Question

In contrast to simple amines, aziridines (three-membered rings containing a nitrogen) can often be separated into enantiomers. For example, the activation energy \(\left(\Delta G^{\frac{4}{*}}\right)\) for the inversion of \(1,2,2\)-trimethylaziridine is about \(18.5 \mathrm{kcal} / \mathrm{mol}(77.5 \mathrm{~kJ} / \mathrm{mol})\), much higher than that for simple amines. Explain.

Short answer

Aziridines' three-membered ring structure causes strain, resulting in higher activation energy for inversion, unlike simple amines with lower activation energies.

Step-by-step solution

Understand the Inversion Concept

Inversion involves the flipping of the nitrogen's lone pair in the molecular structure, leading to the conversion of one enantiomer into another.

Compare Structures

Aziridines have a three-membered ring structure, whereas simple amines do not have such a strained ring. The strain in the aziridine ring increases the activation energy for inversion compared to simple amines.

Calculate Activation Energy Differences

The given activation energy for the inversion of 1,2,2-trimethylaziridine is 18.5 kcal/mol (77.5 kJ/mol). Simple amines typically have much lower activation energies, often in the range of 5-10 kcal/mol, due to less steric strain in their more flexible structures.

Draw Conclusions About Enantiomer Separation

The higher activation energy in aziridines prevents rapid inversion at room temperature, allowing the enantiomers to be separated and studied individually.

Key concepts

Aziridines

Aziridines are fascinating molecules known for their three-membered ring structure which contains one nitrogen atom. This unique ring structure creates significant strain because the bond angles are much smaller than in larger rings or simple amines. This strain impacts various properties of aziridines.
One of the most important characteristics of aziridines is their ability to exist as enantiomers, or non-superimposable mirror images. This is largely due to the rigidity of their ring structure, which prevents easy inversion around the nitrogen atom. In contrast, simple amines lack this rigid ring structure, making inversion much easier and preventing the isolation of enantiomers.
Aziridines are often used in synthetic chemistry for building more complex molecules because they can readily undergo reactions that open their strained ring structure. This makes them versatile tools in the creation of pharmaceuticals and other complex organic compounds.

Enantiomers

Enantiomers are pairs of molecules that are non-superimposable mirror images of each other. They are akin to left and right hands, which cannot be perfectly aligned when placed atop one another. This property makes enantiomers important in many areas of chemistry and biology.
In the context of aziridines, enantiomers are significant because the rigid three-membered ring structure restricts the nitrogen inversion process. As a result, the individual enantiomers of aziridines are stable enough to be separated and studied independently. This contrasts sharply with simple amines, where the lack of a strained ring allows rapid inversion, making the separation of enantiomers challenging.
Enantiomers have identical physical properties, such as melting points and boiling points, but often have vastly different biological activities. This makes their separation critical in fields like pharmaceuticals, where one enantiomer of a drug might be beneficial while its mirror image could be harmful or inert.

Activation Energy

Activation energy is the minimum amount of energy that must be provided for a chemical reaction to occur. In the case of aziridines, the activation energy for the inversion process is key to understanding why these molecules can be separated into enantiomers.
The inversion of 1,2,2-trimethylaziridine, for example, has an activation energy of 18.5 kcal/mol (77.5 kJ/mol). This high value is largely due to the strain in the three-membered ring, which makes inversion more difficult. Because of this high activation energy, the inversion process is slow at room temperature, allowing the enantiomers of aziridines to remain stable and be isolated.
In contrast, simple amines usually have much lower activation energies for inversion, typically in the range of 5-10 kcal/mol. This lower activation energy means that inversion occurs readily at room temperature, preventing the easy separation of enantiomers.

Molecular Inversion

Molecular inversion, also known as nitrogen inversion, is a process where the lone pair of electrons on the nitrogen atom flip to the opposite side, effectively converting one enantiomer into another. This flipping changes the stereochemistry of the molecule.
In simple amines, this inversion occurs relatively easily because there is no ring strain hindering the movement of atoms. As a result, the enantiomers of simple amines cannot be readily separated or isolated due to rapid inversion.
However, in aziridines, molecular inversion is much more challenging due to the strain in the three-membered ring. The rigidity of the ring structure makes it difficult for the nitrogen lone pair to flip to the opposite side, resulting in a higher activation energy for the process. As a result, the inversion occurs very slowly, if at all, at room temperature. This slow inversion rate is what makes it possible to separate and study the enantiomers of aziridines individually. Such properties of aziridines highlight their importance in stereochemical and pharmaceutical studies.