A
reaction intermediate or an
intermediate is a
molecular entityAccording to IUPAC Gold Book a molecular entity is any constitutionally or isotopically distinct atom, molecule, ion, ion pair, radical, radical ion, complex, conformer, etc., identifiable as a separately distinguishable entity....
that is formed from the reactants (or preceding intermediates) and reacts further to give the directly observed products of a
chemical reactionA chemical reaction is a process that leads to the transformation of one set of chemical substances to another. They are studied by chemists under a field of science called chemistry. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, often coming about...
. Most chemical reactions are
stepwiseA stepwise reaction is a chemical reaction with one or more reaction intermediates and involving at least two consecutive elementary reactions....
, that is they take more than one elementary step to complete. An intermediate is the reaction product of each of these steps, except for the last one, which forms the final
productA product is a substance that forms as a result of a biological- or chemical reaction. While the end product of some chemical reactions may be the result of a relatively rapid reaction, nanoseconds to seconds, chemical equilibria in complex systems may require years or even centuries to be...
.
A
reaction intermediate or an
intermediate is a
molecular entityAccording to IUPAC Gold Book a molecular entity is any constitutionally or isotopically distinct atom, molecule, ion, ion pair, radical, radical ion, complex, conformer, etc., identifiable as a separately distinguishable entity....
that is formed from the reactants (or preceding intermediates) and reacts further to give the directly observed products of a
chemical reactionA chemical reaction is a process that leads to the transformation of one set of chemical substances to another. They are studied by chemists under a field of science called chemistry. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, often coming about...
. Most chemical reactions are
stepwiseA stepwise reaction is a chemical reaction with one or more reaction intermediates and involving at least two consecutive elementary reactions....
, that is they take more than one elementary step to complete. An intermediate is the reaction product of each of these steps, except for the last one, which forms the final
productA product is a substance that forms as a result of a biological- or chemical reaction. While the end product of some chemical reactions may be the result of a relatively rapid reaction, nanoseconds to seconds, chemical equilibria in complex systems may require years or even centuries to be...
. Reactive intermediates are usually short lived and are very seldom isolated. Also, owing to the short lifetime, they do not remain in the product mixture.
For example, consider this hypothetical stepwise reaction:
- A + B → C + D
The reaction includes these elementary steps:
- A + B → X*
- X* → C + D
The chemical species X* is an intermediate.
Definition
The IUPAC
Gold BookThe Compendium of Chemical Terminology is a book published by the International Union of Pure and Applied Chemistry containing internationally accepted definitions for terms in chemistry...
defines a
reaction intermediate or an
intermediate as a
molecular entityAccording to IUPAC Gold Book a molecular entity is any constitutionally or isotopically distinct atom, molecule, ion, ion pair, radical, radical ion, complex, conformer, etc., identifiable as a separately distinguishable entity....
(
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...
,
ionAn ion is an atom or molecule where the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge...
,
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...
...) with a
lifetimeLifetime may refer to:*Life expectancy, the length of time a person is alive*Mean lifetime, a certain number that characterizes the rate of reduction of a particle of an assembly...
appreciably longer than a
molecular vibrationA molecular vibration occurs when atoms in a molecule are in periodic motion while the molecule as a whole has constant translational and rotational motion. The frequency of the periodic motion is known as a vibration frequency...
that is formed (directly or indirectly) from the reactants and reacts further to give (either directly or indirectly) the products of a
chemical reactionA chemical reaction is a process that leads to the transformation of one set of chemical substances to another. They are studied by chemists under a field of science called chemistry. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, often coming about...
.
The lifetime distinguishes true, chemically distinct intermediates from vibrational or conformational states (conformers). Their
potential energyPotential energy is energy stored within a physical system as a result of the position or configuration of the different parts of that system. It is called potential energy because it has the potential to be converted into other forms of energy, such as kinetic energy, and to do work in the process...
with respect to reactants or previous intermediates is defined to have a minimum of depth greater than available thermal energy arising from temperature, with an exact value
RT, where
R is
gas constantThe gas constant is a physical constant which is featured in a large number of fundamental equations in the physical sciences, such as the ideal gas law and the Nernst equation...
and
T is temperature.
Many intermediates are short-lived and have a high reactivity, thus having a low concentration in the mixture. When the necessary conditions of the reaction no longer prevail, these intermediates react further and no longer remain in the reaction mixture. Common examples are oxidizing radicals (OOH and OH) found in combustion reactions, which are so reactive that a high temperature is required to constantly produce them to compensate reaction, or the combustion reaction will cease.
