L. D. Starr | USGS Science

USGS2002

Aromatic fluorine compounds. XI. Replacement of chlorine by fluorine in halopyridines

The α -halogenated pyridines react with potassium fluoride in various solvents to give replacement of the α -halogen by fluorine. A 50% yield of 2-fluoropyridine was obtained from 2-chloropyridine by heating with potassium fluoride in dimethyl sulfone or tetramethylene sulfone for twenty-one days; 2-bromopyridine gave a similar yield with a heating period of only seven days. The α -halogens of the polyhalopyridines undergo the exchange reaction more readily than do the halogens of the α -monohalopyridines. The proposed structures of the fluoropyridines are supported by alternate syntheses and by n.m.r. studies.

Journal of Organic Chemistry↗

USGS2002

Aromatic fluorine compounds. X. The 2,3- and 2,6-difluoropyridines

The preparation of difluoropyridines by the Schiemann reaction was investigated. 2-Amino-6-fluoropyridine (IIIa), necessary for the synthesis of 2,6-difluoropyridine (IVa) by the Schiemann reaction, was conveniently prepared by the Curtius degradation of 6-fluoropicolinic hydrazide (IIa) and by the Hofmann reaction on 6-fluoropicolinamide (IId). Since an α -fluorine on a pyridine nucleus is preferentially replaced by hydrazine when it is either adjacent to or opposite a carbomethoxy group, the hydrazides necessary for the synthesis of 3-amino-2- and 6-fluoropyridine could not be prepared. These amines were prepared from the appropriate 2-fluoropyridinecarboxamide by the Hofmann reaction. The preparation of difluoropyridines was successful with two of the aminofluoropyridines and led to the following new compounds: 2,3-difluoro(IVb) and 2,6-difluoropyridine (IVa).

Journal of Organic Chemistry↗