Nucleophilic Aromatic Substitution by Elimination-Addition

SECTION 10.5. NUCLEOPHILIC AROMATIC SUBSTITUTION BY ADDITION-ELIMINATION 

There are several mechanisms by which net nucleophilic aromatic substitution can occur. In this section, we will discuss the addition-elimination mechanism and the elimination-addition mechanism. Substitutions via organometallic intermediates and via aryl diazonium ions will be considered in Part B. 

The addition-elimination mechanism uses one of the vacant tt orbitals as the initial point of attack by the nucleophile. This permits bonding of the nucleophile to the aromatic ring without displacement of any of the existing substituents. If attack occurs at a position occupied by a potential leaving group, net substitution 

Reviews C. F. Bernasconi, in MTP Int. Rev. Set, Organic Series One, Vol. 3, H. Zollinger (ed.), Butterworths, London, 1973 J. A. Zoltewicz, Top. Curr. Chem. 59, 33 (1975) J. Miller, Aromatic Nucleophilic Substitution, Elsevier, Amsterdam, 1968. 

The addition intermediate is isoelectronic with a pentadienyl anion. 

The addition of a nucleophile to an aromatic ring, followed by elimination of a substituent, results in nucleophilic substitution. The major energetic requirement for 

A wide variety of such compounds have been characterized, and recent example include even compounds in which the formal nucleophile is an alkyl group  

Many other nucleophiles, such as cyanide, amines, thiolates, and enolates, add to nitroaromatics to give similar complexes. 

The elimination-addition mechanism involves a highly unstable intermediate. 

A characteristic feature of this mechanism is the substitution pattern in the product. The entering nucleophile need not always enter the ring at the carbon to which the leaving group was bound  

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Nucleophilic Aromatic Substitution by Addition-Elimination (Section 22.3B)... 

Although nucleophilic aromatic substitution by the elimination-addition mecha nism IS most commonly seen with very strong amide bases it also occurs with bases such as hydroxide ion at high temperatures A labeling study revealed that hydroly SIS of chlorobenzene proceeds by way of a benzyne intermediate... 

Nucleophilic aromatic substitution by the elimination-addition mecha nism can lead to substitution on the same carbon that bore the leaving group or on an adjacent carbon... 

Nucleophilic Aromatic Substitution by the Elimination-Addition Mechanism... 

Nucleophilic aromatic substitution by the elimination-addition mechanism is impossible, owing to the absence of any protons that might be abstracted from the substrate. The addition-elimination pathway is available, however. 

Other aryl halides that give stabilized anions can undergo nucleophilic aromatic substitution by the addition-elimination mechanism Two exam pies are hexafluorobenzene and 2 chloropyridme... 

Cycloalkene (Section 5 1) A cyclic hydrocarbon characterized by a double bond between two of the nng carbons Cycloalkyne (Section 9 4) A cyclic hydrocarbon characterized by a tnple bond between two of the nng carbons Cyclohexadienyl anion (Section 23 6) The key intermediate in nucleophilic aromatic substitution by the addition-elimination mechanism It is represented by the general structure shown where Y is the nucleophile and X is the leaving group... 

Cyclohexadienyl anion (Section 23.6) The key intermediate in nucleophilic aromatic substitution by the addition-elimination mechanism. It is represented by the general structure shown, where Y is the nucleophile and X is the leaving group. 

Since chlorine is always in more than a hundred-fold excess compared to bromine the reaction is occurring by pseudo monomolecular kinetics. The reaction occurs via nucleophilic aromatic substitution by an addition-elimination mechanism, the so-called SjsfAr mechanism (ref. 24). 

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