Acetals monothioacetals

These results indicate that the order of reactivity toward acid is generally acetals > monothioacetals dithioacetals. The ease of removal of the latter two groups is determined by essentially the same factors that govern the removal of the thioethers namely, ease of protonation, the stability of the cation formed and the possibility of irreversible reactions which can shift the equilibria in favor of the cleavage products. On the basis of available data the S-monothioacetal derivatives of cysteine appear to react somewhat more cleanly than the S-trityl thioethers but are of similar reactivity whereas the S-dithioacetal derivatives react more nearly like the S-benzyl or S-f-butyl thioethers. 

T AHBr, AcOH, rapid. The 5-isobutoxymethyl monothioacetal is stable lo 2 N hydrochloric acid and to 50% acetic acid some decomposition occurs m2 N sodium hydroxide. ... 

The monothioacetal is also stable to 12 N hydrochloric acid in acetone (used to remove an TV-triphenylmethyl group) and to hydrazine hydrate in refluxing ethanol (used to cleave an A -phthaloyl group). It is cleaved by boron trifluoride etherate in acetic acid, silver nitrate in ethanol, and tiifluoroacetic acid. The monothioacetal is oxidized to a disulfide by thiocyanogen, (SCN)2- ... 

An. S-tetrahydropyranyl monothioacetal is stable to 4 A HCI/CH3OH, 0° and to reduction with Na/NH3. (An O-tetrahydropyranyl acetal is cleaved by 0.1 AHCl,... 

Searching for a method of synthesis of enantiopure lamivudine 1, the compound having a monothioacetal stereogenic centre, Rayner et al. investigated a lipase-catalysed hydrolysis of various racemic a-acetoxysulfides 2. They found out that the reaction was both chemoselective (only the acetate group was hydrolysed with no detectable hydrolysis of the other ester moieties) and stereoselective. As a result of the kinetic resolution, enantiomerically enriched unreacted starting compounds were obtained. However, the hydrolysis products 3 were lost due to decomposition." In this way, the product yields could not exceed 50% (Equation 1). The product 2 (R = CH2CH(OEt)2) was finally transformed into lamivudine 1 and its 4-epimer. ... 

The C-H bond-dissociation energies Z>c-h of the acetals 130 and 131, monothioacetal 132, and the dithioacetal 133 (Figure 7) were calculated from experimental reaction kinetic data <2005MI379>. The C-H dissociation energies of the 1,3-dithiane derivative 133 proved to be lowest, followed by the 1,3-oxathiane derivatives 132,... 

Explain why compound 2 hydrolyzes at a rate that is independent of pH in the range pH 1.5 to 0.1 M NaOH, despite the fact that as a general rule acetals and monothioacetals show strong acid catalysis. 

Eliel and Giza (50) have studied the acid equilibration of the isomeric 2-alkylthio 6-methyltetrahydropyrans 59 and 60 (R=CHj and (CH3I3C). They found about 65% of axial isomer 59 indicating that the monothioacetal function possesses an anomeric effect although it is weaker than that of the acetal function. Zefirov and Skekhtman (58) have arrived at a similar conclusion by studying 2-phenylthio and 2-ethylthiotetrahydropyran. 

The details on the preparation of the glycone synthon 16 have been described in the earlier report on 3 (24). The key reactions in this synthesis is the Suarez radical fragmentation of the 1,2-O-isopropylidene furanose 17 to give the 1-O-acetyl-1,2-isopropylidene 18 (35), and acetal exchange of 18 to the phenylthio monothioacetal 16 (Scheme 2). Overall, 16 is easily obtained on multi-gram scale (ca. 20 g), in 60% yield, over five steps from commercially available D-lyxose. 

Nishiyama, H., Narimatsu, S., Sakuta, K., Itoh, K. Reaction of allylsilanes and monothioacetals in the presence of Lewis acids regioselectivity in the cleavage of the acetals. J. Chem. Soc., Chem. Commun. 1982,459-460. 

Matteson and coworkers have described the deprotonation and alkylation of bis(l,3,2-dioxaborin-2-yOmethane (11). Deprotonation with LiTMP yields the stabilized anion, which can be alkylated with a variety of primary alkyl halides. Oxidation under basic conditions then unmasks the carbonyl group. Matteson has also described the deprotonation of some substituted boronic esters (12 X = SPh, SiMei). - The alkylated products derived from (12 X = SPh) can be treated with A/-chlorosuccinimide under mild basic conditions to yield either the monothioacetals or the acetals. Boron-stabilized carbanions can also be generated by transmetallation of the organostannanes. ... 

The different reactivities of the two substituents on C-l allow selective replacement and conversion of them. Alkyl monothio-acetals [proposed as intermediates in mercury(II)-catalyzed demer-captalation reactions—see Section IV,l,b] have been prepared from a-bromothioethers by the combined action of an alcohol and silver(I) carbonate the introduction of S-nucleophiles is discussed in Section 11,6. Reduction of 81 by lithium aluminum hydride effects hydrogen-olysis of the carbon-halogen bond, whereas the action of Raney nickel on the derived S-ethyl O-methyl monothioacetal specifically cleaves the carbon-sulfur bond to afford the pentaacetate of 1-0-methyl-D-galactitol.327... 

The l,3-bis(trimethylsililoxy)butadienes 130-132, as the equivalent of methyl acetoacetate dianion, constitute the three-carbon fragments with two nucleophilic sites (equation 110). Condensation of 130-132 with various equivalents of -dicarbonyl compounds and titanium(IV) chloride gives substituted methyl salicylates. The differential reactivity of the electrophiles which increases in the order conjugated position of enone > ketone > monothioacetal, acetal and of 130-132 (4-position > 2-position) ensures complete regioselectivity in this combination of two three-carbon units to form phenols such as 133 and 134 °° °. ... 

Organotin compounds with tin-sulfur bonds are useful for the transformations of alkyl halides to sulfides (eq (119)) [114], esters to thiolesters (eq (120)) [115], and acetals to monothioacetals (eq (121)) [116]. 

Monothioacetals are generally formed by fraw.v-ketalization of simple acetals. 

RSH, LiBr, toluene, 0-80°C, 70-99% yield. MOM and MEM groups as well as furanose and pyranone acetals all react to give the monothioacetal, but simple dimethylacetals and dimethylketals react faster than the furanose and pyranose acetals. ... 

The 5-isobutoxymethyl monothioacetal is cleaved by boron trifluoride etherate in acetic acid, by silver nitrate in ethanol, and by trifluoroace-tic acid. The monothioacetal is oxidized to a disulfide by thiocyanogen,... 

Monothioacetalization. One alkoxy group of an acetal can be replaced by a thio group using RSH or RSSiMej when catalyzed by a dicyanoketene acetal or tetra-cyanoethylene. 

If we want to fix glucose in the open-chain form, we must make an acetal of quite a different kind using a thiol (RSH) instead of an alcohol, an aldehyde, or a ketone. The thiol combines with the aldehyde group of the open-chain form to give a stable dithloacetal. The dithioacetal is evidently more stable than the alternative hemiacetals or monothioacetals that could be formed from the pyranose or furanose forms. 

Acetic anhydride Monothioacetals from sulfoxides Protection of tert. alcohol groups as methylthiomethyl ethers... 

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