Synthesis of Schiff and Mannich bases of isatin derivatives with 4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones

Article abstract of DOI:10.3390/molecules13092126

Ethyl imidate hydrochlorides 1 were prepared by passing HCl gas through solutions of substituted benzyl cyanides and absolute ethanol. Ethoxycarbonylhydrazones 2 were synthesized from the reaction of compounds 1 with ethyl carbazate. Treatment of 2 with h

Full text of DOI:10.3390/molecules13092126

Molecules 2008, 13, 2126-2135; DOI: 10.3390/molecules13092126
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molecules
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Article
Synthesis of Schiff and Mannich Bases of Isatin Derivatives with
4-Amino-4,5-Dihydro-1H-1,2,4-Triazole-5-Ones
Olcay Bekircan 1, * and Hakan Bektas 2
1
Department of Chemistry, Karadeniz Technical University, 61080 Trabzon, Turkey
2
Department of Chemistry, Giresun University, 28049 Giresun, Turkey; E-mail:
hakanbektas@ktu.edu.tr
* Author to whom correspondence should be addressed; E-mail: obekircan@gmail.com.
Received: 15 August 2008; in revised form: 28 August 2008 / Accepted: 1 September 2008 / Published:
10 September 2008
Abstract: Ethyl imidate hydrochlorides 1 were prepared by passing HCl gas through
solutions of substituted benzyl cyanides and absolute ethanol. Ethoxycarbonylhydrazones
2 were synthesized from the reaction of compounds 1 with ethyl carbazate. Treatment of 2
with hydrazine hydrate leads to the formation of substituted 4-amino-4,5-dihydro-1H-
1,2,4-triazole-5-ones 3. Isatin and 5-chloroisatin were added to 3 to form Schiff bases 4
and N-Mannich bases 5 of these compounds were synthesized by reacting with
formaldehyde and piperidine. Their chemical structures were confirmed by means of IR,
1H- and 13C-NMR data and by elemental analysis.
Keywords: Ethyl imidate hydrochloride; ethoxycarbonyl hydrazones; 4-amino-1,2,4-
triazole-5-one; isatin; Schiff bases; Mannich bases.
Introduction
Schiff bases are used as substrates in the preparation of a number of industrial and biologically
active compounds via ring closure, cycloaddition and replacement reactions [1]. Moreover, Schiff
bases derived from various heterocycles have been reported to possess cytotoxic [2], anticonvulsant
[3], antiproliferative [4], antimicrobial [5], anticancer [6], and antifungal activities [7]. Mannich bases

Molecules 2008, 13
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have gained importance due to their application in pharmaceutical chemistry. They have been
encountered with antibacterial [8], anticancer [9], analgesic and anti-inflammatory [10], anticonvulsant
[11], antimalarial [12], antiviral [13], and CNS depressant activities [14]. Isatin, chemically known as
1H-indole-2,3-dione, has become a popular topic due to its various uses. The chemistry of isatin and
its derivatives is particularly interesting because of their potential application in medicinal chemistry.
Isatins are very important compounds due to their antifungal properties [15]. Schiff and Mannich bases
of isatin derivatives are reported to show variety of biological activities like antibacterial [16],
antifungal [17], anticonvulsant [18], anti HIV [19], antidepressant [20], and antiinflammatory [21]
activities. Similarly, 1,2,4-triazoles and their derivatives play important roles in medicinal, agricultural
and industrial fields [22-25]. N-bridged heterocyclic derivatives derived from 1,2,4-triazoles show
varied biological activities such as antimicrobial [26], anticonvulsant [27], anticancer [28], analgesic
[29], anti HIV [30], and anti-inflammatory properties [31].
These biological data prompted us to synthesize new isatin derivatives bearing 1,2,4-triazole ring
and the newly synthesized compounds were characterized by elemental analysis, IR, 1H- and 13C-NMR
spectral data.
