,
J ¼ 7.6 Hz), 7.12 (d, 1H, Ring B-H, J ¼ 7.6 Hz); MS (VG, 70 eV): m/z 433
(Mþ þ 1, 3%) consistent with the molecular formula, C25H24N2O5.
4j. IR (KBr,
n
cmꢀ1): 3158 (AreH), 2965 (CeH), 1661 (C]N), 1270
4v. IR (KBr, n
cmꢀ1): 3084 (AreH), 1655 (C]N), 1565(C]C), 1265
(CeO), 1114 (CeO); 1H NMR (300 MHz, CDCl3,
d
ppm):1.43 (s, 3H,
(CeO), 1078 (CeO); MS (VG, 70 eV): m/z 409 (Mþ) consistent with
Ring A-CH3), 3.74 (s, 9H, Ring C-(OCH3)3), 5.42 (s, 2H, eOCH2), 6.84
(s, 2H, Ring C-H), 7.15e7.18 (m, 4H, Ring A-H), 7.32e7.38 (t, 1H, Ring
B-H, J ¼ 7.3 Hz), 7.37e7.40 (t, 1H, Ring B-H, J ¼ 7.3 Hz), 7.45e7.48 (d,
1H, Ring B-H, J ¼ 7.6 Hz), 8.01e8.04 (d, 1H, Ring B-H, J ¼ 7.6 Hz); MS
(VG, 70 eV): m/z 433 (Mþ þ 1, 5%) consistent with the molecular
formula, C25H24N2O5.
the molecular formula, C26H23N3O2.
4w. IR (KBr,
n
cmꢀ1): 3070 (AreH), 1668 (C]N), 1594 (C]C),
1255 (CeO), 1084 (CeO); 1H NMR (300 MHz, CDCl3,
d
ppm):2.34 (s,
3H, Ring A-CH3), 5.54 (s, 2H, eOCH2), 6.76e7.14 (m, 4H, Ring A-H),
7.44e7.58 (m, 2H, Ring B-H), 7.65 (t, 2H, Ring B-H, J ¼ 7.6 Hz),
8.14e9.06 (m, 6H, Ring C-H); MS (VG, 70 eV): m/z 409 (Mþ, 11%).
4k. IR (KBr,
1272 (CeO), 1080 (CeO).
4l. IR (KBr,
cmꢀ1): 3148 (AreH), 2941 (CeH), 1652 (C]N), 1250
(CeO), 1088 (CeO), 748 (CeCl); 1H NMR (300 MHz, CDCl3,
ppm):
n
cmꢀ1): 3164 (AreH), 2954 (CeH), 1666 (C]N),
4x. IR (KBr,
1265 (CeO), 1090 (CeO), 748 (CeCl) cmꢀ1
CDCl3,
n
cmꢀ1): 3084 (AreH), 1654 (C]N), 1588 (C]C),
;
1H NMR (300 MHz,
n
d
ppm):5.62 (s, 2H, eOCH2), 6.94 (d, 2H, Ring A-H, J ¼ 7.6 Hz),
d
7.24 (d, 2H, Ring A-H, J ¼ 7.6 Hz), 7.61e7.78 (m, 4H, Ring B-H),
7.92e8.32 (m, 3H, Ring C-H), 8.81e9.20 (m, 3H, Ring C-H); MS (VG,
70 eV): m/z 431 (M þ 1, 11%).
4.02 (s, 9H, Ring C-(OCH3)3), 5.62 (s, 2H, eOCH2), 7.02 (s, 2H, Ring C-
H), 7.25e7.28 (m, 4H, Ring A-H), 7.42e8.16 (m, 4H, Ring B-H); MS
(VG, 70 eV): m/z 454 (Mþ þ 1) consistent with the molecular
formula, C24H21ClN2O5.
4y. IR (KBr, n
cmꢀ1): 3094 (AreH), 1665 (C]N), 1592(C]C), 1260
(CeO), 1083 (CeO), 611(CeBr); 1H NMR (400 MHz, CDCl3,
d ppm):2.3 (s, 3H, Ring A-CH3), 5.40 (s, 2H, eOCH2), 6.71e6.74 (m,
4m. IR (KBr,
n
cmꢀ1): 3056 (AreH), 2960 (CeH),1665 (C]N),1248
(CeO),1100 (CeO); 1H NMR (300 MHz, CDCl3,
d
ppm):2.33 (s, 3H, Ring
1H, Ring C-H), 6.80e6.96 (m, 3H, Ring C-H), 7.01e7.24 (m, 4H, Ring
B-H), 7.36e7.44 (m, 3H, Ring A-H), 7.46e7.48 (m,1H, Ring A-H); MS
(VG, 70 eV): m/z 422 (Mþ).
A-CH3), 5.65 (s, 2H, eOCH2), 6.85e6.90 (m, 1H, Ring C-H), 7.00e7.03
(m,1H, Ring C-H,), 7.15e7.16 (m, 2H, Ring A-H), 7.25e7.33 (m, 2H, Ring
A-H), 7.47e7.64 (m, 1H/2H, Ring B/C-H), 7.95 (d, 1H, Ring B-H,
J ¼ 7.7 Hz), 8.10e8.18 (m, 2H, Ring B-H); MS (VG, 70 eV): m/z 361
(Mþ þ 1) consistent with the molecular formula, C22H17FN2O2.
