Dehalogenation mechanisms

The photochemistry of aqueous 2-iodophenol was the subject of a subsequent study [19]. Although ring contraction, carbene formation and photohydrolysis took place in this case too, they all were minor pathways (

comparison with homolytic C -1 cleavage forming phenyl radicals and I" atoms (

radical anions. It was concluded that the heterolytic dehalogenation mechanism observed for aqueous 2-chloro- and 2-bromophenol is overruled in the case of 2-iodophenol by a homolytic one promoted by the comparatively weaker carbon-halogen bond [19]. 

Many halogenated hydrocarbons are known as environmental pollutants, for example, polychlorinated biphenyl (PCB), polychlorinated phenols (PCP), polychlorinated benzenes (PCBz), chloro-fluoro aliphatic carbons (CFC), and bromo-fiuoro aliphatic carbons (halone). As described in the previous section, solvated electrons that will attach to the solute whose electron affinity is positive, such as halogenated hydrocarbons, are effectively produced in polar solutions, such as an alcohol or ester. In this section, the dehalogenation mechanism in an alkaline 2-propanol solution (Mucka et al. 1997, Nakagawa 2003, Nakagawa and Shimokawa 2002, Sawai et al. 1974,1975, Shimokawa and Sawai 1977) is presented. The reaction mechanisms are summarized as follows in which R and R+ denote the radical and cation of 2-propanol, respectively, e soiv is the solvated electron, and M-X is the halogenated carbons (Reaction Mechanism 14.4). 

Tri- -butyltin hydride debrominated 1,2-dibromopropane at room temperature in 3 hours, pelding 81% of propylene i io-stilbene dibromide required heating to 100° C for 15 hours for complete reaction, giving 85 % of traw5-stilbene. It is not known whether this is the result of a highly selective irons elimination, or simply the consequence of formation of the most stable isomer 32). A dehalogenation mechanism similar to that involved in dehalogenation by metals such as zinc is unlikely because no cyclopropane is formed in the reaction of 1,3-dibromopropane with tri-n-butyltin hydride. 

The low reactivity of alkyl and/or phenyl substituted organosilanes in reduction processes can be ameliorated in the presence of a catalytic amount of alkanethiols. The reaction mechanism is reported in Scheme 5 and shows that alkyl radicals abstract hydrogen from thiols and the resulting thiyl radical abstracts hydrogen from the silane. This procedure, which was coined polarity-reversal catalysis, has been applied to dehalogenation, deoxygenation, and desulfurization reactions.For example, 1-bromoadamantane is quantitatively reduced with 2 equiv of triethylsilane in the presence of a catalytic amount of ferf-dodecanethiol. 

Aryl halides can be dehalogenated by Friedel-Crafts catalysts. Iodine is the most easily cleaved. Dechlorination is seldom performed and defluorination apparently never. The reaction is most successful when a reducing agent, say, Br or 1 is present to combine with the I" or Br coming off." Except for deiodination, the reaction is seldom used for preparative purposes. Migration of halogen is also found," both intramolecular and intermolecular." The mechanism is probably the reverse of that of 11-11." ... 

Considerable attention has been directed to dehalogenation mediated by corrinoids and porphyrins in the presence of a chemical reductant (references in Gantzer and Wackett 1991 Glod et al. 1997 Workman et al. 1997). Illustrations are provided by the dechlorination and elimination reactions carried out by titanium(III) citrate and hydroxocobala-min (Bosma et al. 1988 Glod et al. 1997). The involvement of corrinoids and porphyrins is consistent with the occurrence of analogous mechanisms for biological reactions that... 

Castro CE (1998) Environmental dehalogenation chemistry and mechanism. Rev Environ Contain Toxicol 155 1-67. 

Schenk T, R Muller, F Lingens (1990) Mechanism of enzymatic dehalogenation of pentachlorophenol by Arthrobacter sp. strain ATCC 33790. J Bacterial 172 7272-7274. 

FIGURE 7.63 Mechanism of dehalogenation. (From Neilson, A.H. and Allard, A.-S., The Handbook of Environmental Chemistry, Vol. 3R, pp. 1-74, Springer, 2002. With permission.)... 

Selifonov SA, JE Gurst, LP Wackett (1995) Regioselective dioxygenation of ortfio-trifluoromethylbenzoate by Pseudomonas aeruginosa 142 evidence for 1,2-dioxygenation as a mechanism in orffio-halobenzoate dehalogenation. Biochem Biophys Res Comm 213 759-767. 

An important synthetic application of this reaction is in dehalogenation of dichloro- and dibromocyclopropanes. The dihalocyclopropanes are accessible via carbene addition reactions (see Section 10.2.3). Reductive dehalogenation can also be used to introduce deuterium at a specific site. The mechanism of the reaction involves electron transfer to form a radical anion, which then fragments with loss of a halide ion. The resulting radical is reduced to a carbanion by a second electron transfer and subsequently protonated. 

The present reaction may be reasonably explained by the smooth oxidative addition of aryl halides to metallic nickel to give aryl nickel halides, followed by disproportionation to bisarylnickels, which upon reductive elimination afford the dehalogenative coupled products. Providing strong support for this mechanism, the intermediates, arylnickel halide and bisarylnickel (Ar=C F ), were isolated as the phosphine complexes. 

The dehalogenation of organic halides by organotin hydrides takes place in most cases with a free-radical mechanism [1, 84, 85], The stereospecific reduction of 1,1-dibromo-l-alkenes with Bu3SnH discovered by Uenishi and coworkers [86-89], however, did not occur in the absence of palladium complexes and did not involve radicals. For the synthesis of (Z)-l-bromo-l-alkenes, [(PPh3)4Pd] proved to be the most effective catalyst which could also be generated in situ. The reaction in Eq. (7) proceeded at room temperature and a wide range of solvents could be used. 

In contrast to [L Pd], oxidative addition of aryl halides on [L Ni] often proceed by single electron transfer mechanism [2, 197]. SN2 and SNAr types of oxidative addition as a step of the catalytic dehalogenation have also been proposed in the literature for low-valent Ti [40, 114], Zr(II) [115], Ru(II) [20, 74, 81, 98],... 

The product-forming steps of dehalogenations by free radical pathways were discussed earlier (see Section 18.3.1.1). In non-radical mechanisms, the dehalo-genated products (RH) will be formed mostly by reductive elimination [193, 194] however, concerted processes lead directly from RX to RH (see Sections 18.3.1.2 and 18.3.1.3). 

Nastainczyk W, Ahr H, Ulrich V, et al. 1982a. The mechanism of the reductive dehalogenation of polyhalogenated compounds by microsomal cytochrome P450. 799-808. 

Halogen dealkylation mimics O-dealkylation both in terms of mechanism and the commonality of the process. Virtually any drug that contains a carbon-hydrogen bond adjacent to a halogen atom will be subject to P450-catalyzed oxidative dehalogenation (Fig. 4.61). 

FIGURE 4.65 Mechanism of oxidative dehalogenation of an aryl halide. 

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