23.823.8

The Elimination-Addition MechanismThe Elimination-Addition Mechanism

of Nucleophilic Aromatic of Nucleophilic Aromatic

Substitution:Substitution:

BenzyneBenzyne

Aryl Halides Undergo Substitution WhenAryl Halides Undergo Substitution WhenTreated With Very Strong BasesTreated With Very Strong Bases

ClCl

NHNH22

KNHKNH22, NH, NH33

––33°C33°C

(52%)(52%)

CHCH33

NHNH22

new substituent becomes attached to eithernew substituent becomes attached to eitherthe carbon that bore the leaving group orthe carbon that bore the leaving group orthe carbon adjacent to itthe carbon adjacent to it

RegiochemistryRegiochemistry

++

NaNHNaNH22,,

NHNH33

––33°C33°C

CHCH33

BrBr

CHCH33

NHNH22

new substituent becomes attached to eithernew substituent becomes attached to eitherthe carbon that bore the leaving group orthe carbon that bore the leaving group orthe carbon adjacent to itthe carbon adjacent to it

RegiochemistryRegiochemistry

CHCH33

BrBr

++NaNHNaNH22, NH, NH33

––33°C33°C

CHCH33

NHNH22

CHCH33

NHNH22

RegiochemistryRegiochemistry

++

NaNHNaNH22, NH, NH33 ––33°C33°C

CHCH33

NHNH22

CHCH33

NHNH22

CHCH33

NHNH22

++

CHCH33

NHNH22

Same result using Same result using 1414C labelC label

ClCl**

KNHKNH22, NH, NH33 ––33°C33°C

NHNH22**++

NHNH22

**

(48%)(48%)(52%)(52%)

MechanismMechanism

•••• NNHH22••••

––

Step 1Step 1Step 1Step 1

HH

HH

•••• ••••

HH

HH

ClCl

HH

••••

MechanismMechanism

•••• NNHH22••••

––

Step 1Step 1Step 1Step 1

HH

HH

•••• ••••

HH

HH

ClCl

HH

••••

HH

HH

HH

HHNNHH22••••

HH

••••••••ClCl••••

••••––

compound formed in this step is called compound formed in this step is called benzynebenzyne

BenzyneBenzyne

HH

HH

HH

HH

Benzyne has a strained triple bond.Benzyne has a strained triple bond.

It cannot be isolated in this reaction, but is It cannot be isolated in this reaction, but is formed as a reactive intermediate.formed as a reactive intermediate.

MechanismMechanism

•••• NNHH22••••

––

Step 2Step 2Step 2Step 2

HH

HH

HH

HH

MechanismMechanism

•••• NNHH22••••

––

Step 2Step 2Step 2Step 2

HH

HH

HH

HH

HH

HH

HH

HH

NNHH22

––••••

••••

Angle strain is relieved. The two Angle strain is relieved. The two spsp-hybridized -hybridized ring carbons in benzyne become ring carbons in benzyne become spsp22 hybridized hybridized in the resulting anion.in the resulting anion.

MechanismMechanism

Step 3Step 3Step 3Step 3

HH

HH

HH

HH

NNHH22

––••••

••••

NNHH22••••

HH

MechanismMechanism

•••• NNHH22••••

––

Step 3Step 3Step 3Step 3

HH

HH

HH

HH

NNHH22

––••••

••••

NNHH22••••

HH

HH

HH

HH

HH

HH NNHH22••••

Hydrolysis of ChlorobenzeneHydrolysis of Chlorobenzene

ClCl**

NaOH, HNaOH, H22OO 395°C395°C

OOHH**++

OOHH

**

(54%)(54%)(43%)(43%)

1414C labeling C labeling indicates that indicates that the high-the high-temperature temperature reaction of reaction of chlorobenzene chlorobenzene with NaOH with NaOH goes via goes via benzyne.benzyne.

23.923.9

Diels-Alder Reactions of BenzyneDiels-Alder Reactions of Benzyne

Other Routes to BenzyneOther Routes to Benzyne

Benzyne can be prepared as a reactive Benzyne can be prepared as a reactive intermediate by methods other than treatment of intermediate by methods other than treatment of chlorobenzene with strong bases.chlorobenzene with strong bases.

Another method involves loss of fluoride ion Another method involves loss of fluoride ion from the Grignard reagent of 1-bromo-2-from the Grignard reagent of 1-bromo-2-fluorobenzene.fluorobenzene.

Other Routes to BenzyneOther Routes to Benzyne

••••

BrBr

FF••••

••••

Mg, THFMg, THF

heatheat ••••

MgMgBrBr

FF••••

••••

FFMgMgBrBr++

Benzyne as a DienophileBenzyne as a Dienophile

Benzyne is a fairly reactive dienophile, and Benzyne is a fairly reactive dienophile, and gives Diels-Alder adducts when generated in gives Diels-Alder adducts when generated in the presence of conjugated dienes.the presence of conjugated dienes.

Benzyne as a DienophileBenzyne as a Dienophile

BrBr

FF

Mg, THFMg, THF

heatheat++

(46%)(46%)