Aldehydes thioacetal formation

Thioacetal formation with subsequent desulfurization with hydrogen and Raney nickel gives us an additional method for converting carbonyl groups of aldehydes and ketones to —CH2— groups ... 

The presence of dithiol centres at the active sites of a variety of additional enzymes has been proposed on the basis of inhibition studies. For example, the investigations on aldehyde dehydrogenase represent one of the earliest uses of arsenite as a dithiol diagnostic reagent The overall data strongly support the presence of a polythiol site as a general feature of aldehyde oxidases, but its functional role has not been established. Because of the ease of thioacetal formation a dithiol would make a chemically attractive... 

Hoechst workers [140] used steps similar to those employed in the (128) to (129) transformation to convert the enone (130), prepared from the hemiacetal (131) by thioacetal formation, Moffat oxidation and olefln bond migration, to the aldehyde (132) which was then elaborated to afford ( )-l l-deoxy-PGE2. 

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. 

H"], HSCH2CH2SH, (-H2O) Cyclic thioacetal formation Ethylene thioglycol can be used to convert an aldehyde or ketone into a cyclic thioacetal. 

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

Our group has exploited 4-phenylthio-l,3-dioxanes as convenient precursors to 4-lithio-l,3-dioxanes [45,65-69]. 4-Phenylthio-l,3-dioxanes 184 were originally prepared from -silyloxy aldehydes 183 [65] (Eq. 28). Lewis acid-promoted addition of phenylthiotrimethylsilane gave an unstable thioacetal intermediate, which could be converted in situ to the corresponding 1,3-dioxane. Yields for this process are variable, as the product is unstable under the conditions of its formation. The reaction slowly evolves to a mixture of the desired product, the phenylthio acetal of 183, the phenylthio acetal of acetone, and a variety of other unidentified products. 

Because 2-trimethylsilyloxy sulfides such as 1154 and 1157 are hemiphenyl thioacetals of aldehydes, they are readily hydrolyzed to aldehydes [8-12] or ketones [13]. Thus alkylation of the lithium salt 1162 with cyclohexyhnethylbromide 1163, gives in nearly quantitative yield, the sulfide 1164, which, after oxidation with m-chloroperbenzoic acid and hydrolysis, rearranges in 70% yield to cyclohexylacetal-dehyde 1165 [8] (Scheme 8.2). A more detailed discussion of the formation of aldehydes is given in Section 8.5. 

Crossed reactions of the two aldehydes under phase-transfer catalytic conditions with the intermediate thioacetates, which can be isolated under controlled reaction conditions [14], leads to the formation of three products [13], as result of retro-Michael reactions (Scheme 4.18). In the case of the reactions involving crotonaldehyde, the major product results from the reaction of the aldehyde with the released thiolacetic acid, with lesser amounts of the expected crossed reaction products (Table 4.23). In contrast, the reaction of acrolein with the thioacetate derived from crotonaldehyde produces, as the major product, the crossed cycloadduct. These observations reflect the relative stabilities of the thioacetates and the relative susceptibilities of acrolein and crotonaldehyde to the Michael reaction. 

The electroreduction of disulfides R2S2 (R = Ar, Aik), in the presence of carbonyl compounds and MesSiCl, includes the formation of intermediate thiosilanes and results in trimethylsilyl ethers of hemithioacetals of ketones and aldehydes or in full thioacetals depending on whether a two-compartment (a) or an undivided (b) cell was used (Scheme 48) [218]. 

Because carbohydrates are so frequently used as substrates in kinetic studies of enzymes and metabolic pathways, we refer the reader to the following topics in Ro-byt s excellent account of chemical reactions used to modify carbohydrates formation of carbohydrate esters, pp. 77-81 sulfonic acid esters, pp. 81-83 ethers [methyl, p. 83 trityl, pp. 83-84 benzyl, pp. 84-85 trialkyl silyl, p. 85] acetals and ketals, pp. 85-92 modifications at C-1 [reduction of aldehydes and ketones, pp. 92-93 reduction of thioacetals, p. 93 oxidation, pp. 93-94 chain elongation, pp. 94-98 chain length reduction, pp. 98-99 substitution at the reducing carbon atom, pp. 99-103 formation of gycosides, pp. 103-105 formation of glycosidic linkages between monosaccharide residues, 105-108] modifications at C-2, pp. 108-113 modifications at C-3, pp. 113-120 modifications at C-4, pp. 121-124 modifications at C-5, pp. 125-128 modifications at C-6 in hexopy-ranoses, pp. 128-134. 

Preparation of a somewhat more complex leukotriene antagonist begins by aldol condensation of the methyl carbanion from quinoline (29-1) with meta-phthalalde-hyde (29-2) to give the stilbene-like derivative (29-3) dimer formation is presumably inhibited by the use of excess aldehyde. Reaction of that product with A,A-dimethyl-3-mercaptopropionamide in the presence of hexa-methylsilazane affords the silyl ether (29-4) of the hemimercaptal. Treatment of that intermediate with ethyl 3-mercaptopropionate leads to the replacement of the silyl ether by sulfur and the formation of the corresponding thioacetal (29-5). Saponification of the ester group leads to the carboxylic acid and thus to verlukast (29-6) [33]. 

Nafion-H exhibits lower activity. In the acetylation of alcohols,673 in the transformation of aldehydes and ketones with trimethyl orthoformate to the corresponding dimethylacetals,674 and in the formation of acylals,675 longer reaction times (several hours) are required to achieve high yields at room temperature. Furthermore, the formation of ethylenedithioacetals in benzene674 and the direct transformation of acetals to thioacetals with ethane-1,2-thiol in dichloromethane676 can only be performed at reflux temperature. 

Compound 24 is obtained as the major reaction product. The mercaptoaldehydes 19 and 20 obtained via 1,6- and 1,4-addition of H2S to the starting aldehydes can be considered as the precursors for compounds 22, 24 and 25. The formation of the thiophene derivative 23 can be explained to proceed via mercaptoaldehyde 18, although the latter could not be detected as its acetate/thioacetate in the crude reaction mixture. 

Hydrolysis of thioacetals. Exposure of the thioacetal 1 to excess methyl iodide in aqueous acetonitrile at reflux results in formation of the lactam 2, an intermediate in the synthesis of quebrachamine. This transformation invoives initiai hydrolysis of 1 to an aldehyde intermediate (4,341), followed by an Hl-catalyzed Pictet-Spengler... 

The formation of thioacetals from aldehydes and ketones involves the reaction with a thiol such as ethane-1,2-dithiol in the presence of a Lewis acid catalyst such as boron trifluoride eiherate. These derivatives have been described earlier. 

Among organic sulfides, those derived from 1,3-dithiane occupy an important place. The interest in these reagents lies not only in their reactivity with electrophilic substrates but also in the synthetic principles which have been developed from work on these compounds. By masking the aldehyde group by the formation of a dithiane, the carbon atom may participate in nucleophilic additions or substitution reactions and after hydrolysis of the thioacetal, the carbonyl group can then be regenerated (Scheme 1). 

Thiols (RSH) add reversibly to aldehydes and ketones in the presence of acid to yield thioacetals. The reaction mechanism is analogous to the formation of acetals. 

Conjugated ketene thioacetals have been successfully prepared starting with aldehyde dimethylhydra-zones. In these reactions, the first-formed azaallyllithium reagent was allowed to react with carbon disulfide to form an intermediate lithium 3-dimethylhydrazonoalkanedithiolate. A second deprotonation of this dithiolate with a second equivalent of LDA then generated a dianion that was successfully alkylated with two equivalents of methyl iodide to yield the ketene thioacetal (e.g. 55 equation 25). This two step sequence avoided competing formation of a methyl dithiocarbamate by addition of LDA to carbon disulfide. 

Kitazume et al. have also investigated the use of [EtDBU][OTf as a medium for the formation of heterocydic compounds [242], Compounds such as 2-hydroxymethylaniline readily condense with benzaldehyde to give the corresponding benzoxazine (Scheme 5.2-105). The product of the reaction is readily extracted vyith solvents such as diethyl ether and the ionic liquid can be recycled and reused. Thioacetals and dithianes formed from the condensation of 2-mercaptoethanol and ethane-l,2-dithiol with aldehydes also form readily in... 

The treatment of styrenes with ammonium thiocyanate and CAN in MeCN results in the formation of dithiocyanates. Under an oxygen atmosphere, phenacyl thiocyanates can be the major products. The thiocyanation of indoles also proceeds under similar conditions. Chemoselective thioacetalization of aldehydes and the conversion of epoxides to their corresponding thiiranes can be operated under mild conditions with the catalysis of CAN. As an extension, selenocyanation can be conducted in a similar fashion with CAN/KSeCN. ... 

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