Aromatic Compounds 2

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Questions and Answers

What is the primary electrophile in Friedel-Crafts alkylation?

Halide ion

Carbocation (R+) (correct)

Benzene derivative

Acylium ion

Which reagent is necessary for the nitration of benzene?

SO3

RCl

HNO3 (correct)

FeBr3

What is the main characteristic feature of the arenium ion during electrophilic substitution?

It directly converts to the final product without any further loss.

It has an increased positive charge on the benzene ring. (correct)

It forms after the loss of a proton.

It retains a full aromatic structure.

Which reaction represents Friedel-Crafts acylation?

RCOCl + AlCl3 → RCO+ + HCl Signup and view all the answers

What is the role of AlCl3 in Friedel-Crafts reactions?

Catalyst Signup and view all the answers

In what type of substitution reaction is the formation of a σ-complex critical?

Electrophilic substitution Signup and view all the answers

What is the purpose of using H2SO4 in the nitration reaction of benzene?

To increase the yield of nitronium ion Signup and view all the answers

What type of compound is typically produced in a Friedel-Crafts alkylation?

Aromatic hydrocarbon Signup and view all the answers

What is the initial step in the Friedel-Crafts alkylation mechanism for tertiary alkyl halides?

Formation of carbocation Signup and view all the answers

What is the primary product of the Friedel-Crafts acylation reaction?

Ketone Signup and view all the answers

In the context of Friedel-Crafts alkylation, how does the mechanism differ for primary alkyl halides compared to tertiary ones?

An electrophilic complex is formed. Signup and view all the answers

Why is the acylium ion more stable than a primary carbocation during a Friedel-Crafts acylation?

It has resonance stabilization. Signup and view all the answers

Which ion is formed during the Friedel-Crafts alkylation process after the loss of a proton from the arenium ion?

AlCl4- Signup and view all the answers

What is the main electrophile in the nitration of benzene?

Nitronium ion (NO2+) Signup and view all the answers

Which component acts as the electrophile in the Friedel-Crafts alkylation mechanism when a primary alkyl halide is used?

Electrophilic complex of alkyl halide and AlCl3 Signup and view all the answers

In Friedel-Crafts reactions, what is a potential issue when using overly reactive alkyl halides?

The reaction may yield multiple products Signup and view all the answers

What role does the π electron cloud play in electrophilic aromatic substitution?

It actively participates in the formation of the σ-bond with the electrophile. Signup and view all the answers

Which of the following statements about acylium ions is true?

They serve as strong electrophiles in acylation. Signup and view all the answers

Which substituent would most likely activate a benzene ring toward electrophilic substitution reactions?

Alkyl group (-R) Signup and view all the answers

What type of reaction mechanism is involved in the halogenation of benzene?

Electrophilic substitution Signup and view all the answers

Which of the following is a necessary condition for the halogenation of benzene?

An acid catalyst Signup and view all the answers

What is a common characteristic of electrophilic substitution reactions in aromatic compounds?

Regeneration of the aromaticity after the reaction Signup and view all the answers

During the electrophilic aromatic substitution mechanism, what intermediate is formed prior to regeneration of the aromatic π system?

Non-aromatic carbocation (arenium ion) Signup and view all the answers

What is the effect of strongly deactivating groups on the rate of electrophilic substitution of benzene?

They slow down or inhibit the reaction. Signup and view all the answers

What types of reagents can be substituted for alkyl halides in Friedel-Crafts alkylation?

Reagents such as alkenes mixed with Brønsted acids or alcohols with Lewis acids can be used. Signup and view all the answers

What factors limit the effectiveness of Friedel-Crafts alkylation reactions?

Aryl and vinyl halides, strong electron-withdrawing substituents, and the presence of amino groups limit the reactions. Signup and view all the answers

What is a potential outcome of using a primary alkyl halide in Friedel-Crafts alkylation?

The primary alkyl halide-AlCl3 complex may undergo rearrangement to form a more stable secondary carbocation. Signup and view all the answers

Can Friedel-Crafts alkylation produce multiple alkylation products? If so, explain why.

Yes, multiple substitutions can occur due to the reactivity of carbocations formed during the process. Signup and view all the answers

How does the use of different acids affect the outcomes of Friedel-Crafts alkylation?

Using different acids can generate varied carbocation species, influencing the selectivity and efficiency of the alkylation. Signup and view all the answers

What stabilizes benzene's special stability during electrophilic substitution reactions?

