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Nucleophilic Aromatic Substitution: From Wikipedia, The Free Encyclopedia

Nucleophilic aromatic substitution is a reaction where a nucleophile displaces a good leaving group, such as a halide, on an aromatic ring. There are 6 mechanisms for these substitutions: SNAr, aromatic SN1, and benzyne. The SNAr mechanism involves the formation of a resonance-stabilized Meisenheimer complex as an intermediate. Nucleophilic aromatic substitutions can occur on arenes as well as heteroarenes like pyridine. Some examples include the Bamberger rearrangement and the Chichibabin reaction. Recently, asymmetric nucleophilic aromatic substitutions have been developed using organocatalysts derived from cinchonidine.

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179 views

Nucleophilic Aromatic Substitution: From Wikipedia, The Free Encyclopedia

Nucleophilic aromatic substitution is a reaction where a nucleophile displaces a good leaving group, such as a halide, on an aromatic ring. There are 6 mechanisms for these substitutions: SNAr, aromatic SN1, and benzyne. The SNAr mechanism involves the formation of a resonance-stabilized Meisenheimer complex as an intermediate. Nucleophilic aromatic substitutions can occur on arenes as well as heteroarenes like pyridine. Some examples include the Bamberger rearrangement and the Chichibabin reaction. Recently, asymmetric nucleophilic aromatic substitutions have been developed using organocatalysts derived from cinchonidine.

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Nucleophilic aromatic substitution

From Wikipedia, the free encyclopedia

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. There are 6 nucleophilic substitution mechanisms encountered with aromatic systems:

the SNAr (addition-elimination) mechanism

the aromatic SN1 mechanism encountered with diazonium salts

the benzyne mechanism

SNAr reaction mechanism[edit source | editbeta]


Aryl halides cannot undergo SN2 reaction.The CBr bond is in the plane of the ring as the carbon atom is trigonal. To attack from the back, the nucleophile would have to appear inside the benzene [1] ring and invert the carbon atom in an absurd way. This reaction is not possible.

SN1 reaction is possible but very unfavourable. It would involve the unaided loss of the leaving [1] group and the formation of an aryl cation.

The following is the reaction mechanism of a nucleophilic aromatic substitution of 2,4dinitrochlorobenzene in a basic aqueous solution.

In this sequence the carbons are numbered clockwise from 16 starting with the 1 carbon at 12 o'clock, which is bonded to the chloride. Since the nitro group is an activator toward nucleophilic substitution, and a meta director, it allows the benzene carbon to which it is bonded to have a negative charge. In the Meisenheimer complex, the nonbonded electrons of the carbanion become bonded to the aromatic pi system which allows the ipso carbon to temporarily bond with the hydroxyl 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.

The formation of the resonance-stabilized Meisenheimer complex 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 again.

Nucleophilic aromatic substitution reactions[edit source | editbeta]


Some typical substitution reactions on arenes are listed below. In the Bamberger rearrangement N-phenylhydroxylamines rearrange to 4-aminophenols. The nucleophile is water. In the Sandmeyer reaction and the Gattermann reaction diazonium salts react with halides. The Smiles rearrangement 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. Pyridines are especially reactive when substituted in thearomatic 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, 1914) in [2] which pyridine is reacted with an alkali-metal amide such as sodium amide to form 2-aminopyridine. In the compound methyl 3-nitropyridine-4-carboxylate, the meta nitro group is actually displaced [3] by fluorine with caesium fluoride in DMSO at 120C.

Asymmetric nucleophilic aromatic substitution[edit source | editbeta]


With carbon nucleophiles such as 1,3-dicarbonyl compounds the reaction has been demonstrated as [4] a method for the asymmetric synthesis of chiral molecules. First reported in 2005, theorganocatalyst (in a dual role with that of a phase transfer catalyst) is derived from cinchonidine (benzylated at N and O).

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