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Q8.18(i):
Give plausible explanation for the following: (i) Cyclohexanone forms cyanohydrin in good yield but 2,2,6-trimethylcyclo-hexanone does not.

Solution :

Given Variables & Initial Setup

The reaction involves the nucleophilic addition of cyanide ion ($CN^-$) to a ketone to form a cyanohydrin. The reaction pathway proceeds via the attack of the nucleophile on the electrophilic carbonyl carbon ($C=O$), resulting in a change of hybridization from $sp^2$ (trigonal planar) to $sp^3$ (tetrahedral).

  • Reactant A: Cyclohexanone
  • Reactant B: 2,2,6-trimethylcyclohexanone
  • Nucleophile: $CN^-$

Step 1: Structural Analysis of Cyclohexanone

In cyclohexanone, the carbonyl carbon is relatively unhindered. When the $CN^-$ nucleophile attacks, the transition state geometry allows for the conversion to the tetrahedral intermediate without significant internal steric clashing. The energy barrier for this transition state is low, facilitating a high yield of cyanohydrin product [Per Transition State Theory].

Step 2: Structural Analysis of 2,2,6-Trimethylcyclohexanone

In 2,2,6-trimethylcyclohexanone, the presence of three methyl groups in the immediate vicinity of the carbonyl center introduces severe steric strain:

  • Two methyl groups at the $C_2$ position create significant 1,2-steric hindrance.
  • One methyl group at the $C_6$ position creates additional 1,6-steric hindrance.

During the nucleophilic attack, the carbonyl carbon must expand its bond angles and accommodate the approaching $CN^-$ group. In this molecule, the methyl groups (especially the axial-like methyls) experience severe van der Waals repulsion with the incoming nucleophile and the existing oxygen atom in the tetrahedral intermediate [Per VSEPR Theory and Steric Inhibition].

Step 3: Steric Crowding Visualization

O Cyclohexanone (Accessible) O 2,2,6-Trimethyl (Sterically Hindered)

Step 4: Thermodynamic and Kinetic Implications

The steric congestion in 2,2,6-trimethylcyclohexanone raises the potential energy of the transition state significantly. Furthermore, the tetrahedral intermediate is inherently less stable due to increased steric crowding compared to the reactant. Thus, the equilibrium constant ($K_{eq}$) for the addition reaction is unfavorable for the trimethyl-substituted derivative [Per Le Chatelier's Principle and Steric Hindrance Effects].

Feature Cyclohexanone 2,2,6-Trimethylcyclohexanone
Steric Hindrance Minimal Severe (due to 3 methyl groups)
Attack Accessibility High Low (Sterically shielded)
Yield High Negligible

Final Solution: Cyclohexanone undergoes cyanohydrin formation readily because the carbonyl carbon is sterically accessible. Conversely, 2,2,6-trimethylcyclohexanone experiences severe steric hindrance from the three methyl groups near the reaction center, which raises the activation energy and destabilizes the tetrahedral intermediate, effectively preventing the formation of the cyanohydrin.


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