Ketal formation from

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

Scheme 4.9. Intramolecular ketal formation from ring opening of a halocyclopropane.

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

Bis(o-nitrophenyl)ethanediol (50) has been proposed as a practical photolabile protecting group for ketones and aldehydes which is superior to the monosub-stituted o-nitrophenylethanediol. The presence of a single stereocentre in the latter leads to the formation of two diastereomers when it is used with another chiral molecule, thus complicating NMR signal patterns, and often making purification difficult. In addition, the obvious alternative of ketal formation from two molecules of o-nitrobenzyl alcohol instead of a diol is usually impractical. On the other hand (50) is easily accessible as a pure enantiomer, and the ketals which it forms with aldehydes and ketones are smoothly deprotected in neutral conditions by irradiation at 350 nm. 

The reaction mechanism is the same for both aldehydes and ketones. If acetone (6) reacts with ethanol in the presence of a catalytic amount of j5-tol-uenesulfonic acid, 53 is formed but not isolated. This compound is formally analogous to the hemiacetal derived from an aldehyde, but it is derived from a ketone. Therefore, it is called a hemiketal. The isolated product is 54 (2,2-diethoxypropane)—again, analogous to the acetal however, the starting material is a ketone rather than an aldehyde, so the final product is called a ketal. A ketal is a compound derived from a ketone that contains two OR groups connected to the same carbon. The mechanism for ketal formation from ketones is identical to that for acetal formation, and every step in this sequence is reversible. The same methods used to remove water from the reaction that was used to drive the equilibrium toward the acetal in that reaction (see Section 18.6.3) can be used here for conversion of the ketone to the 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). 

The grouping C—O—C—O—C is characteristic of an acetal or a ketal (see Section 15-4E), but it also can be regarded as an ether with two ether links to one carbon. Compared to other ethers (except for the oxacyclopropanes), substances with the C—O—C—O—C group are very active toward acidic reagents, as pointed out in connection with their formation from alcohols (Section 15-4E) and their use as protecting groups for the OH function (Section 15-9C). 

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... 

From a biogenetic point of view (Section V) the ketal moiety must be constructed by the intramolecular ketal formation of a plausible dihydroxy-diketone (6a). When treated with 6 N HC1 at 80° for 45 min, daphniphylline as well as the corresponding alcohol was converted into deacetylisodaphniphylline (7a) in quantitative yields which was... 

The effect of reaction time on the major components of the reaction of cystine and DMHF in water is shown in Table IV. It is noteworthy that amounts of 2,4-hexanedione, 3,5-dimethyl-l,2,4-trithiolanes and thiophenones were found at a maximum after one hour. It was also found that the amount of 2-acetylthiazole increased with time and that acetol acetate decreased with time as expected. In the glycerol medium, the effect of reaction time on the major components is shown in Table V. Apparently, the 1,3-dioxo-lane, which is a ketal formed from glycerol and acetone, decreased over time. Also, long reaction time favors the formation of cyclic compounds, including 2,5-dimethyl-2-hydroxy-3(2H)-thiophene, cyclo-pentenones and 4,5-dimethyl-l,2-dithiolenone. 

This figure also shows the potential for using CD as a tool for kinetic analysis. The Cotton effect at 289 nm is due to the concentration of free ketone present. The dimethyl ketal absorbs at much shorter wavelength. Repeated additions of small amounts of water shifts the ketone-ketal equilibrium toward the free ketone, which increases the value of the experimental molecular ellipticity. The formation of ketal also depends upon the structure of the alcohol, as well as on stereochemical factors. Thus cholestan-3-one gives 96% of dimethyl ketal, 84% of diethyl ketal and only 25% of the diisopropyl ketal. The proportion of ketal formed from the 3-keto-5 P- steroids is higher than in the case of their 5 a isomer. 

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... 

In order to synthesize 17-a-hydroxyaldosterone 2a,12 a side chain protection was needed. Otherwise the 18-carbon radical tended to furnish a methylene group and open the 13-17 bond in ring D. A convenient protection for the corticoid side chain is the A/.v-ketal derived from formaldehyde. Thus Msmethyl-enedioxy-1-dehydrohydrocortisone 21 was converted to its nitrite and photolyzed in the usual way. The only product (60 % isolated yield) was the desired isomer 22. When this was treated with nitrous acid, an unusual sequence of reactions took place. The normal nitrosation intermediate underwent ring closure to 24 followed by oxonium ion formation 25 as indicated. The oxonium ion 25 then opened one of the adjacent methylenedioxy groups (25 -> 26) which on hydration with water afforded the isolated product 27. Acetylation of 27 with acetic anhydride and acid catalysis gave the triacetate 28 in 80 % overall yield from the oxime 22. Mild alkaline hydrolysis... 

Lactones are in principle reducible to hydroxyaldehydes, and when applied to lactones of sugar acids the method works well because cyclic acetal or ketal formation stabilizes the carbonyl function and prevents overreduction [3,96-100]. In particular, d-ribose may be prepared from the cathodic reduction of D-ribono-y-lactone as in Eq. (24) the optimum conditions for this reaction include careful buffering of the electrolyte [97-100]. 

Figure 11 The formation of the ketalized compounds from the original adducts under acidic conditions...

When this reaction is conducted on ketones, instead of aldehydes, the equivalent species to the hemiacetal and acetal are now called hemiketal and ketal respectively. However, when simple ketones are reacted with normal monofunctional alcohols, the reaction rarely goes to completion, unlike the situation with aldehydes where the reaction proceeds smoothly. Yet, when a 1,2-diol is reacted with a ketone, then the reaction goes to completion much more readily. Write the complete reaction sequence for the formation of the cyclic ketal starting from propanone and 1,2-ethandiol, under acidic conditions. Also, suggest why the product between one molecule of each reagent is favoured over the alternative product that would result from the reaction between two molecules of the diol and one of the ketone. 

In the commercial utilization of the reduction of esters by sodium, a secondary alcohol such as methyl-isobutylcarbinol is employed. This particular alcohol reacts rather slowly with sodium but rapidly enough with the sodium ester ketal (XXVI) to keep acyloin formation from dominating the reaction. 

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