Mixed acetals, ketals

Glycosides were originally defined as mixed acetals (ketals) derived from cyclic forms of monosaccharides. 

The regiochemical outcomes of Brpnsted acid-catalyzed reactimis of carbohydrate derivatives have been studied in detail, particularly in the context of the selective formation or hydrolysis of acetals and ketals [6, 7]. The group of Nagorny has added a new dimension to this strategy by employing chiral Br0nsted acids for the selective formation of mixed acetals and ketals from pyranoside-derived 1,2-diol... 

The crude ketal from the Birch reduction is dissolved in a mixture of 700 ml ethyl acetate, 1260 ml absolute ethanol and 31.5 ml water. To this solution is added 198 ml of 0.01 Mp-toluenesulfonic acid in absolute ethanol. (Methanol cannot be substituted for the ethanol nor can denatured ethanol containing methanol be used. In the presence of methanol, the diethyl ketal forms the mixed methyl ethyl ketal at C-17 and this mixed ketal hydrolyzes at a much slower rate than does the diethyl ketal.) The mixture is stirred at room temperature under nitrogen for 10 min and 56 ml of 10% potassium bicarbonate solution is added to neutralize the toluenesulfonic acid. The organic solvents are removed in a rotary vacuum evaporator and water is added as the organic solvents distill. When all of the organic solvents have been distilled, the granular precipitate of 1,4-dihydroestrone 3- methyl ether is collected on a filter and washed well with cold water. The solid is sucked dry and is dissolved in 800 ml of methyl ethyl ketone. To this solution is added 1600 ml of 1 1 methanol-water mixture and the resulting mixture is cooled in an ice bath for 1 hr. The solid is collected, rinsed with cold methanol-water (1 1), air-dried, and finally dried in a vacuum oven at 60° yield, 71.5 g (81 % based on estrone methyl ether actually carried into the Birch reduction as the ketal) mp 139-141°, reported mp 141-141.5°. The material has an enol ether assay of 99%, a residual aromatics content of 0.6% and a 19-norandrost-5(10)-ene-3,17-dione content of 0.5% (from hydrolysis of the 3-enol ether). It contains less than 0.1 % of 17-ol and only a trace of ketal formed by addition of ethanol to the 3-enol ether. 

Dichloroquinoxalme (191) and isopropyl 2-lithio-2-methoxy-2-( 1-methoxy-l-methylethoxy)acetate (192) (prepared in situ) gave the mixed ketal intermediate (194) that underwent gentle acid hydrolysis to afford 2-chloro-3-propoxyoxaloquinoxaline (193) [THF-(Me2NO)3PO, —78°C 20°C then 2M HCl, 25°C, 20 min 90%]. ... 

The EtsSiH/tetracyanoethylene combination reduces acetals and ketals to the corresponding ethers but the yields are mixed.500 The full reduction of benz-aldehyde acetals to the toluene derivatives is realized by the initial reduction with Et3SiH/SnBr2-AcBr followed by Bu3SnH/AIBN (azobis(isobutyronitrile)) or LiAlH4.479 The overall yields are excellent. 

The conversion of an a, -unsaturated aldehyde or ketone into an allylic acetal or ketal, followed by SN2 -type attack of a nucleophile, leads, after hydrolysis of an initially formed enol ether, to a fi-sub-stituted carbonyl compound. The overall sequence (Scheme 23) is equivalent to a direct conjugate addition, but has the advantage that it allows the temporary introduction of a chiral auxiliary group if a chiral (C2-symmetric) diol is used in the acetalization step, die subsequent nucleophilic addition leads to a mix-... 

Clayfen (1.13 g, 1.2 mmol of iron(III) nitrate) is thoroughly mixed with neat thioacetal lb (0.227 g, 1 mmol) in the solid state. The material is transferred in a test tube and placed in an alumina bath inside the microwave oven and irradiated (40 s). Upon completion of the reaction, monitored on TLC (hexane-EtOAc, 8 2, v/v), the product was extracted into ethylene chloride. The resulting solution is passed through a small bed of neutral alumina. Evaporation of the solvent delivers pure p-nitrobenzaldehyde 2b in 97% yield. In the case of cyclic thio acetals and ketals, the liberated dithiols bind to the clay surface rather tightly and a simple washing of the clayfen affords clean products. 

Ethylene ketals. The exchange reaction between dialkyl acetals or dialkyl ketals and 1,2-glycols as a route to cyclic acetals and ketals was first described by Delepine. This method in combination with Claisen s orthoester ketalization procedure (1, 1206) constitutes a convenient route to ethylene ketals (1, 376). The mixed orthoester 1 is probably the actual reagent involved in the Delepine method. It is convenient to prepare and use for ketalization of carbonyl compounds under mild conditions. A striking example is the ready conversion of the acid-sensitive 2 into 3, a reaction that proceeds by other known methods in yields of only 30%. 

DIBALH, as well as with other reagents. Ortho esters are easily reduced to acetals by LiAlITj alone, offering a route to aldehydes, which are easily prepared by hydrolysis of the acetals (10-6). Mixed ketals [R(OMe)OR ] can be demethoxylated (to give RHOR ) with Bn3SnCl/NaCHBH3 in the presence of AIBN. ... 

Eliel and co-workers investigated several acetals and ketals and found reduction in ether by mixed hydride to be a general reaction. Best yields are obtained when the ratio of LiAlH4 to AICI3 is 1 4 and the reagent is taken in 100% excess. Typical examples are ... 

Note that some textbooks use the term acetal to describe only the product that forms when an alcohol and an acid catalyst are mixed with an aldehyde, and the term ketal to describe the product that forms when an alcohol and an acid catalyst are mixed with a ketone. Based on this terminology, draw an example of each of the following hemiacetal, acetal, hemiketal, ketal. 

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