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Nucleophilic acyl substitution

 
Nucleophilic Acyl Substitution

 
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Nucleophilic acyl substitution
 
 
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Nucleophilic acyl substitution describes the substitution reaction
Substitution reaction

In a substitution reaction, a functional group in a particular chemical compound is replaced by another group . In organic chemistry, the electrophile and nucleophile substitution reactions are of prime importance....
 involving nucleophile
Nucleophile

In chemistry, a nucleophile is a reagent that forms a chemical bond to its reaction partner by donating both bonding electrons. Because nucleophiles donate electrons, they are by definition Lewis bases ....
s and acyl
Acyl

An acyl group is a functional group derived by the removal of one or more hydroxyl groups from an oxoacid.. In organic chemistry, the acyl group is usually derived from a carboxylic acid of the form RCarbon Oxygen hydroxyl....
 compounds. Acyl compounds are carboxylic acid
Carboxylic acid

Carboxylic acids are organic acids characterized by the presence of a carboxyl group, which has the Chemical formula -COH, usually written -COOH or -CO2H....
 derivatives including ester
Ester

An ester is an often Aroma compound organic chemistry or partially organic compound formed by the reaction between an acid and an alcohol or aromatic alcohol with the elimination of water....
s, amide
Amide

In chemistry, an amide is one of three kinds of compounds:* the organic chemistry functional group characterized by a carbonyl group linked to a nitrogen atom , or a compound that contains this functional group ; or...
s and acid halides. Nucleophiles include anionic reagents such as alkoxide
Alkoxide

An alkoxide is the conjugate base of an alcohol and therefore consists of an organic group bonded to a negatively charged oxygen atom. They can be written as RO–, where R is the organic substituent....
 compounds and enolates or species of high basicity, such as amine
Amine

Amines are organic compounds and functional groups that contain a base nitrogen atom with a lone pair. Amines are derivative s of ammonia, wherein one or more hydrogen atoms are replaced by organic substituents such as alkyl and aryl groups....
s .

reaction of a nucleophile
Nucleophile

In chemistry, a nucleophile is a reagent that forms a chemical bond to its reaction partner by donating both bonding electrons. Because nucleophiles donate electrons, they are by definition Lewis bases ....
 with a polar carbonyl
Carbonyl

In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double bond to an oxygen atom : C=O.The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex ; in this situation, carbon is triple-bonded to oxygen : C=O....
 group such as a ketone
Ketone

In organic chemistry, a ketone is a type of organic compound which contains a carbonyl group bonded to two other carbon atoms in the form:Neither of the substituents R1 and R2 may be equal to hydrogen ....
 or an aldehyde
Aldehyde

An aldehyde is an organic compound containing a terminal carbonyl group. This functional group, which consists of a carbon atom bonded to a hydrogen atom and double bond to an oxygen atom , is called the aldehyde group....
 results in nucleophilic addition
Nucleophilic addition

In organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a p bond is removed by the creation of two new covalent bonds by the addition of a nucleophile ....
 with a tetrahedral
Tetrahedral molecular geometry

In a Tetrahedral molecular geometry a central atom is located at the center with four substituents that are located at the corners of a tetrahedron....
 alkoxide as primary reaction product.






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Nucleophilic acyl substitution describes the substitution reaction
Substitution reaction

In a substitution reaction, a functional group in a particular chemical compound is replaced by another group . In organic chemistry, the electrophile and nucleophile substitution reactions are of prime importance....
 involving nucleophile
Nucleophile

In chemistry, a nucleophile is a reagent that forms a chemical bond to its reaction partner by donating both bonding electrons. Because nucleophiles donate electrons, they are by definition Lewis bases ....
s and acyl
Acyl

An acyl group is a functional group derived by the removal of one or more hydroxyl groups from an oxoacid.. In organic chemistry, the acyl group is usually derived from a carboxylic acid of the form RCarbon Oxygen hydroxyl....
 compounds. Acyl compounds are carboxylic acid
Carboxylic acid

Carboxylic acids are organic acids characterized by the presence of a carboxyl group, which has the Chemical formula -COH, usually written -COOH or -CO2H....
 derivatives including ester
Ester

An ester is an often Aroma compound organic chemistry or partially organic compound formed by the reaction between an acid and an alcohol or aromatic alcohol with the elimination of water....
s, amide
Amide

In chemistry, an amide is one of three kinds of compounds:* the organic chemistry functional group characterized by a carbonyl group linked to a nitrogen atom , or a compound that contains this functional group ; or...
s and acid halides. Nucleophiles include anionic reagents such as alkoxide
Alkoxide

An alkoxide is the conjugate base of an alcohol and therefore consists of an organic group bonded to a negatively charged oxygen atom. They can be written as RO–, where R is the organic substituent....
 compounds and enolates or species of high basicity, such as amine
Amine

Amines are organic compounds and functional groups that contain a base nitrogen atom with a lone pair. Amines are derivative s of ammonia, wherein one or more hydrogen atoms are replaced by organic substituents such as alkyl and aryl groups....
s .

