Acetaldehydes Hemiacetals

Ozone accelerates the autoxidation of acetaldehyde to peracetic acid at below 15°G. Acetaldehyde hemiacetal peracetate, an intermediate product, is... 

Trichloroacetal-dehyde /H2O2/HF Trifluoro- acetaldehyde (hemiacetal) Cr catalyst Gas phase 31... 

The equiiibrium constants for addition of alcohols to carbonyl compounds to give hemiacetals show the same response to structural features as the hydration reaction. Equilibrium constants for addition of methanol to acetaldehyde in both water and chloroform solution are near 0.8 The structural effects of the alcohol group have been examined. " Steric effects result in an order of CH3 C2H5 > (CH3)2CH > (013)30 for acetaldehyde hemiacetals. EWG substituents in the alcohol disfavor hemiacetal formation and this trend is believed to reflect the decreasing n tt hyperconjugation (anomeric effect, see Topic 1.2) as the substituents become more electron withdrawing. 

Scheme 42.51 Asymmetric domino Friedel-Crafts aminoalkylation of imines generated in situ from trifluoro-acetaldehyde hemiacetal and anilines catalyzed by a phosphoric acid.

Nucleophilic Substitution of Hemiacetal Sulfonates. The resolved sulfonates were allowed to react with various organometallic reagents. In contrast to the corresponding acetaldehyde hemiacetal carboxylates, 1 -benzyloxy-2,2,2-trifluoroethyl acetate did not react with Bu2CuLi LiI/BF3 OEt2. However, we were pleased to find that the treatment of (R )-( )-mesylate of 61% ee with triethylaluminum in toluene at -20 °C gave (-)-2-benzyloxy-l,l,l-trifluorobutane in 66% yield with 46% ee. The absolute configuration of the product was determined by the synthesis of an authentic sample from (S)-l,l,l-trifluoro-1,2-epoxy propane. 

Reactions of Vinyl Ethers. Vinyl ethers undergo the typical reactions of activated carbon—carbon double bonds. A key reaction of VEs is acid-catalyzed hydrolysis to the corresponding alcohol and acetaldehyde, ie, addition of water followed by decomposition of the hemiacetal. Eor example, for MVE, the reaction is... 

Q -Hydroxy-3Q (tetrahydropyran-2-yloxy)-2/3-(3Q -tetrahydropyran-2-yloxy-4-phenoxy-trans-1-buten-1 -yl)cyclopent-1Q -yl] -acetaldehyde a-hemiacetal Chromic anhydride Methanesulfonyl isocyanate Acetic acid... 

The lithium etiolate of acetaldehyde DMH has recently been utilized in the opening reaction of the ot-epoxide obtained by DM DO oxidation ofenol ether 142, to provide hemiacetal 143 after mild oxidative acid hydrolysis. The protected carbonyl functionality was subsequently used for the introduction of the trans enyne chain through a Wittig olefmation reaction to provide alcohol 144, which was then transformed into (+)-laurenyne (Scheme 8.37) [71]. 

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. 

The metabolism of NMOR in the rat is outlined in Figure 4. o-Hydroxylation yields the unstable intermediates and the latter hydrolyzes to (2-hydroxyethoxy)acetaldehyde [7] which has been identified as a liver microsomal metabolite by isolation of the corresponding 2,4-dinitrophenylhydrazone (59). (2-Hydroxy-ethoxy)acetaldehyde, which exists predominantly as the cyclic hemiacetal was not detected in the urine of rats gavaged with 125 mg/kg NMOR. However, (2-hydroxyethoxy)acetic acid was a major urinary metabolite (16% of the dose). These transformations are analogous to those observed with NPYR and NNN. 

The triple bond in the benzyne intermediate is very reactive toward a wide range of nucleophiles. The reaction of acetaldehyde with methanol to produce a hemiacetal is also a base-catalyzed reaction. In this reaction, the methoxide ion, CH30, is the base ... 

Sorensen, R Jencks, W. Acid- and base-catalyzed decomposition of acetaldehyde hydrate and hemiacetals in aqneons solntion. J. Am. Chem. Soc. 1987, 109, 4675 690. 

Photocyclization in benzene of p-quinones with an acetaldehyde group, such as 2-(l,4-benzoquinonyl)-2-methylpropionaldehyde, gives 5-hydroxy-3-methylbenzofuran, 3,3-dimethyl-5-hydroxy-2(3f/)-benzo-furanone and the cyclic hemiacetal of 2-(2,5-dihydroxyphenyl)-2-methylpropionaldehyde.322... 

Many aliphatic aldehydes exist primarily as hemiacetals in alcoholic solvents. It has been well understood for many years47 that the actual reducible species, or electrophore , in such media is not the hemiacetal but rather the small amount of the carbonyl compound itself (actually a hydrogen-bonded complex see above) present at equilibrium. Thus reduction is kinetically controlled that is, the overall rate of reduction is governed by the rate of conversion of the hemiacetal to the aldehyde. More recently, this has been confirmed and studied for formaldehyde and acetaldehyde in water at different pH levels48 and the kinetics of the reduction process have been studied for glucose, galactose and lactose49. 

Experiments on the mechanism of the oxidation of /t-cyanoethyl ethers were carried out by Wermeckes and Beck in both a one-compartment and a two-compartment cell. In the electrolysis of ethylpropionitrile (EPN) there is an early appearance of / -oxypropionitrile, which is an intermediate in the formation of NCCH2CH2OCH2CH2CN and acetaldehyde. Evidently Et is being attacked at the CH2 group to give a hemiacetal in a two-electron oxidation (Fig. 11.1). This is split in solution to yield the intermediates mentioned. HCN is found as a side product, and it may come from an anodic attack on the CH2 next to the cyano group. Cyanohydrin would be formed, and this is readily saponified. Wermeckes and Beck made sure that the cleavage of the C-0 bond occurs only under anodic electrochemical conditions, that is, that it is not a solution reaction. 

The product is in fact a hemiacetal. Like hydrates, most hemiacetals are unstable with respect to their parent aldehydes and alcohols for example, the equilibrium constant for reaction of acetaldehyde with simple alcohols is about 0.5 as we saw in Chapter 13. 

We said that a solution of acetaldehyde in methanol contains anew 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 an alcohol plus aldehyde mixture. But, if we add catalytic acid to our acetaldehyde-methanol... 

A particularly elegant application of DERA is the sequential synthesis of thermodynamically stable cyclic hemiacetal. Two DERA-catalyzed aldol reactions convert one equivalent of acceptor and two equivalents of acetaldehyde into this stable compound. A mild subsequent oxidation yielded the corresponding lactone in ex-... 

In DERA reactions, where acetaldehyde is the donor, products are also themselves aldehydes. In certain cases a second aldol reaction will proceed until a product has been formed that can cyclize to a stable hemiacetal.71 For example, when a-substituted aldehydes were used, containing functionality that could not cyclize to a hemiacetal after the first aldol reaction, these products reacted with a second molecule of acetaldehyde to form 2,4-dideoxyhexoses, which then cyclized to a hemiacetal, preventing further reaction. Oxidation of these materials to the corresponding lactone, provided a rapid entry to the mevinic acids and compactins (Scheme 5.43). Similar sequential aldol reactions have been studied, where two enzyme systems have been employed72 (Scheme 5.44). The synthesis of 5-deoxy ketoses with three substitutents in the axial position was accomplished by the application of DERA and RAMA in one-pot (Scheme 5.44). The long reaction time required for the formation of these thermodynamically less stable products, results in some breakdown of the normally observed stereoselectivity of the DERA and FDP aldolases. In a two-pot procedure, DERA and NeuAc aldolase have... 

Higher aldehydes, for example acetaldehyde or n-butyraldehyde, have much less tendency to polymerize compared to formaldehyde [5, 6]. Reasons have been given in thermodynamic terms by referring to the lower enthalpy of polymerization (about —7 kcal mole" ) as compared to formaldehydes (—12 kcal mole" ), which results in ceiling temperatures of —40°C. In terms of reactivity, aliphatic aldehydes undergo hydration and hemiacetal formation to an extent of about 50%. 

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