1.3.4- Oxadiazoles, perfluoroalkyl-, synthesis

An interesting synthesis of targeted 5-perfluoroalkyl-l,2,4-triazoles takes advantage of the aforementioned MNAC [70] photorearrangement of 3-methylamino-l,2,4-oxadiazoles 109 (R = Me) which, when irradiated at 313 nm in methanol and in the presence of various nitrogen nucleophiles (ZH in Scheme 12.32), produces triazoles 119 together with the 1,3,4-oxadiazoles 112 expected from the base-catalyzed RCRE route (Scheme 12.32) [71]. 

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. 

The natural development of the study of this class of compounds has been the synthesis of protic ILs. In this context, a series of 18 samples were prepared by appropriately mixing acid and basic building blocks (Figure 17). By using di- or monocarboxyhc perfluoroalkylic acids, in combination with 1,2,4-oxadiazoles functionalized with either two pyridines or one pyridine and a fluorinated chain, it is possible to obtain symmetric and nonsymmetric fluorous architectures, respectively (2012PCP14306). Many... 

Scheme 3 Synthesis of perfluoroalkylated bis-oxadiazoles 14 by the anudoxime route...

Scheme 15 Synthesis of 3-N-aIkylamino-5- perfluoroalkyl-1,2,4-oxadiazoles 51 by photofragmentation of 3-perfluoroalkanoylamino furazans 50...

In order to maximize yields, the irradiated solution needs to stand in the dark overnight, to complete the final cyclization step of 53 into 51. Although yields are not optimal due to the subsequent photoreactivity of compounds 51 at the used irradiation wavelength (see Sect. 2.3.3), this route appears to be the most accessible synthetic method for the synthesis of 3-(alkyl) amino-5-perfluoroalkyl-l,2,4-oxadiazoles. 

Scheme 17 Synthesis of perfluoroalkylated 1,3,4-oxadiazoles 57 by cyclodehydration of fluorinated diacylhydrazines 58 and Huisgen reaction of fluorinated 2-acyltetrazoles 56...

Scheme 22 The Acyl-Tetrazole Rearrangement Route in the synthesis of fluorinated 1,3,4-oxadiazoles 65, 5-perfluoroalkyl-2-phenyl-l,3,4-oxadiazoles 76 and 1,3-bis(2-phenyl-1,3,4-oxadiazol-5- yl)hexafluoropropane 78...

The preparation, properties and reactivity of 1,3,4-oxadiazoles have been extensively reviewed [173]. The 1,3,4,-oxadiazole most commonly used for the cycloadditions is 2,5-bis(trifluoromethyl)-l,3,4-oxadiazole. Its properties, preparation, and reactivity have also been reviewed [174]. The most commonly used procedure for the synthesis of this and other 1,3,4-oxadiazoles involves dehydration of N,N -diacyUiydrazides using agents such as perfluoroalkyl anhydrides [175], P2O5 [176], BF3 EtjO [177], or SO3 [178] (Scheme 16.85a). Unsymmetrically substituted 1,3,4-oxadiazoles also can be prepared by this route [179]. Alternatively, they may be prepared by oxidation of semicarbazones [180]. For example, an early procedure for the synthesis of 2-amino-5-aIkoxycarbonyl-l,3,4-oxadiazoles involves thebromination of semicarbazones followed by cyclization (Scheme 16.85b). Subsequently, a milder procedure was introduced that involves the preparation of unsymmetrical diacyUiydrazines followed by dehydration with tosyl chloride (Scheme 16.85c) [172]. Sulfonyl groups also activate 1,3,4-oxadiazoles and the preparation of 2-ethylsulfonyl-5-trifluoromethyl-l,3,4-oxadiazole has been described [181]. 

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