Acetal and ketal formation

The conversion of hemiacetals and hemiketals to acetals and ketals occurs in four reversible steps. They occur in rapid succession and parallel many of the reactions of carbocations that we have described previously. 

The acid protonates the oxygen atom of the hemiacetal hydroxyl group. This step is rapid and reversible. 

Water leaves and a carbocation forms. Step 2 occurs readily for two reasons. First, the OH group is protonated to form water, a far better leaving group than hydroxide ion. Second, the oxygen atoms lone pair electrons resonance stabilize the carbocation formed in this Sj,j 1 reaction. 

The proton bonded to the oxygen atom leaves, giving an acetal. The reaction is acid catalyzed. It starts acetal formation by protonating the hemiacetal, and H is regenerated step 4 when the acetal forms. 

Base catalyzes neither acetal formation nor the reverse reaction, called acetal hydrolysis. An Sj 2 displacement of hydroxide by alkoxide would be required in the formation of the acetal. However, we know that hydroxide ion is not a good leaving group. 

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The second stage of acetal and ketal formation, the acid-catalyzed elimination of the hydroxyl group as a water molecule and addition of a second alcohol molecule to the resulting carbocation (Equations 8.37 and 8.38), is most conveniently investigated in the reverse direction starting from the acetal or ketal.88 As Structures 12 and 13 indicate, it is conceivable that either of two bonds could be broken in the hydrolysis. One method of settling the ambiguity is to hydrolyze... 

Stannic chloride has been attached to monomers 21 containing ester (21a), carbazole (21b), pyrrolidone (21c), nitrile (21d) and pyridine (21d) moieties. The polymeric ligands were prepared by copolymerization of styrene, divinylbenzene and functional monomers such as methyl methacrylate, A -vinylcarbazole, Af-vinylpyrrolidone, acrylonitrile and 4-vinylpyridine [33], These polymers were treated with stannic chloride in chloroform to afford the corresponding polymer-supported stannic chloride complexes (Eq. 8). These polymeric complexes have been used as catalysts for such organic reactions including esterification, acetalization, and ketal formation. These complexes had good catalytic activity in the reactions and could be reused many times without loss of activity. Their stability was much better than that of plain polystyrene-stannic chloride complex catalyst. 

Acetal and ketal formation from aldehydes, resp. ketones and alcohols occurs over mordenite and other acidic zeolites [91] slightly above ambient temperatures in the liquid phase. The reaction is not confined to simple alcohols, diols can also be converted (e.g., cyclohexanone reacts with ethylglycol to 1,4, dioxaspiro(4,5)decane [2]). Note that it is likely that desorption controls the rate of such reactions as the product molecules are larger than the reactants and have, hence, a higher adsorption constant. 

Figure 6.33 Basic reactions of acetal and ketal formation. The generation from the carbonyl compound or other acetal can be catalysed by Lewis or Bronsted acids, that from the enol ether by Bronsted acid only. Reactions are shown as involving oxocarbenium ions or not according to the stabilities in water.

Figure 6.35 Thermodynamic products of acetal and ketal formation from various sugars.

Table VI. Dimethyl acetal and ketal formation Rl Yield (%)...

We have shown each of the reactions in acetal and ketal formation as being reversible. Simple hemiacetals and hemiketals are characteristically unstable and easily revert to the starting materials. Acetals and ketals are stable structures, but the reactions may be reversed by using water and an acid catalyst ... 

Table 2. Aldehydes and ketones used for acetal and ketal formation...

Acetal and ketal formation has been widely used in carbohydrate chemistry [8—13], not only for structural and analytical purposes, but also for chromatography [11] and mass spectrometry [14-16]. The formation of ring systems is largely dependent on the availability of ds-1,2- and cis-l,3-diol groupings, and the formation of bi- and tricyclic ring systems is possible where more than one such diol grouping is present. 

Alcohols add reversibly to aldehydes and ketones to give a transient hemiacetal or hemiketal, which then reacts with more alcohol to give an acetal or a ketal. Acetal and ketal formation is reversible. An excess of alcohol drives the reaction toward the acetal or ketal, but an excess of water will convert the acetal or ketal back to the aldehyde or ketone. 1,2-Diols react with aldehydes and ketones to give 1,3-dioxolane derivatives and 1,3-diols react to give 1,3-dioxane derivatives. 

This reaction is simply the reverse of the reaction by which acetals are formed—acetal or ketal formation is favored by excess alcohol, hydrolysis by excess water. The two reactions share the same mechanistic pathway but travel along it in opposite directions. In the following section you ll see how acetal and ketal formation and hydrolysis are applied to synthetic organic chemistry. 

The mechanism of acid-catalyzed esterification involves two stages. The first is formation of a tetrahedral intermediate by nucleophilic addition of the alcohol to the carbonyl group and is analogous to acid-catalyzed acetal and ketal formation of aldehydes and ketones. The second is dehydration of the tetrahedral intermediate. 

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