Synthesis, antibacterial and antifungal evaluation of novel 3-(5-phenyl[1,3,4]oxadiazol-2-yl]-3,4-dihydro-2H-benzo[e][1,3]oxazines

Article abstract of DOI:10.14233/ajchem.2014.16030

Various novel 3-(5-phenyl[1,3,4]oxadiazol-2-yl]-3,4-dihydro-2H-benzo[e][1, 3]oxazines (5a-g) have been synthesized from 5-phenyl- [1,3,4]oxadiazol-2- ylamine (1) and different salicylaldehydes (2a-g) as starting materials and 2-[(5-phenyl[1,3,4]oxadiazol-2- ylimino)methyl]phenols (3a-g) and 2-[(5-phenyl[1,3,4]oxadiazol-2-ylamino)methyl]phenols (4a-g) as intermediates. The newly synthesized compounds after structural confirmation were used to screen their antibacterial, antifungal and nematicidal activities and some of these compounds have been found as potential antimicrobial agents.

Full text of DOI:10.14233/ajchem.2014.16030

Asian Journal of Chemistry; Vol. 26, No. 14 (2014), 4145-4148
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.16030
Synthesis, Antibacterial and Antifungal Evaluation of Novel
3-(5-Phenyl[1,3,4]oxadiazol-2-yl]-3,4-dihydro-2H-benzo[e][1,3]oxazines
1
1,*
2
2
N. VASU , B. BHARATH KUMAR GOUD , Y. BHARATHI KUMARI and B. PULLA RAO
1Suven Life Sciences Ltd, Jeedimetla, Hyderabad-500 055, India
2Department of Chemistry, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad-500 072, India
*Corresponding author: E-mail: goudbk@yahoo.com
Received: 10 July 2013;
Accepted: 28 October 2013;
Published online: 5 July 2014;
AJC-15430
Various novel 3-(5-phenyl[1,3,4]oxadiazol-2-yl]-3,4-dihydro-2H-benzo[e][1,3]oxazines (5a-g) have been synthesized from 5-phenyl-
[1,3,4]oxadiazol-2-ylamine (1) and different salicylaldehydes (2a-g) as starting materials and 2-[(5-phenyl[1,3,4]oxadiazol-2-
ylimino)methyl]phenols (3a-g) and 2-[(5-phenyl[1,3,4]oxadiazol-2-ylamino)methyl]phenols (4a-g) as intermediates. The newly synthesized
compounds after structural confirmation were used to screen their antibacterial, antifungal and nematicidal activities and some of these
compounds have been found as potential antimicrobial agents.
Keywords: 1,3,4-Oxadiazoles, 1,3-Oxazines, Antimicrobial activity, Nematicidal activity.
PerkinElmer BX serried FTIR 5000 spectrometer using KBr
pellet. NMR spectra were recorded on a Varian 300 MHz
spectrometer for 1H NMR and 100 MHz spectrometer for 1H
NMR. The chemical shifts were reported as ppm down field
using TMS as an internal standard. Mass spectra were recorded
on a VG-Micromass 7070 H spectrometer operating at 70 eV.
2-[(5-Phenyl[1,3,4]oxadiazol-2-ylimino)methyl]phenols
(3a-g):A mixture of 5-phenyl-[1,3,4]-oxadiazol-2-ylamine (1)
(0.01 mol) and suitable salicylaldehyde (2) (0.01 mol) was
refluxed in ethanol (10 mL) for 2-3 h. The resultant solution
was cooled and the separated solid was filtered, dried and
recrystallized from pet-ether.
INTRODUCTION
1,3,4-Oxadiazoles are biologically active, synthetically
useful and important heterocyclic compounds and investigation
of their chemical and biological behavior have gained more
importance in recent decades. Different classes of oxadiazoles
possess an extensive spectrum of pharmacological activities
such as antimalarial1, antiinflammatory2, anticonvulsant3,
analgesic4, antimicrobial5, antimycobacterial6, antitumor7,
herbicidal8, vasodialatory9, cytotoxic10, hypolipidemic11 and
antiedema12.