Reaction mechanism

The reaction of a nucleophile
Nucleophile

In chemistry, a nucleophile is a reagent that forms a chemical bond to its reaction partner by donating both bonding electrons. Because nucleophiles donate electrons, they are by definition Lewis bases ....
 with a polar carbonyl
Carbonyl

In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double bond to an oxygen atom : C=O.The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex ; in this situation, carbon is triple-bonded to oxygen : C=O....
 group such as a ketone
Ketone

In organic chemistry, a ketone is a type of organic compound which contains a carbonyl group bonded to two other carbon atoms in the form:Neither of the substituents R1 and R2 may be equal to hydrogen ....
 or an aldehyde
Aldehyde

An aldehyde is an organic compound containing a terminal carbonyl group. This functional group, which consists of a carbon atom bonded to a hydrogen atom and double bond to an oxygen atom , is called the aldehyde group....
 results in nucleophilic addition
Nucleophilic addition

In organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a p bond is removed by the creation of two new covalent bonds by the addition of a nucleophile ....
 with a tetrahedral
Tetrahedral molecular geometry

In a Tetrahedral molecular geometry a central atom is located at the center with four substituents that are located at the corners of a tetrahedron....
 alkoxide as primary reaction product. However, in acyl
Acyl

An acyl group is a functional group derived by the removal of one or more hydroxyl groups from an oxoacid.. In organic chemistry, the acyl group is usually derived from a carboxylic acid of the form RCarbon Oxygen hydroxyl....
 compounds the carbonyl group is bonded to a substituent
Substituent

In organic chemistry, a substituent is an atom or group of atoms substituted in place of a hydrogen atom on the parent chain of a hydrocarbon. The suffix -yl is used when naming organic compounds that contain a substituent....
 that can act as a leaving group
Leaving group

A leaving group in chemistry is an ion or substituent with the ability to detach itself from a molecule. The remaining molecule or fragment remaining is known as the residual or main part....
. Upon attack of the nucleophile at 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
Carbonyl

In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double bond to an oxygen atom : C=O.The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex ; in this situation, carbon is triple-bonded to oxygen : C=O....
 group and at the same time expel the leaving group
Leaving group

A leaving group in chemistry is an ion or substituent with the ability to detach itself from a molecule. The remaining molecule or fragment remaining is known as the residual or main part....
. The nucleophile has taken the position previously occupied by the leaving group.

This mechanism is supported by isotope labeling experiments. The 18O labeled ethoxy oxygen atom in ethyl propionate (leaving group = EtO) winds up exclusively in the ethanol product in a reaction with NaOH .

Acyl substitution is basically a two-step nucleophilic addition
Nucleophilic addition

In organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a p bond is removed by the creation of two new covalent bonds by the addition of a nucleophile ....
 and elimination reaction
Elimination reaction

An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one or two-step mechanism ....
. Both reaction steps are reversible reaction
Reversible reaction

A reversible reaction is a chemical reaction that results in an chemical equilibrium mixture of reactants and Product . For a reaction involving two reactants and two products this can be expressed symbolically asA and B can react to form C and D or, in the reverse reaction, C and D can react to form A and B....
s. The relative strength of both nucleophilic species determines the reaction outcome, but in practical reactions the leaving group is by far the poorest nucleophile.

Carboxylic acids as well as the related esters and amides are often insufficiently reactive to undergo nucleophilic substitution. The carboxlic acid is often activated by conversion to the acyl chloride using thionyl chloride
Thionyl chloride

Thionyl chloride is an inorganic compound with the chemical formula SulfurOxygenChlorine2. It is a reactive chemical reagent used in chlorination chemical reaction....
.

