Reactions and Substituent Effects on Benzenes: A Comprehensive Guide, Study notes of Chemistry

Download Reactions and Substituent Effects on Benzenes: A Comprehensive Guide and more Study notes Chemistry in PDF only on Docsity! 1 Chapter 16: Reactions of Substituted Benzenes Learning 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 Benzenes 16.2 Reactions of Substituents on Benzene 16.3 The Effect of Substituents on Reactivity* 16.4 The Effect of Substituents on Orientation (Regioselectivity)* 16.5 The Effect Substituent on pKa 16.6 The Ortho-para ratio 16.7 Additional Considerations Regarding Substituent Effects 16.8 Designing a Synthesis III: Synthesis of monosubstituted and Disubstituted Benzenes* 16.9 Synthesis of Trisubstituted Benzenes 16.10 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 Benzyne 16.15 Polycyclic Benzenoid Hydrocarbons # 16.16 Electrophilic Substitution Reactions of Naphthalene and Substituted Naphthalene # * Sections that will be focused # Sections that will be skipped Recommended additional problems 16.36 – 6.41, 6.43 – 6.55, 6.57 – 6.60, 6.62 – 6.68 2 Class Note 16.1 Nomenclature of Disubstituted and Polysubstituted Benzenes Br Br Br NO2 NO2 H2N Br OH NO2 Br Cl Br NO2 Cl CH3 Br Cl Br NH2 Cl Br CH3 5 Na2Cr2O7, H +, heat Na2Cr2O7, H +, heat Na2Cr2O7, H +, heat OH MnO2 (no heating needed) OH Na2Cr2O7, H +, heat 6 C. Reduction of Nitro Group H2, PtNO2 NO2 Sn, HCl NO2 Fe, HCl 16.3 The Effect of Substituents on Reactivity and 16.4 The Effect of Substituents on Orientation (Regioselectivity) EDG EWG electron donation group (EDG) electron withdrawing group (EWG) 7 A. Relative rate of electrophilic aromatic substitution Examples: OCH3 NO2 • Rate-determining step (r.d.s) • Resonance effect and inductive effect 10 Moderate deactivating groups (substituents) O H O R O OR O H N R 11 Strong deactivating groups (substituents) SO3H NO2 CN NR3 12 C. Examples (combined with 16.6 The Ortho-para ratio and 16.7 Additional Considerations Regarding Substituent Effects) (i) CH3 Br2, FeCl3 (ii) CH3 HNO3 H2SO4 CH2CH3 HNO3 H2SO4 C(CH3)3 HNO3 H2SO4 (vii) Synthesis of trinitrotoluene GH HNO 3 H)SO, ————> 1S  16 16.5 The Effect Substituent on pKa OHOH CH3 OH OCH3 OH CHO OH Cl OH NO2 I II III IV V VI CO2HCO2H CH3 CO2H OCH3 CO2H CHO CO2H Br CO2H NO2 I II III IV V VI NH3 NH3 CH3 NH3 OCH3 NH3 CHO NH3 Br NH3 NO2 I II III IV V VI 17 16.8 Designing a Synthesis III: Synthesis of monosubstituted and Disubstituted Benzenes and 16.9 Synthesis of Trisubstituted Benzenes Design multiple-step synthesis: * Selectivity: chemoselectivity, regioselectivity, and stereoselectivity * Retrosynthetic analysis: breaking and formation of chemical bonds 20 16.12 Mechanism for the Reaction of Amines with Nitrous Acid and 16.10 Synthesis of Substituted Benzenes Using Arenediazonium Salts A. Formation of diazonium salt R NH2 NaNO2, HCl 0oC R N N Cl diazonium salt Mechanism: 21 B. Reaction of arenediazonium salt with nucleophiles Sandmeyer reation (CuBr, CuCl, and CuCN) Reaction with KI, HBF4, H3O + , and H3PO2 22 16.11 The Arenediazonium Ion as an Electrophile N N Nu * Nucleophile better be bulky * Terminal nitrogen reacts with nucleophile