Nitrogen heterocycles are of special interest because they
constitute an important class of natural and nonnatural products,
many of which exhibite useful biological activities. Investi-
gation of the 1,3-oxazines has shown that they possess varied
pharmacological properties such as analgesic, anticonvulsant,
antitubercular, antibacterial and anticancer13, anti HIV-114 and
therapeutic activity15. The biological significance of these
compounds impelled us to continue the work on the synthesis
of some new and novel oxadiazoles and 1,3-oxazines.
2-[(5-Phenyl[1,3,4]oxadiazol-2-ylamino)methyl]phenols
(4a-g): NaBH4 (1.52 g, 0.04 mol) was added to a solution of
2-[(5-phenyl-[1,3,4]-oxadiazol-2-ylimino)-methyl] phenol (3)
(0.01 mol) in ethanol (10 mL) and the mixture was stirred for
30-45 min room temperature. The solid separated, on pouring
the mixture into ice-cold water, was filtered, dried and purified
by column chromatography using a gradient of hexane-EtOAc
(9:1-7:3).
3-(5-Phenyl[1,3,4]oxadiazol-2-yl]-3,4-dihydro-2H-
benzo[e][1,3]oxazines (5a-g): Compound 2-[(5-phenyl-
[1,3,4]-oxadiazol-2-ylamino)-methyl]-phenol 4 (0.01 mol) and
formalin (37 %, 2 mL) were refluxed on a water bath for 5-6
h in CHCl3 (10 mL). The solvent was evaporated in vacuo and
the residue on purification by column chromatography using
hexane-EtOAc (9:1) gave the desired product.
EXPERIMENTAL
All reagents and solvents were used as purchased without
further purification. Melting points were determined on a
Fisher-johns melting point apparatus and are uncorrected.
Crude products were purified by column chromatography on
silica gel of 60-120 mesh. IR spectra were obtained on a

4146 Vasu et al.
Asian J. Chem.
2-[(5-Phenyl[1,3,4]oxadiazol-2-ylimino)methyl] phenol
(3a): White solid; Yield : 70 %, m.p. 125-127 °C; IR (KBr,
5-Methyl-2-[(5-phenyl[1,3,4]oxadiazol-2-ylamino)
methyl]phenol (4b): Pale yellow solid;Yield: 74 %, m.p. 144-
146 °C; IR (KBr, νmax, cm-1): 3462 (N-H), 3358 (O-H), 3065
(C-H, Ar), 2965 (C-H, CH2), 1654 (C=N), 1621, 1575 (C=C,
Ar); 1H NMR (300 MHz, CDCl3) δ: 2.26 (s, 3H, CH3), 2.62 (s,
2H, CH2), 6.15 (s, 1H, NH), 7.71 (d, 1H, J = 7.2 Hz, Ar-H),
7.75 (d, 1H, J = 7.2 Hz, Ar-H), 7.26 (s, 1H, Ar-H), 7.15-7.76
(m, 5H, Ar-H), 11.21 (s, 1H, OH),; MS: m/z (%) 281 (M+).
2-[(5-Phenyl[1,3,4]oxadiazol-2-ylamino)methyl]-6-
trifluoromethoxy phenol (4c): White solid;Yield: 77 %, m.p.
175-177 °C; IR (KBr, νmax, cm-1): 3415 (N-H), 3385 (O-H),
3058 (C-H, Ar), 2945 (C-H, CH2), 1658 (C=N), 1628, 1575
ν
max, cm-1): 3392 (O-H), 3073 (C-H, Ar), 1665 (C=N), 1623,
1
1582 (C=C, Ar); H NMR (300 MHz, CDCl3) δ: 7.10-8.29
(m, 4H, Ar-H), 7.21-7.89 (m, 5H, Ar-H), 8.29 (s, 1H,CH),
11.69 (s, 1H,OH); MS: m/z (%) 265 (M+).
5-Methyl-2-[(5-phenyl[1,3,4]oxadiazol-2-ylimino)
methyl]phenol (3b): Pale yellow solid;Yield: 78 %, m.p. 145-
147 °C; IR (KBr, νmax, cm-1): 3385 (O-H), 3065 (C-H, Ar),
2972 (C-H, CH3), 1662 (C=N), 1605, 1585 (C=C,Ar); 1H NMR
(300 MHz, CDCl3) δ: 2.29 (s, 3H, CH3), 7.10 (s, 1H, Ar-H),
7.14-7.69 (m, 5H, Ar-H), 7.89 (d, 1H, J = 7.8 Hz), 8.02 (s, 1H,
CH), 8.12 (d, 1H, J = 7.8 Hz), 11.58 (s, 1H, OH); MS: m/z (%)
279 (M+).
