Question

Show how the following transformations might be achieved with the aid of azide derivatives. (a) \(\mathrm{CH}_{2}=\mathrm{CHCH}_{2} \mathrm{CH}_{2} \mathrm{OH} \rightarrow \mathrm{CH}_{2}=\mathrm{CHCH}_{2} \mathrm{CH}_{2} \mathrm{NH}_{2}\)

Short answer

To convert pent-2-en-4-ol to pent-2-en-4-amine using azide derivatives, follow these steps: 1. Convert the alcohol group (OH) to an alkyl halide (Cl) using thionyl chloride (SOCl2). 2. Replace the alkyl halide (Cl) with an azide group (N3) using sodium azide (NaN3) in an SN2 reaction. 3. Reduce the azide group (N3) to an amine group (NH2) using either hydrogen gas (H2) with a metal catalyst (Pd-C or Pt) or lithium aluminum hydride (LiAlH4).

Step-by-step solution

Convert the alcohol group to an alkyl halide

To convert the alcohol group (OH) to an alkyl halide, we can use thionyl chloride (SOCl2) as a reagent. This will convert the hydroxyl group (OH) into a chloro group (Cl). Reactant: \(\mathrm{CH}_{2}=\mathrm{CHCH}_{2} \mathrm{CH}_{2} \mathrm{OH}\) Reagent: \(\mathrm{SOCl}_{2}\) Product: \(\mathrm{CH}_{2}=\mathrm{CHCH}_{2} \mathrm{CH}_{2} \mathrm{Cl}\)

Replace the alkyl halide with an azide group

Next, use sodium azide (NaN3) as a nucleophile to replace the chloro group (Cl) with an azide group (N3). This is an SN2 reaction. Reactant: \(\mathrm{CH}_{2}=\mathrm{CHCH}_{2} \mathrm{CH}_{2} \mathrm{Cl}\) Reagent: \(\mathrm{NaN}_{3}\) Product: \(\mathrm{CH}_{2}=\mathrm{CHCH}_{2} \mathrm{CH}_{2} \mathrm{N}_{3}\)

Reduce the azide group to an amine

For the final step, we will reduce the azide group (N3) to an amine group (NH2) by using either hydrogen gas (H2) with a metal catalyst (such as palladium on carbon or platinum) or using LiAlH\(_{4}\) (lithium aluminum hydride) as the reducing agent. Reactant: \(\mathrm{CH}_{2}=\mathrm{CHCH}_{2} \mathrm{CH}_{2} \mathrm{N}_{3}\) Reagent (option 1): \(\mathrm{H}_{2} / \mathrm{Pd-C}\) (or \(\mathrm{H}_{2} /\mathrm{Pt}\)) Reagent (option 2): \(\mathrm{LiAlH}_{4}\) Product: \(\mathrm{CH}_{2}=\mathrm{CHCH}_{2} \mathrm{CH}_{2} \mathrm{NH}_{2}\) Through these three steps, we have successfully converted pent-2-en-4-ol to pent-2-en-4-amine using azide derivatives.

Key concepts

Alkyl Halide

Alkyl halides, also known as haloalkanes, are organic compounds that contain one or more halogen atoms (such as chlorine, bromine, or iodine) bonded to an alkyl group. They serve as fundamental building blocks in various chemical reactions. In our transformation process, the alkyl halide plays a crucial intermediary role.

When converting an alcohol to an alkyl halide, reagents like thionyl chloride (\( \mathrm{SOCl}_{2} \)) are commonly used. This process involves replacing the hydroxyl group of the alcohol with a halogen atom, resulting in a chloroalkane.

• This step is critical because it activates the molecule for subsequent nucleophilic substitution reactions.
• Alkyl halides are more reactive compared to alcohols, facilitating further transformation steps.

By converting the alcohol into an alkyl halide, the molecule becomes primed for the nucleophilic attack needed in the upcoming SN2 reaction.

SN2 Reaction

The SN2 (Substitution Nucleophilic Bimolecular) reaction is a type of nucleophilic substitution where the nucleophile attacks the electrophile directly, resulting in a one-step reaction mechanism. It is characterized by its simultaneous bond making and bond breaking process, leading to an inversion of stereochemistry at the carbon center.

In this transformation, we used sodium azide (\( \mathrm{NaN_3} \)) to perform an SN2 reaction on the alkyl halide. This forms an azide compound, preparing it for the final conversion to an amine.

• The SN2 reaction requires a strong nucleophile and a suitable electrophile, in this case, a primary alkyl halide.
• Since the reaction proceeds with inversion, it’s important to start with a configuration that leads to the desired final product.
• The reaction occurs in one concerted step, making it highly efficient for transformations like the one highlighted here.

This reaction is ideal for synthesizing compounds where controlling the stereochemical outcome is crucial.

Amine Synthesis

Amine synthesis in the context of our transformation involves converting the azide compound produced from the SN2 reaction into an amine. Amines are organic compounds that contain nitrogen and are widely used in a vast array of chemical processes. The transformation from azide to amine typically involves a reduction step.

There are multiple ways to achieve this reduction, including using catalysts and reagents like hydrogen gas with palladium on carbon (Pd-C) or lithium aluminum hydride (\( \mathrm{LiAlH_4} \)).

• Each approach has its own advantages. Hydrazine-palladium provides high selectivity and yields, whereas \( \mathrm{LiAlH_4} \) is versatile and commonly used in different contexts.
• Choosing the right method depends on the reaction conditions and the desired purity of the final amine product.
• The overall transformation to amine is notable because it provides a method to access compound frameworks that play critical roles in pharmaceuticals and natural products.

By understanding these options, chemists can effectively synthesize a variety of amines using starting materials similar to the alkyl halides and azides in this exercise.