Synthesis and characterisations of some new 2, 4-dihydro-[1, 2, 4]-triazol-3-one derivatives and X-ray crystal structures of 4-(3-phenylallylideneamino)-5- thiophen-2-yl-methyl-2, 4-dihydro-[1, 2, 4]triazol-3-one

Article abstract of DOI:10.3906/kim-0905-1

Compounds 2, were synthesised via the reaction of 4-amino-5-thiophen-2-yl- methyl-2, 4-dihydro-[1, 2, 4]- triazol-3-one (1) with aldehydes. Compounds 3 and 4 were obtained from compounds 2 with bromo acetophenone and ethyl bromoacetate, respectively. The synthesis of compounds 2, 3, and 4 and crystal structure of compound 2a are being reported. The molecular structures were identified by IR, ¹H-NMR, ¹³ C-NMR, MS, and elemental analyses. Compound 2a crystallises in the monoclinic P 2₁ /n space group, with a = 6.565(5) A, b = 18.278(5) A, c = 13.8166(18) A, β= 96.227(5) ° , V = 1553.6(14) A³ , Z = 4. The newly compounds synthesised were screened for their antibacterial and antifungal properties. Among the compounds, 4d showed antimicrobial activity against Candida albicans ATCC 60193 and Candida tropicalis ATCC 13803. TUeBITAK.

Full text of DOI:10.3906/kim-0905-1

Turk J Chem
34 (2010) , 771 – 780.
¨
˙
c
ꢀ TUBITAK
doi:10.3906/kim-0905-1
Synthesis and characterisations of some new
2,4-dihydro-[1,2,4]-triazol-3-one derivatives and X-ray
crystal structures of 4-(3-phenylallylideneamino)-5-
thiophen-2-yl-methyl-2,4-dihydro-[1,2,4]triazol-3-one
∗
1
2
¨
Kemal SANCAK , Yasemin UNVER , Canan KAZAK ,
1
2
¨ ˘
¨
Esra DUGDU , Burcu ARSLAN
1Department of Chemistry, Faculty of Arts and Sciences, Karadeniz Technical University,
61080-Trabzon-TURKEY
e-mail: ksancak@ktu.edu.tr
2Department of Physics, Faculty of Arts and Sciences, Ondokuz Mayıs University,
55139 Samsun-TURKEY
Received 04.05.2009
Compounds 2 were synthesised via the reaction of 4-amino-5-thiophen-2-yl-methyl-2,4-dihydro-[1,2,4]-
triazol-3-one (1) with aldehydes. Compounds 3 and 4 were obtained from compounds 2 with bromo
acetophenone and ethyl bromoacetate, respectively. The synthesis of compounds 2, 3, and 4 and crystal
structure of compound 2a are being reported. The molecular structures were identified by IR, 1 H-NMR,
13 C-NMR, MS, and elemental analyses. Compound 2a crystallises in the monoclinic P 21 /n space group,
◦
3
˚
˚
˚
˚
with a = 6.565(5) A, b = 18.278(5) A, c = 13.8166(18) A, β = 96.227(5) , V = 1553.6(14) A , Z = 4.
The newly compounds synthesised were screened for their antibacterial and antifungal properties. Among
the compounds, 4d showed antimicrobial activity against Candida albicans ATCC 60193 and Candida
tropicalis ATCC 13803.
Key Words: 1,2,4-Triazole, aldehydes, ethyl bromoacetate, bromo acetophenone, X-ray crystallography,
antimicrobial activity
∗Corresponding author
771

Synthesis and characterisations of some new..., K. SANCAK, et al.,
Introduction
The 1,2,4-triazole compounds possess important pharmacology activities such as antifungal and antiviral activ-
ities. Examples of such compounds bearing 1,2,4-triazole residues are fluconazole, the powerful azole antifungal
agent, as well as the potent antiviral N-nucleoside ribavirin.1,2 The 1,2,4-triazole nucleus is associated with
diverse pharmacological activities such as antibacterial, hypoglycemic, antihypertensive, analgesic, and specific
magnetic properties.3,4 In recent years, there has been an increasing interest in the chemistry of thiophenes
because of their biological significance. Many of them have been widely investigated for therapeutic uses, es-
pecially as antifungal, antibacterial, anti-inflammatory, anticonvulsant, anti-asthmatic, and analgesic agents.
They also were known to show anti-HIV, antiproliferative, germicidal, and D2 dopaminergic activities.5 The
azole moiety is an important and frequent insecticidal, agrochemical structural feature of many biologically ac-
tive compounds such as cytochrome P450 enzyme inhibitors1 and peptide analogue inhibitors. Recently, much
attention has been focused on 1H-1,2,4-triazole derivatives for their broad-spectrum activities, such as fungici-
dal, herbicidal, anticonvulsant, and plant growth regulatory activities.6 It was reported that compounds having
triazole moieties such as vorozole, anastrozole, and letrozole appear to be very effective aromatase inhibitors
very useful for preventing breast cancer.7−9
There are antimicrobial agents having different structures that are frequently used in the treatment
of microbial infections. However, there is an increasing resistance to these drugs. Moreover, some of azole
derivatives used as common antibiotics such as Amphotericin B have a toxic effect on humans as well as their
antimicrobial effects.10 To overcome the development of drug resistance, it is crucial to synthesise a new class
of antimicrobials possessing different chemical properties from those used commonly.
In view of these facts, the aim of this present study was to obtain new triazole derivatives (Scheme).
Experimental
Melting points were determined on a Gallenkamp melting point apparatus and are uncorrected. 1 H-NMR and
13 C-NMR spectra were recorded on a Varian-Mercury 200 MHz spectrometer. The IR spectra were measured
as potassium bromide pellets using a Perkin-Elmer 1600 series FTIR spectrometer. Micromass was determined
on a Micromass Quatro LC/ULTIMALC-MS spectrometer. Elemental analyses were carried out on a C,H, N-O
rapid elemental analyser Hewlett-Packard 185 for C, H, and N and the results are within 0.4% of the theoretical
values. All the chemicals were obtained from Fluka Chemie AG Buchs (Switzerland). Compounds 1 and 2c-f
were synthesised using the published method.11,12 Compound 3a is published in Acta Crystallographica.13
General method for the synthesis of 4-[arylidene-amino]-5-thiophen-2-yl-methyl-2,4-dihydro-
[1,2,4]triazol-3-ones (2a-b): The corresponding 4-amino-5-thiophen-2-yl-methyl-2,4-dihydro-[1,2,4]-triazol-
3-one (1) (0.01 mol) and aldehydes (0.01 mol) were heated at 160 ◦ C in an oil bath for 2 h. After cooling it
to room temperature, a solid appeared and it was crystallised from appropriate solvent to afford the desired
compound.
Synthesis of 4-(3-phenylallylideneamino)-5-thiophen-2-yl-methyl-2,4-dihydro-[1,2,4]-triazol-
3-one (2a). Recrystallised from ethanol/water (yield: 82.58%). Mp 178-179 ˚C. IR (KBr) cm−1 : 3164 (νNH ),
1696 (νC=O), 1626 (νC=N ); 1 H-NMR (DMSO-d6)δ 4.20 (s, 2H, thiophen-CH2), 6.94-7.11 (m, 2H, arH), 7.31-
772

Synthesis and characterisations of some new..., K. SANCAK, et al.,
7.43 (m, 5H, arH+vinylH), 7.66-7.71 (m, 3H, arH+vinylH), 9.49 (d, 1H, N=CH), 12.01 (s, 1H, NH); 13 C-NMR
(DMSO-d6)δ 25.60 (thiophen-CH2), thiophen-C: [125.20 (CH), 126.59 (CH), 126.78 (CH), 137.06 (C), ar-C:
[124.70 (CH), 127.53 (CH), 128.78 (CH), 135.17 (C), 129.53 (CH vinyl), 143.52 (CH vinyl)], 145.20 (triazole-
C-3), 150.96 (N=CH), 153.96 (triazole-C-5). Analysis (% calculation/ found): C: 61.92/61.97, H: 4.55/4.58, N:
18.05/18.12. MS: m/z 310.99 (M+1)+ .
N
NH
N
NH2
O
S
1
O
R C H
O
N
NH
O
CH2
N
N
OCH2CH3
O
N
N
CH2
Br
OCH2CH3
N
N
O
S
S
HC
HC
R
(a-f)
R
2
4
(a-f)
O
Br CH2
O
N
N
CH2
N
N
O
S
CH
R
(a-b)
3
Scheme. Synthesis of compounds 2, 3, and 4.
a
b
c
d
e
f
2, 3, 4
R
Cl
HC CH
N
NO2
O
S
S
Cl
4-[(Pyridin-4-ylmethylene)-amino]-5-thiophen-2-yl-methyl-2,4-dihydro-[1,2,4]triazol-3-one
(2b). Recrystallised from ethanol (yield: 81.05%). Mp 214-215 ◦ C. IR (KBr) cm−1 : 3192 (νNH ), 1718
(νC=O), 1607 (νC=N ); 1 H-NMR (DMSO-d6)δ (ppm) 4.34 (s, 2H, thiophen-CH2), 6.95-7.07 (m, 2H, arH),
773

Synthesis and characterisations of some new..., K. SANCAK, et al.,
7.41-7.42 (m, 1H, arH), 7.84 (d, 2H, arH, J=5 Hz), 8.76 (d, 2H, arH, J=7.6 Hz), 9.81 (s, 1H, N=CH), 12.18
(s, 1H, NH); 13 C-NMR (DMSO-d6)δ (ppm) 25.46 (thiophen-CH2), thiophen-C: [125.44 (CH), 126.80 (CH),
127.03 (CH), 137.21 (C)], ar-C: [121.51 (CH), 140.70 (C), 150.50 (CH)], 145.72 (triazole-C-3), 150.75 (N=CH),
150.94 (triazole-C-5). Analysis (% calculation/ found): C: 54.72/54.64, H: 3.89/3.82, N: 24.25/24.31. MS: m/z
285.93 (M+1)+ .
General method for the synthesis of 2-(2-oxo-2-phenyl-ethyl)-4-[arylidene-amino]-5-thiophen-
2-yl-methyl-2,4-dihydro-[1,2,4] triazol-3-one (3): The corresponding 4-[arylidene-amino]-5-thiophen-2-yl-
methyl-2,4-dihydro-[1,2,4]triazol-3-ones (2) (0.01 mol) was refluxed with an equivalent amount of natrium in
absolute ethanol for 1 h. Then bromoacetophenon (0.01 mol) was added and refluxed for an additional 5 h. The
precipitate was filtered off, washed with H2 O, and recrystallised from appropriate solvent to afford the desired
compound.
Synthesis of 2-(2-oxo-2-phenyl-ethyl)-4-[(pyridin-4-ylmethylene)-amino]-5-thiophen-2-yl-
methyl-2,4-dihydro-[1,2,4]triazol-3-one (3b). Recrystallised from ethanol/water (1:2) (yield 66.00%). Mp
130-131 ◦ C. IR (KBr) cm−1 : 1696 (νacetophenonC=O), 1719 (νtriazoleC=O), 1589 (νC=N ); 1 H-NMR (DMSO-
d6)δ 4.41 (s, 2H, thiophen-CH2), 5.52 (s, 2H, NCH2), 6.99-7.10 (m, 2H, arH), 7.43-7.47 (m,1H, arH), 7.58-7.60
(m, 3H, arH), 7.85-7.88 (m, 2H, arH), 9.79 (s, 1H, N=CH); 13 C-NMR (DMSO-d6)δ 25.52 (thiophen-CH2),
52.01 (NCH2), thiophen-C: [125.65 (CH), 126.98 (CH), 127.12 (CH), 136.89 (C)], ar-C: [121.69 (CH), 140.51
(C), 151.41 (CH)], benzene-C: [128.55 (CH), 129.08 (CH), 134.04 (C), 134.36 (CH)], 145.08 (triazole-C-3), 149.99
(N=CH), 150.56 (triazole-C-5), 192.64 (acetophenon-C=O). Analysis (% calculation/ found): C: 62.52/62.58,
H: 4.25/4.20, N: 17.36/17.41. MS: m/z 404.06 (M+1)+ .
General method for the synthesis of {3-oxo–4-[arylidene-amino]-5-(thiophen-2-ylmethyl)-
2,4-dihydro-1,2,4-triazol-2-yl}-acetic acid ethyl ester (4): The corresponding 4-[arylidene-amino]-5-
thiophen-2-yl-methyl-2,4-dihydro-[1,2,4]triazol-3-ones (2) (0.01 mol) were refluxed with an equivalent amount
of natrium in absolute ethanol for 1 h. Then ethyl bromoacetate (0.01 mol) was added and refluxed for an
additional 5 h. The precipitate was filtered off, washed with H2 O, and recrystallised from appropriate solvent
to afford the desired compound.
Synthesis of {3-oxo–4-[(3-phenylallylidene)amino]-5-(thiophen-2-ylmethyl)-2,4-dihydro-1,2,4-
triazol-2-yl}-acetic acid ethyl ester (4a). Recrystallised from ethanol/water (1:2) (yield 81.57%) to afford
the desired compound. Mp 116-117 ◦ C. IR (KBr) cm−1 : 1744 (νester−C=O), 1710 (νtriazole−C=O), 1594
(νC=N ), 1215 (νC−O); 1 H-NMR (DMSO-d6)δ 1.12 (t, 3H, OCH2 CH3 , J= 7.0 Hz), 4.13 (q, 2H, OCH2 CH3 ,
J= 7.0 Hz), 4.30 (s, 2H, thiophen-CH2), 4.61 (s, 2H, NCH2), 6.90-7.12 (m, 2H, arH), 7.35-7.55 (m, 5H,
arH+vinylH), 7.60-7.69 (m, 3H, arH+vinylH), 9.63 (s, 1H, N=CH); 13 C-NMR (DMSO-d6)δ (ppm) 13.96
(OCH2 CH3), 25.53 (thiophen-CH2), 46.48 (NCH2), 61.34 (OCH2), thiophen-C: [125.32 (CH), 126.65 (CH),
127.10 (CH), 136.98 (C)], ar-C: [123.78 (CH), 126.59 (CH), 128.44 (CH),133.17 (C), 129.27 (vinyl CH), 144.24
(vinyl CH)], 149.62 (N=CH), 144.97 (triazole-C-3), 154.15 (triazole-C-5), 167.60 (ester-C=O). Analysis (%
calculation/ found): C: 60.59/60.51, H: 5.08/5.13, N: 14.13/14.17. MS: m/z 381.05 (M+1)+ .
{3-Oxo-4-[(pyridin-4-ylmethylene)-amino]-5-thiophen-2-ylmethyl-2,4-dihydro-[1,2,4] triazole-
2-yl}-acetic acid ethyl ester (4b). Recrystallised from ethanol/water (1:2) (yield: 82.86%). Mp 125-126
◦ C. IR (KBr) (ν , cm−1): 1756 (νester−C=O), 1704 (νtriazole−C=O), 1613 (νC=N ), 1209 (νC−O); 1 H-NMR
(DMSO-d6) δ (ppm) 1.20 (t, 3H, OCH2 CH3 , J= 7.4 Hz), 4.16 (q, 2H, OCH2 CH3 , J= 7.4 Hz), 4.36 (s, 2H,
774

Synthesis and characterisations of some new..., K. SANCAK, et al.,
thiophen-CH2), 4.66 (s, 2H, NCH2), 6.94-7.59 (m, 3H, arH), 7.84 (d, 2H, arH, J=5 Hz), 8.76 (d, 2H, arH, J=5
Hz), 9.81 (s, 1H, N=CH); 13 C-NMR (DMSO-d6)δ (ppm) 13.87 (OCH2 CH3), 25.26 (thiophen-CH2), 46.30
(NCH2), 61.22 (OCH2 CH3), thiophen-C: [125.71 (CH), 126.80 (C), 127.03 (CH), 137.21 (C)], ar-C: [121.51
(CH), 140.70 (C), 152.50 (C)], 146.86 (N=CH), 144.86 (triazole-C-3), 153.33 (triazole-C-5), 167.46 (ester-C=O).
Analysis (% calculation/ found): C: 54.97/54.91, H: 4.61/4.66, N: 18.86/18.81. MS: m/z 372.22 (M+1)+ .
{3-Oxo-5-thiophen-2-yl-methyl-4-[(furan-2-ylmethylene)-amino]-2,4-dihydro-[1,2,4] triazole-
2-yl}-acetic acid ethyl ester (4c). Recrystallised from ethanol/water (1:1) (yield: 82.00%). Mp 106-107
◦ C. IR (KBr) (ν , cm−1) 1745 (νester−C=O), 1713 (νtriazole−C=O), 1599 (νC=N ), 1221 (ν C-O); 1 H-NMR
(DMSO-d6) δ (ppm) 1.19 (t, 3H, OCH2 CH3 , J = 7.0 Hz), 4.14 (q, 2H, OCH2 CH3 , J = 7.0 Hz), 4.27 (s,
2H, thiophen-CH2), 4.63 (s, 2H, NCH2), 6.72-6.74 (m, 1H, arH), 6.95-7.01 (m, 2H, arH), 7.24-7.28 (m, 1H,
arH), 7.38-7.41 (m, 1H, arH), 8.01 (s, 1H, arH), 9.54 (s, 1H, N=CH); 13 C-NMR (DMSO-d6)δ (ppm) 13.88
(OCH2 CH3), 25.23 (thiophen-CH2), 46.33 (NCH2), 61.17 (OCH2 CH3), thiophen-C: [125.44 (CH), 126.81
(C), 126.98 (CH), 136.50 (C)], ar-C: [112.62 (CH), 118.26 (CH), 143.32 (CH), 144.97 (C)], 144.68 (triazole-C-3),
146.99 (N=CH), 152.06 (triazole-C-5), 167.48 (ester-C=O). Analysis (% calculation/found): C: 53.32/53.39, H:
4.47/4.52, N: 15.55/15.59. MS: m/z 361.08 (M+1)+
.
{4[(5-Nitro-thiophen-2-ylmethylene)-amino]-3-oxo-5-thiophen-2-ylmethyl-2,4-dihydro-[1,2,4]
triazole-2-yl}-acetic acid ethyl ester (4d). Recrystallised from ethanol/water (1:1) (yield: 76.25%). Mp
184-185 ◦ C. IR (KBr) (ν , cm−1): 1736 (νester−C=O), 1709 (νtriazole−C=O), 1598 (νC=N ), 1228 (νC−O);
1 H-NMR (DMSO-d6) δ (ppm) 1.20 (t, 3H, OCH2 CH3 , J = 7.0 Hz), 4.15 (q, 2H, OCH2 CH3 , J = 7.0 Hz),
4.31 (s, 2H, thiophen-CH2), 4.66 (s, 2H, NCH2), 6.95-7.05 (m, 2H, arH), 7.42 (m, 1H, arH, J= 5 Hz), 7.83
(d, 1H, arH, J=4 Hz), 8.18 (d, 1H, arH, J=4 Hz), 9.89 (s, 1H, N=CH); 13 C-NMR (DMSO-d6)δ (ppm) 13.89
(OCH2 CH3), 25.27 (thiophen-CH2), 46.43 (NCH2), 61.24 (OCH2 CH3), thiophen-C: [125.57 (CH), 126.80
(CH), 126.92 (CH), 136.46 (C)], ar-C: [128.21 (CH), 132.87 (CH), 144.43 (C), 147.09 (C)], 144.49 (triazole-C-3),
149.24 (N=CH), 152.56 (triazole-C-5), 167.43 (ester-C=O). Analysis (% calculation/found): C: 45.60/45.64, H:
3.59/3.65, N: 16.62/16.67. MS: m/z 421.99 (M+1)+
.
{3-Oxo-5-thiophen-2-yl-methyl-4-[(thiophen-2-ylmethylene)-amino]-2,4-dihydro-[1,2,4] tria-
zole-2-yl}-acetic acid ethyl ester (4e). Recrystallised from ethanol/water (1:1) (yield: 76.86%). Mp 114-
115 ◦ C. IR (KBr) (ν , cm−1) 1746 (νester−C=O), 1703 (νtriazole−C=O), 1597 (νC=N ), 1217 (νC−O); 1 H-NMR
(DMSO-d6)δ (ppm) 1.17 (t, 3H, OCH2 CH3 , J = 2.0 Hz), 4.13 (q, 2H, OCH2 CH3 , J = 2.0 Hz), 4.23 (s, 2H,
thiophen-CH2), 4.61 (s, 2H, NCH2), 6.91-7.00 (m, 2H, arH), 7.17-7.22 (m, 1H, arH), 7.36-7.38 (m, 1H, arH),
7.70-7.72 (m, 1H, arH), 7.84-7.81 (m, 1H, arH), 9.77 (s, 1H, N=CH); 13 C-NMR (DMSO-d6)δ (ppm) 13.89
(OCH2 CH3), 25.37 (thiophen-CH2), 46.37 (NCH2), 61.20 (OCH2 CH3), thiophen-C[125.49(CH), 126.80(CH),
126.84(CH), 137.58 (C)], ar-C: [128.28 (CH), 131.45 (CH), 134.39 (CH), 136.61 (C)], 149.56 (triazole-C-3),
144.50 (triazole-C-5), 149.21 (N=CH), 167.49 (ester-C=O). Analysis (% calculation/found): C: 51.05/51.09, H:
4.28/4.32, N: 14.88/14.92. MS: m/z 376.97 (M+1)+
.
{4-[(2,4-Dichloro-benzyliden)-amino]-3-oxo-5-thiophen-2-ylmethyl-2,4-dihydro-[1,2,4]triazo-
le-2-yl}-acetic acid ethyl ester (4f). Recrystallised from ethanol (yield: 79.38%). Mp 114-115 ◦ C. IR (KBr)
(ν , cm−1): 1751 (νester−C=O), 1723 (νtriazole−C=O), 1595 (νC=N ), 1240 (νC−O); 1 H-NMR (DMSO-d6)δ
(ppm) 1.14 (t, 3H, OCH2 CH3 , J= 7.0 Hz), 4.14 (q, 2H, OCH2 CH3 , J= 7.0 Hz), 4.34 (s, 2H, thiophen-CH2),
4.63 (s, 2H, NCH2), 7.81 (d, 1H, arH), CH2), 6.96-7.01 (m, 2H, arH), 7.38 (d, 1H, arH), 7.58-7.63 (m, 1H, arH),
775

Synthesis and characterisations of some new..., K. SANCAK, et al.,
8.10 (d, 1H, arH), 10.07 (s,1H, N=CH); 13 C-NMR (DMSO-d6)δ (ppm) 13.90 (OCH2 CH3), 25.27 (thiophen-
CH2), 46.33 (NCH2), 61.26 (OCH2 CH3), thiophen-C:[125.48 (CH), 126.82 (CH), 126.90 (CH), 136.86 (C)],
ar-C: [127.96 (CH), 128.17 (CH), 129.51 (CH),129.60 (CH),135.17 (CH), 136.61 (C)], 144.84 (triazole-C-3),
148.17 (N=CH), 149.44 (triazole-C-5), 167.73 (ester-C=O). Analysis (% calculation/found): C: 49.21/49.25, H:
3.67/3.74, N: 16.14/16.19. MS: m/z 439.94 (M+1)+
.
Crystal structure determination of compound 2a
The data collection was performed at 293(2) K for the compound 2a on a Stoe-IPDS–2 diffractometer
˚
equipped with a graphite monochromated Mo-Kα radiation (λ = 0.71069 A). The structure was solved by direct
methods using SHELXS–9714 and refined by a full-matrix least-squares procedure also using SHELXL–97.14 All
hydrogen atoms were placed in idealised locations and refined anisotropically using a riding model. Molecular
graphic were prepared using ORTEP315 and finally the packing diagram was prepared using PLATON.16
Details of crystal data, structure solution, and refinement are given in Table 1.
Table 1. Crystallographic data for 2a.
Chemical formula
Formula weight
C16H14N4SO
310.37
h
k
l
min, hmax
min, kmax
min, lmax
θmin
-7, 8
-16,16
-22,22
1,9
Crystal colour, habit Colourless, prism
Crystal system
Crystal dimensions
Space group
Monoclinic
0.43 × 0.3 × 0.22
P21/n
θmax
Dcalc(g/cm3)
(Mo K ), (cm−1
26
1.327
0.22
˚
a(A)
6.565(5)
)
ꢀ
˚
b(A)
18.278(5)
13.024(5)
90.000(5)
96.227(5)
1553.6(14)
4
Measurement reflection 18000
˚
c(A)
Unique reflections
3048
1265
0.090
0.301
0.895
α(◦), γ(◦)
Observed reflection
(◦)
R
Rw
S
3
˚
V (A )
Z
1
R = ΣllFol-|Fcll/Σ|Fol Rw = [( Σw(lFol-lFcl)2/ΣwFo2)] /2
◦
˚
Table 2. Selected bond distances an bond angles (A, ) for 2a.
Bond Distances
C1—S1 1.625 (8)
C4—S1 1.696 (6)
C7—O1 1.241 (6)
N1—N2 1.380 (6)
N3—N4 1.391 (6)
Bond Angles
C5—C4—S1 122.2 (4) O1—C7—N3 128.8 (5)
N3—C6—C5 124.0 (5) C8—N4—N3 118.3 (4)
776

Synthesis and characterisations of some new..., K. SANCAK, et al.,
Figure 1. Ortep drawing of the crystal structure of 2a.
Results and discussion
In this study, compounds 2 was obtained from the reaction with 4-amino-5-thiophen-2-yl-methyl-2,4-dihydro-
[1,2,4]-triazol-3-one (1) with aldehydes (Scheme 1). In the IR spectra of compounds 2a-b, one sharp absorption
band was seen at 1696 and 1718 cm−1 , belonging to the carbonyl function of the triazole ring. While NH2 was
disappeared, N=CH were observed at 9.49 and 9.81 ppm in the 1 H-NMR spectra of compounds 2. Compounds
3 were synthesised via the reaction of compounds 2 with bromo acetophenone. The IR spectra of compounds 3
showed 2 sharp absorption bands, one of which, appearing at 1719 cm−1 , was attributed to carbonyl function
of 1,2,4-triazole-3-one ring, and the other, observed at 1696 cm−1 , was assigned to -C=O stretching frequency
corresponding to ketone carbonyl. Compounds 4 were synthesised via the reaction of compounds 2 with ethyl
bromoacetate. The IR spectra of compounds 4 showed 2 sharp absorption bands, one of which, appearing at
1702, 1713 cm−1 , was attributed to the carbonyl function of 1,2,4-triazol-3-one ring and the other observed at
1736,1746 cm−1 was assigned to -C=O stretching frequency corresponding to ester carbonyl. While -NH signal
disappeared in the 1 H-NMR of compounds 4, the proton signals due to ester group were recorded between
1.17 and 1.20 ppm (-OCH2 CH3) integrating for 3 protons, and between 4.13 and 4.15 ppm (-OCH2 CH3)
integrating for 2 protons. The 13 C signals of -OCH2 CH3 and -OCH2 CH3 were observed at 13.88-13.89 ppm
and 61.17-61.24 ppm.
Compound 2a consist mainly three bonded planar rings, namely a triazole ring (A), a benzene ring (B)
and a thiophene ring (C). While triazole and benzene rings are nearly coplanar with each other the thiophene
777

Synthesis and characterisations of some new..., K. SANCAK, et al.,
◦
˚
ring is normal to this plane with the angle 112.35 . The r.m.s. deviation of the molecule is 0.08 A. Maximum
˚
deviation in the mean plane of A and B ring system belong to the C9 atom with -0.081 A; in ring C this value
˚
belongs to the C3 atom with -0.139 A.
Figure 2. Packing diagram of compound 2a view along a axis.
The torsion angle S1-C4-C5-C6 (between rings A and C) is -100.2 (5)◦ . C=N double bond distances are
˚
˚
˚
1.273 A in the chain and 1.282 A in the triazole ring and that of the C=O double bond is 1.25(7) A. The packing
of the molecule is shown in Figure 2. Analysis of the crystal packing of compound 2 reveals that the molecule
is linked by means of an intermolecular N-H...O type hydrogen bond between N2 and O1 with symmetry code
◦
˚
(2-x,1-y,-z) [N. . . ..O = 2.774(7) A , N-H2A. . . O1 = 161 ] and intramolecular C-H...O type hydrogen bond
between C8-H8. . . O1. In addition to these interactions the crystal structure presents C-H ....π stacking. This
C-H ....π interaction occurs between C2-H2 ....Cg2 (Cg2 is the centroid of the triazole ring) with symmetry
˚
code (1/2+x, 1/2-y, 1/2+z), with a distance of 3.487(6) A.
778

Synthesis and characterisations of some new..., K. SANCAK, et al.,
Antimicrobial activity
All test microorganisms were obtained from the Refik Saydam Hıfzıssıha Institute (Ankara, Turkey) and are
as follows; Ec: Escherichia coli ATCC 25922, Pa: Pseudomonas aeruginosa ATCC 10145, Yp: Yersinia
pseudotuberculosis ATCC 911, Kp: Klebsiella pneumoniae ATCC 13883, Ef: Enterococcus faecalis ATCC
29212, Sa: Staphylococcus aureus ATCC 25923, Bc: Bacillus cereus 709 roma, Ca: Candida albicans ATCC
60193, Ct: Candida tropicalis ATCC 13803. Some the newly compounds were dissolved in dimethylsulphoxide
(DMSO) to prepare extract stock solution.
The newly compounds synthesised were screened for their antibacterial and antifungal properties. Among
the compounds, 4d exhibited the highest degree of antimicrobial activity against Candida albicans ATCC 60193
and Candida tropicalis ATCC 13803.
Acknowledgements
This work was supported by the Research Fund of Karadeniz Technical University. (2004.111.02.11 )
References
1. Tsukuda, T.; Shiratori, Y.; Watanabe, M.; Ontsuka, H.; Hattori, K.; Shirai, M.; Shimma, N. Bioorg. Med. Chem.
Lett. 1998, 8, 1819-1824.
2. Kumaran, D.; Ponnnuswamy, M.N.; Jayanthi, G.; Ramakrishnan, V.T.; Panneersel, K.; Sorıano-Garcia, M. Cryst.
Res. Technol. 2000, 39, 239-243.
3. Zamani, K.; Faghihi, K.; Reza Sangi, M.; Zolgharnein, J. Turk. J. Chem. 2003, 27, 119-125.
4. Dalloul, H.; Boyle, P. Turk. J. Chem. 2006, 30, 119-124.
5. Zamanı, K.; Faghihi, K.; Tofighi, T.; Reza, M. Turk. J. Chem. 2004, 28, 95-100.
6. Chai, B.; Qian, X.; Cao, S.; Liu, H.; Song, G. Arkivoc, (ii) 2003, 141-145.
7. Goss, P. E.; Strasser-Weippl, K. Best Pract. Res. Clin. End. Met. 2004, 18, 113-130.
8. Santen, J. R. Steroids 2003, 68, 559-567.
9. Clemons, M.; Colemon, R. E.; Verma, S. Cancer Treat. Rev. 2004, 30, 325-332.
10. Collin, X.; Sauleau, A.; Coulon, J. Bioorg. Med. Chem. 2003, 13, 2601-2605.
¨
11. Aylıkcı, V.; Cengiz, E.; Apaydın, G.; Unver, Y.; Sancak, K.; Tırasoglu, E. Chemical Physics Letters, 2008, 461,
332-337.
¨
12. Unver, Y.; Dugdu, E.; Sancak, K.; Er, M.; Karog˘lu, S¸. A. Turk. J. Chem. 2008, 32, 441-455.
13. Ustabas, R.; Unver, Y.; Suleymanoglu, N.; Coruh, U.; Sancak, K. Acta Crystallographica 2009, E65, 1006-1007.
14. Sheldrick, G. M. Acta Cryst. 2008, A64, 112-122.
15. Farrugia, L. J. J. Appl. Cryst. 1997, 30, 565.
16. (a) Spek, A. L. Acta Cryst. 1990, A46, C34. (b) Spek, A. L.; 1998 PLATON, A Multipurpose Crystallographic
Tool, Utrecht University, Utrecht, The Netherlands.
779

Synthesis and characterisations of some new..., K. SANCAK, et al.,
17. Brokaite, K.; Mickevicius, V.; Mikulskiene, G. Arkivoc 2006, 2, 61-67.
18. Mamolo, M. G.; Falagiani, V.; Zampieri, D.; Vio, L.; Banfi, E.; Il Farmaco 2001, 56, 587-592.
19. Todeschini, A. R.; Miranda, A. L. P.; Silva, K. C. M.; Parrini, S. C.; Barreiro, E. J. ;ur. J. Med. Chem. 1998, 33,
189-199.
20. Ribeiro, I. G.; Silva, K. C. M.; Parrini, S. C.; Miranda, A. L. P.; Fraga, C. A. M.; Barreiro, E. J. Eur. J. Med.
Chem. 1998, 33, 225-235.
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