Language
Country/Area
No result found
The secret of the SNAr reaction! Why is chlorobenzene instantly replaced by strong electron attraction?
In organic chemistry, nucleophilic aromatic substitution reaction (SNAr) is a substitution reaction in which a nucleophile replaces a good leaving group, such as a halogen, on an aromatic ring. Although aromatic rings are usually nucleophilic, some aromatic compounds are capable of undergoing nucleophilic substitution reactions under appropriate conditions.
The mechanism of the nucleophilic aromatic substitution reaction is different from the common SN2 reaction because it proceeds on triangular planar carbon atoms.
When performing an SN2 reaction, the nucleophile must approach the carbon atom from the back of the leaving group, but it is affected by steric obstacles on the benzene ring, so this type of reaction almost does not occur. The SN1 mechanism is theoretically possible, but unless the leaving group is extremely good, it is not feasible. This requires the natural release of the leaving group to form an aromatic cation, which is very unfavorable in practice.
Mechanism of nucleophilic aromatic substitution
Nucleophilic substitution of aromatic rings can occur through several different pathways, the most important step being the SNAr (addition-elimination) mechanism. This mechanism is particularly favored when electron-attracting groups such as the nitro group are located in the ortho- or para-position to the halogen leaving group. The electron attracting group can stabilize the electron density on the ring and promote the nucleophilic reaction.
In the reaction mechanism of nucleophilic aromatic substitution, the operation of 2,4-dinitrochlorobenzene in alkaline aqueous solution is very representative.
The nitro group acts as an activator, enhancing the possibility of nucleophilic substitution and stabilizing the attracted electrons through resonance when the nucleophile attacks the carboxyl group. The metastable state formed is called the Masonheimer complex. . When this electron-density-enhanced structure is formed, the hydroxide ions can selectively give up, or the chlorine leaves.
Reaction process
During the reaction, most of the Masonheimer complex undergoes the departure of chlorine to form 2,4-dinitrophenol, while the remainder is returned to the reactants. As the reaction proceeds, 2,4-dinitrophenol will be deprotonated by the alkaline solution, eventually reaching equilibrium. Because this product is in a lower energy state, it does not return to form reactants.
The slow formation of the Meissenheimer complex is a high-energy state caused by reduced aromaticity due to nucleophilic attack.
The reason for the rapid departure of the subsequent chlorine or hydroxyl group is that after losing the leaving group, the aromatic ring will return to aromaticity and release energy. Therefore, the speed of nucleophilic substitution reactions is mainly determined by this rate.
The influence of nucleophiles and leaving groups
In the SNAr reaction, different leaving groups and nucleophiles affect the reaction rate. Usually idle nucleophiles include amines, alcohol phosphonates, sulfides, etc. For the leaving groups of chlorine, bromine and iodine, the reaction rate of fluorine is optimal in the SNAr reaction, a phenomenon that seems to be contrary to the SN2 reaction.
Although fluorine is the strongest bond, it is the most ideal leaving group in the SNAr reaction because the extreme polarity of the C-F bond makes the reaction easier to proceed.
The nucleophile in this reaction can react with a range of organic compounds to form new chemical structures. For example, many nucleophiles of the elements nitrogen, oxygen, or carbon can efficiently carry out substitution reactions to create a variety of different compounds.
Future direction
The ability to perform nucleophilic aromatic substitution reactions is considered a promising synthetic route in a growing field of research. The current work shows that in some cases the Mersenneheimer complex is not just an intermediate but may sometimes be a transition state in the front-end SN2 process.
The asymmetric synthesis method of chiral molecules first reported in 2005 has demonstrated the importance of nucleophilic aromatic substitution in the construction of diverse molecules.
It is worth noting that understanding, or potential future developments, of the underlying mechanisms and mechanisms of such reactions may impact many aspects of organic synthesis. Faced with such a fascinating chemical reaction, are you also looking forward to its future research and applications?
