Organic Chemistry Aromatic Compounds

Arenes:
compounds containing both aliphatic and aromatic parts.
Alkylbenzenes
Alkenylbenzenes
Alkynylbenzenes
Etc.
Emphasis on the effect that one part has on the chemistry of the other half.
Reactivity & orientation

Aromatic Hydrocarbons
hydrocarbons
aliphatic aromatic
alkanes alkenes alkynes

Aliphatic compounds: open-chain compounds and ring compounds that are chemically similar to open-chain compounds. Alkanes, alkenes, alkynes, dienes, alicyclics, etc.
Aromatic compounds: unsaturated ring compounds that are far more stable than they should be and resist the addition reactions typical of unsaturated aliphatic compounds. Benzene and related compounds.

Nomenclature – common names

Nomenclature – common names

Systematic Nomenclature
Monosubstituted benzenes
Hydrocarbon with benzene as parent
C6H5Br = bromobenzene
C6H5NO2 = nitrobenzene
C6H5CH2CH2CH3 = propylbenzene

others named as “alkylbenzenes”:

The Phenyl Group
When a benzene ring is a substituent, the term phenyl is used (for C6H5)
You may also see “Ph” or “φ” in place of “C6H5”
“Benzyl” refers to “C6H5CH2”

Use of phenyl C6H5- = “phenyl”
do not confuse phenyl (C6H5-) with benzyl (C6H5CH2-)

Nomenclature: Side Chains
If side chain has < 6 carbons
Alkyl benzene
If side chain has > 6 carbons
Phenyl alkane

Alkenylbenzenes, nomenclature:

Alkynylbenzenes, nomenclature:

Alcohols, etc., nomenclature:

Nomenclature Disubstituted Benzene
Relative positions on a benzene ring
ortho- (o) on adjacent carbons (1,2)
meta- (m) separated by one carbon (1,3)
para- (p) separated by two carbons (1,4)
Describes reaction patterns (“occurs at the para position”)

Nomenclature More Than Two Substituents
Choose numbers to get lowest possible values
List substituents alphabetically with hyphenated numbers
Common names, such as “toluene” can serve as root name (as in TNT)

Benzene
Three double bonds
Unreactive towards normal reagents (compare to alkenes)
Very stable
Why?
How can we get benzene to react?
Can we control these reactions?

Observations: Reactions of Benzene
Benzene reacts slowly with Br2
Product is bromobenzene
Substitution Product
Addition products are not observed.

Stability of Benzene
KMnO4
Reacts with alkenes
No reaction with benzene
HCl
Reacts with alkenes
No reaction with benzene
HBr
Reacts with alkenes
No reaction with benzene

Stability of Benzene
Heat of Hydrogenation data

Structure of Benzene
C-C bond length
Electrostatic potential
Electron density at C is the same
planar

Structure of Benzene
August Kekule proposed:
1,3,5-cyclohexatriene structure
Explained single monobromo product

Structure of Benzene
Dibromobenzene

Structure of Benzene
Issue was resolved by Kekule

Structure of Benzene
Explains the observed products
Does not explain
Unreactive nature of benzene
Observation of only substitution products
A triene
As reactive as any alkene
Would give addition products
Not expected to be more stable

Structure of Benzene
Resonance Hybrid
Not
Never
-6.023 X 1023 points

Stability of Benzene
MO Description
6 p atomic orbitals combine in cyclic manner
Generate 6 molecular orbitals

Key Ideas on Benzene
Unusually stable
heat of hydrogenation 150 kJ/mol lower than a cyclic triene
Planar hexagon:
bond angles are 120°
carbon–carbon bond lengths 139 pm
Undergoes substitution not addition
Resonance hybrid
One more important factor is the number of electrons in the cyclic orbital

Aromaticity
E Huckel (1931)
Aromaticity is a property of certain molecules
Chemistry would be similar to benzene
Meet the following criteria
Planar
Mono cyclic system
Conjugated pi system
Contains 4n + 2 π electrons
Can apply rules to variety of compounds and determine aromatic nature.
Led to wild chase to make compounds
Met the rules
Violated the rules

Aromaticity and the 4n + 2 Rule
Huckel’s rule, based on calculations – a planar cyclic molecule with alternating double and single bonds has aromatic stability if it has 4n+ 2 π electrons (n is 0,1,2,3,4)
For n=1: 4n+2 = 6
benzene is stable and the electrons are delocalized

Compounds With 4n π Electrons Are Not Aromatic (May be Anti-aromatic)
Planar, cyclic molecules with 4 n π electrons are much less stable than expected (anti-aromatic)
They will distort out of plane and behave like ordinary alkenes
4- and 8-electron compounds are not delocalized
Alternating single and double bonds

