Acetal

The term ketal is sometimes used to identify structures associated with ketones (both R groups are organic fragments rather than hydrogen) rather than aldehydes and, historically, the term acetal was used specifically for the aldehyde-related cases (having at least one hydrogen in place of an R on the central carbon). The IUPAC originally deprecated the usage of the word ketal altogether, but has since reversed its decision. However, in contrast to historical usage, ketals are now a subset of acetals, a term that now encompasses both aldehyde- and ketone-derived structures.

If one of the R groups has an oxygen as the first atom (that is, there are more than two oxygens single-bonded to the central carbon), the functional group is instead an orthoester. In contrast to variations of R, both R' groups are organic fragments. If one R' is a hydrogen, the functional group is instead a hemiacetal, while if both are H, the functional group is a ketone hydrate or aldehyde hydrate.

Formation of an acetal occurs when the hydroxyl group of a hemiacetal becomes protonated and is lost as water. The carbocation that is produced is then rapidly attacked by a molecule of alcohol. Loss of the proton from the attached alcohol gives the acetal.

Acetals are stable compared to hemiacetals but their formation is a reversible equilibrium as with esters. As a reaction to create an acetal proceeds, water must be removed from the reaction mixture, for example, with a Dean–Stark apparatus, lest it hydrolyse the product back to the hemiacetal. The formation of acetals reduces the total number of molecules present (carbonyl + 2 alcohol → acetal + water) and therefore is generally not favourable with regard to entropy. One situation where the reaction is not entropically unfavourable is when a single diol molecule is used rather than two separate alcohol molecules (carbonyl + diol → acetal + water).

Acetalization and ketalization

Acetalization and ketalization are the organic reactions that involve the formation of an acetal (or ketals) from aldehydes and ketones, respectively. These conversions are acid catalysed. They eliminate water. Since each step is often a rapid equilibrium, the reaction must be driven by removal of water. Methods for removing water include azeotropic distillation and trapping water with desiccants like aluminium oxide and molecular sieves. Steps assumed to be involved: protonation of the carbonyl oxygen, addition of the alcohol to the protonated carbonyl, protonolysis of the resulting hemiacetal or hemiketal, and addition of the second alcohol. These steps are illustrated with an aldehyde RCH=O and the alcohol R'OH:

RCH=O + H⁺ ⇌ RCH=OH⁺

RCH=OH⁺ + R'OH ⇌ RCH(OH)(OR') + H⁺

RCH(OH)(OR') + H⁺ ⇌ RC⁺H(OR') + H₂O

RC⁺H(OR') + R'OH ⇌ RCH(OR')₂ + H⁺

Another way to avoid the entropic cost is to perform the synthesis by acetal exchange (transacetalization), using a pre-existing acetal-type reagent as the OR'-group donor rather than simple addition of alcohols themselves. One type of reagent used for this method is an orthoester. In this case, water produced along with the acetal product is destroyed when it hydrolyses residual orthoester molecules, and this side reaction also produces more alcohol to be used in the main reaction.