Question

Using your roadmaps as a guide, show how to convert cyclohexane and ethanol into racemic ethyl 2-oxocyclopentanecarboxylate. 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

Question: Describe a synthesis of racemic ethyl 2-oxocyclopentanecarboxylate using cyclohexane and ethanol as starting materials. Answer: The synthesis involves 4 steps: 1) Ring contraction of cyclohexane to cyclopentene using H2O2, a metal catalyst, CrO3, H2SO4, and selenium; 2) Formation of cyclopentanone via ozonolysis with reductive workup (H2O2); 3) Introduction of carboxylate group through Baeyer-Villiger oxidation using m-chloroperbenzoic acid (mCPBA); 4) Formation of racemic ethyl 2-oxocyclopentanecarboxylate by esterification of the resulting lactone using ethanol and concentrated H2SO4.

Step-by-step solution

Ring contraction of cyclohexane to cyclopentene

To transform cyclohexane into a five-membered ring, we can perform a ring contraction by oxidizing the cyclohexane to cyclohexanol, then converting it to cyclohexanone, and finally to cyclopentene via a rearrangement. The reagents and reaction conditions needed for these reactions are H2O2 and a metal catalyst for the selective oxidation to cyclohexanol, chromic anhydride (CrO3) in sulfuric acid (H2SO4) for oxidation from cyclohexanol to cyclohexanone, and a molecular rearrangement using selenium (Se) for the conversion from cyclohexanone to cyclopentene.

Formation of cyclopentanone

With cyclopentene as an intermediate, we can now introduce a carbonyl group at position 2 by performing the ozonolysis reaction. Ozonolysis involves the reaction of the C=C bond with ozone, followed by reductive or oxidative workup to yield the desired product. In this case, we will use reductive workup (H2O2) in order to prevent over-oxidation of the product. This will give us cyclopentanone.

Introduction of the carboxylate group

To introduce the carboxylate group, we will perform a Baeyer-Villiger oxidation on cyclopentanone. This reaction involves the use of a peroxyacid, such as m-chloroperbenzoic acid (mCPBA), to oxidize the carbonyl carbon of the ketone, leading to an ester product. In this case, mCPBA will form a lactone (2-oxocyclopentanecarboxylic acid) as the product.

Formation of ethyl 2-oxocyclopentanecarboxylate

The final step of the synthesis involves converting the lactone (2-oxocyclopentanecarboxylic acid) into the racemic ethyl ester, ethyl 2-oxocyclopentanecarboxylate, using ethanol as the source for the ethyl group. This can be achieved by performing an esterification reaction of the lactone with ethanol in the presence of an acid catalyst, such as concentrated sulfuric acid (H2SO4). The reaction will yield a racemic mixture of the ethyl 2-oxocyclopentanecarboxylate product. By following these four steps, we have successfully converted cyclohexane and ethanol into racemic ethyl 2-oxocyclopentanecarboxylate, fulfilling the requirements of the given exercise.

Key concepts

Ring Contraction

Ring contraction is a process where a ring of atoms, commonly seen in organic compounds, is made smaller by removing one or more atoms from the ring. This is useful in converting larger rings to smaller ones, which can be helpful for producing specific chemical structures. For example, converting cyclohexane, a six-membered ring, into cyclopentene, a five-membered ring, involves multiple reactions and careful selection of reagents.

To achieve this, we start by oxidizing cyclohexane into cyclohexanol using hydrogen peroxide (\(\text{H}_2\text{O}_2\)) with a metal catalyst. This step introduces a hydroxyl group. Next, oxidize cyclohexanol to cyclohexanone with chromic anhydride (\(\text{CrO}_3\)) and sulfuric acid (\(\text{H}_2\text{SO}_4\)). This creates a ketone, a key step for further transformation. Finally, cyclohexanone undergoes molecular rearrangement to form cyclopentene using selenium (\(\text{Se}\)).

• Start with cyclohexane
• Oxidize to cyclohexanol
• Convert to cyclohexanone
• Rearrange to form cyclopentene

Carboxylate Formation

Carboxylate formation in organic synthesis is about introducing a carboxylic acid group, or its derivatives, into a molecule. It's a crucial step when the target compound requires a carboxylate functional group, usually derived from a ketone.

In this exercise, we focus on transforming cyclopentanone to a carboxylate-containing compound via the Baeyer-Villiger oxidation. This reaction is carried out with the help of a peroxyacid such as m-chloroperbenzoic acid (mCPBA). When mCPBA reacts with cyclopentanone, it forms a lactone, specifically 2-oxocyclopentanecarboxylic acid.

• Start with cyclopentanone
• Use mCPBA for Baeyer-Villiger oxidation
• Form lactone: 2-oxocyclopentanecarboxylic acid

Ozonolysis

Ozonolysis is a powerful reaction for breaking down carbon-carbon double bonds. It is widely used to transform alkenes into smaller carbonyl compounds, such as aldehydes or ketones. This reaction involves ozone (\(\text{O}_3\)) as a reactive agent that cleaves double bonds and adds oxygen at the ends.

In synthesizing cyclopentanone from cyclopentene, ozonolysis plays a significant role. By reacting cyclopentene with ozone, followed by a reductive workup with hydrogen peroxide (\(\text{H}_2\text{O}_2\)), the process avoids over-oxidation and directly leads to the formation of cyclopentanone.

• Begin with cyclopentene
• React with ozone
• Use \(\text{H}_2\text{O}_2\) for reductive workup
• Yield cyclopentanone

Esterification

Esterification is a chemical reaction that forms an ester through the reaction of an acid and an alcohol. Esters have pleasant odors and are often used in fragrances, flavors, and as solvents. In organic synthesis, esterification is crucial for introducing specific ester functional groups.

To convert 2-oxocyclopentanecarboxylic acid into ethyl 2-oxocyclopentanecarboxylate, we perform an esterification reaction with ethanol, using concentrated sulfuric acid (\(\text{H}_2\text{SO}_4\)) as a catalyst. This process replaces the carboxylic acid's hydroxyl group with an ethoxy group, forming the desired ester compound.

• Use 2-oxocyclopentanecarboxylic acid
• React with ethanol
• Add sulfuric acid as a catalyst
• Form ethyl 2-oxocyclopentanecarboxylate