Synthesis of new bis-1,2,4-triazole derivatives

Article abstract of DOI:10.3390/11060469

A series of new 1,2/1,3-bis[o-(N-methylidenamino-3-aryl-5-phenyl-4H-1,2,4- triazole-4-yl)phenoxy]ethane/propane derivatives 4 were prepared in good yields by treatment of 4-amino-3-aryl-5-phenyl-4H-1,2,4-triazoles 2 with certain bis-aldehydes 1. Compounds

Full text of DOI:10.3390/11060469

Molecules 2006, 11, 469-477
molecules
ISSN 1420-3049
http://www.mdpi.org
Full Paper
Synthesis of New Bis-1,2,4-Triazole Derivatives
Olcay Bekircan* and Hakan Bektas
Department of Chemistry, Giresun Faculty of Arts and Sciences, Karadeniz Technical University,
28049, Giresun, Turkey; Fax (+90) 454 2164518
*Author to whom correspondence should be addressed; e-mail: obekircan@ktu.edu.tr
Received: 10 May 2006; in revised form: 20 June 2006 / Accepted: 21 June 2006 / Published: 21 June
2006
Abstract: A series of new 1,2/1,3-bis[o-(N-methylidenamino-3-aryl-5-phenyl-4H-1,2,4-
triazole-4-yl)phenoxy]ethane/propane derivatives 4 were prepared in good yields by
treatment of 4-amino-3-aryl-5-phenyl-4H-1,2,4-triazoles 2 with certain bis-aldehydes 1.
Compounds 4 were reduced with NaBH4 to afford the corresponding 1,2/1,3-bis[o-(N-
methylamino-3-aryl-5-phenyl-4H-1,2,4-triazole-4-yl)phenoxy]ethane/propane derivatives
1
13
5. All new compounds were characterized by IR, H-NMR, C-NMR and mass spectral
data.
Keywords: 4-Amino-4H-1,2,4-triazoles, bis-1,2,4-triazoles, bis-Schiff bases, bis-
aldehydes
Introduction
1,2,4-triazoles and their derivatives are found to be associated with various biological activities
such as anticonvulsant [1-2], antifungal [3-5], anticancer [6-9], antiinflammatory [10-12] and
antibacterial properties [13-16]. Several compounds (Figure 1) containing 1,2,4-triazole rings are well
known as drugs. For example, fluconazole is used as an antimicrobial drug [17], while vorozole,
letrozole and anastrozole are non-steroidal drugs used for the threatment of cancer [18] and loreclezole
is used as an anticonvulsant [19].

Molecules 2006, 11
470
Figure 1
N
N
F
N
N
N
H3C
N
N
N
N
N
CN
N
N
Cl
N
N
CH3
N
H3C
F
N
N
HO
N
Cl
Cl
NC
Cl
N
H3C
CH3
N
Cl
CN
N
Fluconazole
Vorozole
Letrozole
Anastrozole
Loreclezole
Furthermore, in recent years some Schiff base derivatives of 1,2,4-triazoles and their reduced
derivatives have been also found to possess pharmacological activities [20-26]. These biological data
prompted us to synthesize some new bis-1,2,4-triazole derivatives, and in the present study, a novel
series of bis-Schiff base derivatives resulting from the reaction of 4-amino-3-aryl-5-phenyl-4H-1,2,4-
triazoles 3 with bis-aldehydes 1 and their corresponding reduced derivatives were synthesized and
characterized by IR, 1H-NMR, 13C-NMR and mass spectral data.
Results and Discussion
The syntheses of the 1,2/1,3-bis[o-(N-methylidenamino-3-aryl-5-phenyl-4H-1,2,4-triazole-4-yl)-
phenoxy]ethane/propane derivatives 4 were accomplished according to the reactions shown in
Schemes 1-3. First, bis-aldehydes 1 were synthesized using a published method [27], as indicated in
Scheme 1. 3-Aryl-5-phenyl-4-amino-4H-1,2,4-triazoles 3 were obtained from the reaction of ethyl
benzoate benzoylhydrazone derivatives 2 with hydrazine using the published method shown in Scheme
2 [28]. Finally reactions of compounds 1 and 3 afforded the desired compounds 4 (Scheme 3). In
general, reduction of imine type compounds is possible [26, 29], but attempts to reduce imines such as
4 may also lead to a reduction of the heterocyclic ring. For this reason, the selective reduction of the
imino group present in compounds 4 without affecting the heterocyclic ring was another aim of the
study. Thus, a general and convenient method using NaBH4 as a selective reducing agent was
employed for the synthesis in good yields of the 1,2/1,3-bis[o-(N-methylamino-3-aryl,5-phenyl-4H-
1,2,4-triazole-4-yl)phenoxy]ethane/propane derivatives 5 (Scheme 3).
