Acids dithioacetals

A convenient three-component coupling reaction of Meldrum s acid, acrolein, and thioacetic acid was described <1997TL5785> for the synthesis of 2-(l,2-dithiolan-3-yl)acetic acid 315 (Scheme 58). As shown, diacetylthiolated propyl Meldrum s acid 311 was refluxed in methanol affording ester acid dithioacetate 312, which without purification was transformed upon acid-catalyzed methanolysis into diester 313. The subsequent oxidation step led to ester 314 which afforded the final acid 315 by a hydrolysis-decarboxylation sequence. 

Lithium tetrafluoroborate in wet acetonitrile has been described as an effective combination for the hydrolysis of acetals under mild weakly acidic conditions. Dithians were unaffected. Methods for the hydrolysis of thioacetals continue to appear. Reagents that have been described include a polystyryl-mercury(n) trifluoroacetate combination, which retains the metal on the resin, lead(iv) dioxide and boron trifluoride etherate, aqueous hydrochloric acid in dioxan containing dimethyl sulphoxide, methyl-bis(methylthio)sulphonium hexa-chloroantimonate, and iodoxybenzene, catalysed by toluene-p-sulphonic acid. Dithioacetals derived from ethane-1,2-dithiol may be cleaved with dimethyl sulphoxide in combination with either t-butyl or trimethylsilyl bromides and iodides. Regeneration of ketones from ethanediyl-S S -acetals via the lithium-di-isopropylamide-promoted fragmentation to the thioketone and subsequent hydrolytic work-up only gives satisfactory yields for aryl methylketone derivatives. Dithioacetal SS-dioxides are rapidly cleaved in hot methanolic hydrochloric acid solution. ... 

Thioketenes can be prepared in several ways, from carboxyHc acid chlorides by thionation with phosphoms pentasulfide [1314-80-3] 2 5 ketene dithioacetals by -elimination, from l,2,3-thiadia2oles with flash pyrolysis, and from alkynyl sulfides (thioacetylenes). The dimeri2ation of thioketenes to 2,4-bis(alkyHdene)-l,3-dithietane compounds occurs quickly. They can be cleaved back pyrolyticaHy (63). For a review see Reference 18. 

Other Radioprotective Chemicals. The bis-methylthio- and methylthioamino-derivatives of 1-methylquinolinium iodide and l-methylpyridinium-2-dithioacetic acid provide reasonable protection to mice at much lower doses than the aminothiols, which suggests a different mechanism of action (139). One of these compounds, the 2-(methylthio)-2-piperidino derivative of the l-methyl-2-vinyl quinolinium iodide (VQ), interacts with supercoUed plasmic DNA primarily by intercalation. Minor substitutions on the aromatic quinolinium ring system markedly influence this interaction. Like WR-1065, VQ is positively charged at physiological pH, and the DNA-binding affinities of VQ and WR-1065 appear to be similar. 

Hg(OAc)2, H2O, 80% AcOH, HSCH2CH2SH, 25°, 5-20 min H2S, 2 h, high yield. The removal of an 5-benzylthiomethyl protective group from a dithioacetal with mercuiy(II) acetate avoids certain side reactions that occur when an 5-benzyl thioether is cleaved with sodium/ammonia. The dithioacetal is stable to hydrogen bromide/acetic acid used to cleave benzyl carbamates. 

Acetvldiphenylsulfide is reacted with carbon disulfide in an initial step to give 4-phenyl-thiobenzoyl dithioacetic acid. That, in turn, is reacted with o-phenylenediamine. 

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 pivotal step in this sequence is an electrophilic substitution on indole. Although the use of l,3-dithian-2-yl carbanions is well documented, it has been shown only recently that 1,3-dithian-2-yl carbenium ions can be used in a Priedel-Crafts type reaction. This was accomplished initially using 2-methoxy-l,3-dithiane [1,3-Dithiane, 2-methoxy-] or 2-metlioxy-l,3-dithiolane [1,3-Dithiolane, 2-methoxy-] and titanium tetrachloride [Titanate(l —), tetrachloro-] as the Lewis acid catalyst.9 2-Substituted lysergic acid derivatives and 3-substituted indoles have been prepared under these conditions, but the method is limited in scope by the difficulties of preparing substituted 2-methoxy-1,3-dithianes. l,3-Dithian-2-yl carbenium ions have also been prepared by protonation of ketene dithioacetals with trifluoroacetic acid,10 but this reaction cannot be used to introduce 1,3-dithiane moieties into indole. 

In another series of experiments, a novel approach to the determination of nucleotide sequence was adopted by A. S. Jones, Stacey, and their co-workers. For example, when calf thymus DNA was treated with mercaptoacetic acid in the presence of zinc chloride and anhydrous sodium sulfate, it yielded aldehydo-apurinic acid bis(carboxymethyl) dithioacetal. When degraded with dilute alkali, this afforded dialyzable fragments, which were separated into at least 20 components. Some were identified, including mono-, di-, and tri-nucleotides, thereby revealing that DNA contain regions of at least three linked pyrimidine nucleotides. The same procedure was applied to the DNA isolated from M. phlei ... 

The Nucleotide Sequence in Deoxypentosenucleic Acids. Part II. The Alkaline Degradation of Calf-thymus aldehydo Apurinic Acid Di(carboxymethyl) Dithioacetal, A. S. Jones, D. S. Letham, and M. Stacey, J. Chem. Soc., (1956) 2579-2583. 

Enzymic syntheses are considered next. Xylitol is a substrate for sheep-liver L-iditol dehydrogenase, a NAD-linked enzyme. 1-Deoxy-D-xylitol, prepared by Raney nickel reduction of D-xylose diethyl dithioacetal in a 27% overall yield from D-xylose, was also reported31 to be a substrate, although with a higher Km and lower Vmax. The product was assumed to be l-deoxy-D-f/ireo-pentulose because of the appearance of a yellowish fluorescent spot when a chromatogram was sprayed with acidic 3,5-aminobenzoic acid, resembling that formed from 1 -deoxyfructose. There was no more-rigorous characterization. 

C17H21NO2S 1227-99-2) see Tiemonium iodide (phenylthio)acetaldehyde (CgHjOS 66303-55-7) see Sumatriptan (4-phenylthiobenzoyl)dithioacetic acid (C15H12OS3 41054-41-5) see Tibezonium iodide... 

Lewis acid-mediated ionization of acetals also generates electrophilic carbon intermediates that react readily with allylic stannanes.190 Dithioacetals can be activated by the sulfonium salt [(CH3)2SSCH3]+BF4,191... 

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