Transcript Aromatic Compounds - University of Nebraska Omaha

Benzene and its Derivatives
History of Benzene
• Michael Faraday isolated a compound from coal gas
(1825) with the molecular formula C6H6
• Although very unsaturated, the compound was quite
unreactive:
no reaction
KMnO4
C6H6
Br2
no reaction
H2 , 1 atm
Pt
no reaction
• Charles Mansfield isolated “benzene” from coal tar
in 1845.
• Other compounds derived from coal tar also
showed reduced reactivity towards addition and
because of their smell were termed “aromatic
compounds”
• Benzene in the middle of the 19th century was very
much a molecule of mystery.
1. What structure with six carbons could have 4
degrees of unsaturation?
2. Why does a molecule with so much
unsaturation not react like an alkene?
• Some proposed structures for benzene that were wrong.
• Note the formula for all of the compounds is C6H6.
Dewar Benzene
Ladenburg
made in 1962
(Prismane)
made in 1973
Benzvalene
made in 1971
Fulvene
• The mystery of the structure of benzene was
solved by August Kekulé in 1872.
• This structure, however, did not account for the unusual
chemical reactivity (or nonreactivity) of benzene.
• That would come later with Erich Huckel’s ideas of
aromaticity.
Structure of Benzene
• The concepts of hybridization of atomic orbitals
and the theory of resonance, developed in the
1930s, provided the first adequate description of
benzene’s structure.
• The carbon skeleton is a regular hexagon, with all CC-C and H-C-C bond angles 120°.
• The carbon framework; the six parallel 2p orbitals, each
with one electron, are shown uncombined.
• Overlap of the six 2p orbitals forms a continuous pi
cloud, shown as one torus above the plane of the ring,
the other below it.
• We often represent benzene as a hybrid of two
equivalent Kekulé structures.
• Each Kekulé structure makes an equal contribution to
the hybrid.
• The C-C bonds are neither double nor single but
something in between (like a “1½” bond).
• Polycyclic aromatic hydrocarbons (PAH)
• Contain two or more fused aromatic rings.
• Polycyclic aromatic hydrocarbons have
multiple resonance structures as well.
• Many PAHs are carcinogenic.
• Resonance energy: The difference in energy
between a resonance hybrid and its most stable
hypothetical contributing structure in which electrons
are localized on particular atoms and in particular
bonds.
• One way to estimate the resonance energy of benzene is
to compare the heats of hydrogenation of benzene and
cyclohexene.
• Heats of hydrogenation for both cyclohexene and
benzene are negative (heat is liberated).
• Note the heat of hydrogenation for benzene is much
less than 3 times the heat of hydrogenation for
cyclohexene.
• The difference is known as the resonance energy of
benzene.
• Resonance energies [kJ/mol and kcal/mol] for
benzene and several other polycyclic
aromatic hydrocarbons (PAH).
• Know the name and structure for
naphthalene, anthracene, phenanthrene.
Aromaticity
• The criteria for aromaticity were recognized in the
early 1930s by Erich Hückel.
• To be aromatic, a ring must:
1.
2.
3.
have one occupied 2p orbital on each atom of the ring.
be planar or nearly planar, so that overlap of all 2p
orbitals of the ring is continuous or nearly continuous.
have 2, 6, 10, 14, 18, and so forth pi electrons in the
cyclic arrangement of 2p orbitals.
• Benzene meets these criteria
•
It is cyclic, planar, has one 2p orbital on each atom of the
ring, and has 6 pi electrons (the aromatic sextet) in the
cyclic arrangement of its 2p orbitals.
• Aromatic compounds are exceedingly stable because
the pi electrons are spread out.
• The second mystery of benzene is solved!
• The other polycyclic aromatic hydrocarbons are
aromatic as well.
• Hexatriene is not aromatic because it is not cyclic.
• Cycloheptatriene is not aromatic because its double
bonds are not alternating.
• One of the carbons in the ring is an sp3 carbon rather than
an sp2 carbon.
• Naphthalene is aromatic since every carbon is an sp2
carbon and it has 10 pi electrons (not 8 or 12).
• Cyclooctatetraene has alternating double bonds, but
only 8 pi electrons (rather than 6 or 10).
benzene
hexatriene
cycloheptatriene
naphthalene
cyclooctatetraene
aromatic
non-aromatic
non-aromatic
aromatic
non-aromatic
Heterocyclic Aromatics
• Heterocyclic compound: A compound that
contains one or more atoms other than carbon
(heteroatoms) in its ring (nitrogen, oxygen,
sulfur, etc…).
• Heterocyclic aromatic compound: A
heterocyclic compound whose ring is aromatic.
• Pyridine and pyrimidine are heterocyclic analogs of
benzene; each is aromatic.
• Many different compounds are aromatic, including
heterocyclic compounds.
• An example is pyridine C5H5N.
• The nitrogen atom of pyridine is sp2 hybridized.
• The unshared pair of electrons lies in an sp2 hybrid
orbital and is not a part of the six pi electrons of the
aromatic sextet.
• Pyridine has a resonance energy of 32 kcal (134 kJ/mol),
slightly less than that of benzene.
• Other examples of aromatic heterocyclic
compounds are furan and pyrrole.
• Note the difference in the lone pair of each
• In furan, the lone pair is not part of the  system.
• In pyrrole, the lone pair is part of the  system.
Other heterocyclic aromatic compounds
Furan
• Please commit these names and structures to memory
Consumer compounds that are aromatic
2,4-D (Weed-B-Gon)
Dabigatran (anticoagulant)
Atorvastatin
(Lipitor) (anticholestrol drug)
CoQ10 - enzyme in cell organelles
(especially mitochondria) that assists
in ATP (energy) production
Nomenclature
• When benzene is considered to be the parent ring,
functional groups are indicated with prefixes.
NO2
OC2H5
F
C 4H 9
nitrobenzene ethoxybenzene fluorobenzene butylbenzene
• As a branch, the benzene ring is known as a
phenyl branch.
• The term benzyl is reserved for a benzene ring
with an additional carbon as a branch point.
• The carbon at the branch point is called a benzylic
carbon and the hydrogens are benzylic hydrogens.
• Monosubstituted alkylbenzenes are named as
derivatives of benzene.
• Many common names are retained.
• Know these derivatives as well as xylene.
• Xylene = benzene + 2 methyl branches
• Disubstituted benzenes
• Locate substituents by lowest numbers or
• Use the locators ortho (1,2-), meta (1,3-), and para
(1,4-)
• Where one group imparts a special name, name
the compound as a derivative of that molecule.
• Polysubstituted benzenes
• With three or more substituents, number the atoms of
the ring.
• If one group imparts a special name, it becomes the
parent name and the group branches from carbon 1.
• If no group imparts a special name, number to give
the smallest set of numbers, and list alphabetically.
The Benzylic Position
CH2
Br
Br
benzyl bromide is
reactive to both
SN1 or SN2
bromobenzene
does not react via
SN1 or SN2
Nu-
Br
CH2
CH2
Br
X
unstable carbocation
no SN1
Nustable, delocalized carbocation
backside attack not possible
no SN2
backside attack possible
no SN2 and stablized by the
arene ring
Benzylic Oxidation
• Benzene is unaffected by strong oxidizing
agents such as H2CrO4 and KMnO4.
• The benzylic hydrogens are quite acidic.
• An alkyl group with at least one hydrogen on the
benzylic carbon is oxidized to a carboxyl group (and
thus a benzoic acid).
• Halogen and nitro substituents are unaffected by
these reagents.
• If there is more than one one-carbon branch,
each is oxidized to a -COOH group.
• Terephthalic acid is one of the two monomers
required for the synthesis of poly(ethylene
terephthalate) (recycling code 1), a polymer that
can be fabricated into Dacron polyester fibers,
Mylar films as well as soda bottles.
Reactions of Benzene
• The most characteristic reaction of aromatic
compounds is substitution at a ring carbon.
• Other functional groups that can be added to the
benzene ring is the sulfonyl group, and alkyl
group and an acyl group.
Electrophilic Aromatic Substitution
• Electrophilic Aromatic Substitution (EAS): A
reaction in which an electrophile, E+, substitutes
for an H on an aromatic ring.
• In this section, we’ll consider
•
•
•
several common types of electrophiles.
how each electrophile is generated.
the mechanism by which each electrophile replaces
hydrogen.
• All EAS reactions occur by a three-step
mechanism.
• Step 1: Generation of the electrophile.
• Step 2: Reaction of an electrophile and a
nucleophile (pi bond) to form a new covalent bond.
• Step 3: Base takes a proton away to
regenerate the aromatic ring.
Chlorination and Bromination
• Step 1: Formation of the electrophile (a
chloronium ion).
• Fe3+ (a Lewis acid) reacts with chlorine (a Lewis
base) to induce the formation of Cl+, the
chloronium ion.
• Step 2: Reaction of the electrophile (the
chloronium ion and a nucleophile to form a
new covalent bond.
• Step 3: Proton transfer to FeCl4– forms HCl,
regenerates the Lewis acid catalyst, and gives
chlorobenzene.
Nitration
• The electrophile, NO2+, is generated in two steps.
• Step 1: Add a proton (from a strong acid like sulfuric
acid) to nitric acid to make water as a leaving group.
• Step 2: Water breaks off forming the nitronium ion, NO2+.
• Finish reaction by having NO2+ use pi electrons to
create new bond and have proton transfer back
into solution.
Sulfonation
• The electrophile, HSO3+, is generated in two steps.
• Step 1: Add a proton (one molecule of sulfuric acid
protonates another sulfuric acid) to make water as a
leaving group.
• Step 2: Water breaks off forming the sulfonium ion,
HSO3+.
• HSO3+ attacks pi electrons in aromatic ring to
create new bond.
• Proton on ring is transferred back into solution.
benzenesulfonic acid
• Sulfonic acids are very acidic (like sulfuric acid).
• The conjugate bases (sulfonates) are used in
detergents.
Friedel-Crafts Alkylation
• Friedel-Crafts alkylation forms a new C-C bond
between an aromatic ring and an alkyl group.
• Step 1: Formation of an electrophile.
• A Lewis acid (AlCl3) reacts with alkyl chloride to
form carbocation.
• Step 2: Reaction of an electrophile (carbocation) and
a nucleophile (pi electrons) to form a new covalent
bond.
• Step 3: Take a proton away. Metal complex acts a
Lewis base to react with hydrogen ion (a Lewis acid)
to regenerate the aromatic ring.
• There are two major limitations on Friedel-Crafts
alkylations.
• It is practical only with stable carbocations, such as 2°
and 3° carbocations.
• It fails on benzene rings bearing one or more of these
strongly electron-withdrawing groups (more in a little
while).
• Other methods to alkylate an aromatic ring
depend on alternative methods to create
carbocations.
• Treating an alkene with a protic acid, most commonly
H2SO4 or H3PO4.
• Treating an alcohol with H2SO4 or H3PO4.
Friedel-Crafts Acylations
• Treating an aromatic ring with an acid chloride in
the presence of AlCl3.
• Acid (acyl) chloride: a derivative of a carboxylic acid
in which the -OH is replaced by a chlorine.
• Product is a ketone. (with aromatic ring on one
side of the carbonyl group)
• Step 1: Formation of the electrophile.
• Step 2: Reaction of an electrophile (acylium
ion) and a nucleophile (pi electrons) to form a
new covalent bond.
• Step 3: Take a proton away. Proton transfer to
AlCl4– forms HCl, regenerates the Lewis acid
catalyst, and gives a ketone.
Di- and Polysubstituted Benzenes
• Existing groups on a benzene ring influence
further substitution in both orientation and rate.
• Orientation
• Certain substituents direct a new substitution
preferentially toward the ortho-para positions, others
direct preferentially toward the meta positions.
• Rate
• Certain substituents are activating (rxn goes faster)
toward further substitution, others are deactivating
(rxn goes slower) toward further substitution.
Theory of Directing Effects
• The rate of electrophilic aromatic substitution
• The rate of EAS is determined by the slowest step in
the reaction.
• For almost every EAS, the rate-determining step is
attack of E+ on the aromatic ring to give a resonancestabilized cation intermediate.
• The more stable this cation intermediate, the faster
the rate-determining step and the faster the overall
reaction.
• For ortho-para directors, ortho-para attack
forms a more stable cation than meta attack.
• Also, ortho-para products are formed faster than meta
products.
