Aromatic Chemistry

Section 7
•Aromatic Chemistry (3 hr)
•(a) Generalized mechanism—σ-complexes, π-complexes, the role of
Lewis acids, and aromatization as a driving force for substitution
reactions.
•(b) Substitution of monofunctionalized benzene derivatives
•Orientation and reactivity rules governed by the nature of ring
substituents (inductive and mesomeric effects).
•The importance of kinetic and thermodynamic control.
(c)
• Deuteriation: D2SO4/D2O :
• Nitration: HNO3/H2SO4
• Halogenation: Br2/FeBr3
• Sulfonation: SO3/H2SO+ 4
• Diazo coupling: PhN2
• Friedel–Crafts alkylation and acylation: RCl, AlCl3 and RCOCl, AlCl3
• Vilsmeier Formylation: POCl3, Me2NCHO
• : the Reimer–Tiemann reaction
Electrophilic Aromatic Substitution
Reactions
As seen before benzene does not undergo addition
reactions. It undergoes substitution reactions.
No Reaction
Electrophilic
Aromatic Aromatic Aromatic
Substitution
Reactions
Mechanism
The rich aromatic ring
gives electrons to an
electrophile.
The intermediate
arenium ions (sigma
complexes) are less
energy favored than the
starting material and the
product
Not Aromatic
Halogenation
1. Br2 + FeBr3
2. Cl2+ AlCl3 or FeCl‑ 3
3. I2 + oxidizing agent (H2O2,
CuCl)
4. F via Selectafluor
Lewis acid helps form
E+ +
for Br and Cl+
Conjugate base can
take H away to give
product
 Nitration
•Nitration (concentrated HNO3/H2SO4)
•Formation of NO2+ (nitronium ion) = E+
•Reaction with benzene produces nitrobenzene
 Sulfonation
•Sulfonation (SO3/conc. H2SO4). Fuming sulfuric acid.
•Reversible. Can be used to provide
occur at that position. Then removed.a blocking group so reaction will not
•The reactive electrophile as shown is HSO 3+. There are many possible
mechanisms for electrophile formation this is the simplest one.
Hydrolysis oftheSulfonic acid
group
The reversibility of the aromatic
sulfonation reaction allows it to be used
as a protecting group. The following
example shows how it could be used to
prepare the 3-bromo derivative of ortho-
xylene. Direct bromination gives the
4-bromo derivative.
Freidels-Craft Alkylation.
(R-X, AlCl3)
•The formation of "R+"
•Aryl and vinyl halides cannot be used.
Cl-Cl + AlCl3 ➡ Cl+ + AlCl4-
R-Cl + AlCl3 ➡ R+ + AlCl4-
Works best with 3o>2o>1o
+ HCl
 Freidels-Craft Alkylation. (R-X,
AlCl3)
•Watch out for a more substituted carbon in the vicinity.
Freidels-Crafts Acylation
(RCOCl, AlCl 3 )
•Formation of +C=O. There is no possibility for rearrangement so the
expected product is formed.
•Followed by Clemmensen Reduction (Zn(Hg)/HCl), Wolff-Kishner
(NH2NH2, OH-) or H2/Pt/ethanol to give the alkyl group.
 Howdocurrent substituentsaffectthenext
groupthat is addedtothering?
•Is the product ortho-, meta- or para-?
•Is the reaction
benzene? faster or slower than with

•The answer lies in the mechanism!

Ortho, Meta, Para?
Does Z donate or withdrawal electrons from the aromatic ring?
How will that influence the arenium ions and the reactivity of the ring?
DirectingandActivating
Effects
•The most
mechanisticstable
pointarenium
of
to different positions. view ion
why wins, understand
groups from
influence a
addition
•Donating and withdrawal for activating and deactivating.
Activating Ortho/para directing
•Donate
by the e- to the ring by resonance (R) - and withdraw
inductive (I) effect, resonance wins…the ring is
more nucleophilic
•-OR, -OH,
electrons -NR
that is2 - any atom with a free lone pair of
attached to the ring donate by
resonance.
•R donates by an inductive mechanism.
Activating
o and p Ortho product sigma complexes: 4 sigma complexes form
directing
Meta product sigma complexes: 3 sigma complexes form

Para product sigma complexes: 4 sigma complexes form

Alkyl
Groups
Activating Ortho product sigma complexes. More favored
cation.
o and p
directing Meta product sigma complexes.

Para product sigma complexes. More favored

cation.
Deactivating– Ortho-Para
Directing
•Ortho/para directing deactivating
•Donate e- to ring by resonance (R) – o- and p- directing
•Withdraw e- from ring by the inductive effect (I) -
deactivating
•Halides (-Cl, -I, -Br)

•Notice
effect! that this directs by resonance not by the inductive
Deactivating– MetaDirecting
Withdraw e- by the inductive effect and by the resonance
effect, making the ring less nucleophilic. They have a + or
partial (δ) + charge on the atom attached to the benzene ring)
-NR 3+, -NO2, -SO3H, -CN, -C=O-R (carbonyl containing
compounds)
 Deactivating m
directing
The least worst of the possible
structures. No adjacent positive
charges.

Notice how bad the first structure is.

The N has a + charge and the N is
next to a C that has a + charge As bad as ortho.
Activating and deactivating
groups
Deactivate Activate

m- directors o- and p- directors

Halogens –I, -Br, and
-Cl are o-, p- directing
deactivators
Summary
•Substituent
group directs
influence the
reactivityincoming
of the
ring
•activators – direct o- and p-
•have a lone pair of e- attached to
the atom attached to the ring
•an R group
•halides are
deactivatorso- p- directing
•deactivators – direct m-
•+ or δ+ on the atom attached to the
ring
 Nucleophilic Aromatic
Substitution
•Aryl halides with strong electron-withdrawing substituents can also
undergo a nucleophilic substitution reaction
•This happens when the leaving group is ortho and para to the strong
deactivator
 DifferencesBetweenElectrophilicand
NucleophilicAromaticSubstitution
Electrophilic Nucleophilic
substitution substitution
•Favored by
electron-donati ng •Favored by
electron-withdrawi ng
substituents substituents
•Electron-withdrawi
groups cause ring ng •Electron-withdrawi
groups cause ring ng
deactivation activation
•Electron-withdrawing
groups are meta •Electron withdrawing
groups are ortho-para
directors directors for
nucleophile the
•Replaces
on the ringhydrogen •Replaces a leaving
group
Benzy
ne •Benzyne – electronically is a very strained alkyne
•The benzyne C≡C, uses sp2-C atoms, compared to
sp-C in a normal C≡C
•The sp 2 -orbitals of benzyne are 120o apart. This π
bond is very reactive to addition by nucleophiles.
•In the reaction shown below….. equal amounts of
meta- and para-cresols are obtained. Indicating the C
≡C is attacked at either C atom
Benzyn
e •A large group, methoxy in this case, and the ability of its
ether oxygen to stabilize an adjacent anion favor the m-
product in the addition of the amide anion or ammonia.
 Vilsmeier-Haackreaction

The Vilsmeier-Haack reaction is an organic reaction used to convert an

electron rich aromatic ring to an aryl aldehyde using DMF, an acid chloride,
and aqueous work-up. The mechanism begins with the reaction of DMF
with the acid chloride to form an iminium salt known as the "Vilsmeier
reagent". The electron rich aromatic ring then attacks the iminium ion with
loss of aromaticity. A deprotonation step restores aromati-city, which is
followed by the release of a chloride ion to form another iminium
intermediate. Aqueous work-up then leads to the aryl aldehyde final
product.[1]
https://www.name-reaction.com/vilsmeier-haack-r
eaction
 Vilsmeier-
Haack
reaction

https://www.name-reaction.com/vilsmeier-haack-r
eaction
 Reimer-Tiemannreaction

https://www.name-reaction.com/reimer-tiemann-re
action
https://www.name-reaction.com/reimer-tiemann-re
action
 Nucleophilic Aromatic Substitution
SNAr

https://www.masterorganicchemistry.com/2018/09/17/nucleophilic-aromatic-substitution-2-b
enzyne/
 Benzyne

https://www.masterorganicchemistry.com/2018/09/17/nucleophilic-aromatic-substitution-2-b
enzyne/
https://www.masterorganicchemistry.com/2018/09/17/nucleophilic-aromatic-substitution-2-b
enzyne/
https://www.masterorganicchemistry.com/2018/09/17/nucleophilic-aromatic-substitution-2-b
enzyne/
 Benzyne

https://www.masterorganicchemistry.com/2018/09/17/nucleophilic-aromatic-substitution-2-b
enzyne/
https://www.masterorganicchemistry.com/2018/09/17/nucleophilic-aromatic-substitution-2-b
enzyne/
https://www.masterorganicchemistry.com/2018/09/17/nucleophilic-aromatic-substitution-2-b
enzyne/
https://www.masterorganicchemistry.com/2018/09/17/nucleophilic-aromatic-substitution-2-b
enzyne/