A substitution reaction (also known as single displacement reaction or single substitution reaction) is a chemical reaction during which one
functional group in a
chemical compound is replaced by another functional group.
Substitution reactions are of prime importance in
organic chemistry. Substitution reactions in organic chemistry are classified either as
electrophilic
In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carri ...
or
nucleophilic depending upon the reagent involved, whether a
reactive intermediate
In chemistry, a reactive intermediate or an intermediate is a short-lived, high-energy, highly reactive molecule. When generated in a chemical reaction, it will quickly convert into a more stable molecule. Only in exceptional cases can these comp ...
involved in the reaction is a
carbocation
A carbocation is an ion with a positively charged carbon atom. Among the simplest examples are the methenium , methanium and vinyl cations. Occasionally, carbocations that bear more than one positively charged carbon atom are also encountere ...
, a
carbanion
In organic chemistry, a carbanion is an anion in which carbon is trivalent (forms three bonds) and bears a formal negative charge (in at least one significant resonance form).
Formally, a carbanion is the conjugate base of a carbon acid:
:R3C ...
or a
free radical, and whether the
substrate
Substrate may refer to:
Physical layers
*Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached
** Substrate (locomotion), the surface over which an organism lo ...
is
aliphatic or
aromatic. Detailed understanding of a reaction type helps to predict the product outcome in a reaction. It also is helpful for optimizing a reaction with regard to variables such as temperature and choice of
solvent.
A good example of a substitution reaction is
halogenation
In chemistry, halogenation is a chemical reaction that entails the introduction of one or more halogens into a compound. Halide-containing compounds are pervasive, making this type of transformation important, e.g. in the production of polymers, ...
. When
chlorine gas (Cl
2) is irradiated, some of the molecules are split into two chlorine
radicals
Radical may refer to:
Politics and ideology Politics
*Radical politics, the political intent of fundamental societal change
*Radicalism (historical), the Radical Movement that began in late 18th century Britain and spread to continental Europe and ...
(Cl•), whose free electrons are strongly
nucleophilic. One of them breaks a
C–H covalent bond in CH
4 and grabs the hydrogen atom to form the electrically neutral HCl. The other radical reforms a covalent bond with the CH
3• to form CH
3Cl (
methyl chloride).
Nucleophilic substitution
In organic (and inorganic) chemistry,
nucleophilic substitution is a fundamental class of reactions in which a
nucleophile
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...
selectively bonds with or attacks the positive or partially positive charge on an atom or a group of atoms. As it does so, it replaces a weaker nucleophile, which then becomes a
leaving group; the remaining positive or partially positive atom becomes an
electrophile. The whole molecular entity of which the electrophile and the leaving group are part is usually called the
substrate
Substrate may refer to:
Physical layers
*Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached
** Substrate (locomotion), the surface over which an organism lo ...
.
The most general form for the reaction may be given as
:
Nuc\mathbf + R-LG -> R-Nuc + LG\mathbf
where indicates the substrate. The
electron pair
In chemistry, an electron pair or Lewis pair consists of two electrons that occupy the same molecular orbital but have opposite spins. Gilbert N. Lewis introduced the concepts of both the electron pair and the covalent bond in a landmark paper ...
(:) from the nucleophile (Nuc:) attacks the substrate (), forming a new covalent bond . The prior state of charge is restored when the leaving group (LG) departs with an electron pair. The principal product in this case is . In such reactions, the nucleophile is usually electrically neutral or negatively charged, whereas the substrate is typically neutral or positively charged.
An example of nucleophilic substitution is the hydrolysis of an
alkyl bromide, , under basic conditions, where the ''attacking'' nucleophile is the base and the leaving group is :
:
R-Br + OH- -> R-OH + Br-
Nucleophilic substitution reactions are commonplace in organic chemistry, and they can be broadly categorized as taking place at a carbon of a saturated
aliphatic compound
In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane, or ...
carbon or (less often) at an aromatic or other unsaturated carbon center.
Mechanisms
Nucleophilic substitutions on aliphatic carbon centers can proceed by two different mechanisms, unimolecular nucleophilic substitution (
SN1) and bimolecular nucleophilic substitution (
SN2).
