Synthesis and antimicrobial activity of some novel [4-(1,2,3-thiadiazol-4-yl) phenoxy]methylene anchored 1,3,4-triazoles and 1,3,4-thiadiazoles

Article abstract of DOI:10.1002/jhet.1851

A series of novel [4-(1,2,3-thiadiazol-4-yl)phenoxy]methylene anchored 1,3,4-triazoles (8a-h) and 1,3,4-thiadiazoles (9a-i) were synthesized from thiosemicarbazide (7a-j). The structures of these newly synthesized compounds were confirmed on the basis of IR, ¹H-NMR, mass spectral techniques, and elemental analysis. The in vitro antimicrobial screenings of the synthesized compounds were carried out against four bacterial pathogens, namely Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and three fungal pathogens Candida albicans, Aspergillus niger and Aspergillus clavatus, using broth microdilution minimum inhibitory concentration method. The compounds 7d, 7j, 8a, 9a, 9b, and 9i exhibited promising antibacterial activity against the tested strains, whereas some compounds were found to be active against one of the tested bacterial strains.

Full text of DOI:10.1002/jhet.1851

Month 2014 Synthesis and Antimicrobial Activity of Some Novel [4-(1,2,3-thiadiazol-4-yl)
phenoxy]methylene anchored 1,3,4-triazoles and 1,3,4-thiadiazoles
a
b
a
c
A. G. Gadhave, R. B. Gaikar, S. R. Kuchekar, and B. K. Karale *
a
P. G. Department of Chemistry and Research Centre, Padmashri Vikhe Patil College, Pravaranagar, Dist-Ahmednagar
4
13713, India
Centre for Biotechnology, Pravara Institute of Medical Sciences, Loni, India
Department of Chemistry, Radhabai Kale Mahila Mahavidyalaya, Ahmednagar 414001, India
b
c
*
E-mail: bkkarale@yahoo.com
Received June 8, 2012
DOI 10.1002/jhet.1851
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
A series of novel [4-(1,2,3-thiadiazol-4-yl)phenoxy]methylene anchored 1,3,4-triazoles (8a–h) and
,3,4-thiadiazoles (9a–i) were synthesized from thiosemicarbazide (7a–j). The structures of these newly
1
1
synthesized compounds were confirmed on the basis of IR, H-NMR, mass spectral techniques, and
elemental analysis. The in vitro antimicrobial screenings of the synthesized compounds were carried out
against four bacterial pathogens, namely Staphylococcus aureus, Streptococcus pyogenes, Escherichia
coli, Pseudomonas aeruginosa and three fungal pathogens Candida albicans, Aspergillus niger and
Aspergillus clavatus, using broth microdilution minimum inhibitory concentration method. The
compounds 7d, 7j, 8a, 9a, 9b, and 9i exhibited promising antibacterial activity against the tested strains,
whereas some compounds were found to be active against one of the tested bacterial strains.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
inflammatory [15], anticancer [16], and anticonvulsant
17] activities. They have a higher affinity for fungal than
[
An azole is a class of five-membered nitrogen hetero-
cycles containing at least one other non-carbon atom
such as nitrogen, sulfur, or oxygen [1]. It has shown
wide applications in medicinal chemistry due to their
diverse therapeutic properties, which includes dyslipidemia,
antiarthritis, anti-inflammatory, antidiabetes, anticoagulant,
antiobesity, pesticides, antimicrobial, antihypertensive, anti-
convulsant, antidepressants, antioxidants, and so on [2–6].
Thiadiazoles are widely exposed to therapeutic world
because of their known antibacterial [7], antifungal [7],
antitubercular [8], carbonic anhydrase inhibitors [9], anti-
inflammatory [10], analgesic [10], antidepressant [11],
anti-HIV [12], and anticancer [13] activities. 1,3,4-thiadia-
zole scaffold occurs in various drugs such as sulfamethi-
zole (sulfonamide antibiotic), acetazolamide (carbonic
anhydrase inhibitors), ceftezole (cephalosporin antibiotic),
and so on.
mammalian target enzymes, which makes them less toxic
than imidazole compounds such as ketoconazole and mico-
nazole. Thiosemicarbazide are known for their antifungal
[18], antibacterial [18], plant growth promoting [19], and
antiviral [20] activities.
In view of broad spectrum of biological activities associ-
ated with thiadiazole and triazole system, it was thought
worthwhile to combine such biologically important moie-
ties into a single scaffold to produce a novel heterocycles
and explore the effects toward their biological activities.
In radiance of the aforementioned facts and in continuation
of our investigations on the synthesis of biologically active
heterocycles [21], herein we report the synthesis of novel
1
,3,4-thiadiazole and 1,3,4-triazole analogues.
RESULTS AND DISCUSSION
The chemistry of triazoles received considerable atten-
tion because of their synthetic and biological importance.
They have been found to exhibit antifungal [14], anti-
Chemistry.
The 2-[4-(1,2,3-thiadiazol-4-yl)phenoxy]
acetylhydrazide (5) was synthesized from 4-hydroxy
©
2014 HeteroCorporation

A. G. Gadhave, R. Gaikar, S. Kuchekar, and B. Karale
Vol 000
acetophenone as shown in Scheme 1. 4-hydroxy
acetophenone (1) upon reaction with semicarbazide
hydrochloride in presence of sodium acetate in ethanol
gave 1-(4-hydroxyphenyl) ethan-1-one semicarbazone (2).
