Fluorine reaction mechanisms

Mixtures of anhydrous hydrogen fluoride and tetrahydrofuran are successfully used as fluorinating agents to convert 1,1,2-trifluoro-l-allcen-3-ols, easily prepared from bromotrifluoroethene via lithiation followed by the reaction with aldehydes or ketones, to 1,1,1,2-tetrafluoro-2-alkenes The yields are optimal with a 5 1 ratio of hydrogen fluoride to tetrahydrofuran The fluorination reaction involves a fluonde lon-induced rearrangement (Sf,j2 mechanism) of allylic alcohols [65] (equation 40)... 

For toluene fluorination, the impact of micro-reactor processing on the ratio of ortho-, meta- and para-isomers for monofluorinated toluene could be deduced and explained by a change in the type of reaction mechanism. The ortho-, meta- and para-isomer ratio was 5 1 3 for fluorination in a falling film micro reactor and a micro bubble column at a temperature of-16 °C [164,167]. This ratio is in accordance with an electrophilic substitution pathway. In contrast, radical mechanisms are strongly favored for conventional laboratory-scale processing, resulting in much more meta-substitution accompanied by imcontroUed multi-fluorination, addition and polymerization reactions. 

It is assumed that all similar fluorination reactions proceed via an intricate radical chain-reaction mechanism. The overall reactions for the substitution of hydrogen by fluorine (RH + F2 - RF + HF, AH298 -430 kJ/mol per carbon atom) are more exothermic than the reactions for adding fluorine to the double bonds... 

More recently, dealumination was achieved by fluorination of zeolites at ambient temperature with a dilute fluorine-in-air stream, followed by high-temperature calcination (102). The suggested reaction mechanism involves the formation of different aluminum-fluorine compounds along with zeolites containing hydroxyl and fluorine nests. During the high-temperature calcination, it is assumed that silica insertion occurs, similar to the scheme in Figure IB. 

So far only a few dozen organofluorine compounds have been isolated from living organisms, for example fluoroacetic acid, 4-fluorothreonine and rw-fluoro-oleic acid [244-246], The reason that nature has not invested in fluorine chemistry could be a combination of low availability of water-dissolved fluoride in the environment due to its tendency to form insoluble fluoride salts, and the low reactivity of water-solvated fluoride ion. However, in 2002, O Hagan and collaborators [247] published the discovery of a biochemical fluorination reaction in a bacterial protein extract from Streptomyces cattleya converting S-adenosyl-L-methionine (SAM) to 5 -fluoro-5 deoxyadenosine (5 -FDA). The same protein extract contained also the necessary enzymatic activity to convert 5 -FDA into fluoroacetic acid. In 2004, the same authors published the crystal structure of the enzyme and demonstrated a nucleophilic mechanism of fluorination [248,249]. 

C.D. Cadicamo, J. Courtieu, H. Deng, A. Meddour, D. O Hagan, Enzymatic fluorination in Streptomyces cattleya takes place with an inversion of configuration consistent with an Sn2 reaction mechanism, ChemBioChem 5 (2004) 685-690. 

Thus, it is beyond doubt that the fluorination reaction proceeds via an association between the organic substrate (or its protonated derivative) and the electrochemically generated nickel fluoride(s) on the anode surface. However, since the precise nature of this association, and the exact species involved, are not known, the next stage in the mechanism of fluorine substitution is not apparent and it has generally been the practice to make inferences from studies of product analyses. 

As shown in Table 1, with stable fluorine flow rate, at ideal partial pressure, and with control of the fluorination time and temperature, the desired product composition with carbon yield up to 96% can be obtained. Fluorination of carbon above 500 C typically gives low yields due to further fluorination to carbon tetrafluoride as shown by the reaction mechanism below.12... 

For the reaction mechanism between fluorine and carbon, the following should be considered ... 

Extensive work on the interaction of aromatic compounds with xenon difluoride has been carried out in order to investigate the reaction mechanism and the scope of the fluorination depending on the substituents electronic nature.26-59 62 It has been found that benzene and substituted aromatics react with xenon difluoride at room temperature in the presence of hydrogen fluoride to form the typical products of electrophilic fluorination contaminated with low quantities of difluoro-substituted molecules. 

