29-12-2012, 06:41 PM
Synthesis and Characterization of Novel Azole Heterocycles Based on 2,5-Disubstituted Thiadiazole
[attachment=45876]
Introduction
The development of simple synthetic routes to widely used organic compounds using readily available
reagents is one of the main objectives of organic synthesis. Nitrogen heterocycles are of a special interest
because they constitute an important class of natural and nonnatural products, many of which exhibit useful
biological activities. One-pot efficient synthesis of heterocyclic derivatives may permit the development of
novel therapies for the treatment of epilepsy, pain and other neurodegenerative disorders.
Pyrazoles have attracted much attention recently as their synthesis is more accessible and their diverse
properties are appreciated. One of the most important pyrazole activities are the effective antirheumatoidal
(SC-58635 Celecoxib) and antiviral agents (Pyrazomycin), hormone oxytocin agonists (WAY-VNA-932), and
selective Human C1s inhibitors.1
1,2,4-Triazole and its derivatives are found to be associated with various biological activities.2 For
example, Fluconazole is used as an antimicrobial drug, while Vorozole, Letrozole, and Anastrozole are
nonsteroidal used for treatment of cancer and Loreclezole is used as an anticonvulsant.3 Also, the synthesis
of triazoles fused to another heterocyclic ring, especially those in which triazoles fused to thiadiazoles, has
attracted particular attention due to their diverse applications.4
Experimental
General
Melting points were determined on Gallenkamp melting point apparatus and were uncorrected. The IR
spectra of the compounds were recorded on a Shimadzu FTIR-8300 spectrometer as KBr disc; results are
given in cm−1. 1H-NMR and 13C-NMR spectra were recorded at 200.13 and 50.32 MHz, respectively, in
DMSO-d6, except for compound 11 in CDCl3, on a Bruker Avance DPX-200 NMR spectrometer. The
chemical shifts are reported in part per million (ppm) downfield from internal tetramethylsilane (TMS)
(chemical shift in δ values). Electron impact MS spectra were obtained on a Shimadzu QP 1000 instrument
at 70 eV. Elemental analyses were run using a Perkin-Elmer RE 2400 CHNan alyzer. 1H-, 13C-NMR,
elemental analysis, and Mass spectra were performed at Drug and Natural Product Department, University
of Vienna, Australia.
Results and Discussion
The synthesis start from 2-amino-5-mercapto-1,3,4-thiadiazole (1), the thiol group of compound 1 was readily
converted into hydrazino derivative (2) by heating under reflux with an ethanolic solution of hydrazine hydrate.
The resulting 2-amino-5-hydrazino-1,3,4-thiadiazole is used for the synthesis of an interesting derivatives,
it is a versatile key intermediate for the synthesis of some fused heterocyclic ring. Thus, the interaction
of 2 with p-bromophenacyl bromide, acetyl acetone, carbon disulfide, and phthalic anhydride give rise to the
formation of the -amino-4-(p-bromophenyl)-6H-1,2,4-triazino[5,4-b][1,3,4] thiadiazole (3), 2-amino-5-(3,5-
dimethyl-1H-pyrazole-1-yl)-1,3,4-thiadiazole (4), 2-amino-4-mercapto[1,2,4]triazolo[3,4-b][1,3,4] thiadiazole
(5) and 2-amino-5-(1,2-dihydrophthalizin-3,6-dione-1-yl)-1,3,4-thiadiazole (6), respectively (Scheme 1).
[attachment=45876]
Introduction
The development of simple synthetic routes to widely used organic compounds using readily available
reagents is one of the main objectives of organic synthesis. Nitrogen heterocycles are of a special interest
because they constitute an important class of natural and nonnatural products, many of which exhibit useful
biological activities. One-pot efficient synthesis of heterocyclic derivatives may permit the development of
novel therapies for the treatment of epilepsy, pain and other neurodegenerative disorders.
Pyrazoles have attracted much attention recently as their synthesis is more accessible and their diverse
properties are appreciated. One of the most important pyrazole activities are the effective antirheumatoidal
(SC-58635 Celecoxib) and antiviral agents (Pyrazomycin), hormone oxytocin agonists (WAY-VNA-932), and
selective Human C1s inhibitors.1
1,2,4-Triazole and its derivatives are found to be associated with various biological activities.2 For
example, Fluconazole is used as an antimicrobial drug, while Vorozole, Letrozole, and Anastrozole are
nonsteroidal used for treatment of cancer and Loreclezole is used as an anticonvulsant.3 Also, the synthesis
of triazoles fused to another heterocyclic ring, especially those in which triazoles fused to thiadiazoles, has
attracted particular attention due to their diverse applications.4
Experimental
General
Melting points were determined on Gallenkamp melting point apparatus and were uncorrected. The IR
spectra of the compounds were recorded on a Shimadzu FTIR-8300 spectrometer as KBr disc; results are
given in cm−1. 1H-NMR and 13C-NMR spectra were recorded at 200.13 and 50.32 MHz, respectively, in
DMSO-d6, except for compound 11 in CDCl3, on a Bruker Avance DPX-200 NMR spectrometer. The
chemical shifts are reported in part per million (ppm) downfield from internal tetramethylsilane (TMS)
(chemical shift in δ values). Electron impact MS spectra were obtained on a Shimadzu QP 1000 instrument
at 70 eV. Elemental analyses were run using a Perkin-Elmer RE 2400 CHNan alyzer. 1H-, 13C-NMR,
elemental analysis, and Mass spectra were performed at Drug and Natural Product Department, University
of Vienna, Australia.
Results and Discussion
The synthesis start from 2-amino-5-mercapto-1,3,4-thiadiazole (1), the thiol group of compound 1 was readily
converted into hydrazino derivative (2) by heating under reflux with an ethanolic solution of hydrazine hydrate.
The resulting 2-amino-5-hydrazino-1,3,4-thiadiazole is used for the synthesis of an interesting derivatives,
it is a versatile key intermediate for the synthesis of some fused heterocyclic ring. Thus, the interaction
of 2 with p-bromophenacyl bromide, acetyl acetone, carbon disulfide, and phthalic anhydride give rise to the
formation of the -amino-4-(p-bromophenyl)-6H-1,2,4-triazino[5,4-b][1,3,4] thiadiazole (3), 2-amino-5-(3,5-
dimethyl-1H-pyrazole-1-yl)-1,3,4-thiadiazole (4), 2-amino-4-mercapto[1,2,4]triazolo[3,4-b][1,3,4] thiadiazole
(5) and 2-amino-5-(1,2-dihydrophthalizin-3,6-dione-1-yl)-1,3,4-thiadiazole (6), respectively (Scheme 1).