The formation of cyanohydrin involves nucleophilic addition of cyanide ion to the carbonyl carbon. In cyclohexanone, the carbonyl carbon is accessible for nucleophilic attack. However, in 2,2,6-trimethylcyclohexanone, the three methyl groups at positions 2 and 6 create significant steric hindrance around the carbonyl carbon. This steric crowding prevents the nucleophile from approaching effectively, resulting in poor yield of cyanohydrin.

In semicarbazide (H₂N-NH-CO-NH₂), the two -NH₂ groups are not equivalent. The -NH₂ group attached directly to the carbonyl (C=O) is less nucleophilic because the lone pair on nitrogen participates in resonance with the carbonyl group, reducing its electron density. The other -NH₂ group attached to the -NH- moiety is more nucleophilic as it does not participate in such resonance. Therefore, only this -NH₂ group is involved in nucleophilic addition during semicarbazone formation.

Esterification is a reversible reaction: RCOOH + R'OH ⇌ RCOOR' + H₂O. According to Le Chatelier's principle, removing one of the products (water or ester) from the reaction mixture shifts the equilibrium towards the product side. This increases the yield of ester and prevents the reverse reaction (hydrolysis). The context states that esterification involves 'nucleophilic acyl substitution' where water is eliminated as a neutral molecule. Hence, removing water or ester as soon as it forms drives the reaction forward.