One postulated reaction mechanism for electrochemical fluorination involves an intermediate nickel fluoride, with nickel in the oxidation stage +III/ + IV, as the active fluorination agent. The induction period in which the nickel fluoride layer is formed at the nickel surface can thus be explained. A radical fluorination mechanism has also been postulated, with oxidation of the fluoride anion to the radical, or as discussed below in the ECEC mechanism.15 The mechanism of this process is still a matter for debate. Reference should be made to a report that does not support the postulates of this section.21 For partial electrochemical fluorination, the ECEC mechanism is postulated as follows. In the first step the starting material is oxidized at the anode (E = electrochemical step). 

The phenomenon of halotropism occurs in the reaction of tribromoacetic, 2-bromopropanoic and fnm -3,4-dibromocyclopentane-l-carboxylic acid with sulfur tetrafluoride. Tribromoacetic acid reacts at 25 C to give l,l,2-tribromo-l,2,2-trifluoroethane (6a) in 95% yield, while the other two acids give mixtures of trifluoromethyl derivatives 7 and rearranged 1,1,2-tri-fluoroalkanes6.110 The halogen shifts confirm the carbocationic mechanism of the fluorination reaction (vide supra). 

In the case of addition of fluorine to double bonds (Table II), note that the corresponding initiation step (lb) is probably exothermic by 5-36 kcal and thus plays an important role. A second important possibility is the concerted reaction mechanism 2, which is exothermic by 50-68.4 kcal per carbon atom. 

The fact that functionalization of polymers and small molecules is observed to occur predominately on terminal (methyl) carbon atoms does not imply that the oxyfluorination reaction is truly selective. Although the reaction mechanism has not been studied in detail, it is undoubtedly a free-radical process. Molecular oxygen reacts spontaneously with the fluorocarbon—hydrogen radicals generated by fluorine during the fluorination process. Acid fluorides are retained on terminal carbon atoms because they are stable in 1 atm of elemental fluorine. Hypofluorites, which may be short-lived intermediates of oxygen reactions with methylene radical sites along the carbon chain, are not observed in the functionalized polymers. It is probable that, if they are intermediates, they are cleaved and removed by the excess elemental fluorine. 

Use appropriate bond energies to assess the likelihood of this reaction mechanism. What about the possibility of a similar mechanism with elemental fluorine and methane ... 

Cadicamo CD, Courtieu J, Deng H, Meddour A, O Hagan D (2004) Enzymatic Fluorination in Streptomyces cattleya Takes Place with an Inversion of Configuration Consistent with an Sn2 Reaction Mechanism. ChemBioChem 5 685... 

Also the reaction pathways of Sarin decomposition catalyzed by selected forms of MgO were investigated [38]. In the case of the decomposition on the nonhydroxylated MgO surface, the removal of fluorine from Sarin was modeled. Fluorine was transferred from Sarin into binding distance with the Mg atom of the MgO surface (Fig. 13.9). It was revealed that such a structure provides a reliable model for the reaction mechanism. A two-step reaction mechanism was assumed. In the first step, Sarin creates a stable adsorbed complex with MgO through three chemical bonds with the MgO surface (the Al-GB model). It is expected that the transfer of the fluorine atom to the surface of MgO is accompanied by a change in the conformation of Sarin. In the second step, the bond between P and F is broken (the Al(t)-GB model) the fluorine atom is transferred to the Mg atom of the surface and the remaining part of Sarin adopts the most energetically favorable conformation (the Al(f)-GB model). 

Due to the multiple desorption products, the etching of the surface with halogen appears to be quite complex. A multi-step reaction mechanism has been suggested to account for the SiCl2 desorption species. In the case of fluorine atom adsorption, F atom abstraction and dissociative chemisorption mechanisms have been suggested. In order to account for the complex surface reactions, more studies are needed. 

Norbornene, which has been used as a mechanistic probe to elucidate the reaction mechanism of acid-catalyzed liquid-phase fluorination with xenon difluoride69-72, reacted in acetonitrile under photochemical conditions and two unrearranged 2,3-difluoronorbor-nanes (33-51%) were the sole difluoro products formed, while up to three monofluoro-substituted norbornanes were also present in the crude reaction mixture, the amounts and product distribution depending on the reaction conditions73 (Scheme 19). 

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