The S
N1 mechanism has two steps. In the first step, the leaving group departs, forming a
carbocation
A carbocation is an ion with a positively charged carbon atom. Among the simplest examples are the methenium , methanium and vinyl cations. Occasionally, carbocations that bear more than one positively charged carbon atom are also encountere ...
. In the second step, the nucleophilic reagent (Nuc:) attaches to the carbocation and forms a covalent sigma bond. If the substrate has a
chiral carbon, this mechanism can result in either inversion of the
stereochemistry
Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereois ...
or retention of configuration. Usually, both occur without preference. The result is
racemization.
The S
N2 mechanism has just one step. The attack of the reagent and the expulsion of the leaving group happen simultaneously. This mechanism always results in inversion of configuration. If the substrate that is under nucleophilic attack is chiral, the reaction will therefore lead to an inversion of its
stereochemistry
Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereois ...
, called a
Walden inversion.
S
N2 attack may occur if the backside route of attack is not
sterically hindered
Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...
by substituents on the substrate. Therefore, this mechanism usually occurs at an unhindered primary carbon center. If there is steric crowding on the substrate near the leaving group, such as at a tertiary carbon center, the substitution will involve an S
N1 rather than an S
N2 mechanism; an S
N1 would also be more likely in this case because a sufficiently stable carbocation intermediary could be formed.
When the substrate is an
aromatic compound, the reaction type is
nucleophilic aromatic substitution, which occur with various mechanisms.
Carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
derivatives react with nucleophiles in
nucleophilic acyl substitution. This kind of reaction can be useful in preparing compounds.
Electrophilic substitution
Electrophiles are involved in
electrophilic substitution
Electrophilic substitution reactions are chemical reactions in which an electrophile displaces a functional group in a compound, which is typically, but not always, aromatic. Aromatic substitution reactions are characteristic of aromatic compounds ...
reactions, particularly in
electrophilic aromatic substitutions.
In this example, the benzene ring's electron resonance structure is attacked by an electrophile E
+. The resonating bond is broken and a carbocation resonating structure results. Finally a proton is kicked out and a new aromatic compound is formed.
Electrophilic reactions to other unsaturated compounds than
arenes generally lead to
electrophilic addition rather than substitution.
Radical substitution
A
radical substitution reaction involves
radicals
Radical may refer to:
Politics and ideology Politics
*Radical politics, the political intent of fundamental societal change
*Radicalism (historical), the Radical Movement that began in late 18th century Britain and spread to continental Europe and ...
. An example is the
Hunsdiecker reaction.
Organometallic substitution
Coupling reactions are a class of metal-catalyzed reactions involving an
organometallic
Organometallic chemistry is the study of organometallic compounds, chemical compounds containing at least one chemical bond between a carbon atom of an organic molecule and a metal, including alkali, alkaline earth, and transition metals, and so ...
compound RM and an organic halide R′X that together react to form a compound of the type R-R′ with formation of a new
carbon–carbon bond. Examples include the
Heck reaction,
Ullmann reaction, and
Wurtz–Fittig reaction
The Wurtz–Fittig reaction is the chemical reaction of aryl halides with alkyl halides and sodium metal in the presence of dry ether to give substituted aromatic compounds. Charles Adolphe Wurtz reported what is now known as the Wurtz rea ...
. Many variations exist.
Substituted compounds
Substituted compounds are
chemical compounds where one or more
hydrogen atoms of a core structure have been replaced with a
functional group like
alkyl,
hydroxy, or
halogen
The halogens () are a group in the periodic table consisting of five or six chemically related elements: fluorine (F), chlorine (Cl), bromine (Br), iodine (I), astatine (At), and tennessine (Ts). In the modern IUPAC nomenclature, this group is ...
, or with larger
substituent
A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as ''side ...
groups.
For example,
benzene is a
simple aromatic ring
Simple aromatic rings, also known as simple arenes or simple aromatics, are aromatic organic compounds that consist only of a conjugated planar ring system. Many simple aromatic rings have trivial names. They are usually found as substructures of ...
. Benzenes that have undergone substitution are a
heterogeneous
Homogeneity and heterogeneity are concepts often used in the sciences and statistics relating to the uniformity of a substance or organism. A material or image that is homogeneous is uniform in composition or character (i.e. color, shape, siz ...
group of chemicals with a wide spectrum of uses and properties:
References
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