Hemiacetal

In organic chemistry, a hemiacetal or a hemiketal has the general formula R¹R²C(OH)OR, where R¹, R² is hydrogen or an organic substituent. They generally result from the addition of an alcohol (a compound with at least one −OH group) to an aldehyde (R−CH=O) or a ketone (R₂C=O), although the latter are sometimes called hemiketals. Most sugars are hemiacetals.

Nomenclature

According to the IUPAC definition, in R¹R²C(OH)OR R¹ and R² may or may not be a hydrogen. In a hemiketal, neither R-group can be a hydrogen. Hemiketals are regarded as hemiacetals where none of the R-groups are H, and are therefore a subclass of the hemiacetals. The Greek prefix hèmi means half, refers to the fact that a single alcohol has been added to the carbonyl group, in contrast to acetals or ketals, which are formed when a second alkoxy group has been added to the structure.

Cyclic hemiacetals and hemiketals are sometimes called lactols. They often form readily, especially when they are 5- and 6-membered rings. In this case an intramolecular OH group reacts with the carbonyl group. Glucose and many other aldoses exist as cyclic hemiacetals whereas fructose and similar ketoses exist as cyclic hemiketals.

Formation

Formation of hemiacetals

Formation of hemiketals

Solutions of simple aldehydes in alcohols mainly consist of the hemiacetal. The equilibrium is easily reversed and dynamic. The equilibrium is sensitive to steric effects.

Acetalization of aldehydes and ketones

Carbonyl compound	alcohol solvent	%hemiacetal
acetaldehyde	methanol	97
acetaldehyde	ethanol	91
propionaldehyde	methanol	95
bromoacetone	methanol	47

Structures of some readily isolable hemiacetals and hemiketals. Chloral and ethyl glyoxalate illustrate the stabilizing influence of electron-withdrawing groups. The cyclopropanone case illustrates the effect of ring-strain. The two cases on the right illustrate the effect of ring-closure.

Hemiacetals in nature

Arguably, the most common hemiacetals are sugars, for example glucose. The favorability of the formation of a strain-free six-membered ring and the electrophilicity of an aldehyde combine to strongly favor the acetal form.

Left, glucose, a cyclic hemiacetal. Right a lactol of fructose, a cyclic hemiketal.

Reactions

Hemiacetals and hemiketals may be thought of as intermediates in the reaction between alcohols and aldehydes or ketones, with the final product being an acetal or a ketal:

R₂C=O + R'OH ⇌ R₂C(OH)(OR')

R₂C(OH)(OR') + R'OH ⇌ R₂C(OR')₂ + H₂O

Usually, the second reaction is unfavorable. In the presence of a dehydrating agent, it proceeds.