Question

How would you prepare the following compounds from benzene? More than one step is required in each case. (a) \(m\) -Chlorobenzoic acid (b) \(p\) -Bromobenzoic acid (c) Phenylacetic acid, \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{H}\)

Short answer

Use Friedel-Crafts acylation and subsequent oxidation or bromination as needed for each compound.

Step-by-step solution

Preparing m-Chlorobenzoic Acid

1. Begin with benzene. Use Friedel-Crafts acylation to introduce a carbonyl group by reacting benzene with acetyl chloride ( Ce{CH3COCl} ) and AlCl3 as a catalyst to form acetophenone. 2. Convert the acetophenone into benzoic acid using oxidation (such as KMnO4). 3. To chlorinate the benzoic acid at the meta position, use Ce{Cl2} with FeCl3 catalyst to introduce the chlorine group, resulting in m-chlorobenzoic acid.

Preparing p-Bromobenzoic Acid

1. Start with benzene. First, perform a Friedel-Crafts acylation with acyl chloride (such as acetyl chloride Ce{CH3COCl} ) and AlCl3 to introduce an acyl group, forming acetophenone. 2. Oxidize the acetophenone with an oxidizing agent like KMnO4 to convert it into benzoic acid. 3. Perform bromination using Ce{Br2} and FeBr3 as a catalyst. Ensure the substitution occurs at the para position to obtain p-bromobenzoic acid.

Preparing Phenylacetic Acid

1. Start with benzene. Conduct a Friedel-Crafts acylation with chloroacetyl chloride ( Ce{ClCH2COCl} ) and AlCl3, forming phenylacetyl chloride. 2. Perform a hydrolysis reaction on phenylacetyl chloride with water in the presence of a base to convert it into phenylacetic acid ( C6H5CH2CO2H ).

Key concepts

Friedel-Crafts Acylation

Friedel-Crafts Acylation is a versatile reaction used in organic chemistry to introduce acyl groups onto aromatic rings like benzene. This reaction relies on the use of an acyl chloride and a catalyst, typically aluminum chloride (AlCl₃). Here's a breakdown:

- **Mechanism:** The acyl chloride reacts with AlCl₃, forming a complex that generates a strong electrophile (an acylium ion). This ion attacks the pi electrons in the benzene ring, leading to the formation of an acyl-substituted aromatic compound. Once the acylium ion attaches to the ring, the AlCl₃ helps to remove the chloride ion, completing the acylation process. - **Applications:** This reaction is utilized for synthesizing ketones from aromatic compounds. For example, converting benzene to acetophenone in the presence of AlCl₃ and acyl chlorides. - **Considerations:** Friedel-Crafts Acylation doesn't work well with nitro, amino or strongly deactivating substituents already in the benzene ring. It also usually requires the absence of other reactive functional groups that might interfere. Overall, this reaction efficiently extends the carbon framework and prepares aromatic compounds for further modifications.

Oxidation Reactions

Oxidation reactions are key in organic synthesis, particularly when seeking to transform an alkyl group into a carboxylic acid. In the context of organic chemistry, oxidation generally means increasing the number of oxygen atoms or reducing the number of hydrogen atoms attached to carbon.

- **Mechanism:** Using strong oxidizing agents such as potassium permanganate (KMnO₄), it oxidizes the alkyl side chains of aromatic rings. These reactions often involve free radicals or other reactive species to replace hydrogen atoms with oxygen atoms. - **Purpose:** In the exercises, oxidation is crucial for converting oxyphenones like acetophenone into benzoic acid. This process introduces carboxyl groups (\( -COOH \)) into the aromatic rings, which is a significant functional transformation.- **Safety:** These reactions can be quite vigorous and need careful control, often requiring specific conditions such as acidic or basic environments to proceed smoothly.Through oxidation, chemists can introduce highly polar and reactive functional groups necessary for further chemical reactions to create complex molecules.

Electrophilic Aromatic Substitution

Electrophilic Aromatic Substitution (EAS) is a fundamental reaction type for modifying benzene and its derivatives. This process involves replacing a hydrogen atom on the benzene ring with an electrophile.

- **Mechanism:** The reaction begins with the formation of an electrophile. This strong positive ion (or polar molecule) approaches the pi electrons in benzene, forming a carbocation intermediate. The resulting intermediate is stabilized by the aromatic system until a deprotonation step restores aromaticity.- **Examples:** In the provided solutions, both chlorination and bromination exemplify EAS. For instance, using (\( Cl_2 \)) or (\( Br_2 \)) along with metal halide catalysts such as (\( FeCl_3 \)) or (\( FeBr_3 \)), substitution can be controlled to occur at specific positions (ortho, meta, or para) on the benzene ring.- **Directing Effects:** Substituents already present on the benzene influence the position of the incoming group due to electronic effects, determining whether the final product is ortho, para, or meta substituted.Through EAS, a wide variety of functional groups can be introduced into benzene, paving the way for synthesizing complex chemical compounds.

Benzene Derivatives

Benzene derivatives are chemical compounds with structural variations due to substitutions on the benzene ring. This modification alters the compound's chemical properties and reactivity. - **Types of Derivatives:** Simple derivatives include toluene (methylbenzene) and aniline (aminobenzene), whereas more complex derivatives may include multiple or various functional groups like nitro, sulfonic acid, and halogens bonded to the benzene ring. - **Reactive Patterns:** The nature of the groups attached to the ring influences benzene's reactivity. Electron-donating groups make the ring more reactive towards electrophiles, while electron-withdrawing groups make it less reactive. - **Application in Synthesis:** In synthetic chemistry, benzene's derivatives serve as crucial starting materials or intermediates for constructing larger organic molecules. Example processes involve in exercises like Friedel-Crafts Acylation and later modifications through EAS to obtain desired products like chlorobenzoic and bromobenzoic acids. Overall, understanding benzene derivatives allow chemists to strategically design synthetic routes for producing specialized materials or pharmaceuticals with desired properties.