Chemistry of thiols

CHEMISTRY OF THIOLS

Key Notes

Preparation

Thiols can be prepared by the reaction of an alkyl halide with KOH and an excess of hydrogen sulfide. A hydrogen sulfide anion is formed which undergoes an S_N2 reaction with the alkyl halide. Hydrogen sulfide has to be in excess in order to limit further reaction to a thioether. Alternatively, the alkyl halide can be treated with thiourea to form an S-alkylisothiouronium salt which is then hydrolyzed with aqueous base to give the thiol. Disulfides can be reduced to thiols with zinc and acid.

Properties

Hydrogen bonding is weak, resulting in boiling points which are lower than comparable alcohols and similar to comparable thioethers.

Reactivity

Thiols (RSH) contain a large polarizable sulfur atom. The S–H bond is weak compared to alcohols, making thiols prone to oxidation. Thiolate ions are extremely good nucleophiles whilst being weak bases. Thiols are stronger acids than alcohols.

Reactions

Thiols are oxidized by bromine or iodine to give disulfides. Treatment of a thiol with a base results in the formation of a thiolate ion.

Preparation

Thiols can be prepared by the treatment of alkyl halides with an excess of KOH and hydrogen sulfide (Fig. 1a). The preparation is an S_N2 reaction involving the generation of a hydrogen sulfide anion (HS^-) as nucleophile. A problem with this reaction is the possibility of the product being ionized and reacting with a second molecule of alkyl halide to produce a thioether (RSR) as a byproduct. An excess of hydrogen sulfide is normally used to avoid this problem.

The problem of thioether formation can also be avoided by using an alternative procedure involving thiourea (Fig. 1b). The thiourea acts as the nucleophile in an S_N2 reaction to produce an S-alkylisothiouronium salt which is then hydrolyzed with aqueous base to give the thiol.

Thiols can also be formed by reducing disulfides with zinc in the presence of acid (Fig. 1c).

Properties

Thiols form extremely weak hydrogen bonds – much weaker than alcohols – and so thiols have boiling points which are similar to comparable thioethers and which are lower than comparable alcohols. For example, ethanethiol boils at 37°C whereas ethanol boils at 78°C.       

Low molecular weight thiols are notorious for having disagreeable aromas.

Reactivity

Thiols are the sulfur equivalent of alcohols (RSH). The sulfur atom is larger and more polarizable than oxygen which means that sulfur compounds as a whole are more powerful nucleophiles than the corresponding oxygen compounds. Thiolate ions  (e.g.  CH₃CH₂S^- )  are  stronger  nucleophiles  and  weaker  bases  than corresponding alkoxides (CH₃CH₂O^- ). Conversely, thiols are stronger acids than corresponding alcohols.          

The relative size difference between sulfur and oxygen also means that sulfur’s bonding orbitals are more diffuse than oxygen’s bonding orbitals. This results in a poorer bonding interaction between sulfur and hydrogen, than between oxygenand hydrogen. As a result, the S–H bond of thiols is weaker than the O–H bond of alcohols (80 kcal mol^-1 vs. 100 kcal mol ^-1). This in turn means that the S–H bond of thiols is more prone to oxidation than the O–H bond of alcohols.

Eactions

Thiols are easily oxidized by mild oxidizing agents such as bromine or iodine to give disulfides (Fig. 2).

Thiols react with base to form thiolate ions which can act as powerful nucleo- philes.