Finkelstein reaction - a method for the synthesis of alkyl iodides or alkyl fluorides by the interaction of alkyl chlorides or alkyl bromides with alkali metal iodides or fluorides , was proposed by Hans Finkelstein in 1910 as a method for the synthesis of alkyl iodides [1] .
The Finkelstein reaction proceeds according to the mechanism of S N 2 ( bimolecular nucleophilic substitution ) and is equilibrium:
In the classic version of the Finkelstein reaction, to increase the yields of alkyl iodides, it is carried out in solvents in which sodium or potassium iodides are readily soluble, and alkali metal chlorides or bromides formed during the reaction are slightly soluble, for example, by the interaction of alkyl halides with sodium iodide in anhydrous acetone :
- {\ displaystyle {\ mathsf {CH_ {3} CH_ {2} Br + NaI \ rightarrow CH_ {3} CH_ {2} I + NaBr \ downarrow}}}
Due to the equilibrium of the Finkelstein reaction, an isotopic exchange of halogens between a metal halide and an alkyl halide is also possible:
The reactivity of alkyl halides in the Finkelstein reaction depends on both the nature of the halogen and the structure of the alkyl halide: the equilibrium is shifted towards replacing the less nucleophilic halogen (chlorine) with the more nucleophilic (bromine and iodine). The dependence of the reactivity of alkyl halides is typical for the reaction S N 2 and decreases in the series primary - secondary - tertiary alkyl halides, allyl and benzyl halides compounds, as well as Ξ±-halogen-carbonyl compounds:
| Me-cl | Bu-cl | i-Pr-Cl | t-BuCH 2 -Cl | CH 2 = CH-CH 2 -Cl | PhCH 2 -Cl | EtOC (O) CH 2 -Cl | MeC (O) CH 2 -Cl |
|---|---|---|---|---|---|---|---|
| 179 | one | 0.0146 | 0.00003 | 64 | 179 | 1600 | 33000 |
In modern modifications of the Finkelstein reaction, not only halogens, but also sulfonates (usually mesylates or tosylates ) are used as a leaving group exchanged for iodine, which allows converting alcohols to alkyl iodides in high yields [4] :
Such a transformation proceeds under mild conditions, which is used for the regioselective substitution of alcohol hydroxyl for iodine while maintaining the configurations of the chiral centers of the molecule [5] :
Another modification of the Finkelstein reaction is its carrying out under conditions of interphase catalysis . The main difference between this modification and the classical method is the possibility of synthesis of alkyl fluorides due to the solubilization of fluoride ion in non-polar solvents, while it is possible to carry out the reaction both in the system "organic phase / aqueous solution of fluoride" and in the system "organic phase / solid fluoride" Onium salts are usually used as phase transfer catalysts in the first case, crown ethers in the second; fluoride yields from primary alkyl bromides and benzyl bromides are 70β90%. Since the fluoride anion weakly solvated under such conditions acts not only as a nucleophile, but also as a base, in the case of unactivated alkyl halides, the reaction of substitution of halogen for fluorine competes with the elimination reaction , which in some cases becomes predominant (cyclohexyl chloride) [6] .
Notes
- β Finkelstein, Ber. Dtsch. Chem. Ges., 1910, 43, 1528.
- β Streitwieser, A. Solvolytic Displacement Reactions at Saturated Carbon Atoms (Eng.) // Chem. Rev. : journal. - 1956. - Vol. 56 , no. 4 . - P. 571 . - DOI : 10.1021 / cr50010a001 .
- β Bordwell, FG; Brannen, W.T. The Effect of the Carbonyl and Related Groups on the Reactivity of Halides in S N 2 Reactions (Eng.) // J. Am. Chem. Soc. : journal. - 1964. - Vol. 86 , no. 21 . - P. 4645 . - DOI : 10.1021 / ja01075a025 .
- β William F. Bailey, Matthew R. Luderer, Michael J. Mealy, and Eric R. Punzalan. Generation and cyclization of 5-Hexenyllithium: 2-Cyclopentylacetophenone (Ethanone, 2-cyclopentyl-1-phenyl-). Organic Syntheses, Vol. 81, p. 121 (2005).
- β Maloney, DJ; Hecht, SM A Stereocontrolled Synthesis of Ξ΄- trans- Tokotrienoloic Acid (English) // Org. Lett. : journal. - 2005. - Vol. 7 , no. 19 . - P. 4297-4300 . - DOI : 10.1021 / ol051849t . - PMID 16146411 .
- β Demlov E., Demlov Z. Interfacial catalysis. - M .: Mir, 1987. - pp. 109-115