11.14:
Preparation and Reactions of Thiols
Thiols are a class of sulfur-containing organic compounds with an –SH functional group.
They are usually prepared from alkyl halides via an SN2 reaction with a sulfur nucleophile such as a hydrosulfide anion.
For example, 1-bromobutane reacts with sodium hydrosulfide to give 1-butanethiol.
Here, the hydrosulfide anion exerts a strong nucleophilic attack on the carbon bearing the halide group, thus displacing the halide ion in an SN2 manner and forming the thiol.
However, this synthesis method does not work well because the product thiol can undergo a second SN2 reaction with the alkyl halide, generating sulfide as a by-product.
This limitation can be overcome by using a thiourea as the nucleophile. Thiourea displaces the halide ion on the alkyl halide to form an alkyl isothiourea salt intermediate.
The salt then undergoes hydrolysis with an aqueous base and yields thiol as a product.
Thiols readily undergo oxidation to form disulfides, sulfinic, and sulfonic acids owing to the multiple oxidation states of the sulfur atom.
The oxidation of thiols to sulfonic acid via sulfinic acid requires strong oxidizing agents such as hydrogen peroxide or potassium permanganate.
Oxidation of thiols to disulfides can occur with mild oxidizing agents, such as molecular bromine or iodine in base.
For instance, bromine in aqueous sodium hydroxide oxidizes two equivalents of ethanethiol to diethyl disulfide.
The reaction proceeds with the deprotonation of the thiol by the hydroxide ion, generating a thiolate ion.
Subsequently, the thiolate ion acts as a strong nucleophile and attacks the molecular bromine in an SN2 reaction, displacing a bromide ion.
Finally, a second thiolate ion exerts a nucleophilic attack on the electrophilic sulfur in the second round of SN2 reaction to give a disulfide product.
The oxidation of thiols to disulfides is reversible, and the resulting disulfide can be easily reduced back to the thiols using reducing agents such as hydrochloric acid and zinc.
11.14:
Preparation and Reactions of Thiols
Thiols are prepared using the hydrosulfide anion as a nucleophile in a nucleophilic substitution reaction with alkyl halides. For instance, bromobutane reacts with sodium hydrosulfide to give butanethiol.
This reaction fails because the thiol product can undergo a second nucleophilic substitution reaction in the presence of an excess alkyl halide to generate a sulfide as a by-product.
This limitation can be overcome by using thiourea as the nucleophile. The reaction first produces an alkyl isothiourea salt as an intermediate, which forms thiol as a final product upon hydrolysis with an aqueous base.
Thiols can readily oxidize to disulfides, sulfinic acid, and sulfonic acid. The oxidation of thiols to disulfides can even occur in the presence of atmospheric air. Thus, the high susceptibility of thiols to undergo air oxidation necessitates the storage of thiols in an inert atmosphere. Oxidation of thiols to disulfides can also be accomplished using reagents like molecular bromine or iodine in the presence of a base. Disulfides, however, can be easily reduced back to thiols by treatment with reducing agents such as HCl in the presence of zinc. Notably, oxidation of thiols to disulfides is a redox reaction. The interconversion between thiols and disulfides is ascribed to the bond strength of the S–S bond, which is approximately half the strength of other covalent bonds.