The
alpha effect refers to the increased
nucleophilicityIn chemistry, a nucleophile is a reagent that forms a chemical bond to its reaction partner by donating both bonding electrons. Because nucleophiles donate electrons, they are by definition Lewis bases . All molecules or ions with a free pair of electrons can act as nucleophiles...
of a
moleculeA molecule is defined as an electrically neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds. Molecules are distinguished from polyatomic ions in this strict sense...
due to the presence of an adjacent (alpha)
atomThe atom is a basic unit of matter consisting of a dense, central nucleus surrounded by a cloud of negatively charged electrons. The atomic nucleus contains a mix of positively charged protons and electrically neutral neutrons...
with
lone pairA lone pair is a electron pair without bonding or sharing with other atoms. They are found in the outermost electron shell of an atom, so lone pairs are a subset of a molecule's valence electrons...
electronAn electron is a subatomic particle that carries a negative electric charge. It has no known substructure and is believed to be a point particle. An electron has a mass that is approximately 1836 times less than that of the proton. The intrinsic angular momentum of the electron is a half integer...
s . The molecule does not necessarily exhibit increased basicity compared with a similar molecule without the adjacent, electron donating atom. The effect is well established with many theories to explain the effect but without a clear winner.
The effect was first observed by Jencks and Carriuolo in 1960 in a series of
chemical kineticsChemical kinetics, also known as reaction kinetics, is the study of rates of chemical processes. Chemical kinetics includes investigations of how different experimental conditions can influence the speed of a chemical reaction and yield information about the reaction's mechanism and transition...
experiments involving the reaction of the
esterEsters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
p-nitrophenyl acetate with a range of nucleophiles.
The
alpha effect refers to the increased
nucleophilicityIn chemistry, a nucleophile is a reagent that forms a chemical bond to its reaction partner by donating both bonding electrons. Because nucleophiles donate electrons, they are by definition Lewis bases . All molecules or ions with a free pair of electrons can act as nucleophiles...
of a
moleculeA molecule is defined as an electrically neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds. Molecules are distinguished from polyatomic ions in this strict sense...
due to the presence of an adjacent (alpha)
atomThe atom is a basic unit of matter consisting of a dense, central nucleus surrounded by a cloud of negatively charged electrons. The atomic nucleus contains a mix of positively charged protons and electrically neutral neutrons...
with
lone pairA lone pair is a electron pair without bonding or sharing with other atoms. They are found in the outermost electron shell of an atom, so lone pairs are a subset of a molecule's valence electrons...
electronAn electron is a subatomic particle that carries a negative electric charge. It has no known substructure and is believed to be a point particle. An electron has a mass that is approximately 1836 times less than that of the proton. The intrinsic angular momentum of the electron is a half integer...
s . The molecule does not necessarily exhibit increased basicity compared with a similar molecule without the adjacent, electron donating atom. The effect is well established with many theories to explain the effect but without a clear winner.
The effect was first observed by Jencks and Carriuolo in 1960 in a series of
chemical kineticsChemical kinetics, also known as reaction kinetics, is the study of rates of chemical processes. Chemical kinetics includes investigations of how different experimental conditions can influence the speed of a chemical reaction and yield information about the reaction's mechanism and transition...
experiments involving the reaction of the
esterEsters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
p-nitrophenyl acetate with a range of nucleophiles. Regular nucleophiles such as the
fluorideFluoride is the anion F
−, the reduced form of fluorine. Both organic and inorganic compounds containing the element fluorine are sometimes called fluorides. Fluoride, like other halides, is a monovalent ion . Its compounds often have properties that are distinct relative to other...
anion,
anilineAniline, phenylamine or aminobenzene is an organic compound with the formula C
6H
7N. It is the simplest and one of the most important aromatic amines, being used as a precursor to more complex chemicals. Its main application is in the manufacture of polyurethane...
,
pyridinePyridine is a simple aromatic heterocyclic organic compound with the chemical formula C
5H
5N used as a precursor to agrochemicals and pharmaceuticals, and is also an important solvent and reagent. It is structurally related to benzene, wherein one CH group in the aromatic...
