An atom or group departing with the bonding electron pair in a heterolytic substitution. Its stability, basicity and environment affect reactivity; the substrate geometry also controls access to the substitution pathway.
Non-geminal substitution puts incoming groups on different central atoms. On a phosphazene ring, it still permits cis/trans relative configurations and does not by itself specify one stereoisomer.
In geminal substitution, two incoming groups replace substituents on the same central atom. In cyclotriphosphazenes, gives a geminal pair. Primary amino groups can enable a base-catalyzed proton-abstraction/chloride-elimination route that is unavailable after substitution by a secondary amine.
Nucleophile addition to an acyl carbonyl followed by leaving-group elimination, often through a tetrahedral reaction intermediate.
Formation of an ester from an acyl component and an alcohol. Intramolecular esterification of a hydroxy acid makes a lactone. Fischer esterification is the acid-catalysed carboxylic-acid/alcohol case.
Base-promoted bimolecular acyl substitution: nucleophile addition gives a tetrahedral intermediate, then a leaving group departs from the acyl carbon.
Formation of a lactone by intramolecular esterification or acyl substitution. Favourable ring sizes can help trap an intermediate, but do not make the product universally unreactive.
Acid-catalysed ester formation from a carboxylic acid and an alcohol, proceeding through carbonyl addition and elimination with net water formation.
Breaking an ester linkage can proceed by different bonds and mechanisms. Acyl–oxygen and alkyl–oxygen cleavage should be distinguished when explaining protecting-group selectivity.
Breaking the bond between an acyl carbon and the ester alkoxy oxygen. Ordinary hydroxide-promoted ester saponification follows addition–elimination through a tetrahedral intermediate.
Breaking the bond between an ester oxygen and its alkyl substituent. Acid removal of a tert-butyl group can follow this route without requiring water or a tetrahedral acyl-addition intermediate.
Exchange of an ester alkoxy group through reaction with an alcohol, commonly using acid or base catalysis. Excess exchanging alcohol can shift the chemical equilibrium.
For exchange of closely related ester and alcohol groups, an excess alcohol reservoir and dilution of the outgoing alcohol can favour conversion through mixture chemical potentials. Equal molecular stoichiometry does not itself imply a positive standard entropy change; a reaction quotient is needed.
A limiting unimolecular nucleophilic substitution mechanism with rate-determining ionization, commonly producing a carbocation, followed by nucleophile capture. Its ideal rate law is first order in substrate.
In an addition–elimination pathway, a nucleophile attacks an aromatic carbon and forms a Meisenheimer complex; leaving-group loss restores aromaticity. Electron-withdrawing groups ortho or para to the attacked site can stabilize the addition intermediate.
An intramolecular nucleophilic aromatic substitution that transfers an aryl group between sites in one molecule.
An intramolecular aryl transfer to a carbon nucleophile. A tethered carbon anion attacks an aromatic ipso carbon and displaces the original oxygen-, nitrogen- or sulfur-based attachment.
Vicarious nucleophilic substitution replaces aromatic hydrogen using a nucleophile that carries its own leaving group. In nitroarenes, reversible carbanion addition gives a sigma-H adduct; base-induced elimination of the hydrogen and the nucleophile-borne leaving group, followed by protonation, gives substitution without expelling hydride.
A sigma-H adduct forms by nucleophilic addition at an aromatic carbon that initially bears hydrogen. Both the original hydrogen and the incoming nucleophile remain attached at that carbon before the rearomatization steps.
A Meisenheimer complex is a sigma-bonded anionic addition species associated with suitable nucleophilic aromatic substitution reactions. Delocalization into ortho or para nitro groups can stabilize its negative charge.
A tethered nucleophile attacking the ipso carbon of an activated aromatic ring can form a cyclic sigma-adduct sharing one atom with that ring. Rearomatization then cleaves the original aryl–heteroatom bond.
An SN2 reaction couples backside nucleophilic bond formation to leaving-group departure in one elementary substitution step. At a suitable stereogenic reaction centre, the geometry produces inversion.
Approach of a nucleophile opposite the leaving-group bond permits bond formation with inversion at the attacked tetrahedral carbon in an SN2 pathway.
Carbon-centred substitution in a cyclic sulfonate ester. The incoming nucleophile bonds to the oxygen-bound ring carbon and the resulting product retains the carbon–sulfur bond.
Articles by others on the same topic
There are currently no matching articles.