Synthesis and Antimicrobial Activity of Some New 2-Substituted Benzothiazole Derivatives

Some new 2-(5-substituted-1,3,4-oxadiazole-2-yl)-1,3benzothiazole (3a-j) were synthesized by refluxing benzothiazolyl carboxyhydrazide with different aryl acids in phosphoryl chloride. Structures of the synthesized compounds were established on the basis of H NMR and Mass spectral data. The anti microbial activity of the synthesized compounds was evaluated by disc diffusion method.


Experimental
Melting points were determined in open capillary tubes and are uncorrected. 1H NMR were recorded on Varian 200 MHz and Brucker 400 MHz, Mass Spectra were recorded on LCMS Shimadzu spectrophotometer.The physical data of the synthesized compounds were presented in Table 1.

Preparation of ethyl-2-benzothiazole carboxylate (1)
Ethyl-2-benzothiazole carboxylate was synthesized by following method.A mixture of o-aminothiophenol (0.1 mol) and diethyl oxalate (0.2 mol) was heated at mild reflux for 4 h, during which the temperature decreases from 147 to 93 o C.After cooling, the mixture was poured into a solution consisting of 50 mL of conc hydrochloric acid, 150 mL of water and 70 mL of ethanol with stirring, the oil dissolved and a solid formed.The mixture was cooled.The product was filtered and washed with aq.Ethanol, then dried and finally crystallized from pet ether, yield 53%, m.p. 68-70 o C. 1 H NMR (DMSO): δ 1.4 to 1.6 (3H, t, CH 3 of -COOCH 2 CH 3 ), 4.5 to 4.7 (2H, q, CH 2 of -COOCH 2 CH 3 ), 7.5 to 8.3 (4H, m, Ar-H).
After cooling to room temperature it was poured into the crushed ice with stirring.The solid thus obtained was filtered, washed with water and crystallized from ethanol to give compounds 3a-j (Scheme 1).3a: 1 o-Amino thiophenol Diethyl oxalate

Antibacterial activity
All the newly synthesized compounds (3a-j) were evaluated for in vitro antibacterial activity against gram positive and gram negative bacterial strains such as Bacillus subtilis, Bacillus pumilus, Escherichia coli and Pseudomonas aureginosa at concentration 100 µg/mL by disc diffusion method 17 by using DMSO as solvent control and nutrient agar was employed as culture media.After 24 h of incubation at 37 o C, the zone of inhibition were measured in mm.The activity was compared with known antibiotic ciprofloxacin and the data was represented in the Table 2.

Conclusion
All the 10 newly synthesized compounds were screened for antibacterial activity studies at a concentration of 100 µg/mL using DMSO as a control and ciprofloxacin used as standard against gram positive and gram negative bacteria.The data in the Table 2 indicates that among the synthesized compounds 3b, 3d, 3g and 3h compounds was found to posses a broad spectrum activity.However, the activities of the tested compounds are much less than those of standard antibacterial agents used.

Table 1 .
Characterization of the compounds 3a-j.
*Each value is an average of three independent determination ± Standard deviation.Note: '-' denotes no activity, 8-12 mm poor activity, 13-17 mm moderate activity, 18-20 mm and above good activity.