Synthesis and Regioselective Reaction of Some Unsymmetrical Heterocyclic Chalcone Derivatives and Spiro Heterocyclic Compounds as Antibacterial Agents

• Main Authors: Maher A. El-Hashash, Sameh A. Rizk, Saad R. Atta-Allah
• Format: Article
• Language: English
• Published: MDPI AG 2015-12-01
• Series: Molecules
• Subjects: 4-aryl-4-oxo-but-2-enoic acid; oxirane; chalcone; imidazo[2,1-b]thiadiazole; spiropyrazole; spiroisoxazole; spiropyrane
• Online Access: http://www.mdpi.com/1420-3049/20/12/19827

A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl)-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone of imidazo[2,1-b]thiadiazole derivative 4 via two thermal routes. In one pot reaction of 4-bromoacetophenone, diethyloxalate, and 2-amino-5-aryl-1,3,4-thiadiazole derivatives in MW irradiation (W 250 and T 150 °C) under eco-friendly conditions afforded an unsuitable yield of the desired chalcone 4d. The chalcone derivatives 4 were used as a key starting material to synthesize some new spiroheterocyclic compounds via Michael and aza-Michael adducts. The chalcone 4f was similar to the aryl-oxo-vinylamide derivatives for the inhibition of tyrosine kinase and cancer cell growth. The electron-withdrawing substituents, such as halogens, and 2-amino-1,3,4-thiadiazole moeity decreasing the electron density, thereby decreasing the energy of HOMO, and the presence of imidazothiadiazole moiety should improve the antibacterial activity. Thus, the newly synthesized compounds were evaluated for their anti-bacterial activity against (ATCC 25923), (ATCC 10987), (ATCC 274,) and (SM514). The structure of the newly synthesized compounds was confirmed by elemental analysis and spectroscopic data.