Cyclobutadiene
Cyclobutadiene is so unstable that it dimerizes by a self-Diels-Alder reaction at low temperature

Cyclooctatetraene
Cyclooctatetraene has four double bonds
Behaves as if it were 4 separate alkenes
It reacts with Br2, KMnO4, and HCl
Non-planar structure

Aromatic Heterocycles
Heterocyclic compounds contain elements other than carbon in a ring, such as N,S,O,P
There are many heterocyclic aromatic compounds
Cyclic compounds that contain only carbon are called carbocycles
Nomenclature is specialized
Four are important in biological chemistry

Pyridine
A six-membered heterocycle with a nitrogen atom in its ring
π electron structure resembles benzene (6 electrons)
The nitrogen lone pair electrons are not part of the aromatic system (perpendicular orbital)
Pyridine is a relatively weak base compared to normal amines but protonation does not affect aromaticity

Pyrrole
A five-membered heterocycle with one nitrogen
Four sp2-hybridized carbons with 4 p orbitals perpendicular to the ring and 4 p electrons
Nitrogen atom is sp2-hybridized, and lone pair of electrons occupies a p orbital (6 π electrons)
Since lone pair electrons are in the aromatic ring, protonation destroys aromaticity, making pyrrole a very weak base

Pyrimidine
Similar to benzene
3 pi bonds
4n + 2 pi electrons
aromatic

Imidazole
Similar to pyrrole
Pair of non-bonding electrons on N used
4n + 2 pi electrons

Thiophene and Furan
Non-bonding electrons are used
4n + 2 pi electrons

Substitution Reactions of Benzene
Benzene is aromatic: a cyclic conjugated compound with 6 π electrons
Reaction with E+ Leads to Substitution
Aromaticity of Benzene is retained
E+ = Br, Cl, NO2 , SO3H, Alkyl, Acyl, etc

Aromatic Substitutions
The proposed mechanism for the reaction of benzene with electrophiles involves a cationic intermediate
first proposed by G. W. Wheland of the University of Chicago
Often called the Wheland intermediate

Chemistry of the Intermediate
Loss of a proton leads to rearomatization and substitution
Loss of E+ returns to starting material

Halogenation
Add Cl, Br, and I
Must use Lewis acid catalyst
F is too reactive and gives very low yields

Biological Halogenation
Accomplished during biosynthesis of
thyroxine

Aromatic Nitration
The combination of nitric acid and sulfuric acid produces NO2+ (nitronium ion)
The reaction with benzene produces nitrobenzene

Nitrobenzenes: Precursors to Anilines
Nitric acid destroys alkenes through [O]
In sulfuric acid reacts with benzene giving nitrobenzene
Nitrobenzene may be reduced to aniline
Aniline useful precursors to many industrially important organic compounds

Important Anilines

Aromatic Dyes
William Henry Perkin
Age 17 (1856)
Undergraduate student in medicine
Reacted aniline with potassium dichromate
Tarry mess

Aromatic Dyes
Isolated
Mauve - a purple color
Dyed white cloth
Patented material and process
First chemical company

Mauveines -> 1994 !

Some Aniline Chemistry
Anilines readily react with nitrous acid
Diazonium salts
Coupling reaction giving an azo compound
Dyes and sulfa drugs

Aniline Chemistry

How do we make sulfuric acid?
H2SO4 – least expensive manufactured chemical
S (mined pure) + O2 SO3
SO3 + H2O H2SO4
Continue adding SO3 gives
Fuming sulfuric acid: H2SO4/ SO3

Aromatic Sulfonation
Substitution of H by SO3 (sulfonation)
Reaction with a mixture of sulfuric acid and SO3
Reactive species is sulfur trioxide or its conjugate acid
Reaction occurs via Wheland intermediate and is reversible

Benzene Sulfonic Acid
Manufacture of Ion Exchange Resins
Water softening
Water purification
Environmental restoration (removal of toxic metal ions)

Benzene Sulfonic Acid
Starting material for Sulfa Drugs
First useful antibiotics

Hydroxylation
Direct hydroxylation is difficult in lab
Indirect method uses sulfonic acid

Biological Hydroxylation
Frequently conducted
Example,
Coenzyme necessary

Alkylation of Aromatic Rings
The Friedel–Crafts Reaction
Aromatic substitution of a R+ for H
Aluminum chloride promotes the formation of the carbocation
Wheland intermediate forms

Limitations of the Friedel-Crafts Alkylation
Only alkyl halides can be used (F, Cl, I, Br)
Aryl halides and vinylic halides do not react (their carbocations are too hard to form)
Will not work with rings containing an amino group substituent or a strongly electron-withdrawing group

Limitations
Multiple alkylations occur because the first alkyl group activates the ring

polyalkylation
The alkyl group activates the ring making the products more reactive that the reactants leading to polyalkylation. Use of excess aromatic compound minimizes polyalkylation in the lab.

Limitations
Carbocation Rearrangements During Alkylation
Similar to those that occur during electrophilic additions to alkenes
Can involve H or alkyl shifts

Related Reactions
Chloromethylation

Related Reaction
Acylation of Aromatic Rings
Reaction of an acid chloride (RCOCl) with an aromatic ring in the presence of AlCl3 introduces the acyl group,
⎯COR
Benzene with acetyl chloride yields acetophenone
Acyl group deactivates ring
Reaction stops after one group is added

Biological Alkylations
Common reaction
No AlCl3 present
Utilizes an organodiphosphate
Dissociation is facilitated by Mg+2
Important reaction in biosynthesis of Vitamin K1

Ring Substitution Effects
Activation and deactivation of ring
Alkyl activates the ring
Acyl deactivates the ring
Activating Groups
group promotes substitution faster than benzene
Deactivating Groups
group promotes substitution slower than benzene

Activating and Deactivating Groups
Activating groups
electron donating groups
stabilizes the carbocation intermediate
activates through induction or resonance
Deactivating groups
electron withdrawing groups
destabilizes the carbocation intermediate
deactivates through induction or resonance

Common substituent groups and their effect on EAS:
-NH2, -NHR, -NR2
-OH
-OR
-NHCOCH3
-C6H5
-R
-H
-X
-CHO, -COR
-SO3H
-COOH, -COOR
-CN
-NR3+
-NO2
increasing reactivity
ortho/para directors
meta directors

Activating and Deactivating Groups

Origins of Substituent Effects
Inductive effect - withdrawal or donation of electrons through a σ bond
Resonance effect - withdrawal or donation of electrons through a π bond due to the overlap of a p orbital on the substituent with a p orbital on the aromatic ring

Inductive Effects
Controlled by electronegativity and the polarity of bonds in functional groups
Halogens, C=O, CN, and NO2 withdraw electrons through σ bond connected to ring
Alkyl groups donate electrons through σ bond

Resonance Effects: Electron Withdrawal
C=O, CN, NO2 substituents withdraw electrons from the aromatic ring by resonance
π electrons flow from the rings toward the substituent

Resonance Effects: Electron Donation
Halogen, OH, alkoxyl (OR), and amino substituents donate electrons through resonance
π electrons flow from into the ring

Consider the following data

Analysis of Data
Methoxy and Methyl
Activating
Ortho and para products
Nitro and Carbomethoxy
Deactivating
Meta product
Bromine
Deactivating
Ortho and para products

Ring Effects - Conclusions
Activating groups
Substitution is faster than for benzene
Groups direct substitution to o/p positions
Deactivating Groups
Substitution is slower than for benzene
Groups direct substitution to m position
Halogens
Deactivate ring
Substitution is slower than for benzene
Groups direct substitution to o/p positions

Ring Effects – The Explanation
Activating groups donate electrons to the ring, stabilizing the Wheland intermediate (carbocation)
Deactivating groups withdraw electrons from the ring, destabilizing the Wheland intermediate

Important
You need to know this:

Oxidation of Benzene
Toluene is readily oxidized by reagents
Benzene is inert to oxidizing agents
Benzene is toxic to humans
Benzene is a suspected carcinogen
Cytochrom P
strong oxidant in Liver
Primary detoxification process used

Proposed Chemistry

Biological Oxidations of Side Chains
Biosynthesis of norepinephrine

Oxidation of Aromatic Compounds
Alkyl side chains can be oxidized to ⎯CO2H by strong reagents such as KMnO4 and Na2Cr2O7 if they have a C-H next to the ring
Converts an alkylbenzene into a benzoic acid, Ar⎯R → Ar⎯CO2H

Bromination of Alkylbenzene Side Chains
Reaction of an alkylbenzene with N-bromo-succinimide (NBS) and benzoyl peroxide (radical initiator) introduces Br into the side chain

Reduction of Aromatic Compounds
Aromatic rings are inert to catalytic hydrogenation under conditions that reduce alkene double bonds
Can selectively reduce an alkene double bond in the presence of an aromatic ring
Reduction of an aromatic ring requires more powerful reducing conditions (high pressure or rhodium catalysts)

Reduction of Aromatic Compounds
Aromatic Rings can be reduced using Li or Na metal dissolved in liquid ammonia