1.3.4- Oxadiazole, 2-phenyl-, ring synthesi

A development in the synthesis of macromolecular scintillators is the radical co-polymerization of alkenes with the fluorescent co-monomer 2-t-butyl-5-(4 -vinyl-4-biphenylyl)-l,3,4-oxadiazole <89MI 406-04). Basic initiators cause ring opening of 2-phenyl-l,3,4-oxadiazolin-5-one with subsequent anionic polymerisation to form A-benzamido-1-nylon [-N(NHCOPh)CO-] <90PB583>. 

A particular case of a photochemical strategy towards functionalized benzimidazoles regards the synthesis of 2-acylamino derivatives 70, which can be obtained from irradiations in methanol of 3-(o-amino)phenyl-l,2,4-oxadiazoles 68. In this reaction, a photolytic cleavage of the ring O—N bond, followed by migration of the aryl substituent, leads to the carbodiimide intermediate 69, a precursor of the benzimidazole nucleus (Scheme 12.20) [47]. 

The structure of 1,2,4-oxadiazoles has not been in dispute since covalent structures can be drawn from the methods of synthesis. The geometry of the ring was estimated for theoretical calculations years before X-ray measurements were available. Microwave spectra and recently fluorescence spectra have been used to determine the dipole moments of oxadiazoles and oxadiazolines, the latter being high by comparison (Table 7). Electron densities were calculated for 5-methyl-3-phenyl-l,2,4-oxadiazole (88) and its 2,3-dihydro derivative (89) (77JOC1555). 

The paths to the production of compounds containing an oxadiazole ring from isatoic anhydrides are more varied. For example, the synthesis of 5-(2-aminophenyl)-3-phenyl-l,2,4-diazole in two stages was patented a mixture of phenylacetonitrile, hydroxylamine sulfate, and the salt of the dibutylamide of sulfonated oleic acid was kept with an aqueous solution of sodium carbonate at 90°C for 5 h, the anhydride 1 was added, and the reaction mixture was kept at the same temperature with 50% aqueous sodium hydroxide for 1 h [12],... 

Buscemi S, Pace A, Palumbo Picdonello A, Macaluso G, Vivona N, SpineUi D, Gioigi G (2005) Fluorinated heterocyclic compounds. An effective strategy for the synthesis of fluorinated Z-oximes of 3-perfluoroaIkyl-6-phenyl-2H-l,2,4-triazin-5-ones via a ring-enlargement reaction of 3-benzoyl-5-perfluoroaIkyl-l,2,4-oxadiazoles and hydrazine. J Org Chem 70 3288-3291... 

Merck described the S5mthesis of PDE4 inhibitor 107 as a potential antiinflammatory drug, the synthesis of which involved a Knoevenagel condensation between aldehyde 105 and benzyl oxadiazole 106 as the key step. The researchers were concerned about the possibility of the formation of olefin isomers in the condensation, due to the similar sterics of the phenyl and ox diazole rings. They found however, that by performing the reaction in isopropanol (in which both the starting aldehyde 105 and product 107 have limited solubility) the initially-formed mixture of olefin isomers equilibrates, and the desired product crystallizes out of the mixture to provide exclusively the desired isomer. 

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