Scheme 1
CHO
CHO
CHO
CHO
Br
Br
Y DMF
KOH/EtOH
OH
OK
O
O
Y
1

Molecules 2006, 11
471
Scheme 2
O
N
N
NNH C
R
.
NH2NH2 H2O
R
C
+
N
OC2H5
NH2
3
2
Scheme 3
R
N
N
N
CHO
CHO
N
N
N
N
N
R
O
O
N
N
R
+
N
Y
NH2
O
O
1
3
Y
4
R
Compd
1a
Y
(CH )
NaBH4
2 2
1b
(CH )
2 3
2a,3a
2b,3b
2c,3c
4a,5a
4b,5b
4c,5c
4d,5d
4e,5e
R
N
N
H3C
Cl
N
N
N
N
H
H
R
(CH )
2 2
N
N
(CH )
2 3
(CH )
H3C
H3C
Cl
2 2
O
O
(CH )
Y
2 3
5
(CH )
2 2
(CH )
2 3
4f,5f
Cl
In the IR spectra of compounds
4
the characteristic C=N absorption bands appeared at 1597 cm-1.
1
13
The H-NMR signals for the -N=CH group were observed at δ 8.23-8.70 ppm. The C-NMR signals
for the –N=CH- group were recorded at δ 164 ppm. Reduced compounds
5 showed IR absorption
1
bands around 3245-3290 cm-1 (υNH). The H-NMR signals for the -NH-CH2- group of these
compounds were observed as a doublet or strong singlet at around δ 3.55-3.75 ppm and the proton
signals of –NH-CH2- groups were recorded as a triplet or strong singlet between δ 6.95-7.08 ppm. The
13
NH-CH2- carbon signals of compounds
5
were recorded at δ 48 ppm in the C-NMR. In addition to
this, in the 13C-NMR the triazole C3 and C5 of the bis-Schiff base derivatives
4
were observed
were
between δ 148-149 ppm and the triazole C3 and C5 signals of the reduced compounds
observed between δ 152-153 ppm.
5

Molecules 2006, 11
472
Conclusions
In this study, a convenient method was established for the synthesis in good yields of bis[o-(N-
methylidenamino-3-aryl-5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy] alkane derivatives 4a-f and bis[o-
(N-methylamino-3-aryl-5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy] alkane derivatives 5a-f. The twelve
new bis-(4H-1,2,4-triazole) derivatives synthesized in the study are expected to exhibit some
biological activities and these results will be reported in due course.
Experimental
General
Melting points were determined on a Barnstead Electrothermal melting point apparatus and are
1
13
uncorrected. H-NMR and C-NMR spectra (δ, ppm) were recorded on a Varian-Mercury 200 MHz
spectrophotometer using tetramethylsilane as the internal reference. The IR spectra (υ, cm-1) were
obtained with a Perkin-Elmer 1600 FTIR spectrometer in KBr pellets. The mass spectra were recorded
on a MicroMass Quattro LC-MS/MS (70 eV) spectrometer. The necessary chemicals were purchased
from Merck and Fluka.
Synthesis of bis-aldehydes 1a-b
Salicylaldehyde (0.01 mol) was dissolved in hot ethanolic KOH (prepared by dissolving 0.01 mol
of KOH in 100 mL of absolute ethanol) and the solvent was then removed in vacuo. The residue was
dissolved in DMF (25 mL) and the appropriate dihalide (0.005 mol) was added. The reaction mixture
was refluxed for 5 minutes, during which KCl separated out. The solvent was then removed in vacuo
and the remaining material was washed with water and crystallized from an appropriate solvent to give
compounds 1a-b.
1,2-Bis(o-formylphenoxy)ethane (1a). Yield 68%; m.p. 129-130 °C (from ethanol; lit. [27] m.p. 129
°C).