4z. IR (KBr, n
cmꢀ1): 3082 (AreH),1696 (C]N),1570 (C]C),1249
(CeO),1092 (CeO), ꢀ6115 (CeBr); MS (VG, 70 eV): m/z 422 (Mþ).
4a0. IR (KBr,
n cm ): 3094 (AreH),1655 (C]N),1592 (C]C),1254
4n. IR (KBr,
n
cmꢀ1): 3065 (AreH), 2985 (CeH), 1665 (C]N),
(CeO), 1083 (CeO) cmꢀ1; 1H NMR (400 MHz, CDCl3,
d ppm):2.30 (s,
1240 (CeO), 1065 (CeO); 1H NMR (300 MHz, CDCl3,
d
ppm):2.30 (s,
3H, Ring A-CH3), 5.61 (s, 2H, eOCH2), 6.84e6.89 (m, 1H, Ring C-H),
6.94e7.08 (m, 3H, Ring C-H), 7.20 (d, 2H, Ring A-H, J ¼ 7.6 Hz), 7.34 (d,
2H, Ring A-H, J ¼ 7.6 Hz), 7.42 (d,1H, AreH, J ¼ 7.8 Hz), 7.50e7.61 (t,1H,
AreH, J ¼ 7.4 Hz), 7.78e7.86 (t,1H, AreH, J ¼ 7.4 Hz), 7.92e8.0 (d,1H,
AreH, J ¼ 7.7 Hz).
3H, Ring A-CH3), 5.60 (s, 2H, eOCH2), 6.80e7.06 (m, 2H, Ring C-H),
7.18e7.19 (m, 2H, Ring C-H), 7.42e7.63 (m, 3H, Ring A-H), 7.84e7.87
(d,1H, Ring A-H), 8.12e8.22 (m, 4H, Ring B-H).
4o. IR (KBr,
n
cmꢀ1): 3052 (AreH), 3012 (CeH), 1656 (C]N),
1245 (CeO), 1074 (CeO); MS (VG, 70 eV): m/z 361 (Mþ þ 1)
4b0. IR (KBr, cmꢀ1): 3066 (AreH),1661 (C]N),1581(C]C),1260
n
consistent with the molecular formula, C22H17FN2O2.
(CeO), 1062 (CeO), 716 (CeBr); MS (VG, 70 eV): m/z 442 (Mþ þ 1).
4p. IR (KBr,
n
cmꢀ1): 3084 (AreH),1628 (C]N),1255 (CeO),1082
4c0. IR (KBr, cmꢀ1): 3090 (AreH), 1654 (C]N), 1588 (C]C),
n
(CeO), 786 (CeCl); 1H NMR (400 MHz, CDCl3,
d
ppm):5.68 (s, 2H,
1255 (CeO),1092 (CeO); 1H NMR (400 MHz, CDCl3,
d ppm):2.34 (s,
eOCH2), 6.80e7.06 (m, 2H, Ring C-H), 7.18e7.19 (m, 2H, Ring C-H),
7.38e7.43 (d, 2H, Ring A-H, J ¼ 7.6 Hz), 7.64e7.67 (d, 2H, Ring A-H,
J ¼ 7.6 Hz), 8.12e8.16 (t, 2H, Ring B-H, J ¼ 7.5 Hz), 8.18e8.20 (d, 2H,
Ring B-H, J ¼ 7.8 Hz); MS (VG, 70 eV): m/z 382 (Mþ) consistent with
the molecular formula, C21H14ClFN2O2.
3H, Ring A-CH3), 5.63 (s, 2H, eOCH2), 6.78e6.88 (m, 3H, Ring C-H),
7.16e7.27 (m,1H, Ring A-H), 7.42e7.46 (m,1H, Ring A-H), 7.53 (t,1H,
Ring A-H, J ¼ 7.6 Hz), 7.64 (t, 1H, Ring A-H, J ¼ 7.6 Hz), 7.91 (d, 1H,
Ring B-H, J ¼ 8.0 Hz), 7.17 (d, 1H, Ring B-H, J ¼ 8.0 Hz), 8.42 (m, 1H,
Ring B-H), 8.59 (m, 1H, Ring B-H).
4q. IR (KBr,
n
cmꢀ1): 3076 (AreH),1632 (C]N),1245 (CeO),1066
ppm):2.30 (s, 3H, Ring A-CH3),
4d0. IR (KBr, cmꢀ1): 3092 (AreH), 1658 (C]N), 1590(C]C),
n
(CeO); 1H NMR (300 MHz, CDCl3,
d
1084 (CeO); MS (VG, 70 eV): m/z 378 (Mþ) consistent with the
5.68 (s, 2H, eOCH2), 6.80e7.31 (m, 4H, Ring A-H), 7.44 (d, 2H, Ring
C-H, J ¼ 7.7 Hz), 7.56 (d, 2H, Ring C-H, J ¼ 7.7 Hz), 8.26 (t, 2H, Ring B-
H, J ¼ 7.5 Hz), 8.31 (d, 2H, Ring B-H, J ¼ 7.8 Hz).
molecular formula, C21H16ClN3O2.
