Antipyrine, fluorination

Antipyretic agents, (I.2.4]triazolo[l,5-a]-pyrimidines, 57, 126 Antipyrine, fluorination by acetyl hypofluorite, 59, 4... 

Antipyrine (18) a lipophilic compound that has been shown to have a high uptake by the brain is also fluorinated and consequently dehydrofluorinated.75 The cxv-addition mode is exploited for the preparation of the adducts 19 and 20 of 7-oxabicyclo[2.2.1]hept-5-ene and 2-azabicyclo[2.2.1]hept-5-en-3-ones with fluorine which arc used in the preparation of di-fluorodeoxyhexofuranosides and fluoronucleosides.76 Fluorine also undergoes addition to oxazolones 21 for the eventual synthesis of /i-fluorinated a-amino acids.77... 

An indole 9 and antipyrine (11) were fluorinated to give the respective fluoro derivatives 10 and 12. Attempts to fluorinate furan, pyrrole, N-benzylpyrrole, ethyl 2-thienylacetate, and methyl 2-thiophenecarboxylate with various salts were all unsuccessful owing to excessive tar formation (90JA8563). Porphyrins are efficiently fluorinated at meso positions, and tetrasubstituted derivatives, such as meso-tetraphenylporphyrin, are inert. The preparation of a mixture of fluorinated derivatives 14-18 from 13 and monofluorination of 19 to give 20 are instructive. Interestingly, the products 14-18 were separated into pure components by simple silica gel chromatography (92TL1069). 

Antipyrine (254 R = H) reacts with fluorine-18 in acetic acid under nitrogen to yield the fluoro-derivative (254 R = F) in a radiochemical yield... 

Although requiring high temperatures and long reaction times for the fluorination of aromatic compounds, A-fluoro-2,4,6-tri-methyl triflate (2) was also used for the fluorination of estrone, methyl /J-hydroxyphenylacetate, and some heteroaromatic rings such as indoles or antipyrine derivatives. However, furan, pyrrole, A -benzylpyrrole, ethyl 2-thienylacetate, or methyl 2-thio-phenecarboxylate could not be lluorinated with reagent 2. ... 

---