2. Nucleophilic aromatic substitution can
follow two very different paths: the
bimolecular displacement mechanism,
for activated aryl halides; and the
elimination-addition mechanism, which
involves the remarkable intermediate
called benzyne.
AMIT PANDIT, SOP DAVV INDORE 2
3. However, aryl halides do undergo
nucleophilic substitution readily if the
aromatic ring contains, in addition to
halogen, certain other properly placed
groups electron-withdrawing groups like
NO2 , NO, or CN, located ortho or para
to halogen.
AMIT PANDIT, SOP DAVV INDORE 3
4. Addition–Elimination Reactions
It is a two-step addition–elimination
mechanism,
in which addition of the nucleophile to the aryl
halide is followed by elimination of the halide
leaving group.
AMIT PANDIT, SOP DAVV INDORE 4
5. • Groups (such as NO2, CN, and halogen) which
deactivate the ring toward electrophilic
attack, encourage nucleophilic attack.
• These groups are op-directors toward nucleophilic
aromatic substitution.
AMIT PANDIT, SOP DAVV INDORE 5
8. the order of leaving-group
reactivity in nucleophilic
aromatic substitution is the
opposite of that seen in
aliphatic substitution.
Fluoride is the most
reactive leaving group
in nucleophilic aromatic
substitution, iodide the
AMIT PANDIT, SOP DAVV INDORE
least reactive. 8
9. Kinetics: As the observation of second-order
kinetics requires, the rate-determining step
involves both the aryl halide and the
nucleophile.
Rate-enhancing effect of the nitro group.
The high reactivity of aryl fluorides arises
because fluorine is the most electronegative
of the halogens, and its greater ability to
attract electrons increases the rate of
formation of the cyclohexadienyl anion
intermediate in the first step of the
mechanism.
AMIT PANDIT, SOP DAVV INDORE 9
13. Halides derived from certain heterocyclic aromatic
compounds are often quite reactive toward nucleophiles.
2-Chloropyridine, for example, reacts with sodium methoxide
some 230 million times faster than chlorobenzene at 50°C.
•In contrast to chlorobenzene, where the negative charge of the
intermediate
must be borne by carbon, the anionic intermediate in the case of 2-
chloropyridine has its negative charge on nitrogen.
•Since nitrogen is more electronegative than carbon, the intermediate is
more stable and is formed faster than the one from chlorobenzene.
AMIT PANDIT, SOP DAVV INDORE 13
15. THE ELIMINATION–ADDITION MECHANISM
OF NUCLEOPHILIC AROMATIC
SUBSTITUTION: BENZYNE
Very strong bases such as sodium or potassium amide
react readily with aryl halides, even those without
electron-withdrawing substituents, to give products
corresponding to nucleophilic substitution of halide by
the base.
AMIT PANDIT, SOP DAVV INDORE 15
16. o-bromotoluene gave a mixture of o-
methylaniline and m-methylaniline;
p-bromotoluene gave m-methylaniline and p-
methylaniline.
AMIT PANDIT, SOP DAVV INDORE 16
18. Step 1: Elimination stage. Amide ion is a very strong
base and brings about the
dehydrohalogenation of chlorobenzene by abstracting a
proton from the carbon adjacent to the one that bears the
leaving group. The product of this step is an unstable
intermediate called benzyne.
AMIT PANDIT, SOP DAVV INDORE 18
19. Step 2: Beginning of addition phase.
Amide ion acts as a nucleophile and adds to one of the
carbons of the triple bond. The product of this step is a
carbanion.
Step 3: Completion of addition phase.
The aryl anion abstracts a proton from the ammonia used as
the solvent in the reaction.
AMIT PANDIT, SOP DAVV INDORE 19
20. The intermediate formed in this step contains a
triple bond in an aromatic ring and is called
benzyne. Aromatic compounds related to
benzyne are known as arynes.
The triple bond in benzyne is somewhat
different from the usual triple bond of an alkyne,
In benzyne one of the pi components of the
triple bond is part of the delocalized pi system of
the aromatic ring.
The second pi component results from
overlapping sp2-hybridized orbitals (not p-p
overlap), lies in the plane of the ring, and does
not interact with the aromatic pi system
This pi bond is relatively weak
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21. Because the ring prevents linearity of the
C-C≡C-C unit and pi bonding in that unit is
weak, benzyne is strained and highly
reactive.
The sp2 orbitals in the
plane of the ring in
benzyne are not The electrostatic potential
properly aligned for map shows a region of
good overlap, and pi high electron density
bonding is weak. associated with the “triple
bond.”
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22. Although benzyne is too unstable to be isolated, evidence that it is formed
can be
obtained by a trapping experiment. When furan is added to a reaction that
forms a benzyne intermediate, furan traps the benzyne intermediate by
reacting with it in a
Diels–Alder reaction. The product of the Diels–Alder reaction can be
isolated.
AMIT PANDIT, SOP DAVV INDORE 22
