Authored By: Abby L. Parrill and Jacquelyn Gervay
Funded by NSF, The University of Arizona, and The Department of Chemistry

Nucleophiles-General Information

A nucleophile is most simple an electron pair donor. Remember that an electron pair donor is a Lewis base. Any reagent with a pair of electrons can act as a nucleophile. However, better nucleophiles tend to be anions, rather than neutral species. Nucleophilicity is a measure of how fast a Lewis base displaces a leaving group.

Relative Nucleophilicity of Common Nucleophiles (in Methanol)

Reactivity Classification	Nucleophile
Very Good	Iodide(I-), Hydrogen Sulfide(HS-), Alkyl Sulfides(RS-)
Good	Bromide(Br-), Hydroxide(HO-), Alkoxides(RO-), Cyanide(CN-), Azide(N3-)
Fair	Ammonia(NH3), Chloride(Cl-), Fluoride(F-), Carboxylates(RCO2-)
Weak	Water(H2O), Alcohols(ROH)
Very Weak	Carboxylic Acids(RCO2H)

Correlation between Basicity and Nucleophilicity

When the nucleophilic atoms of two reagents are in the same row of the periodic table, the relative nucleophilicty of the reagents is directly related to the relative basicity of the two reagents. For example, F and O are in the same row of the periodic table, therefore we can use basicity to determine whether methoxide (CH3O-) or fluoride (F-) is a stronger nucleophile. Tables of acid dissociation constants (Ka) are widely available. The Ka values for the conjugate acids of the nucleophiles are 10^-5 for HF and 10^-16 for CH3OH. These correspond to pKa's of 5 for HF and 16 for CH3OH. Lower pKa values indicate stronger acids, which have weak conjugate bases and higher pKa values indicate weaker acids, which have stronger conjugate bases. Therefore, we can conclude that methoxide is a stronger nucleophile than fluoride.

Correlation between Aqueous Solvation and Nucleophilicity

Anions (such as many of our nucleophiles) can form strong hydrogen bonds in protic solvents. Protic solvents are ones which can donate hydrogen bonds such as water or alcohols. In general, the smaller an anion (higher in the periodic table), the stronger it hydrogen bonds to protic solvents. In order for a solvated nucleophile to react, it must shed some of its solvent molecules. This hinders the reaction and makes solvated nucleophiles appear to be less reactive than they would be in an aprotic solvent. This is the main reason why bromide is listed as a stronger nucleophile than fluoride in the table above. Fluoride is a much stronger base, but it is much more strongly solvated.

Correlation between Polarizability and Nucleophilicity

Polarizability is a measure of how easily the electron cloud around an atom can distort. In substitution reactions, the transition state involves a longer-than-normal partial bond to the nucleophile. If the nucleophile can allow some of its electron cloud to distort closer to the electrophile (usually a carbon atom), the transition state is more stable and the reaction will proceed more rapidly. Polarizability increases toward the bottom of the periodic table due to the larger distance between the positively charged nucleus and the outermost electrons.