4e0. IR (KBr,
n
cmꢀ1): 3086 (AreH), 1662 (C]N), 1590 (C]C),
1246 (CeO), 1090 (CeO); 1H NMR (300 MHz, CDCl3,
d ppm):2.38 (s,
4r. IR (KBr,
n
cmꢀ1): 3096 (AreH), 1650 (C]N), 1572(C]C), 1248
3H, Ring A-CH3), 5.60 (s, 2H, eOCH2), 6.67e6.71 (m,1H, Ring C-H),
6.76e6.80 (m, 2H, Ring C-H), 7.32 (d, 2H, Ring A-H, J ¼ 7.6 Hz), 7.43
(d, 1H, Ring A-H, J ¼ 7.6 Hz), 7.53 (t, 1H, Ring B-H, Ring A-H,
J ¼ 7.5 Hz), 8.05 (t, 1H, Ring A-H, J ¼ 7.5 Hz), 8.13 (d, 1H, Ring A-H,
J ¼ 7.9 Hz), 8.30 (d, 2H, Ring A-H, J ¼ 7.8 Hz).
(CeO), 1068 (CeO); MS (VG, 70 eV): m/z 378 (Mþ) consistent with
the molecular formula, C22H17ClN2O2.
4s. IR (KBr, n
cmꢀ1): 3090 (AreH), 1654 (C]N), 1570 (C]C),1240
(CeO), 1054 (CeO); MS (VG, 70 eV): m/z 378 (Mþ) consistent with
the molecular formula, C22H17ClN2O2.
4f0. IR (KBr, cmꢀ1): 3074 (AreH), 1660 (C]N), 1592 (C]C),
n
4t. IR (KBr,
n
cmꢀ1): 3054 (AreH), 1645 (C]N), 1244 (CeO), 1068
1249 (CeO), 1078 (CeO), 757 (CeCl); 1H NMR (300 MHz, CDCl3,
d ppm):5.36 (s, 2H, eOCH2), 6.80e6.82 (m,1H, Ring C-H), 6.84e6.88
(CeO) cmꢀ1; 1H NMR (300 MHz, CDCl3,
d
ppm):5.54 (s, 2H, eOCH2),
6.80e7.31 (m, 4H, Ring A-H), 7.44 (d, 2H, Ring C-H, J ¼ 7.7 Hz), 7.56
(d, 2H, Ring C-H, J ¼ 7.7 Hz), 8.26 (t, 2H, Ring B-H, J ¼ 7.5 Hz), 8.31 (d,
2H, Ring B-H, J ¼ 7.8 Hz); MS (VG, 70 eV): m/z 398 (Mþ þ 1)
consistent with the molecular formula, C21H14Cl2N2O2.
(m, 2H, Ring C-H), 7.47 (d, 2H, Ring A-H, J ¼ 7.6 Hz), 7.60 (d, 2H, Ring
A-H, J ¼ 7.6 Hz), 7.88e7.94 (m, 2H, Ring B-H), 8.12e8.16 (m, 2H, Ring
B-H); MS (VG, 70 eV): m/z 399 (Mþ þ 1) consistent with the
molecular formula, C20H13Cl2N3O2.

C.S. Naveena et al. / European Journal of Medicinal Chemistry 45 (2010) 4708e4719
4717
3.5. General procedure for the preparation of 2-(aryloxymethyl)-
1,3,4-oxadiazole-5-thiones (5aed)
4.84 (s, 2H, NeCH2eN), 5.61 (s, 2H, eOCH2), 6.92e7.21 (m, 4H, Ring
A-H), 7.36e7.51 (m, 2H, AreH), 7.68e7.92 (m, 2H, AreH); MS (VG,
70 eV): m/z 419 (Mþ þ 1) consistent with the molecular formula,
C20H20ClN3O3S.
A
mixture of 2-(aryloxymethyl)benzoylhydrazides (3aed)
(0.1 mol), carbon disulphide (0.2 mol) and potassium hydroxide
solution (30%, 5 ml) was refluxed on a water bath for 2 h. The reaction
mixture was cooled and acidified with acetic acid. The product
separated was filtered, washed with water and dried. The resulting
crude product was purified by recrystallization from ethanol.
6e. IR (KBr,
n
cmꢀ1): 3080 (AreH), 1680 (C]N), 1189 (C]S) 1090
(CeF); 1HNMR (300 MHz, CDCl3,
d
ppm): 2.3 (s, 3H, Ring A-CH3), 3.72
(s, 2H, eNHCH2), 4.62 (s,1H, NH), 5.68 (s, 2H, eOCH2), 6.72e6.80 (m,
3H, Ring A-H), 7.11e7.21 (m,1H, Ring A-H), 7.24e7.49 (m, 4H, Ring C-
H), 7.59 (t, 1H, Ring B-H, J ¼ 7.5 Hz), 7.65 (t, 1H, Ring B-H, J ¼ 7.5 Hz),
7.75 (d, 1H, AreH, J ¼ 7.8 Hz), 7.99 (d, 1H, AreH, J ¼ 7.7 Hz).
5a. Colourless solid (85%); mp 140e142 ꢁC; IR (KBr,
n
cmꢀ1):
3142 (NH/SH), 1658 (C]N); 1H NMR (400 MHz, CDCl3,
d
ppm): 12.6
6f. IR (KBr, n
cmꢀ1): 3094 (AreH), 1674 (C]N), 1192 (C]S), 1082
(s,1H, NH/SH), 2.36 (s, 3H, Ring A-CH3), 5.28 (s, 2H, eOCH2),
7.24e7.88 (m, 4H, Ring A-H), 7.94e8.29 (m, 2H, Ring B-H),
8.34e8.37 (d,1H, Ring B-H, J ¼ 7.8 Hz), 8.43 (d,1H, AreH, J ¼ 7.8 Hz).
