Finkelstein reaction

Finkelstein reaction
Named after Hans Finkelstein
Reaction type Substitution reaction
Identifiers
Organic Chemistry Portal finkelstein-reaction
RSC ontology ID RXNO:0000155

The Finkelstein reaction, named after the German chemist Hans Finkelstein,[1] is an SN2 reaction (Substitution Nucleophilic Bimolecular reaction) that involves the exchange of one halogen atom for another. Halide exchange is an equilibrium reaction, but the reaction can be driven to completion by exploiting the differential solubility of halide salts, or by using a large excess of the halide salt.[2]

R–X   +   X′−   ⇌   R–X′   +   X−

The classic Finkelstein reaction entails the conversion of an alkyl chloride or an alkyl bromide to an alkyl iodide by treatment with a solution of sodium iodide in acetone. Sodium iodide is soluble in acetone and sodium chloride and sodium bromide are not.[3] The reaction is driven toward products by mass action due to the precipitation of the insoluble salt. For example, bromoethane can be converted to iodoethane:

CH3CH2Br (acetone)   +   NaI (acetone)   →   CH3CH2I (acetone)   +   NaBr (s)

Alkyl halides differ greatly in the ease with which they undergo the Finkelstein reaction. The reaction works well for primary (except for neopentyl) halides, and exceptionally well for allyl, benzyl, and α-carbonyl halides. Secondary halides are far less reactive. Vinyl, aryl and tertiary alkyl halides are unreactive. Below some relative rates of reaction (NaI in acetone at 60 °C):[4][5]

Me–Cl Bu–Cl i-Pr–Cl t-BuCH2–Cl CH2=CH–CH2–Cl PhCH2–Cl EtOC(O)CH2–Cl MeC(O)CH2–Cl
179 1 0.0146 0.00003 64 179 1600 33000

In modern usage the definition of the reaction has been expanded to include the conversion of alcohols to alkyl halides by first converting the alcohol to a sulfonate ester (tosylates or mesylates are usually used), and then performing the substitution. The example below is from a synthesis of chrysochlamic acid.[6]

Aromatic Finkelstein reaction

The aromatic chlorides and bromides are not easily substituted by iodide, though they may occur when appropriately catalyzed. The so-called "aromatic Finkelstein reaction" is catalyzed by copper(I) iodide in combination with diamine ligands.[7] Nickel bromide and tri-n-butylphosphine have been found to be suitable catalysts as well.[8]

Halex reaction

The halex reaction describes any aryl HALogen EXchange. The chlorine atom in aryl chlorides (with electron-withdrawing substituents) can be replaced by fluorine using a solution of potassium fluoride in polar solvents such as DMF and DMSO and high temperatures.[9]

References

  1. ↑ Finkelstein, Hank (1910). "Darstellung organischer Jodide aus den entsprechenden Bromiden und Chloriden". Ber. Dtsch. Chem. Ges. (in German). 43 (2): 1528–1532. doi:10.1002/cber.19100430257.
  2. ↑ Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, ISBN 0-471-72091-7
  3. ↑ Ervithayasuporn, V. (2013). "One-pot synthesis of halogen exchanged silsesquioxanes: octakis(3-bromopropyl)octasilsesquioxane and octakis(3-iodopropyl)octasilsesquioxane". Dalton Trans. 42: 13747–13753. doi:10.1039/C3DT51373D.
  4. ↑ Streitwieser, A. (1956). "Solvolytic Displacement Reactions at Saturated Carbon Atoms". Chem. Rev. 56 (4): 571–752. doi:10.1021/cr50010a001.
  5. ↑ Bordwell, F. G.; Brannen, W. T. (1964). "The Effect of the Carbonyl and Related Groups on the Reactivity of Halides in SN2 Reactions". J. Am. Chem. Soc. 86 (21): 4645–4650. doi:10.1021/ja01075a025.
  6. ↑ Maloney, D. J.; Hecht, S. M. (2005). "A Stereocontrolled Synthesis of δ-trans-Tocotrienoloic Acid". Org. Lett. 7 (19): 4297–300. PMID 16146411. doi:10.1021/ol051849t.
  7. ↑ Klapars, A.; Buchwald, S. L. (2002). "Copper-Catalyzed Halogen Exchange in Aryl Halides: An Aromatic Finkelstein Reaction". J. Am. Chem. Soc. 124 (50): 14844–14845. PMID 12475315. doi:10.1021/ja028865v.
  8. ↑ Cant, Alastair A.; Bhalla, Rajiv; Pimlott, Sally L.; Sutherland, Andrew (2012). "Nickel-catalysed aromatic Finkelstein reaction of aryl and heteroaryl bromides". Chem. Commun. 48 (33): 3993–5. PMID 22422214. doi:10.1039/c2cc30956d.
  9. ↑ Finger, G. C.; Kruse, C. W. (1956). "Aromatic Fluorine Compounds. VII. Replacement of Aromatic -Cl and -NO2 Groups by -F". J. Am. Chem. Soc. 78 (23): 6034–6037. doi:10.1021/ja01604a022.
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