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 the synthesis of racemic ethyl 2-oxocyclopentanecarboxylate from cyclohexane and ethanol. Answer: The synthesis involves five main steps: 1) Oxidation of cyclohexane to cyclohexanone using KMnO4 and KOH; 2) Baeyer-Villiger oxidation of cyclohexanone to ε-caprolactone using mCPBA; 3) Hydrolysis of ε-caprolactone to 6-hydroxyhexanoic acid using water and NaOH; 4) Decarboxylation of 6-hydroxyhexanoic acid to 5-hydroxypentanal using CuO; and 5) Oxidation of 5-hydroxypentanal into ethyl 2-oxocyclopentanecarboxylate using Na2Cr2O7 and EtOH.

Step-by-step solution

Oxidation of cyclohexane to cyclohexanone

First, we need to oxidize cyclohexane to obtain cyclohexanone. This can be done by using an oxidizing agent like potassium permanganate (KMnO4) in an alkaline medium (for example, KOH). The reaction proceeds via the formation of a cyclic manganese ester, which on hydrolysis gives cyclohexanone. Cyclohexane + KMnO4 + KOH ⟶ Cyclohexanone + MnO2 + K2O + H2O

Baeyer-Villiger oxidation of cyclohexanone to ε-caprolactone

Next, we need to perform a Baeyer-Villiger oxidation of cyclohexanone to obtain ε-caprolactone. For this reaction, we can use a peracid such as meta-chloroperbenzoic acid (mCPBA). This reaction involves the migration of a carbon atom in the cyclohexanone ring, creating an ester. Cyclohexanone + mCPBA ⟶ ε-caprolactone + m-chlorobenzoic acid

Hydrolysis of ε-caprolactone to 6-hydroxyhexanoic acid

Now, we need to hydrolyze ε-caprolactone to obtain 6-hydroxyhexanoic acid. This can be done by refluxing with water and a strong base such as sodium hydroxide (NaOH). ε-caprolactone + H2O + NaOH ⟶ 6-hydroxyhexanoic acid + Na+

Decarboxylation of 6-hydroxyhexanoic acid to 5-hydroxypentanal

Next, we need to perform a decarboxylation reaction on the 6-hydroxyhexanoic acid to remove the carboxyl group and generate 5-hydroxypentanal. This can be achieved under heating with copper(II) oxide (CuO). 6-hydroxyhexanoic acid + CuO ⟶ 5-hydroxypentanal + CO2 + Cu

Oxidation of 5-hydroxypentanal to ethyl 2-oxocyclopentanecarboxylate

Finally, we need to convert 5-hydroxypentanal into the target molecule, ethyl 2-oxocyclopentanecarboxylate. We can carry out this reaction by oxidizing 5-hydroxypentanal using sodium or potassium dichromate (Na2Cr2O7 or K2Cr2O7) in the presence of ethanol, which will simultaneously act as a nucleophile and source of ethyl group. 5-hydroxypentanal + Na2Cr2O7 + EtOH ⟶ Ethyl 2-oxocyclopentanecarboxylate + Na2CrO4 + H2O The overall synthesis involves several steps and transformations, leading to the desired racemic ethyl 2-oxocyclopentanecarboxylate, with all carbon atoms originating from cyclohexane and ethanol.