1.3.4- Oxadiazoles, ring synthesis, from

An interesting example of oxadiazole ring formation from formally O-C-N-N-C-O component 109 is the synthesis of tricyclic system (pyridooxadiazolpyridine) depicted in Scheme 26 <1998MI655>. 

The diversity of reactions that can be performed on substituents attached to the furazan ring is well illustrated by the five-stage synthesis of the thieno[3,4-c][l,2,5]oxadiazole system (82) from the dibenzoyl compound (83 Scheme 16) borohydride reduction affords the... 

Some new methods for the synthesis of the oxadiazole ring have been recently published. 1,2,4-Oxadiazoles can be easily obtained in a one-pot solvent-free process starting from P-keto esters 169 and amidoximes 170. The process is likely to go through an acyl ketene intermediate <07TL2231>. 

The reaction sequence of Scheme 3 might well be classified as an imidazole synthesis from other heterocycles, but it seems more logical to treat this as a cyclization involving formation of the 1,5-bond. The enaminoketone condensation products (12) of 3-amino-l,2,4-oxadiazoles and 1,3-dicarbonyl compounds are cyclized by base to imidazoles (13) in 60-80% yields." Such a reaction makes use of the well-established general attack of a nucleophilic center in the side chain on N-2 of the oxadiazole ring. Benzamidine combines with 2-amino-3-phenacyl-l,3,4-oxadiazolium bromides to produce 1-acyl-amino-2-benzimidoylamino-4-arylimidazoles. ... 

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],... 

Condensed Ring Systems.—, 3A-Thiadiazolo[i,2-a]pyridines. For a synthesis of this ring system from the corresponding oxadiazole analogues, see p. 735. 

The methods A and B can be compared to the divergent synthesis of dendrimers. Method A starts from a central core and involves the reaction of the acid chloride groups and a subsequent cychsation with phosphorous oxychloride to the oxadiazole ring (Chap-... 

The concept of five-membered ring heterocyclic synthesis by transformation of the initial adduct of the ADC compound and substrate is not limited to cyclization of substitution products. l,3,4-Oxadiazol-2-ones (30, Scheme 3) result from heating the initial DEAZD-dichlorocarbene adduct.72 Treatment of the Diels Alder adducts 96 with zinc in acetic acid gives pyrroles in good yield (Eq. 17).151 The reaction has been extended to the synthesis of dipyrroles from the appropriate Diels-Alder adduct (96, R = pyrrol-2-yl). 

The synthesis of 1,3,4-oxadiazoles from tetra-zoles has been reviewed (94ZOB1698). 1,3,4-oxadiazolylacetones 104 (R = H, He, Ph etc) undergo ring-transformation to the isoxazoles 105 by reaction with hydroxylamine (95SYN805). 

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). 

Fused ring systems can be prepared either from an azine precursor or from an oxadiazole or thiadiazole precursor. In the sections on the synthesis of these compounds, the former method is grouped under Azine approach , the latter under Azole approach . 

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