Direct functionalizations 1,2,5-oxadiazole

Functionalization of Furazan. 1,2,5-Oxadiazole belongs to the broader class of furazans that are known to possess potent biological activities. Although this class of compounds are well explored, little is known about direct functionalization of 1,2,5 oxadiazole to access its substituted congeners, which are usually synthesized from their corresponding substituted glyoxime derivatives. Neat 1,2,5-oxadiazole reacts with methyl diazoacetate in the presence of cupric stearate to form 4-methoxycarbonylmethyl 1,2,5-oxadiazole in 12% isolated yield (eq 2). It should be noted that the reaction does not proceed with the use of rhodium acetate. 

Section 5 deals exclusively with oxadiazoles in which a functional group is directly attached to the ring. A number of such compounds have already been mentioned in Section 2 in connection with their formation. 

The direct introduction of functional groups into the oxadiazole nucleus is possible in only a few cases. The protonation of the nuclear nitrogen in acidic media reduces extremely strongly the possibility of electrophilic attack.119 Thus no nitrations or sulfonations of unsubstituted oxadiazoles are known in the literature. Halogenation also has not so far been described although in this case the deactivating effect of the oxadiazole nucleus is not so important.47,61... 

Perfluoroheptyl-l,2,4-oxadiazol-3-yl)pyridine or 3-(5-perfluoroheptyl-l,2, 4- oxadiazole-3-yl)pyridine 26, have been obtained directly (in 90 and 70 % yields, respectively) from the acylation reaction of the corresponding nicotyl amidoxime and isonicotyl amidoxime (Scheme 7) [16], From these derivatives, the corresponding AT-methyl-pyridinium salts have been prepared for possible applications as Self-Organized Functional Organic Salts (SOFOS) [16]. 

Y. Yu, H. Fujita, M. Ohno, S. Eguchi, 1,3-dipolar cydoaddition of nitrile functions with nitrones under high pressure conditions. A new and direct synthesis of 2,3-dihydro-l,2,4-oxadiazole derivatives. Synthesis (1995) 498-500. 

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