Polyhalogenated compound reduction

The radical formed may add directly on the unsaturated lipid bonds or initiate an unsaturated lipid peroxidation or undergo another one-electron reduction. The last reaction yields a carbene that can form a carbenic complex with the iron of the reductive form of cytochrome P-450. Polyhalogenated compound reductions give rise to several reactive intermediates radicals, carbenes and peroxides, whose participation in the toxic effect varies greatly. 

The refractory nature of some pollutants, notably, persistent polyhalogenated compounds, has raised problems of bioremediation of contaminated sites (e.g., sediments and dumping sites). There has been interest in the identification, or the production by genetic manipulation, of strains of microorganisms that can metabolically degrade recalcitrant molecules. For example, there are bacterial strains that can reductively dechlorinate PCBs under anaerobic conditions. 

The reductive removal of halogen can be accomplished with lithium or sodium. Tetrahydrofuran containing /-butanol is a useful reaction medium. Good results have also been achieved with polyhalogenated compounds by using sodium in ethanol. 

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

A number of preparatively useful reductions with removal of halogen was discussed in Part I. Often a stepwise removal of the halogens takes place in a polyhalogenated compound. 4-Methyl-2,6-dichloropyrimidine (288) thus gives three peaks in DMF, the third peak being the reduction of the nucleus. Preparative reduction at the potential of the first peak affords 4-methyl-2-chloropyrimidine436 [Eq. (148)]. 

The [l,2,l]-eliminations as induced by bases or nucleophiles also succeed in the family of the polyhalogen compounds, generally under the influence of organo-lithiums at low temperatures. This suggests initial mctalation. In this way, with a yield of 68-96% the educts 15 react stereoselectively to the (Z)-isomer 16 11 and the alkene 17 opens up an interesting synthesis of the cyclopentyne (18)12), which can be trapped, e.g., to 19 (36%). In the case of several alkenes 20, the reductive [1,2,1]-halogen elimination can be achieved by electrolysis in DMF. Alkynes 21 form in good yields 13). 

Mansuy, D. and J.-P. Battioni (1982). Isolation of sigma-alkyl-iron(Ill) or carbene-iron(II) complexes from reduction of polyhalogenated compounds by iron(Il)-porphyrins The particular case of halothane CFjCHClBr. J. Chem. Soc. Chem. Commun. 638-639. 

The mechanism of reductive dehalogenation of polyhalogenated compounds by microsomal cytochrome P450 has been studied in detail [22]. The main products of the in vitro metabolism of hexa- and pentachloroethane were tetra- and trichloroethene, respectively. In this case, the reductive dehalogenation probably proceeds by two sequential one electron reductions forming first a radical and then a carbanion. The carbanion may undergo... 

In the following we will try to illustrate these general points by discussing two specific types of redox reactions the reduction of aromatic nitro groups (Eq. 14-9) and the reductive dehalogenation of polyhalogenated Cr and C2-compounds (Eqs. 14-6 to 14-8). These two cases represent two very different types of reactions. In the first case, the transfer of the first electron is reversible, whereas in the second case, it is typically irreversible and involves the breaking of a bond. In the latter case, therefore, one speaks of a dissociative electron transfer. Furthermore, compounds... 

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