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Nucleophilic aromatic substitution

 

 
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Nucleophilic aromatic substitution
 
 
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A nucleophilic aromatic substitution is a 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....
 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....
 in which the 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 ....
 displaces a good 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....
, such as a halide
Halide

A halide is a binary compound, of which one part is a halogen atom and the other part is an chemical element or radical that is less electronegative than the halogen, to make a fluoride, chloride, bromide, iodide, or astatide compound....
 on an aromatic ring. There are 6 nucleophilic substitution
Nucleophilic substitution

In organic chemistry and inorganic chemistry, nucleophilic substitution is a fundamental class of substitution reaction in which an "electron rich" nucleophile selectively bonds with or attacks the positive or partially positive charge of an atom attached to a group or atom called the leaving group; the positive or partially positive atom...
 mechanisms encountered with aromatic systems:

The most important of these is the SNAr mechanism, where electron withdrawing groups activate the ring towards nucleophilic attack, for example if there are nitro functional groups positioned ortho or para to the halide
Halide

A halide is a binary compound, of which one part is a halogen atom and the other part is an chemical element or radical that is less electronegative than the halogen, to make a fluoride, chloride, bromide, iodide, or astatide compound....
 leaving group.

his sequence the carbons are numbered clockwise from 1-6 starting with the 1 carbon at 12 o'clock, which is bonded to the chloride.






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A nucleophilic aromatic substitution is a 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....
 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....
 in which the 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 ....
 displaces a good 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....
, such as a halide
Halide

A halide is a binary compound, of which one part is a halogen atom and the other part is an chemical element or radical that is less electronegative than the halogen, to make a fluoride, chloride, bromide, iodide, or astatide compound....
 on an aromatic ring. There are 6 nucleophilic substitution
Nucleophilic substitution

In organic chemistry and inorganic chemistry, nucleophilic substitution is a fundamental class of substitution reaction in which an "electron rich" nucleophile selectively bonds with or attacks the positive or partially positive charge of an atom attached to a group or atom called the leaving group; the positive or partially positive atom...
 mechanisms encountered with aromatic systems:
  • the SNAr (addition-elimination) mechanism
  • the aromatic SN1 mechanism encountered with diazonium salts
  • the benzyne mechanism
  • the free radical SRN1 mechanism


  • the ANRORC mechanism
    ANRORC mechanism

    The ANRORC mechanism in organic chemistry describes a special type of substitution reaction. ANRORC stands for Addition of the Nucleophile, Ring Opening, and Ring Closure in nucleophilic attack on ring systems and it helps to explain product formation and distribution in some nucleophilic substitutions e...
  • Vicarious nucleophilic substitution
    Vicarious nucleophilic substitution

    Vicarious nucleophilic substitution in organic chemistry is a special type of nucleophilic aromatic substitution in which a nucleophile replaces hydrogen and not an aromatic substituent like a halogen that is ordinarily encountered in this reaction type....
    .
The most important of these is the SNAr mechanism, where electron withdrawing groups activate the ring towards nucleophilic attack, for example if there are nitro functional groups positioned ortho or para to the halide
Halide

A halide is a binary compound, of which one part is a halogen atom and the other part is an chemical element or radical that is less electronegative than the halogen, to make a fluoride, chloride, bromide, iodide, or astatide compound....
 leaving group.

SNAr reaction mechanism


The following is the reaction mechanism
Reaction mechanism

In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs .Although only the net chemical change is directly observation for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in a reaction mechanism....
 of a nucleophilic aromatic substitution of 2,4-dinitrochlorobenzene in a basic
Base (chemistry)

In chemistry, a base is most commonly thought of as an aqueous substance that can accept protons. A base is also often referred to as an alkali if OH- ions are involved....
 aqueous solution.

Nas1
In this sequence the carbons are numbered clockwise from 1-6 starting with the 1 carbon at 12 o'clock, which is bonded to the chloride. Since the nitro
Nitro compound

Nitro compounds are organic compounds that contain one or more nitro functional groups . They are often highly explosive, especially when the compound contains more than one nitro group....
 group is an activator toward nucleophilic substitution, and an ortho/para director, it allows the benzene carbon to which it is bonded to have a negative charge. In the Meisenheimer complex
Meisenheimer complex

A Meisenheimer complex or Jackson-Meisenheimer complex in organic chemistry is a 1:1 reaction adduct between an arene compound carrying electron withdrawing groups and nucleophile....
, the nonbonded electrons of the carbanion
Carbanion

A carbanion is an anion in which carbon has an unshared pair of electrons and bears a negative charge usually with three substituents for a total of eight valence electrons ....
 become bonded to the aromatic pi system which allows the ipso carbon to temporarily bond with the hydroxyl
Hydroxyl

Hydroxyl in chemistry stands for a molecule consisting of an oxygen atom and a hydrogen atom connected by a covalent bond. The neutral form is a hydroxyl Radical and the hydroxyl anion is called a hydroxide....
 group (-OH). In order to return to a lower energy state, either the hydroxyl group leaves, or the chloride leaves. In solution both processes happen. A small percentage of the intermediate loses the chloride to become the product (2,4-dinitrophenol), while the rest return to the reactant. Since 2,4-dinitrophenol is in a lower energy state it will not return to form the reactant, so after some time has passed, the reaction reaches chemical equilibrium
Chemical equilibrium

In a chemical process, chemical equilibrium is the state in which the Activity or concentrations of the reactants and products have no net change over time....
.

