Ethanethiol reagent

The optically active a-sulfinyl vinylphosphonate 122 prepared in two different ways (Scheme 38) is an interesting reagent for asymmetric synthesis [80]. This substrate is an asymmetric dienophile and Michael acceptor [80a]. In the Diels-Alder reaction with cyclopentadiene leading to 123, the endo/exo selectivity and the asymmetry induced by the sulfinyl group have been examined in various experimental conditions. The influence of Lewis acid catalysts (which also increase the dienophilic reactivity) appears to be important. The 1,4-addition of ethanethiol gives 124 with a moderate diastereoselectivity. 

British Drug Houses Ltd. reagent grade ethanethiol was distilled from calcium hydride before use (b.p. 36°). 

As in acidolysis (Chap. 6.1), thioacidolysis proceeds mainly by cleavage of arylglycerol-/ -aryl ether linkages. In contrast to acidolysis, however, thioacidolysis is performed in anhydrous media. The ether-cleaving reagent combines a hard Lewis acid, boron trifluoride etherate, and a soft nucleophile, ethanethiol (Node et al. 1976, Fuji et al. 1979). 

The thioacidolysis reagent is prepared immediately before use 2.5ml of BF, etherate and 10 ml of ethanethiol are successively introduced into a 100-ml volumetric flask containing 20ml of dioxane and the final volume is adjusted to 100 ml with dioxane. This reagent is therefore a solution of 0.2 M BF-, etherate (Note 1) in a 8.75 1 (v/v) dioxane/ethanethiol mixture. It is a colorless reagent immediately after preparation. When an inferior grade of dioxane is used, a yellow color is observed this reagent is not suitable for analytical use. 

GlyoxyKc acid dithioethyl acetal, (C2HsS)2CHCOOH (1). Mol. wt. 180.29. This reagent is conveniently prepared in quantitative yield by addition of dichloroacetic acid to 3 equiv. of NaH in THF followed by reaction overnight with an excess of ethanethiol. ... 

The reagent is generated in silu hy the reaction of sodium hydride (60% oil dispersion) with ethanethiol in DMF. 

The keto ether (187) on treatment with diethyl carbonate in presence of sodium hydride in 1,2-dimethoxyethane afforded the keto ether (188), which was made to react with methyl-lithium in ether, to obtain the tertiary alcohol (189). This on being refluxed with methanolic hydrochloric acid yielded the phenol (190). It was methylated to yield(191) and heated with zinc, zinc iodide and acetic acid to produce pisiferol (192). Its methyl derivative (193) on oxidation with Jones reagent at room temperature, followed by esterification, furnished the keto ester (194). Reduction of (194) with metal hydride produced an alcohol whose tosyl derivative on heating with sodium iodide and zinc dust furnished the ester (195). Its identity was confirmed by comparing its spectral data and melting point with an authentic specimen [77]. The transformation of the ester (195) to pisiferic acid (196) was achieved by treatment with aluminium bromide and ethanethiol. The identity of the resulting pisiferic acid (196) was confirmed by comparison of its spectroscopic properties (IR and NMR) with an authentic specimen [77]. 

Other fluorogenic reagents are available. o-Phthalaldehyde reacts rapidly with primary amino groups in the presence of 2-mercaptoethanol at alkaline pH and room temperature (Roth, 1971). The excitation and emission maxima are at 340 and 450 nm, respectively. As with fluorescamine and MDPF, o-phthalaldehyde is nonfluorescent. The reagent is water soluble and is dissolved and stored in the aqueous buffer (pH 10.0) used for the reaction. The fluorophors are less stable than those formed with fluorescamine (Mendez and Gavilanes, 1976). However, the use of ethanethiol, rather than 2-mercaptoethanol, for the fluorogenic reaction has been reported to yield fluorophors with a half-life of 2 days in aqueous solution at pH 9.1 (Simons and Johnson, 1977). 

The use of mercaplopropionic add or of ethanethiol is imperative if amino acids with primary amino groups are reacted first to form isoindoles, and if then a chloro-formate [184] or another fluoiigenic reagent which is capable of reacting with hydroxyl groups is used for the labelling of proline and hydroxyproline. 

Based on considerations of the mechanisms involved in the degradation of the isoindoles formed from OP A, a thiol and a primary amine, it was concluded that 1-alkylthio-2,3-dialkylisoindoles are more stable than the usual 1,2-dialkylisoindoles. For their formation, o-keto-benzaldehydes are suitable. The preparation of OAB (and of 2-benzoylbenzaldehyde) was reported, and it was demonstrated that the condensation product of 4-aminobutyrate with OAB/ethanethiol is much more stable than the corresponding derivative obtained with OPA/ethanethiol. In preliminary experiments, 50 fmol of 4-aminobutyric acid could be detected using HPLC as separation method [381]. Thus, it appears that OAB/ ethanethiol is a promising replacement for the OP. /R-SH reagent. 

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