Synthesis and biological activity of novel 1,3,5-trisubstituted 1,2,4-triazole derivatives

Article abstract of DOI:10.1002/jhet.291

(Chemical Equation Presented) Triazole skeleton is ubiquitous in pharmaceutically important compounds. A novel series of indoline-containing triazole with different amides are described, which exhibit antibacterial and antifungal activities. The chemical

Full text of DOI:10.1002/jhet.291

156
Synthesis and Biological Activity of Novel 1,3,5-Trisubstituted
1,2,4-Triazole Derivatives
Vol 47
Kokila Parmar,* Bharat Suthar, Saraju Prajapati, and Arun Suthar
Department of Chemistry, Hemchandracharya North Gujarat University, Patan 384 265,
Gujarat, India
*E-mail: drkaparmar@gmail.com
Received June 7, 2009
DOI 10.1002/jhet.291
Published online 8 January 2010 in Wiley InterScience (www.interscience.wiley.com).
Triazole skeleton is ubiquitous in pharmaceutically important compounds. A novel series of indoline-
containing triazole with different amides are described, which exhibit antibacterial and antifungal activ-
ities. The chemical synthesis strategies used, the complete characterization of the compounds, their
in vitro screening, and the promising activity as reflected in the MIC values are reported.
J. Heterocyclic Chem., 47, 156 (2010).
INTRODUCTION
elemental analysis. Results of biological activities indi-
cate that some compounds possess potential antimicro-
bial activity.
Developing new antimicrobial agents (antibacterial
and antifungal) continues to attract attention and is an
area of rigorous research. Although a large number of
antibiotics and chemotherapeutics are available for med-
ical use, the antimicrobial resistance created a substan-
tial need of new class of antimicrobial agents in the last
decades [1–3].
RESULTS AND DISCUSSION
Chemistry. The synthetic strategy involved in the
synthesis of intermediate and target compounds is out-
lined in Schemes 1 and 2. The key intermediate [3-(2,3-
Triazole and its derivatives have distinct status as
pharmaceutical agents. They have been found to have
high therapeutic value as antifungal [4–6], anti-inflam-
matory [7], antimalarial [8], antiviral [9], antihyperten-
sive [10], analgesic [11], antihyperuricemic [12], and
anticancer agents [13,14]. Recently, synthesis of trisub-
stituted 1,2,4-triazole derivatives reported as a modula-
tor of nicotinic receptor agonist [15] and antitumor and
antiviral agents [16], in addition triazole derivatives
revealing promising antimicrobial activities [17–23]. In
continued quest of new antimicrobial agents, we
designed and synthesized novel 1,2,4-triazole derivatives
containing indoline ring. Structures of the products were
dihydroindol-1-yl)-5-phenyl[1,2,4]
triazol-1-yl]acetic
acid 7 was prepared as outlined in Scheme 1 [24,25].
Benzoyl chloride reacted with ammonium thiocyanate to
obtain benzoyl thiocyanate 1, which was treated in situ
with indoline to provide the addition product N-benzoyl
thiourea 2 [26]. The addition product 2 was methylated
by methyl iodide to produce N-benzoyl-S-methyliso-
thiourea 3, which was further cyclized with hydrazine
hydrated in refluxing ethanol to give the triazole 4. The
triazole 4 was alkylated by ethyl bromoacetate in the
presence of sodium hydride in dry THF to afford two
regioisomers 5 and 6. The isomer 5 was hydrolyzed in
the presence of aqueous LiOH to give the corresponding
1
characterized by IR, H-NMR, mass spectrometry, and
C
V
2010 HeteroCorporation

January 2010
Synthesis and Biological Activity of Novel 1,3,5-Trisubstituted
1,2,4-Triazole Derivatives
157
Scheme 1. Reagents and conditions: (a) ammonium thiocyanate, acetone, 56ꢀC, 30 min; (b) indoline, acetone, 56ꢀC, 1 h; (c) methyl iodide,
K2CO3, DMF, rt, 1 h; (d) hydrazine hydrate, ethanol, reflux, 5 h; (e) ethyl bromoacetate, NaH, THF, rt, 4 h; (f) aq. LiOH.H2O, THF-methanol, rt,
5 h.
acid derivative 7, which was used as a key intermediate
for the synthesis of target compounds.
