23.8 The Elimination-Addition Mechanism of Nucleophilic Aromatic Substitution: Benzyne

Aryl Halides Undergo Substitution When Treated With Very Strong Bases Cl NH 2 KNH 2, NH 3 –33°C (52%)

CH 3 NH 2 new substituent becomes attached to either the carbon that bore the leaving group or the carbon adjacent to it Regiochemistry + NaNH 2, NH 3 –33°C CH 3 Br NH 2

new substituent becomes attached to either the carbon that bore the leaving group or the carbon adjacent to it Regiochemistry CH 3 Br + NaNH 2, NH 3 –33°C CH 3 NH 2 CH 3 NH 2

Regiochemistry + NaNH 2, NH 3 –33°C CH 3 NH 2 CH 3 NH 2 CH 3 NH 2 + CH 3 NH 2

Same result using 14 C label Cl * KNH 2, NH 3 –33°C NH 2 * + * (48%)(52%)

Mechanism NH2NH2NH2NH2 – Step 1 HH H H Cl H

Mechanism NH2NH2NH2NH2 – Step 1 HH H H Cl H HHH H NH2NH2NH2NH2 H Cl – compound formed in this step is called benzyne

Benzyne HHH H Benzyne has a strained triple bond. It cannot be isolated in this reaction, but is formed as a reactive intermediate.

Mechanism NH2NH2NH2NH2 – Step 2 HHH H

Mechanism NH2NH2NH2NH2 – Step 2 HHH H HHH H NH2NH2NH2NH2 – Angle strain is relieved. The two sp-hybridized ring carbons in benzyne become sp 2 hybridized in the resulting anion.

Mechanism Step 3 HHH H NH2NH2NH2NH2 – NH2NH2NH2NH2 H

Mechanism NH2NH2NH2NH2 – Step 3 HHH H NH2NH2NH2NH2 – NH2NH2NH2NH2 H H HHH H NH2NH2NH2NH2

Hydrolysis of Chlorobenzene Cl * NaOH, H 2 O 395°C OHOHOHOH * + OHOHOHOH* (54%)(43%) 14 C labeling indicates that the high- temperature reaction of chlorobenzene with NaOH goes via benzyne.

23.9 Diels-Alder Reactions of Benzyne

Other Routes to Benzyne Benzyne can be prepared as a reactive intermediate by methods other than treatment of chlorobenzene with strong bases. Another method involves loss of fluoride ion from the Grignard reagent of 1-bromo-2- fluorobenzene.

Other Routes to Benzyne BrF Mg, THF heat MgBr F FMgBr +

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

Benzyne as a Dienophile Br F Mg, THF heat + (46%)