Synthesis of some new quinoxalines bearing pyridinyl thiazole moiety

. Keeping the objective to build up a new structural class of quinoxaline, a new series of quinoxaline derivatives bearing the pyridinyl thiazole nucleus have been synthesized by base-catalyzed chloro-amine condensation reaction approach. The protocol offers expeditious and easy synthesis with excellent yield. The chemical structures of the synthesized compounds were elucidated by 1 H NMR, 13 C NMR, FT-IR, elemental analysis, and mass spectral data.


INTRODUCTION
Quinoxaline and its derivatives are an important class of benzoheterocycles1 displaying a broad spectrum of biological activities which have made them privileged structures in combinatorial drug discovery libraries. Quinoxalines play an important role as a basic skeleton for the design of a number of antibiotics such as echinomycin, actinomycin, and leromycin. It has been reported that these compounds inhibit the growth of gram-positive bacteria, and are active against various transplantable tumors [1,2] The quinoxaline ring is also a constituent of many pharmacologically and biologically active compounds such as insecticides, fungicides, herbicides, and anthelminitics [3,4]. Quinoxaline derivatives have found application in dyes [5], electron luminescent materials [6], organic semiconductors [7], chemically controllable switches [8], as building blocks for the synthesis of anion receptors [9], cavitands [10], dehydroannulenes [11], DNA cleaving agents [12] and also serve as useful rigid subunits in macrocyclic receptors or in molecular recognition [13].

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 way for substituted 2,3-dichloroquinoxaline (1a)
A mixture of appropriate substituted benzene-1,2-diamine (5 mmol), diethyl oxalate (5 mmol) and 1 ml of pyrrolidine in ethanol (10 ml) were charged in 100 ml round bottom flask equipped with condenser. The reaction mixture was stirred at reflux for 4 h. On completion of reaction, monitored by TLC, the the separated substituted quinoxaline-2,3(1H,4H)-dione was filtered and washed with ethanol and dried. Again a mixture of appropriate substituted quinoxaline-2,3(1H,4H)dione (5gm) and 3 ml of DMF in POCl 3 (25 ml) were charged in 100 ml round bottom flask equipped with condenser. The reaction mixture was stirred at reflux for 4 h. On completion of reaction, monitored by TLC, The reaction mixture was poured in to chilled water. The separated solid was filtered, washed well with water and dried to get pure substituted 2,3-dichloroquinoxaline.
The identity of the product determined by 1 H NMR, 13 C NMR, FT-IR spectral data, and molecular weight of some selected compounds were confirmed by mass spectrometry. 1 H NMR (DMSO-d6) spectrum of 4d, molecule of interest, exhibited singlet peak at d 3.92 ppm appeared for aromatic methoxy proton of phenyl ring. Aromatic protons as multiplets appeared at around d 6.88-7.91 ppm. Moreover, it exhibited two singlet peak at d 10.71 ppm and d 10.82 ppm appeared for two -NH-protons. The 13 CNMR spectrum is in consonance with the structure assigned. In the 13 C NMR spectra, signals around d 110. 25-143.80 ppm are attributed to aromatic carbons of compound 4d. Morver 4d exhibited a distinctive signal at d 55.60 ppm for aromatic methoxy carben. The IR spectrum of compound 4d exhibited characteristic absorption band at 3,356 and 3,248 cm -1 for cyclic -NH-group. And 3,021 cm -1 for aromatic C-H stretching. The mass spectra of compounds 4d and 4f, molecules of interest, detected the expected molecular ion signals corresponding to respective molecular formula, i.e., mass spectra of compounds 4d and 4f gave molecular ion peak at m/z 426.1 (M + 1) and m/z 441.1 (M + 1) corresponding to molecular formula C 23 H 18 N 6 OS and C 22 H 15 N 7 O 2 S. 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.
International Letters of Chemistry, Physics and Astronomy Vol. 52 77

CONCLUSION
New substituted quinoxaline derivatives bearing the thiazole and pyridine nucleus have been synthesized through chloro-amine condensation reacton. This synthetic strategy allows the assimilation of three promising heterocycles through an easy way.