Orthothioformates

Orthothioformates HC(SR)3 (R = alkyl or aryl) are smoothly metallated by alkali amides in liquid ammonia and by butyllithium in THF and hexane. The anionic intermediates decompose readily to give thiolates RS- and carbenes (RS)2C [1]. Further reaction of the latter species (presumably with (RS)3C-) gives rise to the formation of dimers (RS)2C=C(SR)2.  

These carbenoid reactions occur already at temperatures in the region of — 40 °C. Good results in functionalization reactions are attainable only with electrophiles that prefer (RS)3C over RS-. Generation of the carbenoids at very low temperatures is also an important condition [2]. 

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In the presence of thiophenate ion the intermediate is trapped as phenyl orthothioformate, even though the reaction of sodium thiophenate with chloroform itself is slower than that of sodium hydroxide, and hence sodium thiophenate can not be competing with hydroxide ion... 

Preparation of Ethyl Orthoformate from Ethyl Orthothioformate [39]... 

Alkyl formates or formic acid and its esters can be converted to trialkyl orthothioformates [74-77] which in turn can be converted to trialkyl orthoformates in good yields [78, 79], It has been reported that acid chlorides of higher carboxylic acids can also be converted to trialkyl orthothioformates [80], but thus far no reports appear in the literature on attempts to convert them to trialkyl ortho esters. 

Ethyl orthoacetate, 48 Ethyl orthobenzoate, 54 Ethyl orthobromoacetate, 60 Ethyl orthodibromoacetate, 60 Ethyl orthoformate, 50 Ethyl orthothioformate, 50 Ethyl a-phenylazo-a-methylacetoacetate, 299... 

Carbanions derived from orthothioformates behave as carboxy anion equivalents through alkylation with electrophiles followed by unmasking of the orthothiocarboxylate group [43]. 

This interchange reaction is a convenient process for making orthoformates. The equilibrium is shifted to the right by removal of the volatile mercaptan to give high yields of the ortho esters. The reaction is catalysed by Frledel-Crafts type catalysts. The ethyl orthothioformate is available in nearly quantitative yield om ethyl formate and ethyl mercaptan. 

A cloudy mixture of 20 g. (0.32 mole) of ethyl mercaptan and 12 g. (0.16 mole) of ethyl formate is cooled in an ice-salt bath while dry hydrogen chloride is introduced until the mixture becomes saturated. Hood.) On the introduction of the hydrogen chloride, the mixture becomes clear for a while, after which the water formed in the reaction causes reappearance of a second liquid phase. After several hours the reaction mixture is washed with water and the oily layer is removed by extraction with ether. After drying over calcium chloride, the ether layer is distilled to give 16 g. of ethyl orthothioformate, b.p. 133°/21 mm. The yield is 82% based on ethyl mercaptan. 

Metallated orthothioformates and their seleno analogs (available by metallation of orthothio- and orthoseleno-formate " with lithium amides or on S/Li or Se/Li exchange between orthothio- and orthoseleno-carbonates react efficiently with methyl iodide > as well as with reactive electrophiles such as benzyl chloride and n-butyl iodide (Scheme 84, entry a). ... 

Oxidation of aldehydes to esters and acids Treatment of 2-lithio-2-alkyl-l,3-dithianes (1) with methyl disulfide in THF gives the corresponding orthothioformates (2) in about 90% yield. These are converted in high yield into esters (3) when refluxed in an aqueous alcohol in the presence of mercuric chloride and mercuric oxide as catalysts. Conversion to acids is accomplished by refluxing (2) in aqueous acetone for 24 hr. with catalysis by mercuric chloride and mercuric oxide. Yields in this case are in the range 40-65 %. 

Orthothioformic esters are the most easily prepared orthothiocarboxylic esters, being obtained from formic acid and a thiol.433... 

Triphenyl orthothioformate treated at -78° under N2 with n-butyllithium in tetrahydrofuran, then cyclohex-2-enone added product. Y 95%. - By Hg2+-catalyzed alcoholysis and subsequent acid treatment, the product can be converted to a y-ketocarboxylic acid ester. F. e. s. A. B. Manas and R. A. J. Smith, Chem. Commun. 1975, 216. 

Lactones, addition of thiols 769 Lead, thiol derivatives 748, 749 Lipoic acid 637-639 Lithiation, of 1,3-dithiane 536 of 1,3,5-trithiane 546, 547 2-Lithio-l,3-dithianes, for preparation of 1-deuterioaldehydes 547 for preparation of orthothioformate 547... 

Treatment of 2-lithio-l,3-dithiane derivatives with methyl disulphide yields the orthothioformate 83, which upon hydrolysis in alcoholic solvents furnishes an ester . This method may provide a useful route for the conversion of sensitive aldehydes to esters and carboxylic adds. 

Dithioacetals and related compounds have a number of uses in synthesis, both in Friedel-Crafts-type reactions and in reactions which exploit the high reactivity of carbanions stabilized by two or more sulphur atoms bonded at the carbanion centre. Benzyl orthothioformate, CH(SCH2Ph)3, may be used to introduce a — CH(SCH2Ph)2 group into 2- and 3-positions of an indole, with TiCU as catalyst at - 5 °C in CHQ3, and has been used in this way for 2-substitution of (79), giving (80) and (81), with further elaboration of (80) into 2-methyl-lysergic acid. Studies of ethyl dithio-... 

Acyclic Thioacetal and Orthothioformate Anions. A number of unusual and synthetically useful ring-forming reactions that are thought to involve thioacetal anions such as (40) and (41) have been reported by Cohen. A procedure... 

Orthothioformate anions have been utilized in the generation of the ester (46) and 1,4-dicarbonyl compounds such as (47). A full report has appeared on the decomposition of orthothioformate anions to bis(arylthio)-carbenes (see also Chap. 1, p. 47). 

Thiobarbituric acid 3686 / -Tolyl alcohol 6999 Triethyl orthothioformate 10689... 

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