Section 3. Fluorine, Hydrogen Fluoride

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

While aromatic amines are discussed in Section 5.2.14., various data for aliphatic amines are listed in Table 20. It is worthwhile remembering that tertiary perfluorinated amines, such as perfluorotributylamine. are completely stable, inert and nontoxic compounds, while some partially fluorinated tertiary amines tend to be unstable, eliminating hydrogen fluoride even at low temperature and are therefore toxie. Primary and secondary aliphatic fluorinated amines carrying CF,N groups have not, so far, been isolated due to their instability. 

Various fluorine compounds, such as xenon(II) fluoride, act under certain conditions (irradiation, gas-phase reaction) as radical fluorinating agents. Electrochemical fluorinations (see Section 7.) carried out in hydrogen fluoride containing systems (ref 7, pp73-76) are further examples of radical-type reactions. 

To overcome problems associated with the removal of iodobenzene and its derivatives formed upon fluorination of arylalkenes and arylalkynes with (difluoroiodo)arenes, polymer-supported (difluoroiodo)arenes were proposed.139 With these agents, the separation procedures are reduced to filtration of the iodinated polymer. For this purpose popcorn polystyrene is io-dinated and then transformed into the difluoroiodide by treatment with xenon difluoride in the presence of hydrogen fluoride in dichloromelhane at 25 C. The amount of active fluorine bonded to iodine atoms on the polymer support is estimated by iodometric titration. The reactions with phenyl-substituted alkenes result in rearranged gew-difluorides. The procedure provides the same fluorination products as with (difluoroiodo)benzenc (see Section 4.13.) but in much higher yields, e.g. PhCF2CH2Ph (96%), PhCF2CH(Me)Ph (95%). PhCH2CF2H (86%), and l,l-difluoro-2-phenylcyclopentanc (91 %). 

Carboxylic acid fluorides, intermediates in the pathway to trifluoromethyl derivatives, are readily formed in reactions of all types of carboxylic acids with sulfur tetrafluoride derivatives (see Section 8.2.4.). Little attention has been paid to fluorination of other carboxylic acid halides. Aroyl chlorides are converted into aroyl fluorides by treatment with sulfur tetrafluoride, e.g. formation of l,41 or to (trifluoromethyl)arenes, e.g. 2 and 3. in the presence of hydrogen fluoride.45 Chlorination of the aromatic ring occurs in some cases.41... 

Adamantanecarboxylic acids, on treatment with sulfur tetrafluoride, react in a conventional manner to give (triiluoromethyl)adamantanes (see Section 8.2.4.1.). However, in the presence of anhydrous hydrogen fluoride in large excess, substitution of bridgehead hydrogen atoms by fluorine occurs in addition to fluorination of carboxylic acid groups di- or trifluoro(tri-fluoromethyl)adamantanes 7 and 8 arc obtained in one step.8 119186... 

In the reaction of rnr-3,6-dimethyl-l,4-dioxane-2,5-dione (m.-lactide) with sulfur tetrafluoride in hydrogen fluoride solution, together with fluorination of both carbonyl groups, substitution of one of the tertiary hydrogen atom by fluorine also occurs a diastcrcomeric mixture of 2,3,3.6,6-pcntafluoro-2,5-dimethyl-l,4-dioxane (12) is formed in 75% yield (cf. Section 8.2.7.).166... 

In contrast to aryl trichloromethyl ethers (see Section 12.1.2.), the replacement of chlorine atoms by fluorine in aryl trichloromethyl sulfides using antimony(III) fluoride (or hydrogen fluoride) proceeds under milder conditions, without a catalyst. Various substituents in the aromatic ring have little effect on the halogen exchange. The yields of aryl trifluoromethyl sulfides are 60 to 90% (see Table 1). 

Due to the corrosive and toxic nature of volatile hydrogen fluoride, the fluorodediazoniation of aromatic and heteroaromatic amines in anhydrous hydrogen fluoride (see Section 26.1.2.), though very efficient, inexpensive and easy to scale up, needs special apparatus and safety measures which are not always available in every laboratory. Thus, the Balz-Schiemann reaction remains the most popular way to substitute aromatic amino groups for fluorine on a laboratory scale. Moreover, special techniques have been developed during the last decade to control formation, storage and decomposition of arenediazonium tetrafluoroborates on a large scale. 