Results and Discussion
In the present study, ethyl imidate hydrochlorides 1 were prepared by passing HCl gas through
solutions of o- or p-fluorobenzyl cyanide in absolute ethanol, followed by precipitation with ether.
Ester ethoxycarbonyl hydrazones 2 were synthesized by the reactions of alkyl imidate hydrochlorides 1
with ethyl carbazate. Treatment of compounds 2 with hydrazine hydrate in water resulted in the
formation of 3-o-fluorobenzyl-4-amino-4,5-dihydro-1H-1,2,4-triazole-5-one (3a) and 3-p-
fluorobenzyl-4-amino-4,5-dihydro-1H-1,2,4-triazole-5-one (3b), respectively. The substituted 4-
amino-4,5-dihydro-1H-1,2,4-triazoles 3 were condensed with isatin derivatives in the presence of a
few drops of glacial acetic acid as a catalyst to produce Schiff bases 4 in rather good yields. Mannich
base formation can take place at both the isatin and triazole NH protons, but it is known that the isatin
1
NH proton is more active than the triazole one [32]. In addition, after the Mannich reactions, the H-
NMR spectra of compounds 5 show NH proton signals at around δ 11.00 ppm, which correspond to a
triazole NH, so we conclude that in the current study, Mannich bases were formed by condensing the
acidic imino group of isatin with formaldehyde and piperidine, instead of the triazole NH proton
(Scheme 1).
Compounds 2 showed absorption bands at around 3277, 1720, and 1659 cm-1 regions, resulting
from the NH, C=O, and C=N functions, respectively. Compounds 3 showed two peaks at around 3220
and 3165 cm-1 due to asymmetric and symmetric vibrations of the primary amino group. Compounds 4
and 5 showed two separate bands belonging to triazole indole C=O functions in the 1733-1750 and
1698-1710 cm-1 regions, and C=N stretching vibrations at around 1650 cm-1. In the IR spectra of 5,
triazole NH stretching vibrations were around 3200 cm-1. The characteristic NH protons of compounds
2 were detected around δ 9.00 ppm. The characteristic NH2 protons of compounds 3 were detected
1
around δ 5.00 ppm. The H-NMR spectra of 4 displayed the NH protons of the triazole moiety (δ
11.07-11.17 ppm) and the indole NH proton (δ 12.09-12.53) as two separate singlets. Compounds 5
displayed characteristic >N-CH2-N< signals at around δ 4.36 ppm (s, 2H, CH2).

Molecules 2008, 13
Scheme 1. Synthetic pathway for preparation of compounds 1 and 5.
2128
H NNHCO C H
2 2 5
+
2
EtOH + HCl (g)
+
CN
NH4Cl
.
C=NNHCO2C2H5
C=NH HCl
R
R
R
OC2H5
OC2H5
1
2
N2H4, H2O, reflux, 5 h
2C2H5OH
H
O
N
N
O
H
N
X
N
O
N
N
N
H
O
N
O
Schiff reaction
NH2
R
N
H
3
R
X
4
Compounds
X
R
1a
1b
2-F
4-F
H N
Mannich
reaction
2a
2b
2-F
4-F
CH2O
3a
3b
2-F
4-F
H
N
N
4a
4b
4c
4d
2-F
4-F
2-F
4-F
H
H
Cl
Cl
O
N
N
O
5a
5b
5c
5d
2-F
4-F
2-F
4-F
H
H
R
N
Cl
Cl
N
X
5
13
In the C-NMR spectra of compounds 2a-b characteristic C=O signals appeared at around δ 171.00
ppm. The triazole C-3 and triazole C-5 signals of compounds 3a-b were recorded at δ 149.38 ppm (C-
3) and δ 156.33 ppm (C-5). Characteristic triazole and indole C=O and the C=N carbon signals of
compounds 4a-d were recorded at around δ 150 ppm, δ 165 ppm, and δ 150 ppm, respectively. In the
13C-NMR spectra of compounds 5a-d characteristic >N-CH2-N< signals belonging to the Mannich
bases were observed at around δ 171.00 ppm.

