Synthesis and Antimicrobial Evaluation of Some Thiazole Derivatives

Reaction of 2-amino-4-phenylthiazole with various aromatic aldehydes afforded 2arylideneamino-4-phenylthiazoles. On the other hand treatment of 2-amino-4phenylthiazole with several acyl halides furnished N-(thiazol-2-yl)-amides. The synthesized compounds have been screened for their antimicrobial activity against Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Shigella dysenteriae, Salmonella typhi, Pseudomonous sp. bacteria and Aspergillus niger, Penicillium notatum, Aspergillus funiculosus, Collectrichum corchori Ikata (Yoshida) and Curvularia lunata fungi respectively. Some of the synthesized compounds exhibited pronounced antimicrobial activities.

Heterocyclic compounds are widely distributed in nature and occupy a prominent place in medicinal chemistry as pharmaceuticals and drug intermediates [1][2][3].They play a significant role in the metabolism of all living cells and many are clinically used for the treatment of various diseases.The therapeutic importance of heterocycles has generated much interest in the synthesis of new classes of heterocyclic systems in order to explore their biodynamic properties [4][5].The search for biologically active substances led us to the investigation of condensed sulfur-and nitrogen-containing heterocycles.Thiazoles are very similar to such skeletons, which are present in many compounds possessing biological activity [6].Some of the thiazole derivatives such as 2-aminothiazoles exhibited antiviral [7], antimicrobial [8], antiulcer [9], anticancer [10][11] and antiinflammatory [12][13] effects.Thiazole ring containing molecules are known pharmaceuticals as well as in agrochemical products [14].For example, ritonavir an anti-HIV drug contains a 5-substituted oxymethylthiazole moiety, and an isostere of the important insecticide, imidacloprid has 2-chloro-5-substituted methylthiazole as part of the molecule.

Imidacloprid isostere
Encouraged by these observations and also in continuation of our search for antimicrobial active molecules [15][16][17][18] we decided to synthesize some thiazole derivatives in order to evaluate their antimicrobial activities.

Physical Measurements
Melting points were recorded with electro thermal melting point apparatus and were uncorrected.Evaporation of solvents was performed under reduced pressure on a Buchi rotatory evaporator.Thin layer chromatography was performed on Kieselgel GF 254 and visualization was accomplished by iodine vapour or UV Flame. 1 H-and 13 C-NMR (270.05MHz and 67.80 MHz) spectra were recorded on a Varian spectrometer in CDCl 3 or DMSO-d 6 solvent.Chemical shifts were reported in δ unit (ppm) with reference to TMS as an internal standard and J values are given in Hz.

General procedure for the synthesis of 2-arylideneamino-4-phenylthiazoles
An equimolecular mixture of 2-amino-4-phenylthiazole (1) and aromatic aldehyde was dissolved in ethanol and refluxed for 6 h.After complete conversion of the reaction (TLC; ethyl acetate: n-hexane; 1:5, v/v), the solvent was evaporated under reduced pressure.The obtained solid mass was recrystallized from ethyl acetate and n-hexane solvent mixture.
The tested compounds were dissolved in N,N-dimethylformamide (DMF) to get a solution of 1 mg mL -1 .The inhibition zones were measured in millimeters at the end of an incubation period of 48 h at (35±2)°C.DMF alone showed no inhibition.Nutrient agar (NA) and potato dextrose agar (PDA) were used as basal media to test the bacteria and fungi, respectively.Commercial antibacterial Ampicillin and antifungal Nystatin were also tested under similar conditions for comparison.

Results and Discussions
The starting material 2-amino-4-phenylthiazole (1) was prepared from acetophenone and thiourea in presence of iodine according to the literature [21].Refluxing of compound 1 with various aromatic aldehydes in ethanol afforded 2-arylideneamino-4-phenylthiazoles (2-8) (Scheme I) in good yields.The structural assignment of compounds (2-8) was confirmed by spectroscopic analysis.All of the synthesized compounds exhibited signal of a one-proton singlet at around δ 7.9 to 9.1 in their 1 H-NMR spectra for benzylidene proton (=CH).The 1 H-NMR spectrum of compound 2 showed two two-proton doublets at δ 8.41 and 8.07 indicating the presence of an aromatic ring and a five-proton multiplet at δ 7.5-7.3for a phenyl group.The spectrum also exhibited a singlet at δ 7.60 for H-5 of the thiazole ring.Its 13 C-NMR spectrum was in agreement with the structure 2. Similarly the peaks in 1 H-NMR and 13 C-NMR spectra of the compounds 3-8 were accordance with assigned structures.Acylation of aminothiazole, 1 with various acyl halides in dry pyridine gave corresponding amides (9-15) (Scheme II) in high yields.The structure of the compounds (9-15) was confirmed from their 1 H-NMR and 13 C-NMR spectra.In the 1 H-NMR and 13 C-NMR spectra of the compound 9, a two-proton triplet at δ 1.88, two two-proton multiplet at δ 1.37 and 0.98, a three-proton triplet at δ 0.69, one carbonyl carbon signal at δ 171.5 and four aliphatic carbons signals at δ 35.5, 26.8, 22.0 and 13.6 were indicative of the presence of one pentanamide group in the molecule.The 13 C-NMR spectrum also displayed the presence of fourteen carbons corresponding to its molecular formula C 14 H 16 N 2 OS.Similarly the 1 H-NMR and 13 C-NMR spectra of the compounds 10-15 were in complete accord with the assigned structures.Amongst the synthesized compounds screened for the antibacterial activity, compound 2 showed highest activity against B. cereus.Some of the compounds showed low antimicrobial activities and some were unable to show inhibition.For the antifungal activity, all compounds, except 6 and 12, showed excellent results against C. lunata.Compound 8 revealed highest activity against A. funiculosus, which was also greater than that of the standard antibiotic, Nystatin.The other tested compounds also exhibited good to excellent results against all the fungi.

Conclusions
In this work, we have demonstrated the syntheses of 2-arylideneamino-4-phenylthiazoles and N-(thiazol-2-yl)-amides with promising antibacterial and antifungal activity.The activity data obtained during the study will be certainly useful to go for further research for drug designing and synthesizing new thiazole derivatives.

Table 1 .
Antibacterial activity of the synthesized compounds.

Table 2 .
Antifungal activity of the synthesized compounds.