Synthesis of Fluoroaromatic Compounds

Fluorinated arenes are widely used as precursors for synthesis of agrochemicals and pharmaceuticals [71] with a volume of several thousand tons per year [72]. More than 20 % of the pharmaceuticals currently in clinical testing contain fluorinated aromatic substructures, for some types of agrochemical the proportion is even exceeding 50% for newly introduced compounds. 

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R.D. Chambers, C.J. Skinner, J. Flutchinson, J. Thomson, Elemental fluorine.1. Synthesis of fluoroaromatic compounds, J. Chem. Soc. Perkin Trans. 1 (1996) 605-609. J.S. Moilliet, The use of elemental fluorine for selective direct fluorinations, J. Fluor. Chem. 109 (2001) 13-17. 

Elimination of two halogen atoms is a frequently used process in the synthesis of alkenes and alkynes, using a variety of conditions, and examples will be given later (see Chapter 7). Normally, fluorine is not easily removed by this process, although there are a number of cases where defluorination has been achieved, for instance in the preparation of fluoroaromatic compounds (Chapter 9). 

Elemental Huonne as a Legitimate Reagent for Selective Fluonnation of Orgamc Compounds Fluoroaromatic Compounds Synthesis, Reactions, and Commercial Applications New Aspects of Carbonylations Catalyzed by Transition Metal Complexes Polyfluoroaromatics An Excursion m Carbamon Chemistry ... 

In fluorine-18 chemistry some enzymatic transformations of compounds already labelled with fluorine-18 have been reported the synthesis of 6-[ F] fluoro-L-DOPA from 4-[ F]catechol by jS-tyrosinase [241], the separation of racemic mixtures of p F]fluoroaromatic amino acids by L-amino acylase [242] and the preparation of the coenzyme uridine diphospho-2-deoxy-2-p F]fluoro-a-o-glucose from [ F]FDG-1-phosphate by UDP-glucose pyrophosphorylase [243]. In living nature compounds exhibiting a carbon-fluorine bond are very rare. 

The above benzaldehydes and bromides are useful for preparation of new radiopharmaceuticals and various amino acids in d, l (50 50) or enriched L form by asymmetric synthesis41. Two general reaction schemes have been proposed42 for the synthesis of [18F]-labelled compounds for routine medical uses starting from substituted [18F]-fluoroaromatic aldehydes 24 and [18F]fluorobenzyl chlorides and [18F]fluorobenzyl bromides 25. The latter have been applied for preparation of 18F-labelled neuroleptics 26 (equation 19)43. 

Scheme 10 C-F bond formation from Pd(II) complexes (a) Proposed reductive elimination step in the synthesis of p-fluoronitrobenzene, (b) No fluoroaromatic compound was observed for aryl groups lacking the strong electron-withdrawing nitro substituent...

Banks RE, Thomson J (1985) Reaction of pyridinium t-butoxycarbonylmethylide with perfluoropropene and with some fluoroaromatic compounds synthesis of some fluorinated indolizines. J Chem Res Miniprint 2 671-689... 

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