Molecules 2008, 13
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Conclusions
It is known that the heterocycle compounds containing both 1,2,4-triazole and isatin rings have
diverse pharmacologic properties [15-20, 25-31, 33]. A general and convenient method was
established for the synthesis of new heterocyclic compounds bearing these two rings. Thus, two new
ester ethoxycarbonyl hydrazones 2, two new amino compounds 3, and eight new Schiff and Mannich
bases of isatin and 5-chloro isatin with substituted 4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones 4-5
were synthesized in good yields. Compounds 4-5 are expected to exhibit biological activities.
Experimental
General
Melting points were determined on a Barnstead Electrothermal melting point apparatus and are
1
uncorrected. H-NMR and 13C-NMR spectra (δ, ppm) were recorded in DMSO-d6 solutions on a
Varian-Mercury 200 MHz spectrometer using tetramethylsilane as the internal reference. The IR
spectra (υ, cm-1) were obtained with a Perkin-Elmer 1600 FTIR spectrometer in KBr pellets. Elemental
analyses were performed on a ECS 4010 Elemental Combustion System. The starting compounds,
alkyl imidate hydrochlorides 1a-b, were synthesized by previously reported routes [34, 35]. The
necessary chemicals were purchased from Merck and Fluka companies.
Synthesis of Ethoxycarbonyl Hydrazones 2a-b
The corresponding ethyl imidate hydrochlorides (1a-b, 0.01 mol) was dissolved in absolute ethanol
(50 mL) with ice-bath cooling, and ethyl carbazate (0.01 mol) dissolved in absolute ethanol (50 mL)
was then added to this solution. After stirring for 6 h at 0-5 °C, the precipitate was filtered to remove
the ammonium chloride which separated from the solution and the filtrate was evaporated at 30-35 °C
under reduced pressure. The solid residue, after drying in a dessicator, was recrystallized from
petroleum ether to yield compounds 2a-b.
Ethyl o-fluorophenylacetate ethoxycarbonyl hydrazone (2a): Yield 82%, m.p. 48-49 °C; IR υ (cm-1):
3277 (NH), 1720 (C=O), 1650 (C=N), 758 (1,2-disubstituted phenyl); 1H-NMR δ (ppm): 1.10-1.20 (m,
6H, 2CH3), 3.74 (s, 2H, benzyl CH2), 3.96-4.09 (m, 4H, 2CH2), 7.11-7.29 (m, 4H, Ar-H), 9.37 (s, 1H,
NH); 13C-NMR δ (ppm): 15.70 (O=COCH2CH3), 16.38 (OCH2CH3), 29.55 (benzyl CH2), 61.96
(O=COCH2CH3), 63.59 (OCH2CH3), Ar-C: [115.58, 124.35, 125.00, 126.32, 130.79, 156.19], 163.11
(C=N), 171.92 (C=O); Calculated (%) for C13H17FN2O3 (268.29); C: 58.20, H: 6.39, N: 10.44, found
(%); C: 58.18, H: 6.40, N: 10.45.
Ethyl p-fluorophenylacetate ethoxycarbonyl hydrazone (2b): Yield 80%, m.p. 58-59 °C; IR υ (cm-1):
3226 (NH), 1724 (C=O), 1659 (C=N), 837 (1,4-disubstituted phenyl); 1H-NMR δ (ppm): 1.11-1.18 (m,
6H, 2CH3), 3.45 (s, 2H, benzyl CH2), 4.00-4.06 (m, 4H, 2CH2), 7.07 (d, 2H, J= 8.80 Hz, Ar-H), 7.21
(d, 2H, J= 8.80 Hz, Ar-H), 9.08 (s, 1H, NH); 13C-NMR δ (ppm): 14.72 (O=COCH2CH3), 15.22

Molecules 2008, 13
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(OCH2CH3), 21.39 (benzyl CH2), 60.44 (O=COCH2CH3), 60.93 (OCH2CH3), Ar-C: [115.55 (2C),
130.85 (2C), 133.19, 160.39], 162.79 (C=N), 171.87 (C=O); Calculated (%) for C13H17FN2O3
(268.29); C: 58.20, H: 6.39, N: 10.44, found (%);C: 58.22, H: 6.40, N: 10.47.