• -OCH3 is ortho-para directing.
• Note the resonance structures for ortho attack of
the methoxy group (which are almost the same
for para attack) are more stable than those from
meta attack.
• The ortho (and para) resonance structures include a
“quasi-tertiary” carbocation that is converted an
oxonium ion that is formed from having a lone pair of
electrons on an atom that is adjacent to a ring. Thus
the positive charge is more delocalized and the cation
is more stable (than the corresponding “meta” cation).
CH3
CH3
CH3
O
O
O
E
E
E
• The resonance structures for meta attack of the
methoxy group are less stable than those for
ortho/para attack.
• These “meta attack” resonance structures are not
unstable, just less stable than those for ortho/para
attack.
CH3
CH3
CH3
O
O
O
E
E
E
• The resonance structures for para attack for
the methoxy group –OCH3 by –NO2.
Activating Directors
• Any resonance effect for electron-donating
groups such as –NH2, –OH, and –OR, which
delocalizes the positive charge on the cation
intermediate, lowers the activation energy for
its formation and activates the ring toward
further EAS.
• These groups on the benzene ring make
electrophilic aromatic substitution faster.
• They direct substitution to the ortho and para
positions.
Possible transition states for ortho, meta or para
attack on an activated arene.
• For meta directors, meta attack forms a more
stable cation than ortho-para attack.
• Also, meta products are formed faster than ortho-para
products.
• -NO2 is meta directing.
• Note the resonance structures for meta attack of
the nitro group versus the resonance structures
for ortho/para.
• The ortho (and para) resonance structures include a
structure where the positive carbocation charge is
adjacent to the positive formal charge of the nitrogen
atom in the nitro group.
O
O
O
O
O
O
N
N
N
E
E
E
• This repulsion makes the resonance structure less
stable.
• Since the meta resonance structures don’t have a
similar structure, by default, such an attack is
preferred.
O
O
O
O
O
N
N
E
O
N
E
E
Deactivating Directors
• Any resonance or inductive effect for electronwithdrawing groups such as –NO2, –C=O,
-SO3H, –NR3+, –CCl3, and –CF3, which
decreases electron density on the ring,
deactivates the ring toward further EAS.
• These groups on the benzene ring make
electrophilic aromatic substitution slower.
• They direct substitution to the meta position.
• Halogens: the resonance and inductive effects
operate in opposite directions.
– The inductive effect: halogens have an electronwithdrawing inductive effect; therefore, aryl halides
react more slowly in EAS than benzene.
– The resonance effect: a halogen ortho or para to the
site of electrophilic attack stabilizes the cation
intermediate by delocalizing the positive charge;
halogen, therefore, is ortho-para directing.
Possible transition states for ortho, meta or para
attack on an deactivated arene.
• Note that activating (and ortho/para) directors
have lone pairs that can participate in
resonance structures.
• Generalizations
1. Groups which are ortho-para directing.
a.
b.
c.
Alkyl groups
Phenyl groups
Substituents in which the atom bonded to the ring has
an unshared pair of electrons
2. All ortho-para directing groups are activating
toward further substitution; the exceptions to
this generalization are the halogens, which are
weakly deactivating.
•
Disubstituted and trisubstituted rings are likely with
excess reagent.
3. All other substituents are meta directing.
4. All meta directing groups carry either a partial or
full positive charge on the atom bonded to the
ring.
• In a multi-step synthesis, the order of steps is
crucial.
Phenols
• The functional group of a phenol is an -OH
group bonded to a benzene ring.
Chemical Properties of Phenols
• Phenols are significantly more acidic than alcohols.
• The greater acidity of phenols compared with
alcohols is the result of the greater stability of the
phenoxide ion relative to an alkoxide ion.
• Electron-withdrawing groups, particularly
halogens and nitro groups, increase the acidity
of phenols by a combination of resonance and
inductive effects.
• Because phenols are stronger weak acids than
most, they are often water-soluble.
• As weak acids, phenols react with strong bases
to form water-soluble salts.
• They do not react with weak bases, such as
sodium bicarbonate.
• Phenols and related compounds act as antioxidants.
• Vitamin E is a natural antioxidant.
• BHT and BHA are synthetic antioxidants.