The semicarbazone (2) on reaction with thionyl chloride
gave 4-(1,2,3-thiadiazol-4-yl)phenol (3). Formation of
spectrum of thiosemicarbazide (7c) showed characteristic
signals for N–H at 8.92, 9.38, and 9.83d as broad singlets
and sharp singlet at 4.78d for –O–CH protons. The proton
2
of 1,2,3-thiadiazole nucleus appeared at 9.22 d. IR spectrum
À1
exhibited characteristic bands at 3294, 3232, 3116cm for
À1
À1
N–H, 1705 cm for C = O, and 1357cm for C = S func-
tions. The compound shows molecular ion peak m/z at 403
(
(
3) takes place by Hurd–Mori reaction [22]. The 4-
1,2,3-thiadiazol-4-yl)phenol (3) on reaction with
+
(M ) confirmed the structure of 7c.
ethylbromoacetate in presence of potassium carbonate in
acetone gave ethyl [4-(1,2,3-thiadiazol-4-yl)phenoxy]
acetate (4), which further on reaction with hydrazine
hydrate in ethanol under reflux condition gave 2-[4-
Thiosemicarbazide (7) on intramolecular cyclization
with 1 N NaOH gave triazole (8). The H-NMR spectrum
of triazole (8b) showed characteristic signal at 14.18 d for
S–H proton while the signals due to NH protons of thiose-
micarbazide were disappeared. This clearly indicates that
thiosemicarbazide is cyclized under alkaline condition to
1
(
1,2,3-thiadiazol-4-yl) phenoxy]acetylhydrazide (5).
The 2-[4-(1,2,3-thiadiazol-4-yl)phenoxy]acetylhydrazide
get triazoles. The protons of –O–CH group resonated at
2
(
5) was treated with aryl isothiocyanates [23] (6) in ethanol
5.04 and 5.11 d as doublets indicating geminal coupling.
The COSY H-NMR spectrum of 8b proves that O–CH2
group protons show a geminal coupling of 12.80 Hz. The
1
to give thiosemicarbazides (7). The formation of compound
1
(7) was confirmed by spectral techniques. H-NMR
Scheme 1. 254 Â 187 mm (96 Â 96 DPI).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis and Antimicrobial Evaluation of Some Novel [4-(1,2,3-thiadiazol-4-yl)
phenoxy]methylene containing 1,3,4-triazoles and 1,3,4-thiadiazoles
similar type of geminal coupling is observed for O–CH2
group protons in compounds 8d and 8g proved by COSY
revealed that the compounds showed moderate to good
activity. Compounds 7d, 7j, 8a, 9a, 9b, and 9i showed
broad spectrum activity against all tested bacterial strains.
Compounds 7a, 7e, 7f, 8b, 8c, 8d, 8e, 9d, 9e, 9g, and 9h
showed promising activity against S. aureus bacterial
strain. Compounds 7f, 7h, 8b, and 9h showed good
activity against P. aeruginosa. Compounds 7c, 7g, 7i, 8g,
9c, 9d, and 9e showed good antibacterial activity against S.
pyogenes, whereas only compound 8h was found to be
active against E. coli. Antifungal activity was evaluated
against Candida albicans, Aspergillus niger, and
Aspergillus clavatus fungal strains using griseofulvin as a
standard. Among the synthesized compounds, 9e, 9f, and
9g exhibited good antifungal activity against C. albicans
fungal strain, whereas remaining compounds were found to
be moderately active. Among the synthesized compounds,
none of them showed promising activity against A. niger
and A. clavatus fungal strains. In general, most of the tested
compounds were found to be more active against gram-
positive rather than gram-negative bacterial strains.
Compounds showed moderate antifungal activity (Table 1).
1
H-NMR. The IR spectrum of 8b exhibited characteristic
À1
band for S–H function at 2620 cm . The compound
+
showed molecular ion peak at m/z at 385 (M ), which
confirms the structure of 8b.
Thiosemicarbazide (7) subjected to cyclodehydration in
1
conc. H SO afforded thiadiazoles (9). The H-NMR spec-
2
4
trum of thiadiazole (9c) resonated a singlet at 10.31 d for
N–H proton. The singlet at 5.44 d was observed because
of the protons of –O–CH group. The IR spectrum of 8b
2
exhibited a characteristic band for N–H function at
À1
3
412 cm . The structure of 9c was also confirmed by its
mass spectral data. In its mass spectrum, the molecular
+
ion peak was noticed at m/z at 385 (M ) corresponding to
its molecular weight.
Antimicrobial activity. The in vitro antibacterial activity
of all synthesized compounds was evaluated against
Staphylococcus aureus, Streptococcus pyogenes, Escherichia
coli, and Pseudomonas aeruginosa using ampicillin as a
standard. The investigation of antibacterial activity results
Table 1
Antibacterial and antifungal activity data of synthesized compounds (7a–j), (8a–h) and (9a–i) indicated by MIC values (mg/ml).
MIC, mg/mL
Gram-positive bacteria
S. aureus S.pyogenes
Gram-negative bacteria
Fungi
Compounds
E. coli
P.aeruginosa
C.albicans
A.niger
A.clavatus
7
7
7
7
7
7
7
7
7
7
8
8
8
8
8
8
8
8
9
9
9
9
9
9
9
9
9
a
b
c
d
e
f
g
h
i
200
250
250
100
125
200
250
250
1000
250
125
100
100
200
200
250
250
250
200
250
250
100
100
250
200
250
200
100
100
125
200
100
250
200
250
250
100
125
200
250
250
200
125
100
250
250
500
500
250
200
100
200
125
250
250
200
125
200
250
100
100
—
250
250
500
250
200
62.5
250
100
250
100
125
62.5
200
250
200
250
200
200
62.5
100
200
250
200
250
200
100
100
100
—
500
500
500
500
1000
1000
1000
500
1000
1000
1000
>1000
1000
>1000
>1000
>1000
>1000
500
1000
1000
1000
1000
>1000
>1000
>1000
>1000
1000
1000
500
>1000
1000
>1000
1000
500
>1000
500
500
1000
250
200
250
500
500
—
500
500
>1000
>1000
>1000
>1000
500
62.5
j
100
250
200
250
200
250
500
100
500
100
125
a
b
c
d
e
f
g
h
a
b
c
d
e
f
500
250
1000
250
>1000
>1000
>1000
>1000
>1000
500
>1000
>1000
500
>1000
>1000
>1000
>1000
>1000
—
>1000
>1000
>1000
>1000
>1000
500
>1000
>1000
500
>1000
>1000
>1000
>1000
>1000
—
62.5
100
100
250
200
125
100
100
—
g
h
i
62.5
100
250
—
Ampicillin
Griseofulvin
100
100
MIC, minimum inhibitory concentration.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. G. Gadhave, R. Gaikar, S. Kuchekar, and B. Karale
Vol 000
EXPERIMENTAL
N-[2-(trifluoromethyl)phenyl]-2-{[4-(1,2,3-thiadiazol-4-yl)
phenoxy]acetyl}hydrazine carbothioamide (7d). This compound
was obtained as faint yellow solid (ethanol), yield 78%; mp
General.
