Reductive dehalogenation alkyl halides

The order of ease of reductive dehalogenation of organic halides in the same type of structural environment is I > Br > Cl F. This order is parallel with the dissociation energy of carbon-halogen bonds (HsC—I 234 kJ mol- H3C—Br 293 kJ mol" H3C—Cl 351 kJ mol- H3C—F 452 kJ moL ) and is generally observed in the reduction of alkyl halides. Consequently, selective reduction of di- or polyhalides containing different halogen atoms is possible. Fluorides are often removed only with difficulty and examples of such reductions are comparatively limited. 

Cyanoborohydride and its modified reagents have been used for reductive dehalogenations. Thus, the combination of sodium or tetrabutylammonium cyanoborohydride, sodium or potassium 9-cyano-9-hydro-9-borabicyclo[3.3.1]nonanate [9-BBNCN] (2) or polymeric cyanoborane (3) in HMPA furnishes an efficient and mild system for the reduction of alkyl halides. The reagents are selective in that other functional groups, including ester, carboxylic acid, amide, cyano, alkene, nitro, sulfone, ketone, aldehyde and epoxide, are essentially inert under the reduction conditions thus, the reduction procedure is attractive for synthetic schemes which demand minimum damage to sensitive portions of the molecule. 

Cr(II) has been used to bring about dehalogenation of alkyl halides involving the production of alkyl radicals, and details have been provided in a substantive review (Castro 1998). The ease of reduction is generally iodides > bromides > chlorides, while tertiary halides are the most reactive and primary halides the least (Castro and Kray 1963, 1966). 

Pletcher and associates [155, 159, 160] have studied the electrochemical reduction of alkyl bromides in the presence of a wide variety of macrocyclic Ni(II) complexes. Depending on the substrate, the mediator, and the reaction conditions, mixtures of the dimer and the disproportionation products of the alkyl radical intermediate were formed (cf. Section 18.4.1). The same group [161] reported that traces of metal ions (e.g., Cu2+) in the catholyte improved the current density and selectivity for several cathodic processes, and thus the conversion of trichloroacetic acid to chloroacetic acid. Electrochemical reductive coupling of organic halides was accompanied several times by hydrodehalogena-tion, especially when Ni complexes were used as mediators. In many of the reactions examined, dehalogenation of the substrate predominated over coupling [162-165]. 

An alternative route to sulphones utilizes the reaction of the appropriate activated halide with sodium dithionite or sodium hydroxymethanesulphinite [6], This procedure is limited to the preparation of symmetrical dialkyl sulphones and, although as a one-step reaction from the alkyl halide it is superior to the two-step oxidative route from the dialkyl sulphides, the overall yields tend to be moderately low (the best yield of 62% for dibenzyl sulphoxide using sodium dithionite is obtained after 20 hours at 120°C). The mechanism proposed for the reaction of sodium hydroxymethanesulphinite is shown in Scheme 4.20. The reaction is promoted by the addition of base and the best yield is obtained using Aliquat in the presence of potassium carbonate. It is noteworthy, however, that a comparable yield can be obtained in the absence of the catalyst. The reaction of phenacyl halides with sodium hydroxy-methane sulphinite leads to reductive dehalogenation [7]. 

Alkenes are obtained by the transformation of various functional groups, e.g. dehydration of alcohols (see Section 5.4.3), dehalogenation of alkyl halides (see Section 5.4.5) and dehalogenation or reduction of alkyl dihalides (see Section 5.4.5). These reactions are known as elimination reactions. An elimination reaction results when a proton and a leaving group are removed from adjacent carbon atoms, giving rise to a tt bond between the two carbon atoms. 

Lithium triethylborohydride (Super-Hydride) is a much more powerful reducing agent than lithium aluminium hydride. It is useful for the reductive dehalogenation of alkyl halides, but unlike lithium aluminium hydride does not affect aryl halides. It is available as solution in tetrahydrofuran in sealed containers under nitrogen. The solutions are flammable and moisture sensitive and should be handled with the same precautions as are taken with other organometallic reagents (see Section 4.2.47, p. 442). 

The reduction potentials for various alkyl halides range from +0.5 to +1.5 V therefore, when Fe° serves as an electron donor, the reaction is thermodynamically favorable. Because three reductants are present in the treatment system (Fe°, H2, and Fe2+), three possible pathways exist. Equation (13.9) represents the oxidation of Fe° by reduction of a halogenated compound. In the second pathway, the ferrous iron behaves as a reductant, as represented in Equation (13.10). This reaction is relatively slow because the ability to reduce a pollutant by ferrous iron is dependent on the speciation ferrous ions, which is determined by the ligands present in the system. The third possible pathway, Equation (13.11), is dehalogenation by hydrogen. This reaction does not occur easily without a catalyst. In addition, if hydrogen levels become too high, corrosion is inhibited (Matheson and Tratnyek, 1994) ... 

In Chapter 4, we saw that Sml2 mediates the dehalogenation of a range of alkyl halides. These reactions proceed by reduction to alkyl radicals that are then... 

Red-Al [sodium bis(2-methoxyethoxy)aluminium hydride] reduces aliphatic halides and aromatic halides to hydrocarbons. Reductive dehalogenation of alkyl halides is most commonly carried out with super hydride. Epoxide ring can also be opened by super hydride. 

The reduction of saturated alkyl halides to alkanes, as represented in equation (1), is the most fundamental reaction of reductive dehalogenations of organic halides. The importance of these reductions has stimulated considerable investigation, and a number of successful approaches have been reported hitherto. Numerous reducing agents or reagent systems are available and many of them have been applied to practical organic synthesis with notable success. 

A classical method using Na- or Li-liquid ammonia (Birch reduction conditions) is effective for reductive dehalogenations of aryl and vinylic halides, but it is not always successfully applied to alkyl halides, although cyclopropyl halides and bridgehead halogens are exceptions.Under such conditions, the reactions are often accompanied by side reactions, such as elimination, the Wurtz coupling reaction, cyclization and reduction of carbonyl compounds. An example, a synthesis of pentaprismane (1), is shown in Scheme 4. ... 

A currently employed method for dehalogenation of alkyl halides is to use a Li- or Na-alcohol reagent system. This method is effective not only for simple alkyl halides but also for the reduction of a halogen atom attached to a bridgehead. Carbon-carbon unsaturated bonds are not affected under the conditions, as shown in Scheme 5. ... 

Reductive dekalogenation of alkyl halides.2 Lithium aluminum hydride has commonly been used only for reductive dehalogenation of reactive substrates organotin hydrides, for example tri-n-butyltin hydride (1, 1192-1193 2, 424 3, 294), have been used for reduction of inert halides. Recently Jefford et al. have reported that supposedly inert halides are reducible by lithium aluminum hydride. Thus the vinyl halide (1) is reduced to (2, em/o-2-phenylbicyclo(3.2.1]octene-3) by lithium aluminum hydride in refluxing ether (24 hr.). 3-Bromobicyclo[3.2.1]octene-2 is reduced to the parent... 

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