1,2,4-Triazole, 3-fluoro-, synthesis

Analogously, ethyl 4-fluoro-3-methylcrotonate is brominated with NBS in the presence of AIBN and then reacted with triethyl phosphite to produce good yields (72-78%) of a-fluorophosphonate, a key intermediate in the synthesis of fluorinated vitamin A esters (Scheme 3.3)7 Following a similar procedure (radical bromination and Michaelis-Arbuzov rearrangement), ( )-l-fluoro-3-(l-trityl-l,2,4-triazol-3-yl)-2-propenylphosphonate, a good inhibitor of imidazoleglycerol phosphate dehydratase, has been prepared in 25% overall yield. ... 

The first synthesis of ring-fluorinated 1,2,4-triazoles was reported in 1973. Reaction of 3(5)-nitrotriazoles with liquid HF at 150°C produces the corresponding 3(5)-fluoro-1,2,4-triazole in good yield (Fig. 3.83). Although an efficient process, the reaction conditions make routine application problematic. 

Zumbrunn, A. The first versatile synthesis of l-alkyl-3-fluoro l/7-[l,2,4]-triazoles. Synthesis 1998, 1357-1361. 

S. Olgen and C. K. Chu, Synthesis and antiviral activity of 2 -deoxy-2 -fluoro-L-arabinofura-nosyl 1,2,3-triazole derivatives, Z. Naturforsck, 56b (2001) 804-811. 

In general the information on the synthesis and properties of the N-fluorinated derivatives of 1,2,3- and 1,2,4-triazoles is very scanty [6]. The data about N-fluorotetrazoles are totally absent today. We discuss below the results of the few publications considering the synthesis of N-fluoro-1,2,3- and l,2,4-fliazoles. This desultory information is difficult to classify since the most of these papers lack any experimental details on the synthesis of the compounds of this type and the proofs confirming the structure. 

An example of synthesis of N-fluoro-1,2,4-triazole was described in the patent of Strazdina and Grinstein [6, 17]. Here l-flnoro-3,5-dibromo-l,2,4-triazole 8 was obtained by treating the heterocyclic substrate with the hypohalous acid or its derivatives at -40 to -h50 C in water or an organic solvent in the presence of bases. Langlet and Oslmark in a patent [18] have described the application of isomeric fluoro-triazolones 9,10 as components of explosive compositions, but the data on the synthesis of these substances have been not reported. 

Miroshnichenko et al. [19] published results on calorimetric investigation of N-F derivatives of various nitroazoles, in particular, of some N-fluoro derivatives of 1,2,3- and 1,2,4-triazoles 11-13 (the values of standard enthalpy of formation AHf°, kJ/mol are given in parentheses). Regretfully, the methods of the synthesis of N-F triazoles and the data confirming their structure and individuality were not reported in this article. 

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