(IMTECH), Chandigarh, India. The MIC values are
given in Table 2. The standard drug used for antibacte-
rial activity was ciprofloxacin and nystatin for antifungal
activity. Mueller Hinton broth was used as nutrient me-
dium for bacteria and Sabouraud dextrose broth for fun-
gal to grow. Inoculum size for test strain was adjusted
to 108 CFU/mL by comparing the turbidity. Serial dilu-
tions were prepared for primary and secondary screen-
ing. The target compounds and standard drugs were dis-
solved in DMSO water at a concentration of 2.0 mg/
mL. In primary screening, 500, 250, and 125 lg/mL
The two regioisomers 5 and 6 were separated by
chromatography on silica gel, and the resulting regio-
isomer ethyl [3-(2,3-dihydroindol-1-yl)-5-phenyl[1,2,4]
triazol-1-yl]acetate 5 was the major product. The struc-
tures of these two regioisomers 5 and 6 were assigned
based on NMR analysis and confirmed by NOE NMR
experiments [24,27] (Fig. 1).
The synthesis of target compounds 8a–e and 9a–e is
outlined in Scheme 2. The amide coupling of [3-(2,3-
dihydroindol-1-yl)-5-phenyl[1,2,4]
triazol-1-yl]acetic
acid 7 was carried out with different amines, in the pres-
ence of EDCI in THF at room temperature, with excel-
lent yield.
The structures of all the intermediates and final com-
pounds 8a–e and 9a–e were found on the basis of ele-
mental analysis and spectrographic (IR, 1H-NMR, and
Mass) data. The physical characterization data are listed
in Table 1.
Biological activities. The newly synthesized deriva-
tives were evaluated for their in vitro antibacterial activ-
ity against gram-negative E. coli, P. aeruginosa, gram-
positive S. aureus, S. pyogenes, and antifungal activity
against C. albicans and A. niger by microbroth dilution
methods [28–30]. The standard strains used for screen-
ing of antibacterial and antifungal activities were pro-
cured from the Institute of Microbial Technology
Figure 1. NOE was observed between 1-methylene and ortho-proton
of phenyl group of compound 5 and between 1-methylene and N-meth-
ylene group of compound 6. Chemical shift of ortho-hydrogen of phe-
nyl in compound 6 was more downfield because of extra deshielding
effect from the triazole ring.
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K. Parmar, B. Suthar, S. Prajapati, and A. Suthar
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Scheme 2. Reagents and conditions: (a) corresponding secondary cyclic amine, EDCI, DIPEA, THF, rt, 5–10 h and (b) corresponding aromatic
amine, EDCI, DIPEA, THF, rt, 5–8 h.
concentrations of the synthesized drugs were taken.
Data were not taken for the initial solution, because of
the high DMSO concentration (10%). The active synthe-
sized drugs found in this primary screening were further
tested in a second set of dilution against all microorgan-
isms. In secondary screening, the drugs found active in
primary screening were similarly diluted to obtain 100,
50, 25, 12.5, and 6.250 lg/mL concentrations. The ino-
culated wells were incubated overnight at 37ꢀC in a
humid atmosphere. The highest dilution showing at least
99% inhibition zone is taken as MIC.
except S. pyogenes. Compound 8e showed excellent ac-
tivity against S. aureus and moderate activity against all
the other tested bacteria. While the other series with
aromatic amide functionality, compounds 9a–e, did not
show comparable inhibition with any tested bacterial
and fungal organisms.
EXPERIMENTAL
Melting points were determined with a Buchi B-545 melting
point apparatus and are uncorrected. IR spectra were recorded
on a Perkin-Elmer PE-1600 FTIR spectrometer in KBr disc.
1H-NMR spectra were recorded on a Varian 400 spectrometer
in DMSO-d6 as a solvent and TMS as an internal standard.
Peak values are shown in d ppm. EI-MS spectra were meas-
ured on a Waters mass spectrometer. Progress of the reaction
was checked by thin layer chromatography (TLC) on silica
gel-coated aluminum sheets (silica gel 60 F254) using a mix-
ture of ethyl acetate and hexane (5:5 v/v). All of the solvents
and materials were reagent grade and purified as required.
