NUCLEOPHILIC AROMATIC NUCLEOPHILIC AROMATIC REACTIONSREACTIONS

Presented by:- NAVEEN KADIAN M Pharma 1st year Dept of Pharmachemistry, K.L.E.S’ College of Pharmacy, Belgaum- 10.

CONTENTSCONTENTS

benzene naphthalene

phenanthrene

C

CCC

CC

H

H

H

H

HH

NUCLEOPHILES A reagent which can donate an electron pair in a reaction is called as

nucleophiles. Nucleophiles are electron rich. {Ex:- Cl-, Br-, I-, CN-, OH- } The displacement of halide ion by a nucleophile is known as nucleophilic

substitution reaction. Nucleophilic substitution in ArX is facilitated by the presence of a strong

electron-withdrawing group, such as NO2, ortho or para to the halogen.

In reactions of this type, fluoride is the best leaving group of the halogens and iodide the poorest.

Electrophilic substitution is by far the most common mode of

substitution in aromatic systems, the nucleophilic substitution is indeed and useful tool in certain cases.

The early industrial synthesis of phenols and anilines were based on nucleophilic aromatic substitution reaction

Nucleophilic Aromatic Substitution

If we draw parallels between nucleophilic substitution in aliphatic and aromatic systems, we realize that the SN1 and SN2 mechanisms are not feasible in aromatic systems.

One of major reasons that p electrons in aromatic systems are in conjugation, back side attack (as in SN2) and inversion is precluded by geometry of ring. SN1 type of substitution require formation of the phenyl cation which is less stable than a primary carbocation.

MechanismsMechanismsSNAr Mechanism - addition / elimination

SN1 Mechanism

benzyne Mechanism - elimination / addition

Srn 1 Mechanism

SSNNAr Mechanism - addition / eliminationAr Mechanism - addition / elimination Nucleophilic aromatic substitutions of the type just shown follow

an addition-elimination mechanism.

The rate-determining intermediate is a cyclohexadienyl anion and is stabilized by electron-withdrawing substituents.

Attack of the strong nucleophile on the halogen substituted aromatic carbon forming an anionic intermediate.

Loss of the leaving group, the halide ion restores the aromaticity. Kinetics of the reaction are observed to be second order. The addition step is the rate determining step (loss of aromaticity).

Nucleophilic substitution, and therefore reaction rate, is facilitated by the presence of a strong electron withdrawing group (esp. NO2) ortho or para to the site of substitution, which stabilize the cyclohexadienyl anion through

resonance.

Aryl halide reactivity :  -F > -Cl > -Br > -I    The more electronegative the group the greater the ability to attract electrons

which increases the rate of formation of the cyclohexadienyl anion.