Reactions

Many condensation reaction
Condensation reaction

A condensation reaction is a chemical reaction in which two molecules or moieties combine to form one single molecule, together with the loss of a small molecule....
s are nucleophilic acyl substitutions. Carboxylic acid
Carboxylic acid

Carboxylic acids are organic acids characterized by the presence of a carboxyl group, which has the Chemical formula -COH, usually written -COOH or -CO2H....
s react with chlorine donors such as thionyl chloride
Thionyl chloride

Thionyl chloride is an inorganic compound with the chemical formula SulfurOxygenChlorine2. It is a reactive chemical reagent used in chlorination chemical reaction....
 or phosphorus trichloride
Phosphorus trichloride

Phosphorus trichloride is the most important of the three phosphorus chlorides. It is an important Chemical industry, being used for the manufacture of organophosphorus compounds for a wide variety of applications....
 to acid chlorides, with alcohol
Alcohol

In chemistry, an alcohol is any organic compound in which a hydroxyl Functional group is bound to a carbon atom of an alkyl or substituted alkyl group....
s to ester
Ester

An ester is an often Aroma compound organic chemistry or partially organic compound formed by the reaction between an acid and an alcohol or aromatic alcohol with the elimination of water....
s in esterfication and carboxylic acids selfcondense
Self-condensation

Self-condensation is an organic reaction in which a chemical compound containing a carbonyl group acts both as the electrophile and the nucleophile in an aldol condensation....
 to acid anhydrides. With amine
Amine

Amines are organic compounds and functional groups that contain a base nitrogen atom with a lone pair. Amines are derivative s of ammonia, wherein one or more hydrogen atoms are replaced by organic substituents such as alkyl and aryl groups....
s they form amide
Amide

In chemistry, an amide is one of three kinds of compounds:* the organic chemistry functional group characterized by a carbonyl group linked to a nitrogen atom , or a compound that contains this functional group ; or...
s. Esters react with Grignard reagents in a nucleophilic acyl substitution followed by a nucleophilic addition
Nucleophilic addition

In organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a p bond is removed by the creation of two new covalent bonds by the addition of a nucleophile ....
 to tertiary alcohols. Esters also react with Enolate nucleophiles. For example ethyl acetate
Ethyl acetate

Ethyl acetate is the organic compound with the formula CH3COOCH2CH3. This colorless liquid has a characteristic sweet smell like certain glues or nail polish removers, in which it is used....
 reacts with acetone
Acetone

Acetone is the organic compound with the chemical formula OC2. This colorless, mobile, flammable liquid is the simplest example of the ketones....
 to acetylacetone
Acetylacetone

Acetylacetone is an organic compound with molecular formula C5H8O2. This diketone is formally named 2,4-pentanedione....
.

The Baker-Venkataraman rearrangement
Baker-Venkataraman rearrangement

The Baker-Venkataraman rearrangement is the chemical reaction of 2-acetoxyacetophenones with base to form 1,3-diketones.This rearrangement reaction proceeds via enolate formation followed by acyl transfer....
 is a nucleophilic acyl substitution used in the synthesis of flavones. In the Weinreb ketone synthesis
Weinreb ketone synthesis

The Weinreb ketone synthesis is a chemical reaction used to transform N,O-dimethylhydroxamic acids into ketones .Addition of the organometallic nucleophile to the Weinreb amide produces a stable tetrahedral chelate , which upon hydrolysis produces the desired ketone....
 ketones are synthesized from carboxylic acid
Carboxylic acid

Carboxylic acids are organic acids characterized by the presence of a carboxyl group, which has the Chemical formula -COH, usually written -COOH or -CO2H....
 precursors. An unusual intramolecular acyl substitution is the Chan rearrangement
Chan rearrangement

The Chan rearrangement is a chemical reaction that involves rearrangement reaction an acyloxy acetate in the presence of a strong base to a 2-hydroxy-3-keto-ester ....
.

See also

  • The substitution reaction
    Substitution reaction

    In a substitution reaction, a functional group in a particular chemical compound is replaced by another group . In organic chemistry, the electrophile and nucleophile substitution reactions are of prime importance....
    s in organic chemistry
    Organic chemistry

    Organic chemistry is a discipline within chemistry which involves the science study of the structure, properties, composition, chemical reaction, and preparation of chemical compounds that contain carbon....
     are nucleophilic acyl substitution, nucleophilic aliphatic substitution and nucleophilic aromatic substitution
    Nucleophilic aromatic substitution

    A nucleophilic aromatic substitution is a substitution reaction in organic chemistry in which the nucleophile displaces a good leaving group, such as a halide on an aromatic ring....
    .


External links

  • Reaction of ethyl acetate
    Ethyl acetate

    Ethyl acetate is the organic compound with the formula CH3COOCH2CH3. This colorless liquid has a characteristic sweet smell like certain glues or nail polish removers, in which it is used....
     with acetone
    Acetone

    Acetone is the organic compound with the chemical formula OC2. This colorless, mobile, flammable liquid is the simplest example of the ketones....
     in Organic Syntheses
    Organic Syntheses

    Organic Syntheses is a scientific journal that since 1921 has provided the chemistry community with annual collections of detailed and checked procedures for the organic synthesis of organic compounds....
     Coll. Vol. 3, p.16; Vol. 20, p.6