Fluorine chemical synthesis

Fluorinated sulflnates are prepared from sodium dithionite and liquid per-fluoroalkyl halides [74] (equation 67). For the transformation of the gaseous and poorly reactive trifluoromethyl bromide, it is necessary to use moderate pressure [75] (equation 68) These reactions are interpreted by a SET between the intermediate sulfur dioxide radical anion and the halide The sodium trifluorometh-anesulfinate thus obtained is an intermediate for a chemical synthesis of triflic acid. 

The possibility of studying the structure and dynamic properties of proteins by F NMR requires the use of labeled proteins with fluorine. Various approaches can be envisioned trifluoroacetylation or derivatization of side chains by direct fluorination or trifluoromethylation or with small fluorinated molecules. It is also possible to incorporate a fluorinated amino acid into a protein, by using either a classical chemical synthesis or a biosynthetic approach. It is obvious that the chemical synthetic... 

In order to give a clear overview, this chapter classically introduces pharmaceuticals according to their respective therapeutic class. Their chemical synthesis is given only when it has a specific interest in fluorine chemistry. The reader will appreciate the marketed names of the cited pharmaceuticals reported under INN names (International Non-proprietary Names) in the appendix. General references about marketed products (or under development) can be found in the Chemical Abstracts by using the INN (italic in the text). 

The first purely chemical synthesis of fluorine was accomplished in 1986 by Christe2 and is remarkable for its simplicity and elegance. The two starting materials, potassium hexa-fluoromanganate(IV) and antimony(V) fluoride, had been known4 5 for almost a century and can be readily prepared from hydrogen fluoride solutions according to ... 

Abstract Boron-doped diamond (BDD) electrodes provide an unusually wide electrochemical window in protic media, since there exist large offset potentials for the evolution of molecular hydrogen and oxygen, respectively. At the anode, alcohols are specifically converted to alkoxyl radicals. These can be used for chemical synthesis. When the enormous reactivity of such intermediate spin centers is not controlled, mineralization or electrochemical incineration dominates. Efficient strategies include either high substrate concentrations or fluorinated alcohols which seem to stabilize the spin centers in the course of reaction. 

All other fluorinated antibiotics were either prepared by a partial chemical synthesis or by cultivations to which fluorine ions were added. All metabolites prepared in this way and initially considered very promising with respect to their increased biological activity were an absolute failure, in spite of the fact that just the contrary was often described in the patent literature. 

An area of research of obvious importance and immense scope involves the incorporation of amino acid analogues into proteins. Incorporation is accomplished either by chemical synthesis or by biochemical synthesis using the protein assembly mechanisms of nature. Halogenated, especially fluorinated, amino acid analogues have been particularly useful tools in this research. In this section, selected examples of research using such analogues will be described to illustrate strategies and principles employed. 

Chemical synthesis has provided an additional route to peptides containing halogenat-ed amino acids. Early 19F-NMR studies of proteins were performed on semi-synthetic polypeptides prepared by attachment of fluorinated probes to the polypeptide. For example, Heustis and Raftery modified ribonuclease by trifluoroacetylation of Lys residues 1 and 7. They then used 19F-NMR to study conformational changes brought about by the presence of inhibitors200. In his review, Gerig provides several other examples of this strategy187. 

Karl O. Christe Chemical synthesis of fluorine by reaction of ShFs with K2MnFg... 

Figure 2 The structures of ceramide 1, a schematic structure of ceramide that illustrates the sites at which structural modifications may be introduced by chemical synthesis, and the structure of a representative ceramide found in human skin (2). Structural changes in the ceramide molecule have been introduced at many sites. Alterations include the configuration at C-2 and C-3 the lengths of the fatty amide chain and of the aliphatic chain attached to C-5 the positions of the unsaturation and the secondary hydroxy group the replacement of the hydroxyl groups with other atoms (hydrogen or fluorine) or functionalities (methoxy, methylthio, and keto) the incorporation of aromatic, heteroaromatic, and other rings in place of the alkenyl side chain of the sphingoid base and the replacement of the carbonyl group of the carboxamide group. In addition, the 2-amino-1,3-diol functionalities have been incorporated into cyclic structures.

Incorporation of fluorine into peptides and proteins is usually achieved through biosynthetic routes, chemical synthesis, or a combination of these two methods. Each method has its own advantages and shortcomings, but each requires a 19F-labeled amino acid. The most commonly used ones are commercially available analogues of aromatic amino acids, such as tryptophan, phenylalanine, tyrosine, and phenylglycine. Aliphatic 19F-labeled amino acids are not commonly available and usually have to be synthesized. The synthesis of most fluorinated amino acids is described in detail in the literature [1, 9,10], For structure analysis of peptides and proteins, it is important that (i) the fluorine label is rigidly attached to the peptide backbone, (ii) the label does not alter the structure or function of the peptide, (iii) the extent of fluorination is restricted to avoid multiple signals, and (iv)... 

Despite the ubiquitous occurrence of fluorides in nature, elemental fluorine itself proved to be quite elusive. Because of its very high redox potential (approx. +3 V, depending on the pH of aqueous systems), chemical synthesis from inorganic fluorides was impeded by the lack of a suitable oxidant. Therefore, H. Moissan s first synthesis of fluorine in 1886 by electrolysis of a solution of KF in aHF in a platinum apparatus [6, 7] was a significant scientific breakthrough, and he was awarded the Nobel Prize for chemistry in 1906 for his discovery (Figure 1.1). 

A purely chemical synthesis of elemental fluorine was achieved by K. O. Christe in 1986 [10] (Scheme 1.1), just in time for the 100 year anniversary of Moissan s first electrochemical fluorine synthesis. Nevertheless, in his paper Christe remarks that all the basic know-how required for this work had already been available 50 years earlier. The key to his simple method is a displacement reaction between potassium hexafluoropermanganate [11] with the strongly fluorophilic Lewis acid antimony pentafluoride at 150 °C. 

Especially interesting is plasma-chemical synthesis in the mixture NF3-ASF5-F2 (composition 1 1 2), which results in the formation of NF4ArF6. This fluorine oxidizer is a derivative from NF5, which is not stably synthesized by itself The mechanism of synthesis... 

Plasma-Chemical Synthesis of Xenon Fluorides and Other Fluorine Oxidizers... 

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