Synthesis of Polyfluorinated Heterocycles by Indirect Fluorination with Silver Fluorides. II. Fluoropyrimidines^1-3

Polychloroheteroaromatic Compounds

“…With nucleophiles (e.g., ammonia [574], n-butylamine [574], primary [574,577] or secondary [577] aromatic amines, diethylamine [574], or alkoxide ions [578] ) tetrachloropyrimidine appears to react almost exclusively in the 4-position. A detectable amount of a 2-substituted product has been isolated from its reaction with diethylamine [574].…”

“…The claim [498,579] that tetrachloropyrimidine gives a 2-substituted product with triethylamine, tri-nbutylamine, NN-dimethylaniline, N-ethylpiperidine, or N-methylmorpholine is suspect in our opinion (see the discussion of the corresponding reactions of 2,4,6-trichloropyrimidine). With two equivalents of a nucleophile, a 2,4-disubstituted pyrimidine is the usual product [578]. An excess of ammonia is reported [533] to give a mixture of 4,6-diaminodichloropyrimidine and 2,4,6-triamino-5-chloropyrimidine, whilst two equivalents of ethylenimine also yield a 4,6-disubstituted derivative [580].…”

“…Tetrachloropyrimidine may be converted into 5-chlorotrifluoropyrimidine by reaction with silver fluoride [578] or into the perfluoro-compound by reaction with anhydrous caesium or potassium fluoride, preferably at elevated temperatures (410-480°) in an autoclave [214,569,583] . When the perchloro-compound is reacted with hydrofluoric acid in a nickel autoclave at 130° for 10 h, it yields a mixture of 5-chlorotrifluoropyrimidine (6%), a dichlorodifluoropyrimidine (39%), which is probably the 5,6-dichloro-2,4difluoro-compound, and a trichlorofluoropyrimidine (47%), which is probably trichloro-4-fluoropyrimidine [584] .…”

“…2,4,6-Trichloropyrimidine is converted into 2,4,6-trifluoropyrimidine on treatment with potassium [583,[585][586][587] or silver fluoride [531,578,588]. Lower fluorinated products may be formed also, depending on the reaction conditions.…”

“…Lower fluorinated products may be formed also, depending on the reaction conditions. Silver difluoride in the presence of triperfluorobutylamine converts the trifluoropyrimidine into perfluoropyrimidine [578,588]. When 2,4,6-trichloropyrimidine is treated with sulphur tetrafluoride at 225°, it gives a mixture of 4,6-dichloro-2-fluoro-and 2,6-dichloro-4-fluoropyrimidine [589].…”