The closed shell molecular orbital configuration of six π electrons stabilizes benzene's structure during electrophilic substitution. Signup and view all the answers

Explain the role of the π electron cloud in the electrophilic substitution of benzene.

The π electron cloud acts as a source of electrons that can be donated to electrophiles during the substitution reaction. Signup and view all the answers

Describe the nature of the intermediate formed during electrophilic substitution of benzene.

The intermediate formed is a delocalized, non-aromatic carbocation known as an arenium ion or σ-complex. Signup and view all the answers

What distinguishes an arene from a phenyl group?

An arene is an aromatic hydrocarbon containing a benzene ring, while a phenyl group is a benzene ring with one hydrogen atom removed. Signup and view all the answers

Why do electrophilic substitutions generally occur instead of addition reactions in benzene?

Electrophilic substitutions occur instead of addition reactions because they allow the aromatic sextet of π electrons to be regenerated. Signup and view all the answers

What occurs to the hydrogen atom during electrophilic substitution of benzene?

The electrophile replaces one of the hydrogen atoms on the benzene ring during the substitution reaction. Signup and view all the answers

What happens to the stability of the arenium ion compared to benzene?

The arenium ion is less stable than benzene due to the loss of aromaticity. Signup and view all the answers

What characteristic feature of electrophiles allows them to react with benzene?

Electrophiles are electron-loving species, making them attracted to the electron-rich π system of benzene. Signup and view all the answers

Explain the role of AlCl3 in Friedel-Crafts acylation.

AlCl3 acts as a Lewis acid that facilitates the generation of the acylium ion from acyl chloride, allowing it to react with benzene. Signup and view all the answers

Why does poly-acylation not occur in Friedel-Crafts acylation?

The electron-withdrawing properties of the acyl group deactivate the substituted benzene ring, preventing further electrophilic substitution. Signup and view all the answers

Describe the first step of the Friedel-Crafts acylation mechanism.

The first step involves the generation of the acylium ion, where the acyl chloride reacts with AlCl3 to form an acylium cation and AlCl4-. Signup and view all the answers

How does the introduction of an acylium ion affect a benzene ring's reactivity?

The introduction of an acylium ion decreases the reactivity of the benzene ring towards further electrophilic substitutions due to the electron-withdrawing nature of the acyl group. Signup and view all the answers

What are the products formed when benzene reacts with acetyl chloride in the presence of AlCl3?

The reaction produces acetophenone and HCl as byproducts. Signup and view all the answers

Explain why rearrangements of the acylium ion do not occur during Friedel-Crafts acylation.

Rearrangements do not occur because the acylium ion is resonance stabilized, which makes it less prone to structural changes. Signup and view all the answers

What is the significance of the reaction temperature in Friedel-Crafts acylation?

The reaction temperature, typically around 80 °C, aids in promoting the reaction rate and facilitating the reaction between benzene and the acylium cation. Signup and view all the answers

Discuss the protonation step that follows the formation of the acyl group during Friedel-Crafts acylation.

After the electrophilic substitution, a protonation step occurs where the arenium ion loses a proton, regenerating the aromatic ring and completing the reaction. Signup and view all the answers

What is the first step in the Friedel-Crafts alkylation mechanism for tertiary alkyl halides?

The first step involves the formation of a carbocation when the alkyl halide reacts with AlCl3. Signup and view all the answers

How does the formation of a complex differ in the Friedel-Crafts alkylation mechanism for primary alkyl halides?

For primary alkyl halides, AlCl3 forms a complex with the alkyl halide, acting as the electrophile instead of forming a carbocation. Signup and view all the answers

What happens during the second step of Friedel-Crafts alkylation involving the arenium ion?

An arenium ion is formed after the electrophile attaches to the aromatic ring, creating a positively charged intermediate. Signup and view all the answers

What is the outcome of the third step in the Friedel-Crafts alkylation process?

The loss of a proton from the arenium ion results in the regeneration of the aromatic system and the formation of the product. Signup and view all the answers

In Friedel-Crafts alkylation, what is a potential drawback when using very reactive alkyl halides?

Using overly reactive alkyl halides can lead to polysubstitution, where multiple alkyl groups may attach to the aromatic ring. Signup and view all the answers

Why is the carbocation generated in Friedel-Crafts alkylation important for the reaction?

The carbocation acts as the electrophile that attacks the aromatic ring, initiating the electrophilic substitution process. Signup and view all the answers

What type of ion is formed after the loss of a proton from the arenium ion during Friedel-Crafts alkylation?