,
ethylene diamineEthylenediamine is the organic compound with the formula C2H42. This colorless liquid with an ammonia-like odor is a strongly basic amine...
and the phenolate ion were found to have pseudo first order reaction rates corresponding to their basicity as measured by their
pKaPKA or pKa may be:* Protein kinase A, a cAMP activated protein kinase* pKa, the symbol for Acid dissociation constant* Pi Kappa Alpha, the North-American social fraternity* Public Key Authentication...
. Other nucleophiles however reacted much faster than was what to expected based on this criterium alone. These include
hydrazineHydrazine is an inorganic chemical compound with the formula N2H4. It is a colourless liquid with an ammonia-like odor and is derived from the same industrial chemistry processes that manufacture ammonia...
,
hydroxylamineHydroxylamine is a reactive chemical with formula NH2OH. It can be considered a hybrid of ammonia and water due to parallels it shares with each...
, the
hypochloriteThe hypochlorite ion is ClO
−. A hypochlorite compound is a chemical compound containing this group, with chlorine in oxidation state +1. Because of this oxidation state, the hypochlorite ion can be alternately named the chlorate ion....
ion,
ethanolamineEthanolamine, also called 2-aminoethanol or monoethanolamine , is an organic chemical compound that is both a primary amine and a primary alcohol . Like other amines, monoethanolamine acts as a weak base...
and the hydroperoxide anion.
In 1962 Edwards and Pearson (the latter of
HSAB theoryThe HSAB concept is an acronym for 'hard and soft acids and bases'. Also known as the Pearson acid base concept, HSAB is widely used in chemistry for explaining stability of compounds, reaction mechanisms and pathways....
fame) introduced the phrase
alpha effect for this anomaly. He offered the suggestion that the effect was caused by a
transition stateThe transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest energy along this reaction coordinate...
(TS) stabilization effect: on entering the TS the free electron pair on the nucleophile moves away from the nucleus causing a partial positive charge which can be stabilized by an adjacent
lone pairA lone pair is a electron pair without bonding or sharing with other atoms. They are found in the outermost electron shell of an atom, so lone pairs are a subset of a molecule's valence electrons...
as for instance happens in any
carbocationA carbocation is an ion with a positively-charged carbon atom. The charged carbon atom in a carbocation is a "sextet", i.e. it has only six electrons in its outer valence shell instead of the eight valence electrons that ensures maximum stability . Therefore carbocations are often reactive,...
.
Over the years many additional theories have been put forward attempting the effect. A ground state stabilizing effect assumes that the alpha lone-pair and nucleophilic electron pair destabilize each other by electronic repulsion thereby increasing the ground state and making it more reactive. Stabilization of the transition state is possible by assuming some TS free radical character or assuming that the TS has more advanced nucleophile-substrate bond formation. The
polarizabilityPolarizability is the relative tendency of a charge distribution, like the electron cloud of an atom or molecule, to be distorted from its normal shape by an external electric field, which may be caused by the presence of a nearby ion or dipole....
of the nucleophile or involvement of
intramolecularIntramolecular in chemistry describes a process or characteristic limited within the structure of a single molecule; a property or phenomenon limited to the extent of a single molecule.- Examples :...
catalysisCatalysis is the process in which the rate of a chemical reaction is either increased or decreased by means of a chemical substance known as a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. The catalyst may participate...
also plays a role. One recent
in silicoIn silico is an expression used to mean "performed on computer or via computer simulation." The phrase is coined in analogy to the Latin phrases in vivo and in vitro which are commonly used in biology and refer to experiments done in living organisms and outside of living organisms, respectively...
contribution did find a correlation between the alpha effect and the so-called deformation energy which is the electronic energy required to bring the two reactants together in the transition state.
The alpha effect is also dependent on
solventA solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution.The most common solvent in everyday life is water. Most other commonly-used solvents are organic chemicals. These are called organic solvents...
but not in a predictable way: it can increase or decrease with solvent mix composition or even go through a maximum.