N-(2,3-Dihydroindole-1-carbothioyl)benzamide (2). Benzoyl
chloride was added to a stirred solution of NH4SCN (3.51 g,
0.046 mol) in acetone (30 mL), and the resultant suspension
was refluxed for 30 min and then cooled to room temperature.
A solution of indoline (5.0 g, 0.042 mol) in acetone (30 mL)
Results of antibacterial and antifungal activities of
screened compounds indicate that some compounds pos-
sess comparable antibacterial activity with respect to
reference drug ciprofloxacin. Compounds 8a–e with sec-
ondary amide functionality exhibited moderate to excel-
lent activity against all the tested bacterial strains, but
not showed satisfactory activity against fungal strains.
Compound 8a exhibited excellent activity against E.
coli, whereas moderate activity against P. aeruginosa
and S. aureus. Compound 8b showed very good active
against P. aeruginosa only, whereas compound 8c
exhibited moderate activity against all the tested bacteria
Table 1
Physical characterization data of compounds 8a–e and 9a–e.
Compound
Physical state
Time (h)
Mp (ꢀC)
Yield (%)
Molecular formula
MW
8a
8b
8c
8d
8e
9a
9b
9c
9d
9e
Off-white crystal
Off-white crystal
White crystal
5
5
4
5
4
4
5
6
5
4
180–181
178–180
129–131
187–189
172–174
183–185
181–183
197–200
179–181
199–201
77
73
69
81
69
83
71
79
73
81
C22H23N5O
C22H23N5O2
C23H25N5O
C29H29N5O
C28H28N6O
C24H21N5O
C25H23N5O
C24H20BrN5O
C27H27N5O
C25H23N5O
373
389
387
463
464
395
409
474
437
409
Off-white crystal
White crystal
White crystal
White crystal
White crystal
Off-white crystal
White crystal
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Synthesis and Biological Activity of Novel 1,3,5-Trisubstituted
1,2,4-Triazole Derivatives
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Table 2
Antimicrobial activity data of newly synthesized compounds 8a–e and 9a–e.
Antibacterial MIC (lg/mL)
Antifungal MIC (lg/mL)
C. albicans A. niger
E.coli
MTCC 443
P. aeruginosa
MTCC 1688
S. aureus
MTCC 96
S. pyogenes
MTCC 442
Compounds
MTCC 227
MTCC 82
8a
8b
8c
8d
8e
9a
9b
9c
9d
9e
50
125
62.5
100
100
250
500
250
500
500
25
100
62.5
100
125
125
500
500
250
500
500
25
125
125
62.5
200
50
500
250
250
500
500
50
500
250
500
500
100
500
500
250
125
500
50
1000
1000
500
1000
1000
500
1000
500
200
200
–
500
1000
1000
500
1000
1000
1000
1000
200
200
Ciprofloxacin
Nystatin
–
100
–
–
–
–
100
was added and the mixture was refluxed for 1 h. Reaction mix-
ture was cooled to room temperature and poured in to water,
and the resulting white solid was filtered and washed with
water. Solid was recrystallized in ethanol giving pure com-
pound 3 as off-white solid. Yield 9.79 g (83.0%), m.p. 140–
142ꢀC; 1H-NMR (DMSO-d6): d 3.17–3.25 (t, 2H, CH2, J ¼
8.5 Hz), 4.10–4.21 (t, 2H, CH2, J ¼ 8.6 Hz), 6.95–7.19 (m,
2H, ArH), 7.23–7.31 (d, 1H, ArH), 7.41–7.56 (m, 3H, ArH),
7.86–8.01 (m, 3H, ArH), 12.3 (bs, 1H, NH); ms: m/z 281 (M-
1). Anal. Calcd. for C16H14N2OS: C, 68.06; H, 5.00; N, 9.92;
Found: C, 68.21; H, 4.89; N, 9.78.