1,3-Bis(o-formylphenoxy)propane (1b). Yield 70%; m.p. 99-100 °C (from ethanol; lit. [27] m.p. 99 °C).
Synthesis of hydrazones 2a-c
A solution of an appropriate hydrazide (0.01 mol) in absolute ethanol (25 mL) was added to a
solution of iminoester hydrochloride (0.01 mol) in absolute ethanol (25 mL). The mixture was stirred
for 6 h at 0-5 °C and subsequently for 2 h at room temperature. The reaction mixture was then poured
into a beaker containing cold water (40 mL) and ice (10 g). The precipitate formed was washed with
ice-water (50 mL), dried and the product was recrystallized from from 2:1 benzene-petroleum ether to
give compounds 2a-c.

Molecules 2006, 11
473
Ethyl benzoate benzoylhydrazone (2a). Yield 79%; m.p. 120-121 °C (lit. [28] m.p. 121°C).
Ethyl p-methylbenzoate benzoylhydrazone (2b). Yield 84%; m.p. 77-78 °C (lit. [26] m.p. 78 °C).
Ethyl p-chlorobenzoate benzoylhydrazone (2c). Yield 72%; m.p. 80-81 °C; IR: 3199 (N-H), 1637
1
(C=O), 1613 (C=N), 702, 730, 759, 839 (aromatic ring); H-NMR (DMSO-d6) δ (ppm): 1.37 (t, 3H,
CH3), 4.10 (q, 2H, CH2), 7.44-7.75 (m, 5H, Ar-H), 8.13 (m, 4H, Ar-H),10.79 (s, 1H, NH).
Synthesis of amino compounds 3a-c
Compounds
2 (0.005 mol) were added to a solution of hydrazine hydrate (0.01 mol) in 1-propanol
(50 mL) and the mixture was refluxed for 24 h. On cooling, a precipitate was formed. This product
was filtered and, after drying, was washed with benzene (20 mL). The product was then recrystallized
from an appropriate solvent to give compounds 3a-c.
4-Amino-3,5-diphenyl-4H-1,2,4-triazole (3a). Yield 80%; m.p. 264-265 °C (from 1-propanol; lit. [28],
m.p. 265 °C).
4-Amino-3-p-tolyl-5-phenyl-4H-1,2,4-triazole (3b). Yield 85%; m.p. 283-284 °C (from 1-propanol; lit.
[26], m.p. 284 °C).
4-Amino-3-p-chlorophenyl-5-phenyl-4H-1,2,4-triazole (3c). Yield 68%; m.p. 284-285 °C (from ethyl
acetate; lit. [28], m.p. 285 °C).
Synthesis of bis-Schiff bases 4a-f
The corresponding bis-aldehyde (0.01 mol) was added to a solution of compound
3 (0.005 mol) in
glacial acetic acid (20 mL) and the mixture was refluxed for 16 h. After cooling, the mixture was
poured into a beaker containing ice-water (100 mL). The precipitate formed was filtered. After drying
in vacuo, the product was recrystallized from 1:2 benzene-petroleum ether to give the desired
compound.
1,2-Bis[o-(N-methylidenamino-3,5-diphenyl-4H-1,2,4-triazole-4-yl)-phenoxy]ethane (4a). Yield 70%;
m.p. 212-213 °C; IR: 1598 (C=N), 693, 770 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 3,98
(s, 4H, OCH2), Ar-H: [6,89-7,04 (m, 4H), 7,33 (m, 10H), 7,70 (m, 6H), 7.44-7.56 (m, 4H), 7,92-8,06
13
(m, 4H)], 8,23 (s, 2H, CH); C-NMR (DMSO-d6) δ (ppm): 164.44 (2C, N=CH), 149.87 (2C, triazole
C3), 149.87 (2C, triazole C5), Ar-C: [158.20 (2C), 134.75 (2C), 129.55 (2C), 128.76 (8C), 128.27 (8C),
126.88 (4C), 126.23 (4C), 121.33 (2C), 119.39 (2C), 113.48 (2C)], 66.86 (2C, OCH2); LC-MS/MS,
m/z (I, %) for C44H34N8O2 (m.w.: 706.81 g/mol): 729.26 [M+Na]+ (50), 707.25 [M+1]+ (30), 221.97
(100), 103.86 (60).

