Hemiacetals stable

There is no generally useful nonhydride method for the direct reduction of carboxylic acid esters to aldehydes. There are, however, procedures which are valuable under particular circumstances. An important example is the one-electron reduction of aldonolactones to aldoses. Two factors presumably contribute to the success of these reactions firstly the presence of electron-withdrawing substituents in the substrates, raising the reactivity of the carbonyl group, and secondly the ability of the products to form cyclic hemiacetals stable to further reduction. 

Compounds that contain both carbonyl and alcohol functional groups are often more stable as cyclic hemiacetals or cyclic acetals than as open chain compounds Examples of several of these are shown Deduce the structure of the open chain form of each... 

Me2S04, 2 N NaOH, MeOH, H2O, reflux, 30 min, 85% yield.In this case the hemiacetal of phthaldehyde is alkylated with methyl sulfate this use is probably restricted to cases that are stable to the strongly basic conditions. 

In contrast to acetals, which are base-stable, hemiacetals undergo base-catalyzed hydrolysis. In the alkaline pH range, the mechanism shifts toward a base-catalyzed elimination. 

Experiments designed to clarify the situation were carried out by Wittig and Mayer (40). It was shown that changing the molar ratio of amine (diethylamine, di- -butylamine, or diisobutylamine) to -butyraldehyde from 1 1 to 2 1 did not affect the yield of enamine (53- 64%, based on the aldehyde). Contrariwise, changing the ratio of amine (morpholine, piperidine, or pyrrolidine) to n-butyraldehyde from 1 1 to 2 1 boosted the yields from 52-57 % to 80-85 %. The authors interpret these data as indicating that the cyclic amines form aminals with n-butyraldehyde, while the open-chain do not. Infrared evidence is stated as having shown that the aminal originates not from attack of excess amine on the enamine, which is stable under the conditions of the reaction, but from the N-hemiacetal (17). 

If the carbonyl and the hydroxyl group are in the same molecule, an intramolecular nucleophilic addition can take place, leading to the formation of a cyclic hemiacetal. Five- and six-membered cyclic hemiacetals are relatively strain-free and particularly stable, and many carbohydrates therefore exist in an equilibrium between open-chain and cyclic forms. Glucose, for instance, exists in aqueous solution primarily in the six-membered, pyranose form resulting from intramolecular nucleophilic addition of the -OH group at C5 to the Cl carbonyl group (Figure 25.4). The name pyranose is derived from pyran, the name of the unsaturated six-membered cyclic ether. 

A retroaldol fragmentation subsequent to the addition of p-TsOI I and a small amount of water to epoxide 206, obtained by oxidation of enol ether 205 with DMDO, resulted in the direct formation of dialdehyde hydrate 208, possessing the spirostructure necessary for the construction of the fused-rings core of ( )-ginkoli-de B. Apparently, hydrolysis of the epoxide produces the hemiacetal 207, which undergoes retroaldol fragmentation of the cydobutane to afford the dialdehyde, which forms the stable hydrate 208 (Scheme 8.52) [94]. 

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. 

Thiols add to aldehydes and ketones to give hemimercaptals and dithioacetals. Hemimercaptals are ordinarily unstable, though they are more stable than the corresponding hemiacetals and can be isolated in certain cases.Dithioacetals, like... 

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. 

A novd example of a catalytic enantioselective domino process1201 is the inter-intramolecular nitro-aldol reaction described by Shibasaki et al which generates substituted indanones. As catalyst a praseodym-heterobimetallic complex with binaph-thol as chiral ligand is employed. Treatment of keto-aldehyde 41 with nitromethane in the presence of the catalyst 46 at -40 °C and successive warming to room temperature affords diredly the produd 42 in an overall yield of 41 % and 96 % ee after several recrystallizations (scheme 9). As intermediates the nitromethane adduct 43 and the hemiacetal 44 can be proposed. In a second aldol reaction 44 leads to 45 which isomerizes to the thermodynamically more stable epimer 42. 

An attractive feature of this dehydrative coupling approach is that it avoids the need for isolation of intermediate glycosyl donors. This can be desirable if a glycosyl donor is not stable to isolation or purification. Moreover, the use of a hemiacetal donor reduces the number of synthetic manipulations of the carbohydrate donor by avoiding hemiacetal derivatization to alternative donor types. In this way, the approach has the potential to streamline time and labor-intensive multiglycosylation sequences. Although there increasingly have been reports of these direct dehydrative... 

Figure 9.5 Cyclic, hemiacetal structures of D-glucose. The reaction between an alcohol and aldehyde group within an aldohexose results in the formation of a hemiacetal. The only stable ring structures are five- or six-membered. Ketohexoses and pentoses also exist as ring structures due to similar internal reactions.

The position of equilibrium, i.e. whether the carbonyl compound or the addition product is favoured, depends on the nature of the reagents. The equilibrium constant is often less than 1, so that the product is not favoured, and many simple hemiacetals and hemiketals are not sufficiently stable to be isolated. However, stable cyclic hemiacetals and hemiketals... 

In aqueous solution, both glucose (hemiacetal) and frnctose (hemiketal) exist as equilibrium mixtures of cyclic and open-chain carbonyl forms. Sucrose, however, is a single stable substance (acetal and ketal), and conversion back to glucose and frnctose requires more rigorous hydrolytic conditions, such as heating with aqueous acid. 

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