Synthesis of Amino Compounds 3a-b
Compounds 2 (0.01 mol) were added to a solution of hydrazine hydrate (0.01 mol) in water (50
mL) and the mixture was refluxed for 5 h. On cooling, a precipitate was formed. This product was
filtered and, after drying, was recrystallized from an appropriate solvent to give compounds 3a-b.
3-o-Fluorobenzyl-4-Amino-4,5-dihydro-1H-1,2,4-triazole-5-one (3a): Recrystallized from water; Yield
87%; m.p. 158-159 °C; IR υ (cm-1): 3316 (NH), 3220-3164 (NH2), 1726 (C=O), 1652 (C=N), 764 (1,2-
disubstituted phenyl); 1H-NMR δ= 3.91 (s, 2H, benzyl CH2), 5.21 (s, 2H, NH2), 7.11-7.36 (m, 4H, Ar-
13
H), 11.44 (s, 1H, NH); C-NMR δ= 25.87 (benzyl CH2), Ar-C: [116.68, 124.65, 121.11, 130.50,
132.92, 164.60], 149.38 (triazole C-3), 156.35 (triazole C-5); Calculated (%) for C9H9FN4O (208.20);
C: 51.92, H: 4.36, N: 26.91, found (%);C: 51.82, H: 4.36, N: 26.96.
3-p-Fluorobenzyl-4-Amino-4,5-dihydro-1H-1,2,4-triazole-5-one (3b): Recrystallized from ethanol-
water (1:2); Yield 82%; m.p. 182-183 °C; IR υ (cm-1): 3318 (NH), 3223-3165 (NH2), 1729 (C=O),
1644 (C=N), 844 (1,4-disubstituted phenyl); 1H-NMR δ= 3.86 (s, 2H, benzyl CH2), 4.60 (s, 2H, NH2),
13
7.13 (d, 2H, J= 6.4 Hz, Ar-H), 7.32 (d, 2H, J= 6.4 Hz, Ar-H), 11.43 (s, 1H, NH); C-NMR δ= 31.61
(benzyl CH2), Ar-C: [116.60 (2C), 132.31 (2C), 134.01, 165.27], 149.38 (triazole C-3), 156.33
(triazole C-5); Calculated (%) for C9H9FN4O (208.20); C: 51.92, H: 4.36, N: 26.91, found (%);C:
51.90, H: 4.35, N:26.94.
Synthesis of Schiff Bases 4a-d
Equimolar quantities (0.01 mol) of isatin or 5-chloroisatin and the corresponding amino compound
3a-b were dissolved in warm ethanol (50 mL) containing glacial acetic acid (0.5 mL). The reaction
mixture was refluxed for 4 h and then kept at room temperature overnight. The resultant solid was
washed with dilute ethanol, dried and recrystallized from ethanol-water (1:2) mixture to afford
compounds 4a-d.