There are some operations where multiple reactions are run in the same batch. For example, in an esterification of a diol, a monoester product is formed first, and may be isolated, but the same reactants and conditions promote a second reaction of the monoester to diester. The lifetime of such an "intermediate" is considerably longer than the lifetime of the intermediates of the esterification reaction itself.
The main carbon reactive intermediates
- Carbocation
A 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,...
s and their stabilized equivalents such as oxonium ionThe oxonium ion in chemistry is any oxygen cation with three bonds. The simplest oxonium ion is the hydronium ion H
3O
+. Another oxonium ion frequently encountered in organic chemistry is obtained by protonation or alkylation of a carbonyl group e.g...
s
- Carbanion
A carbanion is an anion in which carbon has an unshared pair of electrons and bears a negative charge usually with three substituents for a total of eight valence electrons . The carbanion exists in a trigonal pyramidal geometry. Formally a carbanion is the conjugate base of a carbon acid.where B...
s and their stabilized equivalents such as enolates
- Free radicals
- Carbene
In chemistry, a carbene is a organic molecule containing a carbon atom with six valence electrons and having the general formula RR'C:. Carbenes are classified into two varieties, singlets and triplets. Most carbenes are very short lived, although persistent carbenes are known.The prototypical...
s
Common features of carbon intermediates
- Low concentration
In chemistry, concentration is the measure of how much of a given substance there is mixed with another substance. This can apply to any sort of chemical mixture, but most frequently the concept is limited to homogeneous solutions, where it refers to the amount of solute in the solvent.To...
with respect to reaction substrate and final reaction product
- With the exception of carbanions, these intermediates do not obey the lewis octet rule
The octet rule is a simple chemical rule of thumb that states that atoms tend to combine in such a way that they each have eight electrons in their valence shells, giving them the same electronic configuration as a noble gas. The rule is applicable to the main-group elements, especially carbon,...
hence the high reactivity
- Often generated on chemical decomposition
Chemical decomposition or analysis is the separation of a chemical compound into elements or smaller compounds. It is sometimes defined as the opposite of a chemical synthesis. Chemical decomposition is often an undesired chemical reaction...
of a chemical compoundA chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
- It is often possible to prove the existence of this species by spectroscopic
Spectroscopy was originally the study of the interaction between radiation and matter as a function of wavelength . In fact, historically, spectroscopy referred to the use of visible light dispersed according to its wavelength, e.g. by a prism. Later the concept was expanded greatly to comprise...
means
- Cage effects
The cage effect in chemistry describes how properties of a molecule are affected by its surroundings.* In a solvent a molecule is often more accurately described existing in a cage of solvent molecules, the so-called solvent cage....
have to be taken into account
- Often stabilisation by conjugation
A conjugated system occurs in an organic compound where atoms covalently bond with alternating single and multiple bonds and influence each other to produce a region called electron delocalization. In this region electrons do not belong to a single bond or atom, but rather a group...
or resonance
- Often difficult to distinguish from a transition state
The 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...
- Prove existence by means of chemical trapping
In chemistry, a chemical trap is a chemical compound that is used to detect a certain molecule when* the concentration of this molecule is very small and below detection limit...
Other reactive intermediates
- Deprotonated or hydrated forms of the compound, such as the tetrahedral intermediate in esterification
- Aryne
In chemistry, an aryne is an uncharged reactive intermediate derived from an aromatic system by removal of two ortho substituents, leaving two orbitals with two electrons distributed between them....
s
- Carbene
In chemistry, a carbene is a organic molecule containing a carbon atom with six valence electrons and having the general formula RR'C:. Carbenes are classified into two varieties, singlets and triplets. Most carbenes are very short lived, although persistent carbenes are known.The prototypical...
s
- Carbenoid
In chemistry a carbenoid is a reactive intermediate that shares reaction characteristics with a carbene . In the Simmons-Smith reaction the carbenoid intermediate is a zinc / iodine complex that takes the form of...
- Carbocation
A 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,...
s
- Carbyne
In chemistry, a carbyne is a monovalent carbon radical species. It occurs in several ways.- Gas phase :A carbyne can occur as a short-lived reactive intermediate...
- Free radicals
- Nitrene
In chemistry, a nitrene is the nitrogen analogue of a carbene. The nitrogen atom has only 6 electrons available and is therefore considered an electrophile...
s, nitrenium ionA nitrenium ion in organic chemistry is a reactive intermediate based on nitrogen with both an electron lone pair and a positive charge and with two substituents . Nitrenium ions are isoelectronic to carbenes, and can exist in either a singlet or a triplet state...
s
- para-quinone methides, ortho-quinone-methides