Thioketals hydrolysis

Another synthesis of the cortisol side chain from a C17-keto-steroid is shown in Figure 20. Treatment of a C3-protected steroid 3,3-ethanedyidimercapto-androst-4-ene-ll,17-dione [112743-82-5] (144) with a tnhaloacetate, 2inc, and a Lewis acid produces (145). Addition of a phenol and potassium carbonate to (145) in refluxing butanone yields the aryl vinyl ether (146). Concomitant reduction of the C20-ester and the Cll-ketone of (146) with lithium aluminum hydride forms (147). Deprotection of the C3-thioketal, followed by treatment of (148) with y /(7-chlotopetben2oic acid, produces epoxide (149). Hydrolysis of (149) under acidic conditions yields cortisol (29) (181). 

The hydrolysis of dehydrocholic acid trishemithioketal (29) can be performed selectively to yield the 7,12-bishemithioketal (30), the 12-monohemi-thioketal (31) or the free triketone (32). ... 

By hydrolysis of ketals or thioketals Amberlyst ion-exchange resin, 152 Methylthiomethyl p-tolyl sulfone, 192 From oximes... 

To achieve this synthesis, the methanal first is converted to a thioketal, which then is partially oxidized to give 13. Treatment of13 witha strong base converts it to the carbanion, which can be readily alkylated. By using 1,3-dibromopropane and two equivalents of base, a double displacement forms the cyclic product, 14. The sulfur groups of 14 can be removed easily by acid hydrolysis to give cyclobutanone ... 

The hydrolysis reactions of thioacetals or thioketals are also accelerated by soft cations such as silver(i) or mercury(n) (Fig. 4-44). 

This reaction is widely utilised in organic synthesis, when carbonyl groups may be protected as the thioacetals or thioketals. Unlike acetals or ketals, the thio compounds do not undergo acid catalysed hydration, and may be used in acidic reaction conditions. The metal-directed hydrolysis is rationalised in terms of the soft-soft interaction of the sulfur with the metal cation, in contrast to the hard-soft interaction with a proton. Hydrolysis is readily achieved on treatment with aqueous mercury(n) or silver(i) salts. Once again, the... 

Thioacetals and thioketals are the sulphur equivalents of acetals and ketals and are also prepared under acid conditions (Following fig.). These can also be used to protect aldehydes and ketones, but the hydrolysis of these groups is more difficult. Moreover, the thioacetals and thioketals can be removed by reduction and this provides a method of reducing aldehydes and ketones. 

Hydrolysis of thioacetals (7, 364). TTN has been used for selective dethioacetalization of the bis thioketal 1 to the mono thioketal 2. The paper includes examples of hydrolysis of simpler thioacetals. ... 

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. 

Although acetals, ketals, and ortho esters are easily hydrolyzed by acids, they are extremely resistant to hydrolysis by bases. An aldehyde or ketone can therefore be protected from attack by a base by conversion to the acetal or ketal (16-5), and then can be cleaved with acid. Pyridine-HF has also been used for this conver-sion. Thioacetals, thioketals, gem-diamines, and other compounds that contain any two of the groups OR, OCOR, NR2, NHCOR, SR, and halogen on the same carbon can also be hydrolyzed to aldehydes or ketones, in most cases, by acid treatment. Several ArCH(OAc)2 derivatives were hydrolyzed to the aldehyde using Montmoril-... 

Hydrolysis of thioketalsf Thioketals are hydrolyzed to the parent ketone (75-85% yield) by treatment with a tenfold excess of silver oxide in refluxing aqueous methanol (1 10) for 16 hr. to 4 days. 

The synthesis of verazine [(25S)-22,26-epiminocholesta-5,22(iV)-dien-3/3-ol)] (95) from tomatid-5-en-3/S-ol was described [64-66). Reduction of 86 with sodium borohydride in methanol afforded diol 87 which, when acetylated, furnished the iV,0,C>-fn-acetate (88). Alkaline hydrolysis of 88 yielded the diol 89. Through partial oxidation with one equivalent of chromium trioxide, the A-acetyldiol (89) gave the ketone 90. Treatment of this ketone with ethanedithiol—hydrochloric acid, followed by desulfurization of the resulting thioketal 91 with Raney nickel, yielded 92. 

Deoxyserratinine (7) has been derived from serratinine 35). Treatment of the acetate 52 with ethane dithiol gave the corresponding cyclic thioketal at C-8. Desulfurization over nickel gave the acetate 53 which on hydrolysis yielded 8-deoxyserratinine (54). 

Base-hydrolysis of the. lO -acetoxy-isotwistane 246 (3.2.3.) yielded the corresponding alcohol 137, which was also characterized as its tosylate 267 (3.2.3.). The azide 287 (3.2.3.) was catalytically reduced (H2/raney-nickel) to the 10° -amino-iso-twistane 330. Oxidation of the isotwistanol 137 with Jones-reagent gave the ketone 331, which was transformed via desulfuration with raney-nickel of the corresponding thioketal 332 to unsubstituted 2,7-dioxa-isotwistane 128, see also 2.2.2.1.). 

Oxidation of the alcohol 374, obtained by base-hydrolysis of the acetate 311 (3.4.3.), with Jones-reagent yielded the ketone 375. Unsubstituted 2,8-dioxa-homotwistbren-dane 377) was prepared by converting the ketone 375 to its thioketal 376, which on reductive desulfuration with raney-nickel gave 377. The enolacetate 378 was available by reaction of the ketone 375 with triphenylethylUthium as base followed by addition of acetic anhydride. Under acidic conditions only decomposition could be observed and with pyridine as base no reaction took place. 

Conversion of the aldehyde to protected derivatives at the same level of oxidation (such as ketals, oximes, hydrazones) has been long known. A new hydrazone derived from 4-aminothiomorpholine S,S-dioxide has been carefully investigated [134, 138] and some thiazolidine derivatives have been recently evaluated [136]. C-20 thioketals have been recently introduced, which are especially useful as an aldehyde-protecting group when hydrolysis of the acid-labile mycarose is not wanted their synthesis is accomplished by treatment of the aldehyde with diphenyldisulfide and a trialkylphosphine [134, 139]. The aldehyde has also been transformed into ketones with diazoalkanes [134]. 

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