3-[3-(o-Fluorobenzyl)-5-oxo-4,5-dihydro-1,2,4-triazol-1-yl]-iminoisatin (4a): Yield 78%; obtained as
yellowish crystals; m.p. 278-279 °C; IR υ (cm-1): 3182, 3087 (NH), 1750 (triazole C=O), 1709 (isatin
1
C=O), 754 (1,2-disubstituted phenyl); H-NMR δ= 4.02 (s, 2H, benzyl CH2), Ar-H: [ 6.88-6.99 (m,
1H), 7.02-7.15 (m, 4H), 7.20-7.36 (m, 2H), 7.43-7.50 (m, 1H) ], 11.07 (s, 1H, triazole NH), 12.11 (s,
1H, isatin NH) ppm; 13C-NMR δ= 27.03 (benzyl CH2), Ar-C: [116.72, 123.4, 123.73, 126.07, 130.98,
159.75], indole-C: [ 112.92, 117.56, 124.12, 131.04, 133.21, 137.27 (C=N), 146.66, 165.00 (C=O)],
147.96 (triazole C-3), 150.94 (triazole C-5) ppm; Calculated (%) for C17H12FN5O2 (337.31); C: 60.53,
H: 3.59, N: 20.76, found (%);C: 60.54, H: 3.81, N: 20.64.

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3-[3-(p-Fluorobenzyl)-5-oxo-4,5-dihydro-1,2,4-triazol-1-yl]-iminoisatin (4b): Yield 82%; obtained as
yellow-orange crystals; m.p. 253-254 °C; IR υ (cm-1): 3175, 3089 (NH), 1733 (triazole C=O), 1710
(isatin C=O), 842 (1,4-disubstituted phenyl); 1H-NMR δ= 4.00 (s, 2H, benzyl CH2), Ar-H: [ 6.90-7.09
(m, 5H), 7.25-7.32 (m, 2H), 7.42-7.50 (m, 1H) ], 11.15 (s, 1H, triazole NH), 12.20 (s, 1H, isatin NH)
13
ppm; C-NMR δ= 32.51 (benzyl CH2), Ar-C: [116.61 (2C), 132.52 (2C), 132.99, 159.27], indole-C:
[112.91, 117.03, 124.11, 129.71, 132.46, 137.26 (C=N), 147.65, 165.01 (C=O)], 147.91(triazole C-3),
150.73 (triazole C-5) ppm; Calculated (%) for C17H12FN5O2 (337.31); C: 60.53, H: 3.59, N: 20.76,
found (%);C: 60.54, H: 3.58, N: 20.74.
3-[3-(o-Fluorobenzyl)-5-oxo-4,5-dihydro-1,2,4-triazol-1-yl]-imino-5-chloro-isatin (4c): Yield 85%;
obtained as orange crystals; m.p. 302-303 °C; IR υ (cm-1): 3203, 3080 (NH), 1747 (triazole C=O),
1701 (isatin C=O), 755 (1,2-disubstituted phenyl); 1H-NMR δ= 4.04 (s, 2H, benzyl CH2), Ar-H: [6.93-
6.96 (m, 1H), 7.10-7.27 (m, 2H), 7.29-7.37 (m, 2H), 7.54-7.64 (m, 2H)], 11.17 (s, 1H, triazole NH),
12.09 (s, 1H, isatin NH) ppm; 13C-NMR δ= 26.95 (benzyl CH2), Ar-C: [116.73, 123.47, 124.29,
126.07, 130.99, 159.99], indole-C: [114.56, 122.30, 128.38, 131.07, 133.11, 136.36 (C=N), 145.46,
162.87 (C=O)], 145.94 (triazole C-3), 150.46 (triazole C-5) ppm; Calculated (%) for C17H11ClFN5O2
(371.76); C: 54.92, H: 2.98, N: 18.84, found (%);C: 54.94, H: 2.98, N:18.80.
