Acetals reactions Hemiacetals

Vanillin, being an aldehyde, is able to form acetals and hemiacetals. Therefore, in flavor formulations using high concentrations of vanillin in conjunction with carriers such as propylene glycol, a glc analysis often shows a reduced vanillin peak after storage of the compounded flavor, and the presence of new peaks indicating acetal formation. Addition of about 0.5% of water to the formula reverses the reaction, ie, there is a reduction of acetal, and the reappearance of vanillin peaks. 

Acetal and hemiacetal groups are particularly common in carbohydrate chemistry. Glucose, for instance, is a polyhydroxy aldehyde that undergoes an internal nucleophilic addition reaction and exists primarily as a cyclic hemiacetal. 

This variation in the relative rates of C— bond cleavage of analogous orthoesters and hemiorthoesters (and of acetals and hemiacetals) is of course a reflection of the different effect of substituents on the rates of these two classes of reaction. As discussed above, substituents capable of stabilizing carbocations have a greater effect on the rates of C— bond cleavage of orthoesters (and acetals) than of hemiorthoesters (and hemiacetals). 

In any event a model valid for enzymic saccharide syntheses as far apart in behavior as those stemming from substrates with mixed acetal and hemiacetal structures might be expected to carry certain assumptions and implications for the entire discipline. This is the case with the type of reaction mentioned at the outset,... 

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. 

We saw in the previous chapter that aldehydes react with alcohols to form hemi-acetals, and hemiacetals react with another alcohol to afford acetals. Well, the intramolecular reaction of the aldehyde carbon of an aldose monosaccharide with one of the hydroxyl groups in the same molecule affords a cyclic hemiac-etal. An mferaiolecular reaction of this hemiacetal with the hydroxyl group of another sugar molecule provides an acetal functional group. This kind of acetal linkage connects monosaccharides into polysaccharides. Biochemists refer to these acetal (and ketal) bonds as glycoside bonds. 

The imines 12 (X = 4-CH3-QH4-SO2 (Ts), Ar, C02R, COR, etc.) preformed or generated in situ from N,0- or N,N-acetals or hemiacetals are another important class of Mannich reagents frequently used for diastereo- and/or enantioselective aminoalkylation reactions catalyzed by chiral Lewis acids (usually copper or palladium BINAP complexes such as 13). Among other things excellent results were obtained in the aminoalkylation of silyl enol ethers or ketene acetals [24], A typical example is the synthesis of Mannich bases 14 depicted in Scheme 5 [24b], Because of their comparatively high electrophilicity imines 12 could even be used successfully for the asymmetric aminoalkylation of unactivated alkenes 15 (ene reactions, see Scheme 5) [24h, 25], and the diastereo- and/or enantioselective aminoalkyla-... 

Reactions with Aldehydes and Ketones. Alcohols may combine additively with other carbonyl compounds such addition compounds are known as hemiacetals or acetals (Reaction XVII). 

Earlier it was considered that formaldehyde adsorbs onto starch,719 but later papers have shown that chemical reaction takes place with the formation of acetals and hemiacetals.720,721... 

As pointed out by Skrabal and Schiffrer [173], the rate-determining step must be in the transition from acetal to hemiacetal because the rate coefficient for the hydrolysis of methyl ethyl formal is equal to the mean value of those for the hydrolyses of dimethyl formal and diethyl formal. Wolf and Hero Id [174] supplied more direct evidence on this matter. They found that the UV absorption bands of aldehydes slowly decrease in alcoholic solutions. This indicates that a reaction takes place. The product of the reaction immediately splits off aldehyde under the conditions of a bisulfite titration, therefore it cannot be acetal and it must be hemiacetal. Acetals are much more stable, and they are not hydrolyzed in a bisulfite titration. A quantitative kinetic study of the reaction of aldehyde with alcohol was carried out by Lauder (175] with the aid of dilatometric and refractive index measurements. He observed that hemiacetal is formed in a relatively fast reaction which is followed by a slow reaction leading to acetal. 

Iminium salts (2) can commonly be prepared from the reaction of amines with aldehydes or ketones (1 Scheme 1). With formaldehyde as the carbonyl precursor, Eschweiler-Clark-type methylation reactions may occur when using reducing acids such as formic acid. Alternatively, other sp -type, nitrogen-free carbonyl derivatives (3), such as acetals and hemiacetals, can be used, where this is favorable. Highly electron-poor carbonyls, such as chloral (c/. Scheme 10), may show distinctly decreased reactivity in aqueous solution, due to the extended hydrate formation. 

The FTIR spectra showed that the aerosols formed contained hydrates, polymeric forms, acetals and hemiacetals. Several peaks in these spectra closely corresponded to peaks in FTIR spectra of aerosols collected in the Smoky Mountains (Jang et al. 2002). Czoschke et al. (2003) concluded, that in their experiments, isoprene had been oxidised to aldehydes by ozone in the gas phase, and the aldehydes had been converted to the observed products in heterogeneous, acid-catalysed reactions. However, the presented analysis of aerosol yields was very approximate, and did not exclude the possibility of heterogeneous reactions of isoprene in the discussed experiments. All the differences in reactors and techniques given, in the experiments by Limbeck et al. (2003) ozone reacted with isoprene in the gas phase, but decreased the amount of polymers formed. 

Allenylsilanes react with acetals, as they do with aldehydes, by addition, but a simple elimination step completes the substitution reaction (Scheme 48). Propargylsilanes likewise react with acetals in the presence of Lewis acids (Scheme 49). The reaction has en used intramolecularly (Scheme 50), where the first step is likely to be acetal or hemiacetal formation followed by ring closure, and in reactions at the anomeric position of sugars with high levels of axial attack giving allenes. ... 

However, this is not the product t)q)ically isolated from this reaction. Hemiacetals are quite reactive. In the presence of acid and excess alcohol, they imdergo a substitution reaction in which the —OH group of the hemiacetal is exchanged for another —OR group from the alcohol. The product of this reaction is an acetal. Acetal formation is a reversible reaction, as the general equation shows ... 

In addition to the main reactions, aldolization and elimination, we also observed side reactions in some of the e qreriments, such as acetalization of the reacting aldehydes. In fact, when methanol was used as solvent, it reacted with the aldehydes forming the corresponding acetals and hemiacetals. This reaction is highly undesirable, since it partially destroys the reagents. The change of the... 

Acetals and hemiacetals can be reduced with triethylsilane and an acid or Lewis acid. For example, the benzylidene acetal 133 was treated with triethylsilane and boron trifiuoride etherate to give the product 134, in which the 6-benzyl ether was formed selectively (7.123). In a synthesis of the potent anti-tumor agent phorboxa-zole B, the hemiacetal 135 was reduced to a single diastereomer of the cyclic ether 136 (7.124). These types of reactions are thought to take place by co-ordination of the Lewis acid to one of the oxygen atoms (or its protonation when using TFA) followed by formation of an oxonium ion, which is reduced by the silane. 

We said that a solution of acetaldehyde in methanol contains a new compound a hemiacetal. We ve also said that the rate of formation of hemiacetals is increased by adding an acid (or a base) catalyst to the alcohol plus aldehyde mixture. But, if we add catalytic acid to our acetaldehyde-methanol mixture, we find not only that the rate of reaction of the acetaldehyde with the methanol increases, but also that a different product is formed. This product is an acetal the hemiacetal is half-way there. 

Hydroxy ketones can be synthesized via the pyrrolidine sulfonamide- and prolinamide-catalyzed direct aldol reaction of methyl-aryl ketones with aromatic aldehydes [51]. Modest enantioselectivities were obtained for all donors and acceptors studied. Yields are strongly affected by the nature of the substrates (Chart 3.2). These ketones react also with acetals and hemiacetals of ttichloro- or trifluoroacetaldehyde in the presence of prohne-derived tetrazol to provide the desired aldols [28c, 52]. 

Alcoholate anions in alcohol solutions react with aldehydes and ketones forming ketals and acetals, or hemiacetals and hemiketals. The rates of nucleophilic additions on the carbonyl group are enhanced by protonation of the carbonyl oxygen, so these reactions are acid catalysed. 

Formaldehyde is a strong electrophile, allowing acetal to polymerize by nucleophilic, anionic, or cationic addition of an alcohol to ketene carbonyl groups. Relatively weak bases such as pyridine initiate anionic addition polymerization cationic addition polymerization is catalyzed by strong acids. When the cyclic trimer trioxane is used as a copolymer to polymerize acetal copolymers, Lewis acids such as boron tiifluoride promote copolymerization. A more fundamental description is polymerization of an aldehyde or ketone -l- alcohol -i- an acid or base catalyst to form hemiac-etal, which further converts to acetal. The hemiacetal reaction is reversible to aldehyde and alcohol. 

As a special case, the formation of hemiacetals 2 (lactolization) during the hydroformylation of hydroxy-functionalized olefins, such as allyl or homoallyl alcohols, has to be mentioned (1, Y= O, Scheme 5.70). With these substrates, the reaction occurs in an intramolecular manner. In the presence of an external alcohol, the cyclic hemiacetal can further react to give a nonsymmetric cyclic acetal 3. Hemiacetals can be subjected to hydrogenation to afford diols 4. Under reducing conditions and in the presence of amines, amino alcohols 5 are formed both are valuable building blocks in fine chemistry. Alternatively, oxidation gives lactones 6 [5]. By dehydration of hemiacetals, cychc vinyl ethers 7 are formed. The same transformation with allylamines (Y=NR) gives cyclic hemiaminals, A/ ,0-acetals, lactames, or vinyl amines. 

Poly(itaconic acid) has also been prepared in a 0.2M/liter aqueous solution using potassium persulfate at 50 C over a 5-hr period under reduced pressure. After the polymer is reprecipitated twice into methanol-ethyl acetate, a polymer is isolated with a molecular weight of 1.64 x 10, determined by vapor pressure osmometry of a methanolic solution of the methyl ester prepared from the polymer [49]. Unfortunately Tsuchida and coworkers did not report on the quantitative extent to which poly(methyl itaconate) had been formed from this polymer (presumably by reaction with diazomethane). Consequently, there is little in the literature to confirm or dispute the paper by Braun and Azis el Sayed [97], which offered evidence that during the free-radical polymerization of itaconic acid, carbon dioxide evolves to a considerable extent. During the process, it seems that hydroxyl and formyl radicals are generated and incorporated in the macromolecule. It is proposed by these authors that the homopolymer of itaconic acid contains virtually no itaconic acid repeat units but rather intramolecular lactone rings and acetal- or hemiacetal-like moieties. Since the polymer remains soluble in the reaction solvent (dioxane). 

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... 

---