All the chemicals used were of analytical grade.
ꢀ
Melting points were taken in open capillaries and are uncorrected.
The IR spectra were recorded in KBr on a Shimadzu FTIR-8400
spectrophotometer (Tokyo, Japan), and only characteristic peaks
177–178 C; IR: 3279 (NH), 3229 (NH), 3125 (NH), 1698
À1
1
(CO), 1601 (C = C), 1333 (CS), 1233 (C–O) cm ; H-NMR: d
4.73 (s, 2H, –CH –), 7.14 (d, 2H, J = 8.3 Hz, Ar-H), 7.44–7.51
2
À1
1
are reported in cm . The H-NMR spectra were recorded in
DMSO-d on a Bruker Avance spectrometer (Rheinstetten,
(m, 2H, Ar-H), 7.61–7.69 (m, 2H, Ar-H), 8.04 (d, 2H,
J = 8.3 Hz, Ar-H), 9.26 (s, 1H, thiadiazole ring proton), 9.39
(bs, 1H, NH), 9.83 (bs, 1H, NH), 10.35 (bs, 1H, NH); MS: m/z
6
Germany) using TMS as an internal standard at 400 MHz, and
chemical shifts are reported in ppm. Mass spectra were scanned on
a Finnigan mass spectrometer (San Jose, USA). Elemental analysis
was performed on a Perkin–Elmer analyzer (Massachusetts, USA).
Thin-layer chromatography (TLC) (on aluminum plates coated
with silica gel 60 F254, 0.25 mm thickness, Merck) was used for
monitoring the progress of reactions, purity, and homogeneity of
the synthesized compounds.
General procedure for synthesis of 2-[4-(1,2,3-thiadiazol-4-yl)
phenoxy]acetyl hydrazide (5). This compound was synthesized by
following literature known methods [22].
General procedure for synthesis of aryl isothiocyanates (6).
These compounds were synthesized by following literature
+
453 (M ); Anal. Calcd for C H F N O S : C, 47.68%; H,
1
8 14 3 5 2 2
3.11%; N, 15.44%. Found: C, 47.77%; H, 3.22%; N, 15.33%.
N-[3-(trifluoromethyl)phenyl]-2-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
acetyl}hydrazine carbothioamide (7e). This compound was
ꢀ
obtained as white solid (ethanol), yield 71%; mp 181–182 C; IR:
3289 (NH), 3213 (NH), 3101 (NH), 1688 (CO), 1604 (C = C),
À1
1
1327 (CS), 1239 (C–O) cm ; H-NMR: d 4.74 (s, 2H, –CH –),
2
7.16 (d, 2H, J = 8.8 Hz, Ar-H), 7.42–7.44 (m, 1H, Ar-H),
7.49–7.53 (m, 1H, Ar-H), 7.84–7.86 (m, 2H, Ar-H), 8.06 (d,
2H, J = 8.8 Hz, Ar-H), 9.31 (s, 1H, thiadiazole ring proton),
+
9
.89 (bs, 2H, NH), 10.35 (bs, 1H, NH); MS: m/z 453 (M );
Anal. Calcd for C H F N O S : C, 47.68%; H, 3.11%; N,
1
8 14 3 5 2 2
known methods [23].
15.44%. Found: C, 47.59%; H, 3.24%; N, 15.55%.
General procedure for synthesis of N-phenyl-2-{[4-(1,2,3-
N-(2,6-difluorophenyl)-2-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
thiadiazol-4-yl)phenoxy] acetyl}hydrazine carbothioamide (7a–j)
Equimolar amount (0.01 mol) of acid hydrazide (5) and aryl iso-
thiocyanate (6) were dissolved in ethanol (15mL), and the reaction
mixture was heated under reflux condition till completion of reac-
tion (checked by TLC). After completion of reaction, the contents
were allowed to cool; the solid obtained was filtered and recrystal-
lized from ethanol to give pure thiosemicarbazides (7a–j). The char-
acetyl}hydrazine carbothioamide (7f). This compound was
obtained as brownish solid (ethanol), yield 65%; mp 129–130 C;
ꢀ
IR: 3277 (NH), 3225 (NH), 3090 (NH), 1694 (CO), 1599 (C= C),
À1
1
1323 (CS), 1240 (C–O), 1141 (Ar-F) cm
; H-NMR: d 4.73
(s, 2H, –CH –), 6.95-6.99 (m, 2H, Ar-H), 7.14 (d, 2H, J = 8.5 Hz,
2
Ar-H), 7.28–7.30 (m, 1H, Ar-H), 8.02 (d, 2H, J = 8.5 Hz, Ar-H),
8
.84 (s, 1H, thiadiazole ring proton), 9.00 (bs, 2H, NH), 10.24
+
acterization data of synthesized compounds are as follows.
N-phenyl-2-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]acetyl}hydrazine
(
bs, 1H, NH); MS: m/z 421 (M ); Anal. Calcd for
C H F N O S : C, 48.45%; H, 3.11%; N, 16.62%. Found: C,
17 13 2 5 2 2
carbothioamide (7a).
yellow solid (ethanol), yield 72%; mp 168–169 C; IR: 3290
This compound was obtained as faint
4
8.52%; H, 3.22%; N, 16.53%.
