5-Perfluoroalkyl-1,2,4-triazoles

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. 

Perfluoroalkyl substituted oxadiazoles are known to react readily with ammonia at room temperature to produce triazoles, (a) Brown, H.C., and Cheng, M.T. (1962) J. Org. Chem., TJ, 3240-3243. 

Bis(perfluoroalkyl)-l,3,4-oxadiazoles (285) are attacked readily by hydrazine with ring opening and formation of the perfluoroacylated hydrazidines (286). Concurrent dehydration and oxidation of these intermediates with iron(III) chloride produces the corresponding 3,6-bis(perfluoroalkyl)-l,2,4,5-tetrazines (287). Ring closure of (286) without oxidation produces the corresponding 3,5-bis(perfluoroalkyl)-4-amino-l,2,4-triazoles (66JOC781). 

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]. 

In the case of / -chloro-/ -perfluoroalkylvinylacetaldehydes, the reaction with sodium azide affords 4-perfluoroalkyl-substituted triazoles 10 and 11. 

Polyfluorinated target molecules are obtained when both building blocks are fluorinated and/or perfluoroalkylated. A typical example for this type of condensation is the synthesis of a tris(trifluoromethyl)-substituted 1,3,4-triazole from 3,5-bis(trifluoromethyl)benzhydrazide and trifluoroaceta-midine (78BRP1510647). 

Perfluoroalkyl-1,2,4-oxadiazoles 240 underwent an uncommon reaction with hydrazine to afford the corresponding triazoles 241 <03JOC605>. 

Mayot et al. [29] synthesized a series of fluoroalkylated amphiphilic 1,2,3-triazoles (xvi) by the 1,3-dipolar cycloaddition of 2-perfluoroalkyl-ethyl-azides by heating in microwave conditions. 

N-Amino-i-triazoles also can be obtained by a ring transformation of some heterocycles. For instance, hydrazine converts perfluoroalkyl 1,3,4-oxadiazoles, under mild conditions via the acyclic intermediate 168, into... 

Syntheses of quaternary l-alkyl-3-perfluoroalkyl-4,5-dimethyl-l,2,4-triazolium iodides have led to the disclosure of a variety of new quaternary salts <04JOC1397>. Arylation of 3-alkylthio-5-aryl-l,2,4-triazoles under basic conditions gave 5-alkylthio-l,3-diaryl-l,2,4-triazoles in moderate yields <04JHC201>. Acyl hydrazides 155 reacted with imidates 156 to yield 1,2,4-triazoles 157 followed by Mitsunobu reactions with amino alcohols 158 to give regioisomeric... 

FIGURE 3.85 Synthesis of perfluoroalkyl-substituted 1,2,4-triazoles from oxazoles. 

An example of a photochemical conversion of one fluorinated heterocyclic system (fluoropyrazole) to another (fluoroimidazole) was described above. In an another example of photochemical isomerization to access fluorinated heterocyclic systems, irradiation of perfluoroalkylated 3-A-methylamino-oxadiazoles 143 in the presence of an excess of methylamine produces perfluoroalkylated 1,2,4-triazoles 144 along with the isomeric 1,3,4-oxadiazole 145. The formation of an intermediate exo-cyclic diazerene 146 or the open-chain carbodiimide 147 was proposed (Fig. 3.87). If the irradiation is carried out in the presence of methanol and triethylamine. 

From these examples, the versatility of 1,3-cycloaddition reactions in the synthesis of 1,2,3-triazoles is apparent. Other strategies, however, are available. Greif and coworkers developed perfluoroalkyl-substituted p-chlorovinylaldehydes as new building blocks for a number of fluorinated heterocyclic systems such as thiazoles, pyridines, pyrazoles, and benzimidazoles. Reaction of the chlorovinylaldehydes with sodium azide leads to the formation of moderate to good yields of 4-perfluor-... 

Buscemi, S. Pace, A. Pibiri, I. Vivona, N. Spinelli, D. Fluorinated heterocyclic compounds. An expedient route to 4-perfluoroalkyl-l,2,4-triazoles via an unusual hydrazinolysis of 5-perfluoroalkyl-l,2,4-oxadiazoles first examples of an ANRORC-like reaction in 1,2,4-oxadiazole derivatives. J. Org. Chem. 2003, 68, 605-608. 

Hager, C. Miethchen, R. Reinke, H. Organofluorine compounds and fluorinating agents. Part 26. New reversed nucleosides—perfluoroalkyl substituted 1,2,3-triazoles linked to D-galactose and D-altrose. J. Fluorine Chem. 2000, 104, 135-142. 

