Question

Using your reaction roadmaps as a guide, show how to convert cyclohexane and ethanol into racemic 2-acetylcyclohexanone. You must use ethanol and cyclohexane as the source of all carbon atoms in the target molecule. Show all reagents and all molecules synthesized along the way.

Short answer

Answer: The three necessary reactions and their reagents are: 1. Oxidation of Cyclohexane to Cyclohexanone using sodium dichromate (Na2Cr2O7) and sulfuric acid (H2SO4). 2. Synthesis of Ethyl Acetate from Ethanol and Acetic Acid using concentrated sulfuric acid (H2SO4) as a catalyst. 3. Reacting Cyclohexanone with Ethyl Acetate to form 2-Acetylcyclohexanone in the presence of sodium ethoxide (NaOEt).

Step-by-step solution

Oxidation of Cyclohexane to Cyclohexanone

In order to introduce a carbonyl group onto the cyclohexane ring, we first need to oxidize cyclohexane to cyclohexanone. This can be achieved by using a mild oxidizing agent such as sodium dichromate (Na2Cr2O7) in the presence of an acid like sulfuric acid (H2SO4). The reaction proceeds as follows: Cyclohexane + Na2Cr2O7 + H2SO4 -> Cyclohexanone

Synthesis of Ethyl Acetate

In order to create a reagent that allows the introduction of an acetyl group onto the cyclohexanone, we can use ethanol as a starting material. We will convert ethanol into ethyl acetate by a reaction known as esterification. In this reaction, we need to use a catalyst such as concentrated sulfuric acid (H2SO4). The reaction proceeds as follows: Ethanol + Acetic Acid + H2SO4 -> Ethyl Acetate

Reacting Cyclohexanone with Ethyl Acetate - Acetylation

Now that we have our cyclohexanone and ethyl acetate, we can introduce the acetyl group at the alpha-position of cyclohexanone. This step is called acetylation and it can be performed in the presence of a base like sodium ethoxide (NaOEt) to achieve the reaction. The reaction proceeds as follows: Cyclohexanone + Ethyl Acetate + NaOEt -> 2-Acetylcyclohexanone This three-step synthesis leads to the formation of racemic 2-acetylcyclohexanone.

Key concepts

Oxidation Reactions

Oxidation reactions are pivotal processes in organic chemistry, responsible for increasing the oxygen content or decreasing the hydrogen content of a molecule. One of the classic examples is the transformation of a hydrocarbon, like cyclohexane, into a carbonyl-containing compound, such as cyclohexanone.

In the context of our problem, the oxidation of cyclohexane uses a strong oxidizing agent, typically sodium dichromate (Na2Cr2O7) paired with sulfuric acid (H2SO4). The mechanism involves removal of hydrogen atoms from the cyclohexane, which results in the formation of a double-bonded oxygen, also known as the carbonyl group.

The intricacy of the oxidation lies in the specific conditions used. Too harsh conditions might break the carbon ring or overoxidize the compound to undesired products such as carboxylic acids. Thus, controlling the reaction environment is crucial for precision and successful synthesis of the desired cyclohexanone.

Esterification Reaction

Esterification is a fundamental organic chemistry reaction where an acid reacts with an alcohol to form an ester and water. The esterification process is often catalyzed by acid, which makes the reaction proceed more efficiently.

In this specific exercise, ethanol reacts with acetic acid, in the presence of powerful concentrated sulfuric acid (H2SO4), to form ethyl acetate. This reaction is reversible, which means the products can revert back to reactants, but as the ethyl acetate is formed, it shifts the equilibrium to favor more product formation.

Importance in Synthesis

The creation of ethyl acetate is particularly valuable since it serves as a reagent for further chemical transformations, such as the acetylation needed to produce 2-acetylcyclohexanone from cyclohexanone. By understanding esterification, students can manipulate molecular structures and tailor them towards the synthesis of complex molecules.

Acetylation Reaction

Acetylation is a specific type of acylation process that involves the introduction of an acetyl group into a molecule. Central to our exercise, acetylation allows us to alter the cyclohexanone molecule to obtain the desired product, 2-acetylcyclohexanone.

To ensure an accurate acetylation, a base such as sodium ethoxide (NaOEt) is used to deprotonate the alpha carbon next to the carbonyl group on the cyclohexanone. The removal of this proton makes the carbon more nucleophilic, allowing the acetyl group from ethyl acetate to attach at this site.

It's critical to highlight that this reaction introduces an important functional group, the acetyl group, at the precise location on the cyclohexanone to yield 2-acetylcyclohexanone. The mastery of acetylation reactions equips students with the knowledge to tackle complex synthetic pathways and create a wide array of compounds in organic chemistry.