(CeF); MS (VG, 70 eV): m/z 473 (Mþ þ 1) consistent with the
molecular formula, C24H20F3N3O3S.
6g. IR (KBr,
(CeF).
6h. IR (KBr,
n
cmꢀ1): 3086 (AreH), 1668 (C]N), 1186 (C]S), 1096
5b. Colourless solid (83%); mp 152e154 ꢁC; IR (KBr,
3145 (NH/SH), 1658 (C]N).
n
cmꢀ1):
n
cmꢀ1): 3081 (AreH),1666 (C]N),1188 (C]S),1088
5c. Colourless solid (82%); mp 158e160 ꢁC; IR (KBr,
n
cmꢀ1):
(CeF), 755 (CeCl); 1H NMR (300 MHz, CDCl3,
d ppm): 3.68 (s, 2H,
3080 (NH/SH), 1654 (C]N); 1H NMR (400 MHz, CDCl3,
d
ppm): 12.0
eNHCH2), 4.53 (s, 1H, NH), 5.42 (s, 2H, eOCH2), 6.76e6.84 (m, 3H,
Ring C-H), 7.06e7.15 (m, 1H, Ring C-H), 7.18e7.42 (m, 4H, Ring A-H),
7.52e7.64 (m, 2H, Ring B-H), 7.70e7.96 (m, 2H, Ring B-H); MS (VG,
70 eV): m/z 493 (Mþ þ 1) consistent with the molecular formula,
C23H17F3ClN3O3S.
(s,1H, NH/SH), 2.29 (s, 3H, Ring A-CH3), 5.16 (s, 2H, eOCH2),
6.89e6.93 (d, 2H, Ring A-H, J ¼ 7.2 Hz), 7.14e7.29 (d, 2H, Ring A-H,
J ¼ 7.2 Hz), 7.55 (t, 2H, Ring B-H, J ¼ 7.5 Hz), 7.79 (d, 1H, Ring B-H,
J ¼ 7.8 Hz), 8.03 (d, 1H, Ring B-H, J ¼ 7.8 Hz); 13C NMR (100 MHz,
CDCl3,
d
ppm):14.49, 29.16, 59.91, 115.49, 129.38,132.39, 156.04,
6i. IR (KBr,
n
cmꢀ1): 3092 (AreH), 1705 (C]O), 1690 (C]N), 1170
ppm):
159.41, 178.76; DEPT: CH and CH3:
d
14.49, 115.49, 132.39; CH2:
d
(C]S), 1108 (CeF), 755 (CeCl); 1H NMR (300 MHz, CDCl3,
d
29.16, 59.91; MS (VG, 70 eV): m/z 298 (Mþ, 6.5%) consistent with
2.33 (s, 3H, Ring A-CH3), 3.41 (s, 2H, eNHCH2), 4.64 (s, 1H, NH), 5.46
(s, 2H, eOCH2), 6.70e6.83 (m, 3H, Ring C-H), 7.16e7.35 (m, 4H, Ring
A-H), 7.45 (m, 2H, Ring B-H), 7.57 (d, 1H, Ring B-H, J ¼ 7.8 Hz), 7.74
(d, 1H, Ring B-H, J ¼ 7.7 Hz).
the molecular formula, C16H14N2O2S.
5d. Colourless solid (87%); mp 130e132 ꢁC IR (KBr, cmꢀ1): 3098
n
(NH/SH), 1612/1648 (C]N), 748 (CeCl); 1H NMR (400 MHz, CDCl3,
ppm): 11.8 (s,1H, NH/SH), 5.22 (s, 2H, eOCH2), 6.77 (d, 2H, Ring A-H,
d
6j. IR (KBr, n
cmꢀ1): 3096 (AreH), 1703 (C]O), 1687 (C]N), 1178
J¼ 7.8 Hz), 7.16e7.31(d, 2H, Ring A-H, J¼ 7.8 Hz), 7.54e7.76 (m, 2H, Ring
(C]S), 1098 (CeF), 745 (CeCl); MS (VG, 70 eV): m/z 535 (Mþ þ 1)
B-H), 7.91 (d,1H, Ring B-H, J ¼ 7.8 Hz), 8.09 (d,1H, Ring B-H, J ¼ 7.8 Hz).
consistent with the molecular formula, C25H19ClF3N3O2S.
6m. IR (KBr,
n
cmꢀ1): 3085 (AreH), 1674 (C]N), 1182 (C]S) 750
3.6. General procedure for the preparation of Mannich bases (6aep)
(CeCl); 1H NMR (400 MHz, CDCl3,
d ppm): 2.13 (s, 3H, Ring A-CH3),
2.33 (s, 3H, Ring C-CH3), 5.42 (s, 2H, eNHCH2), 5.10 (s, 1H, NH), 5.49
(s, 2H, eOCH2), 6.68e6.81 (m, 4H, Ring A-H), 6.94 (d, 1H, Ring C-H,
J ¼ 7.4 Hz), 7.08e7.25 (m, 2H, Ring B-H), 7.45 (d, 1H, Ring C-H,
J ¼ 7.4 Hz), 7.53e7.57 (m, 1H, Ring C-H), 7.75 (d, 1H, AreH,
J ¼ 7.8 Hz), 7.97 (d, 1H, Ring B-H, J ¼ 7.7 Hz).
