Efficient Synthesis and Computational Studies of Useful Guanylating Agents: 1H‐Benzotriazole‐1‐carboximidamides

• Published in: ChemistrySelect (Weinheim) 2020-11, Vol.5 (44), p.13963-13968
• Main Authors: Bokhtia, Riham M., Panda, Siva S., Girgis, Adel S., Pillai, Girinath G., Ibrahim, Tarek S., Shalaby, ElSayed M., Gigli, Lara, Abdel‐Aal, Eatedal H., Al‐Mahmoudy, Amany M. M.
• Format: Article
• Language: English
• Subjects: Amino acids; Carboximidamides; DFT studies; Guanidines; X-ray diffraction
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202003796

A new synthetic protocol for the synthesis of 1H‐benzotriazole‐1‐carboximidamides starting from aryl amines in presence of acylbenzotriazole has been reported. The versatile guanylating agents could be an efficient synthetic tool for the synthesis of various guanidines. The present approach enables all possible variations of the substituents at different positions of the products. Single crystal of compound 4e was obtained by recrystallization from suitable solvent systems for X‐ray and DFT studies. The reaction goes faster and yields more product with higher purity when Cbz protected aminoacyl benzotriazole used instead of aryl benzotriazole for the synthesis of the 1H‐benzotriazole‐1‐carboximidamides. Computational studies were carried out to elucidate the energy profile and transition states to support the experimental data. Short reaction time, simple workup, high yields, and mild conditions are the key advantages of this protocol. Acyl benzotriazoles explored for the efficient synthesis of 1H‐benzotriazole‐1‐carboximidamides. The synthesized agents were analyzed by spectral studies including X‐ray. The reaction goes faster and yields more when Cbz protected aminoacyl benzotriazole used instead of aryl benzotriazole. The observation was supported by energy profile and transition states which were carried out but computational tools.