Nucleophile
In
Nucleophilic describes the affinity of a nucleophile to bond with positively charged
History
The terms nucleophile and
Properties
In general, in a group across the periodic table, the more basic the ion (the higher the pKa of the conjugate acid) the more reactive it is as a nucleophile. Within a series of nucleophiles with the same attacking element (e.g. oxygen), the order of nucleophilicity will follow basicity. Sulfur is in general a better nucleophile than oxygen.[citation needed]
Nucleophilicity
Many schemes attempting to quantify relative nucleophilic strength have been devised. The following
Swain–Scott equation
The first such attempt is found in the Swain–Scott equation[4][5] derived in 1953:
This
This treatment results in the following values for typical nucleophilic anions:
The equation predicts that, in a
Ritchie equation
The Ritchie equation, derived in 1972, is another free-energy relationship:[6][7][8]
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
or (not displayed) ions based on malachite green. Many other reaction types have since been described.
Typical Ritchie N+ values (in
Mayr–Patz equation
In the Mayr–Patz equation (1994):[9]
The
Many of the constants have been derived from reaction of so-called benzhydrylium ions as the electrophiles:[10]
and a diverse collection of π-nucleophiles:
Typical E values are +6.2 for R =
Typical N values with s in parentheses are −4.47 (1.32) for
The range of organic reactions also include SN2 reactions:[12]
With E = −9.15 for the S-methyldibenzothiophenium ion, typical nucleophile values N (s) are 15.63 (0.64) for
Unified equation
In an effort to unify the above described equations the Mayr equation is rewritten as:[12]
with sE the electrophile-dependent slope parameter and sN the nucleophile-dependent slope 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:
Types
Examples of nucleophiles are anions such as Cl−, or a compound with a lone pair of electrons such as NH3 (ammonia) and PR3.[citation needed]
In the example below, the
Ambident Nucleophile
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 sulfur or the nitrogen. For this reason, the SN2 reaction of an alkyl halide with SCN− often leads to a mixture of an alkyl thiocyanate (R-SCN) and an alkyl isothiocyanate (R-NCS). Similar considerations apply in the Kolbe nitrile synthesis.[citation needed]
Halogens
While the
Carbon
Carbon nucleophiles are often organometallic reagents such as those found in the Grignard reaction, Blaise reaction, Reformatsky reaction, and Barbier reaction or reactions involving organolithium reagents and acetylides. These reagents are often used to perform nucleophilic additions.[citation needed]
Oxygen
Examples of oxygen nucleophiles are water (H2O), hydroxide anion, alcohols, alkoxide anions, hydrogen peroxide, and carboxylate anions. Nucleophilic attack does not take place during intermolecular hydrogen bonding.
Sulfur
Of sulfur nucleophiles, hydrogen sulfide and its salts, thiols (RSH), thiolate anions (RS−), anions of thiolcarboxylic acids (RC(O)-S−), and anions of dithiocarbonates (RO-C(S)-S−) and dithiocarbamates (R2N-C(S)-S−) are used most often.
In general, sulfur is very nucleophilic because of its large size, which makes it readily polarizable, and its lone pairs of electrons are readily accessible.
Nitrogen
Nitrogen nucleophiles include ammonia, azide, amines, nitrites, hydroxylamine, hydrazine, carbazide, phenylhydrazine, semicarbazide, and amide.
Metal centers
Although metal centers (e.g., Li+, Zn2+, Sc3+, etc.) are most commonly cationic and electrophilic (Lewis acidic) in nature, certain metal centers (particularly ones in a low oxidation state and/or carrying a negative charge) are among the strongest recorded nucleophiles and are sometimes referred to as "supernucleophiles." For instance, using methyl iodide as the reference electrophile, Ph3Sn– is about 10000 times more nucleophilic than I–, while the Co(I) form of vitamin B12 (vitamin B12s) is about 107 times more nucleophilic.[14] Other supernucleophilic metal centers include low oxidation state carbonyl metalate anions (e.g., CpFe(CO)2–).[15]
Examples
The following table shows the nucleophilicity of some molecules with methanol as the solvent:[16]
Relative nucleophilicity | Molecules |
---|---|
Very Good | I⁻, HS⁻, RS⁻ |
Good | Br⁻, OH⁻, RO⁻, CN⁻, N3⁻ |
Fair | NH3, Cl⁻, F⁻, RCO2⁻ |
Weak | H2O, ROH |
Very Weak | RCO2H |
See also
- Electrophile – A chemical species that accepts an electron pair from a nucleophile
- Lewis acids and bases – Chemical bond theory
- Nucleophilic abstraction – Type of organometallic reaction
- Addition to pi ligands– Organometallic chemistry rule
References
- ^ Nucleophilicity—Periodic Trends and Connection to Basicity. Einar Uggerud. https://doi.org/10.1002/chem.200500639
- .
- ^ Lapworth, A. (1925). "Replaceability of Halogen Atoms by Hydrogen Atoms". Nature. 115: 625.
- J. Am. Chem. Soc.; 1953; 75(1); 141-147. Abstract
- .
- .
- ^ Nucleophilic reactivities toward cations Calvin D. Ritchie Acc. Chem. Res.; 1972; 5(10); 348-354. Abstract
- J. Am. Chem. Soc.; 1975; 97(5); 1170–1179. Abstract
- .
- S2CID 8392147.
- ^ An internet database for reactivity parameters maintained by the Mayr group is available at http://www.cup.uni-muenchen.de/oc/mayr/
- ^ PMID 16646102.
- ^ Chem 2401 Supplementary Notes. Thompson, Alison and Pincock, James, Dalhousie University Chemistry Department
- PMID 5642073.
- ISSN 0002-7863.
- ^ Ian Hunt. "Chapter 8: Nucleophiles". chem.ucalgary.ca. University of Calgary. Retrieved 15 April 2024.