1 Chapter 15: Reactions of Substituted Benzenes Learning ...

15.2 Some Substituents Increase the Reactivity of a Benzene Ring and SomeDecrease Its Reactivity* and 15.3 The Effect of Substituents on Orientation(Regioselectivity)*electron donation group (EDG)electron withdrawing group (EWG)EDGEWGA. Relative rate of electrophilic aromatic substitutionExamples:OCH 3 NO 2• Rate-determining step (r.d.s)• Resonance effect and inductive effect3

B. Relative reactivity and regioselectivity of substituted benzenesStrong activating groups (substituents)NH 2OH ORModerate activating groups (substituents)OOHNROR4

Weak activating groups (substituents)RWeak deactivating groups (substituents)F Cl Br I5

Moderate deactivating groups (substituents)O H O R O OR OHNR6

Strong deactivating groups (substituents)SO 3 H NO 2 CN NR 37

(iii)BrCl 2 , FeCl 3(iv)ORBr 2 (1 equivalent)FeCl 3ORBr 2 (excess)FeCl 39

(v)NH 2CH 3 COClAlCl 3OHNRCH 3 COClAlCl 3(vi)ORNO 2HNO 3H 2 SO 4HNO 3H 2 SO 410

(vii) Synthesis of trinitrotolueneCH 3HNO 3H 2 SO 411

15.4 The Effect Substituent on pKaI II III IV V VIOHOHOHOHOHOHOCH 3CH 3ClCHONO 2I II III IV V VICO CO 2 HCO 2 HCO 2 H2 HCO 2 HCO 2 HOCH 3CH 3BrCHONO 2IIIIIINH 3NH 3NH 3IV V VINH 3NH 3OCH CHCHO3 3BrNH 3NO 212

15.7 Designing a Synthesis III: Synthesis of monosubstituted and DisubstitutedBenzenes* and 15.8 Synthesis of Trisubstituted BenzenesDesign multiple-step synthesis:* Selectivity: chemoselectivity, regioselectivity, and stereoselectivity* Retrosynthetic analysis: breaking and formation of chemical bonds13

A. Examples(i)OHfrom14

(ii)OCH 3fromO 2 N(iii)OCH 3fromNO 215

15.9 Synthesis of Substituted Benzenes Using Arenediazonium Salts and 15.11Mechanism for the Reaction of Amines with Nitrous Acid*A. Formation of diazonium saltR NH 20 o CNaNO 2 , HClR N N Cldiazonium saltMechanism:16

B. Reaction of arenediazonium salt with nucleophilesSandmeyer reation (CuBr, CuCl, and CuCN)Reaction with KI, HBF 4 , H 3 O + , and H 3 PO 217

15.10 The Arenediazonium Ion as an Electrophile*NNNu* Nucleophile better be bulky* Terminal nitrogen reacts with nucleophile18

15.12 Nucleophilic Aromatic Substitution Reactions (S N Ar): An Addition-EliminationMechanism*A. Comparison of S N Ar, S N 1, and S N 2B. General mechanism19

C. Examples(i)ClOHOHNO 2NO 2ClOHO 2 NNO 2NO 2ClNO 2NO 2OHOHO 2 NNO 2NO 2OHNO 2NO 2(ii)BrNHCH 2 CH 3NO 2 NO 2CH 3 CH 2 NH 2then OHNO 2 NO 220

15.13 Nucleophilic Aromatic Substitution Reactions: An Elimination-AdditionMechanism That Forms a Benzyne Intermediate21