Synthesis of Novel Azetidinone and Thiazolidinones Derivatives and Evaluation of Their Antimicrobial Efficacy

2-Amino-4-(2-naphthalenyl) thiazole (1) was prepared from 2acetylnapthalene. This amine on facile condensation with aromatic aldehydes afford Schiff Base/anils/azomethines(2a-h). These anils on cyclocondensation reaction with chloro acetyl chloride and thio glycolic acid (i.e. mercapto acetic acid) yields 2-azetidinones and 4-thiazolidinones respectively. The prepared compounds have been screened on some stains of bacteria.


Introduction
Thiazoles are one of the most intensively investigated classes of aromatic five membered hetrocycles.Thiazole derivatives find new a variety of applications ranging from bacteriostatics, antibiotics, CNS regulants of high selling diureties [1][2][3][4][5] .All these facts were driving force to develop novel thiozole derivatives with wide structural varation 6 .Thus thiazole derivatives playes pivotal role in medicinal chemistry.
As part of interest in hetrocycles that have been explored for developing pharmaceutically important molecules, 4-thiazolidinones [7][8][9] and 2-azetidinones [10][11][12][13] have played an important role in medicinal chemistry.Moreover they have been studied extensively because of their ready accessibility, diverse chemical reactivity and brode spectrum of biological activity.The area in which the transformation of 2-amino-4-(2naphthalenyl) thiazole into azetidinones and thiazolidinones has not reported so far.Hence it was thought interesting to study such type of moieties shown in scheme-1.

Measurements
Melting points were determined in open capillary tubes and were uncorrected.The IR spectra were recorded in KBR pellets on a nicolet 760D spectrophotometer and 1H NMR spectra in CDCI 3 on Perkin Elmar NMR spectrometer using TMS as an internal standard.
Antimicrobial activity of all the compounds were studied against Gram positive bacteria (Bacillus Subtillies and staphycoccus aureus) and Gram negative bacteria (E.Coli and salmonella typhi) at a concentration of 50µg/ml by agar cup method 15 .Methanol system was used as control in the method.Under similar conditions using penicillin and sulfanilamide as a standard comparison carried at control experiment.The area of inhibition of zone is measured in percentage

Preparation of 2-Azetidionones (4a-h)
A mixture of Schiff base (3a-h) (0.002 mmol) and triethyl amine [TEA] (0.004 mmol) was dissolved in 1,4-dioxane (50 ml), cooled and stirred.To this well-stirred cooled solution chloro acetyl chloride (0.004 mmol) was added drop wise with in a period of 20 min.The reaction mixture was then stirred for an additional 3 hrs and left at room temperature for 48 hrs.The resultant mixture was concentrated, cooled, poured in to ice cold water, filter and then dired.The product thus obtained was purified by column chromatography over silica gel using 30% ethyl acetate: 70% benzene as an eluent.Recrystallization from either / n-Hexane gave 2-azetidinones (4a-h), which were obtained in 55-60% yield.

Results and Discussion
The 2-Amino-4-(2-naphthalenyl)thiazole(2) was dissolved in ethanol and was reacted with aeromatic aldehyde in the presence of piperidine to yield Schiff bases (3a-h).This Schiff bases (3a-h) were then characterized by the elemental analysis, IR spectral studies and NMR spectral studies.The IR spectra of Schiff bases show the prominent band at 1630 cm -1 for the azomethine group 16,17 .
These Schiff bases on cyclo-condensation reaction with chloro acetyl chloride afford 2azetidinone (4a-h) and with thio-glycolic acid afford 4-thiazolidinone (5a-h) respectively.The structures of both these compounds (4a-h) and (5a-h), respectively, have been confirmed by elemental analysis, IR spectral studies, and NMR spectral studies.These compounds shows the band at 1690 cm -1 for cyclic >C=O group 16,17 .All the compounds show the NMR signals for different kinds of protons at their respective positions.The data are shown in Tables 1 and 2. The C, H, N, S analysis of all the compounds of the series are presented in Table 1 and 2. The values are consistent with their predicted structure (Scheme 1).

Table 1
Analytical and spectral Data of Commands 4a-h

Table 2
Analytical and spectral Data of Commands Thiazolidinones, 5a-h