1,3,4-Oxadiazole-5-thiones (5aed) (10 mmol) was dissolved in
methanol, then 40% formaldehyde (1.5 ml) and primary/secondary
amine (10 mmol) in methanol were added with stirring. The
resulting mixture was stirred overnight at room temperature. The
precipitated solids were filtered, washed with water and recrys-
tallized from methanol to yield the title compounds 6 (Table 2).
6n. IR (KBr, n
cmꢀ1): 3058 (AreH), 1671 (C]N), 1180 (C]S), 750
(CeCl); MS (VG, 70 eV): m/z 453 (Mþ þ 1) consistent with the
6a. IR (KBr,
n
cmꢀ1): 3080 (AreH), 1628 (C]N), 1189 (C]S); 1H
molecular formula, C24H22ClN3O2S.
NMR (400 MHz, CDCl3, d ppm): 2.27 (s, 3H, Ring A-CH3), 2.76 (t, 4H,
morpholine-H, J ¼ 4.6 Hz), 3.64 (t, 4H, morpholine-H, J ¼ 4.6 Hz),
5.02 (s, 2H, NeCH2eN), 5.40 (s, 2H, eOCH2), 6.82e6.91 (m, 2H, Ring
A-H), 7.11e7.19 (m, 2H, Ring A-H), 7.49 (t, 1H, Ring B-H, J ¼ 7.6 Hz),
7.61 (t, 1H, Ring B-H, J ¼ 7.5 Hz), 7.82 (d, 1H, Ring B-H, J ¼ 7.8 Hz),
8.04 (d, 1H, Ring B-H, J ¼ 7.8 Hz); 13C NMR (100 MHz, CDCl3,
6p. IR (KBr,
n
cmꢀ1): 3090 (AreH), 1678 (C]N), 1189 (C]S), 748
(CeCl); 1H NMR (400 MHz, CDCl3,
d
ppm): 2.30 (s, 3H, Ring C-CH3),
5.24 (s, 2H, eNHCH2), 5.38 (s, 1H, NH), 5.61 (s, 2H, eOCH2),
6.72e6.85 (m, 4H, Ring A-H), 6.98 (d, 1H, Ring C-H, J ¼ 7.4 Hz),
7.12e7.28 (m, 2H, Ring B-H), 7.40 (d, 1H, Ring C-H, J ¼ 7.4 Hz),
7.50e7.54 (m, 1H, Ring C-H), 7.56e7.58 (d, 1H, Ring B-H, J ¼ 7.8 Hz),
7.82 (d, 1H, Ring B-H, J ¼ 7.8 Hz); MS (VG, 70 eV): m/z 473 (Mþ þ 1)
consistent with the molecular formula, C23H19Cl2N3O2S.
d
ppm):21.12, 67.37, 111.27, 115.42, 118.74, 121.77, 127.54, 127.66,
128.19, 128.88, 132.05, 137.04, 139.26, 157.92, 160.35, 137.53 and
177.13; DEPT: CH and CH3: 21.61, 111.75, 115.90, 122.26, 128.04,
d
128.16, 128.69, 129.37, 132.54; CH2:67.86; MS (VG, 70 eV): m/z 398
3.7. General procedure for the synthesis of 2-thioalkyl/aralkyl-5-(2-
[aryloxymethyl])-1,3,4-oxadiazoles (7aet)
(Mþ þ 1, 17%, consistent with the molecular formula, C21H23N3O3S).
6b. IR (KBr,
NMR (300 MHz, CDCl3,
n
cmꢀ1): 3092 (AreH), 1668 (C]N), 1182 (C]S); 1H
d
ppm): 2.32 (s, 3H, Ring A-CH3), 2.83 (t, 4H,
5-Substituted-1,3,4-oxadiazole-2-thiones (5aed) (1 mmol),
alkyl/aralkyl chloride (1 mmol) and sodium hydroxide (5 mmol) in
ethanol were stirred for 10 h. The completion of reaction was
monitored by thin layer chromatography. After completion of the
reaction, the reaction mixture was concentrated under reduced
pressure to afford the title compounds. The crude product was
purified by crystallization from a suitable solvent. The physico-
chemical data are given in Table 3.
morpholine-H, J ¼ 4.5 Hz), 3.80 (t, 4H, morpholine-H, J ¼ 4.5 Hz),
4.82 (s, 2H, NeCH2eN), 5.51 (s, 2H, eOCH2), 6.68e6.76 (m, 2H, Ring
A-H), 6.84e6.93 (m, 2H, Ring A-H), 7.28 (t, 1H, Ring B-H, J ¼ 7.5 Hz),
7.38 (t, 1H, Ring B-H, J ¼ 7.5 Hz), 7.63 (d, 1H, Ring B-H, J ¼ 7.8 Hz),
7.86 (d, 1H, Ring B-H, J ¼ 7.9 Hz).
6c. IR (KBr,
n
cmꢀ1): 3086 (AreH), 1701 (C]N), 1194 (C]S); MS
(VG,70 eV): m/z 398 (Mþ þ 1) consistent with the molecular
formula, C21H23N3O3S.
