Addition of Alcohols - Hemiacetals and Acetals

The addition of alcohols to aldehydes and ketones under acidic conditions results in the formation of hemiacetals and acetals.  When one equivalent of alcohol is used a hemiacetal forms.  It requires 2 or more equivalents of alcohol to form the acetal.

Here are the overall general transformations.

Mechanism - Hemiacetal Formation

The mechanisms begins with protonation of the carbonyl oxygen, activating the carbonyl for nucleophilic attack by an alcohol molecule.  In step two the alcohol attacks forming a tetrahedral intermediate.  The carbonyl carbon changed hybridization from sp2 to sp3.  Deprotonation of the tetrahedral intermediate yields the hemiacetal 

Hemiacetals are sensitive (reactive) to aqueous acidic or basic solutions.  Treating them with aqueous acid or base simply yields the alcohol and aldehyde/ketone starting materials.  Just like when an aldehyde is dissolved in water it is in equilibrium with its hydrate (gen-diol), when an aldehyde/ketone is dissolved in alcohol it is in equilibrium with the hemiacetal.  Hemiacetals are intermediates in the formation of acetals.

In general hemiacetals are rather unstable and difficult to isolate.  Cyclic hemiacetals on the other hand are stable isolable compounds.

Could you draw a mechanism for the reaction of a hydroxide ion with a hemiacetal?

Mechanism - Acetal Formation

Hemiacetals are intermediates in the formation of acetals.

Protonation of the hemiacetal's hydroxyl group yields the first protonated intermediate.  The protonated hydroxyl gourp is a good leaving group (water) and so is expelled in the second step reforming a C=O bond.  The newly formed C=O bond is very reactive, it resembles a protonated carbonyl and is a very good electrophile.  An alcohol nucleophile then attacks this carbonyl-like compound regenerating the tetrahedral intermediate.  Finally, a deprotonation yields the acetal.

A quick word on protonated carbonyls and the carbonyl-like intermediate.

A protonated carbonyl is really just a resonance stabilized carbocation.

Likewise the carbonyl "like" intermediate is a resonance stabilized carbocation.

Example Reactions

Recall that these reactions require acid (H+) and this often comes in the form of concentrated sulfuric (H₂SO₄) or pTSA (para-toluoylsulphonic acid).

Both alcohols could be on the same molecule.

There are intramolecular variations possible also.  In this example, one equivalent of alcohol is intramolecular while the other (ethanol) is intermolecular.

Both alcohols are intramolecular.