Alkyl iodide, halide displacement

Secondary bromides and tosylates react with inversion of stereochemistry, as in the classical SN2 substitution reaction.24 Alkyl iodides, however, lead to racemized product. Aryl and alkenyl halides are reactive, even though the direct displacement mechanism is not feasible. For these halides, the overall mechanism probably consists of two steps an oxidative addition to the metal, after which the oxidation state of the copper is +3, followed by combination of two of the groups from the copper. This process, which is very common for transition metal intermediates, is called reductive elimination. The [R 2Cu] species is linear and the oxidative addition takes place perpendicular to this moiety, generating a T-shaped structure. The reductive elimination occurs between adjacent R and R groups, accounting for the absence of R — R coupling product. 

Sodium iodide in acetone is a reagent that converts alkyl chlorides and bromides into alkyl iodides by an SN2 mechanism. Pick the alkyl halide in each pair that is more reactive toward SN2 displacement. 

However, this is an equilibrium reaction the product can react with the displaced halide ion and reform the starting material. If the reaction is to be useful in synthesis, some method must be found to favor the product at equilibrium. If acetone is used as the solvent, the reaction of sodium iodide with alkyl chlorides or bromides can be used to prepare alkyl iodides. In this case the equilibrium favors the alkyl iodide because sodium chloride and sodium bromide (but not sodium iodide) are insoluble in acetone and precipitate, thus driving the equilibrium to the right according to Le Chatelier s principle. 

Halogen Exchange Reactions The Sn2 reaction provides a useful method for synthesizing alkyl iodides and fluorides, which are more difficult to make than alkyl chlorides and bromides. Halides can be converted to other halides by halogen exchange reactions, in which one halide displaces another. 

Castro et al. 44) found that the order of reactivity of various halides in coupling reactions with ethynylcopper compounds in DMF is ArSX, ArX > RCOX ArCHaX, RCH=CHCH2X, ArCOCHaX > RCH= CHX, Alkyl-X. A somewhat different order is observed for the reactivity of some organic halides towards perhaloarylcopper reagents in THF (97, 147) Allyl Aryl > Alkyl and perfluoroaryl, perfluoro-vinyl > aryl > perfluoroalkyl. Acid halides were also far more reactive than aryl iodides in ethereal solvents 146). The ease of halide displacement is I > Br > Cl. 

This reaction was initially reported by Finkelstein in 1910. It is a preparation of alkyl iodide from alkyl bromide or chloride with potassium or sodium iodide in acetone. Therefore, this reaction is generally known as the Finkelstein reaction. Occasionally, it is also referred to as the Finkelstein halide exchange, Finkelstein displacement, or Conant-Finkelstein reaction. Mechanistically, this reaction is a simple nucleophilic substitution (often via Sn2), as iodide is a stronger nucleophile than bromide or chloride. The yield of this reaction is very high and can be quantitative if occurs in DMF. It was found that the trifluoromethyl group retards the displacement of bromide when it presents as an a- or /3-substituent but accelerates the reaction as a substituent in an allylic chloride. Under normal conditions, this type of halide displacement does not occur for aryl halides. For dihalides, unsaturated or cyclic compounds may form via carbocation intermediates, which form transient covalent iodides or are reduced directly by iodide to free radicals. However, the aromatic halide exchange reacts smoothly when 10% Cul is present in the reaction... 

Typical conditions for these processes are simply to stir an aqueous solution of the metal salt of Y with the organic substrate alone, or in a solvent such as chloroform or benzene, in the presence of 5—10 mole % of a quaternary ammonium salt as catalyst. A recent example is to be found in a synthesis of alkyl azides from alkyl iodides (or other halides) using commercially available Aliquat 336 [mainly (1)] as catalyst, and a reaction temperature of 100 °C. The conversion of alkyl methanesulphonates to alkyl halides has been used to synthesize optically active secondary fluorides, chlorides and bromides via an 5 n2 inversion mechanism (the iodides racemize before isolation). Ammonium salt (1), or phosphonium salt (2), are used to catalyse these mesylate displacements. ... 

F-Methylation. Phosphonium salts are prepared by the quat-ernization of phosphines with methyl iodide. The displacement reaction is usually conducted in polar solvents such as acetonitrile or DMF. Dialkyl phosphonates are prepared from the reaction of trialkyl phosphites with alkyl halides, commonly known as the Arbuzov reaction. For example, diisopropyl methylphosphonate is prepared by heating a mixture of methyl iodide and Triisopropyl Phosphite (eq 34). ... 

As we have seen the nucleophile attacks the substrate m the rate determining step of the Sn2 mechanism it therefore follows that the rate of substitution may vary from nucleophile to nucleophile Just as some alkyl halides are more reactive than others some nucleophiles are more reactive than others Nucleophilic strength or nucleophilicity, is a measure of how fast a Lewis base displaces a leaving group from a suitable substrate By measuring the rate at which various Lewis bases react with methyl iodide m methanol a list of then nucleophihcities relative to methanol as the standard nucleophile has been compiled It is presented m Table 8 4... 

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