Acetal-ketal formation

Kinetic studies of acetal/ketal formation from cyclohexanone, and hydrolysis (3 X 0 N HCl/dioxane-H20, 20°), indicate the following orders of reactivity ... 

FIGURE 13.1 Formation of an acetal/ketal 3 starting from an aldehyde/ketone 1 in the presence of an alcohol and acid. Mechanistically, acetal/ketal formation in these conditions yields a hemiacetal intermediate 2 and a mole of water. Removal of the water formed during reaction can be difficult to achieve during a polymerization reaction in an effort to obtain high-molecular-weight polyacetal. 

The mechanism of this hydrolysis reaction has been studied in great detail. Tb mechanism is the reverse of that for acetal or ketal formation. 

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. 

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... 

For example, aldehydes and ketones react with excess alcohol to produce acetals or ketals, and organometallic additions followed by hydrolysis produce alcohols. The formal reagents X—Y for formation of acetals/ketals and substituted alcohols are thus ROR and RH, respectively. Equation 34 is a clean chemical equation, as opposed to the real chemical reactions with the accompanying complicating effects of reagents, by-products and solvents. Equation 35 expresses the reaction thermochemically. 

First the isopropylidene ketal at C-3b and C-4b is generated using acetone and an ion-exchange resin at first. There is no further ketal formation at other positions of the lactose. It is also possible to use 2,2-dimethoxypropane (Me)2C(OMe)2 instead of acetone. The problem in this step is the partial formation of hemi-ketals with the other hydroxy groups which lower the yield. They are destroyed by heating to 100 °C in glacial acetic acid.20... 

In this section, consideration will be given to the actual processes of acetal- or ketal-formation and not to the more indirect methods by which acetals and ketals of the polyhydric alcohols may be synthesized from compounds (e.g. derivatives of the monosaccharides) containing preformed alkylidene or arylidene groupings. The condensation of a carbonyl compound with a glycol is facilitated by acidic catalysts, and, since the reaction is reversible, by dehydration. The catalysts most frequently employed are concentrated sulfuric, hydrochloric and hydro-bromic acids, gaseous hydrogen chloride, zinc chloride and cupric sulfate others are phosphorus pentoxide, sulfosalicylic acid, and anhydrous sodium sulfate. The formation of benzylidene compounds is promoted less efficiently by phosphorus pentoxide than by either concentrated sulfuric acid or concentrated hydrochloric acid 1" the reaction is assisted by chloro- and nitro-substituents on the aromatic nucleus, but hindered by methyl- and methoxy-groups.18... 

Carbonyl addition reactions include hydration, reduction and oxidation, the al-dol reaction, formation of hemiacetals and acetals (ketals), cyanohydrins, imines (Schiff bases), and enamines [54]. In all these reactions, some activation of the carbonyl bond is required, despite the polar nature of the C=0 bond. A general feature in hydration and acetal formation in solution is that the reactions have a minimum rate for intermediate values of the pH, and that they are subject to general acid and general base catalysis [121-123]. There has been some discussion on how this should be interpreted mechanistically, but quantum chemical calculations have demonstrated the bifunctional catalytic activity of a chain of water molecules (also including other molecules) in formaldehyde hydration [124-128]. In this picture the idealised situation of the gas phase addition of a single water molecule to protonated formaldehyde (first step of Fig. 5) represents the extreme low pH behaviour. 

The diols (97) from asymmetric dil droxylation are easily converted to cyclic sii e esters (98) and thence to cyclic sulfate esters (99).This two-step process, reaction of the diol (97) with thionyl chloride followed by ruthenium tetroxide catalyzed oxidation, can be done in one pot if desired and transforms the relatively unreactive diol into an epoxide mimic, ue. the 1,2-cyclic sulfate (99), which is an excellent electrophile. A survey of reactions shows that cyclic sulfates can be opened by hydride, azide, fluoride, thiocyanide, carboxylate and nitrate ions. Benzylmagnesium chloride and thie anion of dimethyl malonate can also be used to open the cyclic sulfates. Opening by a nucleophile leads to formation of an intermediate 3-sidfate aiuon (100) which is easily hydrolyzed to a -hydroxy compound (101). Conditions for cat ytic acid hydrolysis have been developed that allow for selective removal of the sulfate ester in the presence of other acid sensitive groups such as acetals, ketals and silyl ethers. 

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. 

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