Fluoroaromatics synthesis

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 ... 

Table 3. Synthesis of ort/io-Substituted Fluoroaromatics from Nitrite Esters, Boron Trifluoride, and Hydrogen Fluoride [26]...

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. 

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. 

C. Lemaire, M. Guillaume, L. Christiaens, A.J. Palmer, R. Cantineau, A new route for the synthesis of [F-18]fluoroaromatic substituted amino-acids—No carrier added i-p-[F-18]fluorophenylalanine, Appl. Radiat. Isot. 38 (1987) 1033-1038. 

The decomposition of arenediazonium tetrafluoroborates in the resulting fluoroarene as solvent has also been utilized.179 This method is very fruitful in the synthesis of fluorobenzene (96% yield) or fluorotoluenes (85-88% yield for the three isomers) but fails with substrates such as anisolediazonium tetrafluoroborates which probably arylate the reactive fluoroaromatic solvent. In contrast, perfluorinated tertiary amines (EF-L 174, F-C 40), perfluorinated alkyl tetrahydropyran (EF-L 102), perfluorodecahydronaphthalene (Flutec PP7) or other per-fluorocycloalkanes (Flutec s) are claimed to be the best media for fluorodediazoniation of all types of diazonium tetrafluoroborates.224 These media seem to be more efficient, at least in the synthesis of 1,2-difluorobenzene, than silicone oil which has also been claimed to improve fluorodediazoniation.225... 

Fluoroaromatic Compounds Synthesis, Reactions, and Commercial Applications ... 

C. D. Hewitt, M. J. Silvester, Fluoroaromatic Compounds Synthesis, Reactions and Commercial Applications, Aldrichim. Acta 1988, 21, 3-10. 

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. 

Perchloryl fluoride, which is a gentle reagent, does not react with alcohols, aldehydes and normal double bonds but does react with aliphatic or aromatic anions. It was instrumental in the synthesis of chlorofluoro and difluoro malonaldehydes (equation 127)227 and of fluoroaromatics such as fluoroveratrole228 and fluorotamoxifen 22 (equation 128)229, both having considerable biological potential. 

Figure 38 Synthesis of PAEKs incorporating various types of functional groups. Types of X groups incorporated imide, amide, sulfone, ester, azo, quinoxaline, aliphatic, fluoroaliphatic, fluoroaromatic. (From Ref. 164.)...

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). 

Anhydrous tetrabutylammonium fluoride (TBAF) has been reported as being a very powerful fluoride source for the preparation of fluoroaromatic derivatives, via fluorodenitration, under mild reaction conditions.5 In fact, this reagent is not totally anhydrous and water, in less than one molar equivalent, is present together with <10 mol% of decomposition products that arise during the synthesis of TBAF from commercially available tetrabutylammonium fluoride trihydrate. 

Potassium organophosphide reagents also continue to find applications in synthesis. Direct displacement of fluoride from fluoroaromatic substrates by potassium diphenylphosphide is the key step in the synthesis of the phosphi-noarylsulfoxides (88), water-soluble phosphino-amino acid systems, e.g. (89), ° and the chiral benzoxazine system (90). Related displacement of fluoride by potassium monophenylphosphide has been used to prepare a series of hydrophilic triarylphosphines, e.g. (91). Among new phosphines prepared by conventional displacement reactions by potassium diphenylphosphide on... 

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...

Synthesis of this fluorine-containing intermediate poses a special synthetic problem. Several proposals for making 3-bromo-4-fluorotoluene 291, -benzaldehyde 290 or -benzoic acid are matter of patent applications. The next Reaction schemes 207/208 outline the reactions starting with fluoroaromatics. 

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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