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Do you know how to make the chlorine atoms leave the aromatic ring?
In organic chemistry, nucleophilic aromatic substitution (SNAr) is a special substitution reaction in which a nucleophile replaces a good leaving group, such as a halogen, on an aromatic ring. Although aromatic rings generally behave like nucleophiles, in certain circumstances they can participate in nucleophilic substitution reactions. In fact, common nucleophilic olefins can also undergo conjugated substitution under the influence of electron-withdrawing substituents, and aromatic rings can also show electrophilicity under the influence of specific substituents.
The nucleophilic aromatic substitution reaction differs in that it occurs at a trihedral carbon atom rather than a tetrahedral carbon.
The mechanism of nucleophilic aromatic substitution reactions is different from the general SN2 reaction because the carbon atom that undergoes nucleophilic attack in the aromatic ring is sp2 hybridized. This means that the nucleophile must attack from the rear, which is not easy in molecules with a benzene ring because the steric hindrance of the benzene ring makes this process challenging. The situation is similarly bleak for the SN1 mechanism, unless the leaving group is a very good one, which usually involves the formation of an aromatic cation, which is chemically very unfavorable.
Mechanism of nucleophilic aromatic substitution
Aromatic rings can undergo nucleophilic substitution via a variety of pathways, including the SNAr (addition-elimination) mechanism, the SN1 mechanism, the benzyne mechanism, the free radical SRN1 mechanism, the ANRORC mechanism, and alternative nucleophilic substitution. Among them, the SNAr mechanism is the most important one. Electron-withdrawing groups can effectively activate aromatic rings, making them more susceptible to nucleophilic attack. For example, when the nitro group is located in the ortho or para position to the halogen leaving group, the occurrence of the SNAr mechanism is more favorable.
In SNAr reactions, the presence of the nitro group helps stabilize the Meisenheimer complex that is produced when the hydroxyl nucleophile attacks the aromatic compound.
Taking the nucleophilic aromatic substitution reaction of 2,4-dinitrochlorobenzene in a basic solution of water as an example, the nitro group, as an activator of nucleophilic substitution, can stabilize the aromatic substitution reaction formed by the attack of hydroxide. Meisenheimer Complex. The formation of this complex is relatively slow because the loss of aromaticity increases the energy. However, once the chlorine leaves and aromaticity is restored, the process occurs rapidly. As time progresses, the reaction will eventually reach chemical equilibrium, favoring the formation of 2,4-dinitrophenol.
Common Examples of Nucleophilic Aromatic Substitution Reactions
Nucleophilic aromatic substitution reactions are not limited to benzene compounds; heteroaromatic compounds such as pyridine can be even more reactive in some cases. For example, pyridine is particularly reactive in substitution reactions at the ortho or para position of an aromatic ring because the negative charge is effectively delocalized at the nitrogen atom. Among them, the Chichibabin reaction is a classic example of the reaction of sodium amide and pyridine to form 2-aminopyridine.
Nucleophilic aromatic substitution reactions are also developing. Recent studies have shown that the Meisenheimer complex is not just an intermediate in some cases, but may be a transition state of the "front-end SN2 process", which changes the previous understanding of Understanding of the reaction mechanism.
Although the C-F bond of fluoride is very strong, fluorine is an ideal leaving group in SNAr reactions because of its extremely high electronegativity.
Research on nucleophilic aromatic substitution reactions continues to bring new insights, and with the advent of new catalysts, these reactions may even be used for asymmetric syntheses. Since it was first reported in 2005, this reaction has gradually demonstrated its potential in the synthesis of chiral molecules.
Can this basic knowledge improve our understanding and application of aromatic ring chemistry?
