Question

Show how to use alkylation or acylation of an enamine to convert acetophenone to the following compounds.

Short answer

Question: Describe the process of converting acetophenone to an alkylated and acylated product using alkylation or acylation of an enamine. Answer: The conversion process involves three main steps: 1) Formation of the enamine intermediate, where acetophenone is reacted with a secondary amine like pyrrolidine. 2) Alkylation or acylation of the enamine intermediate, where it reacts with an alkyl halide (e.g., ethyl bromide) for alkylation or an acyl halide/anhydride (e.g., acetyl chloride) for acylation. 3) Hydrolysis and tautomerization, where the iminium ion formed in step 2 is hydrolyzed and tautomerizes to yield the final alkylated or acylated product.

Step-by-step solution

Identification of target compounds and their corresponding enamine

First, let's identify the desired compounds and their corresponding enamine: Compound 1: Acetophenone Enamine 1: Since we're converting acetophenone, there's no need to identify an enamine here. Compound 2: An alkylated product of acetophenone Enamine 2: To achieve this, we'll need to convert acetophenone to its corresponding enamine by reacting it with a secondary amine. Compound 3: An acylated product of acetophenone Enamine 3: To achieve this, we'll need to convert acetophenone to its corresponding enamine by reacting it with a secondary amine, as well. Now, let's provide the step-by-step solutions for these transformations:

Formation of the enamine intermediate

To form the enamine intermediate, we need to react acetophenone with a secondary amine such as pyrrolidine in the presence of a suitable acid catalyst (e.g., p-toluenesulfonic acid) under mild heating conditions. This will form the corresponding enamine, by removing a water molecule as a result of an amine reacting with the carbonyl group in acetophenone.

Alkylation of the enamine intermediate

For the conversion to Compound 2, we will alkylate the enamine intermediate. To do this, we will need an alkyl halide (e.g., ethyl bromide). React the enamine with the alkyl halide in a polar, aprotic solvent (e.g., DMF). The enamine will act as a nucleophile and perform a nucleophilic substitution (S_N2) reaction with the alkyl halide. This process results in an alkylated iminium ion.

Hydrolysis and tautomerization to the alkylated product

Following alkylation, the iminium ion will be hydrolyzed in the presence of water and an acid (e.g., HCl) to yield the hydrolyzed ketone. The imine tautomerizes to the ketone, and thus, we obtain the final alkylated product (Compound 2).

Acylation of the enamine intermediate

For the conversion to Compound 3, we will instead acylate the enamine intermediate. Acylation involves reacting the enamine with an acyl halide or anhydride (e.g., acetyl chloride or acetic anhydride) in a suitable solvent (e.g., DCM). The enamine will attack the acyl group, forming an iminium ion with an acyl group attached.

Hydrolysis and tautomerization to the acylated product

Following acylation, the iminium ion is hydrolyzed in the presence of water and an acid (e.g., HCl) to yield the hydrolyzed ketone. The imine tautomerizes to the ketone, and thus, we obtain the final acylated product (Compound 3). These step-by-step solutions demonstrate how alkylation or acylation of an enamine can be used to convert acetophenone to the desired compounds.

Key concepts

Understanding Alkylation

Alkylation is an essential process in the field of organic chemistry, especially when dealing with enamine chemistry. This process involves the transfer of an alkyl group from one molecule to another. When it comes to the conversion of acetophenone, the alkylation step plays a pivotal role.

In this context, we start by forming an enamine from acetophenone. This is done by reacting acetophenone with a secondary amine, such as pyrrolidine, in the presence of an acid catalyst like p-toluenesulfonic acid.

This step removes a water molecule from the mixture, creating the enamine, which is a compound containing a nitrogen atom connected to an alkene carbon. The newly formed enamine then acts as a powerful nucleophile, meaning it is highly reactive and seeks positively charged atoms or molecules.

During the alkylation process, the enamine reacts with an alkyl halide (like ethyl bromide) in a polar aprotic solvent such as dimethylformamide (DMF). This results in a nucleophilic substitution reaction, specifically an S_N2 reaction, where the enamine replaces the halide ion with its nitrogen atom, forming an alkylated iminium ion. This step is crucial in turning acetophenone into an alkylated product.

Exploring Acylation

Acylation is akin to alkylation, but instead of transferring an alkyl group, an acyl group gets transferred. This process is commonly used to modify enamines derived from acetophenone into their acylated forms.

The first step is, once again, creating an enamine from acetophenone using a secondary amine and an acid catalyst. Once the enamine is constructed, it is ready for acylation.

In this reaction, an acyl halide or anhydride, such as acetyl chloride or acetic anhydride, is introduced. The enamine acts as a nucleophile that attacks the acyl group. The reaction takes place in a solvent like dichloromethane (DCM), leading to the formation of an iminium ion with an acyl group attached.

Hydrolysis follows, where water and an acid like hydrochloric acid are used to hydrolyze the iminium ion. This process effectively breaks the iminium down, which then tautomerizes—shifts the position of hydrogen atoms and double bonds—to eventually generate the acylated ketone. This is how acetophenone is converted into an acylated compound.

Acetophenone Conversion

The conversion of acetophenone through enamine chemistry is a fascinating topic that demonstrates the versatility of organic chemistry. Acetophenone serves as our starting material, which, through transformations like alkylation and acylation, can form a range of different compounds.

The core of these transformations lies in the enamine formation. By converting acetophenone to an enamine, usually using a secondary amine and a catalyst, we open up two paths.

• For alkylation, the enamine reacts with an alkyl halide, which alters acetophenone into an alkylated ketone. This transformation hinges on nucleophilic substitution reactions.
• For acylation, the enamine reacts with an acyl halide, forming an acylated product where the carbonyl carbon undergoes nucleophilic attack.

Each pathway requires careful execution in terms of reagents and conditions. They both end with a hydrolysis step where the intermediate iminium ion is broken down, leading the reaction to tautomerize back to the initial ketone structure, albeit modified by the addition of the new alkyl or acyl group.

Through understanding and applying these reactions, chemists can efficiently transform simple molecules like acetophenone into more complex structures necessary for various applications.