N-(2,3-dichlorophenyl)-2-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
ꢀ
(
(
7
(
NH), 3210 (NH), 3122 (NH), 1688 (CO), 1605 (C = C), 1320
acetyl}hydrazine carbothioamide (7g).
obtained as white solid (ethanol), yield 71%; mp 138–139 C;
This compound was
À1
1
ꢀ
CS), 1225 (C–O) cm
.14–7.16 (m, 3H, Ar-H), 7.28–7.34 (m, 2H, Ar-H), 7.49–7.51
m, 2H, Ar-H), 8.02 (d, 2H, J = 8.4 Hz, Ar-H), 9.01 (s, 1H,
;
H-NMR: d 4.74 (s, 2H, –CH –),
2
IR: 3283 (NH), 3235 (NH), 3101 (NH), 1681 (CO), 1603
À1
1
(C = C), 1315 (CS), 1223 (C–O) cm ; H-NMR: d 4.74 (s, 2H,
thiadiazole ring proton), 9.55 (bs, 2H, NH), 10.22 (bs, 1H,
–CH –), 7.14 (d, 2H, J = 8.6 Hz, Ar-H), 7.25–7.29 (m, 1H,
2
+
NH); MS: m/z 385 (M ); Anal. Calcd for C H N O S : C,
Ar-H), 7.39–7.52 (m, 2H, Ar-H), 8.04 (d, 2H, J = 8.6 Hz, Ar-H),
1
7 15 5 2 2
5
2.97%; H, 3.92%; N, 18.17%. Found: C, 52.90%; H, 3.88%;
9.14 (s, 1H, thiadiazole ring proton), 9.46 (bs, 1H, NH), 9.90
+
N, 18.24%.
(bs, 1H, NH), 10.39 (bs, 1H, NH); MS: m/z 454 (M ), 456
+
+
N-(2-fluorophenyl)-2-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]acetyl}
(
M +2), 458 (M +4); Anal. Calcd for C H Cl N O S : C,
17 13 2 5 2 2
hydrazine carbothioamide (7b). This compound was obtained as
faint yellow solid (ethanol), yield 75%; mp 176-177 C; IR: 3285
4
4.94%; H, 2.88%; N, 15.41%. Found: C, 44.85%; H, 2.97%;
ꢀ
N, 15.55%.
(NH), 3219 (NH), 3126 (NH), 1699 (CO), 1601 (C = C), 1335
N-(3,5-dichlorophenyl)-2-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
À1
1
(CS), 1235 (C–O), 1140 (Ar-F) cm ; H-NMR: d 4.73 (s, 2H, –
acetyl}hydrazine carbothioamide (7h). This compound was
ꢀ
CH –), 7.10–7.16 (m, 5H, Ar-H), 7.90 (s, 1H, Ar-H), 8.03 (d, 2H,
obtained as white solid (ethanol), yield 66%; mp 202–203 C;
2
J = 8.7Hz, Ar-H), 9.10 (s, 1H, thiadiazole ring proton), 9.41(bs,
IR: 3299 (NH), 3220 (NH), 3129 (NH), 1693 (CO), 1595
À1
1
1
H, NH), 9.84 (bs, 1H, NH), 10.35 (bs, 1H, NH); MS: m/z 403
(C = C), 1340 (CS), 1243 (C–O) cm ; H-NMR: d 4.73 (s, 2H,
–CH –), 7.08–7.12 (m, 1H, Ar-H), 7.15 (d, 2H, J= 8.6 Hz, Ar-H),
+
5 2 2
(M ); Anal. Calcd for C17H14FN O S : C, 50.61%; H, 3.50%; N,
2
1
7.36%. Found: C, 50.55%; H, 3.61%; N, 17.29%.
7.68–7.75 (m, 2H, Ar-H), 8.06 (d, 2H, J = 8.6 Hz, Ar-H),
N-(4-fluorophenyl)-2-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]acetyl}
9.29 (s, 1H, thiadiazole ring proton), 9.79 (bs, 1H, NH),
+
hydrazine carbothioamide (7c). This compound was obtained as
off-white solid (ethanol), yield 69%; mp 173–174 C; IR: 3294
9
4
.96 (bs, 1H, NH), 10.41 (bs, 1H, NH); MS: m/z 454 (M ),
ꢀ
+
+
2 5 2 2
56 (M +2), 458 (M +4); Anal. Calcd for C17H13Cl N O S :
(NH), 3232 (NH), 3116 (NH), 1705 (CO), 1612 (C = C), 1357
C, 44.94%; H, 2.88%; N, 15.41%. Found: C, 45.01%; H,
À1
1
(
CS), 1222 (C-O), 1148 (Ar-F) cm ; H-NMR: d 4.78 (s, 2H, –
–), 7.03–7.07 (m, 2H, Ar-H), 7.20 (d, 2H, J = 8.4Hz, Ar-H),
.49–7.52 (m, 2H, Ar-H), 8.11 (d, 2H, J = 8.4 Hz, Ar-H), 8.92
bs, 1H, NH), 9.22 (s, 1H, thiadiazole ring proton), 9.38 (bs, 1H,
2.76%; N, 15.50%.
CH
7
(
2
N-(2,4-dichlorophenyl)-2-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
acetyl}hydrazine carbothioamide (7i). This compound was
ꢀ
obtained as white solid (ethanol), yield 69%; mp 159–160 C;
+
NH), 9.83 (bs, 1H, NH); MS: m/z 403 (M ); Anal. Calcd for
: C, 50.61%; H, 3.50%; N, 17.36%. Found: C,
0.54%; H, 3.57%; N, 17.27%.
IR: 3291 (NH), 3230 (NH), 3117 (NH), 1694 (CO), 1610
À1
1
C
5
H14FN O S
17 5 2 2
(C = C), 1348 (CS), 1239 (C–O) cm ; H-NMR: d 4.75 (s, 2H,
–CH
–), 7.14 (d, 2H, J = 8.6 Hz, Ar-H), 7.25 (dd, 1H, J = 8.8 &
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis and Antimicrobial Evaluation of Some Novel [4-(1,2,3-thiadiazol-4-yl)
phenoxy]methylene containing 1,3,4-triazoles and 1,3,4-thiadiazoles
2
.2 Hz, Ar-H), 7.42 (d, 1H, J = 2.2 Hz, Ar-H), 8.00–8.05 (m, 3H,
6.92 (d, 2H, J = 8.0 Hz, Ar-H), 7.54 (d, 1H, J = 7.8 Hz, Ar-H),
7.74–7.92 (m, 3H, Ar-H), 7.97 (d, 2H, J = 8.0 Hz, Ar-H), 9.30
Ar-H), 8.97 (s, 1H, thiadiazole ring proton), 9.26 (bs, 1H, NH),
+
9
.71 (bs, 1H, NH), 10.34 (bs, 1H, NH); MS: m/z 454 (M ), 456
(s, 1H, thiadiazole ring proton), 14.09 (s, 1H, SH); MS: m/z
+
+
+
(
M +2), 458 (M +4); Anal. Calcd for C17
H
13Cl
2
N
5
O
2
S
2
: C,
435 (M ); Anal. Calcd for C18
H
12
F
3
N
5
OS
2
: C, 49.65%; H,
4
4.94%; H, 2.88%; N, 15.41%. Found: C, 44.81%; H, 2.95%;
2.78%; N, 16.08%. Found: C, 49.54%; H, 2.86%; N, 16.20%.
