Synthesis and antimicrobial activity of 5-oxo-1-thioxo-4 , 5-dihydro [ 1 , 3 ] thiazolo [ 3 , 4-a ] quinazolines

A three-component condensation of methyl-2-isothiocyanatobenzoate, sulfur and cyanoacetamides or cyanoacetic esters furnishes compounds containing the new heterocyclic system-1-thioxo[1,3]thiazolo[3,4-a]quinazolin-5(4H)-one. The antimicrobial and fungicidal activities of these synthesized compounds were tested.

The obtained products are yellow crystals, easily soluble in DMSO and DMF and poorly soluble in ethanol and isopropanol.They are insoluble in water and chloroform.In the H 1 -NMRspectra of the synthesized compounds 5, the peak of the aromatic proton in the 9th position of the heterocycle is shifted downfields (10,5-11,5) due to the influence of the spatially nearby sulphur atom in the thioxo-group in the first position.This fact, together with the methyl ester and amino group signals' disappearance in position 4 of compound 4, is evidence of the proposed structure.The NH-proton in the 4th position of compound 5 was observed at 11,5-12,5 ppm, or found in an exchange with the solvent.The structures of obtained compounds were also confirmed by C 13 -NMR spectroscopy, mass-spectrometry and elemental microanalysis.The condensation was performed in dimethylformamide, using an equimolar amount of triethylamine.After heating the reaction mixture for 1 hour and dissolving all of the components at 50°C, 1thioxo [1,3]thiazolo [3,4-a]quinazolin-5(4H)-ones (5) were isolated as a solid.

Antimicrobial activity
The antibacterial activity of the synthesized compounds was studied by diffusion in agar and determination of diameters of growth delay areas.During the course of experiment, standard test cultures of different taxonomical groups of microorganisms recommended by Worldwide organization of health care were used.The diffusion in agar method was conducted on two layers of nourishing environments.x -No activity, 11-15 mm -low activity, 16-25 mm -medium activity, >25 mm -high activity.
It is evident from Table 1 that all tested compounds showed antibacterial activity in one or more degrees.However, compounds 5g and 5h also showed a high level of activity on S. Aureus, and medium level on B. Subtilis, but not active on E.Coli and Proteus Vulgaris.

Experimental Section
General Procedures.Melting points (m.p.) were determined on a Koeffler model melting point apparatus and are uncorrected. 1H NMR spectra were obtained at 500 MHz and 13 C NMR spectra were obtained at 125 MHz, in DMSO-d 6 on a Bruker model DRX-500 spectrometer; chemical shifts are reported in δ units (ppm) downfield from TMS as an internal standard.The microanalyses were carried out by the microanalyses service of the Institute of Organic Chemistry n.Zelinsky, Russian Academy of Sciences, Moskow.Analytical TLC was carried out on 5 cm x 10 cm glass plates precoated with a 0.25 mm layer of silica gel 60 F 254 (Merck, Germany).The plates were illuminated with UV light at 254 nm.All solvents and reagents were obtained from commercial sources and were used without additional purification.Dimethyl 2isothiocyanatotereftalate was synthesized by standard methods from dimethyl 2-aminotereftalate and thiofosgene 7,8 .

Conclusions
Offered here is a simple high-yield method for synthesizing the new class of heterocyclic system derivatives, 1-thioxo [1,3]thiazolo [3,4-a]quinazolin-5(4Н)ones.Synthesized compounds showed antibacterial activity and this class can be recommended for the searching of new antibacterial drugs.