Microwave Assisted Synthesis and Biological Activity of Novel Coumarinyltriazolothiadiazoles

A series of new 3-(4-methylcoumarinyl-7-oxymethyl)-6-substitutedphenyl-5,6-dihydro-s-triazolo (3,4-b)(1,3,4)-thiadiazoles 2(a-j) have been synthesized by reacting 5-(4-methyl coumarinyl-7-oxymethyl)-4-amino-3-mercapto(4H)-1,2,4-triazole with various aromatic aldehydes by microwave assisted organic synthesis. The structure of the compounds 2 (a-j) has been confirmed by IR, 1H NMR and mass spectral data. All the compounds were screened for antimicrobial and antioxidant activity. Among the compounds tested, compounds 2d (4-dimethyl amino phenyl derivative) and 2h (3,4-dimethoxy phenyl derivative) showed better antimicrobial and antioxidant activity than rest of the compounds in the series.

Melting points were determined in open capillary tubes and are uncorrected.All the chemicals and solvents used were of laboratory grade and solvents were purified by suitable methods.IR spectra (KBr, cm -1 ) were recorded on a Jasco FT/ IR-410 spectrometer. 1 H NMR spectra was recorded in DMSO-d 6 using TMS as internal standard at IICT, Hyderabad, India.Mass spectra were recorded at IIT Chennai, India.Reactions were carried out in a Daewoo KOG-370A domestic microwave oven at 2450 MHz.The purity of the products was checked using TLC (Silica Gel-G, Merck).
As shown in Scheme 1, the synthesis of 3 -( 4 -m e t h y l c o u m a r i n y l -7 -o x y m e t h y l ) -6substitutedphenyl-5,6-dihydro-s-triazolo (3,4-b) (1,3,4)-thiadiazoles [1] 2(a-j) was carried out by taking a mixture of 5-(4-methyl coumarinyl-7-oxymethyl)-4amino-3-mercapto (4H)-1,2,4-triazole (1) (3.04 g, 0.01 mol), substituted benzaldehyde (0.01 mol), p-toluene sulphonic acid (30 mg) and DMF (15 ml) in 100 ml borosil beaker, which was zapped inside a microwave oven for period of 3-4 min at 100% power.The reaction mixture was cooled and poured over ice cold water.The product so obtained was fi ltered, washed with water, dried and recrystallized using dimethyl formamide.The purity was established by a single spot on TLC plate.The solvent system used was chloroform:acetone (5:5).The characterization data of synthesized compounds are given in Table 1.Antimicrobial activity was determined using disc diffusion method [10] by measuring the inhibition zone in mm.All the compounds 2(a-j) were screened in vitro for antibacterial activity against Staphylococcus aureus and Escherichia coli and antifungal activity against Candida albicans at 500 μg/ml.Standard antibacterial drug ciprofl oxacin and antifungal drug fluconazole at 10 μg/disc were also tested under similar conditions and these compounds showed highest activity (23-28 mm) against all these organisms tested.The data of compounds with their activity are given in Table 2.
The compounds synthesized were evaluated for antioxidant activity and compared with standard drug (ascorbic acid).The activity was evaluated using the DPPH method [9] .One millilitre of 0.3 mM DPPH ethanol solution was added to 2.5 ml of sample solutions of different concentrations (2, 4, 6, 8 and 10 μg/ml) and allowed to react at room temperature.After 30 min the absorbance values were measured at 518 nm and converted into the percentage antioxidant activity (AA) using the formula, AA% = 100-(Abs sample -Abs blank )×100/Abs control ).
Ethanol (1.0 ml) plus drug solution (2.5 ml) was used as a blank.DPPH solution (1.0 ml, 0.3 mM) plus ethanol (2.5 ml) was used as a negative control.The positive controls were those using the standard solution (ascorbic acid

TABLE 1 : CHARACTERIZATION DATA OF THE SYNTHESISED COMPOUNDS
Solvent system used for TLC is benzene:methanol (9:1) #