In organic chemistry, a hemiacetal is a functional group the general formula , where is a hydrogen atom or an organic substituent. They generally result from the nucleophilic addition of an alcohol (a compound with at least one hydroxy group) to an aldehyde () or a ketone () under acidic conditions. The addition of an alcohol to a ketone is more commonly referred to as a hemiketal. Common examples of hemiacetals include cyclic Monosaccharide. Hemiacetals have use as a protecting group and in synthesizing oxygenated heterocycles like Tetrahydrofuran.
Nomenclature
According to the
IUPAC definition of a hemiacetal, the R
1 and R
2 groups may or may not be hydrogen. In a hemiketal, both of these R-groups must not be hydrogen. Thus, hemiketals are regarded as a subclass of hemiacetals.
The prefix
hemi, meaning half, refers to the one alcohol added to the
carbonyl group. This is half of the required alcohols to form
acetal or
ketal.
Cyclic hemiacetals can sometimes be referred to as
.
[IUPAC Gold Book lactols]
Formation
Hemiacetals form in the reaction between alcohols and aldehydes or ketones. Using an acid catalyst, the reaction proceeds via nucleophilic attack of the carbonyl group by the alcohol.
A subsequent nucleophilic attack of the hemiacetal by the alcohol results in an
acetal.
Solutions of simple aldehydes in alcohols mainly consist of the hemiacetal. The equilibrium is dynamic and can be easily reversed via
hydrolysis. The equilibrium is sensitive to steric effects.
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Cyclic hemiacetals often form readily, especially when they are 5- and 6-membered rings. In this case, a hydroxy group reacts with a carbonyl group within the same molecule to undergo an intramolecular cyclization reaction.
Hemiacetals in nature
Hemiacetals commonly exist in nature as
Aldose such as
glucose, and hemiketals commonly exist in nature as
Ketose such as
fructose. 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.
Usage
Tetrahydrofuran can be synthesized from nucleophilic addition to hemiacetals with high stereoselectivity, which can be further used to form polymers such as
Lignan.
Hemiacetals can also undergo acid-catalyzed Spiro compound or metal-catalyzed addition/elimination to afford spiroacetals. These reactions are moderately stereoselective, although the thermodynamically-favoured isomer is often produced.
One method of producing linear hemiacetal esters is through the condensation of stabilized hemiacetals by anhydrides; this creates a stable hemiketal intermediate that subsequently undergoes acetylation into the hemiacetal ester. Hemiacetal esters are primarily used in polymer chemistry as a polymerization initiator and as a protecting group for Carboxylic acid
