Question

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

Short answer

Question: Outline the steps to convert ethanol (C2H5OH) into 2-pentanone (C5H10O) using ethanol as the exclusive carbon source. Answer: To convert ethanol into 2-pentanone, follow these steps: 1. Oxidize ethanol into acetaldehyde using pyridinium chlorochromate (PCC). 2. Add a cyanide ion to the acetaldehyde to form cyanohydrin using NaCN or KCN. 3. Reduce cyanohydrin's cyanide group to a primary amine with lithium aluminum hydride (LAH). 4. Oxidize the primary amine to nitrile using tetranitromethane (TNM). 5. Convert another ethanol molecule into bromoethane with PBr3, then into an ethyl Grignard reagent using magnesium (Mg). 6. Add the Grignard reagent to the nitrile from step 4, forming a new carbon-carbon bond. 7. Hydrolyze the product with aqueous acid, then remove the hydroxyl group, resulting in the final product, 2-pentanone.

Step-by-step solution

Oxidation of Ethanol to Acetaldehyde

For the first step, we need to oxidize ethanol to form an aldehyde (acetaldehyde). We can use a mild oxidizing agent like Pyridinium Chlorochromate (PCC) to achieve selective oxidation of ethanol to acetaldehyde without over-oxidizing to carboxylic acid. C2H5OH + PCC -> CH3CHO

Addition of Cyanide Ion to Acetaldehyde

Next, we perform a nucleophilic addition of cyanide ion to the carbonyl carbon of acetaldehyde, forming a cyanohydrin. We can use a source of cyanide ion like NaCN or KCN for this reaction. The cyanide ion will attack the carbonyl carbon, and the carbonyl oxygen will rebound with the remaining proton from the reaction mixture. CH3CHO + CN^- -> CH3(CH(OH)CN)

Reduction of Cyanohydrin to Primary Amine

Now, we need to reduce the cyanide group in the cyanohydrin to form a primary amine. We can use a reducing agent like Lithium Aluminum Hydride (LAH) in this step. CH3(CH(OH)CN) + LiAlH4 -> CH3(CH(OH)CH2NH2)

Oxidation of Primary Amine to Nitrile

In this step, we need to oxidize the primary amine to a nitrile. This can be done with tetranitromethane (TNM) as the oxidizing agent. CH3(CH(OH)CH2NH2) + TNM -> CH3(CH(OH)CH2CN)

Grignard Formation from Ethanol

Now, we will create a Grignard reagent from another molecule of ethanol. To make this possible, first, we need to convert ethanol to bromoethane by reacting it with PBr3. C2H5OH + PBr3 -> C2H5Br In the presence of magnesium, bromoethane can then form an ethyl Grignard reagent: C2H5Br + Mg -> C2H5MgBr

Nitrile Addition to Grignard Reagent

Finally, we will add the Grignard reagent to the nitrile obtained in step 4. This will create a new carbon-carbon bond, resulting in a product with all five carbons needed for the target molecule. CH3(CH(OH)CH2CN) + C2H5MgBr -> CH3(CH(OH)CH2CH2CH2MgBr-CN)

Hydrolysis of the Grignard Product

In the final step, we need to hydrolyze the product obtained in step 6 to get our desired molecule, 2-pentanone. This can be achieved by treating the product with aqueous acid. CH3(CH(OH)CH2CH2CH2MgBr-CN) + H3O+ -> CH3(CH(OH)CH2CH2CH2-CO) + MgBr(OH) + NH3 Upon the removal of the hydroxyl group, we now have our final product, 2-pentanone: CH3(CH(OH)CH2CH2CH2-CO) -> CH3COCH2CH2CH3 Now, we have successfully converted ethanol into 2-pentanone, and the overall synthesis is complete.

Key concepts

Ethanol Oxidation

Ethanol oxidation is the process of converting ethanol ( ext{C}_2 ext{H}_5 ext{OH}) to an aldehyde or a carboxylic acid. In organic synthesis, the choice of the oxidizing agent is essential to control the product.

• For mild oxidation, we often use ext{Pyridinium Chlorochromate} (PCC), which selectively oxidizes primary alcohols like ethanol to aldehydes such as acetaldehyde ( ext{CH}_3 ext{CHO}).
• This process prevents further oxidation to carboxylic acids, which is ideal when an aldehyde is required as an intermediate product.

The reaction is straightforward:\[ ext{C}_2 ext{H}_5 ext{OH} + ext{PCC} ightarrow ext{CH}_3 ext{CHO} \]This reaction is crucial as it sets up a reactive carbonyl group in acetaldehyde, enabling further chemical transformations such as nucleophilic additions.

Cyanohydrin Formation

Cyanohydrin formation is an excellent example of nucleophilic addition to a carbonyl group. Once we have acetaldehyde, the carbon double-bonded to oxygen is highly electrophilic.

• The cyanide ion ( ext{CN}^-) acts as a nucleophile, attacking the carbonyl carbon atom and forming a bond.
• This reaction results in a cyanohydrin, where a hydroxyl group and a nitrile group are attached to the same carbon atom.

The typical reaction can be described as:\[ ext{CH}_3 ext{CHO} + ext{CN}^- ightarrow ext{CH}_3 ext{CH}(OH) ext{CN}\]Cyanohydrin synthesis is important because it introduces a versatile ext{nitrile} group, allowing for further functional group transformations, such as reduction to amines or conversion to carboxylic acids.

Grignard Reagent

A Grignard reagent is a powerful tool in organic synthesis, used primarily to form carbon-carbon bonds. It is typically created by reacting an alkyl halide with magnesium in anhydrous ether.

• In our ethanol oxidation synthesis, we initially convert ethanol to an alkyl bromide like bromoethane.
• Then, by reaction with magnesium, we produce the Grignard reagent ext{C}_2 ext{H}_5 ext{MgBr}.

The reaction pathway is shown as:\[ ext{C}_2 ext{H}_5 ext{Br} + ext{Mg} ightarrow ext{C}_2 ext{H}_5 ext{MgBr}\]This Grignard reagent is highly reactive, particularly with carbonyl compounds, enabling the formation of new carbon bonds. For instance, reacting with the nitrile group gives us a ketone, completing the synthesis pathway for 2-pentanone when further processed.