Finkelstein exchange

The nucleophilic reactivity of the alkali metal fluorides decreases in the order CsF RbF KF NaF LiF, because of the increasing lattice energy of the fluorides with decreasing ion radius of the cation (CsF 177.7 kcal mol RbF 186.4 kcal mol KF 194.0 kcal mol NaF 218.4 kcal mol LiF 247.0 kcal mol ) [32]. To avoid this problem, crown ethers or phase-transfer catalysts with large, lipophilic cations are often used to render nucleophilic fluorina-tions more efficient. 

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For alkylation with some alkyl bromides or chlorides, Finkelstein exchange wfith r is required ... 

I 2 Synthesis of Complex Organofluorine Compounds 2.1.3.1 Finkelstein Exchange... 

Scheme 2.11 Finkelstein exchange of tosylates by fluoride. The volatile alkyl fluoride is removed from the reaction mixture by distillation [30].

In order to remove the primary hydroxy group, the protected triol 24 was acet-ylated and treated with pyridinium tosylate to yield the monoester 25. Selective tosylation of the primary hydroxy group followed by Finkelstein exchange for iodine yielded the iodo derivative 26 which was transformed into the protected cyclohexene diol 27 by reductive removal of the iodine with tributyltin hydride followed by protection of the tertiary hydroxy group with dihydopyran. After removal of the benzoyl group by alkaline saponification the resulting allylic alcohol was oxidised to the desired enone 28 with pyridinium chlorochromate in buffered solution (ref. 16). 

Secondary or tertiary alkyl halides are much less reactive. For example an alkyl dichloride with a primary and a secondary chloride substituent reacts selectively by exchange of the primary chloride. The reactivity with respect to the Finkelstein reaction is thus opposite to the reactivity for the hydrolysis of alkyl chlorides. For the Finkelstein reaction on secondary and tertiary substrates Lewis acids may be used," e.g. ZnCla, FeCls or MesAl. 

Halide exchange, sometimes call the Finkelstein reaction, is an equilibrium process, but it is often possible to shift the equilibrium." The reaction is most often applied to the preparation of iodides and fluorides. Iodides can be prepared from chlorides or bromides by taking advantage of the fact that sodium iodide, but not the bromide or chloride, is soluble in acetone. When an alkyl chloride or bromide is treated with a solution of sodium iodide in acetone, the equilibrium is shifted by the precipitation of sodium chloride or bromide. Since the mechanism is Sn2, the reaction is much more successful for primary halides than for secondary or tertiary halides sodium iodide in acetone can be used as a test for primary bromides or chlorides. Tertiary chlorides can be converted to iodides by treatment with excess Nal in CS2, with ZnCl2 as catalyst. " Vinylic bromides give vinylic iodides with retention of configuration when treated with KI and a nickel bromide-zinc catalyst," or with KI and Cul in hot HMPA." ... 

The constant C, however, depends on the nature of the interaction between a pair of electrons. If it is mainly of exchange type then C is positive and of order unity, as we have seen. There is also a term of Hartree type—namely that due to direct interaction between the electrons. This has the opposite sign. Finkelstein (1983) and Altshuler and Aronov (1983) found that when the Hartree term is included C should be multiplied by... 

Halide exchange reactions ( transhalogenation or Finkelstein reaction) have been, until recently, of particular synthetic importance only in the synthesis of alkyl (and strongly activated aryl) fluorides or iodides, where thermodynamic stability (for the fluorides) and solubility differences (for the iodides) shift the reversible exchange processes in the desired direction. With the advent of phase transfer catalysis (PTC) and transition metal catalysis (mainly homogeneous) this important family of reactions has been extended to practically all aromatic and aliphatic halides. 

In the presence of molar amounts of catalyst, the chloride/iodide exchange reaction is more effective as has been shown by Brandsrom178 for the conversion of chloroaceto-2,6-xylidide into the corresponding iodide. The Finkelstein reaction is also catalyzed by phos-phonium and arsonium salts1. 

An example of reaction type (d) in Table 5-4 is the Finkelstein halide exchange reaction between iodomethane and radioactive labeled iodide ion. The rate constant for this reaction decreases by about 10" on going from less polar acetone to water as solvent [66]. 

Halide exchange from the lower halides to iodine is often desirable due to the higher reactivity of iodides in nucleophilic substitutions, reductions, organometallic or radical reactions (Scheme 30). Conversion of chlorides and bromides to iodides with sodium iodide in acetone is called the Finkelstein reaction. This halide exchange is an equilibrium process, which is shifted to the iodinated products due to precipitation of the less soluble sodium bromide or chloride from acetone. Best results are obtained when the reaction mixture is free of water. 

Finkelstein reaction Equilibrium exchange of the halogen atom in alkyl halides for another halogen atom. 170... 

Williams, R., Kennedy, A., Hijji, Y., Tadesse, S. Finkelstein halogen exchange reaction using microwave energy and a binary solvent system. Proceedings - NOBCChE 2001, 28, 58-63. 

Hayami, J., Koyanagi, T., Kaji, A. Sn2 reactions in dipolar aprotic solvents. VIII. Chlorine isotopic exchange reaction of (arylsulfonyl)chloromethanes, (arylsulfinyl)chloromethanes, and 2-chloro-1-arylethanones in acetonitrile. A role of the nucleophile-substrate interaction in the Finkelstein reaction. Bull. Chem. Soc. Jpn. 1979, 52, 1441-1446. 

Finkelstein reaction The exchange of one halide for another in aliphatic compounds, resulting in the equilibrium mixture being formed. 

In 1967, Pedersen described the preparation and properties of crown ethers,3 which are macrocyclic polyethers capable of sequestering metal cations. These catalysts can enhance the solubility and reactivity of salts in nonpolar solvents. For example, 18-crown-6, i.e., yxo-anhydro-hexaethylene glycol, forms a host-guest complex with potassium cation (K+) (Equation (1)). This association enables ionic potassium fluoride (KF) to dissociate in nonpolar benzene. And since the nucleophilic F counterions are not complexed,4 the yield of the Finkelstein reaction,5 i.e., halide-halide exchange, is increased 6... 

Nachliel, E., Finkelstein, Y., Gutman, M., The mechanism of monensin-mediated cation exchange based on real time measurements, Biochim. Biophys. Acta, 1996, 1285, 131-145. 

Transport of molecules across the cell membrane occurs by passive and facilitated diffusion and active transport (Stein, 1986 Finkelstein, 1987). Passive transport is governed by a mass-transfer coefficient, surface area for exchange, transmembrane concentration difference, and a partition coefficient. The partition coefficient can be modified by charge, pH, temperature, and presence of other drugs. Facilitated transport may be most simply described by Michaelis-Menten kinetics. Depending upon the carrier system, symmetric or asymmetric models may be used. 

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