Scheme for dehalogenation reaction (R = alkyl or aryl group, X = I, Cl, Br, F)

organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J.; ...

, dehalogenation is a set of

chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...

s that involve the cleavage of

carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent In chemistry, the valence (US spelling) or valency (British spelling) of an element is the measure of its combining capacity with o ...

halogen The halogens () are a group in the periodic table consisting of five or six chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), astatine (At), and tennessine (Ts). In the modern IUPAC nomenclature, this group is ...

bonds; as such, it is the inverse reaction of

halogenation In chemistry, halogenation is a chemical reaction that entails the introduction of one or more halogens into a compound. Halide-containing compounds are pervasive, making this type of transformation important, e.g. in the production of polymers, ...

. Dehalogenations come in many varieties, including defluorination (removal of

fluorine Fluorine is a chemical element with the symbol F and atomic number 9. It is the lightest halogen and exists at standard conditions as a highly toxic, pale yellow diatomic gas. As the most electronegative reactive element, it is extremely reacti ...

), dechlorination (removal of

chlorine Chlorine is a chemical element with the Symbol (chemistry), symbol Cl and atomic number 17. The second-lightest of the halogens, it appears between fluorine and bromine in the periodic table and its properties are mostly intermediate betwee ...

), debromination (removal of

bromine Bromine is a chemical element with the symbol Br and atomic number 35. It is the third-lightest element in group 17 of the periodic table (halogens) and is a volatile red-brown liquid at room temperature that evaporates readily to form a simila ...

), and deiodination (removal of

iodine Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , and boils to a vi ...

). Incentives to investigate dehalogenations include both constructive and destructive goals. Complicated organic compounds such as pharmaceutical drugs are occasionally generated by dehalogenation. Many

organohalide Halocarbon compounds are chemicals in which one or more carbon atoms are linked by covalent bonds with one or more halogen atoms (fluorine, chlorine, bromine or iodine – ) resulting in the formation of organofluorine compounds, organochlorin ...

s are hazardous, so their dehalogenation is one route for their detoxification.

Pathways

Removal of one halogen atom from an organohalides generates highly reactive radicals. This fact has multiple consequences: *monodehalogenation is usually accompanied by coupling of the resulting radical: *:2 R-X + 2 Li -> R-R + 2LiX *when a pair of halides are mutually adjacent (vicinal), their removal favored. Vicinal alkyl dihalides convert to alkenes. Magnesium can be used: *:R2C(X)C(X)R2 + Mg -> R2C=CR2 + MgX2 *dehalogenations can be effected by

hydrogenolysis Hydrogenolysis is a chemical reaction whereby a carbon–carbon or carbon–heteroatom single bond is cleaved or undergoes lysis (breakdown) by hydrogen.Ralph Connor, Homer Adkins. Hydrogenolysis Of Oxygenated Organic Compounds. J. Am. Chem. Soc. ...

, the replacement of a bond by a bond. Such reactions are amenable to catalysis: *:R-X + H2 -> R-H + H-X

Fluoride vs chloride vs bromide vs iodide

The rate of dehalogenation depends on the bond strength between the carbon and halogen atom. The

bond dissociation energies The bond-dissociation energy (BDE, ''D''0, or ''DH°'') is one measure of the strength of a chemical bond . It can be defined as the standard enthalpy change when is cleaved by homolysis to give fragments A and B, which are usually radical s ...

of carbon-halogen bonds are described as: (234 kJ/mol), (293 kJ/mol), (351 kJ/mol), and (452 kJ/mol). Thus, for the same structures the bond dissociation rate for dehalogenation will be: . Additionally, the rate of dehalogenation for alkyl halide also varies with

steric Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...

environment and follows this trend: halides.

Applications

Since organochlorine compounds are the most abundant organohalides, most dehalogenations entail manipulation of C-Cl bonds.

Alkali and alkaline earth metals

Highly electropositive metals react with many organic halides in a metal-halogen exchange: :R-X + 2 M -> R-M + M-X The resulting organometallic compound is susceptible to hydrolysis: :R-M + H2O -> R-H + M-OH Heavily studied examples are found in

organolithium chemistry In organometallic chemistry, organolithium reagents are chemical compounds that contain carbon–lithium (C–Li) bonds. These reagents are important in organic synthesis, and are frequently used to transfer the organic group or the lithium atom ...

and

organomagnesium chemistry Magnesium anthracenide with three thf ligands. Group 2 organometallic chemistry refers to the chemistry of compounds containing carbon bonded to any group 2 element. By far the most common group 2 organometallic compounds are the magnesium-contain ...

. Some illustrative cases follow. Lithium-halogen exchange provides one trivial route to dehalogenation. Sodium metal has been used for dehalogenation process. Removal of halogen atom from arene-halides in the presence of Grignard agent and water for the formation of new compound is known as Grignard degradation. Dehalogenation using Grignard reagents is a two steps hydrodehalogenation process. The reaction begins with the formation of alkyl/arene-magnesium-halogen compound, followed by addition of proton source to form dehalogenated product. Egorov and his co-workers have reported dehalogenation of benzyl halides using atomic magnesium in 3P state at 600°C. Toluene and bi-benzyls were produced as the product of the reaction. Morrison and his co-workers also reported dehalogenation of organic halides by flash vacuum pyrolysis using magnesium.

With transition metal complexes

Many low-valent and electron-rich transition metals effect stoichiometric dehalogenation. The reaction achieves practical interest in the context of organic synthesis, e.g. Cu-promoted Ullmann coupling. Examples can be found with vanadium, chromium, manganese, and iron and cobalt.

Vitamin B12 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. It ...

and

coenzyme F430 F430 is the Cofactor (biochemistry), cofactor (sometimes called the coenzyme) of the enzyme methyl coenzyme M reductase (MCR). MCR catalyzes the reaction that releases methane in the final step of methanogenesis: : + coenzyme B, HS–CoB → ...

were capable of sequentially dechlorinating tetrachloroethene to ethene, while hematin was demonstrated to dechlorinate tetrachloroethene to vinyl chloride.Gantzer, C.; Wackett, L. Reductive dichlorination catalyzed by bacterial transition-metal coenzymes. Environ. Sci. Technol. 1991, 25, 715-722 Structure of macromolecules used in dehalogenation reaction

Structure of macromolecules used in dehalogenation reaction

Dehalogenation using Lithium chromium(I) dihydride

Hydrodefluorination of fluorinated olefins

Jayant and his coworkers developed two phase systems for dehalogenation of trichloroethenes. The kinetic model provides reaction process to take place in one phase while mass transfer between two phases.

References