Question

Write a mechanism for the acid-catalyzed hydrolysis of a THP ether to regenerate the original alcohol. Into what compound is the THP group converted?

Short answer

Answer: After a THP ether undergoes acid-catalyzed hydrolysis, a THP diol is formed as the final THP compound. The acid catalyst, such as HCl, provides the necessary protons (H+) needed for the protonation and deprotonation steps in the reaction mechanism, making the THP O-atom more susceptible to nucleophilic attack and facilitating the overall hydrolysis process.

Step-by-step solution

Protonation of the THP O-atom

A strong acid, usually HCl, is used as a catalyst for this reaction. The electron pair on the oxygen atom of the THP ether attacks and accepts a proton (H+) from HCl. This makes the O-atom positively charged and more susceptible to nucleophilic attack.

Attack of a water molecule

A water molecule acts as a nucleophile and attacks the positively charged oxygen atom of the protonated THP ether. This results in the formation of an oxonium ion intermediate, with water attached to the THP O-atom.

Formation of the THP ring-opened intermediate

In this step, electrons from one of the C-O bonds in THP migrate back to the positively charged oxygen atom, causing the ring to open up. This results in the THP ring-opened intermediate with a positive charge on one of the terminal carbons.

Deprotonation of the water molecule

A negatively charged nucleophile, such as the Cl- ion, attacks the positively charged carbon in the THP ring-opened intermediate and removes a proton from the water molecule attached to the O-atom during the attack. This leads to the formation of the alcohol and a positively charged THP molecule with an HCl molecule attached to the terminal carbon.

Regeneration of the alcohol and formation of the final THP compound

Finally, another water molecule attacks the positively charged terminal carbon of the THP molecule, causing the HCl to leave as a leaving group. This completes the hydrolysis of the THP ether and results in the formation of the original alcohol and a THP diol as the final THP compound. In conclusion, the THP group is converted into a THP diol after hydrolysis.