Reactions thioacetalization

In the presence of sodium acetate, thioacetic acid reacts with 2,4-pentanedione and various a-acetylenic ketones to give l,6,6aS -trithiapentalenes (Scheme 8). In this reaction thioacetic acid reacts both as acylating and sulfurating agent. 

The synthesis of 11-oxaprostaglandlns from o-glucose uses the typical reactions of gl cofuranose diacetonide outlined on p. 267. Reduction of the hemiacetal group is achieved a thioacetal. The carbon chains are introduced by Wittig reactions on the aldehyde grou] which are liberated by periodate oxidation and laaone reduction (S. Hanessian, 1979 G Lourens, 1975). 

Thioacetyl derivatives (155) are obtained by direct heterocyclization reactions (365. 378, 563) and by a sulfur-oxygen exchange" reaction involving thioacetic acid and A-2-oxazoline-5-one (154) or A-2-thiazoline-5-one (156) (Scheme 81) (365, 378, 379). Ra-Ni reduction of 155 affords the 5-unsubstituted thiazole (379). 

Miscellaneous Curing Reactions. Other functional groups can react with the thiol terminal groups of the polysulfides to cross-link the polymer chains and build molecular weight. For example, aldehydes can form thioacetals and water. Organic and inorganic acids or esters can form thioesters. Active dienes such as diacrylates can add to the thiols (3). Examples of these have been mentioned in the Hterature, but none have achieved... 

The preparation of quinazoline-2(and 4)-thiones follows those of the corresponding pyrimidines (67HC(24-1)270) but there is at least one special primary synthesis for quinazoline-4(3H)-thiones, illustrated by the reaction of o-aminobenzonitrile with thioacetic acid at 110 °C to give 2-methylquinazoline-4(3H)-thione in 90% yield (53JA675). 

At low temperature a 1 1 adduct of thioacetic acid and an enamine could be prepared (709). The previously described reaction of aminomethylene ketones with hydrogen peroxide was extended to bisaminomethylene compounds. However, acylated cyclohexenamines led to cyclopentane-carboxamides (770), Trichloromethyl adducts of enamines and the rearranged amine derivatives were described in a further study (777). 

The mechanism of the Fiesselmann reaction between methylthioglycolate and a,P-acetylenic esters proceeds via consecutive base-catalyzed 1,4-conjugate addition reactions to form thioacetal Enolate formation, as a result of treatment with a stronger base, causes a Dieckmann condensation to occur providing ketone 8. Elimination of methylthioglycolate and tautomerization driven by aromaticity provides the 3-hydroxy thiophene dicarboxylate 9. 

Complications often arise in the use of 1,3-diketones under the above reaction conditions. This is primarily due to the lack of regioselectivity with regard to formation of the intermediate thioacetal. However, when benzoyl acetone derivatives are employed, the thioketal forms preferentially with the aromatic ketone. ... 

The hetero Diels-Alder [4+2] cycloaddition (HDA reaction) is a very efficient methodology to perform pyrimidine-to-pyridine transformations. Normal (NHDA) and Inverse (IHDA) cycloaddition reactions, intramolecular as well as intermolecular, are reported, although the IHDA cycloadditions are more frequently observed. The NHDA reactions require an electron-rich heterocycle, which reacts with an electron-poor dienophile, while in the IHDA cycloadditions a n-electron-deficient heterocycle reacts with electron-rich dienophiles, such as 0,0- and 0,S-ketene acetals, S,S-ketene thioacetals, N,N-ketene acetals, enamines, enol ethers, ynamines, etc. 

The much simpler steroid, 253, was fortuitously found to fulfill this role when injected into animals. Its lack of oral activity was overcome by incorporation of the 7a-thioacetate group. Reaction of the ethisterone intermediate, 77b, with a large excess of an organomagnesium halide leads to the corresponding acetylide salt carbonation with CO2 affords the carboxyllic acid, 251. This is then hydrogenated and the hydroxy acid cy-clized to the spirolactone. Oppenauer oxidation followed by treatment with chloranil affords the 4,6-dehydro-3-ketone (254). Conjugate addition of thiolacetic acid completes the synthesis of spironolactone (255), an orally active aldosterone antagonist. ... 

Aldehydes and ketones react with thiols to yield thioacetals just as they react with alcohols to yield acetals. Predict the product of the following reaction, and propose a mechanism ... 

Thiamin, structure of, 530, 1045 thiazolium ring in, 530 Thiamin diphosphate, p/Ca of, 1151 reaction with pyruvate, 1151-1153 structure of. 1151 ylide from. 1151 Thiazole, basicity of. 948 thio-, thioester name ending, 787 Thioacetal, synthesis of, 743 Thioanisole, electrostatic potential map of. 777... 

The aldehyde function at C-85 in 25 is unmasked by oxidative hydrolysis of the thioacetal group (I2, NaHCOs) (98 % yield), and the resulting aldehyde 26 is coupled to Z-iodoolefin 10 by a NiCh/CrCH-mediated process to afford a ca. 3 2 mixture of diaste-reoisomeric allylic alcohols 27, epimeric at C-85 (90 % yield). The low stereoselectivity of this coupling reaction is, of course, inconsequential, since the next operation involves oxidation [pyridinium dichromate (PDC)] to the corresponding enone and. olefination with methylene triphenylphosphorane to furnish the desired diene system (70-75% overall yield from dithioacetal 9). Deprotection of the C-77 primary hydroxyl group by mild acid hydrolysis (PPTS, MeOH-ClHhCh), followed by Swem oxidation, then leads to the C77-C115 aldehyde 28 in excellent overall yield. 

The C j-symnietric A, A"-bis(4-tnethylphenylsulfonyl)-l,2-diphcnyl-l,2-cthanediamine (see Sections 1.3.4.2.2.1. and 1.3.4.2.2.2.) also provides remarkable induced stereoselectivity in thioac-etatc aldol additions51. For example, (5)-phenyl thioacetate reacts with the bromoborolane available from the reaction of the diamine with tribromoborane to give the enolate. Subsequent addition to aldehydes affords the /5-hydroxy thioestcrs in good yield and enantiomeric excess51. 

When aldol reactions of thioacetates are mediated with the following computer-designed bromoborolane [available in 26% yield from ( )-menthone] /(-hydroxy thioesters are obtained in 85-96.7% ee. The yields range from 60 90%t,4c. 

Considerable efforts have been devoted to the stereoselective introduction of a /(-methyl function in intermediates for the synthesis of 1 jS-methylcarbapenems. While the trimethylsilyl trifluoromethanesulfonate catalyzed reaction of a 4-acetoxyazetidinone derivative with ketene acetals shows no selectivity, ketene thioacetals lead to stereoselective formation of the a-methyl isomer108. The zirconium enolate, however, shows high /(-methyl selectivity. 

The addition reactions of alkyllithium-lithium bromide complexes to a-trimethylsilyl vinyl sulfones that have as a chiral auxiliary a y-mono-thioacetal moiety derived from ( + )-camphor are highly diastereoselective. A transition state that involves chelation of the organolithium reagent to the oxygen of the thioacetal moiety has been invoked. The adducts are readily converted via hydrolysis, to chiral a-substituted aldehydes22. 

Similar reactions have been carried out with other thioacetals, as well as with compounds containing three thioether groups on a carbon. ... 

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... 

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. ... 

The temperature at which elimination of thiophenol occurs depends on the substituents on the sulfur-bearing carbon. Thioke-tals react rapidly at 25°. In some cases the elimination of thiophenol from the less reactive thioacetals may also be performed at 25°. However, in the present case the combined inductive effects of the vinyl and methoxy groups evidently destabilize the incipient car-bonium ion and necessitate a higher temperature for the reaction. 

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. 

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