Hemiacetal Formation

The reaction is analogous to hydrate formation, except that the attacking species is the oxygen of an alcohol molecule. Hemiacetals ("half an acetal") are relatively unstable and the equilibria are usually shifted toward the starting materials.

Video (in Spanish): Quick theft or professional robbery. A glucose story (Learn Organic Chemistry with me) — Hurto rápido o robo profesional: una historia de glucosa (in Spanish: "Quick theft or professional robbery: a glucose story")

Acid-catalyzed formation of a hemiacetal

A very important exception is the intramolecular formation of hemiacetals in carbohydrates (sugars), where the resulting cyclic hemiacetals are very stable.

Cyclization of glucose: the OH on carbon 5 attacks the aldehyde and two hemiacetals epimeric at the anomeric carbon are formed

Sugars such as glucose are most stable as five- or six-membered rings, formed by intramolecular hemiacetal formation. The attack of the OH group at position 5 on the upper or the lower face of the carbonyl gives a pair of diastereomers in different proportions.

Attack of the OH at C5 on one face of the carbonyl, leading to the axial epimer.

Attack of the OH at C5 on the opposite face of the carbonyl, leading to the equatorial epimer.

Animation of the attack of the OH on one face of the glucose carbonyl

Since the configuration of the other stereocenters of glucose does not change and a new one is created at the former carbonyl carbon, two diastereomers with different physical and chemical properties are formed.

Animation of the attack of the OH on the opposite face of the glucose carbonyl

Click here to learn what the mutarotation of glucose is.