Unusually substituted Fluoroheterocycles

Abstract

The research described in this thesis may be divided into five areas:1, Direct reduction methods involving reactions of pentafluoropyridine with metal hydrides were investigated in order to gain access to unusually substituted fluoro heterocycles. For example, 2,3,5-trifluoropyridine (7) was obtained by reaction of pentafluoropyridine with lithium aluminium hydride.2, The synthesis of a variety of unusually substituted fluoro heterocycles has been achieved via indirect reduction methods. For example, pentafluoropyridine was converted into 2,4,6-tribromo-3,5-difluoropyridine (11), which, following catalytic hydrogenolysis, gave 3,5-difluoropyridine (5). This chemistry was applied to the pyrimidine and quinoxaline ring systems.3, Reactions of the bromo fluoro heterocycles with a variety of nucleophiles gave fascinating results: hard nucleophiles such as sodium methoxide reacted with 2,4,6-tribromo-3,5-difluoropyridine (11) giving exclusive displacement of fluorine, whilst soft nucleophiles such as sodium thiophenoxide displaced bromine.4, Palladium mediated coupling reactions of the bromo fluoro heterocycles with alkynes proceeded with ease. The reaction of (11) gave fascinating results with the 2- and 6- position reacting in preference to the 4- position. Also, lithium-bromine exchange of (11) with butyl lithium afforded a stable 4-lithio pyridine derivative.5, As part of a strategy aimed at synthesising energetic materials, the reactions of 3,5-difluoro-4-nitropyridine-N-oxide (35a) and 3,5-dichloro-4-nitropyridine-N-oxide (36) with ammonia were compared. Interestingly, (35a) gave exclusive displacement of fluorine, whilst (36) gave exclusive displacement of the nitro group. Therefore, the relative order of mobility for this system was found to be F > NO(_2) > CI, which is entirely consistent with established data.