Oxadiazole, 2- 1,3,4-, synthesis

Microwave irradiation coupled with polyethylene glycol)-supported Burgess reagent reduced the reaction time to 2-4 min and led to improved yields. Use of harsh reagents, e. g. SOCl2, POCl3, and polyphosphoric acid, for the cydodehydration were avoided. 

In recent decades, the Biginelli-type dihydropyrimidinones (DHPM) have received considerable attention, because of the interesting pharmacological properties of this heterocydic scaffold [30]. It was soon established that DHPM has a similar pharmacological profile to the well-known dihydropyridine (DHP) caldum-channel modulations of the Hantzsch type [31]. 

Simultaneously the reaction time is reduced from typically 4—8 h under reflux (traditional heating) to a few minutes (MW irradiation). 

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Scheme 27 Oxadiazole synthesis using the Burgess reagent...

Fig. 7.8 Polystyrene-bound dehydrating agent (left) and polymer-supported phosphazene base PS-BEMP (right) utilized for oxadiazole synthesis.

Even though N-acylated amidoximes have never been isolated, their existence as intermediates in some reactions involving the formation of the oxadiazole ring cannot be excluded. Indeed, the formation of N-acyl-amidoximes is postulated in the following methods of oxadiazole synthesis. 

In the same publication, it was reported that this cyclo-dehydration could also be affected by using tosyl chloride and the polymer-supported phosphazene base PS-BEMP, and again, microwave heating was found to be advantageous (Scheme 6.25). In utilising this protocol, no scavenger purification strategy was deemed necessary and the authors note that this is the most efficient 1,3,4-oxadiazole synthesis of the three polymer-supported methods described. 

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