1
(C=C, Ar), 1328 (C-F), 1165 (C-O); H NMR (300 MHz,
CDCl3) δ: 2.42 (s, 2H, CH2), 6.12 (s, 1H, NH), 7.20-8.04 (m,
3H, Ar-H), 7.15-7.98 (m, 5H, Ar-H), 10.93 (s, 1H, OH); MS:
m/z (%) 351 (M+).
2-[(5-Phenyl[1,3,4]oxadiazol-2-ylimino)methyl]-6-
trifluoromethoxy phenol (3c):White solid;Yield: 72 %, m.p.
160-162 °C; IR (KBr, νmax, cm-1): 3402 (O-H), 3056 (C-H,
Ar), 1658 (C=N), 1632, 1565 (C=C, Ar), 1318 (C-F), 1158
2-[(5-Phenyl[1,3,4]oxadiazol-2-ylamino)methyl]-4-
trifluoromethoxy phenol (4d): Pale yellow solid;Yield: 71 %,
m.p. 156-158 °C; IR (KBr, νmax, cm-1): 3448 (N-H), 3365 (O-H),
3045 (C-H, Ar), 2952 (C-H, CH2), 1654 (C=N), 1618, 1574
1
(C-O); H NMR (300 MHz, CDCl3) δ: 7.15-8.08 (m, 3H,
Ar-H), 7.12-7.80 (m, 5H, Ar-H), 8.12 (s, 1H, CH), 11.25 (s,
1H, OH); MS: m/z (%) 349 (M+).
1
(C=C, Ar), 1315 (C-F), 1146 (C-O); H NMR (300 MHz,
2-[(5-Phenyl[1,3,4]oxadiazol-2-ylimino)methyl]-4-
trifluoromethoxy phenol (3d):Yellow solid;Yield: 76 %, m.p.
140-142 °C; IR (KBr, νmax, cm-1): 3385 (O-H), 3069 (C-H,
Ar), 1654 (C=N), 1625, 1578 (C=C, Ar), 1325 (C-F), 1145
(C-O); 1H NMR (300 MHz, CDCl3) δ: 7.16 (s, 1H,Ar-H), 7.25-
7.92 (m, 5H, Ar-H), 7.75 (d, 1H, J = 7.5 Hz), 8.16 (d, 1H, J =
7.5 Hz), 7.98 (s, 1H, CH), 11.21 (s, 1H, OH); MS: m/z (%)
349 (M+).
CDCl3) δ: 2.56 (s, 2H, CH2), 5.98 (s, 1H, NH), 7.18 (s, 1H,
Ar-H), 7.12-7.96 (m, 5H, Ar-H), 7.73 (d, 1H, J = 7.8 Hz), 7.86
(d, 1H, J = 7.4 Hz), 11.12 (s, 1H,OH); MS: m/z (%) 351 (M+).
4-Chloro-2-[(5-phenyl[1,3,4]oxadiazol-2-ylamino)
methyl]phenol (4e): Yellow solid; Yield: 73 %, m.p. 168-
170 °C; IR (KBr, νmax, cm-1): 3445 (N-H), 3365 (O-H), 3045
(C-H, Ar), 2963 (C-H, CH2), 1651 (C=N), 1645, 1568 (C=C,
Ar), 1225 (C-Cl); 1H NMR (300 MHz, CDCl3) δ: 2.49 (s, 2H,
CH2), 5.96 (s, 1H, NH), 7.21 (s, 1H, Ar-H), 7.25-7.90 (m, 5H,
Ar-H), 7.74 (d, 1H, J = 7.6 Hz, Ar-H), 7.84 (d, 1H, J = 7.6 Hz,
Ar-H), 11.01 (s, 1H, OH); MS: m/z (%) 301 (M+).
4-Chloro-2-[(5-phenyl[1,3,4]oxadiazol-2-ylimino)
methyl] phenol (3e): Pale yellow solid; Yield: 73 %, m.p.
