3-Alkylamino-1,2,4-oxadiazoles

Other non-traditional preparations of 1,2,3-triazoles have been reported. The rearrangement in dioxane/water of (Z)-arylhydrazones of 5-amino-3-benzoyl-l,2,4-oxadiazole into (2-aryl-5-phenyl-27/-l,2,3-triazol-4-yl)ureas was investigated mechanistically in terms of substituents on different pathways <06JOC5616>. A general and efficient method for the preparation of 2,4-diary 1-1,2,3-triazoles 140 from a-hydroxyacetophenones 139 and arylhydrazines is reported <06SC2461>. 5-Alkylamino-] //-], 2,3-triazoles were obtained by base-mediated cleavage of cycloadducts of azides to cyclic ketene acetals <06S1943>. Oxidation of N-... 

The 1,3-dipolar cycloaddition reaction of l,2-0-isopropylidene-a-D-xylopentodialdo-l,4-furanose oxime 262 with 3-(2-propynylthio)-l/f-l,2,4-triazole affords 3,4-bis-(l,2-0-isopropylidene-a-D-threofuranos 4-yl)-l,2,5-oxadiazole-2-oxide 263 as a main product (Scheme 68) <2000CHC393>. Synthesis of 3,4-bis(alkylamino)-l,2,5-oxadiazoles 265... 

The photochemistry of 3-amino- <2002JOC6253> and some 3-iV-alkylamino-5-perfluoroalkyl-l,2,4-oxadiazoles <2004JOC4108> was investigated. The latter reaction led to 5-perfluoroalkyl-l,3,4-oxadiazoles followed eventually by their conversion into 5-perfluoroalkyl-l,2,4-triazoles. 1,3,4-Oxadiazoles were also obtained by photochemical interconversion of 3-acylamino-l,2,5-oxadiazole derivatives. Mechanisms of these reactions were proposed <2004JOC4108>. Examples of these interconversions are shown in Scheme 37. 

Buscemi, S., Vivona, N. and Caronna, T. (1995) A generalized and efficient synthesis of 3-amino-, 3-(N-alkylamino)-, 3-(N, N-dialkylamino)-5-alkyl-l, 2,4-oxadiazoles by irradiation of 3-alkanoylamino-4-phenyl-l, 2,5-oxadiazoles (furazans). Synthesis, (8), 917-919. 

Buscemi, S., Pace, A. and Vivona, N. (2000) Fluoro heterocycles. A photochemical methodology for the synthesis of 3-amino- and 3-(N-alkylamino)-5-perfluoroalkyl-l,2,4-oxadiazoles. Tetrahedron Letters, 41 (41), 7977-7981. 

A solid phase synthesis of substituted 3-alkylamino-l,2,4-oxadiazoles has been developed. The synthesis started from TV-acyl-1 //-bcnzotriazole-1 -carboximidamides 228. Treatment with hydroxylamine afforded the oxadiazole skeleton 229 in high yield <02TL5043>. 

Irradiation of 3-[o-(alkylamino)phenyl]-5-methyl-l,2,4-oxadiazole 1507 leads to concomitant formation of benzimidazoles 1509 and indazoles 1508, presumably arising from a common photolytic species, as shown in Scheme 390 <1996JOC8397>. 

More recently, a solid-phase synthesis of 5-substituted 3-alkylamino-l,2,4-oxadia-zoles has been developed [99]. The method utilizes immobilized N-acyl-lH-benzo-triazole-l-carboximidamides as key intermediates. Cyclization with hydroxylamine under mild conditions furnished the oxadiazole template regioselectively. 

Oxadiazoles can also be prepared from amides via acylamidines, ° or via the cycloaddition of nitrile oxides to nitriles, as illustrated. "" 3-Alkylamino-l,2,4-oxadiazoles result from the reaction of N-acyl-l-benzotriazolyl-l-carboximidamides with hydroxylamine. " ... 

A variety of alditol-l-yl substituted heteiocyclic derivatives have been synthesized. The tetiazole derivative (94) was derived riom maltose, and convened into the corresponding 1,3,4-oxadiazoles (95) on acetylation or benzoylation. Reaction of l-arylamino- or 1-alkylamino-l-deoxy-D-arabino-hexuloses with cyanamide gave the imidazole derivatives (96). Fructosazine (97) and deoxyfiructosazine (98) were simultaneously formed by self-condensation of 2-amino-2-deoxy-D-glucose in neutral to basic aqueous solutions, and were shown to have DNA strand breaking activity. Condensation of 2-amino-2-deoxy-D-glucose with aryl isocyanates gave adducts such as (99) that exist in solution as (R,5)-mixtures in which the (R)-fonn predominates. ... 

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