The formation of the resonance-stabilized Meisenheimer complex
Meisenheimer complex

A Meisenheimer complex or Jackson-Meisenheimer complex in organic chemistry is a 1:1 reaction adduct between an arene compound carrying electron withdrawing groups and nucleophile....
 is slow because it is in a higher energy state than the aromatic reactant. The loss of the chloride is fast, because the ring becomes aromatic once again.

Nucleophilic aromatic substitution reactions

Some typical substitution reactions on arenes are listed below.
  • In the Bamberger rearrangement
    Bamberger rearrangement

    The Bamberger rearrangement is the chemical reaction of N-phenylhydroxylamines with strong aqueous acid, which will rearrangement reaction to give 4-aminophenols....
     N-phenylhydroxylamines rearrange to 4-aminophenols. The nucleophile is water.
  • In the Sandmeyer reaction
    Sandmeyer reaction

    The Sandmeyer reaction is a chemical reaction used to synthesize aryl halides from aryl diazonium salts. It is named after the Swiss chemist Traugott Sandmeyer....
     and the Gattermann reaction
    Gattermann reaction

    The Gattermann rection, named for the German chemist Ludwig Gattermann, in organic chemistry refers to a reaction of hydrocyanic acid with an aromatic compound, in this case benzene, under catalysis with Friedel-Crafts catalyst ....
     diazonium salts react with halides.
  • The Smiles rearrangement
    Smiles rearrangement

    The Smiles rearrangement is an organic reaction and a rearrangement reaction. It is an intramolecular nucleophilic aromatic substitution of the type:...
     is the intramolecular version of this reaction type.
Nucleophilic aromatic substitution is not limited to arenes, however; the reaction takes place even more readily with heteroarenes. Pyridine
Pyridine

Pyridine is a simple and important heterocyclic aromatic organic compound with the formula CarbonHydrogenNitrogen. This colorless liquid with a distinctive fish-like odor is structurally related to benzene, wherein one CH group in the six-membered ring is replaced by a nitrogen atom....
s are especially reactive when substituted in the aromatic ortho position or aromatic para position because then the negative charge is effectively delocalized at the nitrogen position. One classic reaction is the Chichibabin reaction (Aleksei Chichibabin
Aleksei Chichibabin

Aleks?y Yevg?nyevich Chichib?bin was a Soviet/Russian organic chemist. His name is also written Alexei Yevgenievich Chichibabin and Alexei Euguenievich Tchitchibabine....
, 1914) in which pyridine is reacted with an alkali-metal amide such as sodium amide
Sodium amide

Sodium amide, commonly called sodamide, is the chemical compound with the chemical formula NaNH2. This solid, which is dangerously reactive toward water, is white when pure, but commercial samples are typically gray due to the presence of small quantities of metallic iron from the manufacturing process....
 to form 2-aminopyridine .

In the compound methyl 3-nitropyridine-4-carboxylate, the meta nitro group is actually displaced by fluorine
Fluorine

Fluorine is the chemical element with the symbol F and atomic number 9. Fluorine forms a single bond with itself in elemental form, resulting in the diatomic F2 molecule....
 with caesium fluoride
Caesium fluoride

Caesium fluoride , is an ionic compound usually found as a hygroscopic white solid. It is more soluble and more readily Dissociation than sodium fluoride or potassium fluoride....
 in DMSO
Dimethyl sulfoxide

Dimethyl sulfoxide is the chemical compound with the chemical formula 2SO. It was first synthesized in 1866 by the Russian scientist Alexander Saytzeff, who reported his findings in a German chemistry journal in 1867....
 at 120°C.

Nuarsubpyr

Asymmetric nucleophilic aromatic substitution

With prochiral
Prochiral

In chemistry, prochiral molecules are those which can be converted from achiral to Chirality in a single step.If two identical substituents are attached to an orbital hybridisation-hybridized atom, the descriptors pro-R and pro-S are used to distinguish between the two....
 carbon nucleophiles such as 1,3-dicarbonyl compounds the reaction has been demonstrated as an asymmetric synthesis in asymmetric nucleophilic aromatic substitution . First reported in 2005, the organocatalyst (in a dual role with that of a phase transfer catalyst
Phase transfer catalyst

A phase transfer catalyst or PTC in chemistry is a catalyst which facilitates the migration of a reactant in a heterogeneous system from one phase into another phase where reaction can take place....
) is derived from cinchonidine
Cinchonidine

Cinchonidine is an alkaloid used in asymmetric synthesis in organic chemistry. It is the stereoisomer of cinchonine....
 (benzyl
Benzyl

In organic chemistry, benzyl is the term used to describe the substituent or molecular fragment possessing the structure C6H5CH2-....
ated at N and benzoylated at 9-OH):


See also

  • The nucleophilic 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 aliphatic substitution including SN1 reaction
    SN1 reaction

    The SN1 reaction is a substitution reaction in organic chemistry. "SN" stands for nucleophilic substitution and the "1" represents the fact that the rate-determining step is molecule....
    s, SN2 reaction
    SN2 reaction

    The SN2 reaction is a type of nucleophilic substitution, where a lone pair from a nucleophile attacks an electron deficient electrophile center and covalent bond to it, expelling another group called a leaving group....
    s, and SNi reactions, nucleophilic aromatic substitution, and nucleophilic acyl substitution
    Nucleophilic acyl substitution

    Nucleophilic acyl substitution describes the substitution reaction involving nucleophiles and acyl compounds. Acyl compounds are carboxylic acid derivatives including esters, amides and acid halides....
    .
  • List of publications in organic chemistry
    List of publications in chemistry

    This is a list of important publications in chemistry, organized by field.Some reasons why a particular publication might be regarded as important:...