165-167 °C; IR (KBr, νmax, cm-1): 3378 (O-H), 3071 (C-H,
Ar), 1661 (C=N), 1625, 1582 (C=C,Ar), 1210 (C-Cl); 1H NMR
(300 MHz, CDCl3) δ: 7.26 (s, 1H, Ar-H), 7.15-7.78 (m, 5H,
Ar-H), 7.84 (d, 1H, J = 7.6 Hz, Ar-H), 7.85 (s, 1H, CH), 8.06
(d, 1H, J = 7.6 Hz), 10.98 (s, 1H,OH); MS: m/z (%) 299 (M+).
4-Amino-2-[(5-phenyl[1,3,4]oxadiazol-2-ylimino)
methyl]phenol (3f): White solid; Yield: 71 %, m.p. 150-152
°C; IR (KBr, νmax, cm-1): 3452 (N-H), 3374 (O-H), 3066 (C-H,
Ar), 1672 (C=N), 1619, 1565 (C=C, Ar); 1H NMR (300 MHz,
CDCl3) δ: 5.73 (s, 2H, NH2), 7.23 (s, 1H, , Ar-H), 7.15-7.75
(m, 5H, Ar-H, Ar-H), 7.78 (d, 1H, J = 7.4 Hz, Ar-H), 7.85 (s,
1H, CH), 7.98 (d, 1H, J = 7.4 Hz, Ar-H), 10.85 (s, 1H, OH);
MS: m/z (%) 280 (M+).
4-Amino-2-[(5-phenyl[1,3,4]oxadiazol-2-ylamino)
methyl]phenol (4f): Pale yellow solid;Yield: 76 %, m.p. 142-
144 °C; IR (KBr, νmax, cm-1): 3418 (N-H), 3363 (O-H), 3069
(C-H, Ar), 2945 (C-H, CH2), 1672 (C=N), 1632, 1564 (C=C,
Ar); 1H NMR (300 MHz, CDCl3) δ: 2.42 (s, 2H, CH2), 5.70 (s,
2H, NH2), 6.12 (s, 1H, NH), 7.23 (s, 1H, Ar-H), 7.12-7.75 (m,
5H, Ar-H), 7.80 (d, 1H, J = 7.8 Hz, Ar-H), 7.95 (d, 1H, J = 7.8
Hz, Ar-H), 10.85 (s, 1H, OH); MS: m/z (%) 282 (M+).
4-Nitro-2-[(5-phenyl[1,3,4]oxadiazol-2-ylamino)
methyl]phenol (4g): White solid;Yield : 74 %, m.p. 135-137
°C; IR (KBr, νmax, cm-1): 3428 (N-H), 3374 (O-H), 3062 (C-H,
Ar), 2965 (C-H, CH2), 1654 (C=N), 1632, 1575 (C=C, Ar),
1348 (N=O); 1H NMR (300 MHz, CDCl3) δ: 2.45 (s, 2H, CH2),
6.09 (s, 1H, NH), 7.16 (s, 1H, Ar-H), 7.12-7.98 (m, 5H,
Ar-H), 7.69 (d, 1H, J = 7.6 Hz, Ar-H), 7.75 (d, 1H, J = 7.6 Hz,
Ar-H), 10.98 (s, 1H,OH); MS: m/z (%) 312 (M+).
4-Nitro-2-[(5-phenyl[1,3,4]oxadiazol-2-ylimino)
methyl]phenol (3g):Yellow solid;Yield: 75 %, m.p. 154-156
°C; IR (KBr, νmax, cm-1): 3384 (O-H), 3062 (C-H, Ar), 1658
1
(C=N), 1619, 1562 (C=C, Ar), 1365 (N=O); H NMR (300
MHz, CDCl3) δ: 7.12 (s, 1H, , Ar-H), 7.26-7.95 (m, 5H,
Ar-H), 7.72 (d, 1H, J = 7.8 Hz, Ar-H), 7.84 (s, 1H, CH), 8.06
(d, 1H, J = 7.8 Hz, Ar-H), 11.06 (s, 1H, OH); MS: m/z (%)
310 (M+).
