Huisgen Cycloaddition Reaction of Nitrile Imines With Acyl Phosphonates: Synthesis of Phosphonate Containing 1,3,4-Oxadiazoles and DFT Analysis

Polat-Cakir S., ALTINIŞIK S.

JOURNAL OF HETEROCYCLIC CHEMISTRY, cilt.62, sa.11, ss.1620-1628, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 62 Sayı: 11
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1002/jhet.70067
  • Dergi Adı: JOURNAL OF HETEROCYCLIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), Chemical Abstracts Core, Chimica
  • Sayfa Sayıları: ss.1620-1628
  • Anahtar Kelimeler: acyl phosphonates, DFT, Huisgen cycloaddition, nitrile imines, oxadiazole
  • Çanakkale Onsekiz Mart Üniversitesi Adresli: Evet

Özet

The application of the Huisgen cycloaddition reaction between acyl phosphonates (dipolarophile) and highly reactive intermediate nitrile imines (NI) as a 1,3-dipole in situ generated by the conversion of hydrazonyl chlorides in the presence of a base is reported to synthesize the phosphonate-containing 1,3,4-oxadiazole compounds in 53%-89% yields. Oxadiazole compounds stand out as significant target molecules in drug design and development due to their potential biological activities. Having a phosphonate group in the structure of the 1,3,4-oxadiazole may enhance biological activity be enhanced. We have synthesized 10 new phosphonate-containing oxadiazole compounds that are fully characterized by using spectroscopic analysis. Density Functional Theory (DFT) calculations were carried out to compare the energies of the frontier orbitals of the acyl phosphonates (dipolarophile) and NI (1,3 dipole) to determine the nature of the interaction between the dipolarophile and the 1,3-dipole. The relevant Huisgen cycloaddition reaction proceeds via a normal-electron demand (NED) pathway.