Synthesis of 2-aryl-5H-[1,3,4]-thiadiazolo[2,3-b]quinazolin-5-ones

Abstract

3-Amino-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-one (1) contains two reactive centers -thioxo and amino groups -and can be used for the synthesis of condensed heterocycles [1][2][3][4][5], including some with antihypertonic, antibacterial, and fungicidal properties [4,5]. Hence it is a timely synthetic problem to prepare new heterocycles containing the quinazolin-4-one unit.The aim of the present study was the synthesis of 2-aryl-5H-[1,3,4]thiadiazolo[2,3-b]quinazolin-5-ones, which, using the general methods for the synthesis of condensed systems containing 1,3,4-thiadiazole [6], may be obtained by the condensation of compound 1 with carboxylic acids in the presence of dehydrating agents, and also by the oxidative cyclization of 3-arylmethylidenamino-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-ones.We have established that 2-aryl-5H-[1,3,4]thiadiazolo[2,3-b]quinazolin-5-ones 3a-e are formed when compound 1 was heated with aromatic carboxylic acids 2a-e in POCl 3 for 2 h. The yields of 3a-e were 66-73%.In the 1 H NMR spectra of compounds 3a-e there are characteristic signals of the protons of the quinazoline and aromatic rings (7.11-8.41 ppm), while absorption bands for the C=O and C=N groups (1690-1710 and 1580-1610 cm -1 respectively) were observed in their IR spectra.3-Arylmethylidenamino-2-thioxo-1,2,3,4-tetrahydroquinazolin-4-ones 5a-d were obtained in 67-79% yields by the reaction of compound 1 with the aromatic aldehydes 4a-d in acetic acid. The characteristic signals of the protons of the azomethine (N=CH) and thioamide groups (NH-C=S) at 8.51-8.91 and 13.00-13.21 ppm respectively were observed in the 1 H NMR spectra of the azomethine 5a-d.In attempting to carry out the oxidative cyclization of the azomethines 5a,b,d into the [1,3,4]thiadiazolo[2,3-b]quinazolin-5-ones 3 by heating in nitrobenzene (as was suggested for the preparation of [1,2,4]thiazolo [3,4-b][1,3,4]thiadiazole from 5-thioxo-4-phenylmethylidenamino-4H-1,2,4-thiazole [7]), we established that cyclization did not occur under these conditions but instead the azomethines 5a,b,d underwent deamination to give 2-thioxo-1,2,3,4-tetrahydroquinazolin-4-one 6 and the aryl nitriles 7a-c. The same conversion occurred on heating azomethines 5a,b,d at 200°C without a solvent.