3-(5-Phenyl[1,3,4]oxadiazol-2-yl]-3,4-dihydro-2H-
benzo[e][1,3]oxazine (5a): Pale yellow solid; Yield: 70 %,
m.p. 154-156 °C; IR (KBr, νmax, cm-1): 3065 (C-H, Ar), 2945
(C-H, CH2), 1658 (C=N), 1612, 1548 (C=C, Ar), 1146 (C-O);
1H NMR (300 MHz, CDCl3) δ: 3.98 (s, 2H, OCH2), 4.23 (s,
2H, NCH2), 7.12-8.02 (m, 4H, Ar-H), 7.19-7.82 (m, 5H,
Ar-H); MS: m/z (%) 279 (M+).
2-[(5-Phenyl[1,3,4]oxadiazol-2-ylamino)methyl]phenol
(4a): Yellow solid; Yield: 70 %, m.p. 130-132 °C; IR (KBr,
ν
max, cm-1): 3452 (N-H), 3385 (O-H), 3054 (C-H, Ar), 2954
1
(C-H, CH2), 1662 (C=N), 1605, 1545 (C=C, Ar); H NMR
(300 MHz, CDCl3) δ: 2.55 (s, 2H, CH2), 6.05 (s, 1H, NH),
7.24-8.12 (m, 4H, Ar-H), 7.32-7.89 (m, 5H, Ar-H), 11.12 (s,
1H, OH); MS: m/z (%) 267 (M+).
7-Methyl-3-(5-phenyl[1,3,4]oxadiazol-2-yl]-3,4-
dihydro-2H-benzo[e][1,3]oxazine (5b):Yellow solid;Yield:
74 %, m.p. 180-182 °C; IR (KBr, νmax, cm-1): 3052 (C-H, Ar),
2948 (C-H, CH2), 1654 (C=N), 1614, 1538 (C=C, Ar), 1142

Vol. 26, No. 14 (2014)
Synthesis, Antibacterial and Antifungal Evaluation of 1,3,4-Oxadiazoles 4147
(C-O); 1H NMR (300 MHz, CDCl3) δ: 2.32 (s, 3H, CH3), 4.02
(s, 2H, OCH2), 4.32 (s, 2H, NCH2), 7.18 (s, 1H, Ar-H), 7.23-
7.81 (m, 5H, Ar-H), 7.78 (d, 1H, J = 7.4 Hz, Ar-H), 7.95 (d,
1H, J = 7.4 Hz, Ar-H); MS: m/z (%) 293 (M+).
Ar-H), 7.65 (d, 1H, J = 7.6 Hz, Ar-H), 7.89 (d, 1H, J = 7.6 Hz,
Ar-H); MS: m/z (%) 324 (M+).
RESULTS AND DISCUSSION
On the basis of these findings and as a part of our ongoing
research involving the synthesis of biologically active com-
pounds, we have reported this work on synthesis and biological
properties of various novel 3-(5-phenyl[1,3,4]oxadiazol-2-yl]-
3,4-dihydro2H-benzo[e][1,3]oxazines (5a-g).Accordingly, the
synthetic route leading to the title compounds (5a-g) is summa-
rized in Scheme-I. The key intermediates, 2-[(5-phenyl[1,3,4]-
oxadiazol-2-ylimino)methyl]phenols (3a-g) have been prepared
from the condensation reaction between commercially
available 5-phenyl[1,3,4]oxadiazol-2-ylamine (1) and different
salicylaldehydes (2a-g) in ethanol under reflux for 2-3 h. The
reduction of compounds 3a-g with sodium borohydride in
ethanol at room temperature for 30-45 min afforded the subse-
quent intermediates 2-[(5-phenyl[1,3,4]oxadiazol-2-ylamino)-
methyl]phenols (4a-g). Further, the target compounds 5a-g
were prepared in good to excellent yields through Mannich
type condensation followed by cyclization of compounds
4a-g with formaldehyde in chloroform at reflux temperature
for 5-6 h. The chemical structures of all the newly synthesized
compounds were confirmed by their IR, 1H, 13C NMR, mass
spectral data and elemental analysis. Further these compounds
have been screened for their antibacterial, antifungal and
nematicidal activities. On the other hand, there is no report on
the synthesis of 3-(5-phenyl[1,3,4]oxadiazol-2-yl]-3,4-dihydro-
2H-benzo[e][1,3]-oxazines (5a-g) from any compound
including 5-phenyl[1,3,4]oxadiazol-2-ylamine (1) and salicyl-
aldehyde (2).
