2- Fluoropyridine from 2-aminopyridines

One of the typical examples of the Baltz-Schiemann reaction is synthesis of fluoro-substituted pyridines 26 from aminopyridines 25 (Scheme 6.10). In this variation, the Baltz-Schiemann reaction is most often used for the synthesis of 2-fluoropyridines. In the first step, a diazonium tetrafluoroborate is generated from 2-aminopyridine, NaN02, and solution of HF and BF3 (HBF4), while subsequent thermal decomposition of the diazonium salt leads to formation of 2-fluoropyridines. In this chapter, we present several literature examples of synthesis of 2-fluoropyridines and examples of specific use of the Baltz-Schiemann reaction for preparation of biologically active derivatives of 2-fluoropyridines. 

The first compound having a C — F linkage in a heterocyclic ring was reported from Russia in 1915 by Chichibabin (Knunyants mentor, see ref 46) and Rjazancev. 2-Fluoropyridine was made by diazotization of 2-aminopyridine in concentrated hydrofluoric acid. 

Aminopyridines, from chloro-fluoropyridines, 48 frcia pyridines, 53 stabilization by charge separated forms, 734 tautomerism, 734 3-Ainino-2-pYridinesulfonic... 

Substituted 2,5-difluoropyridines 206 are obtained from the corresponding aminopyridines 205 by Baltz-Schiemann reaction, which are used in various areas of organic synthesis, including synthesis of biologically active compounds [108, 131-133]. For example, by few steps reaction 2-amino-3-bromo-5-fluoropyridine (205) was converted to biologically active compounds (210) by few steps [133] (Scheme 65). 

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