New Hydrazonothiophene Derivatives: Synthesis, DFT Calculations, and Prediction for Biological Activity

Seven new thiophene hydrazide derivatives were prepared through the coupling of active methylene of 2-cyano-N'-(thiophen-2-ylmethylene)acetohydrazide with diazonium salts of aromatic amines, and heterocyclic amines at 0–5°C in pyridine. The new hydrazonothiophene derivatives could exist in two possible tautomeric forms, which are the enol and keto tautomer. The optimized molecular structures and calculation of the total energies of both tautomers revealed that the enol tautomer is energetically lower than its corresponding keto form. A prediction study for the biological activities of the newly synthesized thiophene hydrazide derivatives were performed via using PASS online software, which displayed promising activities in the treatment of posttraumatic stress disorder, as phosphodiesterase X inhibitor, and as sarcosine oxidase inhibitor. In addition, DFT calculations showed that the new hydrazonothiophene derivatives containing CH₃, OCH₃, and COOH groups have chemical activity among all the newly synthesized compounds due to their lower band gaps.