Hemiacetals of aldehydes

Like their hydrates, the hemiacetals of most ketones (sometimes called hemiketals) are even less stable than those of aldehydes. On the other hand, some hemiacetals of aldehydes bearing electron-withdrawing groups, and those of cyclopropanones, are stable, just like the hydrates of the same molecules. 

The mechanism of the above reaction involves hydride abstraction from a coordinated alcohol [100]. It can be seen from this that aldehydes which tend to hydrate to a small extent in solution can themselves act as alcohols and undergo further /f-abstraction to form the carboxylic acid. Esters can be formed from this acid and the starting alcohol, or from oxidation of the hemiacetal of aldehyde and alcohol. Hence, other oxidation methods are required for primary alcohols. 

The condensation of aldehydes or ketones with secondary amines leads to "encunines via N-hemiacetals and immonium hydroxides, when the water is removed. In these conjugated systems electron density and nudeophilicity are largely transferred from the nitrogen to the a-carbon atom, and thus enamines are useful electroneutral d -reagents (G.A. Cook, 1969 S.F. Dyke, 1973). A bulky heterocyclic substituent supports regio- and stereoselective reactions. 

Many of the most interesting and useful reactions of aldehydes and ketones involve trans formation of the initial product of nucleophilic addition to some other substance under the reaction conditions An example is the reaction of aldehydes with alcohols under con ditions of acid catalysis The expected product of nucleophilic addition of the alcohol to the carbonyl group is called a hemiacetal The product actually isolated however cor responds to reaction of one mole of the aldehyde with two moles of alcohol to give gem mal diethers known as acetals... 

Additional evidence that a dynamic equilibrium exists between an enamine, N-hemiacetal, and aminal has been presented by Marchese (41). It should be noted that no acid catalysts were used in the reactions of aldehydes and amines discussed thus far. The piperidino enamine of 2-ethylhexanal (0.125 mole), morpholine (0.375 mole), and p-toluene-sulfonic acid (1.25 x 10 mole) diluted with benzene to 500 ml were refluxed for 5 hr. At the end of this time the enamine mixture was analyzed by vapor-phase chromatography, which revealed that exchange of the amino residue had occurred in a ratio of eight morpholine to one piperidine. Marchese proposed a scheme [Eqs. (4), (5) and (6)] to account for these... 

Hemiacetals themselves are no more stable than the corresponding hydrates (16-1). As with hydrates, hemiacetals of cyclopropanones and of polychloro and polyfluoro aldehydes and ketones may be quite stable. 

When catalyzed by acids, low molecular weight aldehydes add to each other to give cyclic acetals, the most common product being the trimer. The cyclic trimer of formaldehyde is called trioxane, and that of acetaldehyde is known as paraldehyde. Under certain conditions, it is possible to get tetramers or dimers. Aldehydes can also polymerize to linear polymers, but here a small amount of water is required to form hemiacetal groups at the ends of the chains. The linear polymer formed from formaldehyde is called paraformaldehyde. Since trimers and polymers of aldehydes are acetals, they are stable to bases but can be hydrolyzed by acids. Because formaldehyde and acetaldehyde have low boiling points, it is often convenient to use them in the form of their trimers or polymers. 

Dimethyl acetals of aldehydes and ketones, for example benzaldehyde dimethyl acetal 121, and hemiacetals, react with allyltrimethylsilane 82 at -78 °C in CH2CI2, in the presence of TMSOTf 20 [169], trimethyhodosilane TIS 17 [159, 170],... 

When alcohols are added to the reaction mixture, unsymmetrical ether products may be obtained. Starting with a mixture of aldehydes can also give rise to the formation of unsymmetrical ethers. These ether products are formed under conditions different from those used in the formation of ethers directly from alcohols. Thus, it is postulated that the reaction sequence that leads from the carbonyl substrate to the ether involves the intermediate formation of hemiacetals, acetals, or their protonated forms and alkoxycarbenium ions, which are intercepted and reduced to the final ether products by the organosilicon hydrides present in the reaction mix. The probable mechanistic scheme that is followed when Brpnsted acids are present is outlined in Scheme 2.311-327 328... 

Halocarbons, ketone-alcohol reduction, 84 Halogenation, 4-methylbenzyl chloride [reductive halogenation of aldehyde to benzyl chloride], 124 Hemiacetals, reduction of, 97-99 Hemiaminals, reduction of, 99-100 Hemiketals, reduction of, 97-99 Heptene derivatives, alkene to alkane reductions, disubstituted alkenes, 36-38... 

The synthetic pathway starts with the preakuammicine structure (Figure 42) by hydrolysis, decarboxylation and condensation reactions to aldehyde (Wieland-Gumlich), and subsequently reacts with acetyl-CoA to make a hemiacetal form of aldehyde (Wieland-Gumlich) and strychnine (Figure 43). 

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). 

The position of equilibrium in acetal and hemiacetal formation is rather sensitive to steric hindrance. Large groups in either the aldehyde or the alcohol tend to make the reaction less favorable. Table 15-3 shows some typical conversions in acetal formation when 1 mole of aldehyde is allowed to come to equilibrium with 5 moles of alcohol. For ketones, the equilibria are still less favorable than for aldehydes, and to obtain reasonable conversion the water must be removed as it is formed. 

Although the crystalline forms of a- and /3-D-glucose are quite stable, in solution each form slowly changes into an equilibrium mixture of both. The process can be observed as a decrease in the optical rotation of the a anomer (+112°) or an increase for the /3 anomer (+18.7°) to the equilibrium value of 52.5°. The phenomenon is known as mutarotation and commonly is observed for reducing sugars. Both acids and bases catalyze mutarotation the mechanism, Equation 20-1, is virtually the same as described for acid- and base-catalyzed hemiacetal and hemiketal equilibria of aldehydes and ketones (see Section 15-4E) ... 

The aldehyde reacts with the starting alcohol, yielding a stable hemiacetal that can be further oxidized to a dimeric ester. The formation of the dimeric ester can be minimized by the use of high dilution and the slow addition of the alcohol to the oxidant, resulting in a reaction giving an optimized 5 2 ratio of aldehyde to dimeric ester. 

A typical reaction of aldehydes and ketones is addition to the C—O ji bond. Examples of addition reagents are H2 (resulting in reduction to the corresponding alcohol), ROH (to give a hemiacetal or hemiketal) and RM (yielding a metal alkoxide). Only the hydrogenation reaction produces an addition product for which there is any useful quantity of thermochemical data, however. Equation 34 represents an overall reaction of the carbonyl compound with a (hypothetical) reagent XY, an equation which includes any reaction, subsequent to an initial addition reaction, to form products for which there are sufficient data. 

Reactions of aldehydes with alcohols produce either hemiacetals (a functional group consisting of one —OH group and one —OR group... 

The aluminium alkoxide acts as a Lewis acid to coordinate with one molecule of the aldehyde, and to facilitate the addition of a second equivalent of aldehyde, generating a hemiacetal intermediate ... 

With acid catalysis, alcohols add to the carbonyl group of aldehydes to give hemiacetals [RCH(OH)OR ]. Further reaction with excess alcohol gives acetals [RCH(OR )2]- Ketones react similarly. These reactions are reversible that is, acetals can be readily hydrolyzed by aqueous acid to their alcohol and carbonyl components. Water adds similarly to the carbonyl group of certain aldehydes (for example, formaldehyde and chloral) to give hydrates. Hydrogen cyanide adds to carbonyl compounds as a carbon nucleophile to give cyanohydrins [R2C(OH)CN],... 

Detailed studies of the periodate oxidation of dextran and inulin (4-6) have shown evidence for the occurrence of hemiacetal structures formed by reaction of aldehydes with hydroxyl groups of either the same unit (intra-residual) or a neighbouring unit (inter-residual). Inter-residual hemiacetal formation reduces the number of diol struc-... 

The substance has the properties of an aldehyde.3 It gives a positive reaction with the Schiff reagent, strongly reduces hot Fehling solution, and gives as a d-hydroxyaldehyde a cyclic hemiacetal of glycoside type.u-17... 

RCHO - RCOOCH,. This conversion can be effected by oxidation of aldehydes with Br2 in CH3OH via a hemiacetal (equation I). The method is applicable o optically pure aldehydes obtained from sugars. Yields are moderate in the reaction with aromatic aldehydes.1... 

Although monosaccharides exist predominantly as hemiacetals, enough aldehyde or ketone is present at equilibrium that the sugars give most of the reactions of these functional groups. In addition, monosaccharides exhibit the reactions of alcohols. Of course, the presence of bodi functional groups may perturb the reactions of either of them. 

As a conceptually new allylation of aldehydes, an allylic functionality of the homoallyl alcohols is transferred to aldehydes via the formation of a hemiacetal and the elimination of acetone to give a-adduct homoallylic alcohols in the presence of a catalytic amount of Sn(OTf)2 (Equation (107)).274... 

The formation of a ring by the open-chain form of D-glucose can be considered to be the result of a reaction between the hydroxyl group on C-5 and the aldehyde group to give a hemiacetal. The aldehyde carbon becomes chiral as a result, thus giving rise to two hemiacetals, a- and /3-D-glucose. 

In this series of equilibrium steps, the hemiacetal ring of a-glucose opens to yield the free aldehyde. Bond rotation is followed by formation of the cyclic hemiacetal of 6-glucose. The reaction is catalyzed by both acid and base. 

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