Current Pharmaceutical Biotechnology
Two efficient, scalable routes to bis-1,2,4-oxadiazole have been developed by tandem Staudinger/aza-Wittig reaction from the same starting material diaziglyoxime, isocyanates and triphenylphosphonium in good yields, providing proficient methods of making nitrogen-containing heterocyclic rings.
Abstract
Two efficient, scalable routes to bis-1,2,4-oxadiazole have been developed by tandem Staudinger/aza-Wittig reaction from the same starting material diaziglyoxime, isocyanates and triphenylphosphonium in good yields. Background: Two convenient and efficient routes for synthesizing diamino derivatives of bis-1,2,4oxadiazoles were described. Objective: This study provides a simple protocol for the synthesis of bis-1,2,4-oxadiazoles. Methods: The two procedures were based on a tandem Staudinger/aza-Wittig reaction from the same starting material of diaziglyoxime, isocyanates and triphenylphosphonium. Results: In synthesis method I, diaziglyoxime 1 was treated with various aromatic or aliphatic isocyanates to give diazioxalimides 2 a high yield. Diazioxalimides 2 reacted with Ph3P to produce the iminophosphoranes 4; the reaction was directly heated from room temperature to 115 °C to get the desired diamino derivatives of bis-1,2,4-oxadiazole 4 in 72-92% yields. In synthesis method II, the same target compounds 4 were synthesized in a one-pot reaction by Ph3P and aromatic or aliphatic isocyanates in toluene for 10 h under 115 °C in 53-71% yields. Conclusion: The two procedures provide proficient methods of making nitrogen-containing heterocyclic rings. The structures of target compounds 4 were identified by IR, HNMR, CNMR and HRMS. A R T I C L E H I S T O R Y Received: July 09, 2022 Revised: September 07, 2022 Accepted: September 13, 2022 DOI: 10.2174/1570179420666221006113032