1,3,4-oxadiazoles, microwave-assisted

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. 

Nicewonger R, Baldino C, Evans M (2003) The accelerated development of an optimized synthesis of 1,2,4-oxadiazoles. Tetrahedron Lett 44 9337-9341 Ondruschka B, Nuchter M, Bonrath W (2004) Microwave assisted synthesis— a critical technology overview. Green Chem 6 128-141 Regan J, Breitfelder S Cirillo P (2002) Pyrazole urea-based inhibitors of p38 MAP kinase from lead compound to clinical candidate. J Med Chem 45 2994-3008... 

Adib M, Jahromi AH, Tavoosi N et al (2006) Microwave-assisted efficient, one-pot, three-component synthesis of 3, 5-disubstituted 1, 2, 4-oxadiazoles under solvent-free conditions. Tetrahedron Lett 47(17) 2965-2967... 

A related series of 5-substituted-2-amino-oxadiazole compounds have also been prepared in a one-pot procedure using a microwave-assisted cyclisation procedure (Scheme 6.26)164. Rapid preparation of the pre-requisite ureas from the mono acyl hydrazines and various isocyanates (or the isothiocyanate) was easily achieved by simple mixing. The resulting products were then cyclo dehydrated by one of the two procedures either by the addition of polymer-supported DMAP and tosyl chloride or alternatively with an immobilised carbodiimide and catalytic sulphonic acid. Purity in most cases was excellent after only filtration through a small plug of silica but an SCX-2 cartridge (sulphonic acid functionalised - catch and release) could be used in the cases where reactions required additional purification. 

Kidwai, M., Kumar, P., Goel, Y. and Kumar, K., Microwave assisted synthesis of 5-methyl- 1,3,4-thiadiazol-2-ylthio/tetrazol-l-yl substituted pyrazoles, 2-azetidinones, 4-thiazolidinones, benzopyran-2-ones and 1,3,4-oxadiazoles, Indian. J. Chem., Sect. B, 1997, 36, 281. 

The microwave assisted synthesis of new lanthanum (III) and praseodymium (III) complexes with oxadiazole functionalized dithiocarbazinates, [M(L)3] is described [40]. 

Han et al. [41] gave the microwave assisted synthesis of novel alkyl substituted fructose-based oxadiazoles and investigated them for their cytotoxic activity... 

Xu et al. [44] reported the microwave assisted synthesis and antifungal activity of 2,5-disubstituted-l,3,4-oxadiazoles containing azulene moiety. The 5-aryl-2-(3-methylazulen-l-yl)-l,3,4-oxadiazoles (Lv) were obtained by the microwave... 

Sangshetti JN, Chabukswar AR et al (2011) Microwave assisted one-pot synthesis of some novel 2,5-disubstituted 1,3,4-oxadiazoles as antifungal agents. Bioorg Med Chem Lett 21 444-448... 

Natero R, Koltun DO et al (2004) Microwave-assisted one-step synthesis of substituted 2-chloromethyl-l,3,4-oxadiazoles. Synth Commun 34 2523-2529... 

Frank PV, Girish KS et al (2007) Solvent-free microwave-assisted synthesis of oxadiazoles containing imidazole moiety. J Chem Sci 119 41 6... 

Wang LN, Han D et al (2009) Microwave-assisted efficient synthesis of glucose-based 3-acetyl-5-alkyl-2,3-dihydro-l,3,4-oxadiazole derivatives catalyzed by sodium acetate. Carbohydr Res 344 2113-2119... 

The development of modem and reliable procedures for microwave-assisted organic synthesis has also been used advantageously for 1,2,4-oxadiazole synthesis by avoiding time-consuming steps, using green solvents or solvent-free conditions, or by directly employing acids rather... 

Scheme 6.21 Microwave assisted convenient synthesis of 7-(5-alkyl-l,3,4-thiadiazol/oxadiazol-...

PS-PPI13. A combination of PS-PPI13 and CCI3CN not only facilitated the formation of intermediate 1,2-diacylhydrazides by in situ conversion of carboxylic acids to acid chlorides, but also assisted subsequent cyclization to 1,3,4-oxadiazoles. The workup comprised simple filtration of the resin and evaporation of solvents, followed by flash chromatography. The cyclocondensation occurred within 20 min when heated in acetonitrile by microwaves in a sealed vial at 150 °C (68 °C above the boiling point) [92] (Scheme 32). 

A novel approach to synthesize the glucose-based 3-acetyl-5-alkyl-2,3-dihy-dro-l,3,4-oxadiazoles with the assistance of microwave irradiation was developed by Wang et al. [42]. The reaction of a mixture of E/Z hydrazones (xLvii, xLviii) with acetic anhydride under microwave irradiation above 160 °C, to produce the target 1,3,4-oxadiazoles (xLix, L), which are a parr of isomers on the C-3 of furan ring. 

In the preparation of novel 1,3,4-oxadiazoles 25 from 1,2-diacylhydrazines 24, Brain et al. used a highly efficient cyclodehydration assisted by use of microwaves,... 

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