7a. IR (KBr,
n
cmꢀ1): 3078 (AreH), 2926 (CeH), 1674 (C]N), 1230
ppm): 1.2 (t, 3H,
6d. IR (KBr,
(CeCl); 1H NMR (300 MHz, CDCl3,
pholine-H, J ¼ 4.5 Hz), 3.41e3.44 (t, 4H, morpholine-H, J ¼ 4.5 Hz),
n
cmꢀ1): 3006 (AreH), 1670 (C]N), 1184 (C]S), 758
(CeO), 1084 (CeO); 1H NMR (400 M Hz, CDCl3,
d
d
ppm): 2.78e2.81 (t, 4H, mor-
eSCH2eCH3, J ¼ 6.7 Hz), 2.38 (s, 3H, Ring A-CH3), 3.12 (q, 2H, eSCH2e,
J ¼ 6.7 Hz), 5.62 (s, 2H, eOCH2), 6.86e7.95 (m, 3H, Ring A-H),

4718
C.S. Naveena et al. / European Journal of Medicinal Chemistry 45 (2010) 4708e4719
7.04e7.19 (m, 1H, Ring A-H), 7.22e7.27 (m, 2H, Ring B-H), 7.40 (d, 1H,
Ring B-H, J ¼ 7.8 Hz), 7.77 (d,1H, AreH, J ¼ 7.9 Hz); MS (VG,70 eV): m/z
326(Mþ) consistent with the molecular formula, C18H18N2O2S.
d ppm): 4.51 (s, 2H, eSCH2), 5.64 (s, 2H, eOCH2), 6.74e6.86 (m, 2H,
Ring C-H), 7.02e7.07 (m, 2H, Ring C-H), 7.18e7.19 (m, 2H, Ring B-H),
7.23e7.28 (m, 2H, Ring B-H), 7.48 (d, 2H, Ring A-H, J ¼ 7.3 Hz), 7.64
(m, 2H, Ring A-H, J ¼ 7.3 Hz).
7b. IR (KBr,
n
cmꢀ1): 3094 (AreH), 2942 (CeH), 1673 (C]N), 1238
(CeO), 1080 (CeO); 1H NMR (400 M Hz, CDCl3,
d
ppm): 1.21 (t, 3H,
7q. IR (KBr, n
cmꢀ1): 3064 (AreH), 2935 (CeH), 1650 (C]N),
eSCH2eCH3, J ¼ 6.9 Hz), 2.28 (s, 3H, Ring A-CH3), 3.21 (q, 2H, eSCH2,
J¼ 6.9Hz), 5.48(s, 2H, eOCH2),6.81e7.92(m, 3H, RingA-H), 7.05e7.11
(d,1H, Ring A-H), 7.38e7.55 (t, 2H, AreH, Ring B-H, J ¼ 7.5 Hz), 7.78 (d,
1H, Ring B-H, J ¼ 7.8 Hz), 7.84e7.87 (d, 1H, Ring B-H, J ¼ 7.9 Hz).
1248 (CeO), 1132 (CeO); 1H NMR (400 MHz, CDCl3,
d ppm): 1.95 (s,
3H, Ring C-CH3), 2.33 (s, 3H, Ring A-CH3), 4.49 (s, 2H, eSCH2), 5.55
(s, 2H, eOCH2), 6.86e6.91 (t, 1H, Ring C-H, J ¼ 7.2 Hz), 6.97 (d, 1H,
Ring C-H, J ¼ 7.2 Hz), 7.16 (t, 2H, Ring C-H, J ¼ 7.2 Hz), 7.24 (d, 1H,
Ring A-H, J ¼ 7.6 Hz), 7.41e7.46 (m, 3H, Ring A-H,), 7.43 (t, 1H, Ring
B-H, J ¼ 7.4 Hz), 7.58 (t,1H, AreH, J ¼ 7.3 Hz), 7.90e7.95 (m, 2H, Ring
B-H); MS (VG, 70 eV): m/z 403 (Mþ þ 1, 17%) consistent with the
molecular formula, C24H22N2O2S.
7c. IR (KBr, n
cmꢀ1): 3097 (AreH), 2961 (CeH),1680 (C]N),1241
(CeO), 1088 (CeO); MS (VG, 70 eV): m/z 326(Mþ) consistent with
the molecular formula, C18H18N2O2S.