N-[1-(2,3-Dihydroindol-1-yl)-1-methylsulfanyl-methylidene]
benzamide (3). Methyl iodide (2.38 mL, 0.038 mol) was
added to a stirred suspension of compound 2 (9.0 g, 0.031
mol) and anhydrous K2CO3 (6.4 g, 0.046 mol) in DMF (50
mL) and stirred for 1 h at room temperature. Reaction mixture
was poured in water (200 mL) and stirred for 15 min. The
resulting off-white solid was filtered, washed with water, and
dried in vacuo. Solid was crystallized from rectified spirit to
give compound 3 as off-white solid. Yield 7.33 g (78.0%),
m.p. 87–89ꢀC; 1H-NMR (DMSO-d6): d 2.234 (s, 3H, CH3);
3.17–3.25 (t, 2H, CH2, J ¼ 8.5 Hz), 4.17–4.25 (t, 2H, CH2, J
¼ 8.5 Hz), 7.02–7.20 (m, 2H, ArH), 7.28–7.32 (d, 1H, ArH),
7.43–7.58 (m, 3H, ArH), 8.02–8.09 (m, 3H, ArH); ms: m/z
297 (Mþ1). Anal. Calcd. for C17H16N2OS: C, 68.89; H, 5.44;
N, 9.45; Found: C, 68.77; H, 5.58; N, 9.33.
1-(5-Phenyl-1H-[1,2,4]triazol-3-yl)-2,3-dihydro-1H-indole
(4). A solution of compound 3 (7.0 g, 0.023 mol) and hydra-
zine hydrate (1.78 mL, 0.035 mol) in ethanol (50 mL) was
refluxed for 5 h, cooled, and poured into water (100 mL), and
the mixture was stirred at room temperature. The resulting
white solid was collected by filtration and washed with water
to give a crude compound 3. The solid was recrystallized in
ethanol to give a pure compound 4 as white solid. Yield 4.64
g (75%), m.p. 131–133ꢀC; 1H-NMR (DMSO-d6): d 3.16–3.25
(t, 2H, CH2, J ¼ 8.2 Hz), 3.92–4.01 (t, 2H, CH2, J ¼ 8.2 Hz),
6.72–6.81 (t, 1H, ArH), 7.13–7.21 (m, 2H, ArH), 7.49–7.53
(m, 3H, ArH), 7.69–7.73 (m, 2H, ArH), 7.81–7.86 (m, 1H,
ArH), 12.9 (s, 1H, NH); ms: m/z 263 (Mþ1). Anal. Calcd. for
C16H14N4: C, 73.26; H, 5.38; N, 21.36; Found: C, 73.12; H,
5.51; N, 21.48.
Ethyl[3-(2,3-dihydroindol-1-yl)-5-phenyl[1,2,4]triazol-1-yl]
acetate (5) and ethyl[5-(2,3-dihydroindol-1-yl)-3-phenyl[1,
2,4]triazol-1-yl]acetate (6). A solution of compound 4 (4.5 g,
0.017 mol) in dry THF was treated with NaH (1.0 g, 0.025
mol) at room temperature for 20 min, followed by ethyl bro-
moacetate (2.0 mL, 0.018 mol). The reaction mixture was
stirred for 4 h at room temperature, and TLC indicated two
products. The mixture was evaporated and the product was
separated by chromatography on silica gel (20% EtOAc/hex-
ane) to afford 5 and 6.
5. The major product, white solid. Yield 3.76 g (63%), m.p.
1
160–162ꢀC; H-NMR (DMSO-d6): d 1.28–1.30 (t, 3H, CH3, J
¼ 7.10 Hz), 3.17–3.20 (t, 2H, CH2, J ¼ 8.30 Hz), 4.02–4.06
(t, 2H, CH2, J ¼ 8.30 Hz), 4.11–4.13 (q, 2H, CH2, J ¼ 7.11
Hz), 4.99 (s, 2H, CH2), 6.77–6.81 (t, 1H, ArH), 7.11–7.15 (t,
1H, ArH), 7.17–7.19 (d, 1H, ArH), 7.55–7.57 (m, 3H, ArH),
7.70–7.73 (m, 2H, ArH), 7.84–7.86 (d, 1H, ArH); ms: m/z 349
(Mþ1). Anal. Calcd. for C20H20N4O2: C, 68.95; H, 5.79; N,
16.08; Found: C, 68.73; H, 5.93; N, 15.90.