N, 15.54%.
4-[3-(trifluoromethyl)phenyl]-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
N-(3-methoxyphenyl)-2-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
methyl}-4H-1,2,4-triazole-3-thiol (8e). This compound was
acetyl}hydrazine carbothioamide (7j). This compound was
obtained as yellowish solid (ethanol), yield 73%; mp 150–151 C;
obtained as brownish solid (1: 1, DMF : H O), yield 77%; mp
2
ꢀ
ꢀ
200–201 C; IR: 2587 (SH), 1643 (C = N), 1610 (C = C), 1239
À1
1
IR: 3289 (NH), 3210 (NH), 3127 (NH), 1695 (CO), 1596 (C = C),
2
(C–O) cm ; H-NMR: d 5.06 (s, 2H, –CH –), 6.94 (d, 2H,
À1
1
1
339 (CS), 1240 (C–O) cm
Ar-OCH ), 4.73 (s, 2H, –CH
.02–7.04 (m, 1H, Ar-H), 7.14–7.22 (m, 4H, Ar-H), 8.06 (d,
;
H-NMR: d 3.76 (s, 3H,
J = 8.5 Hz, Ar-H), 7.18–7.82 (m, 4H, Ar-H), 7.98 (d, 2H,
3
2
–), 6.72–6.74 (m, 1H, Ar-H),
J = 8.5 Hz, Ar-H), 9.14 (s, 1H, thiadiazole ring proton), 14.11
+
7
2
9
(s, 1H, SH); MS: m/z 435 (M ); Anal. Calcd for
H, J = 8.8 Hz, Ar-H), 9.32 (s, 1H, thiadiazole ring proton),
.67 (bs, 2H, NH), 10.30 (bs, 1H, NH); MS: m/z 415 (M );
C H F N OS : C, 49.65%; H, 2.78%; N, 16.08%. Found: C,
18
12
3
5
2
+
49.59%; H, 2.65%; N, 16.19%.
Anal. Calcd for C18
6.86%. Found: C, 51.95%; H, 4.24%; N, 16.97%.
General method for synthesis of 4-phenyl-5-{[4-(1,2,3-
H
17
N
5
O
3
S
2
: C, 52.03%; H, 4.12%; N,
4-(2,6-difluorophenyl)-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
1
methyl}-4H-1,2,4-triazole-3-thiol (8f). This compound was
obtained as brownish solid (1: 1, DMF : H O), yield 68%; mp
2
ꢀ
thiadiazol-4-yl)phenoxy]methyl}-4H-1,2,4-triazole-3-thiol (8a–h).
Thiosemicarbazide (7) (0.001mol) was taken in 1 N NaOH
189–190 C; IR: 2594 (SH), 1641 (C = N), 1616 (C = C), 1247
À1
1
(C–O), 1179 (Ar-F) cm
; H-NMR: d 5.07 (s, 2H, –CH –),
2
(10mL), and the reaction mixture was heated under mild reflux
6.92 (d, 2H, J= 8.8 Hz, Ar-H), 7.22–7.26 (m, 2H, Ar-H), 7.59–7.63
(m, 1H, Ar-H), 7.97 (d, 2H, J= 8.8 Hz, Ar-H), 9.21 (s, 1H,
condition till completion of reaction (checked by TLC). After
completion of reaction, the contents were allowed to cool, poured
into crushed ice, and acidified with glacial acetic acid. The
product obtained was separated and recrystallized from DMF and
water (1: 1) to give pure triazoles (8a–h). The characterization
data of synthesized compounds are as follows.
+
thiadiazole ring proton), 14.20 (s, 1H, SH); MS: m/z 403 (M );
Anal. Calcd for C H F N OS : C, 50.61%; H, 2.75%; N,
17
11
2
5
2
17.36%. Found: C, 50.74%; H, 2.86%; N, 17.20%.
4-(2,3-dichlorophenyl)-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
methyl}-4H-1,2,4-triazole-3-thiol (8g). This compound was
4
-phenyl-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]methyl}-4H-
obtained as faint yellow solid (1 : 1, DMF : H O), yield 76%;
2
ꢀ
1
,2,4-triazole-3-thiol (8a).
This compound was obtained as
mp 210–211 C; IR: 2612 (SH), 1635 (C = N), 1601 (C = C),
ꢀ
À1
1
yellow solid (1: 1, DMF : H O), yield 76%; mp 217–218 C; IR:
1245 (C–O) cm
; H-NMR: d 4.98 (d, 1H, J = 13.04 Hz,
2
À1
2
595 (SH), 1640 (C = N), 1601 (C= C), 1241 (C–O) cm
;
O–CH – proton), 5.04 (d, 1H, J = 13.04 Hz, O–CH – proton),
2
2
1
H-NMR: d 5.03 (s, 2H, –CH –), 6.96 (d, 2H, J = 8.7Hz, Ar-H),
6.92 (d, 2H, J = 8.8 Hz, Ar-H), 7.46–7.52 (m, 2H, Ar-H),
7.69–7.72 (m, 1H, Ar-H), 7.97 (d, 2H, J = 8.8 Hz, Ar-H),
9.24 (s, 1H, thiadiazole ring proton), 14.12 (s, 1H, SH); MS:
2
7
.45–7.55 (m, 5H, Ar-H), 7.98 (d, 2H, J = 8.7 Hz, Ar-H), 9.28
(
s, 1H, thiadiazole ring proton), 14.02 (s, 1H, SH); MS: m/z 367
+
+
+
+
(M ); Anal. Calcd for C H N OS : C, 55.57%; H, 3.57%; N,
m/z 436 (M ), 438 (M +2), 440 (M +4); Anal. Calcd for
1
7
13
5
2
1
9.06%. Found: C, 55.49%; H, 3.70%; N, 18.97%.
