Polyfluorinated pyridines, from

Scheme 6.39 shows methods of synthesis oftri- and tetrafluoropyridines 130,131, and 135 from corresponding di- and trifluoropyridines 99,108, and 132. The starting material is first lithiated by -BuLi and then transformed into chlorofluoropyridines 128,129, and 134. The last step of the synthesis is based on Halex exchange reaction using spray-dried KF in anhydrous DMSO to give the corresponding polyfluorinated pyridines 130, 131, and 135" (Scheme 6.39). 

Mixtures of polyfluorinated pyridines can be obtained from the corresponding pyridines by fluorination with tefrafluorocobaltates(III) however, this reaction has a low selectivity. For example, the reaction mixture derived from the reaction of pyridine with KC0F4 at 220°C is reported to contain more than seven fluoropyridines, two fluoro-2-azahexenes, three azahexadienes, and two fluoro-Al-methylpyrrolidines. Four fluorinated products were isolated from a fluorination of pyridine by C0F3 at 150°C a 2-azahexene, two Al-methylpyrrolidines, and 4//-nona-fluoropiperidine. ... 

Patent literature dealing with the alkylation of polyfluorinated pyridines and related compounds by carbanions generated in situ from fluoro-oleflns... 

Using cobalt(III) fluoride at 150 , pyridine gives94 mainly perfluoro(l-methylpyrrolidine) and its 3H derivative, together with a small quantity of an open-chain compound. With potassium tetrafluorocobaltate(III),94 95 open-chain compounds predominate, the main ones being perfluoro(A-methylbutan-l-imine) and 2//,3//-heptafluoro(Af-methylbut-2-en-l-imine). Also formed are smaller amounts of polyfluorinated 1-methylpyrrolidines (ca. 5 % of the product mixture) and polyfluoropyridines (ca. 10%). 4-Methylpyridine gives95 only open-chain products, akin to those formed from pyridine, over potassium tetrafluorocobaltate(III) at 200-220 CC. 

The fluorination of quinoline was performed in a microstructured reactor operated in the annular-flow regime, which contained one microchannel with two consecutive feeds for gas and liquid [311,312]. The role of the solvent was large. The reaction was totally unselective in acetonitrile and gave only tarlike products. With formic acid, a mixture of mono- and polyfluorinated products besides tar was formed. No tar formation was observed with concentrated sulfuric acid as solvent at 0-5 °C. In this way, a high selectivity of about 91% at medium conversion was achieved. Substitution was effective only in the electron-rich benzenoid core and not in the electron-poor pyridine-type core. The reactivity at the various positions in the quinoline molecule is 5 > 8 > 6 and thus driven by the vicinity to the heteroatom nitrogen that corresponds to the electrophilic reactivity known from proton/deuterium exchange studies in strong acid media. 

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