6. The minor product, white solid. Yield 0.59 g (10%), m.p.
1
171–163ꢀC; H-NMR (DMSO-d6): d 1.27–1.29 (t, 3H, CH3, J
¼ 7.10 Hz), 3.14–3.16 (t, 2H, CH2, J ¼ 8.25 Hz), 3.28–3.34
(m, 2H, CH2), 4.10–4.12 (q, 2H, CH2, J ¼ 7.10 Hz), 5.05 (s,
2H, CH2), 6.85–6.89 (t, 1H, ArH), 7.17–7.19 (t, 1H, ArH),
7.22–7.24 (t, 1H, ArH), 7.57–7.60 (m, 3H, ArH), 7.77–7.79
(m, 2H, ArH), 7.91–7.93 (dd, 1H, ArH); ms: m/z 349 (Mþ1).
Anal. Calcd. for C20H20N4O2: C, 68.95; H, 5.79; N, 16.08;
Found: C, 68.76; H, 5.87; N, 15.88.
[3-(2,3-Dihydro-indol-1-yl)-5-phenyl[1,2,4]triazol-1-yl]ace-
tic acid (7). A solution of compound 6 (3.70 g, 0.010 mol) in
THF-MeOH (20:20 mL) was treated with LiOH.H20 (0.89 g,
0.021 mol) at room temperature for 5 h, and the mixture was
evaporated in vacuo. Water (50 mL) was added to the residue
and washed with ethyl acetate (20 mL). Aqueous layer was
acidified to pH 4 by adding dil. HCl, and the resulting precipi-
tate was filtered, washed with water, and dried in vacuo to
give compound 7 as white solid. Yield 2.75 g (81%), m.p.
1
200–202ꢀC; H-NMR (DMSO-d6): d 3.13–3.21 (t, 2H, CH2, J
¼ 8.31 Hz), 4.00–4.08 (t, 2H, CH2, J ¼ 8.31 Hz), 4.99 (s, 2H,
CH2), 6.75–6.83 (t, 1H, ArH), 7.10–7.20 (m, 2H, ArH), 7.54–
7.57 (m, 3H, ArH), 7.70–7.74 (m, 2H, ArH), 7.84–7.88 (d, 1H,
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ArH), 13.51 (s, 1H, COOH); ms: m/z 319 (M-1). Anal. Calcd.
for C18H16N4O2: C, 67.49; H, 5.03; N, 17.49; Found: C,
67.57; H, 5.16; N, 17.31.
2[3-(2,3-Dihydro-indol-1-yl)-5-phenyl[1,2,4]triazol-1-yl]-N-
phenyl-acetamide (9a). IR t (cmꢁ1): 3415 (NAH), 1674
(C¼¼O); 1H-NMR (DMSO-d6): d 3.16–3.18 (t, 2H, CH2, J ¼
8.24 Hz), 3.97–4.12 (t, 2H, CH2, J ¼ 8.22 Hz), 5.13 (s, 2H,
CH2), 6.78–6.86 (t, 1H, ArH), 7.08–7.18 (m, 3H, ArH), 7.32–
7.41 (t, 2H, ArH), 7.55–7.60 (m, 5H, ArH), 7.81–7.97 (m, 3H,
ArH), 10.56 (bs, 1H, NH); ms: m/z 396 (Mþ1). Anal. Calcd.
for C24H21N5O: C, 72.89; H, 5.35; N, 17.71; Found: C, 72.77;
H, 5.43; N, 17.83.
2[3-(2,3-Dihydro-indol-1-yl)-5-phenyl[1,2,4]triazol-1-yl]-N-p-
tolyl-acetamide (9b). IR t (cmꢁ1): 3450 (NAH), 1679 (C¼¼O);
1H-NMR (DMSO-d6): d 2.41 (s, 3H, CH3), 3.20–3.21 (t, 2H,
CH2, J ¼ 8.21 Hz), 3.89–3.93 (t, 2H, CH2, J ¼ 8.20 Hz), 5.10
(s, 2H, CH2), 6.80–6.82 (m, 1H, ArH), 7.10–7.16 (m, 3H,
ArH), 7.30–7.37 (m, 2H, ArH), 7.60–7.65 (m, 4H, ArH), 7.91–
7.97 (m, 3H, ArH), 10.66 (bs, 1H, NH); ms: m/z 410 (Mþ1).
Anal. Calcd. for C25H23N5O: C, 73.33; H, 5.66; N, 17.10;
Found: C, 73.47; H, 5.51; N, 16.91.
