Acetal from hemiacetals

General Procedure for the Preparation of 1,2-O-Stannyl Acetals from Hemiacetals and the Glycosylation... 

FIGURE 7.16 Acetals and ketals can be formed from hemiacetals and hemiketals, respectively. 

Further, and just to stress that this is not new or novel chemistry, let us go back and compare imine formation with acetal formation from hemiacetals (see Section 7.2). 

If you look in older texts, you may still see the terms hemiketal and ketal. At one time, four terms were used for the products of alcohols with carbonyl groups hemiacetal, acetal, hemiketal, and ketal. A hemiketal is now a type of hemiacetal and a ketal is now a type of acetal. Originally, acetals and hemiacetals came from aldehydes and ketals and hemiketals came from ketones. The structures of hemiacetals and acetals contained a C-H bond, but ketals and hemiketals did not. 

Imines and (Af,(9)-acetals from fluoral are useful precursors of trifluoromethyl nitrogen-containing molecules amines, amino alcohols, amino acids, peptidomimetic units, heterocycles, and so on (Figure 2.50). These simple Af-derivatives of fluoral are easily prepared from the hydrate or the hemiacetal. Imines of fluoral react in [2 + 1 ]... 

Perfluoroalkylidene acetals derived from sugars are not accessible via conventional methods. Indeed, the intermediate of the formation of the acetal from the hemiacetal is... 

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,... 

Each base has a nitrogen atom capable of forming an acetal-like bond to the anomeric (or hemiacetal) carbon of deoxyribose. Recall that formation of an acetal from an alcohol and a hemiacetal involves elimination of water. We can envision that the water molecule is formed from the hydroxyl group of the hemiacetal and a hydrogen atom from the alcohol (or, in this case, the amine). Figure 12.57 illustrates this reaction for a purine base and for a pyrimidine base. 

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-... 

First you must decide what products are formed by hydrolysis of the acetal. In dealing with acetals and hemiacetals, any carbon atom with two bonds to oxygen is derived from a carbonyl group. 

Loss of a proton to give the acetal acid-catalysed acetal formation from hemiacetal... 

This is about as complex a mechanism as you have seen and it will help you to recall it if you see it in two halves, each very similar to the other. First, form the hemiacetal hy adding an alcohol to the C=0 7T bond then lose the OH group by breaking what was the C=0 a bond to form an oxonium ion and add a second alcohol to form the acetal. From your complete mechanism you should also be able to verily that acetal formation is indeed catalytic in acid. 

Electrochemical oxidation gives, S,0-acctals199 (e. g. conversion of 11 to 12) and -V,( -acctals200 in high yields. A. O-Acetals or hemiacetals are also synthesized starting from the corresponding pyrimidines201 or pyridinium salts.202... 

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. 

Problem 14.22. Show the formation of an acetal from ethanol and the hemiacetal of Problem 14.21. Ans. 

Problem 1439. Write equations to show the formation of hemiacetal and acetal from the reaction of butanal with ethanol. 

To answer this problem, one must know the structures of the molecules in question and a couple of definitions. By definition, epimers are a pair of molecules that differ from each other only in their configuration at a single asymmetric center. Anomers are special epimers that differ only in their configuration at a carbonyl carbon hence, they are usually acetals or hemiacetals. An aldose-ketose pair is obvious. Inspection of Fischer representations of the molecular pairs leads to the conclusion that (a), (c), and (e) are aldose-ketose pairs (b) and (f) are epimers and (e) are anomers. 

Another acylating system utilizing EIbN, DMAP, and acetic anhydride was used in the formation of mixed acetals from an in s/itt-generated hemiacetal in good yields (eq 10). Similar... 

There have been a significant number of reports of the reductive removal of alcohols and ethers from hemiacetals (eq 59), hemiacyliminals (eq 60), and acetals (eqs 61 and 62) 7 These reactions employ a variety of Lewis acids that are best suited for the activation of the leaving group. In many cases the processes are both high yielding and diastereoselective. Either the ether/amide products (eqs 59, 60 and 62) or the alcohol products (eq 61) can be isolated from these reactions. 

---