Question

Using your reaction roadmap as a guide, show how to convert 1-bromopropane and carbon dioxide into 4-heptanone. You must use 1-bromopropane and carbon dioxide as the source of all carbon atoms in the target molecule. Show all reagents and all molecules synthesized along the way.

Short answer

Question: Provide a step-by-step synthesis of 4-heptanone from 1-bromopropane and carbon dioxide. Answer: The synthesis of 4-heptanone from 1-bromopropane and carbon dioxide can be achieved through the following steps: 1. Conversion of 1-bromopropane to propyl magnesium bromide (Grignard reagent) using magnesium in ether solvent. 2. Carboxylation of the Grignard reagent by reacting it with carbon dioxide, forming potassium magnesium propionate. 3. Hydrolysis of potassium magnesium propionate with water and HCl to form 4-pentanone and magnesium bromide. 4. Formation of ethyl magnesium bromide (another Grignard reagent) from ethyl bromide using magnesium in ether solvent. 5. Reaction of 4-pentanone with ethyl magnesium bromide, yielding 4-heptanol and magnesium bromide. 6. Oxidation of 4-heptanol to 4-heptanone using an oxidizing agent like chromium trioxide (CrO3) or potassium permanganate (KMnO4) in acidic conditions.

Step-by-step solution

1. Identify the starting compounds and target molecule

We are given two starting compounds: 1-bromopropane (CH3CH2CH2Br) and carbon dioxide (CO2). The target molecule is 4-heptanone (CH3CH2CH2CH2C(O)CH2CH3)

2. Formation of Grignard reagent from 1-bromopropane

To start, we convert 1-bromopropane into a Grignard reagent. We treat 1-bromopropane with magnesium in an ether solvent to generate the corresponding Grignard reagent, propyl magnesium bromide (CH3CH2CH2MgBr). Reaction: CH3CH2CH2Br + Mg -> CH3CH2CH2MgBr

3. Reagent for carboxylation

Next, we need a reagent to react with the Grignard reagent to introduce the carbon atom from carbon dioxide into the target molecule. We can use carbon dioxide itself as the reagent for this step.

4. Carboxylation of Grignard reagent

Now, we react the propyl magnesium bromide with carbon dioxide to form potassium magnesium propionate (CH3CH2CH2COOMgBr). This step is called carboxylation. Reaction: CH3CH2CH2MgBr + CO2 -> CH3CH2CH2COOMgBr

5. Formation of 4-pentanone

We hydrolyze potassium magnesium propionate with water to form 4-pentanone and magnesium bromide. This hydrolysis reaction is completed using H2O and HCl. Reaction: CH3CH2CH2COOMgBr + H2O + HCl -> CH3CH2CH2COCH3 + MgBr2 At this point, we have 4-pentanone (CH3CH2CH2COCH3), which is a five-carbon molecule with a carbonyl group in the middle. We now need to add two more carbon atoms to reach our target of 4-heptanone.

6. Formation of Grignard reagent from ethyl bromide

To do this, we will first form another Grignard reagent using ethyl bromide (CH3CH2Br). We treat ethyl bromide with magnesium in an ether solvent to generate the corresponding Grignard reagent, ethyl magnesium bromide (CH3CH2MgBr). Reaction: CH3CH2Br + Mg -> CH3CH2MgBr

7. Grignard reaction with 4-pentanone

In this final step, we react 4-pentanone (CH3CH2CH2COCH3) with the newly formed Grignard reagent, ethyl magnesium bromide (CH3CH2MgBr). This reaction yields 4-heptanol, an alcohol intermediate. Reaction: CH3CH2CH2COCH3 + CH3CH2MgBr -> CH3CH2CH2CH2CH(OH)CH2CH3 + MgBr2

8. Oxidation of 4-heptanol to 4-heptanone

Lastly, we can convert 4-heptanol into 4-heptanone by oxidation using an oxidizing agent like chromium trioxide (CrO3) or potassium permanganate (KMnO4) in acidic conditions to achieve the target molecule. Reaction: CH3CH2CH2CH2CH(OH)CH2CH3 +CrO3/H+ -> CH3CH2CH2CH2C(O)CH2CH3 In summary, through a series of Grignard reactions, carboxylation, hydrolysis, and oxidation, we can convert 1-bromopropane and carbon dioxide into the target molecule, 4-heptanone.

Key concepts

Grignard Reagent Formation

Beginning with the synthesis of 4-heptanone, the Grignard reagent formation is the first crucial step. A Grignard reagent is created when an alkyl halide reacts with magnesium in the presence of an ether solvent. Using 1-bromopropane in our reaction, we treat it with magnesium shavings to yield propyl magnesium bromide, a reactive organometallic compound.

The Grignard reagent acts as a carbanion, a carbon bearing a negative charge, which is highly nucleophilic. This means it's eager to donate electrons and bond with positively charged or electron-deficient areas in other molecules. The formation of this reagent is essential in the synthesis pathway because it sets the stage for the carbon skeleton of 4-heptanone to be constructed.

It's important to carry out this reaction under anhydrous conditions, meaning without any water, as water would react with the Grignard reagent, rendering it useless for further reactions.

Carboxylation Reaction

The carboxylation reaction is where we expand our carbon chain. The freshly formed Grignard reagent from the previous step is treated with carbon dioxide to form a new carboxylic acid salt. This process is crucial in incorporating the carbon from carbon dioxide into our molecule, which will eventually become part of the ketone functional group.

When propyl magnesium bromide comes into contact with carbon dioxide, a carboxylation reaction occurs, resulting in potassium magnesium propionate, an intermediate step towards our final product. Essentially, this step adds a new carbon atom to the molecule, extending the carbon chain needed to reach our target molecule, 4-heptanone. Carboxylation is a straightforward yet powerful tool in organic synthesis, enabling the formation of complex carbon structures from simpler ones.

Grignard Reaction with Ketones

The Grignard reaction with ketones, such as 4-pentanone in our process, is a transformative step in constructing the desired carbon skeleton. After generating a second Grignard reagent, this time from ethyl bromide, we introduce it to the 4-pentanone produced earlier.

The Grignard reagent acts as a nucleophile and attacks the carbonyl group of the ketone. The carbon-to-carbon bond formation that follows is vital as it lengthens the carbon chain, resulting in the formation of 4-heptanol, an alcohol that is one step away from becoming the target ketone.

Importance of Reaction Conditions

The success of this reaction hinges on reacting under strictly controlled conditions to prevent side reactions.

Oxidation of Alcohols

In the final leg of our journey, the oxidation of alcohols step is what converts the 4-heptanol, an intermediate alcohol, into 4-heptanone, our desired ketone. Using an oxidizing agent such as chromium trioxide (CrO3) or potassium permanganate (KMnO4), the alcohol group is carefully converted into a carbonyl group.

The choice of oxidizing agent and the control of the reaction conditions ensure that we achieve the desired oxidation level without overoxidizing to a carboxylic acid. The oxidation reaction transforms the secondary alcohol of 4-heptanol into the ketone functional group of 4-heptanone. It's a critical conversion that completes the synthesis and highlights the versatility and utility of alcohols as intermediates in chemical synthesis.