3-[3-(p-Fluorobenzyl)-5-oxo-4,5-dihydro-1,2,4-triazol-1-yl]-imino-5-chloro-isatin (4d): Yield 80%;
obtained as orange crystals; m.p. 194-195 °C; IR υ (cm-1): 3193, 3078 (NH), 1750 (triazole C=O),
1698 (isatin C=O), 841 (1,4-disubstituted phenyl); 1H-NMR δ= 3.96 (s, 2H, benzyl CH2), Ar-H: [6.93-
7.13 (m, 3H), 7.28-7.35 (m, 2H), 7.56-7.66 (m, 2H)], 11.15 (s, 1H, triazole NH), 12.53 (s, 1H, isatin
NH) ppm; 13C-NMR δ= 31.61 (benzyl CH2), Ar-C: [115.61 (2C), 132.48 (2C), 133.87, 155.32],
indole-C: [117.03, 120.92, 125.92, 128.04, 132.33, 134.09 (C=N), 139.10, 160.92 (C=O)], 149.38
(triazole C-3), 150.93 (triazole C-5) ppm; Calculated (%) for C17H11ClFN5O2 (371.76); C: 54.92, H:
2.98, N: 18.84, found (%);C: 54.96, H: 2.66, N:18.72.
Synthesis of Mannich Bases 5a-d
The corresponding Schiff bases 4a-d (0.002 mol) were dissolved in absolute ethanol (100 mL).
Then formaldehyde (37%, 0.5 mL) and piperidine (0.002 mol) were added dropwise with vigorous
stirring. After combining all reagents, the reaction mixture was stirred at room temperature for 12 h.
The mixture was cooled, the solid product was filtered and washed with petroleum ether. The solid that
separated was recrystallized from ethanol-dioxane (1:2) to yield the title compounds 5a-d.
1-Piperidinomethyl-3-[3-(o-fluorobenzyl)-5-oxo-4,5-dihydro-1,2,4-triazol-1-yl]-iminoisatin
(5a):
Yield 72%; obtained as yellow crystals; m.p. 115-116 °C; IR υ (cm-1): 3247 (NH), 2936 (aliphatic
CH2), 1745 (triazole C=O), 1709 (isatin C=O), 757 (1,2-disubstituted phenyl); 1H-NMR δ= 1.45 (br, s,
6H, piperidine 3CH2), 2.51 (br, s, 4H, piperidine 2CH2), 4.01 (s, 2H, benzyl CH2), 4.36 (s, 2H, N-CH2-
N), 6.91-7.11 (m, 3H, Ar-H), 7.26-7.30 (m, 2H, Ar-H), 7.50-7.70 (m, 3H, Ar-H), 11.16 (s, 1H, triazole
NH) ppm; 13C-NMR δ= 25.40 (piperidine C), 27.12 (piperidine 2C), 31.28 (benzyl CH2), 52.93
(piperidine 2C), 69.32 (N-CH2-N), Ar-C: [115.65, 125.40, 125.99, 127.74, 128.63, 161.00], indole-C:

Molecules 2008, 13
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[117.20, 120.98, 126.04, 129.41, 130.99, 139.07 (C=N), 146.88, 164.54 (C=O)], 147.27 (triazole C-3),
151.04 (triazole C-5) ppm; Calculated (%) for C23H23FN6O2 (434.47); C: 63.58, H: 5.34, N: 19.34,
found (%);C: 63.19, H: 5.33, N:19.54.
1-Piperidinomethyl-3-[3-(p-fluorobenzyl)-5-oxo-4,5-dihydro-1,2,4-triazol-1-yl]-iminoisatin
(5b):
Yield 65%; obtained as yellow crystals; m.p. 141-142 °C; IR υ (cm-1): 3236 (NH), 2936 (aliphatic
CH2), 1740 (triazole C=O), 1705 (isatin C=O), 856 (1,4-disubstituted phenyl); 1H-NMR δ= 1.46 (br, s,
6H, piperidine 3CH2), 2.50 (br, s, 4H, piperidine 2CH2), 4.00 (s, 2H, benzyl CH2), 4.59 (s, 2H, N-CH2-
N), 6.93-7.07 (m, 5H, Ar-H), 7.23-7.30 (m, 2H, Ar-H), 7.42-7.50 (m, 1H, Ar-H), 11.11 (s, 1H, triazole
NH) ppm; 13C-NMR δ= 25.39 (piperidine C), 27.33 (piperidine 2C), 32.40 (benzyl CH2), 52.75
(piperidine 2C), 69.37 (N-CH2-N), Ar-C: [116.62 (2C), 129.99 (2C), 132.36, 159.77], indole-C:
[117.09, 123.91, 124.45, 129.37, 132.53, 137.52 (C=N), 148.09, 164.46 (C=O)], 149.55 (triazole C-3),
154.90 (triazole C-5) ppm; Calculated (%) for C23H23FN6O2 (434.47); C: 63.58, H: 5.34, N: 19.34,
found (%);C: 63.58, H: 5.36, N:19.36.
