470
T. Singh et al.
Arch. Pharm. Chem. Life Sci. 2006, 339, 466–472
C10H7N3S3. IR (KBr) m in cm– 1: 3260 (N–H), 3028 (C–H aromatic),
1615 (C=N), 1570 (C…C of aromatic ring), 1150 (C–N), 676 (C–S–
C). 1H-NMR (CDCl3) d in ppm: 7.45–7.10 (m, 5H, Ar-H), 6.10 (s, 2H,
NH2, exchangeable with D2O). MS m/z: 265 [M]+.
The proposed mass spectral fragmentation of compound 5b is
illustrated in Scheme 2. On electron impact, compound 5b gave
the molecular ion peak [M]+ at m/z 473, which was not a base
peak. The molecular ion underwent disintegration via different
pathways, i. e. I, II, and III.
Pathway I involved the fission through benzothiazole ring to
give ion [a]+ at m/z 108 and pathway II exhibited cleavage
between the benzothiazole and thiazole rings to yield the ion
[b]+ with m/z 134. A similar type of fragmentation pattern of a
benzothiazole ring has been reported by [11] and [12].
2-[(29-Substitutedarylidenylimino-19,39-thiazol-49-
yl)thio]benzothiazoles 3a–3e
To a solution of compound 2 (0.01 mol) in methanol (100 mL),
proper aromatic aldehyde (0.01 mol) along with few drops of gla-
cial acetic acid were added. This resulting mixture was refluxed
for 10 h, while progress and completion of the reaction was
monitored by TLC. The reaction mixture was distilled off, cooled,
and then poured onto crushed ice and filtered. The solid thus
separated out was recrystallized from appropriate solvent giving
compound 3. By this procedure, compounds 3a–3e were
obtained starting from benzaldehyde, o-hydroxy-m-methoxyben-
zaldehyde, o-hydroxybenzaldehyde, p-methoxybenzaldehyde,
and p-hydroxybenzaldehyde, respectively. Their physical data
are given in Table 3. Compound 3b: IR (KBr) m in cm– 1: 3530 (O–
H), 3014 (C-H aromatic), 2966 (C–H aliphatic), 1623 (C=N), 1588
(C…C of aromatic ring), 1161 (C–N), 1093 (C–O–C), 678 (C–S–C).
1H-NMR (CDCl3) d in ppm: 11.20 (s, 1H, OH, exchangeable with
D2O), 7.40–6.95 (m, 8H, Ar-H), 8.54 (s, 1H, CH-Ar), 3.48 (s, 3H,
OCH3). MS m/z: 399 [M]+.
Pathway III possessed splitting across the thiazole ring giving
the fragment [c]+ at m/z 281 [13]. Fragment [c]+ was further bro-
ken up via a- and b-routes (see Scheme 2) to yield [d]+ and [e]+ with
m/z 210 and 57, respectively. Ion [e]+ was found to be as base
peak. Radical ion [c]+ exhibited CH-S bond cleavage (b-cleavage)
followed by a rearrangement through a 1,4-hydrogen shift lead-
ing to the formation of ion [f]+ at m/z 208 (loss of SCHCO) [14]. By
the cleavage of ion [f]+ a radical ion [g]+ has been observed at m/z
123. Fragment [g]+ readily removed the OH radical to give the ani-
sole radical ion [h]+ at m/z 106. This radical ion, on expulsion of
methyl radical (CH3) and followed by rearrangement, gave ion
[i]+ at m/z 91, which was further rearranged into [j]+ ion with the
same m/z value. Finally, a carbonyl radical (CO) was ejected from
fragment [j]+ to give the cation [k]+ at m/z 63 [15].
Biological evaluation
Various compounds 3a–3e, 4a–4e, and 5a–5e have been evalu-
ated for insecticidal activity against male or female cockroaches
(Periplaneta americana). These compounds were also assayed in
vitro for their antifungal and antibacterial activities.