3-(5-Phenyl[1,3,4]oxadiazol-2-yl]-8-trifluoromethoxy-
3,4-dihydro-2H-benzo[e][1,3]oxazine (5c): Pale yellow solid;
Yield: 76 %, m.p. 170-172 °C; IR (KBr, νmax, cm-1): 3038
(C-H, Ar), 2942 (C-H, CH2), 1668 (C=N), 1645, 1538 (C=C,
Ar), 1328 (C-F), 1142 (C-O), 1154 (C-O); 1H NMR (300 MHz,
CDCl3) δ: 3.85 (s, 2H, OCH2), 4.19 (s, 2H, NCH2), 7.15-7.98
(m, 3H,Ar-H), 7.25-7.79 (m, 5H,Ar-H); MS: m/z (%) 363 (M+).
3-(5-Phenyl[1,3,4]oxadiazol-2-yl]-6-trifluoromethoxy-
3,4-dihydro-2H-benzo[e][1,3]-oxazine (5d): Pale yellow
solid;Yield: 78 %, m.p. 154-156 °C; IR (KBr, νmax, cm-1): 3054
(C-H, Ar), 2954 (C-H, CH2), 1662 (C=N), 1605, 1545 (C=C,
Ar), 1321 (C-F), 1146 (C-O), 1138 (C-O); 1H NMR (300 MHz,
CDCl3) δ: 3.85 (s, 2H, OCH2), 4.15 (s, 2H, NCH2), 7.25 (s,
1H, Ar-H), 7.12-7.65 (m, 5H, Ar-H), 7.75 (d, 1H, J = 7.6 Hz,
Ar-H), 8.05 (d, 1H, J = 7.6 Hz, Ar-H); MS: m/z (%) 363 (M+).
6-Chloro-3-(5-phenyl[1,3,4]oxadiazol-2-yl]-3,4-
dihydro-2H-benzo[e][1,3]oxazine (5e): Pale yellow solid;
Yield: 72 %, m.p. 160-162 °C; IR (KBr, νmax, cm-1): 3036
(C-H, Ar), 2942 (C-H, CH2), 1652 (C=N), 1625, 1565 (C=C,
Ar), 1234 (C-Cl), 1132 (C-O); 1H NMR (300 MHz, CDCl3) δ:
4.05 (s, 2H, OCH2), 4.36 (s, 2H, NCH2), 7.18 (s, 1H, Ar-H),
7.14-7.85 (m, 5H, Ar-H), 7.82 (d, 1H, J = 7.8 Hz, Ar-H), 8.08
(d, 1H, J = 7.8 Hz, Ar-H); MS: m/z (%) 313 (M+).
6-Amino-3-(5-phenyl[1,3,4]oxadiazol-2-yl]-3,4-
dihydro-2H-benzo[e][1,3]oxazine (5f): White solid; Yield:
75 %, m.p. 166-168 °C; IR (KBr, νmax, cm-1): 3426 (N-H),
3045 (C-H, Ar), 2958 (C-H, CH2), 1654 (C=N), 1628, 1536
(C=C, Ar), 1148 (C-O); 1H NMR (300 MHz, CDCl3) δ: 3.84
(s, 2H, OCH2), 4.12 (s, 2H, NCH2), 5.85 (s, 2H, NH2), 7.15 (s,
1H, Ar-H), 7.25-8.02 (m, 5H, Ar-H), 7.95 (d, 1H, J = 7.4 Hz,
Ar-H), 8.06 (d, 1H, J = 7.4 Hz, Ar-H); MS: m/z (%) 294 (M+).
6-Nitro-3-(5-phenyl[1,3,4]oxadiazol-2-yl]-3,4-dihydro-
2H-benzo[e][1,3]oxazine (5g): Yellow solid;Yield: 73 %, m.p.
148-150 °C; IR (KBr, νmax, cm-1): 3048 (C-H, Ar), 2965 (C-H,
CH2), 1646 (C=N), 1626, 1534 (C=C, Ar), 1356 (N=O), 1142
Antibacterial activity: The newly synthesized novel
compounds 5a-g, were assayed for their antibacterial activity
against three Gram-positive bacteria viz., Bacillus subtilis,
Staphylococcus aureus and Micrococcus luteus and three
Gram-negative bacteria viz., Proteus vulgaris, Salmonella
typhimurium and Escherichia coli by the broth dilution method16.
