Nucleophilic acyl substitution
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Nucleophilic acyl substitution is a type of substitution reaction between nucleophiles and acyl compounds. Acyl compounds are carboxylic acid derivatives such as esters, amides and acid halides. Nucleophiles are a diverse group of reactive intermediates such as alkoxide compounds and enolates.
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[edit] Reaction mechanism
The reaction of a nucleophile with a polar carbonyl group such as a ketone or an aldehyde results in nucleophilic addition with a tetrahedral alkoxide as primary reaction product. However, in acyl compounds the carbonyl group is bonded to a substituent that can act as a leaving group. Upon attack of the nucleophile to the carbonyl group, as before, a tetrahedral intermediate is formed with the nucleophile, the leaving group and the oxygen anion attached to the central carbon atom. The alkoxy group can now revert back to the carbonyl group and at the same time expel the leaving group. The leaving group has in effect taken over the position previously occupied by the nucleophile as a free anion.
Acyl substitution is basically a two-step nucleophilic addition and elimination reaction. Both reaction steps are reversible reactions and the process can in principle revert. The relative strength of both nucleophilic species determines the reaction outcome but in practical reactions the leaving group is by far the poorest nucleophile.
[edit] Reactions
Many condensation reactions are nucleophilic acyl substitutions. Carboxylic acids react with chlorine donors such as thionyl chloride or phosphorus trichloride to acid chlorides, with alcohols to esters in esterfication and carboxylic acids selfcondense to acid anhydrides. With amines they form amides. Esters react with Grignard reagents in a nucleophilic acyl substitution followed by a nucleophilic addition to tertiary alcohols. Esters also react with Enolate nucleophiles. For example ethyl acetate reacts with acetone to acetylacetone.
The Baker-Venkataraman rearrangement is a nucleophilic acyl substitution used in the synthesis of flavones. In the Weinreb ketone synthesis ketones are synthesized from carboxylic acid precursors. An unusual intramolecular acyl substitution is the Chan rearrangement.
Show below is the synthesis of an acyl chloride from a carboxylic acid using dichlorosulfoxide. Note the formation of SO2, a gas, which increases the entropy of the products, resulting in the favorable formation of the more reactive (less stable) acyl chloride from the less reactive (more stable) carboxylic acid.
[edit] See also
- The substitution reactions in organic chemistry are nucleophilic acyl substitution, nucleophilic aliphatic substitution and nucleophilic aromatic substitution.
[edit] External links
- Reaction of ethyl acetate with acetone in Organic Syntheses Coll. Vol. 3, p.16; Vol. 20, p.6 Article
[edit] References
- Organic Chemistry John McMurry 2nd Ed. ISBN 0-534-07968-7
