Synthesis of Some New 1,3,4-Thiadiazole, Thiazole and Pyridine Derivatives Containing 1,2,3-Triazole Moiety

In this study, 1-(5-Methyl-1-(p-tolyl)-1H-1,2,3-triazol-4-yl)ethan-1-one, was reacted with Thiosemicarbazide, alkyl carbodithioate and benzaldehyde to give thiosemicarbazone, alkylidenehydrazinecarbodithioate and 3-phenylprop-2-en-1-one-1,2,3-triazole derivatives. The 1,3,4-thiadiazole derivatives containing the 1,2,3-triazole moiety were obtained via reaction of alkylidenecarbodithioate with hydrazonoyl halides. Also, hydrazonoyl halides were reacted with thiosemicarbazone and pyrazolylthioamide to give 1,3-thiazoles derivatives. Subsequently, 3-phenyl-2-en-1-one was used to synthesize substituted pyridines and substituted nicotinic acid ester. The latter was converted to its azide compound which was reacted with aromatic amines and phenol to give substituted urea and phenylcarbamate containing 1,2,3-triazole moiety. The newly synthesized compounds were established by elemental analysis, spectral data and alternative synthesis whenever possible.


Introduction
In synthesis, 1,2,3-triazoles are useful building blocks and are additionally important due to their broad range of biological activities [1,2]-they are stable to moisture, oxygen, light and metabolic process. A series of novel 1,2,3-triazoles were synthesized [3] and found to have cytotoxic activity against human cancer cell lines such as U937, THP-1, HL60 and B16-F10. The 1,3,4-thiadiazole ring is one of the most important and well-known heterocyclic nuclei, as a common and integral feature of a variety of natural products and medicinal agents. As a core structural component, 1,2,4-thiadiazole is present in an array of drug categories such as antimicrobial, anti-inflammatory, analgesic, antiepileptic, antiviral, antineoplastic, antitubercular and antinociceptive agents [4,5]. Thiazoles display a broad range of biological activities and are found in many potent biologically active molecules such as antimicrobial, antifungal and antineoplastic drugs [6]. However, they are mostly known for their anticancer [7] and antimicrobial [8] activities. Also, pyridine derivatives, including those bearing various heterocyclic nuclei, have shown potent pharmacological properties, including antifungal [9,10], antitubercular [11], antimalarial [12], antibacterial [13], antimicrobial [14], or insecticide [15]. We report here the synthesis of new 1,3,4-thiadiazoles, 5-arylazothiazoles, and pyridines containing 1,2,3-triazole moiety.
The latter suffers dehydration to the final product 20.
Treatment of 17 with 3b in ethanolic triethylamine gave 2- (22) in a good yield. Structure 22 was confirmed by elemental analysis and spectral data.
Next, treatment of compound 23 with each of ethyl acetoacetate, acetylacetone, malononitrile, ethyl cyanoacetate, cyanothioacetamide and benzoylacetonitrile in acetic acid containing ammonium acetate afforded pyridine derivatives 24-29, respectively (Scheme 5). Structures 24-29 were elucidated on the basis of elemental analysis, spectral data and chemical transformation (cf. Experimental and Scheme 5). 1  In the light of these results, the mechanism outlined in Scheme 4 seems to be the most plausible pathway for the formation of 20 from the reaction of 17 with 3. The reaction involves initial formation of thiohydrazonate 18, which undergoes cyclization as soon as it is formed to yield the intermediate 19. The latter suffers dehydration to the final product 20.
Treatment of 17 with 3b in ethanolic triethylamine gave 2- (22) in a good yield. Structure 22 was confirmed by elemental analysis and spectral data.

Materials and Methods
All meeting points were determined on an electro thermal Gallen Kamp melting point apparatus (Laim George, Calgary, AB, Canada) and are uncorrected. IR (cm −1 ) spectra were recorded on KBr disk on a FTIR-8201 spectrophotometer (Shimadzu, Tokyo, Japan). 1 H-NMR and 13 C-NMR spectra were measured in deuterated dimethyl sulfoxide (DMSO-d6) using a Varian Gemini 300 NMR spectrometer Scheme 6. Synthesis of pyrazoles, urea, quinazoline and carbamate.

Materials and Methods
All meeting points were determined on an electro thermal Gallen Kamp melting point apparatus (Laim George, Calgary, AB, Canada) and are uncorrected. IR (cm −1 ) spectra were recorded on KBr disk on a FTIR-8201 spectrophotometer (Shimadzu, Tokyo, Japan). 1 H-NMR and 13 C-NMR spectra were measured in deuterated dimethyl sulfoxide (DMSO-d6) using a Varian Gemini 300 NMR spectrometer (Varian, Inc., Karlsruhe, Germany). Mass spectra were recorded on a Shimadzu GCMS-QP1000 EX mass spectrometer (Tokyo, Japan) at 70 eV. Measurements of the elemental analysis were carried out at the Microanalytical Centre of Cairo University, Giza, Egypt. All reactions were followed by TLC (Silica gel, Merck, Kenilworth, NJ, USA). Hydrazonoyl halides were prepared as previously reported [28][29][30][31]

Conclusions
Compound 1 proved to be useful for synthesis of a new series of novel functionalized 1,3,4-thiadiazoles, 1,3-thiazoles and pyridines containing 1,2,3-triazole moiety using hydrazonoyl halides as precursors. Also, compound 31 proved to be a useful precursor in the synthesis of various pyrazoles, urea and carbamate derivatives. The biological activities of the synthesized products will be reported in extended work.