Table of contents

1. A Review of General Chemistry5h 5m
2. Molecular Representations1h 14m
3. Acids and Bases2h 46m
4. Alkanes and Cycloalkanes4h 17m
5. Chirality3h 39m
6. Thermodynamics and Kinetics1h 22m
7. Substitution Reactions1h 48m
8. Elimination Reactions2h 30m
9. Alkenes and Alkynes2h 9m
10. Addition Reactions3h 19m
11. Radical Reactions1h 58m
12. Alcohols, Ethers, Epoxides and Thiols2h 42m
13. Alcohols and Carbonyl Compounds2h 17m
14. Synthetic Techniques1h 26m
15. Analytical Techniques:IR, NMR, Mass Spect7h 3m
16. Conjugated Systems6h 13m
17. Ultraviolet Spectroscopy51m
18. Aromaticity2h 34m
19. Reactions of Aromatics: EAS and Beyond5h 1m
20. Phenols55m
21. Aldehydes and Ketones: Nucleophilic Addition4h 56m
22. Carboxylic Acid Derivatives: NAS2h 51m
23. The Chemistry of Thioesters, Phophate Ester and Phosphate Anhydrides1h 10m
24. Enolate Chemistry: Reactions at the Alpha-Carbon1h 53m
25. Condensation Chemistry2h 9m
26. Amines1h 43m
27. Heterocycles2h 0m
28. Carbohydrates5h 53m
29. Amino Acids4h 20m
30. Peptides and Proteins2h 42m
31. Catalysis in Organic Reactions1h 30m
32. Lipids 2h 50m
33. The Organic Chemistry of Metabolic Pathways2h 52m
34. Nucleic Acids1h 32m
35. Transition Metals6h 14m
36. Synthetic Polymers1h 49m

19. Reactions of Aromatics: EAS and Beyond

EAS:Retrosynthesis

Organic Chemistry

19. Reactions of Aromatics: EAS and Beyond

EAS:Retrosynthesis

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Problem 83

Textbook Question

Fluoxetine, an antidepressant, is better known as Prozac®. Suggest reagents that could be used to make the indicated C–O bond of fluoxetine. [Note that CF₃, an electron-withdrawing group, is para to where the new bond will be formed.]

Verified step by step guidance

Identify the type of reaction needed to form the C–O bond in fluoxetine. This is typically an ether formation reaction.

Consider the electronic effects of the CF3 group, which is an electron-withdrawing group. This will influence the reactivity of the aromatic ring.

Select a suitable phenol or alcohol that can react with the aromatic ring to form the ether linkage. The presence of the CF3 group suggests that the reaction may require activation.

Choose a reagent that can facilitate the formation of the C–O bond. Common reagents for ether formation include strong bases or catalysts that can activate the alcohol or phenol.

Consider using a method such as the Williamson ether synthesis, which involves the deprotonation of an alcohol to form an alkoxide ion, followed by a nucleophilic substitution reaction with an aryl halide.

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

Nucleophilic Aromatic Substitution

Nucleophilic aromatic substitution (NAS) is a reaction where a nucleophile replaces a leaving group on an aromatic ring. This process is facilitated by electron-withdrawing groups, such as CF3, which stabilize the negative charge in the intermediate. In fluoxetine, the CF3 group is para to the site of substitution, enhancing the reactivity of the aromatic ring towards nucleophiles.

Role of Electron-Withdrawing Groups

Electron-withdrawing groups (EWGs) like CF3 increase the electrophilicity of the aromatic ring by pulling electron density away from it. This makes the ring more susceptible to attack by nucleophiles. In the context of fluoxetine, the CF3 group enhances the likelihood of forming the C–O bond by stabilizing the transition state during the reaction.

Formation of Ether Bonds

The formation of ether bonds typically involves the reaction of an alcohol with an alkyl halide or through the Williamson ether synthesis. In the case of fluoxetine, the formation of the C–O bond can be achieved by using a suitable nucleophile, such as an alkoxide ion, which attacks the electrophilic carbon on the aromatic ring, facilitated by the presence of the CF3 group.

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Textbook Question

Pyrrole undergoes electrophilic aromatic substitution more readily than benzene, and mild reagents and conditions are sufficient. These reactions normally occur at the 2-position rather than the 3-position, as shown in the following example.

a. Propose a mechanism for the acetylation of pyrrole just shown. You may begin with pyrrole and the acylium ion, CH3C≡O+. Be careful to draw all the resonance structures of the intermediate.

Textbook Question

Suggest a synthesis of each of the molecules shown beginning with benzene.

(c)

Textbook Question

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Predict the product(s) of each of the following multistep reactions.

(b)

Open Question

Provide the reaction for each of the following reaction steps

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Beginning from Benzene, synthesize the following compound.