A neutral aromatic product is formed after the arenium ion loses a proton. Signup and view all the answers

Explain how the role of AlCl3 in Friedel-Crafts reactions impacts the formation of the electrophile.

AlCl3 facilitates the ionization of alkyl halides, generating a carbocation that serves as the electrophile for the reaction. Signup and view all the answers

Why is the AlCl3-Friedel Crafts complex for primary alkyl halides not a simple carbocation?

The complex formed is not a simple carbocation because it involves a bonding interaction between the alkyl halide and AlCl3. Signup and view all the answers

What role does the arenium ion play in the Friedel-Crafts alkylation mechanism?

The arenium ion acts as a key intermediate that undergoes deprotonation to yield the final alkylated aromatic product. Signup and view all the answers

What potential issues can arise from using highly reactive alkyl halides in Friedel-Crafts alkylation?

Using highly reactive alkyl halides can lead to polysubstitution, where multiple alkyl groups attach to the aromatic ring, reducing selectivity. Signup and view all the answers

Describe the significance of the arenium ion in the context of electrophilic substitution reactions.

The arenium ion is a critical intermediate that temporarily stabilizes the system before regeneration of the aromaticity of the benzene ring. Signup and view all the answers

How do the mechanisms of Friedel-Crafts alkylation differ for primary and tertiary alkyl halides?

Tertiary alkyl halides form more stable carbocations and react faster, while primary alkyl halides can lead to carbocation rearrangements or slower reactions. Signup and view all the answers

In the context of electrophilic aromatic substitution, what is the importance of the σ-complex?

The σ-complex is an essential intermediate that illustrates the temporary loss of aromatic character and the formation of a cyclohexadiene-like structure. Signup and view all the answers

What role does FeCl3 play in the halogenation of benzene?

FeCl3 acts as a Lewis acid catalyst that facilitates the generation of the electrophile (halo cation) during the halogenation process. Signup and view all the answers

What is the effect of substituents that deactivate a benzene ring on electrophilic substitution reactions?

Deactivating substituents slow down the rate of electrophilic substitution, making the ring less reactive toward electrophiles. Signup and view all the answers

Explain why I2 requires an oxidizing agent for the iodination of benzene.

I2 is unreactive with benzene under normal conditions, so it needs an oxidizing agent like HNO3 to generate an effective electrophile for the reaction. Signup and view all the answers

What distinguishes Friedel-Crafts acylation from alkylation in terms of the generated electrophile?

Friedel-Crafts acylation utilizes an acylium ion as the electrophile, which is generally more stable than the carbocation used in alkylation. Signup and view all the answers

Describe the role of H2SO4 in the nitration of benzene.

H2SO4 increases the concentration of the nitronium ion (NO2+), which is the electrophile in the nitration reaction, thereby speeding up the reaction. Signup and view all the answers

What mechanism is involved in the formation of the arenium ion during electrophilic aromatic substitution?

The arenium ion is formed when the benzene ring attacks the electrophile, leading to a temporary loss of aromaticity. Signup and view all the answers

Identify the key steps involved in the electrophilic attack during the halogenation of benzene.

The key steps involve the formation of the halo cation and the subsequent electrophilic attack on the benzene ring, resulting in the arenium ion. Signup and view all the answers

What is the final product when benzene undergoes nitration with concentrated HNO3 and H2SO4?

The final product is nitrobenzene, which results from the electrophilic substitution of a nitro group onto the benzene ring. Signup and view all the answers

Why does fluorination of benzene require special conditions?

Fluorination is highly reactive due to the strength of the F-F bond, necessitating controlled conditions to manage the reaction. Signup and view all the answers

What illustrates the difference in reactivity between bromination and iodination of benzene?

Bromination occurs readily with a Lewis acid, while iodination requires an oxidizing agent due to the low reactivity of I2. Signup and view all the answers

Study Notes

Pharmaceutical Chemistry - Aromatic Compounds (Lecture 2)

Arenes: Aromatic hydrocarbons are called arenes.
Phenyl Group: A benzene ring with one hydrogen atom removed (C₆H₅−) is the phenyl group, denoted by Ph−.
Aryl Group: Aromatic hydrocarbons with one removed hydrogen atom are aryl groups, designated by Ar−. These are substituted benzene rings.
Electrophile: Electron-loving or electron-deficient species. Example: +C(CH₃)₃ (tertiary carbocation)
Electrophilic Substitution of Benzene: An electrophile (E+) reacts with a benzene ring and replaces a hydrogen atom. Benzene's stable closed-shell MO configuration of six π electrons allows substitution reactions over addition reactions.
Mechanism of Electrophilic Substitution:
- Step 1: Electrophile takes two electrons from the six π electron system forming a σ bond with a carbon atom. This forms an arenium ion (σ-complex) that is non-aromatic.
- Step 2: The arenium ion loses a proton from the carbon atom with the electrophile. This regenerates the aromatic ring's six π electrons.

