1.2.5- Oxadiazoles, amino-, fluorination

Fokin et al. directly fluorinated several aminofurazans (Scheme 14) to prepare 3-(difluoramino)furazans [109,110]. Similarly, certain N-alkyl-5-amino-tetrazoles were amenable to direct fluorination to 5-(difluoramino)tetrazole derivatives [111,112]. NF2-containing 1,2,4-oxadiazoles were prepared by Shreeve and coworkers by reactions of sodium 5-[(difluoraminomethyl)di-fluoromethyl]tetrazolate with oxalyl chloride [113]. 

Few examples are reported in the literature regarding the reactivity of fluorinated 1,2,5-oxadiazoles. As for many azoles, the nucleophilic substimtion of a fluorine atom is relatively easy and provided high yields. Huorofurazans A react with bisfuraza-nopyrazine dianion 194 yielding a disubstituted compound 195 (73 %) containing two tris (furazanyl)-amino moieties [98], The same reaction performed on fluoro-derivative B gave compound 196 (85 %), the precursor of macrocycle 197 synthesised by oxidative cyclization with dibromoisocyanurate (DBI) (Scheme 50). 

The application of fluorinated furazan is rather limited for synthesis and reactivity. Most studied derivative is 3-amino-4-trifluoromethyl-l,2,5-oxadiazole, which is commercially available. Nevertheless, in recent years, some perspective applications have been envisaged. In the agrochemical field a large library (more than 300 derivatives) of A-(4-triflnoromethyl-l,2,5-oxadiazol-3-yl)benzamides 257 has been prepared and considered for herbicidal activity [ 140], while l-(4-fluoro-1,2,5-oxadiazol-3-yl)pyrazole derivatives 258 were claimed as herbicides and plant growth regulators (Fig. 14) [141]. 

Buscemi S, Pace A, Pibiri 1, Vivona N (2002) Fluorinated heterocyclic compounds. Synthesis of 5-amino-, 5-N-aflsylamino-, and 5-N, N-dialkylamino-3-perfluoroheptyl-1,2,4-oxadiazoles. Heterocycles 57 1891-1896... 

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