Polymer-supported reagents 1,3,4-oxadiazole synthesis

From a medicinal chemist s point of view, oxadiazoles are among the most important heterocycles as they are one of the most commonly used bioisosters for amide and ester groups [67]. As such it is hardly surprising that the two regioisomeric oxadiazole scaffolds received the most interest in the field of microwave-assisted synthesis using polymer-supported reagents. 

Scheme 12.12 Synthesis of 1,3,4-oxadiazoles by use of polymer-supported reagents.

The use of polymer-supported reagents in combinatorial chemistry has received much attention in recent years, and a polymer-supported acylating reagent (supported on a ROMPGEL) has been used for the synthesis of 1,2,4-oxadiazoles in solution, (see Equation 37), <2000CCHT131>. 

Brain, C.T. and Brunton, S.A., Synthesis of 1,3,4-oxadiazoles using polymer-supported reagents, Synlett, 2001, 382-384. 

A one-step synthesis of 1,3,4-oxadiazoles from readily available carboxylic acids and acid hydrazides was mediated by the polymer-supported reagent... 

In related work, rapid synthesis of 1,2,4-oxadiazoles was achieved on polymer-supported reagents [109]. Two independent pathways were used to prepare these heterocycles from carboxylic acids and amidoximes under the action of microwave irradiation. In accordance with the conventional method using HBTU and N,N-diisopropylethylamine (DIEA) for synthesis of this heterocycle, a method utilizing polymer-supported bases was employed. The use of PS-BEMP in the presence of HBTU proved to be beneficial in the microwave procedure. Heating for 15 min in acetonitrile at 160 °C furnished high yields for a series of substrates. 1,2,4-Oxadiazoles can also be synthesized from carboxylic acid chlorides. Because these... 

Brain, C.T., Paul, J.M., Loong, Y. and Oakley, P.J., Novel procedure for the synthesis of 1,3,4-oxadiazoles from 1,2-diacylhydrazines using polymer-supported Burgess reagent under microwave conditions, Tetrahedron Lett., 1999, 40, 3275. 

Li Z, Yu J et al (2004) Microwave accelerated solvent-free synthesis of 1,3,4-oxadiazoles using polymer supported dehydration reagent. Synth Commun 34 2981-2986... 

Brain et al. [86] suggested the synthesis of 1,3,4-oxadiazoles using a polymer-supported Buigess reagent (Scheme 11.33). Reactant 1,2-diacylhydiazines were taken and the product was purified by filtration through siUca gel. The product was obtained with up to 96% yield under microwave irradiation within 2-10 min. Kidwai et al. [87] reported iV-alkylation with 71-79% yield of the product under microwave irradiation (Scheme 11.34). 

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