Nucleophilic aromatic substitution is a classical reaction in which a nucleophile displaces a leaving group on an aromatic ring. The presence of the electron-withdrawing group increases the rate of nucleophilic aromatic substitution. The nucleophilic compound doesn’t give a substitution reaction easily.
Full Answer
What is a nucleophilic aromatic substitution?
A nucleophilic aromatic substitution is a substitution reaction in organic chemistry in which the nucleophile displaces a good leaving group, such as a halide, on an aromatic ring. There are 6 nucleophilic substitution mechanisms encountered with aromatic systems:
Why do most reactions of aromatic compounds involve Electrophilic substitution?
We have seen that most reactions of aromatic compounds involve electrophilic substitutions because the π electrons make the aromatic ring electron-rich and therefore, nucleophilic.
Are aromatic rings nucleophilic or electrophilic?
Aromatic rings are usually nucleophilic, but some aromatic compounds do undergo nucleophilic substitution. Just as normally nucleophilic alkenes can be made to undergo conjugate substitution if they carry electron-withdrawing substituents, so normally nucleophilic aromatic rings also become electrophilic if they have the right substituents.
What is the mechanism of nucleophilic aromatic substitution of phenyl halide?
The mechanism of nucleophilic aromatic substitution, however, is different than what we learned in the S N 1 and S N 2 reactions. The key difference is that aryl halides cannot undergo an SN2 by a backside attack of the nucleophile and, unlike S N 1, the loss of the leaving group cannot occur since the phenyl cations are very unstable:
Why aromatic nucleophilic substitution reactions are difficult?
Because of the presence of delocalised electron clouds on benzene ring nucleophilic attack, it is difficult and thus does not generally undergo nucleophilic replacement reaction.
Why is nucleophilic aromatic substitution difficult in benzene?
Nucleophiles are electron-rich. Due to the presence of an electron cloud of delocalized electrons on the benzene ring nucleophilic attack is difficult. Hence, they are repelled by benzene. Hence, benzene undergoes nucleophilic substitutions with difficulty.
Can aromatic compounds undergo nucleophilic substitution?
A nucleophilic aromatic substitution is a substitution reaction in organic chemistry in which the nucleophile displaces a good leaving group, such as a halide, on an aromatic ring. Aromatic rings are usually nucleophilic, but some aromatic compounds do undergo nucleophilic substitution.
Why does benzene undergo electrophilic substitution reaction easily and nucleophilic substitutions with difficulty?
Solution : Benzene is a planar molecule having delocalized electrons above and below the plane of ring. Hence, it is electron-rich. As a result, it is highly attractive to electron deficient species i.e., electrophiles.
Therefore, it undergoes electrophilic substitution reactions very easily.
Why is nucleophilic substitution difficult in Haloarenes?
The, C—Cl bond length in haloalkane is greater than in haloarene. Since it is difficult to break a shorter bond than a longer bond, therefore, Haloarenes are less reactive than haloalkanes towards nucleophilic substitution reaction.
Why electrophilic substitution takes place more readily in aromatic amines than benzene?
Solution : Due to resonance, the electrons on the N-atom in aniline are delocalized over the benzene ring. As a result, the electron density on the benzene ring increases as compared to benzene itself. In other words, aniline gets activated and hence electrophilic substitution occurs more readily in aniline.
Which of the aromatic compound undergoes nucleophilic substitution reaction most easily?
The p-chloronitrobenzene can easily undergo the nucleophilic substitution reaction.
Which compound reacts fastest in aromatic nucleophilic substitution reaction?
Therefore, p−chloro nitrobenzene has the highest reactivity.
What is the difference between electrophilic aromatic substitution and nucleophilic aromatic substitution?
The main difference between electrophilic and nucleophilic aromatic substitution is that electrophilic aromatic substitution involves the replacement of an atom of the aromatic compound with an electrophile whereas nucleophilic aromatic substitution involves the replacement of an atom of the aromatic compound with a ...
Why do benzene and other aromatic compounds undergo electrophilic aromatic substitution with ease while they struggle to undergo nucleophilic substitution reactions?
Benzene is a planar molecule having delocalized electrons above and below the plane of ring. Hence, it is electron-rich. As a result, it is highly attractive to electron deficient species i.e., electrophiles. Therefore, it undergoes electrophilic substitution reactions easily.
Why electrophilic substitution reaction occurs slowly in nitrobenzene than benzene?
Nitrobenzene, C6H5NO2, undergoes the reaction millions of times more slowly. These observations are consistent with the role of the aromatic as a nucleophile in this reaction. Substituents that draw electron density away from the aromatic ring slow the reaction down.
Why does benzene undergo electrophilic substitution and not addition?
There are delocalised electrons above and below the plane of the ring. The presence of the delocalised electrons makes benzene particularly stable. Benzene resists addition reactions because that would involve breaking the delocalisation and losing that stability.
Why do benzene and other aromatic compounds undergo electrophilic aromatic substitution with ease while they struggle to undergo nucleophilic substitution reaction?
Benzene is a planar molecule having delocalized electrons above and below the plane of ring. Hence, it is electron-rich. As a result, it is highly attractive to electron deficient species i.e., electrophiles. Therefore, it undergoes electrophilic substitution reactions easily.
What is the difference between electrophilic aromatic substitution and nucleophilic aromatic substitution?
The main difference between electrophilic and nucleophilic aromatic substitution is that electrophilic aromatic substitution involves the replacement of an atom of the aromatic compound with an electrophile whereas nucleophilic aromatic substitution involves the replacement of an atom of the aromatic compound with a ...
Why is benzene more reactive with an electrophile than a nucleophile?
Because the benzene acts as a nucleophile in electrophilic aromatic substitution, substituents that make the benzene more electron-rich can accelerate the reaction.
Which compound reacts fastest in aromatic nucleophilic substitution reaction?
Therefore, p−chloro nitrobenzene has the highest reactivity.
How many nucleophilic substitutions are there in aromatic systems?
There are 6 nucleophilic substitution mechanisms encountered with aromatic systems:
What is nucleophilic substitution?
A nucleophilic aromatic substitution is a substitution reaction in organic chemistry in which the nucleophile displaces a good leaving group, such as a halide, on an aromatic ring. Aromatic rings are usually nucleophilic, but some aromatic compounds do undergo nucleophilic substitution.
Why is the formation of the resonance-stabilized Meisenheimer complex slow?
The formation of the resonance-stabilized Meisenheimer complex is slow because it is in a higher energy state than the aromatic reactant. The loss of the chloride is fast, because the ring becomes aromatic again. Recent work indicates that, sometimes, the Meisenheimer complex is not always a true intermediate but may be the transition state of a 'frontside S N 2' process, particularly if stabilization by electron-withdrawing groups is not very strong. A 2019 review argues that such 'concerted S N Ar' reactions are more prevalent than previously assumed.
How many different mechanisms are involved in nucleophilic substitution?
The are six different mechanism by which aromatic rings undergo nucleophilic substitution.
What is the nucleophile of the Bamberger rearrangement?
In the Bamberger rearrangement N-phenylhydroxylamines rearrange to 4-aminophenols. The nucleophile is water.
What is the clockwise order of carbons in the benzene carbon sequence?
In this sequence the carbons are numbered clockwise from 1–6 starting with the 1 carbon at 12 o'clock, which is bonded to the chloride. Since the nitro group is an activator toward nucleophilic substitution, and a meta director, it allows the benzene carbon to which it is bonded to have a negative charge.
Why does S N 2 not occur?
The mechanism of S N 2 reaction doesn't occur due to steric hindrance of the benzene ring. In order to attack the C atom, the nucleophile must approach in line with the C-LG (leaving group) bond from the back, where the benzene ring lies. It follows the general rule for which S N 2 reactions occur only at a tetrahedral carbon atom.
What is nucleophilic aromatic substitution?
Nucleophilic aromatic substitution generally requires the presence of electron-withdrawing groups on the arene. Thus, although it is one of the standard methods of preparation of manganese alkyls, nucleophilic substitution of arenes by manganese anions only occurs for activated arenes such as pentafluoropyridine.131
What is the ipso nucleophilic aromatic substitution of the nitro group by fluoride anions?
ipso-Nucleophilic aromatic substitution of the nitro group by fluoride anions can be used for the synthesis of the 18 F-labeled compounds. This reaction requires the presence of electron-withdrawing groups (e.g., carbonyl) at ortho or para positions to the nitro group to stabilize the intermediate Meisenheimer complex. 18 F-labeled 4- (2′-methoxyphenyl)-1- [2′- (N-2″-pyridinyl)-4-fluorobenzamido]ethylpiperazine ( p -MPPF), a PET tracer for selective imaging of a serotonin receptor, 5-hydroxytryptamine-1A (5-HT 1A) receptor, is prepared by this method in a fully automated way 45; The carbonyl 11 C-labeled version of the p -MPPF, WAY-100635, has been widely used for selective PET imaging of 5-HT 1A receptors. 46
What is the name of the atom that gives ortho or para to the carbonyl group?
Nucleophilic aromatic substitutions of tetramethylammonium group, ortho or para to the carbonyl group, by 18 F-fluoride ion gives ortho - or para - [ 18 F]fluorobenzaldehydes in high RCYs; these compounds are useful starting materials for the preparation of various 18 F-labeled amino acids ( Figure 18 ). 36
When was the first kinetic study of the reaction of halobenchrotrenes with an anionic nucleophil?
The first kinetic study of the reaction of halobenchrotrenes with an anionic nucleophile was reported 103 in 1966. Later studies have investigated reactions with amines, 104 ring-substituent, 105,106 salt 107 and solvent 107 effects, and the effect of changing the metal. 107 Relative second-order rate constants ( krel) for reactions with MeO − in MeOH are given in Table 4.
Which scheme is the aminolysis of 2,4-dinitrophenylsulfonyl chloride?
Scheme 9. The aminolysis of 2,4-dinitrophenylsulfonyl chloride 42, that proceeds through a nucleophilic aromatic substitution mechanism and has been considered in ionic liquids. 43
Which liquids were used to correlate rate constant to Gutmann's donor number for the reaction shown in Scheme 8?
Fig. 6. The ionic liquids 37 – 41 which were used to correlate rate constant to Gutmann's donor number for the reaction shown in Scheme 8. 41
Does chlorobenchrotrene have nucleophilic displacement?
It has been observed that nucleophilic displacement of chloride from chloroben chrotrene does not occur when more reactive carbanionic reagents are used ( e.g. MeLi, PhLi, HC CLi, NCCH 2 Li); this has been interpreted 94 to indicate that, in these cases, nucleophilic addition occurs only at unsubstituted ring positions to give intermediates of the type ( 37) which do not equilibrate with ( 36) under the usual reaction conditions.
What is a nucleophilic replacement reaction?
Nucleophilic replacement reactions are a class of reactions in which a positively charged electrophile is attacked by an electron rich nucleophile to replace a leaving group.
Why is benzene not a nucleophilic replacement?
Because of the presence of delocalised electron clouds on benzene ring nucleophilic attack, it is difficult and thus does not generally undergo nucleophilic replacement reaction. Two examples of electrophilic aromatic substitution are nitration and sulfonation of benzene.
What are electrophiles?
The electrophiles are nitronium ion (NO 2+) and sulphur trioxide (SO 3) and react with benzene individually to produce nitrobenzene and benzenesulfonic acid, respectively. A significant class of reactions that allow the interconversion of functional groups are nucleophilic substitution reactions.
Who created the addition-elimination mechanism?
The addition-elimination mechanism. Created by Jay.
Is aromatic ring highly resonance stabilized?
So yes, the product is highly resonance stabilized.
Overview
A nucleophilic aromatic substitution is a substitution reaction in organic chemistry in which the nucleophile displaces a good leaving group, such as a halide, on an aromatic ring. Aromatic rings are usually nucleophilic, but some aromatic compounds do undergo nucleophilic substitution. Just as normally nucleophilic alkenes can be made to undergo conjugate substitution if they carry electron …
Nucleophilic aromatic substitution mechanisms
There are 6 nucleophilic substitution mechanisms encountered with aromatic systems:
1. The SNAr (addition-elimination) mechanism
2. The aromatic SN1 mechanism encountered with diazonium salts
SNAr reaction mechanism
The following is the reaction mechanism of a nucleophilic aromatic substitution of 2,4-dinitrochlorobenzene in a basic solution in water.
In this sequence the carbons are numbered clockwise from 1–6 starting with the 1 carbon at 12 o'clock, which is bonded to the chloride. Since the nitro group is an activator toward nucleophilic substitution, and a meta director, it allows t…
Nucleophilic aromatic substitution reactions
Some typical substitution reactions on arenes are listed below.
• In the Bamberger rearrangement N-phenylhydroxylamines rearrange to 4-aminophenols. The nucleophile is water.
• In the Sandmeyer reaction and the Gattermann reaction diazonium salts react with halides.
Asymmetric nucleophilic aromatic substitution
With carbon nucleophiles such as 1,3-dicarbonyl compounds the reaction has been demonstrated as a method for the asymmetric synthesis of chiral molecules. First reported in 2005, the organocatalyst (in a dual role with that of a phase transfer catalyst) is derived from cinchonidine (benzylated at N and O).
See also
• Electrophilic aromatic substitution
• Nucleophile
• Substitution reaction
• SN1 reaction
• SN2 reaction