Fluorination aromatic

A. E. Pavlath and J. E. Aromatic Fluorine Compounds, Reiohold Publishing Corp., New York, 1962. 

Nucleophilic Displacement Reactions. The presence of activating groups, eg, o,p mX.1.0 groups, makes aromatic fluorine reactive in nucleophilic displacement reactions. This has been demonstrated by deterrnination of the relative fluorine—chlorine displacement ratios from the reaction of halonitroben2enes with sodium methoxide in methanol (137) F is displaced 200—300 times more readily than Cl. 

Handbook of Aromatic Fluorine Compounds, Olin Corp., Stamford, Coim., 1976. 

R. H. Shiley, D. R. Dickerson, and G. C. Finger, Aromatic Fluorine Chemisty at the Illinois State Geological Survey, circular 501, Urbana, lU., 1978. 

Aromatic Fluorine Chemistry at the Illinois Shiley, R H, Dickerson D R... 

The preparation of aromatic fluorine compounds may be accomplished by direct fluorination or by fluonnation of organometallic intermediates. Tlte ipso fluorination of an aryl organometallic derivative with a positive fluorine reagent allows control over the regioselectivity of the fluorination and offers advantages in the preparation of F-labeled materials [II, 50],... 

Pavlath, A E, Lefffler, A J Aromatic Fluorine Compounds Monograph... 

Replacement of an aromatic fluorine atom by a carbon nucleophile is facihtated by the presence of electron-withdrawmg groups [82] (equation 44) Replacement of an activated aryl hydrogen can occur in preference to a nonactivated aryl fluorine [Si] (equation 45) in reactions known as vicarious subsututions. 

The mfluoromethyl group activates the fluorine in position 4 ofperfluorotolu ene toward reaction with carbon nucleophiles Examples on che use of perfluoro-toluene as an arylation agent abound, and in all cases, the 4-fluonne atom is replaced predommantly or exclusively [% 87,88,89, 90 (equation 48) In perjluoromesity-lene, the aromatic fluorine atoms are activated toward Ar reaction, and a reaction... 

He has published more than 100 research papers and holds 25 patents. He has written three books, one of them ACS Monograph 155, Aromatic Fluorine Compounds, in 1963. In 1976, he received the ACS California Section Award for Outstanding ConUibution to Chemistry for his work of a quarter century on various aspects of fluorine chemistry. In addition to his scientific activities, he is also serving his second term on the ACS Board nf ri... 

Since the aerobic degradation of halogenated phenols takes place by monooxygenation and is discussed in Part 2 of this chapter, it is not discussed here except to note the production of chlorocat-echols from chlorophenols and chloroanilines. Emphasis is placed on chlorinated substrates, and reference may be made to a review (Allard and Neilson 2003) for details of their brominated and iodinated analogs. The degradation of aromatic fluorinated compounds is discussed in Part 3 of this chapter. 

Drivers for Performing Aromatic Fluorination in Micro Reactors... 

Aromatic fluorination certainly is one of the best candidate reactions for micro reactors. Fluorinated compounds are of high industrial interest. For instance, they find wide application as pharmaceuticals, dyes, liquid crystals and crop-protection agents [3,13,16, 38] about every third drug contains a fluorine moiety. The introduction of fluorine moieties in molecules has unique effects on biological activity (see original citations in [16]). 

Beneficial Micro Reactor Properties for Aromatic Fluorination... 

Fluorination can be carried out using fluorine diluted with an inert gas. However, great care is necessary to avoid uncontrolled reaction.21 Several other reagents have been devised that are capable of aromatic fluorination.22 Acetyl hypofluorite can be prepared in situ from fluorine and sodium acetate.23 This reagent effects fluorination... 

Several A-fluoro derivatives of l,4-diazabicyclo[2.2.2]octane are useful for aromatic fluorination.25... 

The physiological effects of the fluoride ion were reviewed by McClure 74) in 1933. Lehmann 72) published an article on the toxicity of aromatic fluorine compounds in 1928. However, it has been impossible to investigate the toxicity of the organofluorine compounds as thoroughly as that of the organochlorine compounds. 

Being electron-rich aromatics, fluorine nuclei on fluoropyrroles are generally somewhat shielded relative to those of fluorobenzenes, but the chemical shifts can be significantly affected by further substitution (Scheme 3.63). Fluorines at the 2-position are much more deshielded than those at the 3-position. 

Figure 4.19 DFDNB is a small crosslinker able to form covalent bonds between amine-containing molecules. The aromatic fluorine atoms are readily displaced by nucleophiles.

Aromatic fluorination can be carried out by a regiospecific destannylation process shown in reaction 69. This is an effective method for producing fluorinated m-tyrosine and other radiopharmaceuticals, as shown in reaction 70. The process can be applied for radiolabelling with 18F, denoted as F in these reactions, and the products used as radioactive tracers for clinical and fundamental investigations318-321. 

The N-fluoroimide effects direct aromatic fluorination at 22°, with high preference for ort/io-substitution of substituted arenes. It also converts NaC(CH3)-(COOC2H5)2 into FC(CH,)(COOC2Hs)2 in 96% yield.1... 

Finger, G. C., Reed, F. H. and Tehon, L. R. (1955). Aromatic Fluorine Compounds as Fungicides. Illinois State Geological Survey. 

Aromatic Fluorinations Under Phase Transfer Conditions... 

Aubagnac, J.-L. Gilles, I. Claramunt, R.M. Escolastico, C. Sanz, D. Elguero, J. Reduction of Aromatic Fluorine Compounds in FAB-MS. Rapid Commun. Mass Spectrom. 1995,9,156-159. 

Balz, G. Schiemann. G. Ber. Dtsch. Chem. Ges. 1927, 60, 1186. Gunther Schiemann was bom in Breslau, Germany in 1899. In 1925, he received his doctorate at Breslau, where he became an assistant professor. In 1950, he became the Chair of Technical Chemistry at Istanbul, where he extensively studied aromatic fluorine compounds. 

Aromatic fluorine for halogen (F-X) exchange reactions (DMSO, 160°C, 20 min) in an [ F]fluoride-cryptand-oxalate system using 4 -halo-acetophe-nones (F, Cl, Br and I) has also been studied. The relative efficacy of the exchange is the following one F-F > F-Cl > F-Br > F-I, the radiochemical yield for the exchange F-F being similar to that of the commonly employed NO2 or +NMej displacements [113]. 

---