The heterocyclization of fluorine-containing acyclic systems many various types of which are known, or direct introduction of fluorine or a perfluoroalkyl group into existing heterocyclic system [1, 7-15], So far the problems of the synthesis of highly nitrogenated cyclic systems, especially of 1,2,3-triazoles and tetrazoles have been poorly understood. It should be noted that quite a big number of original publications has appeared in this held within the last decade. 

The most conunon synthetic procedure for the preparation of perfluoroalkylated 1,2,3-triazole derivatives is 1,3-dipolar cycloaddition of azides to diverse unsaturated dipolarophiles containing perfluoroalkyl substituents. Thus, in 1966 Carpenter et al. carried out the cycloaddition of benzyl azide to perfluoroalkyl substituted acetylene derivatives leading to the formation of trifluoro-methyl-l,2,3-triazolines and 1,2,3-triazoles [39]. In this paper a synthesis of l-benzyl-4,5-bistrifluoromethyl-l,2,3-triazole 31 from hexafluoro-2-butyne was described. 

Some approaches to the synthesis of trifluoromethyl-l,2,3-triazoles by the azidation of compounds containing not a triple but a double C=C bond were described. In this case apparently a functional group elimination occurs in situ to provide the formation of an additional carbon-carbon bond. For instance, Miethchen et al. described a synthesis of 4-trifluoromethyl-1,2,3-triazole 53 linked to the C -atom of D-galactose and D-altrose. 1,3-Dipolar cycloaddition using the monosaccharide azides and the perfluoroalkyl- substituted phenylvi-nylsulfones was performed [55, 56],... 

According to Shreeve et al 4-trifluoromethyl-l,2,3-triazole 58 may be synthesized as a result of 1,3-dipolar cycloaddition of TMSNj to trifluoropro-pyne in the presence of Cu(I) [62], The synthesis of perfluoroalkyl-l,2,3-tri-azoles was also described in the earlier cited paper of Taylor et al. [35], In this study the reaction was investigated between perflnoropropadiene with phenyl azide resulting in regioisomeric 1,2,3-triazole containing at the endocyclic carbon atoms both the fluorine atom and the CFj-gronp. 

An example of the direct incorporation of a perfluoroalkyl group into the structure of an already formed 1,2,3-triazole was given [70]. In this paper a method of synthesis of 1-trifuoromethyl-substituted benzotriazole 67 is described by the chlorination of the corresponding methyl 1-azoledithiocarboxylates 68 followed by the fluorination of the resulting 1-trichloromethyl derivatives 69 using anhydrous HF [70],... 

Brown et al. also suggested a version of the synthesis of 3,5-bis(perfluoroalkyl)-4H-1,2,4-triazoles 71 from perfluoroalkylhydrazides and from bis-(perfluoroalkyl)-l,2-dihydro-l,2,4,5-tetrazines [73]. 

Lopyrev et al. developed an original method for the synthesis of 3-perfluoroalkyl-5-amino-l,2,4-triazoles 79 in nearly quantitative yields based on the cyclization of perfluoroacylaminoguanidines that in their turn were obtained in good yields (60-81 %) from hydrazides of perfluorocarboxylic acids and S-methylisothiourea [78]. 

New energetic materials were prepared from by perfluoroalkyl-l,2,4-triazoles. For instance, Shreeve et al. obtained 3-nitro-5-trifluoromethyl-1,2,4-triazole 90 by the diazotization of 3-amino-5-trifluoromethyl-l,2,4-triazole in the concentrated sulfuric acid [87], In its turn 3-amino-l,2,4-triazole and 3-nitro-5-trifluoromethyl-1,2,4-triazole were used in the preparation of energetic 3-amino-l,2,4-triazolium 3-nitro-5-trifluoromethyl-l,2,4-triazolate 91. Energetic polymeric material 92 was synthesized containing in the monomer unit ions of 3-nitro-5-trifluoromethyl-1,2,4-triazolate. The yield of polymer is unknown [88]. 

Read et al. synthesized surface-active derivatives of 1,2,3-triazole 49,50 containing at the nitrogen atom perfluoroalkyl (lipophilic) substituents, and at the carbon atom perfluoroalkoxy or alkoxy (hydrophilic) groups. It is significant that the surfactant properties of these compounds can be purposefully regulated varying the length of the fluoroalkyl chain [49, 50],... 

Wei J, Chen J, Xu J, Cao L, Deng H, Sheng W, Zhang H, Cao W (2012) Scope and regi-oselectivity of the 1,3-dipolar cycloaddition of azides with methyl 2-perfluoroalkynoates for an easy, metal-free route to perfluoroalkylated 1,2,3-triazoles. J Eluorine Chem 133 146-154... 

A combination of perfluoroalkyl and triazole moeties are used to promote emulsion formation in dichloromethane/water and to stabilize TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) used in the oxidation of alcohols to aldehydes . 

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