Fluorine-Containing Compounds

Florisil Trade name of a magnesium silicate used for chromatography, especially of fluorine-containing compounds. 

Most fluorine-containing compounds can be reduced to the fluoride ion, F , which can be detected by the tests given below. 

Chemicals. Both organic and inorganic fluorine-containing compounds, most of which have highly speciali2ed and valuable properties, are produced from HF. Typically these fluorinated chemicals are relatively complex, sometimes difficult to manufacture, and of high value. These materials include products used as fabric and fiber treatments, herbicide and pharmaceutical intermediates, fluoroelastomers, and fluorinated inert Hquids. Other products include BF, SF, and fluoborates. 

The synthesis of new perfluoroaliphatic compounds of magnesium and lithium has continued, although at a reduced effort Perfluoroorganometallics offer a variety of reactions with numerous substrates, which contributed to the development of the chemistry of fluorine containing compounds... 

Fluorovinyllithium compounds, as well as perfluoroalkyllithium and per-fluoroalkyletherlithium compounds [f ], are important intermediates m the synthesis of a variety of fluorine-containing compounds Although experimental details must be carefully adhered to, these synthons provide a convenient route to many fluoro compounds... 

Fluorine technology and the applications of fluorine-containing compounds have developed dramatically during the twentieth century. Some highlights are included in Table 17.2 and will be discussed more fully in later sections. 

The active part of the molecule is the fluoride ion, which is why two other fluorine-containing compounds, sodium fluoride and sodium monofluorophosphate, are also used. 

The discovery of the phenomenal insecticidal activity of 1,1, l-trichloro-2,2-bis(p-chlorophenyl)-ethane (DDT), which occurred less than 10 years ago, opened up a new field of endeavor for the chemist, biologist, and toxicologist. The activity in this field is considerable, and a portion of it has been directed toward efforts-to locate useful insecticides among the fluorine-containing compounds. Some of the fluorine compounds known to be insecticidal were re-evaluated, other compounds were tested biologically for the first time, and new compounds were prepared to be subjected to such tests. 

Then, once the desired fluorine-containing compounds have been synthesized, the real fun begins as the world of fluorine NMR is entered. However, one s first encounter with fluorine NMR can also present a problem because although most synthetic organic chemists are thoroughly familiar with the use of proton and carbon NMR for compound characterization, few have much experience with the use of fluorine NMR for that purpose. Moreover, there is presently no single place where a person can turn to obtain a concise but thorough introduction to fluorine NMR itself and, just as importantly, to learn how the presence of fluorine substituents can enhance the efficacy of both proton and carbon NMR as tools for structure characterization. 

There will usually not be much variation observed in fluorine chemical shifts for the three most common solvents used for obtaining NMR spectra, that is CDC13, DMSO-d6, and acetone-, as can be seen in the data presented in Table 2.3 for spectra of a series of typical fluorine-containing compounds in various solvent. The variation in fluorine chemicals shifts for these three solvents is no more than 1 ppm. Thus, in reporting chemical shifts in this book, no mention of specific solvent will be made, although the vast majority of spectra will have been measured in CDC13. 

Although the spectra of fluorine containing compounds are non-exceptional, other than for the F—H coupling, and are highly predicable, typical proton chemical shift and coupling constant data will be provided within each chapter for each class of fluoroorganic compound. 

The heterobimetallic asymmetric catalyst, Sm-Li-(/ )-BINOL, catalyzes the nitro-aldol reaction of ot,ot-difluoroaldehydes with nitromethane in a good enantioselective manner, as shown in Eq. 3.78. In general, catalytic asymmetric syntheses of fluorine containing compounds have been rather difficult. The S configuration of the nitro-aldol adduct of Eq. 3.78 shows that the nitronate reacts preferentially on the Si face of aldehydes in the presence of (R)-LLB. In general, (R)-LLB causes attack on the Re face. Thus, enantiotopic face selection for a,a-difluoroaldehydes is opposite to that for nonfluorinated aldehydes. The stereoselectivity for a,a-difluoroaldehydes is identical to that of (3-alkoxyaldehydes, as shown in Scheme 3.19, suggesting that the fluorine atoms at the a-position have a great influence on enantioface selection. 

Stannous fluoride, a compound of tin and fluorine, is much less dangerous. It is added to drinking water and toothpaste to strengthen the enamel in the teeth of the user. Another compound of fluorine is teflon, a plastic made of carbon and fluorine, which is used in kitchenware. The fluorine-containing compound freon is used in air-conditioners and refrigerators, and is harmless. 

Stille coupling involves the use of tin reactants. Tin is both toxic and difficult to remove. In an elegant extension of the pioneering work of Horvath [59], Curran and his coworkers prepared fluorous tin reactants that facilitated Stille reactions and enabled the convenient isolation and separation of products afterwards [60], Probably owing to low solubility of fluorine-containing compounds in organic solvents, the reactions normally required about one day at 80 °C. With microwave heating, they were completed within minutes [61]. 

Besides the above-mentioned catalytic asymmetric hydrogenation method for preparing fluorine-containing compounds, other reactions such as asymmetric reduction of achiral fluorine-containing ketones are also feasible methods for preparing chiral fluorinated compounds. For example, the oxazabor-olidine system, which has been discussed in Chapter 6, can also be employed in the catalytic reduction of trifluoromethyl ketones. Scheme 8 40 depicts some examples.85... 

Fluorine-containing compounds can also be synthesized via enantioselective Reformatsky reaction using bromo-difluoroacetate as the nucleophile and chiral amino alcohol as the chiral-inducing agent.86 As shown in Scheme 8-41, 1 equivalent of benzaldehyde is treated with 3 equivalents of 111 in the presence of 2 equivalents of 113, providing a,a-difluoro-/ -hydroxy ester 112 at 61% yield with 84% ee. Poor results are observed for aliphatic aldehyde substrates. For example, product 116 is obtained in only 46% ee. 

Simons, J. H. General chemistry of fluorine containing compounds. Fluorine Chem. 5, 1 (1964). 

More recently, other heavier than water products have been developed for temporary internal tamponade. These are fluorosilicones [46,47], semifluorinated alkanes [1,7], heavy fluorocarbon liquid (HFCL) oligomers [5,7] and solutions of fluorine-containing compound and silicone oil [8-10,47],... 

In this content, we developed and studied a solution of a fluorine-containing compound, RMN3, and silicone oil. This so-called heavy silicone oil has been on the market since May 2003 under the name of Oxane Hd . 

The formulation of silicone oil and RMN3 is therefore a solution of a fluorine-containing compound, RMN3, and of a 5700-cSt silicone oil. It is the result of cooperation between the IMRCP laboratory of the Paul Sabatier University in Toulouse (Dr. Rico-Lattes), the Ophthalmology Department team of the Rangueil Teaching Hospital of Toulouse (Professor Mathis) and Chauvin Baush Lomb Laboratories and Opsia companies (Toulouse). This heavy silicone oil has been marketed since May 2003 by Chauvin Baush Lomb Laboratories. The characteristics of Oxane Hd are summarised in Table 2. 

Several fluorine-containing compounds are being marketed or investigated as antiepileptics, as antidegeneratives in Azheimer and Parkinson diseases, and as sleep inductors. Several of these compounds are also being developed for other indications at the same time. 

As well as having theoretical interest, this reaction has been used as a key step in the synthesis of more complex enantiomerically pure fluorine containing compounds. For example, fluorine has been added to i) 5,6-unsubstituted and... 

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