Synthesis and Antifungal Activity of Azetidinone and Thiazolidinones Derivatives of 2-Amino-6-( 2-naphthalenyl ) thiazolo [ 3 , 2-d ] thiadiazole

2-amino-6-(2-naphthalenyl)thiazolo[3,2-d]thiadiazole [1] was prepared by treatment of KCNS and Br2 on 2-Amino-4-(2-naphthalenyl) thiazole. 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) afford 2azetidinones and 4-thiazolidinones respectively. The prepared compounds have been screened on some stains of fungai.


Introduction
Thiazoles are one of the most intensively investigated classes of aromatic five membered hetrocycles.Thiazole derivatives find 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 broad spectrum of biological activity.The area in which the transformation of 2-amino-4-(2-naphthalenyl) thiazole into azetidinones and thiazolidinones has been reported recently by us 14 .In continuous at this work 14

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.Antifungal activity of all the compounds were studied against various fungi (Tables -3 & 4) at a concentration of 100ppm by agar cup method 16 .Methanol system was used as control in the method.Under similar conditions using penicillin and sulfanilamide as a standard.The comparison carried at control experiment.The area of inhibition of zone is measured as percentage.

Preparation of 2-amino-6-(2-naphthalenyl)thiazolo[3,2-d]thiadiazole
In a three necked flask, a solution of 2-amino-4-(2-naphthalenyl) thiazole (0.02 mole) in 1,4dioxane was placed.Then the flask was kept in an ice-bath.The mechanical stirrer was fitted.The KCNS (0.08 mole) was added gradually into the solution with constant stirring.Finally Br 2 (16 ml) in acetic acid (100 ml) was added slowly with constant stirring.The whole assembly with stirrer was kept in an ice-bath for 6 hrs.The resultant mixture was kept aside until reached room temperature.The product was poured into ice-water, filtered and washed with 1,4-dioxane.The product thus was recrystallized by 1,4-dioxane-ethanol [50:50(v/v)] mixture and checked on TLC.Finally the product was purified by column chromatography over silica gel using ethyl acetate: benzene (30:70) as an eluent.Yield was 48%.M.p.156-7 0 C uncorrected.

Preparation of 2-Azetidionones (4a-h)
General Procedure A mixture of Schiff base (3a-h) (0.002 mol) and triethyl amine [TEA] (0.004 mol) 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 45-55% yield.

Results and Discussion
2-amino-6-naphthalenylthiazolo [3,2-d] thiadiazole was prepared according to method reported for benzthiazole from aniline 17 .The elemental contents and IR-NMR spectral features shown in experimental section consistent with the predicted structure.The 2-amino-6-naphthalenylthiazolo [3,2-d] thiadiazole (2) was dissolved in dioxane:ethanol (50:50) and was reacted with aromatic aldehyde in the presence of piperidine to yield Schiff bases (3ah).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 [18][19][20] .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 17,18 .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 Tables 1 and 2. The values are consistent with their predicted structure (Scheme 1).
The antifungal activity of both the series (4a-h) and (5a-h), respectively, have been carried out against some strain of fungi.The results show that the prepared compounds are toxic against the bacteria.Compound 4c, 4d, 4b, 5b, 5d and 5f were found more active against the above fungi.The comparison of the antibacterial activity of these compounds with penicillin and sulphanilamide shows that these compounds have almost similar activity.

Table 1 .
Analytical and spectral Data of Commands 4a-h All the NMR spectra containing multiplate between 7.8 to 8.2 which assigned aromatic ring + C 4 H and thiazole CH.

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

Table 3 .
Antifungal Activity of compounds 4a-h

Table . 4
Antifungal Activity of compounds 5a-h