Friedel-Crafts Alkylation

Development: Developed in 1877 by Charles Friedel and James Crafts.
Electrophile: The carbocation, R+. This carbocation forms from the ionization of RX with an aluminum chloride catalyst.
Reaction: An electrophilic aromatic substitution reaction where the electrophile is a carbocation. Example RX = isopropyl chloride.
Mechanism Steps:
- Step 1: Formation of the carbocation: Example: AICI₃ reacting with tert-butyl chloride to form tert-butyl-cations.
- Step 2: Formation of the arenium ion: The carbocation attacks the benzene ring and forms a temporary non-aromatic structure.
- Step 3: Loss of proton and regneration of the aromatic ring: The arenium ion loses proton and the ring is reformed.

Friedel-Crafts Alkylation - Mechanism for Primary Alkyl Halides

Difference to tertiary: In primary alkyl halide reactions, the AICI₃ forms a complex with the alkyl halide. This complex acts as the electrophile.
Electrophilic attack: The complex transfers a positive alkyl group to the aromatic ring.

Examples of Friedel-Crafts Alkylation

Alkenes and Broonsted acids: Alkene mixed with Brønsted Acid forms the electrophile needed for substitution. Example: Propane (CH₃CH=CH₂) with Hydrogen Fluoride (HF).
Aromatics and Lewis acids: An alcohol (for example: cyclohexanol) reacts with a Lewis acid (for example: BF₃) to form an electrophile, enabling substitution.

Limitations to Friedel-Crafts Alkylation

Aromatic/Vinyl/Alkyl halides: Aromatic, alkyl, and vinyl halides do not work for the reaction.
Electron-Withdrawing Substituents: Reactions will not occur with strong electron-withdrawing groups (e.g. -NO₂, -CN, -CHO, -COR,...). or if the ring has -NH₂, -NHR, or -NR₂ groups
Multiple Substitutions: Multiple substitutions on the ring can occur.
Carbocation Rearrangements: Carbocation rearrangements may occur.
Primary alkyl halide mechanism: Primary alkyl halides form complex with the AICI₃, which subsequently attacks the benzene ring and substitutes a positive alkyl group to the ring.

Friedel–Crafts Acylation

Acyl Group Introduction: Reacting benzene with an acid chloride to introduce an acyl group (COR). Example: CH₃COCl.
Reaction Conditions: AICI₃ as a catalyst and excess benzene, 80°C.
Preparation of Acid Chlorides: Preparing acid chlorides can be done by treating carboxylic acids with thionyl chloride or phosphorus pentachloride.

Friedel-Crafts Acylation - Mechanism

Step 1: Generation of acyl cation.: The acid chloride reacts with AICI₃ to form an acyl cation.
Step 2: Attack by acyl cation on benzene ring.: The acyl cation attacks the benzene ring, forming a temporary non-aromatic structure.

Halogenation of Benzene

Reaction with Lewis Acid: In the presence of anhydrous Lewis acids (e.g., FeCl₃), benzene readily reacts with either bromine or chlorine to form halogenated benzenes. Example: chlorobenzene.
Reactivity: F₂ reacts very quickly, requiring more extensive apparatus. I₂ is not reactive and requires oxidising agents (e.g., HNO₃) to perform iodination.

Nitration of Benzene

Reaction with Nitric Acid: Benzene reacts slowly with hot concentrated nitric acid (HNO₃) to form nitrobenzene.
Using Sulfuric Acid: Using concentrated sulfuric acid (H₂SO₄) alongside nitric acid increases the rate.
Electrophile: The nitronium ion (NO₂⁺) acts as the electrophile.

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Description

Explore the key concepts of aromatic compounds in this second lecture on Pharmaceutical Chemistry. Learn about arenes, phenyl and aryl groups, and the mechanism of electrophilic substitution of benzene. This quiz will test your understanding of the essential topics covered in the lecture.