Question

A primary or secondary alcohol can be protected by conversion to its tetrahydropyranyl ether. Why is formation of THP ethers by this reaction limited to primary and secondary alcohols?

Short answer

Answer: The formation of THP ethers is limited to primary and secondary alcohols because they are less sterically hindered compared to tertiary alcohols, allowing for an easier nucleophilic attack by the oxygen atom of the alcohol on the THP ether precursor.

Step-by-step solution

Understand the structure of primary and secondary alcohols

Primary and secondary alcohols are different in terms of their attachment to the carbon atoms. In primary alcohols, the carbon atom (which is attached to the hydroxyl group) is connected to only one other carbon atom. In secondary alcohols, the carbon atom attached to the hydroxyl group is connected to two other carbon atoms.

Understand the structure of THP ethers

Tetrahydropyranyl (THP) ethers are cyclic ethers, consisting of a six-membered ring with an oxygen atom and five carbons. One of these carbons is also connected to an oxygen atom, which is bonded to the alcohol molecule. In a THP ether, the oxygen atom of the alcohol forms an ether linkage with the THP ring.

Understand the reaction mechanism for the formation of THP ethers

The reaction mechanism for the formation of THP ethers involves the attack of the oxygen atom from an alcohol molecule on the THP ether precursor (e.g. DHP, dihydropyran) via a nucleophilic substitution reaction. This results in the ether linkage between the THP ring and the alcohol and the cleavage of a double bond in the precursor.

Explain the limitation of THP ether formation to primary and secondary alcohols

The reason behind the limitation of THP ether formation to primary and secondary alcohols is sterics. Tertiary alcohols have the hydroxyl group attached to a carbon that is connected to three other carbon atoms, making it more sterically hindered. This steric hindrance hinders the nucleophilic attack by the oxygen atom in tertiary alcohols and makes the reaction less feasible. In contrast, primary and secondary alcohols, being less sterically hindered, can easily undergo the nucleophilic attack and form THP ethers. In conclusion, formation of tetrahydropyranyl ethers is limited to primary and secondary alcohols because they are less sterically hindered compared to tertiary alcohols, allowing for an easier nucleophilic attack by the oxygen atom of the alcohol on the THP ether precursor.