2-{[29-(399-Chloro-299-oxo-499-substitutedaryl-199-azetidinyl)-
19,39-thiazol-49-yl]thio}benzothiazoles 4a–4e
To a solution of the proper compound 3 (0.01 mol) in absolute
ethanol (70 mL), chloroacetyl chloride (0.02 mol) and triethyla-
mine (0.02 mol) were added with constant stirring. This reaction
mixture was refluxed for 8 h and excess of solvent was distilled
off. The precipitated product was cooled, poured in ice water,
then filtered and recrystallized from appropriate solvent to give
compound 4. By this procedure compounds 4a-4e were obtained
starting from 3a–3e, respectively. The physical data of com-
pounds 4a–4e are depicted in Table 3. Compound 4b: IR (KBr) m
in cm– 1: 3534 (O–H), 3033 (C–H aromatic), 2930 (C–H alipha-
tic), 1735 (C=O), 1600 (C=N), 1575 (C…C of aromatic ring), 1123 (C–
Insecticidal activity
The insecticidal activity was determined by the method of Joshi
and Tholia [16]. The cockroaches of either sex were divided in
groups having five cockroaches each. An acetone solution
(0.02 mL of 5 g/L) of standard insecticide parathion and different
test compounds were injected on the ventral side of the insect,
between the fourth and fifth abdominal segments with the help
of a micrometer syringe. Insects receiving 0.02 mL of acetone by
the same route served as control. The treated cockroaches were
kept under observation to record the time taken until 100% mor-
tality. During this period, no food was given. In another set of
experiments, most active compound of each series at two graded
doses, i. e. 0.02 mL of 10 and 20 g/L were also injected into groups
of insects with identical doses of parathion. The statistical signif-
icance of the difference between the data of standard and test
compounds was calculated by employing student's t-test.
1
N), 1080 (C– O– C), 670 (C– S–C). H-NMR (CDCl3) d in ppm: 11.15 (s,
1H, OH, exchangeable with D2O), 7.34–6.82 (m, 8H, Ar-H), 5.0 (d, J = 8.5
Hz, 1H, CH-Cl), 4.75 (d, J = 5.6 Hz, 1H, CH-Ar), 3.37 (s, 3H, OCH3). MS m/
z: 475 [M]+.
2-{[(29-(299-Substitutedaryl-499-thiazolidinon-399-yl)-19,39-
thiazol-49-yl]thio}benzothiazoles 5a–5e
A solution of proper compound 3 (0.01 mol) and thioglycolic
acid (0.01 mol) in absolute ethanol (50 mL) in the presence of
anhydrous ZnCl2 (2 g) was refluxed for 10 h. Excess of solvent
was removed through distillation, the solid thus obtained was
poured onto crushed ice, filtered, dried, and recrystallized from
the appropriate solvent to yield compound 5. By this procedure,
compounds 5a–5e were synthesized starting from 3a–3e,
respectively. Their physical data are shown in Table 3. Com-
pound 5b: IR (KBr) m in cm– 1: 3510 (OH), 3030 (C–H aromatic),
2928 (C–H aliphatic), 1688 (C=O), 1603 (C=N), 1580 (C…C of aro-
matic ring), 1120 (C– N), 676 (C–S– C). 1H-NMR (CDCl3) d in ppm:
11.20 (ss, 1H, OH, exchangeable with D2O), 7.40–6.80 (m, 8H, Ar-H),
4.85 (s, 1H, CH-Ar), 4.10 (s, 2H, CH2 of thiazolidinone ring), 3.45 (s, 3H,
OCH3).
Antifungal activity
The standard agar disc diffusion method [17] was performed to
evaluate the antifungal property of the test compounds and
standard fluconazole. Aspergillus fumigatus, Candida albicans
ATCC 2091, Candida albicans ATCC 10231, Candida Krusei GO3, and
Candida glabrata HO5 were used in this study. All cultures were
routinely maintained on SDA and incubated at 3008C. In order
to prepare homogeneous suspensions of these fungi for disc
assays, they were grown overnight in sabouraud broth, centri-
fuged to collect the pellet, and resuspended in sterile phosphate
buffered saline. The fungal pellet was homogenized in a sterile
hand-held homogenizer. This suspension was then plated onto
SDA using a bacterial spreader to obtain an even growth field.
i 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim