Chapter 15: Benzene and Aromatic Compounds - Key Terms and Reactions

drugs commonly contain

at least one aromatic ring

ex) lipitor

naming monosubstituted benzenes

- "benzene" is parent name

- does not need a number for the substituent

common names for benzene derivatives accepted by the IUPAC

toluene

phenol

benzoic acid

benzaldehyde

naming disubstituted benzenes

- use parent name "xylene

- show different HNMRs

- ortho, meta, or para indicate the relative location of the substituents

ortho-xylene

1,2-dimethylbenzene

meta-xylene

1,3-dimethylbenzene

para-xylene

1,4-dimethylbenzene

substituted benzenes

arene

naming substituted benzenes

1) identify the parent stem, such as "benzene," "phenol," "aniline," etc.

2) name all substituents.

3) number the stem carbons.

4) write the name with the substituents arranged in alphabetical order, each preceded by its locant.

benzene aromaticity

- aromatic compounds associated with fragrant aromas

ex) cinnamaldehyde and vanillan

fragrant compounds from natural sources had unexpected properties

- low H:C ratio

benzene

C6H6

low H:C

unreactive

discovery about benzene in the 1930's

planar with equal C-C bond lengths (x-ray diffraction)

structure of benzene

- all C's are sp2 hybridized

- unhybridized p orbitals

- continuous p orbital overlap

resonance of benzene

- 2 resonance structures with equal contribution to hybrid

- large delocalization energy

heat of hydrogenation of benzene reveals

resonance energy/delocalization energy

- cyclohexatriene (theoretical noninteracting 3 pi bonds) should have a ΔHhyd 3x as large as cyclohexene

- actual ΔHhyd of benzene is lower by -36 kcal/mol at -49 kcal/mol

aromatic compounds are

- cyclic: containing some conjugated π bonds

- every atom contains an unhybridized p orbitals

- planar

- delocalization lowers energy of the system

- Huckel's rule

Huckel's rule

4n+ 2 pi electrons

- n is any integer

- rule in making a structure aromatic

molecular orbital diagram of benzene

- degenerate orbitals: π2 and π3; π4 and π5

- filled bonding orbitals --> closed bonding shell stability

aromatic HNMR

- for benzene: 5 H's multiplet at 7-8 ppm

- H's on C adjacent to ring: 2 H's quartet at 2 to 3 ppm

- H's on terminal methyl group of ethyl substituent: 3 H's triplet at 0-1 ppm

# signals of same substituent, disubstitued para-benzene

HNMR: 1

CNMR: 2

# signals of diff substituent, disubstitued para-benzene

HNMR: 2 dd

CNMR: 4

# signals of diff substituent, disubstitued ortho-benzene

HNMR: 4 dttd

CNMR: 6

# signals of diff substituent, disubstitued meta-benzene

HNMR: 4

CNMR: 6

anti-aromatic compounds

- cyclic: containing some conjugated π bonds

- every atom contains an unhybridized p orbitals

- planar

- delocalization increases E

- 4n π electrons, n=integer

cyclobutadiene

- antiaromatic (4 π e-)

- very reactive

reactivity of cyclobutadiene

diels-alder reaction with itself rapidly (hard to isolate it at room temperature) yields mix of endo and exo products

cyclooctatraene

- nonplanar so nonaromatic

- 4n π e-; n=2

bond angle in cyclooctatraene

- ideal: 120º

- in planar: 135º

angular strain (expansion)

shape of cyclooctatraene

to reduce angle strain, it adopts a tub shape

- loses p orbital overlap

- nonplanar

reactivity of cyclooctatraene (non-aromatic)

behaves like typical alkene

nonaromatic compounds

do not have a continuous ring of overlapping p orbitals and may be nonplanar

[n]-annulenes

higher cyclic, conjugated polyenes where n = # of atoms in the ring

example of aromatic annulene

[14]-annulene

- 4n+2 where n=3

- planar and ok bond angles

[10]-annulene

- 10 π electrons: 4n+2 --> expect aromatic

- nonplanar shape to avoid steric interference of H's so

non-aromatic

frost circle analysis (inscribed polygon method)

represents MO's and can show reactivity for planar, conjugated cyclic systems

- draw the ring inside a circle with a point at the bottom the circle where each point of ring touches the circle

frost circle analysis of benzene

shows closed bonding shell --> explains stability

frost circle analysis of cyclobutadiene

- shows unpaired electrons: diradical character --> very reactive

aromatic ions

huckel's rule applies if charge can be delocalized around the ring

cyclopentadiene

-conjugate base is aromatic

-planar conjugated system with 6 pi electrons

-produces stable free radical

- pKa = 16

cyclopentadiene to form cyclopentadienyl anion

- deprotonate with a base

cyclopentadienyl anion

aromatic anion: closed bonding orbital

- 5 resonance structures

cycloheptatrienyl cation

formed from the nonaromatic cycloheptatriene by radical halogenation followed by SN2

- stabilized by 7 resonance forms

- aromatic: 6 π electrons

1,3,5,7-cyclooctatetraene

- nonplanar

- nonaromatic

how to turn 1,3,5,7-cyclooctatetraene into aromatic?

treat with 2 K⁰ - 2 electron reduction

- produces a planar that is delocalized by resonance

- also produces 2 K+

2π electrons (4n+2, n=0)

aromatic

4π electrons

anti-aromatic

reactive

6π electrons

aromatic

heterocyclic aromatic compounds

aromatic compounds that contain at least one atom other than carbon within the ring

ex) pyridine and imidazole

pyridine

- 6 π electrons = aromatic

- LP is not part of π system bc sp² hybridized

imidazole

- 6 π electrons = aromatic

- LP that can be delocalized in part of π system

- LP not in π system (sp² hybridized) is more basic

electrophilic aromatic substitution

reaction of benzene with EX to substitute a hydrogen for X

5 types of electrophilic aromatic substitution

halogenation

nitration

sulfonation

Friedel-Crafts alkylation

Fridel-Crafts acylation

overall reaction of aromatic halogenation

benzene + AlX₃ + X₂ → X-substituted benzene + HX + AlX₃

reagents of aromatic halogenation

X₂ = Cl₂, Br₂

lewis acid catalyst = AlX₃, FeX₃; X matches the halogen

halogenation of benzene becomes more exothermic as

we proceed from I₂ (endothermic) to F₂ (exothermic and explosive)

step 1 of aromatic halogenation

activation of electrophile

- RDS

- LP from Br₂ undergoes lewis acid-base reaction with AlBr₃ to form an electrophile

step 2 of aromatic halogenation

electrophilic attachment

- pi bond attacks the partial positive Br and AlBr₄ leaves

- forms a resonance stabilized cation: arenium ion/σ complex

step 3 of aromatic halogenation

rearomatization

- the arenium ion undergoes an E1 like process in which AlBr₄ acts as a base and deprotonates it, with the bond to H transferred to the cation

- regenerates the catalyst and completes substitution

energy of aromatic halogenation

exothermic: bonds broken weaker than bonds formed

PE diagram of aromatic halogenation

step 1 of aromatic nitration

activation of electrophile

- LP on oxygen of nitric acid deprotonates H₂SO₄

- OH₂+ is a good leaving group, so LP from oxygen can form another N-O double bond and kick out water

- active electrophile = nitronium

step 2 of aromatic nitration

electrophilic attack

- pi bond attacks the positive N of nitronium, with the N-O pi bond migrating to the oxygen

- forms resonance stabilized cation

step 3 of aromatic nitration

rearomatizaton

- E1 like process in which HSO₄ deprotonates the cation, transferring the bond to the carbocation

- completes the substitution and regenerates catalyst

aniline

benzene with NH2

how to form aniline

react benzene with

1) HNO₃ and H₂SO₄

2) H₂, Pd-C or Fe, HCl

sulfonation overall reaction

benzene + H₂SO₄, SO₃ (8%)

step 1 of sulfonation

- no electrophile activation needed

- fuming sulfuric acid is an active electrophile

step 2 of sulfonation

- slow RDS

- pi bond attacks the SO₃

- forms a arenium ion with resonance

step 3 of sulfonation

- deprotonation by HSO4 regenerates the aromaticity

- protonation of one of the oxygens gives the final product

folic acid biosynthesis

sulfonation reversibility

reversible reaction: hydrolysis

fridel-crafts alkylation overall reaction

benzene reacts with R-X and lewis acid catalyst (AlX3 or FeX3) to form a new carbon-carbon bond and H-X

mechanism of friedel-crafts alkylation (primary haloalkane)

1) activation of the electrophile: halogen of the alkyl halide attacks the AlX3 = slow RDS (lewis A-B) to form an intermediate with carbocation character

2) electrophilic attack on the positively charge R, kicking out AlCl4, forming arenium ion

3) rearomatization (fast and exothermic) through deprotonation, regenerating the catalyst, forming HCl, and the new C-C bond to benzene

scope of friedel-crafts alkylation

1) intramolecular reaction

2) alcohols as precursor

3) alkenes as carbocation precursors

4) epoxide

friedel-crafts alkylation: intramolecular reaction

can be used to fuse a new ring onto the benzene

friedel-crafts alkylation: alcohols as (carbocation) precursor

treating alcohol with BF3 forms a carbocation which can be attacked by the benzene pi bond and deprotonated

friedel-crafts alkylation: alkenes as precursors

treating alkene with H-X can form a carbocation that gets attacked by benzene and deprotonated by the X-

limitations of friedel-crafts alkylation

1) carbocation rearrangements

2) polyalkylation

3) FC rxns do not work on deactivated pi systems

4) vinyl/aryl halides do not work

limitation #1 FC alkylation: carbocation rearrangement

the carbocation formed can undergo rearrangements (alkyl or hydride shifts) to form a more stable carbocation, changing the ratio of major and minor products

FC carbocation rearrangement with primary alkyl halide

incipient primary carbocation rearrangement: simultaneous hydride shift with the leaving group leaving

limitation #2 FC alkylation: polyalkylation

- benzene can be alkylated to form toluene

- toluene is more reactive than benzene because of the added alkyl substituents

limitation #3 FC alkylation does not work on deactivated systems

- electron withdrawing groups (EWGs) slow rxn

limitation #4 FC alkylation does not work with vinyl/aryl halides

- can be done by using a Suzuki (or Heck) reaction

FC acylation is

more useful than alkylation

FC acylation overall reaction

benzene --> ketone

treat benzene with acid chloride, AlCl3 or FeBr3

then perform aqueous workup

mechanism of FC acylation

1) activation of electrophile: acid chloride loses a Cl to AlCl3 to form an acylium ion and AlCl4

2) electrophilic addition: benzene can attack the acylium ion to form a carbocation

3) deprotonation by Cl of AlCl4 forms the ketone and AlCl3

4) aqueous workup after side reaction

side reaction of FC acylation product

- the ketone and AlCl3 can react to produce a product less reaction that benzene (EWG)

- so aqueous workup is necessary to reform the ketone

clemmenson reduction

an alternative to alkylation using FC acylation

- after acylation to form ketone, treat with Zn(Hg) and HCl to form the alkane substituent on benzene