Substitution reaction

The stability of a carbocation (C⁺) depends on how many other carbon atoms are bonded to it. This results in S_N1 reactions usually occurring on atoms with at least two carbons bonded to them. A more detailed explanation of this can be found in the main SN1 reaction page. 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, called a Walden inversion.

S_N2 attack may occur if the backside route of attack is not sterically hindered 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. Other types of nucleophilic substitution include, nucleophilic acyl substitution, and nucleophilic aromatic substitution. Acyl substitution occurs when a nucleophile attacks a carbon that is doubly bonded to one oxygen and singly bonded to another oxygen (can be N or S or a halogen), called an Acyl group group. The nucleophile attacks the carbon causing the double bond to break into a single bond. The double can then reform, kicking off the leaving group in the process.

Aromatic substitution occurs on compounds with systems of double bonds connected in rings. See aromatic compounds for more.

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 Arene generally lead to electrophilic addition rather than substitution.

Associative substitution, for example, is typically applied to organometallic and coordination complexes, but resembles the Sn2 mechanism in organic chemistry. The opposite pathway is dissociative substitution, being analogous to the Sn1 pathway.

Examples of associative mechanisms are commonly found in the chemistry of 16e square planar metal complexes, e.g. Vaska's complex and tetrachloroplatinate. The rate law is governed by the Eigen–Wilkins Mechanism.

Dissociative substitution resembles the S_N1 mechanism in organic chemistry. This pathway can be well described by the cis effect, or the labilization of CO ligands in the cis position. Complexes that undergo dissociative substitution are often coordinatively saturated and often have octahedral molecular geometry. The entropy of activation is characteristically positive for these reactions, which indicates that the disorder of the reacting system increases in the rate-determining step. Dissociative pathways are characterized by a rate determining step that involves release of a ligand from the coordination sphere of the metal undergoing substitution. The concentration of the substituting nucleophile has no influence on this rate, and an intermediate of reduced coordination number can be detected. The reaction can be described with k₁, k₋₁ and k₂, which are the of their corresponding intermediate reaction steps:

L_\mathit{n}M-L <=>-\mathrm+\mathrm L_\mathit{n}M-\Box ->+\mathrm L_\mathit{n}M-L'

Rate = {\mathit k_1 L_{\mathit{n}}M-L}

• Imyanitov, Naum S. (1993). "Is This Reaction a Substitution, Oxidation-Reduction, or Transfer?". J. Chem. Educ. 70 (1): 14–16. Bibcode:1993JChEd..70...14I. doi:10.1021/ed070p14.