Ketals, formation

Ketal formation of a,p-unsaturated carbonyls are usually slower than for the saturated case. 

In equation 7, ttimer radical (4) is produced when (3) dissociates. Whenever (4) couples with the other product of equation 7, ie, the 2,6-dimethylphenoxy radical, the tetramer is produced as described. These redistribution reactions of oligomers that proceed by ketal formation and subsequent dissociation ultimately generate terminal quinol ethers which enolize to the more stable terminal phenol (eq. 8). 

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

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

Ketals bearing the double bond at the 4,5-position are prepared by reaction with glycol in the presence of weak acids such as adipic acid. In this case ketal formation proceeds via the intermediate 2,4-dien-3-ol ether. Hemithioketals (71) of A -3-ketones are prepared by reaction with mer-... 

During the preparation of the dihalo-(usually dibromo) 20-ketopregnanes, other reactive sites must be protected (e.g., addition of bromine to the A -double bond, ketal formation with a 3-ketone). An elegant method which avoids such problems has been devised by the Upjohn group in their studies on the conversion of 11-ketoprogesterone to hydrocortisone. The former is reacted with ethyl oxalate at C-2 and C-21, then addition of three moles of bromine gives a 2,21,21-tribromide. Alkaline rearrangement produces the side chain unsaturated acid, and the bromine at C-2 is subsequently removed with zinc. 

The following reaction provides an example of selective ketal formation. The product of the reaction is a single ketone-ketal with the formula CnHigOs. 

In order to predict the structure of the product, you must identify the factors that will tend to favor selective ketal formation. Consider selective carbonyl protonation first. Obtain energies and atomic charges, and display electrostatic potential maps of the alternative protonated ketones (protonated ketone A, protonated ketone B). Identify the more stable isomer. Compare geometries and draw whatever Lewis structures are needed to account for your data. Why is one isomer more stable than the other Is the more stable isomer also that in which the positive charge is better delocalized Will the more stable isomer undergo nucleophilic attack more or less easily than the other Explain. 

Since all of the steps in ketal formation are reversible, we expect the more stable ketal to form selectively. Obtain the energies of the alternative ketone-ketal s (ketone-ketal A and ketone-ketal B). Which one is more stable What factors do you think contribute to the stability of this ketal ... 

This ether formation arises from conversion of the phenol to a cyclohexanone, and ketal formation catalyzed by Pd-Hj and hydrogenolysis. With Ru-on-C, the alcohol is formed solely (84). 

A quantitative comparison of metals in the hydrogenation of vinyl ethers has been made, The extent of hydrogenolysis in hydrogenation of l-ethoxy-3-methylcyclohexene decreased in the order Pt Os > Rh Ir > Pd > Ru U24e)-, in the case of ethyl 4-methyl-1-cyclohexenyl ether, the order was Pt Ir > Rh > Os Ru Pd (124d). In ethanol, ketal formation is a... 

Finally, the synthesis of both attenols was accomplished by employing both electrophiles 106 and 112 as shown in Scheme 1.2.24. The alkylation of dithiane 113 with 106 proceeded cleanly in 96% yield. The second alkylation using 112 had to be carried out in the presence of HMPA and yielded 115 in 84% yield. Copper-mediated hydrolysis of the dithiane and p-toluenesulfonic acid catalyzed ketal formation finally gave a mixture of the title compounds 100 (57%) and 101 (9%), each over two steps. This synthesis is so far the shortest and most efficient one [60]. 

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. 

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