Fluorinated moieties

This reaction scheme involves two substitutions of fluorine moieties at the aromatic ring by amines, yielding the final product for pharmaceutical applications [83, 118]. In total, five synthesis steps are actually required to obtain the target molecule. 

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]). 

GL 1] [R 1] [R 3[ [P la-d[ A ratio of ortho-, meta- and para-isomers for mono-fluorinated toluene amounting to 5 1 3 was found for the falling film micro reactor and the micro bubble column at a temperature of -16 °C (3, 38]. This is in accordance with an electrophilic substitution pathway. The relatively high amoimt of ortho-isomers is due to the small size of the fluorine moiety as the ortho position is amenable to steric effects. 

Fortuitously for this project, the drug substance, and not the excipients, contained a fluorine moiety. Fluorine-19 MAS spectra were therefore also acquired at 500 MHz on the two samples, and they are shown to the right of the corresponding carbon spectra for each sample in Fig. 10.25. The fluorine-19 chemical shifts are sensitive enough in this example to show the API-excipients interaction directly. This is evident from the dramatic change in spectral line shape. 

The lUPAC-authorized italicized prefixal symbol F conveys the sense of perfluoro (e.g., F-alkyl = perfluoroalkyl = Cnp2n+i. By extension, the symbol F- will be used to designate entities (F-chains, F-compounds, F-amphiphiles, F-colloids) that comprise a highly fluorinated moiety or phase. 

Binding constants of several fluorinated and nonfluorinated analogues and corresponding diastereomers of the general structure A have also been determined in order to study the influence of the fluorine moiety and the stereochemical requirements on the inhibition of MAO A and B (Table 2) [92],... 

These effects result from the impact of fluorination on the properties of the peptide at the level of (1) the lipophilicity/hydrophobicity balance and p faJ (2) the conformation, because of the more demanding volume of the fluorinated moiety and (3) the hydrolytic and metabolic stability. 

There are many years between the search for a hit, development of a lead, and then its launch as a drug. Thus, the inventory of currently marketed dmgs gives only an imperfect view of the synthetic challenges that medicinal chemists have to face. For this reason, this chapter ends with exemples of fluorinated moieties recently introduced in medicinal chemistry. These functional structural patterns, which are present on new drugs or on molecules at an early stage of development, will possibly have a strong impact in medicinal chemistry in the future. 

Direct Fluorination of Heterocyclic Aromatics Selective fluorination of quinoline aromatics leads to various commercially important products such as 5-fluoroadl, 5-fluoroprimaquine and ciprofloxacin with the fluorine moiety being decisive of their chemical and biological properties. 

The reactions of trimethyl(perfluoroalkyl)silanes RFTMS [RF = CF3, CF2CF3, (CF2)2CF3] with a variety of fluorinated organic and inorganic substrates containing a S —O or C —O double bond have received attention. Perfluoroalkyl- and perfluoroarylsilancs can also be effectively used to directly replace active fluorine atoms bound to carbon by a variety of fluorinated moieties. 

Fluorinated Moieties for Replacement of Amide and Peptide Bonds... 

Nucleophilic trifluoromethylation and introduction of fluorinated moieties in the syntheses of bioactive fluorinated heterocycles 03S185. 

This tendency suggests that interaction of fluorinated moieties with various types of... 

Perfluoroalkyl segments, -(CF2)nF, are intrinsically liquid-crystalline and can be used as building blocks in self-assembling materials. In combination with other units, such as short alkyl segments, they generate highly organized mesophases [97], Another important property of the semi-fluorinated moieties is that they can... 

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