Ch. 23 - Benzene I: Aromatic Stability and Substitution Reactions

Mullins - Organic Chemistry: A Learner Centered Approach 1st Edition

Mullins1st EditionOrganic Chemistry: A Learner Centered ApproachISBN: 9780137566471Not the one you use?Change textbook

Mullins 1st Edition

Ch. 23 - Benzene I: Aromatic Stability and Substitution Reactions

Problem 83

Chapter 22, Problem 83

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.

Verified video answer for a similar problem:

This video solution was recommended by our tutors as helpful for the problem above.

Was this helpful?

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.

Recommended video:

2:01

Disulfide Bonds Concept 1

Related Practice

Textbook Question

Protonation of aniline slows electrophilic aromatic substitution and directs electrophiles to the meta position. Why?

views

Textbook Question

How might you use ¹³C NMR spectroscopy to differentiate between the possible ortho, meta, and para products of the electrophilic aromatic substitution reaction shown?

views

Textbook Question

Would you expect chlorination to occur ortho, para, or meta to the pyridinium ion in the following molecule? Explain your answer.

views

Textbook Question

Indigo is a dye that was originally isolated from coal tar. In 1905, Johann Friedrich Wilhelm Adolf von Baeyer won a Nobel Prize for a method that allowed indigo to be isolated from plants [a green chemist ahead of his time.] If you nitrated indigo using the reaction learned in this chapter, at which carbon would you expect the nitro group to attach?

views

Textbook Question

Addition by the benzyne mechanism is not usually regioselective. Explain the fact that the reaction shown is highly regioselective for the product shown.

Textbook Question

Acetohexamide is used to treat type 2 diabetes that cannot be well controlled by diet alone. Fill in the blanks of the synthetic scheme used to synthesize acetohexamide. [Hints have been provided below each step.]

views

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 video answer for a similar problem:

Key Concepts

Nucleophilic Aromatic Substitution

Role of Electron-Withdrawing Groups

Formation of Ether Bonds

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.]