Cascade synthesis of substituted 4-amino-1,2,4-triazol-3-ones from aldehyde hydrazones and azodicarboxylates

Mechanisms of the cascade synthesis of substituted 4‐amino‐1,2,4‐triazol‐3‐one from huisgen zwitterion and aldehyde hydrazone: A DFT study

“…The highest energy barrier of channel 3 is 29.41 kcal/mol, a reasonable obstacle for the experimental conditions. [27]…”

“…This means that the mixed molar ratio of the three reactants should be R1 / R2 / R3 = 2/1/1, which is perfectly consistent with the ratio of the best yield selected in the experiment. [27]…”

“…The computational model studied in this project was selected based on the experimental results. [27] As it was stated, the two highest yields of the titled product occur when the substituent groups R 1 = Bn/Et, R 2 = 4‐NO 2 C 6 H 4 , R 3 = Ph and the yields come up to 98%/97%, respectively. Taking the computational cost into account, we set R 1 = Et, R 2 = 4‐NO 2 C 6 H 4 , and R 3 = Ph.…”

“…All theoretical calculations were performed using the Gaussian 03[28] program, with the density functional theory (DFT) which has been widely utilized in the study of reaction mechanism. [29] Noteworthy, the solvent effects of toluene (chosen from the available experiment[27]) were included and simulated by the polarized continuum model (PCM)[30–34] in all the following stated geometry optimizations and vibrational frequency calculations. All structures of the reactants, product, transition states, and intermediates were optimized at the B3LYP/6‐31G(d,p)[35–37] level (level A).…”

“…Inspired by all these works, more recently, Wang and coworkers developed another effective cascade synthesis of a series of substituted 4‐amino‐1,2,4‐triazol‐3‐ones 3 from Huisgen zwitterions, which is produced via the reaction of dialkyl azodicarboxylates 1 with PPh 3 and the aldehyde hydrazones 2 (as shown in Scheme ). [27] The procedure was validated to be most efficient when compounds 1 , 2 and PPh 3 were mixed at a molar ratio of 2/1/1 in toluene at 80°C for 1 h. The reaction was performed in a single step and the process was general and efficient.…”