7d. IR (KBr,
n
cmꢀ1): 3063 (AreH), 2930 (CeH), 1674 (C]N),
1230 (CeO), 1045 (CeO); 1H NMR (400 MHz, CDCl3,
d
ppm): 1.21 (t,
7r. IR (KBr,
n
cmꢀ1): 3072 (AreH), 2928 (CeH), 1674 (C]N), 1068
ppm): 1.98 (s, 3H, Ring C-CH3),
3H, eSCH2eCH3, J ¼ 6.5 Hz), 2.35 (s, 3H, Ring A-CH3), 3.32 (q, 2H,
eSCH2, J ¼ 6.5 Hz), 5.56 (s, 2H, eOCH2), 6.82 (d, 2H, Ring A-H,
J ¼ 7.7 Hz), 7.18 (d, 2H, Ring A-H, J ¼ 7.7 Hz), 7.45 (t, 1H, Ring B-H,
J ¼ 7.5 Hz), 7.57 (t, 1H, Ring B-H, J ¼ 7.5 Hz), 7.88 (d, 1H, AreH,
J ¼ 7.9 Hz), 7.96 (d, 1H, AreH, J ¼ 7.9 Hz); 13C NMR (100 MHz, CDCl3,
(CeO); 1H NMR (400 MHz, CDCl3,
d
2.42 (s, 3H, Ring A-CH3), 4.61 (s, 2H, eSCH2), 5.58 (s, 2H,eOCH2),
6.78e6.83 (m, 1H, Ring C-H), 6.86e6.89 (m, 1H, Ring C-H),
6.96e7.02 (m, 2H, Ring C-H), 7.31e7.33 (m, 1H, Ring A-H), 7.52e7.58
(m, 3H, Ring A-H), 7.661e7.82 (m, 2H, Ring B-H), 7.98e8.03 (m, 2H,
Ring B-H); MS (VG, 70 eV): m/z 403 (Mþ þ 1), consistent with the
molecular formula, C24H22N2O2S.
d
ppm): 14.49, 29.16, 59.91, 115.49, 129.38, 132.39, 156.04, 159.41,
178.76; DEPT: CH and CH3: 14.49, 115.49, 132.39; CH2: 29.16, 59.91.
7e. IR (KBr,
cmꢀ1): 3081 (AreH), 2941 (CeH),1680 (C]N),1247
(CeO), 1093 (CeO); 1H NMR (400 MHz, CDCl3,
ppm): 2.24 (s, 3H,
n
7s. IR (KBr,
n
cmꢀ1): 3090 (AreH), 2952 (CeH), 1677 (C]N), 1074
ppm):1.96(s, 3H, RingC-CH3), 2.31
d
(CeO);1HNMR(400MHz,CDCl3,
d
Ring A-CH3), 4.51 (s, 2H, eSCH2), 5.42 (s, 2H, eOCH2), 6.71e7.13 (m,
3H, Ring A-H), 7.15e7.25 (m, 1H, Ring A-H), 7.28e7.56 (m, 5H, Ring
C-H), 7.48 (t, 2H, Ring B-H, J ¼ 7.5 Hz), 7.78 (d, 1H, AreH, J ¼ 7.8 Hz),
7.94 (d, 1H, AreH, J ¼ 7.8 Hz); MS (VG, 70 eV): m/z 388 (Mþ, 21%,
consistent with the molecular formula, C23H20N2O2S).
(s, 3H, Ring A-CH3), 4.45 (s, 2H, eSCH2), 5.62 (s, 2H, eOCH2), 6.88e7.18
(m, 3H, Ring C-H), 7.28 (d,1H, Ring C-H, J ¼ 7.3 Hz), 7.22e7.40 (m, 4H,
Ring A-H), 7.57 (t, 1H, AreH, J ¼ 7.2 Hz), 7.72 (t, 1H, AreH, J ¼ 7.2 Hz),
7.81e7.86 (t, 2H, AreH, J ¼ 7.7 Hz); MS (VG, 70 eV): m/z 403 (Mþ þ 1)
consistent with the molecular formula, C24H22N2O2S.
7g. IR (KBr,
n
cmꢀ1): 3088 (AreH), 2998 (CeH), 1675 (C]N),
ppm): 2.32 (s,
7t. IR (KBr,
n
cmꢀ1): 3088(AreH), 2948 (CeH), 1664 (C]N), 1068
ppm): 1.95 (s, 3H,
1242 (CeO), 1077 (CeO); 1H NMR (400 MHz, CDCl3,
d
(CeO), 758 (CeCl); 1H NMR (400 MHz, CDCl3,
d
3H, Ring A-CH3), 4.56 (s, 2H, eSCH2), 5.61 (s, 2H, eOCH2), 6.89 (d,
2H, Ring A-H, J ¼ 7.6 Hz), 7.10 (d, 2H, Ring A-H, J ¼ 7.6 Hz), 7.31e7.64
(m, 5H, Ring C-H), 7.47 (t, 2H, Ring B-H, J ¼ 7.5 Hz), 7.75 (d, 2H, Ring
B-H, J ¼ 7.8 Hz); MS (VG, 70 eV): m/z 388 (Mþ, 21%, consistent with
the molecular formula, C23H20N2O2S).
Ring C-CH3), 4.36 (s, 2H, eSCH2), 5.44 (s, 2H, eOCH2), 6.94e7.22 (m,
4H, Ring C-H), 7.33 (d, 2H, Ring A-H, J ¼ 7.4 Hz), 7.52e7.57 (m, 4H,
Ring A/B-H), 7.66e8.08 (m, 2H, Ring B-H); MS (VG, 70 eV): m/z 424
(Mþ þ 1) consistent with the molecular formula, C23H19N2ClO2S.
7i. IR (KBr,
n
cmꢀ1): 3085 (AreH), 2968 (CeH), 1676 (C]N), 1251
ppm): 2.30 (s, 3H,
4. Conclusions
(CeO), 1035 (CeO); 1H NMR (400 MHz, CDCl3,
d
Ring A-CH3), 4.56 (s, 2H, eSCH2), 5.64 (s, 2H, eOCH2), 6.79 (d, 2H,
Ring C-H, J ¼ 7.4 Hz), 6.91 (s, 1H, Ring C-H), 7.31e7.32 (m, 2H, Ring
B-H), 7.88e7.93 (m, 1H, Ring A-H), 7.41e7.57 (m, 3H, Ring A-H),
7.60e7.63 (m, 2H, Ring B-H).