Molecules 2006, 11
474
1,3-Bis[o-(N-methylidenamino-3,5-diphenyl-4H-1,2,4-triazole-4-yl)-phenoxy]propane (4b). Yield 72%;
m.p. 189-190 °C; IR: 1595 (C=N), 694, 754 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 1,65
(q, 2H, -CH2-), 3,77 (t, 4H, OCH2), Ar-H: [6,97-7,16 (m, 6H), 7,51 (m, 12H), 7,80 (m, 8H), 7,97 (m,
2H)], 8,67 (s, 2H, CH); 13C-NMR (DMSO-d6) δ (ppm): 164.73 (2C, N=CH), 150.00 (2C, triazole C3),
150.00 (2C, triazole C5), Ar-C: [158.36 (2C), 134.93 (2C), 129.60 (2C), 128.66 (8C), 128.23 (8C),
126.95 (4C), 126.48 (4C), 120.97 (2C), 119.29 (2C), 112.93 (2C)], 64.29 (2C, OCH2), 27.75 (C, CH2);
LC-MS/MS, m/z (I, %) for C45H36N8O2 (m.w.: 720.83 g/mol): 743.18 [M+Na]+ (25), 721.23 [M+1]+
(60), 500.16 (12), 221.96 (100), 114.83 (28), 103.82 (32).
1,2-Bis[o-(N-methylidenamino-3-p-tolyl-5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]ethane (4c). Yield
72%; m.p. 271-272 °C; IR: 1597 (C=N), 696, 721, 757, 823 cm-1 (aromatic ring); 1H-NMR (DMSO-d6)
δ (ppm): 2,52 (s, 6H, CH3), 4,00 (s, 4H, OCH2), Ar-H: [7,12 (m, 8H), 7,32 (bs, 6H), 7,49-7,68 (m,
13
10H), 7,94(m, 2H)], 8,25 (s, 2H, CH); C-NMR (DMSO-d6) δ (ppm): 164.34 (2C, N=CH), 149.90
(2C, triazole C3), 149.72 (2C, triazole C5), Ar-C: [158.45 (2C), 139.30 (2C), 134.72 (2C), 129.50 (2C),
129.16 (4C), 128.56 (4C), 128.09 (4C), 128.00 (4C), 126.93 (2C), 126.31 (2C), 123.42 (2C), 121.36
(2C), 119.50 (2C), 113.56 (2C)], 66.86 (2C, OCH2), 20.73 (2C, CH3); LC-MS/MS, m/z (I, %) for
C46H38N8O2 (m.w.: 734.86 g/mol): 757.18 [M+Na]+ (100), 735.14 [M+1]+ (70), 555.17 (22), 503.05
(14), 288.99 (98), 251.00 (35), 104.75 (27).
1,3-Bis[o-(N-methylidenamino-3-p-tolyl-5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]propane
(4d).
Yield 62%; m.p. 229-230 °C; IR: 1597 (C=N), 697, 723, 765, 822 cm-1 (aromatic ring); H-NMR
(DMSO-d6) δ (ppm): 2.51 (s, 6H, CH3), 1,69 (q, 2H, -CH2-), 3,78 (t, 4H, OCH2), Ar-H: [6.98-7.13 (m,
1
13
4H), 7.24 (m, 4H), 7.49 (m, 10H), 7.78 (m, 3H), 7.82 (m, 3H), 7.98 (m, 2H)], 8.69 (s, 2H,CH); C-
NMR (DMSO-d6) δ (ppm): 164.65 (2C, N=CH), 150.04 (2C, triazole C3), 149.87 (2C, triazole C5), Ar-
C: [158.33 (2C), 139.25 (2C), 134.90 (2C), 129.52 (2C), 129.20 (4C), 128.62 (4C), 128.17 (4C),
128.11 (4C), 126.96 (2C), 126.54 (2C), 123.61 (2C), 120.94 (2C), 119.31 (2C), 112.88 (2C)], 64.26
(2C, OCH2), 27.72 (C, CH2), 20.68 (2C, CH3); LC-MS/MS, m/z (I, %) for C47H40N8O2 (m.w.: 748.89
g/mol): 771.20 [M+Na]+ (55), 749.24 [M+1]+ (40), 475.31 (42), 235.88 (15), 155.88 (26), 148.83 (32),
117.86(100).
