哥伦比亚大学有机化学 23 Aryl Halides (缺23.1-23.7).pptVIP

23.8The Elimination-Addition Mechanismof Nucleophilic Aromatic Substitution:Benzyne Aryl Halides Undergo Substitution WhenTreated With Very Strong Bases Regiochemistry new substituent becomes attached to eitherthe carbon that bore the leaving group orthe carbon adjacent to it Regiochemistry new substituent becomes attached to eitherthe carbon that bore the leaving group orthe carbon adjacent to it Regiochemistry Same result using 14C label Mechanism Mechanism compound formed in this step is called benzyne Benzyne Benzyne has a strained triple bond. It cannot be isolated in this reaction, but is formed as a reactive intermediate. Mechanism Mechanism Angle strain is relieved. The two sp-hybridized ring carbons in benzyne become sp2 hybridized in the resulting anion. Mechanism Mechanism Hydrolysis of Chlorobenzene 14C labeling indicates that the high-temperature reaction of chlorobenzene with NaOH goes via benzyne. 23.9Diels-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 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 Cl NH2 KNH2, NH3 –33°C (52%) CH3 NH2 + NaNH2,NH3 –33°C CH3 Br CH3 NH2 CH3 Br + NaNH2, NH3 –33°C CH3 NH2 CH3 NH2 + NaNH2, NH3 –33°C CH3 NH2 CH3 NH2 CH3 NH2 + CH3 NH2 Cl * KNH2, NH3 –33°C NH2 * + NH2 * (48%) (52%) ?? NH2 ?? – Step 1 H H ?? ?? H H Cl H ?? ?? NH2 ?? – Step 1 H H ?? ?? H H Cl H ?? H H H H NH2 ?? H ?? ?? Cl ?? ?? – H H H H ?? NH2 ?? – Step 2 H H H H ?? NH2 ?? – Step 2 H H H H H H H H NH2 – ?? ?? Step 3 H H H H NH2 – ?? ?? NH2 ?? H ?? NH2 ?? – Step 3 H H H H NH2 – ?? ?? NH2 ?? H H H H H H NH2 ?? Cl * NaOH, H2O 395°C OH * + OH * (54%) (43%) ?? Br F ?? ?? Mg, THF