The elimination of hydrogen fluoride has also been found as a side reaction in the thermally induced elimination of fluorine (see Section 3.2.1.). 

Stable dialkyl ether poly(hydrogen fluoride) complexes (R20-[HF]n, R = Me, Et, n-Pr) have recently been developed by Prakash, Olah, and colleagues.33 DFT calculations suggest a cyclic poly(hydrogen fluoride) bridged structure. Dimethyl ether-5 HF (DMEPHF) was shown to be a convenient and effective fluorinating agent (see Section 5.10.1). 

Fluorine. The distinguished chemist Henri Moissan first prepared fluorine by the electrolysis of a solution of potassium fluoride in liquid hydrogen fluoride. Because of the extreme chemical activity of this element, the electrolytic cell employed had to be made of platinum. At the present time, fluorine is produced in the laboratory and commercially by the electrolysis of fused potassium hydrogen fluoride (KHF2) in the manner described in the section on electrolysis. 

Oxidative fluorination of toluene derivatives to the corresponding fluoromethylben-zenes is possible using appropriate lead or nickel complexes in liquid hydrogen fluoride, but fluorination becomes more difficult as the reaction progresses because fluorine substituents increase the oxidation potential of the substrate [146] (Figure 3.20). Consequently, it seems unlikely that the ECF process (Chapter 2, Section III) could proceed to perfluorination by an analogous mechanism. 

Either fusion with alkali metals or reaction with aUcali-metal complexes with aromatic hydrocarbons will break down most fluorocarbon systems, due to the high electron affinities of these systems. Such reactions form the basis of some methods of elemental analysis [13], the fluorine being estimated as hydrogen fluoride after ion exchange. Surface defluorination of PTFE occurs with alkali metals and using other techniques [14]. Per-fluorocycloalkanes give aromatic compounds by passage over hot iron and this provides a potential route to a variety of perfluoroaromatic systems (Chapter 9, Section IB). 

It is important to note that most of the simple highly fluorinated, commercially significant fluoroalkenes are synthesised from materials obtained by the Swarfs reaction (Chapter 2, Section llA) involving catalysed reactions of anhydrous hydrogen fluoride with chloroalkanes [54] (Figure 7.11) or bromoalkanes. 

Table 17 indicates some limitations of the amine hydrofluorides in the reaction with glycidic esters. In the least-substituted case (entry 1) the yield is low. On the other hand, the fully substituted glycidic esters (entries 8 and 9) do not react at all with the amine hydrofluoride, probably due to steric hindrance. This type of epoxide gives better results with other fluorination reagents, e.g. they can be opened to the fluorohydrins in good yield with hydrogen fluoride in the presence of the boron trifluoride-diethyl ether complex (sec Section 1.1.4.3.2.1.2.).37... 

The first reported preparations of sulfur chloride penta-fluoride involved the fluorination of sulfur(II) chloride, the chlorination of disulfur decafluoride, and the electrolysis of sulfur(II) chloride-hydrogen fluoride mixtures. Newer methods utilize the reaction between chlorine monofluoride and sulfur(IV) fluoride or the reaction between chlorine, cesium fluoride, and sulfur(IV) fluoride. The directions described here for the reaction between chlorine monofluoride and sulfur(IV) fluoride are for the preparation of substantial quantities if only a 1- or 2-g. sample is required, the modifications described in the last paragraph of the Procedure section may be employed or a batch pro-... 

A cyclopropylfluorosilane was formed in excellent yield on reaction of a l-(allyldimethyl-silyl)bicyclo[4.1. Ojheptane derivative 1 with a slight excess of bromine and then with pyridinium poly(hydrogen fluoride). The reaction appears to be sensitive to the nature of the neighboring groups and the quality of the fluorinating agent (see Section 5.2.5.1.9.2.). ... 

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