Name: thiols: making and oxidizing sulfur compounds
Uploaded: 2023-04-30T18:28:41.000Z
Duration: 2 min 33 s
Channel: JoVE

Thiols are a class of sulfur-containing organic compounds with an &#8211;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.

preparation and reactions of thiols

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.
<img alt="Organic substitution reaction equation; bromide to thiol conversion using NaSH reagent." src="/files/ftp_upload/12112/12112Figure%201.svg" style="text-align: center; height: 28px;" data-altupdatedat="1761830439000" data-alt="Figure1" />
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.
<img alt="Alkyl halide reaction, NaSH nucleophilic substitution, product formation diagram." src="/files/ftp_upload/12112/12112Figure%202.svg" style="text-align: center; height: 140px;" data-altupdatedat="1761830439000" data-alt="Figure2" />
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.
<img alt="Nucleophilic substitution reaction diagram; bromine and thiourea to form thiol and urea with mechanism." src="/files/ftp_upload/12112/12112Figure%203.svg" style="text-align: center; height: 220px;" data-altupdatedat="1761830439000" data-alt="Figure3" />
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&#8211;S bond, which is approximately half the strength of other covalent bonds.

Thiols are prepared using the hydrosulfide anion as a nucleophile in a nucleophilic substitution reaction with alkyl halides. For instance, bromobutane ...

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Organic Chemistry

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Ethers, Epoxides, Sulfides

KEY TERMS AND CONCEPTS

thiols: making and oxidizing sulfur compounds

Thiols are sulfur compounds that can be made by nucleophilic substitution with alkyl halides. In one route, the hydrosulfide anion acts as the nucleophile. For example, bromobutane reacts with sodium hydrosulfide to form butanethiol.

That direct method has a limitation. If excess alkyl halide is present, the thiol product can react again and form a sulfide as a by-product. A better route uses thiourea as the nucleophile. This reaction first gives an alkyl isothiourea salt as an intermediate. The thiol is then released after hydrolysis with an aqueous base.

Thiols also oxidize easily. They can form disulfides, sulfinic acid, and sulfonic acid. The conversion to disulfides can happen even in air, so thiols must be stored in an inert atmosphere. Oxidation to disulfides can also use molecular bromine or iodine with a base.

Disulfides can be reduced back to thiols with reducing agents such as HCl in the presence of zinc. The change from thiol to disulfide is a redox reaction. This interconversion is linked to the S-S bond, which is about half as strong as other covalent bonds.

Thiols: Making and Oxidizing Sulfur Compounds

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Why Stored Ethers Can Form Explosive Peroxides

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Sulfur in Thiols and Sulfides

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Thiols are sulfur compounds that can be made by nucleophilic substitution with alkyl halides. In one route, the hydrosulfide anion acts as the nucleophile. For example, bromobutane reacts with sodium hydrosulfide to form butanethiol. That direct method has a limitation. If excess alkyl halide is present, the thiol product can react again and form a sulfide as a by-product. A better route uses thiourea as the nucleophile. This reaction first gives an alkyl isothiourea salt as an intermediate.

preparation and reactions of sulfides

Sulfide Synthesis and Oxidation

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key terms and concepts

Learn how thiols form from alkyl halides, why thiourea can help make them, and how thiols oxidize to disulfides and back again.

Thiols: Making and Oxidizing Sulfur Compounds | JoVE K12

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Thiols: Making and Oxidizing Sulfur Compounds

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