1.2.5- Oxadiazoles, synthesis from oximes

Examples include the synthesis of 3-amino-l,2,4-oxadiazoles starting from 3-acylamino-5-methyl-l,2,4-oxadiazole <2002H811> and 2-aryl-l,2,3-triazoles from l,2,4-oxadiazole-3-ketone arylhydrazones <1999T12885, 2006JOC5616>. Oximes, hydrazones, formamidines, and thioureas of the furazan series also undergo base-catalyzed mononuclear rearrangements <2004RCB1121>. Nucleophilic attack at N(3) takes place in the benzofuroxan series. For example, reaction with secondary amines leads to o-nitroarylhydrazines (Scheme 55). 

Oxadiazoles can be prepared by acylation of amidoximes. A variation of this method gives a one-pot synthesis from the amidoxime, an organic acid and a peptide coupling agent the method is sufficiently mild that there is no racemisation when mandelic acid is used. 1,2,4-Oxadiazoles can also be prepared from amides via acylamidines, " or via the cycloaddition of nitrile oxides to nitriles, as illustrated, or to 6>-methyl oximes. ... 

The usual method of synthesis of this system is by condensation of a diketone with 3,4-diamino-oxadiazoles (151). The alternative use of butyllithium followed by a bis-chlorooxime leads to the formation of the derivative (152) <91JHC1677> which can be cyclized to a bis(oxadiazolo)pyrazine (Equation (20)). Tetrahydro derivatives are formed from the bis-oximes (153) which give either the furoxan derivatives (155) (70-98%) by oxidation with potassium ferricyanide or the oxadiazoles (154) (55-70%) on heating (Scheme 14) <85JOC5l23>. 

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