Question

Using your roadmaps as a guide, show how to convert (2-bromoethyl)benzene into 2-chloro-1-phenylethanone. Show all reagents and all molecules synthesized along the way.

Short answer

Question: Outline the steps to convert (2-bromoethyl)benzene into 2-chloro-1-phenylethanone. Answer: The conversion can be achieved through the following steps: 1. Perform an SN2 reaction with sodium cyanide (NaCN) to obtain (2-cyanoethyl)benzene. 2. Hydrolyze the nitrile group using acid-catalyzed hydrolysis with H₂O and HCl, producing 2-phenylpropanoic acid. 3. Convert the carboxylic acid group to an acyl chloride using thionyl chloride (SOCl₂), resulting in 2-phenylpropionyl chloride. 4. Perform Friedel-Crafts acylation with aluminum chloride (AlCl₃) to obtain 2-chloro-1-phenylethanone.

Step-by-step solution

Bromine Atom to Nitrile Group

To convert the bromine atom on (2-bromoethyl)benzene to a nitrile group, we perform an SN2 reaction with sodium cyanide (NaCN) as the nucleophile. This will give us (2-cyanoethyl)benzene as the product. The reaction is as follows: (2-Bromoethyl)benzene + NaCN → (2-Cyanoethyl)benzene + NaBr

Hydrolyze the Nitrile Group

Now that we have a nitrile group, we can hydrolyze it to a carboxylic acid using an acid-catalyzed hydrolysis. Combine the (2-cyanoethyl)benzene with H₂O and HCl, then heat the mixture to obtain the corresponding carboxylic acid: 2-phenylpropanoic acid. The reaction is as follows: (2-Cyanoethyl)benzene + H₂O + HCl (heat) → 2-Phenylpropanoic acid

Convert the Carboxylic Acid Group to an Acyl Chloride

We need to convert the carboxylic acid group to an acyl chloride to form 2-chloro-1-phenylethanone. We can achieve this by using thionyl chloride (SOCl₂). The reaction of 2-phenylpropanoic acid with thionyl chloride gives 2-phenylpropionyl chloride. It can be written as follows: 2-Phenylpropanoic acid + SOCl₂ → 2-Phenylpropionyl chloride + SO₂ + HCl

Perform Friedel-Crafts Acylation

Finally, we will perform Friedel-Crafts acylation to transform 2-phenylpropionyl chloride into 2-chloro-1-phenylethanone. In this reaction, we use aluminum chloride (AlCl₃) as a Lewis acid catalyst. It can be written as follows: 2-Phenylpropionyl chloride + Benzene + AlCl₃ → 2-Chloro-1-phenylethanone + AlCl₃*HCl Now, we have successfully converted (2-bromoethyl)benzene into 2-chloro-1-phenylethanone following these steps with the corresponding reagents and molecules.

Key concepts

SN2 Reaction

The SN2 reaction plays an essential role in organic synthesis and is characterized by its 'bimolecular' nature, indicating that both the substrate and nucleophile are involved in the rate-determining step. This type of mechanism means that the reaction occurs in one concerted step, involving a backside attack by the nucleophile.

During the process, the nucleophile collides with the opposite side of the carbon that bears the leaving group. Hence, SN2 stands for substitution nucleophilic bimolecular. This simultaneous breaking and forming of bonds leads to an inversion of configuration at the carbon center, often compared to an 'umbrella turning inside out in a strong wind.'

In the exercise, we utilized sodium cyanide (NaCN) as a nucleophile to displace the bromine atom on (2-bromoethyl)benzene in an SN2 reaction, forming (2-cyanoethyl)benzene as a result. This reaction underscores the nucleophile's ability to forge a new bond while the leaving group – bromide in this case – departs with the electron pair formerly shared with the carbon atom.

Acid-Catalyzed Hydrolysis

Acid-catalyzed hydrolysis is fundamental in organic chemistry, especially when transforming nitriles into valuable carboxylic acids. In this process, an acid, such as hydrochloric acid (HCl), donates a proton to the nitrile, making it a better electrophile. Water, a weak nucleophile, can then attack the positively charged carbon, leading to a series of steps that eventually result in the nitrile converting to an amide and finally to a carboxylic acid upon hydrolysis.

The presence of the acid and heat provides the requisite conditions to promote the transformation. Following this concept, our exercise demonstrates the conversion of the nitrile group in (2-cyanoethyl)benzene to a carboxylic acid, specifically 2-phenylpropanoic acid. This transformation is crucial as it sets the stage for subsequent reactions in the synthetic pathway.

Friedel-Crafts Acylation

The Friedel-Crafts acylation is a pivotal reaction in creating aromatic ketones. Utilizing a Lewis acid catalyst, such as aluminum chloride (AlCl₃), enhances the reactivity of an acyl chloride, making it a highly electrophilic species. In this reaction, the carbocation (also known as the acylium ion) formed is resonance stabilized, which mitigates the risk of carbocation rearrangements that often occur in Friedel-Crafts alkylation.

In our specific pathway, 2-phenylpropionyl chloride, an acyl chloride, undergoes Friedel-Crafts acylation with benzene to produce 2-chloro-1-phenylethanone. The Lewis acid catalyst plays a crucial role, facilitating the formation of the electrophilic acylium ion and orchestrating the reaction to attach the acyl group to the benzene ring. Through this operation, it culminates the transformation we tackled, elucidating the elegance and versatility of Friedel-Crafts acylation in crafting complex molecular architectures.