1,2-Bis[o-(N-methylidenamino-3-p-chlorophenyl-5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]
ethane
(
4e). Yield 75%; m.p. 213-214 °C; IR υ (cm-1): 1598 (C=N), 695, 723, 758, 834 cm-1 (aromatic ring);
1H-NMR (DMSO-d6) δ (ppm): 4,02 (s, 4H, OCH2), Ar-H: [7,01-7,10 (m, 3H), 7,30-7,37 (m, 6H),
7,42-7,55 (m, 10H), 7,64-7,73 (m, 3H), 7,81 (d, 3H), 7,94 (m, 1H)], 8,30(s, 2H, CH); 13C-NMR
(DMSO-d6) δ (ppm): 164.68 (2C, N=CH), 149.85 (2C, triazole C3), 149.10 (2C, triazole C5), Ar-C:
[158.47(2C), 134.85 (2C), 134.46 (2C), 129.74 (4C), 129.56 (4C), 128.74 (4C), 128.57 (4C), 128.17
(2C), 127.01 (2C), 126.07 (2C), 125.11 (2C), 121.36 (2C), 119.35 (2C), 113.51 (2C)], 66.87 (2C,
OCH2); LC-MS/MS, m/z (I, %) for C44H32Cl2N8O2 (m.w.: 775.70 g/mol): 798.11 [M+Na]+ (20),
775.13 [M]+ (18), 255.93 (10), 166.84 (15), 164.84 (43), 134.83(100).
1,3-Bis[o-(N-methylidenamino-3-p-chlorophenyl-5-phenyl-4H-1,2,4-triazol-4-yl)-phenoxy]propane
(
4f). Yield 77%; m.p. 189-190 °C; IR: 1597 (C=N), 690, 723, 757, 833 cm-1 (aromatic ring); 1H-NMR
(DMSO-d6) δ (ppm): 1,69 (bs, 2H, -CH3-), 3,80 (bs, 4H, OCH2), Ar-H: [6,99-7,14 (m, 6H), 7,44-7,56

Molecules 2006, 11
475
(m, 12H), 7,83-7,99 (m, 8H)], 8,70 (s, 2H, CH); 13C-NMR (DMSO-d6) δ (ppm): 163.88 (2C, N=CH),
149.08 (2C, triazol C3), 148.21 (2C, triazol C5), Ar-C: [157.41 (2C), 133.99 (2C), 133.47 (2C), 128.89
(4C), 127.78 (4C), 127.66 (4C), 127.24 (4C), 126.03 (2C), 125.35 (2C), 124.35 (2C), 124.23 (2C),
119.99 (2C), 118.25 (2C), 111.91 (2C)], 63.31 (2C, OCH2), 26.79 (CH2); LC-MS/MS, m/z (I, %) for
C45H34Cl2N8O2 (m.w.: 789.72 g/mol): 811.19 [M+Na]+ (60), 789.31 [M]+ (56), 559.18 (13), 256.03
(53), 134.93 (84), 104.86 (100).
Synthesis of reduced rompounds 5a-f
The corresponding compound 4a-f (0.005 mol) was dissolved in dried methanol (50 mL) and
NaBH4 (0.01 mol) was added in small portions to this solution. The mixture was refluxed for 20 min
and then allowed to cool. After evaporation at 30-35 °C under reduced pressure, the solid residue was
washed with cold water. After drying in vacuo, the solid product was recrystallized from an
appropriate solvent (1:1 ethanol-water, unless otherwise noted) to afford the desired compound.
1,2-Bis[o-(N-methylamino-3,5-diphenyl-4H-1,2,4-triazole-4-yl)-phenoxy]ethane (5a). Yield 85%; m.p.
242-243 °C; IR: 3245 (NH), 1600 (C=N), 692, 720, 756 cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ
(ppm): 3.63 (d, 4H, -NH-CH2), 3.86 (s, 4H, OCH2), 6.95 (t, 2H, NH), Ar-H: [6.70 (d, 6H), 7.09-7.16
13
(m, 2H), 7.42 (m, 12H), 7.85-7.90 (m, 8H); C-NMR (DMSO-d6) δ (ppm): 153.57 (2C, triazole C3),
153.57 (2C, triazole C5), Ar-C: [156.20 (2C), 130.02 (2C), 129.47 (4C), 129.05 (2C), 128.29 (8C),
127.68 (8C), 126.97 (4C), 123.41 (2C), 120.11 (2C), 111.47 (2C)], 65.96 (2C, OCH2), 48.78 (2C,CH2-
NH); LC-MS/MS, m/z (I, %) for C44H38N8O2 (m.w.: 710.84 g/mol): 733.22 [M+Na]+ (15), 711.22
[M+1]+ (35), 490.18 (8), 269.02 (11), 221.96 (28), 147.85 (100).
