Thiols, substitutions, 2- ethanethiol

The first 1,6-addition reactions of thiolates to steroid dienones were examined well before the discovery of the antiestrogenic properties of 7o -substituted steroids. Ralls and coworkers129 and Djerassi and coworkers130 studied thiol additions to A3,5-steroids for example, the reaction of 3,5-cholestadien-7-one with ethanethiol was reported to proceed with high 1,6-regioselectivity and -stereoselectivity (equation 47)129. In a series of papers, Brueggemeier and coworkers131-137 described the synthesis and biochemical evaluation of numerous 7at-sul fur-substituted steroids which were prepared by Michael addition to steroid dienones. Thus, 4,6-androsta-3,17-dienone was treated with various... 

A characteristic of organic sulfur compounds, especially volatile (low molecular mass) thiols, is their disagreeable odors. For example, 3-methyl-1-butanethiol and 2-butene-1-thiol are ingredients of a skunk s perfume, and methanethiol or ethanethiol is usually added, in small amounts, to natural gas, which is odorless by itself, so that leaks can be readily detected. The chemical properties of thiols and sulfides differ from those of alcohols and ethers in that thiols are somewhat stronger acids than alcohols and the sulfur atoms of these compounds are considerably more nucleophilic than the oxygen of their analogs. They are excellent nucleophiles in substitution reactions. 

Thiol Substitution Reactions. Vital to the usefulness of 2-(trimethylsilyl)ethanethiol is that it behaves as a typical thiol. Base mediated reactions that proceed as expected include alkylation and nucleophilic ring openings. Moreover, addition-eliminations on unsaturated systems, Michael additions, and c -additions to triple bonds (eq 2) are all routine. To access 2-(trimethylsilyl)ethyl thioethers, a useful procedure is hydrolysis of 2-(trimethylsilyl)ethyl thiolacetate and alkylation of the thiolate in a single pot. ... 

Trimethylsilyl)ethanethiol will also participate in aromatic and heteroaromatic displacements of halogen atoms. A recent example shows that 2-(trimethylsilyl)ethanethiol is an alternative for the commonly employed potassium ethyl xanthate as a latent thiol in nitrogen displacement chemistry of aromatic di-azonium ions (eq 3). The low 3neld occurs in the substitution step, and is believed to be due to the sensitive doubly brominated substrate. ... 

Reactions at acid centers to create 5 -2-(trimethylsilyl) ethanethiolesters are also common. Carboxylic 5-thiolesters are formed in high yield by the DCC/DMAP mediated coupling of 2-(trimethylsilyl)ethanethiol and carboxylic acids or by thiol substitution on a carboxylic acid chloride. 5 -2-(Tiimethylsilyl) ethyl p-toluenethiolsulfonate is formed by treating 2-(trimethyl-silyl)ethanethiol with tosyl bromide (eq 4). The product is a useful electrophile for carbon nucleophiles, allowing the introduction of the 2-(trimethylsilyl)ethylthio unit by an alternative mechanism. Independent of the thiol, aryl and alkyl 2-trimethylsilylethyl thioethers may be prepared by the radical addition of the appropriate arene- or aikanethiol to vinyl trimethyl-silane in a reaction comparable to that of eq l7 ... 

In order for the 2-(trimethylsilyl)ethylthio unit to lose its protecting group upon treatment with the fluoride, the sulfur must be attached to an unsaturated carbon. Hence the fluoride mediated sulfur deprotection is feasible for 2-(trimethyl-silyl)ethylthio substituted (het)arenes, alkenes, alkynes, and acid derivatives such as carboxylic and selenothiophosphinic acid salts. In thiolate form, the substrates have value for the formation of self-assembled monolayers or as metal complexing agents. Simple addition of acid to the thiolate to give a stable thiol characterizes 2-(trimethylsilyl)ethanethiol as a simple M" (HS) equivalent that is only capable of a single substitution reaction. ... 

Spinach contains two enzymes catalysing the sulphuration of O-acetylserine. One enzyme possesses the additional ability to produce S-methyl-L-cysteine (4) or S-ethyl-L-cysteine from 0-acetyl-L-serine and methanethiol or ethanethiol, respectively. The second enzyme also catalyses these processes but, in addition, catalyses the formation of L-methionine, L-ethionine, and L-homocysteine from 0-acetyl-L-homoserine and methanethiol, ethanethiol, and sulphide, respectively. Enzymes from turnip and kidney beans are able to catalyse the formation of S-methylcysteine from O-acetylserine and methanethiol C-labelled serine, when fed to Allium cepa and A. sativum along with thiols, is converted into S-substituted cysteines. ... 

---