Chemistry 234 Chapter 16 Problem Set Electrophilic Aromatic Substitution 1) Predict the product and draw the mechanism for electrophile generation for each of the following reactions. Cl (a) 2 FeCl3 HNO3 (b) H2SO4 SO (c) 3 H2SO4 2) Explain why reaction of benzene with Br2/FeBr3 results in the product bromobenzne instead of 5,6-dibromo-1,3-cyclohexadiene. 3) Predict the product and draw the active electrophile for each reaction shown below. Cl (a) AlCl3 Cl (b) AlCl3 Cl O (c) AlCl3 Page 1 of 13 Chem. 234 – Chapter 16 Problem Set 4) Explain why each of the following substrates do not undergo Freidel-Crafts reactions. NH2 NO2 N(CH3)3 NH 5) Arrange the following benzene substituents in order of reactivity in electrophilic aromatic substitution reactions. O Cl Ph Ph N Ph Ph H O N H S Ph N Ph Ph Ph O O 6) Predict the maJor products when the following benzene derivatives are treated to nitration conditions (HNO3/H2SO4). a. O Br b. NH2 Br c. NO2 Cl 7) Write the full electron pushing mechanism for the nitration of toluene. Page 2 of 13 Chem. 234 – Chapter 16 Problem Set 8) Predict the product(s) when each of the following benzene derivatives is treated to chloroethane and AlCl3. a. Br b. NH2 Cl c. OH Br d. OH Cl Cl e. NO2 Cl Cl f. Br Br g. SO3H Page 3 of 13 Chem. 234 – Chapter 16 Problem Set 9) Predict the product(s) when the following benzene derivatives are subjected to electrophilic chlorination conditions (Cl2, FeCl3). a. NO2 O OH b. OH NO2 c. d. SO3H Br 10) Predict the product(s) for each of the following reactions. a. O Br O Cl2 H3CO OCH3 FeCl3 b. HNO3 H2SO4 OCH3 c. SO3 H2SO4 d. HO SO3 H2SO4 Br NO2 Page 4 of 13 Chem. 234 – Chapter 16 Problem Set 11) Predict the product for each benzene side-chain modification reaction shown below. a. KMnO4 b. H2CrO4 c. NBS light d. NO2 H2 Pd/C e. NO2 Sn HCl f. O Zn(Hg) HCl g. O N2H2 HO- 12) Propose a synthesis for each of the following compounds starting with benzene. a. COOH NO2 COOH Page 5 of 13 Chem. 234 – Chapter 16 Problem Set b. NH2 Cl c. Cl Br NO2 d. O NO2 Cl e. COOH Cl NO2 Br Page 6 of 13 Chem. 234 – Chapter 16 Problem Set f. Cl NO2 O g. Br O2N Diazonium Ion Reactions 13) Write out the synthetic sequence to prepare phenol and acetanilide (Ph-NHCOCH3) from benzene. Page 7 of 13 Chem. 234 – Chapter 16 Problem Set 14) Provide syntheses for each of the following compounds, free of other isomers. Your starting material should be benzene in each case. a. Br OH b. I Cl c. F Br Br Page 8 of 13 Chem. 234 – Chapter 16 Problem Set d. NC Nucleophilic Aromatic Substitution 15) For each reaction shown below, determine if the reaction is (a) electrophilic aromatic substitution, (b) Nucleophilic Aromatic Substitution: Addition-Elimination, or (c) Nucleophilic Aromatic Substitution: Benzyne Mechanism. Cl NaOH a. 350 °C Cl NaNH2 b. NH3 Cl H C NaNH c. 3 2 NH3 Cl d. NaOH NO2 Cl HNO3 e. H2SO4 Br NO2 NaOCH3 f. NO2 Page 9 of 13 Chem. 234 – Chapter 16 Problem Set 16) Show the full electron pushing mechanism for reaction 15c. 17) Show the full electron pushing mechanism for reaction 15d. 18) Explain why the reaction shown below does not occur. Cl OH NaOH Heat O2N NO2 O2N NO2 19) Consider the reaction shown below. Theoretically, there are three possible products. Draw each of these products. In reality only one of these products is formed. Which one is the observed product? Cl Cl OCH3 NO2 Page 10 of 13 Chem. 234 – Chapter 16 Problem Set 20) Show two methods to synthesize the molecule shown below starting with benzene. One route should use diazonium ion chemistry while the other route should not. NO2 OH 21) Show the reaction of phenol with NaOH. 22) Show the reaction of benzoic acid with NaOH. 23) Is phenol or benzoic acid a stronger acid? Explain. 24) Show the reaction of aniline with HCl. Page 11 of 13 Chem. 234 – Chapter 16 Problem Set 25) Rank the compounds in each set below in order of increasing acidity. Br O O NH2 OH (a) OH OH NO OH 2 OH O N OH OH 2 (b) 26) Rank the aniline derivatives below in order of increasing basicity. NH 2 NH 2 NH2 NH2 O2N O O Challenge Problems 27) Write a mechanism for the following reaction. Cl O H H HCl Page 12 of 13 Chem. 234 – Chapter 16 Problem Set 28) Predict the maJor product for the reaction of pyrrole with Br2, FeBr3. Hint: use resonance analysis of the intermediate to determine the preferred regioselectivity of the reaction. H N Br2 FeBr3 29) Show the electron pushing mechanism for the reaction shown below. OH NaH NO2 O SO2 NO2 SO2 30) Substituted pyridines are known to undergo nucleophilic aromatic substitution via an addition elimination mechanism. Predict the product and show the mechanism for the reaction shown below. OH N Br Page 13 of 13 .