Fluorobenzene Fluorobenzoic acid

However, this achievement was then marred by an unfortunate error. The calcium salt of 4-fluorobenzoic acid was heated in admixture with calcium hydroxide, and fluorobenzene was claimed to be formed by decarboxylation. Later, it was shown16 that the product, a solid, was phenol. It had been analyzed only for carbon and hydrogen content an early warning to all workers in fluorine chemistry of the need for quantitative assays for fluorine in their products. Being more activated than fluorobenzene towards nucleophilic attack, the fluorobenzoate anion itself probably lost fluorine before decarboxylation occurred. A benzyne-type process seems to be a less likely reaction pathway. 

Dihalo-5-fluorobenzoic acids, obtained by oxidation of the corresponding acetophenones, have received considerable attention as intermediates for antibacterial fluoroquinolones [28, 29], In this regard, 1,2,4-trifluorobenzene reacts with acetyl chloride to give 2,4,5-trifluoroacetophenone [29] (equation 19) 1,3,5-Tn-fluorobenzene and 1,2-difluorobenzene yield 2,4,6-trifluoroacetophenone and 3,4-difluoroacetophenone, respectively [30] (equations 20 and 21). 

The reader is referred to the synthesis of 4,4 -difluorobiphenyl,S8 4-fluorobenzoic acid,59 fluorobenzene,60 and l-bromo-2-fluorobenzene,61 published in Organic Syntheses, and to the syntheses of 3-fluorotoluene, 3-nitrofluorobenzene, 4-fluorobromobenzene, 4-fluoroanisole, 2-fluoronaphthalene, 3-fluoropyridine, and 4,4 -difluorobiphenyl published in Organic Reactions... 

In one of his papers [180] Gilman reports on the metallation of fluorobenzene. Interaction at — 50 °C between this compound and BuLi in THF for 7 hours, followed by carboxylation gave a reasonable yield of fluorobenzoic acid. Fluorine activates vicinal protons exclusively by its (strong) -I effect, and it should be possible to shorten the reaction time by using more strongly basic systems. Indeed, if the reaction in THF is carried out with BuLi TMEDA, the formation of... 

---