Protection Of ketone

20-Bisethylenedioxypregn-5-ene. Method A. A mixture of progesterone (10 g), freshly distilled ethylene glycol (80 ml) and benzene (350 ml) is slowly distilled for 15 min to remove traces of water. p-Toluenesulfonic acid monohydrate (0.3 g) is added and the mixture is heated under reflux with stirring for 5 hr with a water separator. Saturated sodium bicarbonate solution is added to the cooled mixture and the benzene layer is separated. The organic layer is washed twice with water, dried and evaporated in vacuo. The residue is crystallized twice from acetone-methanol to give 4.15 g (32%) of bisketal, mp 178-181°. 

An improved yield of ketal is obtained by heating a solution of 2 g of progesterone in 16 ml of ethylene glycol and 70 ml of toluene containing 65 mg of / -toluenesulfonic acid monohydrate at reflux for 4 hr. The yield of bisethy-lene ketal is 1.34 g (67%), mp 178-182°. 

i-Ethylenedioxy- l(i,2 -dihydroxypregn-5-ene-, 20-dione 21-Acetate. A stirred mixture of cortisone acetate (9.5 g), ethylene glycol (200 ml) and p-toluenesulfonic acid monohydrate (0.3 g) is distilled over a period of hrs at about 1-2 mm (temperature of reaction mixture 72-81°, still-head temperature 60-8()°). The reaction mixture is made alkaline with alcoholic potassium hydroxide and poured into water. The solid is collected, dried [9.25 g (88% crude yield)], mp 260-265°, and crystallized from pyridine-water to give 8.2 g (78%), mp 268-271°. 

Testosterone. 3,3-Ethylenedioxyandrost-5-en-17 -ol (1 g) is dissolved in anhydrous acetone (50 ml), p-toluenesulfonic acid monohydrate (50 mg) is added and the mixture is heated under reflux for 14 hr. Concentration of the resulting solution to a small volume (10 ml) and precipitation with water gives a quantitative yield of slightly impure testosterone (0,87 g, 100%), mp 147-151°. Recrystallizatioii from ether furnishes the pure product of mp 152-154° [ ]d 109° (CHCI3). 

20-Ethylenedioxy-2l-acetoxypregn-4-en-3-one A solution containing 3,3 20,20-bisethylenedioxypregn-5-en-21-ol acetate (120 mg) and /7-toluene-sulfonic acid hydrate (12 mg) in dry acetone (3 ml) is allowed to stand at 22° for 14 hr. Sodium bicarbonate solution and ether are added and the organic layer is separated, washed with water, dried and evaporated. Crystallization of the residue from hexane yields 81 mg (75%) of 20-monoketal, mp 140-141°. 

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Section 180A (Protection of Ketones). Also via Acetylenic Esters Section 306 (Alkyne - Ester). 

III. Experimental Procedures / 406 Protection of ketones / 406 Protection of hydroxyl groups / 413... 

This Chapter contains reactions which prepare the oxides of nitrogen, sulfur, and selenium. Included are N-oxides, nitroso, nitro compounds, nitrile oxides, sulfoxides, selenoxides, and sulfones. Oximes are found in Sections 60A (Protection of Aldehydes) and 180A (Protection of Ketones). Preparation of sulfonic acid derivatives are found in Chapter Two and the preparation of sulfonates in Chapter Ten. 

Related Methods Protection of Aldehydes (Section 60A) Protection of Ketones (Section 180A)... 

Protection of ketones as eniminium salts, during electrophilic reactions elsewhere B. Gadsby and M. R. G. Leeming, Chem. Commun., 1968) 596. 

Cleavage of tkhkeuds. Protection of ketones and aldehydes by conversion to thioketals is rarely u.sed because thioketals are resistant to both acid- and base-catalyzed hydrolysis. Use of mercuric salts has been the most useful procedure known (1, 654 2, 182 3, 136). Japanese chemists now report that cleavage can be effected readily through alkylation with triethyloxonium fluoroborate. Thus alkylation of cyclohexanone ethylenethioketal (I) with the reagent affords the salt (2). Alkaline hydrolysis of (2) gives cyclohexanone in only 36% yield. However, if the salt (2) is shaken with 3% CUSO4 solution in methylene chloride, cyclohexanone is obtained in 81 % yield. 

The same ketone was also produced by protection of ketone 376 as the ketalamine 383, which could then be reduced with lithium aluminum hydride and hydrolyzed to ketone 382. In this ketone Bohlmann bands... 

Many derivatives of 1,2- and 1,3-dithiols have been used as protecting groups, but those discussed are the most common. Greene and Wuts discuss other methods for protection of ketones and aldehydes, including cyanohydrins, hydrazones, oximes, oxazolidines, and imidazolidines. 9 Most of these are rather specialized and will not be discussed in this general presentation. 

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