Dehalogenation

In organic chemistry, dehalogenation is a set of chemical reactions that involve the cleavage of carbon-halogen bonds; as such, it is the inverse reaction of halogenation. Dehalogenations come in many varieties, including defluorination (removal of fluorine), dechlorination (removal of chlorine), debromination (removal of bromine), and deiodination (removal of iodine). Incentives to investigate dehalogenations include both constructive and destructive goals. Complicated organic compounds such as pharmaceutical drugs are occasionally generated by dehalogenation. Many organohalides are hazardous, so their dehalogenation is one route for their detoxification.

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

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:
  • when a pair of halides are mutually adjacent (vicinal), their removal favored. Vicinal alkyl dihalides convert to alkenes. Magnesium can be used:
  • dehalogenations can be effected by hydrogenolysis, the replacement of a C−X bond by a C−H bond. Such reactions are amenable to catalysis:

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 of carbon-halogen bonds are described as: H3C−I (234 kJ/mol), H3C−Br (293 kJ/mol), H3C−Cl (351 kJ/mol), and H3C−F (452 kJ/mol). Thus, for the same structures the bond dissociation rate for dehalogenation will be: F < Cl < Br < I.[1] Additionally, the rate of dehalogenation for alkyl halide also varies with steric environment and follows this trend: primary > secondary > tertiary halides.[1]

Applications
Main article: Reductive dechlorination

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:

The resulting organometallic compound is susceptible to hydrolysis:

Heavily studied examples are found in organolithium chemistry and organomagnesium chemistry. Some illustrative cases follow.

Lithium-halogen exchange provides one trivial route to dehalogenation.[2][3][4] Sodium metal has been used for dehalogenation process.[5][6] 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.[7] Morrison and his co-workers also reported dehalogenation of organic halides by flash vacuum pyrolysis using magnesium.[8]

With transition metal complexes

Many low-valent and electron-rich transition metals effect stoichiometric dehalogenation.[9] The reaction achieves practical interest in the context of organic synthesis, e.g. Cu-promoted Ullmann coupling.

Examples can be found with vanadium,[10] chromium,[11] manganese,[12] and iron and cobalt.[13][14] Vitamin B12 and coenzyme F430 were capable of sequentially dechlorinating tetrachloroethene to ethene, while hematin was demonstrated to dechlorinate tetrachloroethene to vinyl chloride.[15]

Structure of macromolecules used in dehalogenation reaction
Dehalogenation using lithium chromium(I) dihydride
Hydrodefluorination of fluorinated alkenes

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.

Further reading
  • Gotpagar, J.; Grulke, E.; Bhattacharyya, D.; Reductive dehalogenation of trichloroethylene: kinetic models and *Hetflejš, J.; Czakkoova, M.; Rericha, R.; Vcelak, J. Catalyzed dehalogenation of delor 103 by sodium hydridoaluminate. Chemosphere 2001, 44, 1521.
  • Kagoshima, H.; Hashimoto, Y.; Oguro, D.; Kutsuna, T.; Saigo, K. Trophenylphosphine/germanium (IV) chloride combination: A new agent for the reduction of α-bromo carboxylic acid derivatives. Tetrahedron, 1998, 39, 1203-1206

References
  1. Trost, Barry M.; Fleming, Ian (1991). Comprehensive Organic Synthesis – Selectivity, Strategy and Efficiency in Modern Organic Chemistry. Vol. 1–9. Elsevier. pp. 793–809. ISBN 0080359299.
  2. Ramón, D.; Yus, M. Masked lithium bishomoenolates: Useful intermediates in organic synthesis, J. Org. Chem. 1991, 56, 3825-3831.
  3. Guijarro, A.; Ramón, D.; Yus, M. Naphthalene-catalysed lithiation of functionalized chloroarenes: regioselective preparation and reactivity of functionalized lithioarenes, Tetrahedron, 1993, 49, 469-482.
  4. Yus, M.; Ramón, D. Arene-catalysed lithiation reactions with lithium at low temperature, Chem. Comm. 1991, 398-400.
  5. Hawari, J. Regioselectivity of dechlorination: reductive dechlorination of polychlorobiphenyls by polymethylhydrosiloxane-alkali metal. J. Organomet. Chem. 1992, 437, 91-98.
  6. Mackenzie, K.; Kopinke, F.-D. Debromination of duroplastic flame-retarded polymers. Chemosphere, 1996, 33, 2423-2428.
  7. Tarakanova, A.; Anisimov, A.; Egorov, A. Low-temperature dehalogenation of benzyl halides with atomic magnesium in the 3P state. Russian Chemical Bulletin, 1999, 48, 147-151.
  8. Aitken, R.; Hodgson, P; Oyewale, A.’ Morrison, J. Dehalogenation of organic halides by flash vacuum pyrolysis over magnesium: a versatile synthetic method. Chem. Commun. 1997, 1163-1164.
  9. Grushin, V.; Alper, H. Activation of otherwise unreactive C-Cl bonds. Top. Organomet. Chem. 1999, 3, 193-226.
  10. Hirao, T.; Hirano, K.; Hasegawa, T.; Oshiro, Y.; Ikeda, I. A novel system consisting of low-valent vanadium and diethyl phosphonate or triethyl phosphite for the highly stereoselective reduction of gem-dibromocyclopropanes. J. Org. Chem. 1993, 58, 6529-6530
  11. Eisch, J.; Alila, J. Lithium chromium(I) dihydride: a novel reagent for the versatile reductive metathesis, reductive cyclization, oligomerization, or polymerization of diverse organic substrates. Organometallics, 2000, 19, 1211-1213
  12. Cahiez, G.; Benard, D.; Normant, J. Reduction des halogenures vinyliques et aryliques par les organomagnesiens en presence de manganese(II). J. organomet. Chem. 1976, 113, 107-113
  13. Fakhfakh, M.; Franck, X.; Hocquemiller, R.’ Figadere, B. Iron catalyzed hydrodebromination of 2-aryl-1,1-dibromo-1-alkenes. J. Organomet. Chem. 2001, 624, 131-135
  14. Vela, J.; Smith, J; Yu, Y.; Ketterer, N.; Flaschenriem, C.; Lachicotte, R.; Holland, P. Synthesis and reactivity of low-coordinate iron (II) fluoride complexes and their use in the catalytic hydrodefluorination of fluorocarbons. J. Am. Chem. Soc. 2005, 127, 7857-7870
  15. Gantzer, C.; Wackett, L. Reductive dichlorination catalyzed by bacterial transition-metal coenzymes. Environ. Sci. Technol. 1991, 25, 715-722
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