Ketones also form hemiacetals

Hydroxyketones also form hemiacetals, but (as you should now expect) they usually do so less readily than hydroxyaldehydes. However, this hydroxyketone must exist solely as the cyclic hemiacetal because it shows no C=0 stretch in its IR spectrum. The reason The starting hydroxyketone is already cyclic, with the hydroxyl group poised to attack the ketone—it can t get away, so cyclization is highly favoured. 

Well, you saw a diagram like this in the last chapter when we were discussing kinetic and thermodynamic products (p. 329) and you can probably also apply something of what you now know about the reactivity of carbonyl compounds towards nucleophiles to work out what is happening in this reaction between a carbonyl compound and an amine. The hydroxylamine first adds to the ketone to form an unstable intermediate similar to a hemiacetal. 

In Section 12.6, we saw that aldehydes and ketones react with alcohols to form hemiacetals. We also saw that cyclic hemiacetals form very readily when hydroxyl and carbonyl groups are parts of the same molecule and their interaction can form a five- or six-membered ring. For example, 4-hydroxypentanal forms a five-membered cyclic hemiacetal. Note that 4-hydroxypentanal contains one stereocenter and that a second stereocenter is generated at carbon 1 as a result of hemiacetal formation ... 

Certain aldehydes and ketones, generally those that for steric or electronic reasons also form stable hydrates or hemiacetals, can... 

Hemiacetals are more readily formed from aldehydes than from ketones.77 4-Hydroxybutanal and 5-hydroxypentanal exist preponderantly as cyclic hemiacetals, containing only 11.4 and 6.1%, respectively, of the free aldehyde.79 These often-quoted data were, however, obtained for solutions in 3 1 1,4-dioxane-water, and, if experience gained with the hydroxyketones75 is also valid for the hydroxyaldehydes, the proportion of aldehyde would be much higher in aqueous solution (for which data are not yet available). 

Aldehydes and ketones both may be reduced to alcohols by hydrogenation (see the alcohol dehydrogenation reaction, equation 5). Aldehydes may react with either water or alcohol to form aldehyde hydrates or hemiacetals, respectively (also see figure 7 for intramolecular hemiacetals formed by sugars). Reaction of an aldehyde with two molecules of alcohol leads to acetal formation. 

Acylphosphonates, e.g. (5), possess highly reactive carbonyl groups and—somewhat like trilialomethyl ketones—exhibit both ketone and carboxy character, forming oximes and adducts, and also carboxylate derivatives via C—P bond cleavage.7 Their hemiacetal derivatives have been studied by 31P-NMR in the presence of alcohols, for the representative acetyl and benzoyl compounds (5 R = Me, Ph). Equilibrium and... 

Acid-catalyzed removal of a TMS protecting group from a bicyclic lactone in methanol solution proceeded with intramolecular acetylation after conjugate addition of methanol to an a,/ -unsatu-rated ketone side chain. By this route the 6-5-5 tricyclic acetal (27) is obtained in excellent yield (Equation (7)) <90JCS(Pl)75i>. Hemiacetal derivatives of the acetals were also prepared, and were found to exist in equilibrium with their open hydroxy-ketone forms by H NMR. 

The base is important because it removes the proton from the alcohol as it attacks the carbonyl group. A base commonly used for this is pyridine. If tbe electrophile had been an aldehyde or a ketone, we would have got an unstable hemiacetal, which would collapse back to starting materials by eliminating the alcohol. With an acyl chloride, the alkoxide intermediate we get is also unstable. It collapses again by an elimination reaction, this time losing chloride ion, and forming the ester. 

Just as protonated carbonyl groups are much more electrophilic than unprotonated ones, these oxonium ions are powerful electrophiles. They can react rapidly with a second molecule of alcohol to form new, stable compounds known as acetals. An oxonium ion was also an intermediate in the formation of hemiacetals in acid solution. Before reading any further, it would be worthwhile to write out the whole mechanism of acetal formation from aldehyde or ketone plus alcohol through the hemiacetal to the acetal, preferably without looking at the fragments of mechanism above, or the answer below. 

Acetalization and ketalization, like esterification, are also important candidate reactions for RD. It is a reversible reaction between aldehyde/ketone and alcohol that generates one molecule of water with one molecule of acetal/ketal. Various acetals, such as methylal and dioxalane, are useful solvents in the chemical industry. Ma-samuto and Matsuzaki (1994) first prepared methylal from formaldehyde and methanol in the presence of cation-exchange resins using a laboratory scale RD column conveniently packed in the form of tea-bag structures [31]. Kolah et al. studied this reaction in both batch and continuous RD column, as shown in Fig. 1.6, with a theoretical analysis of multiple reactions in the RD column [32]. Along with the acetal, formation of dimers and hemiacetals also takes place with substantial con-... 

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