Several disubstituted-1,3,4-oxadaiazoles, 1,3,4-oxadaiazole
Mannich bases and S-alkylated derivatives derived from 2-(aryloxy-
methyl)benzoic acids were successfully synthesized in 70e85%
yields. The structures of all the compounds were confirmed by
recording their 1H NMR,13C NMR, Mass and IR spectra. All the newly
synthesized compounds were screened for their in vitro antibacte-
rial and antifungal properties. Among the screened samples,
compounds 4l, 4p, 4f0, 6d and 7l showed excellent antibacterial
activity against S. aureus, B. subtilis and P. aeruginosa even at low
7j. IR (KBr, n
cmꢀ1): 3097 (AreH), 2974 (CeH), 1674 (C]N), 1258
(CeO), 1074 (CeO); MS (VG, 70 eV): m/z 458(Mþ) consistent with
the molecular formula, C23H18Cl2N2O2S.
7k. IR (KBr,
n
cmꢀ1): 3085 (AreH), 2968 (CeH), 1687 (C]N),
1262 (CeO), 1065 (CeO); MS (VG, 70 eV): m/z 458 (Mþ) consistent
with the molecular formula, C23H18Cl2N2O2S.
concentration of 3 mg/ml. The excellent antibacterial activity shown
7l. IR (KBr,
n
cmꢀ1): 3080 (AreH), 2970 (CeH), 1678 (C]N), 1254
by these molecules may be due to the presence of 4-chlorophenyl,
3,4,5-trimethoxyphenyl, 2-flourophenyl-, 2-chloronicotinyl, mor-
pholino and 2,4-dichlorobenzyl groups attached to the oxadiazole
moiety. Remaining compounds have showed significant antibacte-
rialactivity. The significant activityof 4h, 4i, 4j, 4p, 4u, 4x, 4y, 4c0, 4d0,
4f0, 6d, 6i, 6j, 6k, 6l, 7j, 7s and 7t might be due to dimethylphenyl,
trimethoxyphenyl, 2-flourophenyl, quinolinyl, chloronicotinyl,
morpholino, trifluoromethylphenyl, chlorophenyl and tolyl groups.
Antifungal screening was carried out on P. Marneffei and A. fla-
vus. Among the tested compounds, 4i and 4x showed highest
(CeO), 1085 (CeO), 750 (CeCl); 1H NMR (400 MHz, CDCl3,
d
ppm):
4.42 (s, 2H, eSCH2), 5.48 (s, 2H, eOCH2), 6.65 (d, 2H, Ring C-H,
J ¼ 7.4 Hz), 6.82 (s, 1H, Ring C-H), 6.99 (d, 2H, Ring A-H, J ¼ 7.3 Hz),
7.09e7.14 (m, 2H, Ring B-H), 7.69 (d, 2H, Ring A-H, J ¼ 7.3 Hz),
7.83e7.85 (m, 2H, Ring B-H).
7m. IR (KBr,
n
cmꢀ1): 3084 (AreH), 2946 (CeH), 1680 (C]N),
ppm): 2.33 (s,
1246 (CeO), 1084 (CeO); 1H NMR (400 MHz, CDCl3,
d
3H, Ring A-CH3), 4.48 (s, 2H, eSCH2), 5.57 (s, 2H, eOCH2),
6.88e6.98 (m, 2H, Ring C-H), 7.15e7.19 (m, 2H, Ring C-H), 7.27e7.28
(m, 2H, Ring B-H), 7.91e7.95 (m, 2H, Ring B-H), 7.32e7.47 (m, 3H,
Ring A-H), 7.57e7.60 (m, 1H, Ring A-H); MS (VG, 70 eV): m/z 424
(Mþ þ 1), consistent with the molecular formula, C23H19ClN2O2S.
inhibition at 3 mg/ml concentration. 4i and 4x have trimethoxy and
quinoline groups respectively (Table 4). The significant antifungal
activities of the compounds 4h, 4j, 4k, 4u, 4y, 4a0, 4c0, 4d0, 6e, 6f, 6g,
6h, 6l, 7c, 7d and 7t may be due to dimethylphenyl, trimethoxy-
phenyl, flourophenyl, quinolinyl, chloronicotinyl, morpholino, tri-
fluoromethylphenyl and dichlorophenyl groups. The screening
studies have demonstrated that the newly synthesized compounds
exhibit promising antibacterial and antifungal properties.
7n. IR (KBr,
n
cmꢀ1): 3084 (AreH), 2952 (CeH), 1676 (C]N),
1240 (CeO), 1078 (CeO); MS (VG, 70 eV): m/z 424(Mþ þ 1),
consistent with the molecular formula, C23H19ClN2O2S.
7p. IR (KBr,
n
cmꢀ1): 3076 (AreH), 2948 (CeH), 1675 (C]N),
1244 (CeO), 1092 (CeO), 746 (CeCl); 1H NMR (400 MHz, CDCl3,

C.S. Naveena et al. / European Journal of Medicinal Chemistry 45 (2010) 4708e4719
4719
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We are grateful to the Managing Director, SeQuent Scientific Ltd.,
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