Cyclohexanone dimethyl acetal

Conversely, most acetals are hydrolyzed simply by shaking them with dilute acid in water. The large excess of water drives the equilibrium toward the ketone or aldehyde. The mechanism is simply the reverse of acetal formation. For example, cyclohexanone dimethyl acetal is quantitatively hydrolyzed to cyclohexanone by brief treatment with dilute aqueous acid. 

Propose a mechanism for the acid-catalyzed hydrolysis of cyclohexanone dimethyl acetal. 

Cyclohexanone dimethyl acetal Cyclohexanone (49 g), dimethyl sulfite (60 g), methanol (60 ml), and ca. 10% methanolic hydrochloric acid (1 ml) are boiled together on the water-bath under reflux. Vigorous evolution of sulfur dioxide begins after a few minutes, then the solution is heated for 3 h, allowed to cool, made alkaline with a few drops of sodium methoxide,... 

Addition of acetone cyanohydrin to 606 in the presence of a catalytic amount of triethyl-amine affords cyanohydrin 607 as a mixture of isomers. Ketalization with cyclohexanone dimethyl acetal gives a near statistical mixture (45 55) of (2S, 3 S)-608 and (2R, 3 S)-609, which is separable by column chromatography (96% overall yield). Each isomer, with an optical purity greater than 95%, is a versatile intermediate, and they have been used in the synthesis of amino sugars A-benzoyl-L-acosamine (614) [189] (Scheme 85) and A-benzoyl-L-daunosamine (615) [190]. 

Aldehydes and ketones react reversibly with 2 equivalents of an alcohol in the presence of an acid catalyst to yield acetals, R2C(OR )2, sometimes called ketals if derived from a ketone. Cyclohexanone, for instance, reacts with methanol in the presence of HCl to give the corresponding dimethyl acetal. 

A solution of 1-trimethylsilyloxycyclohex-l-ene (5.12 mmol) and benzaldehyde dimethyl acetal (5.47 mmol) in dichloromethane (15 ml) was cooled to —78°C, and to this was added TMSOTf (0.05 mmol) in dichloromethane (0.5 ml). The mixture was stirred at -78°C for 8h, and then quenched by the addition of water at —78 °C. Dichloromethane (50 ml) was added, and the mixture was washed with saturated sodium hydrogen carbonate solution and brine, and dried. Concentration provided a crude oil consisting of a 93 7 mixture of erythro- and r/jreo-2-(methoxyphenyl-methyl)cyclohexanone. Chromatography on silica gel (20g, eluant petroleum ether ether 10 1) gave the pure erythro (82%) and threo (6.7%) isomers as oils. 

Acetalization or ketalization with silylated glycols or 1,3-propanediols and the formation of thioketals by use of silylated 1,2-ethylenedithiols and silylated 2-mer-captoethylamines have already been discussed in Sections 5.1.1 and 5.1.5. For cyclizations of ketones such as cyclohexanone or of benzaldehyde dimethyl acetal 121 with co-silyl oxyallyltrimethylsilanes 640 to form unsaturated spiro ethers 642 and substituted tetrahydrofurans such as 647, see also Section 5.1.4. (cf. also the reaction of 654 to give 655 in Section 5.2) Likewise, Sila-Pummerer cyclizations have been discussed in Chapter 8 (Schemes 8.17-8.20). 

Commercial acetone dimethyl acetal and allyl alcohol from The Dow Chemical Company and cyclohexanone from Eastman Kodak Company were used without further treatment. 

In hydrogenolyses with HAICU, the dimethyl acetals of cyclobutanone and cyclohexanone are cleaved more slowly than that of 3-pentanone, while those of cyclopentanone and cycloheptanone are cleaved more rapidly (Table 1), as would be expected for a carbonium ion process. The differences in rate are small, suggesting that carbonium ion character is not strongly developed in the transition state. With the dimethyl acetal of 4-t-butylcyclohexanone, the hydride addition step occurs with strongly predominating axial addition when HAlCh is used Zn(BH4)2 with TMS-Cl, and TMS-H with TMSO-Tf are less selective (Table 2). Equatorial attack predominates, however, in the reduction of the ketone itself with TBDMS-H and TBDMS-OTf. ... 

Nucleophilic addition of an alcohol to the carbonyl group initially yields a hydroxy ether called a hemiacetal, analogous to the gem diol formed by addition of water (Section 19.6). Hemiacetals are formed reversibly, with the equilibrium normally favoring the carbonyl compound. In the presence of acid, however, a further reaction can occur. Protonation of the -OH group followed by an El-like loss of water leads to an oxonium ion, R2C=OR, which undergoes a second nucleophilic addition of alcohol to yield the acetal. For example, reaction of cyclohexanone with methanol yields the dimethyl acetal. The mechanism is shown in Figure 19.12 (p. 778). 

Butoxyethanol Butyl acetate Cyclohexanone Dimethyl acetamide... 

An interesting result (17-35% ee) was reported in the TMSOTf-catalyzed condensation of benzalde-hyde dimethyl acetal with a cyclohexanone silyl enol ether bearing an optically pure binaphthylic derivative at silicon. ... 

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