General procedure for the synthesis of compounds 8a–e
and 9a–e. A stirred solution of compound 6 (0.625 mmol),
corresponding amino derivative (0.687 mmol), and diisopropy-
lethylamine (1.25 mmol) in anhydrous THF (10 mL) was
cooled to 0ꢀC. EDCI (0.750 mmol) was added to the above
mixture, and the resulting solution was stirred at room temper-
ature for 5–7 h. The reaction mixture was evaporated in vacuo,
and water (50 mL) was added to the residue and acidified to
pH 4 by adding dil. HCl. The solid separated was collected by
filtration, washed with water, and dried. Compound was
recrystallized from 95% ethanol to give pure compounds 8a–e
and 9a–e. The yield, the reaction time, and the physical prop-
erties are reported in Table 1.
2-[3-(2,3-Dihydro-indol-1-yl)-5-phenyl-[1,2,4]triazol-1-yl]-1-
1
pyrrolidin-1-yl-ethanone (8a). IR t (cmꢁ1): 1675 (C¼¼O); H-
NMR (DMSO-d6): d 2.12–2.20 (m, 4H, 2CH2), 3.12–3.23 (t,
2H, CH2, J ¼ 8.25 Hz), 3.41–3.63 (m, 4H, 2CH2), 3.91–4.00
(t, 2H, CH2, J ¼ 8.25 Hz), 5.21 (s, 2H, CH2), 6.78–6.80 (t,
1H, ArH), 7.13–7.19 (m, 2H, ArH), 7.52–7.55 (t, 3H, ArH),
7.66–7.80 (m, 2H, ArH), 7.85–7.90 (dd, 1H, ArH); ms: m/z
374 (Mþ1). Anal. Calcd. for C22H23N5O: C, 70.76; H, 6.21;
N, 18.75; Found: C, 70.89; H, 6.09; N, 18.84.
N-(4-Bromo-phenyl)-2-[3-(2,3-dihydro-indol-1-yl)-5-phenyl[1,
2,4]triazol-1-yl]acetamide (9c). IR t (cmꢁ1): 3446 (NAH),
1
1683 (C¼¼O); H-NMR (DMSO-d6): d 3.18–3.21 (t, 2H, CH2,
J ¼ 8.22 Hz), 3.96–4.10 (t, 2H, CH2, J ¼ 8.21 Hz), 5.31 (s,
2H, CH2), 6.78–6.86 (t, 1H, ArH), 7.12–7.16 (m, 3H, ArH),
7.55–7.60 (m, 5H, ArH), 7.81–7.97 (m, 4H, ArH), 10.86 (bs,
1H, NH); ms: m/z 475 (Mþ1). Anal. Calcd. for C24H20BrN5O:
C, 60.77; H, 4.25; N, 14.76; Found: C, 60.81; H, 4.38; N,
14.59.
2-[3-(2,3-Dihydro-indol-1-yl)-5-phenyl-[1,2,4]triazol-1-yl]-1-
1
morpholin-4-yl-ethanone (8b). IR t (cmꢁ1): 1678 (C¼¼O); H-
NMR (DMSO-d6): d 3.11–3.25 (t, 2H, CH2, J ¼ 8.20 Hz),
3.45–3.68 (m, 8H, 4CH2), 3.99–4.05 (t, 2H, CH2, J ¼ 8.20
Hz), 5.22 (s, 2H, CH2), 6.77–6.80 (t, 1H, ArH), 7.11–7.19 (m,
2H, ArH), 7.54–7.57 (t, 3H, ArH), 7.68–7.85 (m, 2H, ArH),
7.87–7.94 (dd, 1H, ArH); ms: m/z 390 (Mþ1). Anal. Calcd.
for C22H23N5O2: C, 67.85; H, 5.95; N, 17.98; Found: C,
67.91; H, 5.81; N, 17.81.