1,3-Bis[o-(N-methylamino-3,5-diphenyl-4H-1,2,4-triazole-4-yl)-phenoxy]propane (5b). Yield 74%;
m.p. 216-217 °C; IR: 3253 (NH), 1601 (C=N), 694, 717, 745 cm-1 (aromatic ring); 1H-NMR (DMSO-
d6) δ (ppm): 1.88 (q, 2H, -CH2-), 3.55 ( bs, 4H, OCH2 + 4H, -NH-CH2 ), 7.04 ( m, 2H, 2NH + 2H, Ar-
13
H ), Ar-H: [6.66 (m, 4H), 7.47 (bs, 14H), 7.94 (bs, 8H); C-NMR (DMSO-d6) δ (ppm): 153.65 (2C,
triazole C3), 153.65 (2C, triazole C5), Ar-C: [156.24 (2C), 129.96 (2C), 129.54 (4C), 129.07 (2C),
128,34 (8C), 127.76 (8C), 127.07 (4C), 123,31 (2C), 119.81 (2C), 111.09 (2C)], 63.90 (2C, OCH2),
48.87 (2C, CH2-NH), 28.17 (CH2); LC-MS/MS, m/z (I, %) for C45H40N8O2 (m.w.: 724.87 g/mol):
747.26 [M+Na]+ (95), 725.28 [M+1]+ (100), 272.98 (52), 234.97 (100), 104.86 (16).
1,2-Bis[o-(N-methylamino-3-p-tolyl,5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]ethane (5c). Yield 79%;
1
m.p. 192-193 °C; IR: 3261(NH), 1601(C=N), 690, 729, 748, 820 cm-1 (aromatic ring); H-NMR
(DMSO-d6) δ (ppm): 2.29 (s, 6H, CH3), 3.64 (d, 4H, -NH-CH2-), 3.88 (s, 4H, OCH2), 6.92 (t, 2H, NH),
Ar-H: [6.72 (d, 4H), 7.22 (d, 4H), 7.37-7.43 (m, 10H), 7.78-7.87 (m, 8H); 13C-NMR (DMSO-d6) δ
(ppm): 153.51 (2C, triazole C3), 153.47 (2C, triazole C5), Ar-C: [156.23 (2C), 139.15 (2C), 130.03
(2C), 129.40 (2C), 129.04 (2C), 128.92 (4C), 128.23 (4C), 127.71 (4C), 127.53 (4C), 127.05 (2C),
124.20 (2C), 123.48 (2C), 120.14 (2C), 111.48 (2C)], 65.98 (2C, OCH2), 48.76 (2C, CH2-NH), 20.80
(2C, CH3); LC-MS/MS, m/z (I, %) for C46H42N8O2 (m.w.: 738.65 g/mol): 740.30 [M+2]+ (55), 739.23
[M+1]+ (100), 414.95 (12), 370.13 (15), 216.93 (16), 156.88 (38).

Molecules 2006, 11
476
1,3-Bis[o-(N-methylamino-3-p-tolyl,5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]propane
(
5d). Yield
78%; m.p. 181-182 °C; IR: 3249 (NH), 1601 (C=N), 692, 729, 749, 823 cm-1 (aromatic ring); 1H-NMR
(DMSO-d6) δ (ppm): 2.33 (s, 6H, CH3), 1.89 (q, 2H, -CH2-), 3.76 ( bs, 4H, OCH2 + 4H, -NH-CH2),
7.04 (t, 2H, NH), Ar-H: [6.63-6.74 (m, 6H), 7.11-7.16 (m, 2H), 7.26-7.37 (m, 5H), 7.45 (m, 5H), 7.82-
7.93 (m, 8H)]; 13C-NMR (DMSO-d6) δ (ppm): 153.57 (2C, triazole C3), 153.48 (2C, triazole C5), Ar-
C: [156.25 (2C), 139.22 (2C), 129.97 (2C), 129.44 (2C), 129.05 (2C), 128.94 (4C), 128.28 (4C),
127.77 (4C), 127.62 (4C), 127.12 (2C), 124.29 (2C), 123.37 (2C), 119.82 (2C), 111.06 (2C)], 63.93
(2C, OCH2), 28.19 (C, CH2), 48.82 (2C, CH2-NH), 20.83 (2C, CH3); LC-MS/MS, m/z (I, %) for
C47H44N8O2 (m.w.: 752.85 g/mol): 775.23 [M+Na]+ (65), 753.33 [M+1]+ (100), 235.94 (5), 105.02 (5).
