Leaving groups in aromatic nucleophilic substitution

So why is fluoride often preferred in nucleophilic aromatic substitution and why does it react faster than the other halogens when the reverse is true with other reactions You will notice that we have not said that fluoride is a better leaving group in nucleophilic aromatic substitution. It isn t The explanation depends on abetter understanding of the mechanism of the reaction. We shall use azide ion as our nucleophile because this has been well studied, and because it is one of the best. 

Indeed, the order of leaving-group reactivity in nucleophilic aromatic substitution is the opposite of that seen in aliphatic substitution. Fluoride is the most reactive leaving group in nucleophilic aromatic substitution, iodide the least reactive. 

In general, the more nitro groups present on the aromatic ring the easier the leaving group displacement. Nucleophilic aromatic substitution is therefore a very important reaction in the chemistry of polynitroarylenes. While the use of such reactions has been extensive in the synthesis of explosives, the reaction also has important implications for the chemical stability of many polynitroarylenes (discussed in Section 4.8.2). 

The presence of strong electron-withdrawing groups such as NO2 ortho or para to a potential leaving group favors nucleophilic aromatic substitution by the addition-elimination mechanism. Without such groups in these positions, the benzyne mechanism is favored. 

It has also been shown that phase transfer conditions are effective for promoting carbanion arylation by nucleophilic aromatic substitution. 2-Phenylpropionitrile reacts with 4-nitrochlorobenzene to give 2-phenyl-2-(4-nitrophenyl)-propionitrile in 82% yield (see Eq. 10.23) [33]. Similar results were observed for several other chlorinated nitroaromatics, but two cases deserve special attention. First, the reaction of 2-phenylpropionitrile with 4-bromo-4-nitrobenzophenone affords the aromatic substitution product, but the leaving group in this reaction is nitrite, not bromide (see Eq. 10.24) [34]. Nitrite is known to be a good leaving group in nucleophilic aromatic... 

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... 

Indeed, the order of leaving-group reactivity in nucleophilic aromatic substitution is the... 

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. 

Leaving groups at C5 of 2-substituted 1,2,3-triazoles are predicted to be the most reactive in nucleophilic aromatic substitution reactions following an AE mechanism (see Section 1.4.2). Accordingly, chlorine at C5 of 360 could be replaced by strong nucleophiles like methanethiolate or methoxide to give 377 or 378. The unactivated 2-phenyl-4-chloro-l,2,3-triazole 380 (R=Ph) was inert toward these nucleophiles (1981JCS(P1)503) (Scheme 115). 

Nucleophilic aromatic substitution is much more restrictive in its applications than electrophilic aromatic substitution. In nucleophilic aromatic substitution, a strong nucleophile replaces a leaving group such as a halide. The mechanism cannot be the Sn2 mechanism because aryl halides cannot achieve the correct geometry for backside displacement. The aromatic ring blocks approach of the nucleophile to the back of the carbon bearing the halogen. 

Quaternary aza aromatic compounds are suitable substrates for investigating fundamental topics in organic chemistry. The behavior and use of pyridines as neutral leaving groups in nucleophilic substitution at a satu-... 

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