Sulphurous Acid, Reaction Thiols

Substituted thioindigoid dyes are usually obtained via the appropriate benzenethiol in a Heumann-type synthesis. The final cyclisation of the phenylthioglycolic acid derivative can often be achieved in concentrated sulphuric acid or by using chlorosulphonic acid. Several routes make use of the Herz reaction (Scheme 6.22), in which a substituted aniline is converted into the corresponding o-aminothiophenol by reaction with sulphur monochloride followed by hydrolysis of the intermediate dithiazolium salt [47]. After reaction between the thiol and chloroacetic acid, the amino group is converted into a nitrile group by a Sandmeyer reaction. Hydrolysis of the nitrile leads to the formation of the required thioindoxyl derivative. 

Compounds of sulphur(II) undergo the expected oxidations with DIB thiols to disulphides and sulphides to sulphoxides. Thiols form initially unstable iodine(III) intermediates which react with alkynes (Section 3.7). With some sulphides, DIB proved to be uniquely efficient, for example in the oxidation of thioxanthone [132]. The best conditions for high yields involved the use of acetic acid as solvent and catalytic amounts of sulphuric acid no heating was required and the reaction was completed in about 5 minutes [133]. 

Neighbouring-group participation by a 5a-acetoxy-group in the substitution of a 3fi-OR group is paralleled by Sa-acetylthio-groups. The crystalline 3a,5a-cyclic onium perchlorate (31) was generated by reaction of the 3j9-hydroxy-compound (29) with acetic anhydride-sulphuric acid [via the 3/1-acetyl sulphate (30)], followed by the addition of perchloric acid. Hydrolysis of the onium salt gave the 3a-acetoxy-5a-thiol (32). 

In the absence of added nucleophiles, nitrosation occurs virtually irreversibly by an acid-catalysed pathway, presumably by attack by HjNO or NO". The third order rate constant from the rate equation equivalent to (46) has a value of 840 dm moF s- at 31°C (c/. 456 and 6960 dm mol- s for cysteine and thiourea respectively at 25°C) which suggests that for this neutral substrate the reaction rate is somewhat less than that expected for an encounter-controlled process. There is a major difference between the nitrosation of alcohols and that of thiols in that, whilst the former reactions are reversible (with equilibrium constants around 1), the reactions of thiols are virtually irreversible. It is possible to effect denitrosation of thionitrites but only at high acidity and in the presence of a nitrous acid trap to ensure reversibility (Al-Kaabi et al., 1982). Direct comparisons are not possible, but it is likely that nitrosation at sulphur is much more favoured than reaction at oxygen (by comparison of the reactions of N-acetylpenicillamine and t-butyl alcohol). This is in line with the greater nucleophilicity expected of the sulphur atom in the thiol. For the reverse reaction of denitrosation [(52) and (53)], the acid catalysis observed suggests the intermediacy of the protonated forms... 

Ethane thiol reacts more readily than the methyl compound, but the main features of the reaction (e.g. the effect of reactant concentration) are similar. The products include some acid (assumed to be peracetic or acetic) as well as sulphur dioxide and acetaldehyde the large sulphur deficit is again ascribed to disulphide formation. In oxygen-rich mixtures all the sulphur is converted to sulphur dioxide. 

The combustion of dimethyl disulphide was studied at 240 °C. The reaction is autocatalytic, the principal products being sulphur dioxide, methanol and carbon monoxide with smaller amounts of formaldehyde, methane thiol and an acid [111]. 

Homocysteine lactonizes readily in acidic solutions, and a study of the aqueous radiation chemistry of this thiolactone was undertaken to see how bonding of the sulphur to a carbonyl carbon modifies its reactivity to the aquated electron . (The normal H atom abstraction from sulphur by OH cannot occur.) The dissodative electron capture reaction which gives H S in the case of free thiols can be formulated ... 

It also appears that thiol pyruvate can serve as sulphur donor for some biological transsulphurations. The thiol nucleotides which occur in small quantities in certain nucleic acids appear to derive their sulphur, at least in part, from thiol pyruvate rather than directly from cysteine. While these reactions have not been extensively studied as yet, ATP is required possibly to activate a group for intermediate thioether formation. Pyruvate elimination could then proceed through an enolate or an intermediate enzyme-bound Schiff base. 

Mercapturic acid production seems to have first call on the sulphur amino acid reserves and serious deficiency states can be induced in rats by hepatotoxic hydrocarbons. Diets high in cysteine and methionine will protect against the liver damage. Some mercapturic acid production may also result from reaction of protein thiol groups with the hydrocarbons, hydrolysis of the protein to the S-substituted cysteine and its N-acylation. However, the vast majority is formed via the glutathione adducts if the hydrocarbon dose is not so great as to deplete the glutathione reserves of the liver. 

Oxygen—alkyl bonds are easily cleaved by thiol salt. An intramolecular reaction of this type would result in migration of an alkyl group from oxygen to sulphur. Indeed, treatment of methyl 2-mercapto-benzoate (8) with alkali gives 73% of 2-methylthiobenzoic acid (9) . 

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