C H Cl N OS : C, 46.79%; H, 2.54%; N, 16.05%. Found:
1
7
11
2
5
2
4
-(2-fluorophenyl)-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]methyl}-
C, 46.67%; H, 2.42%; N, 16.21%.
4
H-1,2,4-triazole-3-thiol (8b). This compound was obtained as
4-(3-methoxyphenyl)-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
ꢀ
yellow solid (1: 1, DMF : H O), yield 73%; mp 183–184 C; IR:
methyl}-4H-1,2,4-triazole-3-thiol (8h). This compound was
2
2
620 (SH), 1640 (C =N), 1608 (C= C), 1240 (C–O), 1172 (Ar-F)
obtained as faint yellow solid (1 : 1, DMF : H O), yield 68%;
2
À1
1
ꢀ
cm
5
;
H-NMR: d 5.04 (d, 1H, J = 12.8Hz, O–CH
– proton), 6.96 (d, 2H, J = 8.4Hz,
Ar-H), 7.34–7.38 (m, 1H, Ar-H), 7.45–7.49 (m, 1H, Ar-H), 7.55–
.62 (m, 2H, Ar-H), 7.99 (d, 2H, J = 8.4Hz, Ar-H), 9.47 (s, 1H,
2
– proton),
mp 182–183 C; IR: 2580 (SH), 1622 (C = N), 1596 (C = C),
À1
1
.11 (d, 1H, J =12.8 Hz, O–CH
2
1233 (C–O) cm ; H-NMR: d 3.79 (s, 3H, Ar-OCH ), 5.03
3
(s, 2H, –CH –), 6.98–7.04 (m, 5H, Ar-H), 7.40–7.44 (m, 1H,
2
7
Ar-H), 7.99 (d, 2H, J = 8.8 Hz, Ar-H), 9.20 (s, 1H, thiadiazole
+
+
thiadiazole ring proton), 14.18 (s, 1H, SH); MS: m/z 385 (M );
Anal. Calcd for C17 OS : C, 52.97%; H, 3.14%; N,
8.17%. Found: C, 53.09%; H, 3.06%; N, 18.30%.
-(4-fluorophenyl)-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]methyl}-
ring proton), 14.00 (s, 1H, SH); MS: m/z 397 (M ); Anal. Calcd
H
12FN
5
2
for C H N O S : C, 54.39%; H, 3.80%; N, 17.62%. Found:
1
8 15 5 2 2
1
C, 54.51%; H, 3.71%; N, 17.72%.
4
General method for synthesis of N-phenyl-5-{[4-(1,2,3-
4
H-1,2,4-triazole-3-thiol (8c). This compound was obtained as faint
thiadiazol-4-yl)phenoxy]methyl}-1,3,4-thiadiazol-2-amine(9a–i).
ꢀ
yellow solid (1: 1, DMF : H
2
O), yield 69%; mp 205–206 C; IR:
Thiosemicarbazide (7) (0.001 mol) was dissolved in conc. H SO4
2
2
601 (SH), 1633 (C =N), 1606 (C= C), 1231 (C–O), 1175 (Ar-F)
(3mL), and the reaction mixture was stirred at room temperature
À1
1
cm ; H-NMR: d 5.03 (s, 2H, –CH –), 6.97 (d, 2H, J = 8.6Hz,
Ar-H), 7.24–7.28 (m, 2H, Ar-H), 7.47–7.50 (m, 2H, Ar-H), 7.99
for 3 h. After completion of reaction (checked by TLC), the
contents were poured over crushed ice. The solid obtained was
separated and recrystallized from DMF and water (1 : 1) to give
pure thiadiazoles (9a–i). The characterization data of synthesized
2
(d, 2H, J = 8.6 Hz, Ar-H), 9.16 (s, 1H, thiadiazole ring proton),
+
14.03 (s, 1H, SH); MS: m/z 385 (M ); Anal. Calcd for
C H FN OS : C, 52.97%; H, 3.14%; N, 18.17%. Found: C,
compounds are as follows.
17
12
5
2
N-phenyl-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]methyl}-1,3,4-
5
2.85%; H, 3.25%; N, 18.06%.
-[2-(trifluoromethyl)phenyl]-5-{[4-(1,2,3-thiadiazol-4-yl)
phenoxy]methyl}-4H-1,2,4-triazole-3-thiol (8d). This compound
4
thiadiazol-2-amine (9a). This compound was obtained as faint
yellow solid (1 : 1, DMF : H
ꢀ
2
O), yield 71%; mp 205–206 C; IR:
À1
was obtained as brownish solid (1 : 1, DMF : H
2
O), yield 73%; mp
3421 (NH), 1608 (C = N), 1550 (C = C), 1249 (C–O) cm
;
ꢀ
1
1
1
20–121 C; IR: 2591 (SH), 1622 (C = N), 1599 (C = C),
2
H-NMR: d 5.47 (s, 2H, –CH – ), 7.00–7.02 (m, 2H, Ar-H),
À1
1
233 (C–O) cm
;
H-NMR: d 4.87 (d, 1H, J = 13.0 Hz,
7.19 (d, 2H, J = 8.0 Hz, Ar-H), 7.60–7.66 (m, 3H, Ar-H), 8.04
O–CH – proton), 5.07 (d, 1H, J = 13.0 Hz, O–CH – proton),
(d, 2H, J = 8.0 Hz, Ar-H), 9.45 (s, 1H, thiadiazole ring
2
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. G. Gadhave, R. Gaikar, S. Kuchekar, and B. Karale
Vol 000
+
proton), 10.02 (bs, 1H, NH); MS: m/z 367 (M ); Anal. Calcd
Anal. Calcd for C H Cl N OS : C, 46.79%; H, 2.54%; N,
17 11 2 5 2
for C H N OS : C, 55.57%; H, 3.57%; N, 19.06%. Found:
C, 55.45%; H, 3.66%; N, 19.15%.
