CH 391: 4th Problem Set

# More on Aromatic Substitution

1.  Write the detailed mechanism for the reaction of benzene with a general electrophile (E+). What is the generic name given to the type of intermediate involved in this reaction? Provide three resonance structures for the intermediate, summerize as a DL/PC stucture,  and characterize the intermediate.

2. Since two of the above canonical structures are equivalent and the third is nearly equivalent in energy, what conclusions could be drawn, using resonance theory, concerning the magnitude (qualitatively) of the resonance stabilization?

3.For the rds of this reaction, use resonance theory to derive a TS model, summarize as a DL/PC, and provide a characterization of the TS model. Then, use the Hammond Principle to refine your characterization. Is the resonance stabilization of the TS large or small? What effect would this stabilization, taken alone, have on the reaction rate? In view of this, explain why reactions of electrophiles with benzene are typically slower than with simple alkenes.

4. Adapt the general model to the specific case of nitration. Then use this model to explain why nitration of toluene occurs preferentially at the o, p positions. This will require you to use the method of competing TS’s, i.e., showing the specific DL/PC’s for ortho, meta, and para nitration of toluene, and comparing their characters.

6. Write the detailed mechanism for the base-catalyzed hydration of a carbonyl compound. Explain why the first step is not an rds.

7. Use resonance theory to derive a TS model for the slow step, summarize as a DL/PC,  and characterize this model. Use this model to explain why nucleophilic addition to carbonyl compounds is much more facile than to simple alkenes, even though the carbonyl pi bond is much stronger than the alkene pi bond. You should provide a comparative TS for the alkene addition and provide at least two reasons for the faster addition to carbonyl compounds.

8. Explain why 3-pentanone reacts more slowly than acetone. Why does cyclohexanone react more rapidly than acetone? Would you expect chloroacetone (i.e. chloromethyl methyl ketone) to react more or less rapidly in the hydration reaction? Explain in terms of a TS character.

9. Provide a detailed mechanism for the acid-catalyzed hydration of a general carbonyl compound, and derive and characterize a DL/PC model for the slow step. Explain why electronic effects (EWG’s and EDG’s) are very small in acid-catalyzed hydration.

Ester Hydrolysis.

10. Write the detailed mechanism for the acid-catalyzed hydrolysis of a general ester. What is the overall reaction type? What are the reaction types of each stage of the reaction? Explain how it was experimentally determined that acyl-oxygen rather than alkyl oxygen cleavage typically occurs. How can a direct displacement be ruled out?

11. Give the structure of a specific ester which undergoes alkyl-oxygen cleavage via an S­N1 –like mechanism; via an S­N2 –like mechanism.