Radical halogenation with fluorine

Selectivity in Radical Halogenation with Fluorine and Bromine CHAPTER 3... 

SELECTIVITY IN RADICAL HALOGENATION WITH FLUORINE AND BROMINE... 

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives.134 The acids or their chlorides or anhydrides can be a chlorinated by treatment with CuCl in polar inert solvents (e.g., sulfolane).135 Acyl halides can be a brominated or chlorinated by use of N-bromo- or N-chlorosuccinimide and HBr or HC1.136 The latter is an ionic, not a free-radical halogenation (see 4-2). Direct iodination of carboxylic acids has been achieved with L-Cu(II) acetate in HO Ac.137 Acyl chlorides can be a iodinated with L and a trace of HI.138 Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium N-isopropylcyclohexylamide in THF and treatment of this solution at - 78° with I2138 or with a carbon tetrahalide.139 Carboxylic acids, esters, and amides have been a fluorinated at -78°C with F2 diluted in Ni.,4°... 

Free-radical halogenation of hydrocarbons induced thermally or photochemically can be performed with all four halogens, each exhibiting certain specificities. Because of the thermodynamics of the process, however, only chlorination (and bromination) are of practical importance.31,106-108 Fluorination with elemental fluorine is also possible. This reaction, as discussed above (see Section 10.1.1), follows an electrophilic mechanism in the solution phase.109,110 Under specific conditions, however, free-radical fluorination can be performed. 

Fluorine is usually so reactive that its use results in numerous side reactions, such as halogen-fluorine exchange, replacement of hydrogen, rearrangements or dimerization of radical intermediates. The addition of fluorine may be controlled, if fluorine is diluted with an inert gas and the temperature is lowered, or by using the Jet Fluorination technique, which was developed by Bigelow and co-workers (see also Vol. ElOa, pl59ff). 

The fluorine radical is the most reactive of the halogen radicals, and it reacts violently with alkanes (AH° = -31 kcal/mol). In contrast, the iodine radical is the least reactive of the halogen radicals. In fact, it is so unreactive (AH° = 34 kcal/mol) that it is unable to abstract a hydrogen atom from an alkane. Consequently, it reacts with another iodine radical and reforms I2. 

For halogenation with, for example, fluorine [169, 170] and chlorine [170], it is first necessary to activate the halogen gas to form free radicals this is typically achieved using high temperature, UHV conditions. A milder approach... 

As in the radical halogenation of alkanes (Section 3-8), the exothermic nature of aromatic halogenation decreases down the periodic table. Huorination is so exothermic that direct reaction of fluorine with benzene is explosive. Chlorination, on the other hand, is controllable but requires the presence of an activating catalyst, such as aluminum chloride or ferric chloride. The mechanism of this reaction is identical with that of bromination. Finally, electrophilic iodination with iodine is endothermic and thus not normally possible. Much like the radical halogenation of alkanes, electrophilic chlorination and bromination of benzene (and substituted benzenes. Chapter 16) introduces functionality that can be utilized in further reactions, in particular C-C bond formations through organometallic reagents (see Problem 54, Section 13-9, and Real Life 13-1). 

Primary alkyl chlorides are fairly stable to fluorine displacement. When fluorinated, 1-chloropropane is converted to 1-chloroheptafluoropropane and 1-chloto-2-methylbutane produces 39% l-chlorononafluoro-2-methylbutane and 19% perfluoro-2-methylbutane. Secondary and tertiary alkyl chlorides can undergo 1,2-chlorine shifts to afford perfluonnated primary alkyl chlorides 2-Chloro-2-methylpropane gives l-chlorononafluoro-2-methylpropane, and three products are obtained by the fluorination of 3-chloropentane [7] (equation 1). Aerosol fluorina-tion of dichloromethane produces dichlorodifluoromethane which is isolated in 98% purity [4 (equation 2). If the molecule contains only carbon and halogens, the picture is different. Molecular beam analysis has shown that the reaction of fluorine with carbon tetrachlonde, lodotrichloromethane, or bromotrichloromethane proceeds first by abstraction of halogen to form a trichloromethyl radical [5]... 

In order to minimize the degradation of macromolecules, the choice of solvent is not a trivial matter. Hydrogen-containing solvents are obviously not suitable, but even halogenated ones such as CFC13 or CC12FCF2C1, usually stable to fluorine, can react violently with this element when irradiated at temperatures near 0°C. We chose two perfluorinated solvents that have been proven safe and suitable for radical fluorination perfluoro-2-(butyl)-tetrahydro-duran (FC-75 Fluorinert from 3M) and hexafluoropropylene oxide (HFPO) oligomers known as Krytox +... 

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