Aldehydes acetal formation

The position of equilibrium is favorable for acetal formation from most aldehydes especially when excess alcohol is present as the reaction solvent For most ketones the position of equilibrium is unfavorable and other methods must be used for the prepara tion of acetals from ketones... 

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. 

X0 to hydroxy compounds. Lower temperatures favor ketone formation and sterically hindered carbonyls, such as 2-thienyl t-butyl ketone, are not reduced. The sensitivity of desulfurization to steric factors is evident by the failure to desulfurize 2,5-di-i-butyl-3-acetylthiophene. The carbonyl groups of both aldehydes and ketones can be protected by acetal formation, as particularly cyclic acetals are stable during desulfurization in methanol at room temperature. " The free aldehydes give primary alcohols on desulfurization. Another method to obtain only keto compounds is to oxidize the mixtures of ketone and secondary alcohol with CrOs after the desulfurization. - Through the desulfurization of 5,5 -diacetyl-2,2, 5, 2"-terthienyl (228), 2,15-hexadecandione (229) has been obtained, which... 

Acetal formation is similar to the hydration reaction discussed in Section 19.5. Like water, alcohols are weak nucleophiles that add to aldehydes and ketones only slowly under neutral conditions. Under acidic conditions, however, the reactivity of the carbonyl group is increased by protonation, so addition of an alcohol occurs rapidly. 

Mechanism of acid-catalyzed acetal formation by reaction of an aldehyde or ketone with an alcohol. 

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

On reacting aldehydes such as benzaldehyde or cyclohexanecarboxaldehyde 720 with silylated alcohols such as 718 or 721, or with triethylsilane 84b in the presence of TMSOTf 20 at low temperatures, acetal formation and reduction is achieved in one step to afford ethers 719 and 722 in high yields [215] (Scheme 5.74). 

Halide ions will also act as nucleophiles towards aldehydes under acid catalysis, but the resultant, for example, 1,1-hydroxychloro compound (35) is highly unstable, the equilibrium lying over in favour of starting material. With HC1 in solution in an alcohol, ROH, the equilibrium is more favourable, and 1,1-alkoxychloro compounds may be prepared, e.g. 1-chloro-l-methoxymethane (36, a-chloromethyl ether ) from CH20 and MeOH (cf. acetal formation, p. 209), provided the reaction mixture is neutralised before isolation is attempted ... 

At even higher temperature, the polysaccharides decompose further by extensive C-C bond breaking. This leads to the formation of C2 4 oxygenates such as glycol aldehyde, acetic acid and hydroxyacetone (CH3-CO-CH2OH). The formation of these products can be rationalized by a series of reactions that include,... 

Acetalization of oxo aldehydes is used to protect sensitive aldehyde products, especially in asymmetric hydroformylation preventing racemization of an a-chiral aldehyde product [18-22,27]. Acetal formation can also be applied to the synthesis of monocyclic or spirocyclic pyranes as potential precursors and building blocks for natural products such as pheromones or antibiotics. A representative example is the synthesis of the pyranone subunit of the Prelog-Djerassi lactone. For this purpose, various 1,2-disubstituted homoal-lylic alcohols were used (Scheme 3) [32],... 

The introduction of CHj requires that the terminal alkyne C first become a carbanion and then be methylated. Such a carbanion, acting like the R group of RMgX, would react with the C==0 group of another molecule before it could be methylated. To prevent this, C==0 is protected by acetal formation before the carbanion is formed. The acetal is stable under the basic conditions of the methylation reactions. The aldehyde is later unmasked by acid-catalyzed hydrolysis. 

In a similar fashion to the formation of hydrate with water, aldehyde and ketone react with alcohol to form acetal and ketal, respectively. In the formation of an acetal, two molecules of alcohol add to the aldehyde, and one mole of water is eliminated. An alcohol, like water, is a poor nucleophile. Therefore, the acetal formation only occurs in the presence of anhydrous acid catalyst. Acetal or ketal formation is a reversible reaction, and the formation follows the same mechanism. The equilibrium lies towards the formation of acetal when an excess of alcohol is used. In hot aqueous acidic solution, acetals or ketals are hydrolysed back to the carbonyl compounds and alcohols. 

This mechanism (which is an SnIcA or A1 mechanism) is the reverse of that for acetal formation by reaction of an aldehyde and an alcohol (6-6). Among the facts supporting the... 

The metabolism of isopropanol is via oxidation by aldehyde dehydrogenase (ADH) to acetone. In common with other a-substituted (secondary) alcohols, isopropanol is a relatively poor substrate for ADH (WHO, 1990 Light et al., 1992). The primary metabolite, acetone, is eliminated in the expired air and in the urine and also undergoes further oxidation to acetate, formate and, ultimately, CO,. 

Monoacetals of substituted succinaldehydes (162), readily prepared by hydroformylation of optically active a,(3-unsaturated aldehyde acetals, were used to synthesize 3-substituted thiophenes having an optically active substituent (163). In these cases, while the use of hydrogen sulfide and HC1 in methanol at room temperature was more convenient, comparison with formation of (163) by the Paal synthesis from an appropriately substituted succinic acid salt gave products having about the same amount of racemization (73JOC2361). 

Meso-tartrate is joined to glucuronic acid in glycosidic linkage and by acetal formation to the aldehyde gly-oxylic acid, HOOC—CHO, which is also joined in an ether linkage to the next repeating unit.130 Similar open acetal linkages join monosaccharide units in some bacterial lipopolysaccharides and may occur more widely.1303... 

Resin-bound diols, amino alcohols, and dithiols, which reversibly form cyclic acetals with aldehydes and ketones, have been successfully used as linkers for carbonyl compounds (Entries 5-11, Table 3.40). Acetal formation on insoluble supports can be achieved by azeotropic removal of water (C6H6, TsOH, reflux [720]), whereas dithio-acetals can be prepared by acid-catalysis alone (BF3 OEt2 or TMSC1 CHCI3,0 °C, 2 h [721]). /V-Acylaminals such as R-CFI(OMe)NFI-CO-Pol have been prepared by treatment of resin-bound amides H2NCO-Pol with aldehydes in the presence of HC(OMe)3 and TFA [722],... 

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. 

A reaction closely related to acetal formation is the polymerization of aldehydes. Both linear and cyclic polymers are obtained. For example, methanal in water solution polymerizes to a solid long-chain polymer called paraformaldehyde or polyoxymethylene ... 

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. 

An interesting problem in stereoisomerism is found in the aldol reactions of the achiral aldehydes which are obtained by ozonolysis of the homoallylic alcohols 174. After stereospecific conversion by the FruA [230], the products can be readily induced to form an intramolecular glycoside 175 by acidic (R=OH) or alkaline treatment (R=C1), under which conditions the two equatorial ring hydroxyl groups completely direct the stereogenic acetal formation [234]. The corresponding RhuA catalyzed reactions deliver the enantiomeric... 

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