1,2-Bis[o-(N-methylamino-3-p-chlorophenyl,5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]ethane
(5e).
Yield 69%; m.p. 219-220 °C (from 1:2 ethanol-water); IR: 3249 (NH), 1601 (C=N), 689, 729, 749,
1
833 cm-1 (aromatic ring); H-NMR (DMSO-d6) δ (ppm): 3.63 (bs, 4H, -NH-CH2-), 3.89 (bs, 4H, -
13
OCH2), 6.99 (bs, 2H, NH), Ar-H: [6.71 (bs ,6H), 7.14 (bs, 2H), 7.45 (bs, 10H), 7.88 (m, 8H); C-
NMR (DMSO-d6) δ (ppm): 153.81 (2C, triazole C3), 152.65 (2C, triazole C5), Ar-C: [156.21 (2C),
134.27 (2C), 130.20 (2C), 129.65 (2C), 129.35 (4C), 129.17 (4C), 128.41 (4C), 128.30 (4C), 127.66
(2C), 126.79 (2C), 125.69 (2C), 123.29 (2C), 120.14 (2C), 111.40 (2C)], 65.95 (2C, OCH2), 48.79 (2C,
CH2-NH); LC-MS/MS, m/z (I, %) for C44H36Cl2N8O2 (m.w.: 778.24 g/mol): 801.12 [M+Na]+(48),
779.15 [M+1]+ (18), 747.26 (21), 725.22 (20), 214.93 (13), 164.84 (43), 134.83 (100).
1,3-Bis[o-(N-methylamino-3-p-chlorophenyl,5-phenyl-4H-1,2,4-triazole-4-yl)-phenoxy]propane
(5f).
Yield 72%; m.p. 126-127 °C (from 1:2 ethanol-water); IR: 3291(NH), 1601(C=N), 690, 734, 754, 835
cm-1 (aromatic ring); 1H-NMR (DMSO-d6) δ (ppm): 1.89 (bs, 2H, -CH2-), 3.75 ( bs, 4H, OCH2 + 4H, -
13
NH-CH2 ), 7.08 ( m,2H, 2NH + 2H, Ar-H ), Ar-H: [6.65(m, 6H), 7.50 (m, 10H), 7.93 (m, 8H)]; C-
NMR (DMSO-d6) δ (ppm): 153.81 (2C, triazole C3), 152.78 (2C, triazole C5), Ar-C: [156.21 (2C),
134.29 (2C), 130.11 (2C), 129.68 (2C), 129.44 (4C), 129.15 (2C), 128.45 (4C), 128.30 (4C), 127.69
(4C), 126.90 (2C), 125.78 (2C), 123.17 (2C), 119.78 (2C), 110.94 (2C)], 64.20 (2C, OCH2), 48.82 (2C,
CH2-NH), 28.19 (C, CH2); LC-MS/MS, m/z (I, %) for C45H38Cl2N8O2 (m.w.: 792.25 g/mol): 815.26
[M+Na]+ (100), 793.25 [M+1]+ (45), 563.18 (28), 283.10 (12), 34.93 (15).
Referances
1.
2.
Kane, J.M.; Baron, B.M.; Dudley, M.W.; Sorensen, S.M.; Staeger, M.A.; Miller, F.P. J. Med.
Chem. 1990, 33, 2772-2777.
Küçükgüzel, İ.; Küçükgüzel, Ş.G.; Rollas, S.; Ötük-Sanış, G.; Özdemir, O.; Bayrak, İ.; Altuğ, T.;
Stables, J.P. Il Farmaco 2004, 59, 893-901.
