An efficient and clean synthesis of thiophenyl thiazole depended novel triazolo[4,3- a ]quinoxaline derivatives

. A simple and efficient approach for the synthesis of thiophenyl thiazole based triazolo[4,3- a ]quinoxaline derivatives is described. In this methodology, 3-hydrazinyl- N -(4-(thiophen-2-yl)thiazol-2-yl)quinoxalin-2-amine derivatives treated with various aromatic aldehyde to form Schiff base which on treatment with iodobenzene diacetate in dichloromethane at room temperature to furnish title compounds. The synthesized compounds were characterized by 1 H NMR, 13 C NMR, FT-IR, elemental analysis, and mass spectral data.


INTRODUCTION
1,2,4-triazoles are very interesting targets for medicinal and pharmaceutical applications. The recent literatures are enriched with progressive findings about the synthesis and pharmacological action of fused heterocyclic systems. The structural diversity and biological importance of nitrogen containing heterocyclic systems have made them attractive synthetic targets over many years and they are found in various natural products [1]. Quinoxalines are an important class of nitrogen containing heterocycles with a variety of biological activities. In particular quinoxaline scaffolds were found as a core unit in a number of biologically active compounds. These include anticancer [2,3], antibacterial [4], antiviral [5], anti-inflammatory [6], anti HIV [7,8] and antihelmintic activities [9]. Quinoxaline derivatives are also used in the development of novel organic dyes and organic semiconductors. Triazolo [4,3-a]quinoxaline [10] have been reported to possess antiviral, and antimicrobial activities. Many other triazolo quinoxaline derivatives have been reported [11][12][13] to possess other types of biological properties. Thus, triazolo quinoxaline derivatives continue to attract much attention as these molecules are of potential biological interest.

EXPERIMENTAL
Required all reagents were obtained commercially. Solvents were purified and dried before being used. All melting points were taken in open capillaries and are uncorrected. Thin-layer chromatography (TLC, on aluminium plates precoated with silica gel, 60F 254 , 0.25 mm thickness) (Merck, Darmstadt, Germany) was used for monitoring the progress of all reactions, purity and homogeneity of the synthesized compounds; eluent-hexane:ethyl acetate: (3:7). UV radiation and/or iodine were used as the visualizing agents. Elemental analysis (% C, H, N) was carried out by Perkin-Elmer 2400 series-II elemental analyzer (Perkin-Elmer, USA) and all compounds are within ±0.4% of theory specified. The IR spectra were recorded in KBr on a Perkin-Elmer Spectrum GX FT-IR Spectrophotometer (Perkin-Elmer, USA) and only the characteristic peaks are reported in cm -1 . 1 H NMR and 13 C NMR spectra were recorded in DMSO-d 6 on a Bruker Avance 400F (MHz) spectrometer (Bruker Scientific Corporation Ltd., Switzerland) using solvent peak as internal standard at 400 MHz and 100 MHz respectively. Chemical shifts are reported in parts per million (ppm). Mass spectra were scanned on a Shimadzu LCMS 2010 spectrometer (Shimadzu, Tokyo, Japan).

Synthetic route for the synthesis of compound (1a)
Dry ethanol (10 ml), piperidine (1 ml), Substituted benzene-1,2-diamine (5 mmol), diethyl oxalate (5 mmol) were charged in a 100-ml round bottom flask with mechanical stirrer and condenser. The reaction mixture refluxed for 4 h. After the completion of reaction (checked by TLC), the separated substituted quinoxaline-2,3(1H,4H)-dione was filtered and washed with ethanol and dried. Now thionyl chloride (25 mmol) was added to a solution of substituted quinoxaline-2,3(1H,4H)-dione (10gm) in dry DCM (50 mL). Upon the addition of 1-2 drop of DMF a mixture was heated at reflux for 1 h. After the completion of reaction a mixture was washed with water followed by saturated NaHCO 3 solution. The organic phase was dried over anhydrous Na 2 SO 4 and solvent was removed under reduced pressure to afford pure substituted 2,3-dichloroquinoxaline.
The structures of all the new synthesized compounds were confirmed by 1 H NMR, 13 C NMR, FTIR, elemental analysis, and molecular weight of some selected compounds confirmed by mass spectrometry. In 1 H NMR (DMSO-d6) spectrum of compound 4c exhibited singlet peak at d 10.30 ppm for -NH-proton while multiplets around d 6.92-7.84 ppm for aromatic protons. Also exhibited singlet peak at d 3.70 ppm for methoxy protons. In the 13 C NMR spectrum of compound 4c showed signals around d 109.22-142.10 ppm for aromatic carbons and d 57.94 for aromatic methoxy carben. The IR spectrum of compound 4c exhibited characteristic absorption band at 3265 cm -1 for cyclic -NH-and 3,038 cm -1 for aromatic C-H stretching vibration. The mass spectra detected the expected molecular ion signals corresponding to respective molecular formula of synthesized compounds. Mass spectra of compound 4c gave molecular ion peak at 456.0 (M + 1) corresponding to molecular formula C 23 H 16 N 6 OS 2. The obtained elemental analysis values are in good agreement with theoretical data. Similarly, all these compounds were characterized on the basis of spectral studies. All spectroscopic data have been given in spectral data.  13 13

CONCLUSION
In summary, novel series of triazolo quinoxalines having thiophene and thiazole moiety synthesized by dehydrogenative cylisation reaction through iodobenzene diacetate. The synthetic method produced a single scaffold with triazole, quinoxaline ,thophene and thiazole hetrocyclic systems.