Thioacetals and thioketals

Sulphur.—Thioacetals and Thioketals. The widespread utilization of lithiated thio-acetals and thioketals as acyl carbanion equivalents (see Section on Li) renders information about other reactions of such species important in general synthetic methodology. Several methods for dethioacetalization have appeared, and in-clude transthioacetalization using glyoxalic acid in acetic acid, and oxidative hydrolysis using S02Cl2-wet silica gel or Tl nitrate. 

Thioacetals can exert dual purpose activity. In addition to their use as acyl carbanion equivalents, they can often be used as electrophilic species. Thus, 1,3-dithian is chlorinated between the two S atoms with iV-chlorosuccinimide, and the product is susceptible to attack by nucleophiles (PhSH, imidazole). Readily available 2-alkoxy-l,3-benzodithioles are also attacked by active methylene compounds such as )8-dicarbonyl compounds or ethyl cyanoacetate, to give excellent yields of the substitutioq products. The utility of 1,3-benzodithioles is further 

Reagents (i), PhjC CI04 (ii), NaBD4 (iii), chloramine-T. HgClj 

A novel approach to a-alkylthionitriles involves treatment of thioketals with Hg(CN)2-l2 in MeCN.2 3 

A variety of conjugated dienes possessing PhS substituents, (120)—(123), have been prepared and applied in Diels-Alder reactions. The Diels-Alder products have self-evident synthetic potential. 

Thiols are the sulfur analogs of alcohols (Section 15.11). The sulfur atom of a thiol is a better nucleophile than the oxygen atom of an alcohol. Thus, thiols react with aldehydes or ketones to form thioacetals or thioketals by a mechanism similar to that described for acetals and ketals. These sulfur derivatives form in high yield because the equdibrium constant for thioacetal formation is much greater than that for acetal formation. We use Lewis acids such as BFj or ZnCl2 rather than protic acids to catalyze the formation of the thioacetal. Both 1,2-ethanedithiol and 1,3-propanedithiol are used to form cyclic thioacetals and thioketals. 

Like acetals, thioacetals are stable in basic solution. However, thioacetals also survive under the acidic conditions that would hydrolyTe an acetal. Thus, they protect a carbonyl group and allow us to react many other functional groups under acidic or basic conditions. Because thioacetals are stable in acid, their hydrolysis requires use of mercuric chloride in aqueous acetonitrile. The formation of an insoluble mercury(II) sulfide provides the driving force for the reaction. 

Thioacetals are valuable intermediates for organic synthesis in their own right. For example, thioacetals are desulfurized by Raney nickel to give the corresponding hydrocarbon. This provides another path from an aldehyde or ketone to a methylene group that does not require either strong acid or strong base. Therefore, this method complements the Wolff—Kishner and Clemmensen reductions. 

Draw the structures of the products of each of the following combination of reagents. 

Outline the steps required to accomplish the following synthesis using a thioacetal derivative in one of the steps. 

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Part C of the present procedure illustrates a mild method for effecting the elimination of thiophenol from thioacetals and thioketals under essentially neutral conditions. The reaction of simple thioacetals and thioketals with bis[copper(I) trifluoro-methanesulfonate] benzene complex in benzene-tetrahydrofuran at room temperature affords vinyl sulfides in high yield (Table I). The reaction presumably occurs by coordination of the thiophilic copper(I) reagent with sulfur, heterolysis to a phenylthio-stabilized... 

Vinyl Sulfides from Thioacetals and Thioketals with Copper(I) Trifluoromethanesulfonate... 

Thioacetals and thioketals can also be made to undergo desul-phurisation with Raney nickel catalyst, thus effecting, overall, the indirect conversion of C=0— CH2 ... 

Thioacetals and thioketals have significant synthetic potential for use in organic chemistry but are often neglected because of their unpleasant odor. A polymeric reagent for the preparation of ketones via 1,3-dithianes has been reported using... 

As a consequence, thiols are preferred to alcohols for the protection of aldehyde and ketone groups in synthetic procedures. Thioacetals and thioketals are... 

DetkioketaKzation. Various thioacetals and thioketals are readily hydrolyzed by pyridinium bromide perbromide (1 equivalent) under phase-transfer conditions. Tetrabutylammonium bromide is used as catalyst and aqueous methylene chloride as solvent. The reaction is more efficient in the presence of pyridine as buffer. Yields are generally 75-90%.1... 

Thioacetal and thioketal carbon shieldings (45-65 ppm) [328, 329] also reflect the heavy atom influence when compared with acetal and ketal carbon shifts (100 + 5 ppm). 

The cleavage of the sulfur-carbon bond of thioacetals and thioketals,671 thioortho-formates672 [Eq. (3.101)], and tetraalkyl thioorthocarbonates673 [Eq. (3.102)] leads to the corresponding mono-, di-, and trithiocarbenium ions, respectively. Trimethylthio-carbenium ion 361 was also prepared by methylating dimethyl trithiocarbonate [Eq. (3.102)]. 

Cyclization of thioketals. The reagent (1) converts thioacetals and thioketals... 

In addition to developing a facile route to the synthesis of thioacetals and thioketals, optimization of the reagents residence time within the packed bed enabled the authors to demonstrate the chemoselective protection of aldehydic functionalities in the presence of ketonic moieties (Scheme 34). 

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. 

DMP (2), like IBX (5), has shown to be a mild and effective method for the removal of thioacetals and thioketals.28 For example, 74 was converted to the desired a,p-unsaturated ketone (75) in 91% yield after 12 hours. No detectable loss of the TBDPS ether or olefin isomerization was observed. 

Aldehydes and ketones react with thiols to form thioacetals and thioketals. The mechanism for addition of a thiol is the same as that for addition of an alcohol. Recall that thiols are sulfur analogs of alcohols (Section 12.10). 

Desulfurization of thioacetals and thioketals forms alkanes (Section 18.9) ... 

Vinyl phenyl sulfides. Treatment of diphenyl thioacetals and thioketals with this soluble Cu(l) salt induces elimination of thiophenol at 25° ... 

Thioketalization. This silane converts aldehydes and ketones into dimethyl thioacetals and thioketals in high yield at 20 without acid catalysis. The rate... 

Thioacetals and ketals are important protecting groups used in organic manipulations. The regeneration of carbonyl compounds by cleavage of acid and base-stable thioacetals and thioketals is a challenging task. Cleavage of thioacetals normally requires use of toxic heavy metals such as Ti +, Hg, Ag, Tl +, or uncom-... 

Thioacetals and thioketals 450 are efficiently cleaved to carbonyl compounds 451 with PhI(OCOCF3)2 or PhI(OAc)2 under mild conditions (Scheme 3.178). This reaction is especially useful for the selective deprotection of either thioacetals or thioketals and is compatible with various other functional groups [537-541]. 

The cleavage of thioacetals and thioketals which are stable in acid and base is quite a challenging problem and invariably requires the use of toxic heavy metals such... 

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