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In chemistry, a nucleophile (literally nucleus lover as in nucleus and phile) is a reagent that forms a chemical bond to its reaction partner (the electrophile) by donating both bonding electrons . Because nucleophiles donate electrons, they are by definition Lewis bases (see acid-base reaction theories). All molecules or ions with a free pair of electrons can act as nucleophiles, although negative ions (anions) are more potent than neutral reagents. Neutral nucleophilic reactions with solvents such as alcohols and water are named solvolysis. Nucleophiles may take part in nucleophilic substitution, whereby a nucleophile becomes attracted to a full or partial positive charge on an element and displaces the group it is bonded to. Nucleophilic is an adjective that describes the affinity of a nucleophile to the nuclei, while nucleophilicity or nucleophile strength refers to the nucleophilic character. Nucleophilicity is often used to compare an atom's relative affinity to another's. In general, the more basic the ion (the lower the pKa of the conjugate acid), the more reactive it is as a nucleophile. Polarizability is also important in the determination of the nucleophilicity: the easier it is to distort the electron cloud around an atom or molecule, the more readily it will react. e.g., the iodide ion (I−) is more nucleophilic than the fluoride ion (F−). An ambident nucleophile is one that can attack from two or more places, resulting in two or more products. For example, the thiocyanate ion (SCN−) may attack from either the or the . For this reason, the SN2 reaction of an alkyl halide with SCN− often leads to a mixture of RSCN (an alkyl thiocyanate) and RNCS (an alkyl isothiocyanate). The terms nucleophile and electrophile were introduced by Christopher Kelk Ingold in 1929 , replacing the terms cationoid and anionoid proposed earlier by A. J. Lapworth in 1925 . Common examples In the example below, the oxygen of the hydroxide ion donates an electron to bond with the carbon at the end of the bromopropane molecule. The bond between the carbon and the bromine then undergoes heterolytic fission, with the bromine atom taking the pair of electrons and becoming the bromide ion (Br−): Carbon nucleophiles Carbon nucleophiles are alkyl metal halides found in the Grignard reaction, Blaise reaction, Reformatsky reaction, and Barbier reaction, organolithium reagents and anions of a terminal alkyne Oxygen nucleophiles Examples of oxygen nucleophiles are Water (H2O) and Alcohols Sulphur nucleophiles Sulphur nucleophiles are Thiols (HS−) Nitrogen nucleophiles Nitrogen nucleophiles are Ammonia and Amines Nucleophilicity scales Many schemes have been devised attempting to quantify relative nucleophilic strength. The following empirical data have been obtained by measuring reaction rates for a large number of reactions involving a large number of nucleophiles and electrophiles and linear regression. Swain-Scott equation The first such attempt is found in the so-called Swain-Scott equation derived in 1953: This free-energy relationship relates the the pseudo first order reaction rate constant (in water at 25°C), k, of a reaction, normalized to the reaction rate, k0, of a standard reaction with water as the nucleophile, to a nucleophilic constant n for a given nucleophile and a substrate constant s that depends on the sensitivity of a substrate to nucleophilic attack (defined as 1 for methyl bromide). This treatment results in the following values for typical nucleophilic anions: acetate 2.7, chloride 3.0, azide 4.0, hydroxide 4.2, aniline 4.5, iodide 5.0 and thiosulfate 6.4. Typical substrate constants are 0.66 for ethyl tosylate, 0.77 for β-propiolactone, 1.00 for 2,3-epoxypropanol, 0.87 for benzyl chloride and 1.43 for benzoyl chloride. The equation predicts that in a nucleophilic displacement on benzyl chloride, the azide anion reacts 3000 times faster than water. Richie equation The Richie equation named after its creator and derived in 1972 is another free-energy relationship or where N+ is the nucleophile dependent parameter and k0 the reaction rate constant for water. In this equation a substrate dependent parameter like s in the Swain-Scott equation is absent. The equation states that two nucleophiles react with the same relative reactivity regardless of the nature of the electrophile which is in violation of the Reactivity–selectivity principle. For this reason this equation is also called the constant selectivity relationship. In the original publication the data were obtained by reactions of selected nucleophiles with selected electrophilic carbocations such as tropylium cations: or diazonium cations: or (not displayed) ions based on Malachite green. Subsequently many other reaction types were described. Typical Richie N+ values (in methanol) are: 0.5 for methanol, 5.9 for the cyanide anion, 7.5 for the methoxide anion , 8.5 for the azide anion and 10.7 for the thiophenol anion. The values for the relative cation reactivities are -0.4 for the malachite green cation, +2.6 for the benzenediazonium cation and +4.5 for the tropylium cation. Mayr-Patz equation
Unified equation In an effort to unify the above described equations the Mayr equation is rewritten as : with sE the electrophile-dependent slope parameter and sN the nucleophile-dependent slop parameter. This equation can be rewritten in several ways: or the original Scott-Swain equation written as: or the original Ritchie equation written as: See also | |||||||||
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