Benzyne Intermediate Mechanism: SN-Ar Reaction:

The mechanisms that accounts for the experimental observations involves formation of a benzene intermediate which has two equivalent carbon atoms to which amino group can be attached. Benzyne has an extra (Pi) bond between two adjacent carbon atoms of benzene and can be formed as

Step-(1): Strong base NH₂- removes a proton from the position ortho to halogen:

Step-(2): Anion formed in step (1) eliminates the halide ion, thereby forming Benzyne:

The incoming nucleophile can attack either of the carbons of the “triple bond” of benzyne. Protonation of the resulting anion form the substitution product. The overall reaction is an elimination-addition reaction; benzyne is formed in an elimination reaction and immediately undergoes an addition reaction.

Substitution at the carbon (C-14) that was attached to the leaving group is called direct substitution product (DSP). Substitution at the adjacent labeled carbon (C-14) of is called cine substitution product (CSP).

SN-Ar-Elimination-Addition: Benzyne Intermediate Mechanism:

SN-Ar-Elimination-Addition:  An aryl halide can undergo a nucleophilic substitutoin reaction in the presence of a very strongbase such as NH2 When chlorobenzene – that has the carbon to which chlorine is attached isotopically labeled with Cabon-14 –is treated with amide ion in liquid ammonia,  aniline is obtained as a product. Half of the product has the amino group attached to the isotopically labelled carbon (14) as expected, but the other half has the amino group attached to the carbon adjacent to the labelled carbon.

The mechanisms that accounts for the experimental observations involves formation of a benzene intermediate which has two equivalent carbon atoms to which amino group can be attached. Benzyne has an extra (Pi) bond between two adjacent carbon atoms of benzene and can be formed as:

Benzyne Intermediate Mechanism:

Step-(1): Strong base NH₂- removes a proton from the position ortho to halogen:

Step-(2): Anion formed in step (1) eliminates the halide ion, thereby forming Benzyne:

The incoming nucleophile can attack either of the carbons of the “triple bond” of benzyne. Protonation of the resulting anion form the substitution product. The overall reaction is an elimination-addition reaction; benzyne is formed in an elimination reaction and immediately undergoes an addition reaction.

Important Note:  Substitution at the carbon (C-14) that was attached to the leaving group is called direct substitution product (DSP). Substitution at the adjacent labeled carbon (C-14) of is called cine substitution product (CSP).

Characteristic of Benzyne reaction:

(1) It is a S_N-E_A reaction  proceed via elimination –Addition Nucleophilic Substitution reaction.

(2) Aryl halide + strong base required

(3) Presence of beta hydrogen must be needed.

(4) NaNH₂ and KNH₂ can be considered to be essentially the same for our purposes

(5) For symmetrical intermediate which is attacked equally on either side. so that the roughly   50:50 ratio of products are obtained .

Prediction of Major products Benzynes reactions:

SN-Ar-:Meisenheimer complex Intermediate:

S_N2-Ar Mechanism:

Nucleophilic aromatic substitution takes place by a two-step reaction known as an S_N2-Ar (S_N2 –Aromatic bimolecular.) reaction. The S_N2-Ar mechanism and involves a resonance-stabilized anionic intermediate called the Meisenheimer complex.

ILLUSTRATIVE EXAMPLE:

Meisenheimer complex Intermediate:

Step-(1):  An Addition

Step-(2): An Elimination:

Thus, the overall mechanism is an Addition–Elimination Mechanism. the Meisenheimer complex is stable enough to form only if an electron-withdrawing group therein can stabilize the negative charge by resonance.

Characteristics of S_N2-Ar reaction:

(1) It is a Nucleophilic aromatic Substitution reaction by Addition–Elimination Mechanism.

(2) Rate of this reaction depends upon concentration of halide and nucleophile both

(3) Order of reaction is (2) Bimolecular reaction.

(4) Carbanion is intermediate. Hence rearrangement not possible.

(5) Rate of reaction increase on increasing number of EWG which stabilized Meisenheimer complex.

(6) Rate of fluorine derivative (fluoro benzene) is most reactive because of high (–I) inductive effect

.

(7) Only those halogen replace which are ortho or para position with compared to nitro group.

Other Examples:

 (3) Substitution of unactivated hydrogen: (Benzyne Mechanism):

SN-Ar-( NUCLEOPHILIC AROMATIC SUBSTITUTION:

S_N2 (Aromatic) Type: Chloro benzene does not under goes Nucleophilic substitution reaction in ordinary condition due to following reason.

C–X bond in aryl halide is stable due to delocalisation of electrons by resonance. Also (C–X) bond possesses a double bond character like vinyl chloride and is stronger than C–X bond in alkyl halide.

Case-(1): Hence, SN reaction is not possible in benzene nucleus under ordinary conditions. However, under high temperature and pressure, SN reaction is made possible.

 Case-(2): However Nucleophilic substitutions occur in the presence of one or more electron withdrawing (EWG) at ortho and para position. These electron-withdrawing groups must be positioned ortho or para to the leaving group. The greater the number of electron-withdrawing substituents, the easier it will be to carry out the nucleophilic aromatic substitution reactions. 

EXAMPLE:

While electron releasing group (ERG) destabilizes carbanium ion and deactivated.

OTHER EXAMPLES:

SN-Ar-(SUBSTITUTION OF GROUP OTHER THAN HYDROGEN:

Nucleophilic substitution not occurs in aromatic compound but few Nucleophilic substitutions occur in the presence of strong nucleophile. These reactions may be S_N1 -Aromatic unimolecular and S_N2 –Aromatic bimolecular.

S_N1 (Aromatic) Type: The decomposition of diazonium salt in polar medium and formation of different product in the presence of different nucleophile are example of Nucleophilic Aromatic Substitution (S_N1-Ar). The rate of reaction depends upon only concentration of Aryl cation only hence it is unimolecular reaction.

Aryl cation is very reactive and takes up any nucleophile present recombined with elimination of N₂. Therefore reaction is reversible.

Although aryl cation is very unstable , the driving force for it formation of elimination of very stable due to very high bond dissociation of  nitrogen molecule.