2[3-(2,3-Dihydro-indol-1-yl)-5-phenyl[1,2,4]triazol-1-yl]-N-(4-
isopropyl-phenyl)acetamide (9d). IR t (cmꢁ1): 3433 (NAH),
1678 (C¼¼O); 1H-NMR (DMSO-d6): d 1.32–1.41 (d, 6H,
2CH3), 3.16–3.23 (m, 3H, CH2 and CH), 3.93–4.02 (t, 2H, CH2,
J ¼ 8.22 Hz), 5.23 (s, 2H, CH2), 6.86–7.16 (m, 4H, ArH),
7.55–7.60 (m, 5H, ArH), 7.81–7.97 (m, 4H, ArH), 10.71 (bs,
1H, NH); ms: m/z 438 (Mþ1). Anal. Calcd. for C27H27N5O: C,
74.12; H, 6.22; N, 16.01; Found: C, 74.01; H, 6.37; N, 16.17.
N-Benzyl-2-[3-(2,3-dihydro-indol-1-yl)-5-phenyl[1,2,4]triazol-
1-yl]acetamide (9e). IR t (cmꢁ1): 3411 (NAH), 1683 (C¼¼O);
1H-NMR (DMSO-d6): d 3.26–3.31 (t, 2H,CH2, J ¼ 8.20 Hz),
3.93–4.17 (t, 2H, CH2, J ¼ 8.20 Hz), 4.56–4.61 (d, 2H, CH2),
5.23 (s, 2H, CH2), 6.89–7.14 (m, 4H, ArH), 7.32–7.41 (m, 5H,
ArH), 7.55–7.60 (m, 3H, ArH), 7.73–7.80 (m, 2H, ArH), 9.81
(bs, 1H, NH); ms: m/z 410 (Mþ1). Anal. Calcd. for
C25H23N5O: C, 73.33; H, 5.66; N, 17.10; Found: C, 73.12; H,
5.79; N, 17.22.
2-[3-(2,3-Dihydro-indol-1-yl)-5-phenyl-[1,2,4]triazol-1-yl]-1-
piperidin-1-yl-ethanone (8c). IR t (cmꢁ1): 1664 (C¼¼O); 1H-
NMR (DMSO-d6): d 1.62–1.71 (m, 6H, 3CH2), 3.13–3.24 (t,
2H, CH2, J ¼ 8.20 Hz), 3.38–3.43 (m, 4H, 2CH2), 3.91–3.99
(t, 2H, CH2, J ¼ 8.20 Hz), 5.20 (s, 2H, CH2), 6.80–7.19 (m,
3H, ArH), 7.54–7.57 (t, 3H, ArH), 7.69–7.81 (m, 2H, ArH),
7.85–7.90 (m, 1H, ArH); ms: m/z 388 (Mþ1). Anal. Calcd. for
C23H25N5O: C, 71.29; H, 6.50; N, 18.07; Found: C, 71.42; H,
6.37; N, 18.23.
2[3-(2,3-Dihydro-indol-1-yl)-5-phenyl[1,2,4]triazol-1-yl]-1-(4-
phenyl-piperidin-1-yl) ethanone (8d). IR
t
(cmꢁ1): 1679
(C¼¼O); 1H-NMR (DMSO-d6): d 1.80–1.86 (m, 4H, 2CH2),
2.78–2.81 (m, 1H, CH), 3.13–3.24 (t, 2H, CH2, J ¼ 8.25 Hz),
3.40–3.44 (m, 4H, 2CH2), 3.96–4.07 (t, 2H, CH2, J ¼ 8.25
Hz), 5.21 (s, 2H, CH2), 6.80–7.19 (m, 3H, ArH), 7.54–7.57 (t,
5H, ArH), 7.69–7.81 (m, 5H, ArH), 7.85–7.90 (m, 1H, ArH);
ms: m/z 464 (Mþ1). Anal. Calcd. for C29H29N5O: C, 75.14;
H, 6.31; N, 15.11; Found: C, 75.29; H, 6.19; N, 15.23.
Acknowledgments. The authors gratefully acknowledge the
most willing help and co-operation shown by CDRI, Lucknow,
India, for spectroscopic analysis and Microcare Laboratory and
Tuberculosis Research Center, Surat, Gujarat, India, for biologi-
cal activity acquisition coordinating facility.
REFERENCES AND NOTES
2[3-(2,3-Dihydro-indol-1-yl)-5-phenyl[1,2,4]triazol-1-yl]-1-(4-
phenyl-piperazin-1-yl) ethanone (8e). IR
t
(cmꢁ1): 1668
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