One pot synthesis of novel thiazolo[3,2-b][1,2,4]triazoles: A useful synthetic application of the acidified acetic acid method

Abstract

Thiazolo[3,2-b][1,2,4]triazoles and some of its analogues were firstly synthesized starting from 3-benzyl-1,2,4-triazole-5-thiol (13). 3-Benzyl-1,2,4-triazole-5-thiol (13) was synthesized and reacted with aromatic ketones using the acidified acetic acid method (AcOH/H⁺) to give directly the cyclized 5-aryl-2-benzyl-1,3-thiazolo[3,2-b][1,2,4]triazoles (15a-f) rather the thioketones 14. The isomeric 2-benzyl[2,3-c]-1,2,4-triazoles 16 could not be obtained using this method. The reaction of 1-phenylacetyl-3-thiosemicarbazide (17) with phenyl bromomethyl ketones in refluxing ethanol afforded the 2-(phenylacetyl-hydrazino)-4-phenylthiazole (18) which, cyclized into 16a upon refluxing in POCl₃. The tricyclic system 20a–d was successfully prepared in one pot reaction using the acidified acetic acid in high reaction yield and short reaction time. Formation of both 15a–l and or 16a–c was assigned by the molecular minimization energy (MME) calculations which indicated that the formation of 15 is more favorable than the isomeric compounds 16. Examination of the biological activity against the selected bacteria and fungi revealed that the title compounds possess significant growth promoting effect.

Keywords:

• Thiazolotriazoles
• Synthesis
• Acidified acetic acid method
• Cyclocondensation
• MME calculations and biological activity

Acknowledgements

The authors wish to offer grateful thanks to Assiut University (Egypt) for supporting this work.