3.
4.
5.
Rollas, S.; Kalyoncuoglu, N. ; Sur-Altiner, D.; Yegenoglu, Y. Pharmazie 1993, 48, 308-309.
Chollet, J.F.; Bonnemain, J.L.; Miginiac, L.; Rohr, O. J. Pestic. Sci. 1990, 29, 427-435.
Murabayashi, A.; Masuko, M.; Niikawa, M.; Shirane, N.; Futura, T.; Hayashi, Y.; Makisumi, Y.
J. Pestic. Sci. 1991, 16, 419-427.
6.
7.
8.
Gilbert, B.E.; Knight, V. Antimicrob. Agents Chemother. 1986, 30, 201-205.
Holla, B.S.; Veerendra, B.; Shivananda, M.K.; Poojary, B. Eur. J. Med. Chem. 2003, 38, 759-767.
Turan-Zitouni, G.; Sıvacı, M.F.; Kılıç, S.; Erol, K. Eur. J. Med. Chem. 2001, 36, 685-689.

Molecules 2006, 11
9. Bekircan, O.; Kucuk, M.; Kahveci, B; Kolaylı, S. Arch. Pharm. 2005, 338, 365-372.
477
10. Wade, P.C.; Vogt, B.R.; Kissick, T.P.; Simpkins, L.M.; Palmer, D.M.; Millonig, R.C. J. Med.
Chem. 1982, 25, 331-333.
11. Gruta, A.K.; Bhargava, K.P. Pharmazie 1978, 33, 430-434.
12. Modzelewska, B.; Kalabun, J. Pharmazie 1999, 54, 503-505.
13. Malbec, F.; Milcent, R.; Vicart, P.; Bure, A.M. J. Heterocycl. Chem. 1984, 21, 1769-1774.
14. Milcent, R.; Vicart, P. ; Bure, A.M., Eur. J. Med. Chim. 1983, 18, 215-220.
15. Gülerman, N.; Rollas, S.; Kiraz, M.; Ekinci, A.C.; Vidin A. Il Farmaco 1997, 52, 691-695.
16. Ikizler, A.A.; Johansson, C.B.; Bekircan, O.; Çelik, C. Acta Polon Pharm-Drug Res. 1999, 56,
283-288.
17. Shujuan, S.; Hongxiang, L.; Gao, Y.; Fan, P.; Ma, B.; Ge, W.; Wang, X. J. Pharm. Miomed. Anal.
2004, 34, 1117-1124.
18. Clemons, M.; Coleman, R.E.; Verma, S. Cancer Treat. Rev. 2004, 30, 325-332.
19. Johnston, G.A.R. Curr. Top.Med. Chem. 2002, 2, 903-913.
20. Bhat, A.R.; Bhat, G.V.; Shenoy, G.G. J. Pharm. Pharmacol. 2001, 53, 267-272.
21. Demirbas, N.; Ugurluoglu, R.; Demirbas, A. Bioorg. Med. Chem. 2002, 10, 3717-3723.
22. Kahveci, B.; Bekircan, O.; Serdar, M.; Ikizler, A.A. Indian J. Chem. Sec-B. 2003, 42B, 1527-
1530.
23. Bhat, K.I.; Kumar, V.; Kalluraya, B. Asian J. Chem. 2004, 16, 96-102.
24. Bekircan, O.; Gümrükçüoğlu, N. Indian J. Chem. Sec-B. 2005, 44B, 2107-2114.
25. Kahveci B., Bekircan, O.; Karaoglu, S.A., Indian J. Chem. Sec-B. 2005, 44B, 2614-2617.
26. Bekircan, O.; Kahveci, B.; Kucuk, M. Turk J. Chem. 2006, 30, 29-40.
27. Ibrahim, Y.A.; Elwahy, A.H.M.; Elkareish, G.M.M. J. Chem. Res. (S) 1994, 11, 2321-2331.
28. Milcent, R.; Redeuilh, C. J. Heterocycl. Chem. 1977, 14, 53-58.
29. Katritzky, A.R.; Laurenzo, K.S. J. Org. Chem. 1988, 53, 3978-3982.
Sample availability: Contact the authors.
© 2006 by MDPI (http://www.mdpi.org). Reproduction is permitted for noncommercial purposes.