Finkelstein reaction

The Finkelstein reaction, named for the German chemist Hans Finkelstein ^[1], is an S_N2 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 taking advantage of differential solubility of halide salts, or by using a large excess of the halide salt.

R-X + X′⁻ ⇌ R-X′ + X⁻

The classic Finkelstein reaction involves the conversion of an alkyl chloride or an alkyl bromide to an alkyl iodide by the addition of sodium iodide in acetone. Because sodium iodide is soluble in acetone and sodium chloride and sodium bromide are not, the equilibrium is shifted by 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 substrates are marginal. Vinyl, aryl and tertiary alkyl halides are unreactive. Below some relative rates of reaction (NaI in acetone at 60°):^[2]^[3]

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.^[4]

Halex reaction

The halex reaction describes any aryl HALogen EXchange. The chlorine atom in aryl chlorides (with electron-withdrawing substituents) is replaced by fluorine with potassium fluoride using polar solvents such as DMF and DMSO and high temperatures ^[5].

References

^ Finkelstein, H. Ber., 1910, 43, 1528.
^ Streitwieser, A. (1956). "Solvolytic Displacement Reactions at Saturated Carbon Atoms". Chem. Rev. 56: 571. doi:10.1021/cr50010a001.
^ Bordwell, F. G.; Brannen, W. T. (1964). "The Effect of the Carbonyl and Related Groups on the Reactivity of Halides in S_N2 Reactions". J. Am. Chem. Soc. 86: 4645. doi:10.1021/ja01075a025.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Maloney, D. J.; Hecht, S. M. (2005). "A Stereocontrolled Synthesis of δ-trans-Tocotrienoloic Acid". Org. Lett. 7 (19): 4297. doi:10.1021/ol051849t. PMID 16146411.
^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1021/ja01604a022, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1021/ja01604a022 instead.

[1] Finkelstein, H. Ber., 1910, 43, 1528.

[2] Streitwieser, A. (1956). "Solvolytic Displacement Reactions at Saturated Carbon Atoms". Chem. Rev. 56: 571. doi:10.1021/cr50010a001.

[3] Bordwell, F. G.; Brannen, W. T. (1964). "The Effect of the Carbonyl and Related Groups on the Reactivity of Halides in S_N2 Reactions". J. Am. Chem. Soc. 86: 4645. doi:10.1021/ja01075a025.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[4] Maloney, D. J.; Hecht, S. M. (2005). "A Stereocontrolled Synthesis of δ-trans-Tocotrienoloic Acid". Org. Lett. 7 (19): 4297. doi:10.1021/ol051849t. PMID 16146411.

[5] Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1021/ja01604a022, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1021/ja01604a022 instead.

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