The minimum inhibitory concentration (MIC, µg/mL) was
determined for all the compounds and standard control
ampicillin. The investigation of antibacterial screening data
revealed that the compound containing 3-trifluoro methoxy
1
(C-O); H NMR (300 MHz, CDCl3) δ: 3.84 (s, 2H, OCH2),
4.19 (s, 2H, NCH2), 7.04 (s, 1H, Ar-H), 7.22-7.85 (m, 5H,
HO
N
N
N
N
HO
(i)
CH
O
3a-g
N
R
+
NH2
O
1
R
OHC
2a-g
(ii)
HO
O
N
N
N
N
(iii)
N
R
CH2
O
4a-g
NH
O
5a-g
R
Scheme-I: (i) EtOH, Reflux, 2-3 h; (ii) NaBH4, EtOH, RT, 30-45 min; (iii) Formalin, CHCl3, Reflux, 5-6 h, 3-5 R (a) = H, (b) = 4-CH3, (c) = 3-OCF3, (d) =
5-OCF3, (e) = 5-Cl, (f) = 5-NH2, (g) = 5-NO2

4148 Vasu et al.
Asian J. Chem.
group on salicylaldehyde ring 5c is highly active against all
the microorganisms employed except E. coli at 1.56 µg/mL
concentration which is equal to the standard. Compound 5g
with nitro moiety on same ring is also exhibited high active
against M. luteus and P. vulgaris at the same concentration as
5c. The compound having 5-trifluoro methoxy substituent on
salicylaldehyde ring 5d also showed good antibacterial activity
against all the organisms tested. Compound 5a is almost
inactive towards M. luteus and E. coli. The remaining com-
pounds showed moderate to good activity (Table-1).
Nematicidal activity: All the newly synthesized compounds
5a-g, were also assayed for their nematicidal activity against
Ditylenchus myceliophagus and Caenorhabditis elegans by
aqueous in vitro screening technique17 at various concentra-
tions. The nematicidal activity of each tested compound was
compared with the standard drug Levamisole. The results are
expressed in terms of LD50 i.e. median lethal dose at which
50 % of nematodes became immobile (dead). The nematicidal
screening data (Table-3) revealed that the compound 5e is the
most effective against D. myceliophagus and C. elegans with
LD50 of 160 and 180 ppm, respectively and is almost equally
active as the standard. Compounds 5f and 5g are also most active
against C. elegans with LD50 of 190 ppm and D. myceliophagus
with LD50 of 180 ppm, respectively. The other tested com-
pounds showed moderate activity.
TABLE-1
ANTIBACTERIAL ACTIVITY OF 3-(5-PHENYL-[1,3,4]-
OXADIAZOL-2-YL]-3,4-DIHYDRO-2H-BENZO[e][1,3]-
OXAZINES (5a-g) (ZONE OF INHIBITION IN mm AT 100 µg/mL)
B.
S.
M.
P.
S. typhi-
subtilis aureus luteus vulgaris murium
E.
coli
S. No
TABLE-3
MEDIAN LETHAL DOSE (LD50, ppm) OF COMPOUNDS 5a-g
12.5
6.25
1.56
3.12
6.25
12.5
6.25
12.5
12.5
1.56
6.25
6.25
6.25
12.5
1.56
–
12.5
6.25
1.56
1.56
–
12.5
6.25
1.56
3.12
12.5
6.25
12.5
3.12
25
5a
5b
5c
5d
5e
5f
6.25
1.56
1.56
6.25
3.12
1.56
1.56
12.5
12.5
1.56
6.25
12.5
12.5
12.5
S. No.
Dm
5a
5b
5c
5d
5e
5f
5g Levmisole
780 840 550 260 160 420 180
750 760 350 210 180 190 760
160
170
Ce
12.5
1.56
3.12
Dm = D. myceliophagus; Ce = C. elegans
5g
Ampicillin 1.56
— Indicates bacteria are resistant to the compound > 50 µg/mL
concentration.
