Hemiacetal
In organic chemistry, a hemiacetal is a functional group the general formula Template:Chem2, where Template:Chem2 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 (Template:Chem2) or a ketone (Template:Chem2) 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 monosaccharides. Hemiacetals have use as a protecting group and in synthesizing oxygenated heterocycles like tetrahydrofurans.
Nomenclature
[edit]According to the IUPAC definition of a hemiacetal, the R1 and R2 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.<ref>Template:GoldBookRef</ref> The prefix hemi, meaning half, refers to the one alcohol added to the carbonyl group. This is half of the required alcohols to form acetals or ketals.<ref name=":0">Template:Cite book</ref> Cyclic hemiacetals can sometimes be referred to as lactols.<ref>IUPAC Gold Book lactols</ref>
Formation
[edit]Template:Multiple image 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.<ref>Template:Cite journal</ref> A subsequent nucleophilic attack of the hemiacetal by the alcohol results in an acetal.<ref name=":0" /> 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.<ref name="Patai">Template:Cite book</ref>
| Carbonyl compound | alcohol solvent | %hemiacetal |
|---|---|---|
| acetaldehyde | methanol | 97 |
| acetaldehyde | ethanol | 91 |
| propionaldehyde | methanol | 95 |
| bromoacetone | methanol | 47 |
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.<ref name=":1">Template:Cite book</ref>
Hemiacetals in nature
[edit]Hemiacetals commonly exist in nature as aldoses such as glucose, and hemiketals commonly exist in nature as ketoses 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.<ref>Template:Cite web</ref>
Usage
[edit]Tetrahydrofurans can be synthesized from nucleophilic addition to hemiacetals with high stereoselectivity, which can be further used to form polymers such as lignans.<ref>Template:Citation</ref>
Hemiacetals can also undergo acid-catalyzed spirocyclization or metal-catalyzed addition/elimination to afford spiroacetals. These reactions are moderately stereoselective, although the thermodynamically-favoured isomer is often produced.<ref>Template:Citation</ref> Drug discovery programs synthesize spiroacetal scaffolds to generate libraries of spiroacetal-containing molecules. These spiroacetal derivatives have potential use in treating diseases such as CLL leukemia.<ref>Template:Citation</ref>
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 acids.<ref>Template:Cite journal</ref>
References
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