1-Piperidinomethyl-3-[3-(o-fluorobenzyl)-5-oxo-4,5-dihydro-1,2,4-triazol-1-yl]-imino-5-chloroisatin
(5c): Yield 64%; obtained as reddish-orange crystals; m.p. 155-156 °C; IR υ (cm-1): 3224 (NH), 2935
1
(aliphatic CH2), 1748 (triazole C=O), 1708 (isatin C=O), 756 (1,2-disubstituted phenyl); H-NMR δ=
1.22 (br, s, 6H, piperidine 3CH2), 2.26 (br, s, 4H, piperidine 2CH2), 3.82 (s, 2H, benzyl CH2), 4.35 (s,
2H, N-CH2-N), 6.99-7.04 (m, 5H, Ar-H), 7.28-7.34 (m, 2H, Ar-H), 11.13 (s, 1H, triazole NH) ppm;
13C-NMR δ= 25.30 (piperidine C), 27.40 (piperidine 2C), 31.24 (benzyl CH2), 52.50 (piperidine 2C),
69.67 (N-CH2-N), Ar-C: [116.57, 124.06, 124.16, 125.98, 130.64, 159.66], indole-C: [117.09, 123.75,
130.49, 132.94, 133.00, 139.73 (C=N), 146.26, 164.55 (C=O) ], 146.33 (triazole C-3), 154.54 (triazole
C-5) ppm; Calculated (%) for C23H22ClFN6O2 (468.92); C: 58.91, H: 4.73, N: 17.92, found (%);C:
58.64, H: 4.70, N: 17.86.
1-Piperidinomethyl-3-[3-(p-fluorobenzyl)-5-oxo-4,5-dihydro-1,2,4-triazol-1-yl]-imino-5-chloroisatin
(5d): Yield 67%; obtained as reddish-orange crystals; m.p. 126-127 °C; IR υ (cm-1): 3251 (NH), 2937
1
(aliphatic CH2), 1748 (triazole C=O), 1708 (isatin C=O), 846 (1,4-disubstituted phenyl); H-NMR δ=
1.46 (br, s, 6H, piperidine 3CH2), 2.51 (br, s, 4H, piperidine 2CH2), 4.02 (s, 2H, benzyl CH2), 4.36 (s,
2H, N-CH2-N), 6.91-7.11 (m, 3H, Ar-H), 7.26-7.30 (m, 2H, Ar-H), 7.50-7.70 (m, 2H, Ar-H), 11.16 (s,
13
1H, triazole NH) ppm; C-NMR δ= 25.40 (piperidine C), 27.26 (piperidine 2C), 32.11 (benzyl CH2),
52.69 (piperidine 2C), 69.45(N-CH2-N), Ar-C: [115.59 (2C), 125.97 (2C), 132.66, 160.99], indole-C:
[117.10, 120.87, 125.40, 128.55, 132.45, 139.67 (C=N), 146.85, 164.87 (C=O)], 149.17 (triazole C-3),
151.07 (triazole C-5); Calculated (%) for C23H22ClFN6O2 (468.92); C: 58.91, H: 4.73, N: 17.92, found
(%);C: 58.95, H: 4.71, N:17.95.
Acknowledgements
This work was supported by Karadeniz Technical University Research Fund (Project No:
2004.122.002.01).

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Sample Availability: Samples of the compounds are available from authors
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