History of Benzene• Michael Faraday isolated a compound from coal gas

(1825) with the molecular formula C6H6

Benzene and its Derivatives

• Although very unsaturated, the compound was quite unreactive:

C6H6

Br2no reaction

H2 , 1 atm

Ptno reaction

KMnO4

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?

Dewar Benzene

made in 1962

Ladenburg

(Prismane)

made in 1973

Benzvalene

made in 1971

Fulvene

• Some proposed structures for benzene that were wrong. • Note the formula for all of the compounds is C6H6.

• 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 C-

C-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. have one occupied 2p orbital on each atom of the ring.2. be planar or nearly planar, so that overlap of all 2p

orbitals of the ring is continuous or nearly continuous.3. 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.

benzene

aromatic

naphthalene

aromatic

cycloheptatriene

non-aromatic

cyclooctatetraene

non-aromatic

hexatriene

non-aromatic

• 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).

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

2,4-D (Weed-B-Gon)Atorvastatin

(Lipitor) (anticholestrol drug)

Dabigatran (anticoagulant)CoQ10 - enzyme in cell organelles

(especially mitochondria) that assistsin ATP (energy) production

Consumer compounds that are aromatic

Nomenclature• When benzene is considered to be the parent ring,

functional groups are indicated with prefixes.

NO2 OC2H5 F C4H9

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

Br

bromobenzenedoes not react viaSN1 or SN2

unstable carbocationno SN1

Br

Nu-

X

backside attack not possibleno SN2

CH2

benzyl bromide is reactive to both SN1 or SN2

stable, delocalized carbocation

Nu-

backside attack possibleno SN2 and stablized by the arene ring

Br

CH2 CH2 Br

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

+.

H O S

O

O

O H H O S

O

O

O H

H O S

O

O

O H O S

O

O

O H

H

S

O

O

O H

• HSO3+ attacks pi electrons in aromatic ring to

create new bond.• Proton on ring is transferred back into solution.

• Sulfonic acids are very acidic (like sulfuric acid). • The conjugate bases (sulfonates) are used in

detergents.

S

O

O

O H

benzenesulfonic acid

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 resonance-stabilized cation intermediate.

• The more stable this cation intermediate, the faster the rate-determining step and the faster the overall reaction.

• -OCH3 is ortho-para directing.

• 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.

• 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).

O

CH3

E

O

CH3

E

O

CH3

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.

O

CH3

O

CH3

E E

O

CH3

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.

• -NO2 is meta directing.

• For meta directors, meta attack forms a more stable cation than ortho-para attack.• Also, meta products are formed faster than ortho-para

products.

• 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.

N N N

O O O O O O

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.

N N

E E

N

E

O O O O O O

• Any resonance or inductive effect for electron-withdrawing 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.

Deactivating Directors

• Halogens: the resonance and inductive effects operate in opposite directions.– The inductive effect: halogens have an electron-

withdrawing 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.

• Generalizations1. Groups which are ortho-para directing.

a. Alkyl groupsb. Phenyl groupsc. Substituents in which the atom bonded to the ring has

an unshared pair of electrons2. 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.

• Vitamin E is a natural antioxidant.

• BHT and BHA are synthetic antioxidants.

• Phenols and related compounds act as antioxidants.