N-(2-fluorophenyl)-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]methyl}-
16.05%. Found: C, 46.70%; H, 2.48%; N, 16.20%.
17
13
5
2
N-(3,5-dichlorophenyl)-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
methyl}-1,3,4-thiadiazol-2-amine (9h). This compound was
1
,3,4-thiadiazol-2-amine (9b). This compound was obtained as
obtained as white solid (1 : 1, DMF : H O), yield 69%; mp 239–
2
ꢀ
ꢀ
brownish solid (1 : 1, DMF : H
2
O), yield 77%; mp 209–210 C; IR:
240 C; IR: 3431 (NH), 1601 (C = N), 1548 (C= C), 1231 (C–O)
À1
1
3
415 (NH), 1602 (C= N), 1540 (C = C), 1236 (C–O), 1187 (Ar-F)
cm ; H-NMR: d 5.46 (s, 2H, –CH –), 6.97–6.98 (m, 1H, Ar-
2
À1
1
cm
;
H-NMR: d 5.44 (s, 2H, –CH –), 6.95–7.01 (m, 1H,
H), 7.17 (d, 2H, J = 8.8 Hz, Ar-H), 7.67–7.68 (m, 2H, Ar-H),
2
Ar-H), 7.10–7.19 (m, 4H, Ar-H), 8.05 (d, 2H, J = 8.0Hz, Ar-H),
8.04–8.07 (m, 2H, Ar-H), 9.12 (s, 1H, thiadiazole ring proton),
+
+
+
8
1
.40–8.44 (m, 1H, Ar-H), 9.20 (s, 1H, thiadiazole ring proton),
0.11 (bs, 1H, NH); MS: m/z 385 (M ); Anal. Calcd for
10.61 (bs, 1H, NH); MS: m/z 436 (M ), 438 (M +2), 440 (M +4);
Anal. Calcd for C H Cl N OS : C, 46.79%; H, 2.54%; N,
+
17
11
2
5
2
C H FN OS : C, 52.97%; H, 3.14%; N, 18.17%. Found: C,
16.05%. Found: C, 46.64%; H, 2.62%; N, 16.15%.
17
12
5
2
5
3.09%; H, 3.23; N, 18.28%.
N-(4-fluorophenyl)-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]methyl}-
N-(2,4-dichlorophenyl)-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
methyl}-1,3,4-thiadiazol-2-amine (9i). This compound was
1
,3,4-thiadiazol-2-amine (9c). This compound was obtained as
obtained as white solid (1 : 1, DMF : H O), yield 73%; mp
2
ꢀ
ꢀ
faint yellow solid (1: 1, DMF: H
2
O), yield 70%; mp 247–248 C;
211–212 C; IR: 3419 (NH), 1597 (C = N), 1539 (C = C), 1245
C–O) cm ; H-NMR: d 5.46 (s, 2H, –CH –), 7.18 (d, 2H,
2
À1
1
IR: 3412 (NH), 1599 (C = N), 1545 (C= C), 1241 (C–O), 1178
(
À1
1
(
Ar-F) cm ; H-NMR: d 5.44 (s, 2H, –CH
Ar-H), 7.18 (d, 2H, J = 8.8 Hz, Ar-H), 7.62–7.65 (m, 2H, Ar-H),
.06 (d, 2H, J = 8.8 Hz, Ar-H), 9.28 (s, 1H, thiadiazole ring
2
–), 7.03–7.08 (m, 2H,
J = 8.4 Hz, Ar-H), 7.31–7.34 (m, 1H, Ar-H), 7.46–7.47 (m, 1H,
Ar-H), 8.07 (d, 2H, J = 8.4 Hz, Ar-H), 8.42–8.44 (m, 1H, Ar-H),
8
9
.30 (s, 1H, thiadiazole ring proton), 9.87 (bs, 1H, NH); MS:
+
+
+
+
proton), 10.31 (bs, 1H, NH); MS: m/z 385 (M ); Anal. Calcd for
OS : C, 52.97%; H, 3.14%; N, 18.17%. Found: C,
m/z 436 (M ), 438 (M +2), 440 (M +4); Anal. Calcd for
OS : C, 46.79%; H, 2.54%; N, 16.05%. Found:
C
17
H
12FN
5
2
C
H11Cl N
17 2 5
2
5
2.85%; H, 3.04%; N, 18.24%.
N-[2-(trifluoromethyl)phenyl]-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
C, 46.88%; H, 2.61%; N, 16.21%.
General procedure for in vitro antimicrobial screening. All
newly synthesized compounds were evaluated for their antimicrobial
activity by broth microdilution method according to the National
Committee for Clinical Laboratory Standards [24]. The results
were determined using minimum inhibitory concentration (MIC)
values in mg/mL. Antibacterial activity was screened against two
gram-positive (S. aureus MTCC 96 and S. pyogenes MTCC 443)
and two gram-negative (E. coli MTCC 442 and P. aeruginosa
methyl}-1,3,4-thiadiazol-2-amine (9d). This compound was
obtained as faint yellow solid (1 : 1, DMF : H O), yield 67%; mp
2
ꢀ
1
(
98–199 C; IR: 3429 (NH), 1595 (C= N), 1551 (C =C), 1247
C–O) cm ; H-NMR: d 5.38 (s, 2H, –CH –), 7.15 (d, 2H,
2
À1
1
J = 8.4Hz, Ar-H), 7.26–7.30 (m, 1H, Ar-H), 7.58–7.66 (m, 2H,
Ar-H), 7.94 (s, 2H, Ar-H & NH), 8.05 (d, 2H, J = 8.4Hz, Ar-H),
+
9
.15 (s, 1H, thiadiazole ring proton); MS: m/z 435 (M ); Anal.
12 3 5 2
Calcd for C18H F N OS : C, 49.65%; H, 2.78%; N, 16.08%.
Found: C, 49.73%; H, 2.87%; N, 15.97%.
