mercaptan

General chemical structure of the thiol functional group

In organic chemistry, a thiol is a compound that contains the functional group composed of a sulfur-hydrogen bond (-SH). Being the sulfur analogue of an alcohol group (-OH), this functional group is referred to either as a thiol group or a sulfhydryl group. More traditionally, thiols are often referred to as mercaptans.^[1][2]

Structure and bonding

Thiols and alcohols have similar molecular structure. The major difference being the size of the chalcogenide, C-S bond lengths being around 180 picometers in length. The C-S-H angles approach 90°. In the solid or molten liquids, the hydrogen-bonding between individual thiol groups is weak, the main cohesive force being van der Waals interactions between the highly polarizable divalent sulfur centers.

Due to the small electronegativity difference between sulfur and hydrogen, an S-H bond is less polar than the hydroxyl group. Thiols have a lower dipole moment relative to the corresponding alcohol.

Nomenclature

Several ways of naming the alkylthiols:

• The preferred method (used by the IUPAC) is to add the suffix -thiol to the name of the alkane. The method is nearly identical to naming an alcohol. Example: CH₃SH would be methanethiol.
• An older method, the word mercaptan replaces alcohol in the name of the equivalent alcohol compound. Example: CH₃SH would be methyl mercaptan, just as CH₃OH is called methyl alcohol.
• As a prefix, the terms sulfanyl or mercapto are used. Example: mercaptopurine.

Physical properties

Odor

Many thiols have strong odors resembling that of garlic. The odor of thiols is often strong and repulsive, particularly for those of low molecular weight. Natural gas distributors began adding thiols, originally ethanethiol, to natural gas, which is naturally odorless, after the deadly 1937 New London School explosion in New London, Texas. Most gas odorants utilized in the world contain mixtures of mercaptans and sulfides, with t-butyl mercaptan as the main odor constituent. Thiols are also responsible for a class of wine faults caused by an unintended reaction between sulfur and yeast and the "skunky" odor of beer which has been exposed to ultraviolet light. However, not all thiols have unpleasant odors. For example, grapefruit mercaptan, a monoterpenoid thiol, is responsible for the characteristic scent of grapefruit. This effect is present only at low concentrations. The pure mercaptan has an unpleasant odor.

Boiling points and solubility

Thiols show little association by hydrogen bonding, with both water molecules and among themselves. Hence, they have lower boiling points and are less soluble in water and other polar solvents than alcohols of similar molecular weight. Thiols and thioethers have similar solubility characteristics and boiling points.

Characterization

Volatile thiols are easily and almost unerringly detected by their distinctive odor. S-specific analyzers for gas chromatographs are useful. Spectroscopic indicators are the D₂O-exchangeable SH signal in the ¹H NMR spectrum (S has no useful "NMR isotopes"). The ν_SH band appears near 2400 cm⁻¹ in the IR spectrum.^[1]

Preparation

In industry, thiols are mainly prepared by the reaction of hydrogen sulfide with the related alcohol. This method is employed for the industrial synthesis of methanethiol and ethanethiol:

CH₃OH + H₂S → CH₃SH + H₂O

Such reactions are conducted in the presence of acidic catalysts. The other principal route to thiols involves the addition of hydrogen sulfide to alkenes. Such reactions are usually conducted in the presence of a metal catalyst.^[3]

Laboratory methods

Many methods are useful for the synthesis of thiols on the laboratory scale. The direct reaction of a halogenoalkane with sodium hydrosulfide is generally inefficient owing to the competing formation of thioethers:

CH₃CH₂Br + NaSH → CH₃CH₂SH + NaBr

CH₃CH₂Br + CH₃CH₂SH → (CH₃CH₂)₂S + HBr

Instead, alkyl halides are converted to thiols via a multistep, one-pot process. S-alkylation of thiourea gives an intermediate isothiouronium salt, which is hydrolyzed in a separate step:^[4]

CH₃CH₂Br + SC(NH₂)₂ → [CH₃CH₂SC(NH₂)₂]Br

[CH₃CH₂SC(NH₂)₂]Br + NaOH → (CH₃CH₂SH + OC(NH₂)₂ + NaBr

The thiourea route works well with primary halides, especially activated ones. Secondary and tertiary thiols are less easily prepared. Secondary thiols can be prepared from the ketone via the corresponding [[[dithioketal]]s.^[5]

Organolithium compounds and Grignard reagents react with sulfur to give the thiolates, which are readily hydrolyzed:^[6]

RLi + S → RSLi

RSLi + HCl → RSH + LiCl

Phenols can be converted to the thiophenols via rearrangement of their O-aryl dialkylthiocarbamates.^[7]

Reactions

Akin to the chemistry of alcohols, thiols form thioethers, thioacetals and thioesters, which are analogous to ethers, acetals, and esters. Thiols and alcohols are also very different in their reactivity, thiols being easily oxidized and thiolates being highly potent nucleophiles.

S-alkylation

Thiols, or more particularly their conjugate bases, are readily alkylated to give thioethers:

RSH + R'Br + base → RSR' + [Hbase]Br

Acidity

Relative to the alcohols, thiols are fairly acidic. Butylthiol has a pK_a's of 10.5 vs 15 for butanol. Thiophenol has a pK_a's of 6 vs 10 for phenol. Thus, thiolates are obtained from thiols by treatment with alkali hydroxides.

Synthesis of thiophenolate from thiophenol

Redox

Thiols, especially in the presence of base, are readily oxidized by reagents such as iodine to give an organic disulfide (R-S-S-R).

2 R-SH + Br₂ → R-S-S-R + 2 HBr

Oxidation by more powerful reagents such as sodium hypochlorite or hydrogen peroxide yields sulfonic acids (RSO₃H).

R-SH + 3H₂O₂ → RSO₃H + 3H₂O

Thiols participate in thiol-disulfide exchange:

RS-SR + 2 R'SH → 2 RSH + R'S-SR'

This reaction is especially important in nature.

Metal ion complexation

Thiolates, the conjugate bases derived from thiols, form strong complexes with many metal ions, especially those classified as soft. The term mercaptan is derived from the Latin mercurium captans, meaning 'laying hold of mercury,' because the –SH group reacts with mercury compounds. The stability of metal thiolates parallels their occurence of the corresponding sulfide mineral.

Biological importance

Cysteine and cystine

As the functional group of the amino acid cysteine, the thiol group plays an important role in biology. When the thiol groups of two cysteine residues (as in monomers or constituent units) are brought near each other in the course of protein folding, an oxidation reaction can generate a cystine unit with a disulfide bond (-S-S-). Disulfide bonds can contribute to a protein's tertiary structure if the cysteines are part of the same peptide chain, or contribute to the quaternary structure of multi-unit proteins by forming fairly strong covalent bonds between different peptide chains. A physical manifestation of cysteine-cystine equilibrium is provided by hair straightening technologies.

Sulfhydryl groups in the active site of an enzyme can form noncovalent bonds with the enzyme's substrate as well, contributing to catalytic activity. