In chemistry, a reaction intermediate, or intermediate, is a molecular entity arising within the sequence of a stepwise chemical reaction. It is formed as the reaction product of an elementary step, from the reactants and/or preceding intermediates, but is consumed in a later step. It does not appear in the chemical equation for the overall reaction.
For example, consider this hypothetical reaction: A + B -> C + D If this overall reaction comprises two elementary steps thus: A + B -> X X -> C + D then X is a reaction intermediate.
The phrase itself, reaction intermediate, is very often abbreviated to the single word intermediate, and this is IUPAC's preferred form of the term.<ref ></ref> But this shorter form has other uses. It often refers to reactive intermediates. It is also used more widely for chemicals such as cumene which are traded within the chemical industry but are not generally of value outside it.
IUPAC definition
The IUPAC Gold Book defines an intermediate as a compound that has a lifetime greater than a molecular vibration, is formed (directly or indirectly) from the reactants, and reacts further to give (either directly or indirectly) the products of a chemical reaction. The lifetime condition distinguishes true, chemically distinct intermediates, both from vibrational states and from transition states (which, by definition, have lifetimes close to that of molecular vibration).
The different steps of a multi-step reaction often differ widely in their reaction rates. Where the difference is significant, an intermediate consumed more quickly than another may be described as a relative intermediate. A reactive intermediate is one which due to its short lifetime does not remain in the product mixture. Reactive intermediates are usually high-energy, are unstable and are seldom isolated.
Common reaction intermediates
Carbocations
Cations, often carbocations, serve as intermediates in various types of reactions to synthesize new compounds.
Carbocation intermediates in alkene addition
Carbocations are formed in two major alkene addition reactions. In an HX addition reaction, the pi bond of an alkene acts as a nucleophile and bonds with the proton of an HX molecule, where the X is a halogen atom. This forms a carbocation intermediate, and the X then bonds to the positive carbon that is available, as in the following two-step reaction.
CH2CH2 + HX → CH2CH3+ + X-
CH2CH3+ + X- → CH2XCH3
Similarly, in an H2O addition reaction, the pi bond of an alkene acts as a nucleophile and bonds with the proton of an H3O+ molecule. This forms a carbocation intermediate (and an H2O atom); the oxygen atom of H2O then bonds with the positive carbon of the intermediate. The oxygen finally deprotonates to form a final alcohol product, as follows.
CH2CH2 + H3O+ → CH2CH3+ + H2O
CH2CH3+ + H2O → CH2OH2CH3+
CH2OH2CH3+ + H2O → CH2OHCH3 +H3O+
Carbocation intermediates in nucleophilic substitution
Nucleophilic substitution reactions occur when a nucleophilic molecule attacks a positive or partially positive electrophilic center by breaking and creating a new bond. SN1 and SN2 are two different mechanisms for nucleophilic substitution, and SN1 involves a carbocation intermediate. In SN1, a leaving group is broken off to create a carbocation reaction intermediate. Then, a nucleophile attacks and forms a new bond with the carbocation intermediate to form the final, substituted product, as shown in the reaction of 2-bromo-2-methylpropane to form 2-methyl-2-propanol.
(CH3)3CBr → (CH3)3C+
(CH3)3C+ + H2O → (CH3)3OH2+
(CH3)3OH2+ → (CH3)3OH + H+
In this reaction, (CH3)3C+ is the formed carbocation intermediate to form the alcohol product.
Carbocation intermediates in elimination reactions
β-elimination or elimination reactions occur through the loss of a substituent leaving group and loss of a proton to form a pi bond. E1 and E2 are two different mechanisms for elimination reactions, and E1 involves a carbocation intermediate. In E1, a leaving group detaches from a carbon to form a carbocation reaction intermediate. Then, a solvent removes a proton, but the electrons used to form the proton bond form a pi bond, as shown in the pictured reaction on the right.
Carbanions
A carbanion is a organic molecule where a carbon atom is not electron deficient but contain an overall negative charge. Carbanions are strong nucleophiles, which can be used to extend an alkene's carbon backbone in the synthesis reaction shown below.