nucleophile - Nucleophilicity scales

An entity with an excess of electrons which tends to react at a positively charged centre. Anions and molecules with lone pairs of electrons (eg H₂O and NH₃) are nucleophiles.

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.

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. 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.

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 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).

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 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.

Mayr-Patz equation

In the Mayr-patz equation (1994):

The second order reaction rate constant k at 20°C for a reaction is related to a nucleophilicity parameter N, an electrophilicity parameter E and a nucleophile-dependent slope parameter s.

Many of the constants have been derived from reaction of so-called benzhydrylium ions as the electrophiles:

and a diverse collection of π-nucleophiles:

.

Typical N values with s in parenthesis are -4.47 (1.32) for electrophilic aromatic substitution to toluene (1), -1.41 (1.12) for electrophilic addition to 1-phenyl-2-propene (2) and 0.96 (1) for addition to 2-methyl-1-pentene (3), -0.13 (1.21) for reaction with triphenylallylsilane (4), 3.61 (1.11) for reaction with 2-methylfuran (5), +7.48 (0.89) for reaction with isobutenyltributylstannane (6) and +13.36 (0.81) for reaction with the enamine 7.

The range of organic reactions also include SN2 reactions:

With E = -9.15 for the S-methyldibenzothiophenium ion, typical nucleophile values N (s) are 15.63 (0.64) for piperidine, 10.49 (0.68) for methoxide and 5.20 (0.89) for water.

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:

with sE = 1 for carbocations this equation is equal to the original Mayr-Patz equation of 1994, with sN = 0.6 for most n nucleophiles the equation becomes or the original Scott-Swain equation written as: with sE = 1 for carbocations and sN = 0.6 the equation becomes: or the original Ritchie equation written as: