Problem 3 - Advanced Organic Chemistry. Part A. Structure and Mechanisms

Question

Offer an explanation for the following observations. a. Base-catalyzed exchange rates indicate that the hydrocarbon cubane is much more acidic than cyclobutane, and even more acidic than cyclopropane. b. Cyclopropyl phenyl ketone \((\mathrm{p} K=28.2)\) is less acidic than acetophenone ( \(\mathrm{p} K=24.7\) ) and undergoes \(\mathrm{C}-\mathrm{H}\) exchange more slowly than phenyl \(i\)-propyl ketone, despite the fact that its most acidic hydrogen is located on a cyclopropyl ring. c. The order of acidity for cyclopentadiene, indene, and fluorene in DMSO is indicated below. The gas phase acidity is in the opposite direction, as measured by the proton affinity. Why does the fusion of benzene rings decrease the solution acidity relative to cyclopentadiene? d. The rotational barrier of the allyl anion in THF, as measured by NMR, is dependent on the identity of the cation present.

Step-by-Step Solution

Answer

Increased strain and hybridization affect acidity; conjugate base stabilization by resonance also matters.

Step 1: Analyze the Structure of Cubane and Cyclobutane

Cubane is a highly strained molecule due to its cubic structure, which gives it unusual properties such as increased acidity compared to cyclobutane. Its bonds are more strained and the carbon atoms are closer to being sp-hybridized, increasing the acidity due to more percent s-character in the C-H bond.

Step 2: Compare Cyclopropane Acidity

Due to the angle strain in cyclopropane's triangular structure, its C-H bonds have increased s-character compared to cyclobutane. This makes cyclopropane more acidic than cyclobutane.

Step 3: Evaluate Cyclopropyl Phenyl Ketone vs. Acetophenone

Even though cyclopropyl rings have angle strain, acetophenone is more acidic because its conjugate base (enolate) can resonate with the aromatic ring in acetophenone, stabilizing the negative charge more effectively than in cyclopropyl phenyl ketone.

Step 4: Acidity Comparison in Different Phases

In DMSO, cyclopentadiene is more acidic because it can form a stabilized aromatic dianion after deprotonation. Fusion with benzene rings like in indene or fluorene reduces this effect, due to less efficient electron delocalization as the conjugate base becomes larger and less resonance-stabilized.

Step 5: Impact of Cation on Allyl Anion Rotation

The rotational barrier in the allyl anion is influenced by the cation's ability to stabilize or destabilize the anion. Different cations interact with the electron cloud of the allyl anion to different extents, affecting the rotational energy barrier observed by NMR.

Key Concepts

Cubane vs Cyclobutane

Cubane and cyclobutane are fascinating molecules that exhibit unique properties due to their structural configuration. Cubane, a cube-shaped molecule, has all its carbon atoms forming 90-degree angles. This configuration causes high angular strain in its bonds, impacting its chemical properties significantly.

One of the key consequences of this strain is increased acidity. The carbon-hydrogen (\(\text{C-H}\) ) bonds in cubane contain a greater percentage of \(s\)-character due to the strain and near \(\text{sp}\)-hybridization of the orbitals. This \(s\)-character makes the hydrogen atoms more acidic as they are held more tightly to the carbon nucleus.

On the other hand, cyclobutane has a less strained, square planar structure, with bond angles closer to \(109.5^{\circ}\) typical of sp\(^3\) hybridization, making the \(\text{C-H}\) bonds less acidic. In summary, the higher angle strain in cubane results in increased acidity compared to cyclobutane, and a greater acidity than cyclopropane due to a similar rationale.

Cyclopropyl Phenyl Ketone

Cyclopropyl phenyl ketone is another interesting molecule when discussing acidity, especially compared to acetophenone. \(\text{Cyclopropyl phenyl ketone}\) exhibits less acidity despite the presence of a cyclopropyl ring, a typically strained system, due to the nature of the resonance stabilization of its conjugate base.

In acetophenone, once deprotonation occurs to form the conjugate base, the negative charge can resonate through the aromatic phenyl ring. This efficient resonance greatly stabilizes the charge, hence why acetophenone is more acidic.

Conversely, the cyclopropyl phenyl ketone, although it possesses angle strain within the cyclopropyl ring, does not allow the conjugate base formed post-deprotonation to effectively resonate through the molecule. This lack of effective resonance stabilization leads to its lower acidity and slower \(\text{C-H}\) exchange compared to acetophenone.

Cyclopentadiene and Aromaticity

Cyclopentadiene is known for its unique trait of being a surprisingly acidic hydrocarbon. This is because upon deprotonation, it forms a stable aromatic dianion. Its acidity is higher in solution as it can achieve this aromatic state, yet when compared to indene and fluorene in DMSO, it stands even more acidic.

The fusion of benzene rings to form indene or fluorene adds additional \(\text{p}\)-orbitals that align along the macrocycle when deprotonated. This enlarged conjugated system results in less efficient electron delocalization, weakening the stability of the anion formed, thus effectively reducing acidity in solvents such as DMSO.

Therefore, while benzene fusion offers some delocalization, it does so less efficiently across the larger system, explaining why cyclopentadiene is more acidic in certain solvents, but exhibits the reverse trend in the gas phase.

Effect of Cations on Allyl Anion

The allyl anion is a versatile entity in organic chemistry, particularly noted for its resonance stabilization. The rotational barrier within the anion is uniquely influenced by different cations present in the solvent. When ions such as \(\text{Na}^+\), \(\text{K}^+\) , or larger cations are introduced, they will interact differently with the negatively charged electron cloud of the allyl anion.

This interaction either stabilizes or destabilizes the anion, subsequently affecting the rotational barrier. Cations that are good at interacting closely with the electron cloud will lower the energy barrier, allowing easier rotation.

Thus, the choice of cation dramatically alters the dynamics observed in the allyl anion, which is visible through techniques such as NMR, highlighting important intermolecular forces at play in these systems.