Fluorine introduction into organic compounds

One of the major activities of chemists in industry and academia is the search for special-effect chemicals, i.e. systems with new chemistry and with novel properties that can be exploited by industry. There are, of course, many ways of creating novel systems but the introduction of carbon-fluorine bonds into organic compounds has led to spectacular industrial developments, together with an exciting field of organic chemistry and biochemistry. 

Selective introduction of a fluorine atom into organic compounds is important due to the unique biological and physical properties of fluorinated compounds. One useful method for C-F bond formation is desulfurative fluorina-tion realized by a cleavage of C-S bonds of dithioacetals. Thus, 1,3-ditholane derivatives undergo a facile reaction... 

Other than pol5mierization into homo- and copolymers, VF is used for the introduction of fluorine atoms into organic compounds and polymers, eg, by grafting into fibers. The net consequence of fluorine incorporation is increased chemical and... 

Due to the unique properties of fluorinated compounds there has been a growing interest in the selective introduction of one or more fluorine atoms into organic molecules (Shimizu and Hiyama 2005 Welch and Eswarakrishnan 1991 Soloshonok 1999 Chambers 2004). In particular, the resistance to many metabolic transformations, as well as the increased lipophilicity and stability of fluorine-containing compounds is of importance to the pharmaceutical and agrochemical industry... 

The trifluoromethyl group is the most prominent fluorinated side chain. An excellent review on all aspects of the introduction of the trifluoromethyl group into organic compounds is available (92T6555). The trifluoromethyl group can be introduced as radical, nucleophilic and electrophilic species as well as by functional group transformations. 

The best source of information on techniques for the introduction of fluorine into organic compounds and for information on preparative methods is the excellent treatise by Hudlicky (25), Houben-Weyl s Methoden der Organischen Chemie(65), as well as the books of Shephard and Sharts (25) and Chambers (24). More recently, methods for the fluorination of organic molecules have been reviewed by several authors (15,69-75). More... 

Three fluoride derivatives (192-194) from 191 were prepared given the potential effects of the introduction of fluorine into organic compounds. Fig. (51). The results obtained in the antimicrobial assay showed that the effect of scutione (191) and its fluoride derivatives 192-194 was limited to Gram-positive bacteria (Table 9), and unexpectedly scutione was more active than the fluoride derivatives. 

Late In the 19th Century the Belgiam chemist Swartz established the chemistry for the introduction of fluorine into organic compounds which first achieved commercial status in the fluorocarbon refrigerant Industry. 

Electrophilic fluorination is one of the most direct methods for selective introduction of fluorine into organic compounds. Historically first electrophilic fluorination of diazine derivatives was accomphshed in 1960. Silver difluoride has been used in the final stage of an earlier synthesis of tetrafluoropyrimidine 6 from trifluoropyrimidine 5 [14]. Later the similar transformation was carried out using CIF5 in 15 % yield and was found that side chlorination occurs in 9 % yield [15] (Scheme 1). 

The development of synthetic methods for the selective introduction of short-chain perfluoroalkyl groups into organic molecules is of interest in drug development [464]. Fluoromodifications often confer unique properties on a molecule, for example in terms of increased metabolic stability and lipophilicity and, as a consequence, the pharmacokinetic profiles are often improved [465]. Burger and coworkers developed a domino process consisting of a SN reaction combined with a Claisen and a Cope rearrangement which allows the transformation of simple fluorinated compounds into more complex molecules with fluoro atoms [466]. Treatment of furan 2-917 with 2-hydroxymethyl thiophene (2-918) in the presence... 

Low-temperature fluorination of sodium acetate in suspension gives a mixture of acetyl hypo-fluorite (AcOF, 1, R = Me) and alkyl hypofluorite the crude mixture can be used, in some cases, directly for the introduction of fluorine into organic molecules. The course of the reaction strongly depends on the reaction conditions and, when the fluoride anion is quenched with hydrogen fluoride or water, trifluoroacetyl hypofluorite (1, R = CF3), 3 acetyl hypofluorite (1, R = Me) and long-chain acid fluorites are obtained.4-6 On the other hand, an excess of fluorine can lead to the formation of alkyl fluoroxy compounds 2 or geminal bis(fluoroxy) products 3. 

Modern Methods for the Introduction of Fluorine into Organic Molecules An Approach to Compounds with Altered Chemical and Biological Activities ... 

Tetr 34 3 (1978) (Introduction of Fluorine into Organic Molecules Why and How) 47 5329 (1991) (The Combination of Hydrogen Fluoride with Organic Bases as Fluorination Agents) 49 9385 (1993) (Synthesis of Chiral and Bioactive Fluoroorganic Compounds)... 

In addition to the use of elemental fluorine 63 and DAST 64, Miyake and Kitazume (2003) demonstrated the introduction of fluorine into a series of small organic compounds via trifluoromethylation of carbonyl compounds (Table 7), Michael addition (Scheme 20a), and Homer-Wadsworth-Emmons (Scheme 20b) reactions. 

These zinc reagents provide a useful entry into compounds containing the dialkoxyphosphinyldifluoromethyl group.36 Introduction of this moiety into organic molecules has attracted attention due to biological properties exhibited by these derivatives as compared to their non-fluorinated analogues.37... 

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