Question

In the given transformation, which of the following is the most appropriate reagent? CC(=O)C=CC1CCC(O)CC1 CCC=CC1CCC(O)CC1 (A) \(\mathrm{NaBH}_{4}\) (B) (i) \(\mathrm{NH}_{2} \mathrm{NH}_{2}\) (ii) \(\stackrel{\ominus}{\mathrm{O}} \mathrm{H}, \Delta\) (C) \(\mathrm{Zn}-\mathrm{Hg} / \mathrm{HCl}\) (D) \(\mathrm{Na}\), Liq. \(\mathrm{NH}_{3}\)

Short answer

The most appropriate reagent for the given transformation is (B) (i) \(\mathrm{NH}_{2} \mathrm{NH}_{2}\) (ii) \(\stackrel{\ominus}{\mathrm{O}} \mathrm{H}, \Delta\), as it reduces the carbonyl group to a methylene group (CH2) via the Wolff-Kishner reduction process.

Step-by-step solution

Convert SMILES to Molecular Structures

First, let's convert the given SMILES strings into molecular structures to better understand the transformation. Reactant: CC(=O)C=CC1CCC(O)CC1 Product: CCC=CC1CCC(O)CC1

Identify Structural Changes

Observe the differences between the reactant and product structures. 1. In the reactant molecule, there is a carbonyl (C=O) group. In the product molecule, the carbonyl group is reduced to a single bond CH2. 2. In the product molecule, we see one extra carbon in the alkene chain compared to the reactant.

Compare the Reagents

Now, let's examine each reagent to see which one can make the necessary structural change. (A) NaBH4: Sodium borohydride is a reducing agent that can reduce carbonyl groups. However, it does not have the ability to extend the carbon chain. (B) (i) \(\mathrm{NH}_{2} \mathrm{NH}_{2}\) (ii) \(\stackrel{\ominus}{\mathrm{O}} \mathrm{H}, \Delta\): This reagent combination (i.e., hydrazine followed by hydroxide ions and heat) is used for the Wolff-Kishner reduction to reduce carbonyl groups to methylene (CH2) groups. However, it does not have the ability to extend the carbon chain. (C) Zn-Hg / HCl: The Clemmensen reduction is used to reduce carbonyl groups to methylene (CH2) groups. However, it does not have the ability to extend the carbon chain. (D) Na, Liq. NH3: This combination is used for the Birch reduction. It involves the reduction of aromatic rings and can reduce alkynes to alkenes. However, it does not reduce carbonyls and does not match the required transformation in this case. Based on this comparison:

Choose the Correct Reagent

The most appropriate reagent for the given transformation is: (B) (i) \(\mathrm{NH}_{2} \mathrm{NH}_{2}\) (ii) \(\stackrel{\ominus}{\mathrm{O}} \mathrm{H}, \Delta\) This reagent combination reduces the carbonyl group to a methylene group (CH2) via the Wolff-Kishner reduction process. Although it does not explicitly extend the carbon chain, the observed change in the structure suggests that the necessary intermediate steps, such as alkylation, have been omitted from the question for simplicity. Therefore, the given reagent (B) is the correct answer as it displays the main transformation of the carbonyl group.

Key concepts

Wolff-Kishner reduction

The Wolff-Kishner reduction is a reliable method to convert carbonyl groups, such as aldehydes and ketones, into methylene groups (\( \text{CH}_2 \)). This reaction is particularly useful when you want to remove the oxygen atom from a carbonyl group and replace it with hydrogen, effectively reducing the group to a simple hydrocarbon.

The process begins with the formation of a hydrazone, which is created by reacting the carbonyl compound with hydrazine (\( \text{NH}_2 \text{NH}_2 \)). The reaction involves the addition of a strong base, typically hydroxide ions (\( \text{OH}^- \)), along with heat, which results in nitrogen gas leaving the compound and effectively transforming the carbonyl group. The key to the Wolff-Kishner reaction is the complete removal of the carbonyl oxygen without affecting other functional groups.

However, it is crucial to note that this reduction is performed under strongly basic conditions, which means it is not suitable for substances that are sensitive to bases. Additionally, while this reduction successfully converts carbonyls to methylene groups, it does not alter the carbon skeleton or extend the carbon chain, which is a factor to consider when analyzing transformations.

Clemmensen reduction

The Clemmensen reduction is another technique used for converting carbonyl groups directly to methylene groups. However, unlike the Wolff-Kishner reduction, the Clemmensen reduction occurs in acidic conditions. Typically, zinc amalgam (\( \text{Zn-Hg} \)) is utilized in the presence of hydrochloric acid (\( \text{HCl} \)) to achieve this conversion.

This method is favorable for substrates that are stable under acidic conditions but sensitive to bases. The acid conditions of the Clemmensen reduction work efficiently on simple ketones and aldehydes, providing a clean transformation from \( \text{C=O} \) to \( \text{-CH}_2- \). It shares the same objective as the Wolff-Kishner reduction but provides an alternative procedure when possible.

Although highly effective, the Clemmensen method is not suitable for molecules that are reactive to acids or that may undergo side reactions under such conditions. This method, much like the Wolff-Kishner reduction, will not extend a carbon chain as it strictly targets the carbonyl groups.

Birch reduction

The Birch reduction is a distinct and versatile process that mainly targets aromatic rings and alkynes, reducing them to less saturated forms. You'd typically see the Birch reduction being used on benzene rings, transforming them into non-aromatic cyclic dienes.

This reaction employs sodium (\( \text{Na} \)) or sometimes lithium (\( \text{Li} \)) in liquid ammonia (\( \text{NH}_3 \)), providing a highly reactive yet selective environment. Alcohols, like tertiary butanol (\( \text{tBuOH} \)), are often added as proton sources during the process. The Birch reduction stands out because it avoids converting aromatic rings into closed-chain alkanes, offering partially saturated products instead, which can serve as interesting intermediates in organic synthesis.

Despite its versatility, the Birch reduction is not applicable for reducing carbonyl groups, which are better suited for treatments like the Wolff-Kishner or Clemmensen reductions. This reduction allows for specific modifications to unsaturated systems, making it a highly targeted and powerful tool in synthetic chemistry.