厦门大学化学化工学院：《有机化学》课程教学资源（课件讲稿，双语版）第二十一章 酚和芳香卤代烃：芳香亲核取代反应（21.11-21.12）

ORGANIC CHEMISTRY Chapter 21 21 11 Aryl Halide and nucleophilic Aromatic substitution Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 21 21.11 Aryl Halide and Nucleophilic Aromatic Substitution

ORGANIC CHEMISTRY Chapter 21 o Simple aryl halides are much less reactive than alkyl halides in nucleophilic substitution reactions HO t Naoh no substitution reflux o The c-X bonds of aryl halides are stronger and shorter than those of alkyl halides g aryl cations are very unstable sl do not occur The optimal transition-state geometry required for SN2 processes cannot be achieved no reaction Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 21 Simple aryl halides are much less reactive than alkyl halides in nucleophilic substitution reactions. Cl + NaOH H2O reflux no substitution The C–X bonds of aryl halides are stronger and shorter than those of alkyl halides. Aryl cations are very unstable. SN1 do not occur. The optimal transition-state geometry required for SN2 processes cannot be achieved. Nu X × no reaction

ORGANIC CHEMISTRY Chapter 21 21 11A Nucleophilic Aromatic Substitution by addition-Elimination The Sar mechanism o Nucleophilic substitution can occur when strong electron-withdrawing groups are ortho or para to the halogen atom NO-NO2一CF3=CRCN CO2H -SO3 Br -I-CO2 -C6H5 Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 21 21.11A Nucleophilic Aromatic Substitution by Addition-Elimination: The SNAr Mechanism Nucleophilic substitution can occur when strong electron-withdrawing groups are ortho or para to the halogen atom. N2 N NO NO2 CO2H CF3 CR CN O SO3 Cl Br I CO2 C6H5

ORGANIC CHEMISTRY Chapter 21 C OH 10% NaOH pressur,135~160℃ NO NO NO? Na, CO3, H,O NO 100℃ NO 2 NO 2 CI OH NO NO HO 35°C NO NO Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 21 pressur, 135~160℃ Cl OH NO2 10% NaOH NO2 H+ 100℃ Cl OH NO2 Na2CO3, H2O NO2 NO2 NO2 H+ Cl NO2 O2N NO2 OH NO2 O2N NO2 H2O H+ 35°C

ORGANIC CHEMISTRY Chapter 21 Mechanism u A slow ast +N ddition imination O O O u N N u 00000O-OO Addition-elimination mechanism(加成一消除机制) Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 21 Mechanism Mechanism L N O O + Nu slow L N O O Nu Nu N O O fast addition elimination L N O O Nu L N O O Nu L N O O Nu L N O O Nu Addition-elimination mechanism (加成－消除 机制)

ORGANIC CHEMISTRY Chapter 21 21 11B Nucleophilic Aromatic Substitution through an Elimination-Addition Mechanism: Benzyne o Chlorobenzene can be converted to phenol by heating it with aqueous naoh in a pressurized reactor at 350C o Bromobenzene reacts with KnH, in liquid ammonia OH 10%NaoH Cu H20 350℃.28MPa Br NH 2 NH +KNH-33°C Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 21 21.11B Nucleophilic Aromatic Substitution through an Elimination-Addition Mechanism: Benzyne Chlorobenzene can be converted to phenol by heating it with aqueous NaOH in a pressurized reactor at 350°C. Bromobenzene reacts with KNH2 in liquid ammonia. Cl 10%NaOH , Cu 350℃ , 28MPa OH H3O+ Br + KNH2 NH3 33°C NH2

ORGANIC CHEMISTRY Chapter 21 o 2-1odo-1, 3-dimethylbenzene do not react with nanh, CH NCH3 NaNH no substitution NH3(O 2-lodo-1, 3-dimethy benzene o p-Chlorotoluene reacts with nanh, to yield a mixture of p-and m-toluidine CH CH NanH, NH NH 2 p-Chlorotoluene p-Toluidine m-toluidine Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 21 2-Iodo-1,3-dimethylbenzene do not react with NaNH2: p-Chlorotoluene reacts with NaNH2 to yield a mixture of p- and m-toluidine: I CH3 CH3 NH3(l) NaNH2 no substitution 2-Iodo-1,3-dimethylbenzene CH3 Cl CH3 NH2 NH3(l) CH3 NH2 + NaNH2 p-Chlorotoluene p-Toluidine m-Toluidine

ORGANIC CHEMISTRY Chapter 21 Mechanism o These reaction take place through an elimination- addition mechanism that involves the formation of an intermediate called benzyne +1NH2 H Elimination Benzyne NH NH3 NH NH3 H nH2 Addition Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 21 Mechanism Mechanism These reaction take place through an elimination￾addition mechanism that involves the formation of an intermediate called benzyne. Cl H Cl + NH2 Elimination Benzyne + NH2 NH2 NH2 NH3 H+ NH3 Addition

ORGANIC CHEMISTRY Chapter 21 Benzyne The first piece of clear-cut evidence was an experiment done by j d. Roberts in 1953 Br NH2 米NH KNH2 NH 2 (50%)(50%) Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 21 Benzyne SP2 The first piece of clear-cut evidence was an experiment done by J. D. Roberts in 1953. Br KNH2 * * NH2- NH2 * * NH2 + (50%) (50%)

ORGANIC CHEMISTRY Chapter 21 o Benzyne intermediates have been "trapped" though the use of Diels-Alder reactions COH C-0 ch3 (ch2)4ONO CHoC NH2 CO O Br KNH2 Department of Chemistry, Xiamen University

ORGANIC CHEMISTRY Department of Chemistry, Xiamen University Chapter 21 Benzyne intermediates have been “trapped” though the use of Diels-Alder reactions. CO2H NH2 + CH3(CH2)4ONO H+ CH2Cl2 C N2+ O O CO2 N2 O O Br KNH2 * O O * *