Leaving groups, reactivity in nucleophilic aromatic substitution

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

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. 

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). 

Similarly this order of reactivity is not usually observed in nucleophilic aromatic substitution reactions as loss of the leaving group is usually not the r.d.s. 

Since pyridine is less reactive than benzene in electrophilic aromatic substitution reactions, it should not be surprising that pyridine is more reactive than benzene in nucleophilic aromatic substitution reactions. The electron-withdrawing nitrogen atom that destabilizes the intermediate in electrophilic aromatic substitution stabilizes the intermediate in nucleophilic aromatic substitution. Notice that, in nucleophilic aromatic substitution reactions, the ring has a leaving group that can be replaced by a nucleophile. 

Halopyridines and other re-deficient nitrogen heterocycles are excellent reactants for nucleophilic aromatic substitution.112 Substitution reactions also occur readily for other heterocyclic systems, such as 2-haloquinolines and 1-haloisoquinolines, in which a potential leaving group is adjacent to a pyridine-type nitrogen. 4-Halopyridines and related heterocyclic compounds can also undergo substitution by nucleophilic addition-elimination but are somewhat less reactive. 

Nucleophilic aromatic substitutions Pyrimidine is more reactive than pyridine towards nucleophilic aromatic substitution, again due to the presence of the second electron-withdrawing nitrogen in the pyrimidine ring. Leaving groups at C-2, C-4 or C-6 positions of pyrimidine can be displaced by nucleophiles. 

Nucleophilic aromatic substitution (reaction 4 in Review Table 3t occurs by addition of a nucleophile to an electrophilic aromatic ring, followed by elimination of the leaving group. The ring is made electrophilic, and hence reactive, only when substituted by strong electron-withdrawing groups such a nitro, cyano, and carbonyl. 

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