N-[3-(trifluoromethyl)phenyl]5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
MTCC 441) bacteria by using ampicillin as
a standard
antibacterial agent. Antifungal activity was screened against three
fungal species (C. albicans MTCC 227, A. niger MTCC 282, and
A. clavatus MTCC 1323) where griseofulvin was used as standard
antifungal agent.
methyl}-1,3,4-thiadiazol-2-amine (9e). This compound was
obtained as white solid (1 : 1, DMF: H O), yield 70%; mp
2
ꢀ
2
(
38–239 C; IR: 3425 (NH), 1591 (C= N), 1541 (C =C), 1243
C–O) cm ; H-NMR: d 5.48 (s, 2H, –CH –), 7.20 (d, 2H,
2
À1
1
All MTCC cultures were collected from Institute of Microbial
Technology, Chandigarh and tested against abovementioned
known drugs. Mueller–Hinton broth was used as nutrient medium
to grow and dilute the drug suspension for the test. Inoculum’s
J = 8.0Hz, Ar-H), 7.25–7.27 (m, 1H, Ar-H), 7.48–7.52 (m, 1H,
Ar-H), 7.76–7.79 (m, 1H, Ar-H), 8.07 (d, 2H, J = 8.0 Hz,
Ar-H), 8.15 (s, 1H, Ar-H), 9.34 (s, 1H, thiadiazole ring proton),
8
+
size for test strain was adjusted to 10 colony-forming unit
1
0.68 (bs, 1H, NH); MS: m/z 435 (M ); Anal. Calcd for
(
CFU)/mL by comparing the turbidity. The control tube contain-
18 12 3 5 2
C H F N OS : C, 49.65%; H, 2.78%; N, 16.08%. Found: C,
ing no antibiotic was immediately subcultured (before inocula-
tion) by spreading a loopful evenly over a quarter plate of
medium suitable for the growth of the test organism and put for
4
9.76%; H, 2.67%; N, 16.22%.
N-(2,6-difluorophenyl)-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
methyl}-1,3,4-thiadiazol-2-amine (9f). This compound was
ꢀ
incubation at 37 C overnight. The tubes were then incubated
obtained as white solid (1 : 1, DMF : H O), yield 64%; mp
2
ꢀ
overnight. The MIC of the control organism was read to check
the accuracy of the compound concentration. The MIC was
defined as the lowest concentration of the antibiotic or test sample
allowing no visible growth. All tubes showing no visible growth
2
(
7
7
15–216 C; IR: 3423 (NH), 1596 (C = N), 1550 (C = C), 1225
-
À1
1
C–O), 1173 (Ar-F) cm ; H- NMR: d 5.38 (s, 2H, –CH
2
–),
.01-7.05 (m, 2H, Ar-H), 7.15 (d, 2H, J = 8.8 Hz, Ar-H),
.21–7.28 (m, 1H, Ar-H), 7.93 (bs, 1H, NH), 8.04 (d, 2H,
(
same as control tube) were subcultured and incubated overnight
J = 8.8 Hz, Ar-H), 9.15 (s, 1H, thiadiazole ring proton); MS:
ꢀ
+
at 37 C. The amount of growth from the control tube before incu-
bation (which represents the original inoculums) was compared.
Subcultures might show the following: similar number of colo-
nies indicating bacteriostatic, a reduced number of colonies indi-
cating a partial or slow bactericidal activity and no growth if the
whole inoculum has been killed. The test must include a second
set of the same dilutions inoculated with an organism of known
sensitivity. DMSO was used as diluents to obtain the desired con-
centration of compounds to test upon standard bacterial strains.
Each synthesized compound was diluted obtaining 2000mg/mL
concentrations as a stock solution. Serial dilutions were prepared
m/z 403 (M ); Anal. Calcd for C17
11 2 5 2
H F N OS : C, 50.61%;
H, 2.75%; N, 17.36%. Found: C, 50.53%; H, 2.82%; N,
1
7.25%.
N-(2,3-dichlorophenyl)-5-{[4-(1,2,3-thiadiazol-4-yl)phenoxy]
methyl}-1,3,4-thiadiazol-2-amine (9g). This compound was
obtained as white solid (1: 1, DMF: H O), yield 72%; mp 209–
10 C; IR: 3429 (NH), 1599 (C =N), 1551 (C= C), 1239 (C–O)
2
ꢀ
À1
2
1
cm ; H-NMR: d 5.44 (s, 2H, –CH –), 7.16–7.20 (m, 3H, Ar-
2
H), 7.25–7.29 (m, 1H, Ar-H), 8.05 (d, 2H, J = 8.8Hz, Ar-H), 8.34
(
9
d, 2H, J = 8.4 Hz, Ar-H), 9.12 (s, 1H, thiadiazole ring proton),
.84 (bs, 1H, NH); MS: m/z 436 (M ), 438 (M +2), 440 (M +4);
+
+
+
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis and Antimicrobial Evaluation of Some Novel [4-(1,2,3-thiadiazol-4-yl)
phenoxy]methylene containing 1,3,4-triazoles and 1,3,4-thiadiazoles
in primary and secondary screening. In primary screening, 500, 250,
and 200 mg/mL concentrations of the synthesized compounds were
taken. The compounds found active in primary screening
were further tested in a second set of dilutions 100, 62.5, 50, and
[9] Casini, A.; Scozzafava, A.; Mincione, F.; Menabuoni,
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[
2
5mg/mL concentrations against all microorganisms.
[
[
Acknowledgments. The authors are thankful to Dr. S. R. Walunj
Principal, PVP College, Pravaranagar, Dist-Ahmednagar-413713,
India), Dr. T. N. Gholap (Principal, RKMM, Ahmednagar-
14001, India) and Management, PRES (A/P-Loni Kd, Tal-
[
(
[
4
Rahata, Dist-Ahmednagar-413713, India) for providing necessary
facilities and constant encouragement. We are thankful to the
Director, Sophisticated Analytical Instrumentation Facility (Punjab
University, Chandigarh, India) for spectral analysis. We are
thankful to the Director, Microcare Laboratory, (Surat-395003,
India) for antimicrobial activity.
1
2
[
[
[
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4
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2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet