Synthesis and spectral properties of novel thiadiazolotriazinone derivatives

Article abstract of DOI:10.2298/JSC110930217G

A series of new 7-substitued-4H-1,3,4-thiadiazolo[2,3-c][1,2,4]-triazin-4- ones were synthesized in good yields by the reaction of 4-amino-3-mercapto-1,2, 4-triazin-5(4H)-one with various aromatic carboxylic acids in the presence of phosphorus oxychloride. All the synthesized compounds were confirmed by FT-IR, NMR (1H and 13C) and ESI-MS spectroscopic techniques and analytical methods.

Full text of DOI:10.2298/JSC110930217G

J. Serb. Chem. Soc. 77 (7) 867–871 (2012)
JSCS–4315
UDC 547.7+547–304.9+66.095.25:542.913:
535.33.004.12
Short communication
SHORT COMMUNICATION
Synthesis and spectral properties of novel
thiadiazolotriazinone derivatives
DEMET GÜRBÜZ* and SÜLEYMAN TANYOLAÇ
Istanbul University, Faculty of Engineering, Department of Chemistry,
34320, Avcilar, Istanbul, Turkey
(Received 30 September, revised 7 December 2011)
Abstract: A series of new 7-substitued-4H-1,3,4-thiadiazolo[2,3-c][1,2,4]-tri-
azin-4-ones were synthesized in good yields by the reaction of 4-amino-3-mer-
capto-1,2,4-triazin-5(4H)-one with various aromatic carboxylic acids in the
presence of phosphorus oxychloride. All the synthesized compounds were con-
firmed by FT-IR, NMR (1H and 13C) and ESI-MS spectroscopic techniques
and analytical methods.
Keywords: heterocyclic; 1,2,4-triazine; cyclization; thiadiazolotriazinones.
INTRODUCTION
Triazines and their derivatives are important groups of heterocyclic com-
pounds. They have attracted considerable interest because of their great biolo-
1,2
3
4
5
gical importance, such as their antitumor, anti-HIV, antiviral, antimalarial,
6
7
8
antibacterial, antifungal and antioxidant activities.
9,10
Triazines have also found wide applications as herbicides
cides in the field of agriculture. In addition, a number of thiadiazole derivatives
exhibit a broad range of biological activities due to the presence of the NCS
and pesti-
11
12
moiety.
Herein, the synthesis of 7-substitued-4H-1,3,4-thiadiazolo[2,3-c][1,2,4]tri-
azin-4-ones 3 (Scheme 1) by condensation of 4-amino-3-mercapto-1,2,4-triazin-
5(4H)-one 1 with various aromatic carboxylic acids 2 and their characterization
using analytical and spectroscopic techniques are described.
*Corresponding author. E-mail: demet@istanbul.edu.tr
doi: 10.2298/JSC110930217G
867
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GÜRBÜZ and TANYOLAÇ
RESULTS AND DISCUSSION
For the present work, 4-amino-3-mercapto-1,2,4-triazin-5(4H)-one 1 was
prepared by the reaction of thiocarbohydrazide with glyoxalic acid monohydrate
13
following a literature method. Thirteen novel thiadiazolotriazine derivatives
were synthesized for the first time in this study. The physical and chemical data
of the synthesized compounds are given in Table I.
Scheme 1. Synthesis of 7-substitued-4H-[1,3,4]thiadiazolo[2,3-c][1,2,4]triazin-4-ones.
TABLE I. Physical and chemical data of the synthesized compounds
Solvent for
Compound
R1
Formula
M.p., °C Yield, %
crystallization
3a
3b
3c
3d
3e
3f
3g
3h
3i
2-Cl
4-F
C10H5ClN4OS 200–201.5
52
62
75
92
55
87
55
79
65
87
40
80
83
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
C10H5FN4OS
C11H8N4OS
C11H9N4O2S
C11H9N4O2S
C11H9N4OS2
190–192
217–219
208–209
240–241.5
183–184
4-CH3
3-OCH3
4-OCH3
4-SCH3
4-CF3
Dioxane–ethanol (1:1)
Dioxane–ethanol (1:1)
Dioxane
C11H6F3N4OS 219.5–221
249–250
C10H4Cl2N4OS2 205–207
C10H4Cl2N4OS2 246–248
3-CH3-4-NO2 C11H7N5O3S
2,4-Cl
3,4-Cl
3,4-OH
3,4-CH3
3,4-OCH3
Dioxane
Dioxane
Dioxane
Dioxane
3j
3k
3l
C10H6N4O3S
C12H10N4OS
C12H12N4O3S
307–308.5
212–214
245–247
3m
Dioxane
The IR spectra of all cyclized compounds (3a–m) showed no absorption
band due to the NH and SH groups. These observations gave clear evidence for
2
the formation of a fused ring system. The IR spectrum of 3c showed absorption
–1
–1
bands at 1715 cm due to carbonyl group and 1615 cm assigned to the C=N
stretching mode. The characteristic C–H modes of the ring residues were ob-
–1
served at 3061 cm . The C–H stretching vibration bands of the CH group were
3
–1
at 2984–2938 cm . The presence of aromatic rings was identified by their cha-
–1
–1
racteristic ring vibrations at 1461 cm and in the 821–715 cm range. Simi-
larly, the IR spectrum of 3i exhibited absorption bands at 3092 cm due to aro-
matic protons and at 1707 cm due to the C=O of the triazine carbonyl group.
–1
–1
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NOVEL THIADIAZOLOTRIAZINONE DERIVATIVES
869
Other absorption bands were observed at 1584 (C=N), 1469 (C=C) and at 869
–1
and 715cm (C–Cl).
1
In the H-NMR spectra of the cyclized compounds, peaks due to NH and
2
SH groups were absent, which confirmed the involvement of these functional
1
groups in the cyclization of triazine to thiadiazolotriazines. The H-NMR
(DMSO-d ) spectrum of compound 3c showed a singlet at δ 2.40 ppm, inte-
6
grating for three protons arising from CH groups. The protons of the p-me-
3
thylphenyl ring resonated as two doublets at δ 7.45 ppm (J = 8.3 Hz) and 7.91
ppm (J = 8.29 Hz), each integrating for two protons. The signal due to the
13
triazine ring proton appeared as a singlet at 8.58 ppm. The C-NMR (DMSO-d )
6
spectrum of compound 3c showed signals at 21.88, 125.42, 128.46, 131.03,
144.89, 146.06, 148.57, 160.53 and 162.03 ppm. According to this APT spectral
2
6
3
5
data, C ′ and C ′ as well as C ’ and C ’ are magnetically equivalent to each
other. They exhibited a single signal at 128.46 and 131.03 ppm, respectively. The
1
H-NMR (DMSO-d ) spectrum of compound 3i showed a doublet of doublets at
6
6.73 ppm (J = 1.96, 8.79) and two doublets at 8.01 ppm (J =1.96 Hz) and 8.10
ppm (J = 8.79 Hz), confirming the presence of the aromatic group. The signal
13
due to the triazine ring appeared as a singlet at 8.63 ppm. The C-NMR (DMSO-
d ) spectrum of 3i showed the following signals 126.06, 129.41, 131.38, 133.17,
6
134.05, 138.97, 146.01, 148.45, 156.62 and 161.92 ppm, which account for the
ten different carbon atoms present in the molecule.
The molecular ion peaks were determined for all the synthesized compounds.
The mass spectrum of 3c showed a protonated molecular ion peak at m/z =
+
= 245.15 (100, [M+1] ), which is consistent with molecular formula C H N OS.
11
8 4
The mass spectrum of 3i showed the presence of a molecular ion peak at m/z =
+
= 299.27 (100, [M] ), which is in agreement with the molecular formula
C H Cl N OS. The spectral data of all the newly synthesized compounds are
10
4
2 4
presented in the Supplementary Material to this paper.
EXPERIMENTAL
All chemicals and solvents were of reagent grade and used without further purification.
The reactions were monitored by thin layer chromatography (TLC) using Merck silica gel 60
F254 coated alumina plates with ultraviolet light detection. The elemental data were obtained
with a Thermo Finnigan Flash EA 1112 analyzer. The melting points were determined using a
Büchi melting point apparatus. The FT-IR spectra were recorded in KBr disks on a Mattson
1
1000 FT-IR spectrometer. The H- and 13C-NMR spectra were recorded on a Varian Unity
Inova instrument operating at 500 MHz. The residual DMSO-d6 signal was also used as an in-
ternal reference. The Electron Spray Ionization-Mass Spectroscopy (ESI–MS) analyses were
realized in positive ion modes using a Thermo Finnigan LCQ Advantage MAX LC/MS/MS
spectrometer.
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GÜRBÜZ and TANYOLAÇ
General procedure for the synthesis of compounds 3a–m
A mixture of 4-amino-3-mercapto-1,2,4-triazin-5(4H)-one 1 (0.001 mol) and mono- or
di-substituted carboxylic acids 2 (0.001 mol) in 10 mL phosphorus oxychloride was refluxed
on a water bath for about 8–10 h. The extent of the reaction was monitored by TLC. After
cooling, the excess of phosphorus oxychloride was removed under vacuum. The reaction mix-
ture was poured onto crushed ice. The precipitate was filtered, washed with sodium bicarbo-
nate and water. The crude product was recrystallized from appropriate solvents, given in
Table I.
CONCLUSIONS
In conclusion, thirteen novel 7-substitued-4H-1,3,4-thiadiazolo[2,3-c]1,2,4-
-triazin-4-ones (3a–m) were synthesized for the first time in this study. The
1
13
structures of products were determined by FT-IR, NMR ( H and C) and ESI-MS
spectroscopic techniques and analytical methods.
SUPPLEMENTARY MATERIAL
Analytic and spectral data of the synthesized compounds are available electronically
from http://www.shd.org.rs/JSCS/, or from the corresponding author on request.
Acknowledgement. This work was supported by the Research Fund of Istanbul Univer-
sity, Project No.: 2085.
И З В О Д
СИНТЕЗА И СПЕКТРАЛНЕ КАРАКТЕРИСТИКЕ НОВИХ ДЕРИВАТА
ТИЈАДИАЗОЛОТРИАЗИНОНА
DEMET GÜRBÜZ и SÜLEYMAN TANYOLAÇ
Istanbul University, Faculty of Engineering, Department of Chemistry, 34320, Avcilar, Istanbul, Turkey
Синтетисана је серија 7-супституисаних деривата 4H-1,3,4-тијадиазоло[2,3-c][1,2,4]-
-триазин-4-oна, у добром приносу, реакцијом 4-амино-3-меркапто-1,2,4-триазин-5(4H)-oна
са различитим ароматичним карбоксилним киселинама у присуству фосфор-оксихлорида.
Структура свих добијених деривата потврђена је помоћу FT-IR, NMR (1H и 13C) и ESI-MS
спектроскопских и аналитичких метода.
(Примљено 30. септембра, ревидирано 7. децембра 2011)
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