Simple and Efficient Synthesis of Diamino Derivatives of bis-1,2,4-oxadiazole via Tandem Staudinger/aza-Wittig Reaction

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-1,2,4- oxadiazoles 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 ℃ 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 ℃ 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, 1HNMR, 13CNMR and HRMS.

Keywords: 2; 4-oxadiazole; Diamino derivatives of bis-1; Staudinger reaction; aza-Wittig reaction; diaziglyoxime; diazioxalimides; heterocyclic compounds.