REFERENCES
1. M.P. Hutt, E.F. Elslager and L.M. Werbel, J. Heterocycl. Chem., 7, 511
(1970).
Antifungal activity: Compounds 5a-g were also screened
for their antifungal activity against four fungal organisms viz.
Candida albicans, Aspergillus fumigatus, Trichophyton rubrum
and Trichophyton mentagrophytes in dimethyl sulfoxide by
broth dilution method16. The minimum inhibitory concentration
(MIC, µg/mL) were measured and compared with the standard
drug amphotericin B. The MIC values of the screened compounds
are given in Table-2. The antifungal screening data showed
good activity of the tested compounds. Among the screened
compounds 5c ishighlyactiveagainst T. rubrum,T. mentagrophytes,
5e is also active against only C. albicans and 5d is highly
active against C. albicans, T. mentagrophytes, the activity of
these compounds are almost equal to the standard. It is
interesting to note that 5d and 5e showed excellent antifungal
activity towards C. albicans at the concentration of 3.12 µg/
mL, which is less than the concentration of the standard. The
remaining compounds performed moderate to good activity.
2. F.A. Omar, N.M. Mahfouz and M.A. Rahman, Eur. J. Med. Chem., 31,
819 (1996).
3. A. Zarghi, S.A. Tabatabai, M. Faizi, A.Ahadian, P. Navabi, V. Zanganeh
and A. Shafiee, Bioorg. Med. Chem. Lett., 15, 1863 (2005).
4. A. Husain and M. Ajmal, Acta Pharm., 59, 223 (2009).
5. S.L. Gaonkar, K.M. Rai and B. Prabhuswamy, Eur. J. Med. Chem., 41,
841 (2006).
6. M.A.Ali and M. Shaharyar, Bioorg. Med. Chem. Lett., 17, 3314 (2007).
7. Z.H Luo, S.Y. He, B.Q. Chen, Y.P. Shi, Y.M. Liu, C.W. Li and Q.S.
Wang, Chem. Pharm. Bull., 60, 887 (2012).
8. V.J. Ram, U.K. Singha and P.Y. Guru, Eur. J. Med. Chem., 25, 533
(1990).
9. P.J. Shirote and M.S. Bhatia, Chin. J. Chem., 28, 1429 (2010).
10. V. Padmavathi, G. Sudhakar Reddy, A. Padmaja, P. Kondaiah and Ali-
Shazia, Eur. J. Med. Chem., 44, 2106 (2009).
11. B. Jayashankar, K.M. Lokanath Rai, N. Baskaran and H.S. Sathish,
Eur. J. Med. Chem., 44, 3898 (2009).
12. F.A. Omar, N.M. Mahfouz and M.A. Rahman, Eur. J. Med. Chem., 31,
819 (1996).
13. M. Adib, E. Sheibani, M. Mostofi, K. Ghanbary and H.R. Bijanzadeh,
Tetrahedron, 62, 3435 (2006).
14. N. Zanatta, A.M.C. Squizani, L. Fantinel, F.M. Nachtigall, D.M.
Borchhardt, H.G. Bonacorso and A.P. Martins, J. Braz. Chem. Soc.,
16(6a), 1255 (2005).
TABLE-2
ANTIFUNGAL ACTIVITY OF COMPOUNDS 5a-g
(ZONE OF INHIBITION IN mm AT 100 µg/mL)
15. F.A.J. Kerdesky, Tetrahedron Lett., 46, 1711 (2005).
16. C.W. McBeth and G.B. Bergeson, Phytopathology, 43, 264 (1953).
17. National Committee for Clinical Laboratory Standards (NCCLS), Stan-
dard Methods for Dilution Antimicrobial Susceptibility Tests for Bac-
teria, Nat. Comm. Lab. Stands, Villanova, 242 (1982).
C.
albicans fumigatus rubrum mentagropytes
A.
T.
T.
S. No.
25.0
25.0
12.5
3.12
3.12
50.0
25.0
6.25
12.5
25.0
6.25
6.25
12.5
25.0
25.0
3.12
>50.0
25.0
3.12
6.25
12.5
12.5
12.5
3.12
25.0
25.0
3.12
3.12
25.0
12.5
3.12
3.12
5a
5b
5c
5d
5e
5f
5g
Amphotericin B