Chapter 16: Reactions of Substituted BenzenesLearning Objectives:1. Be able to recognize and utilize the oxidative and reductive reactions involving the substituents on benzene.2. Recognize whether a substituent on a benzene ring is activating or deactivating toward electrophilic aromatic substitution reaction, and why it is so.3. Predict the effect a substituent will have on the regioselectivity of an electrophilic substitution reaction.4. Predict the effect a substituent will have on pKa.5. Be able to design the synthesis of a multisubstituted benzene.6. Be able to recognize and utilize the reactions involving arenediazonium salts.7. Recognize and be able to write the mechanism of nucleophilic aromatic substitution.8. Recognize the structure of benzyne, be able to explain how it is formed, and how it reacts.Sections:16.1 Nomenclature of Disubstituted and Polysubstituted Benzenes16.2 Reactions of Substituents on Benzene16.3 The Effect of Substituents on Reactivity*16.4 The Effect of Substituents on Orientation (Regioselectivity)*16.5 The Effect Substituent on pKa16.6 The Ortho-para ratio16.7 Additional Considerations Regarding Substituent Effects16.8 Designing a Synthesis III: Synthesis of monosubstituted and Disubstituted Benzenes*16.9 Synthesis of Trisubstituted Benzenes16.10 Synthesis of Substituted Benzenes Using Arenediazonium Salts*16.11 The Arenediazonium Ion as an Electrophile*16.12 Mechanism for the Reaction of Amines with Nitrous Acid*16.13 Nucleophilic Aromatic Substitution Reactions*16.14 Benzyne16.15 Polycyclic Benzenoid Hydrocarbons#16.16 Electrophilic Substitution Reactions of Naphthalene and Substituted Naphthalene#* Sections that will be focused# Sections that will be skippedRecommended additional problems16.36 – 6.41, 6.43 – 6.55, 6.57 – 6.60, 6.62 – 6.681Class Note16.1 Nomenclature of Disubstituted and Polysubstituted BenzenesBrBrBrNO2NO2H2NBrOHNO2BrClBrNO2ClCH3BrClBrNH2ClBrCH3216.2 Reactions of Substituents on BenzeneA. Reactions of Alkyl SubstituentsNBSperoxideor hBrOHCNtert-BuO3H2, PtNOH2, PtH2, PtB. Oxidations of Alkyl Substituents1. KMnO4, heat (reflux)2. H+Na2Cr2O7, H+, heat4Na2Cr2O7, H+, heatNa2Cr2O7, H+, heatNa2Cr2O7, H+, heatOHMnO2 (no heating needed)OHNa2Cr2O7, H+, heat5C. Reduction of Nitro GroupH2, PtNO2NO2Sn, HClNO2Fe, HCl16.3 The Effect of Substituents on Reactivity and 16.4 The Effect of Substituents on Orientation (Regioselectivity)EDGEWGelectron donation group (EDG)electron withdrawing group (EWG)6A. Relative rate of electrophilic aromatic substitutionExamples:OCH3NO2- Rate-determining step (r.d.s)- Resonance effect and inductive effect7B. Relative reactivity and regioselectivity of substituted benzenesStrong activating groups (substituents)NH2OHORModerate activating groups (substituents)HNOOROR8Weak activating groups (substituents)RWeak deactivating groups (substituents)F Cl Br I9Moderate deactivating groups (substituents)OHOROOROHNR10Strong deactivating groups (substituents)SO3H NO2CN NR311C. Examples (combined with 16.6 The Ortho-para ratio and 16.7 Additional Considerations Regarding Substituent Effects)(i) CH3Br2, FeCl3(ii)CH3HNO3H2SO4CH2CH3HNO3H2SO4C(CH3)3HNO3H2SO412(iii)BrCl2, FeCl3(iv)ORBr2 (1 equivalent) FeCl3ORBr2 (excess) FeCl313(v)NH2HNORCH3COClAlCl3CH3COClAlCl3(vi)ORNO2HNO3H2SO4HNO3H2SO414(vii) Synthesis of trinitrotolueneCH3HNO3H2SO41516.5 The Effect Substituent on pKaOHOHCH3OHOCH3OHCHOOHClOHNO2IIIIII IVVVICO2HCO2HCH3CO2HOCH3CO2HCHOCO2HBrCO2HNO2IIIIII IVVVINH3NH3CH3NH3OCH3NH3CHONH3BrNH3NO2IIIIIIIVVVI1616.8 Designing a Synthesis III: Synthesis of monosubstituted and Disubstituted Benzenes and 16.9 Synthesis of Trisubstituted BenzenesDesign multiple-step synthesis: * Selectivity: chemoselectivity, regioselectivity, and stereoselectivity* Retrosynthetic analysis: breaking and formation of chemical bonds17A. Examples(i)fromOH18(ii)fromCH3OO2N(iii)fromCH3NO2O1916.12 Mechanism for the Reaction of Amines with Nitrous Acid and 16.10 Synthesis of Substituted Benzenes Using Arenediazonium SaltsA. Formation of diazonium saltR NH2NaNO2, HCl0oCR N N Cldiazonium saltMechanism:20B. Reaction of arenediazonium salt with nucleophilesSandmeyer reation (CuBr, CuCl, and CuCN)Reaction with KI, HBF4, H3O+, and H3PO22116.11 The Arenediazonium Ion as an ElectrophileNNNu* Nucleophile better be bulky* Terminal nitrogen reacts with nucleophile2216.13 Nucleophilic Aromatic Substitution (SNAr) ReactionsA. Comparison of SNAr, SN1, and SN2B. General mechanism23C. Examples(i)ClNO2ClNO2ClNO2NO2NO2O2NOHOHOHOHNO2OHNO2OHNO2NO2NO2O2N(ii)BrNO2NO2NHCH2CH3NO2NO2CH3CH2NH2then OH2416.14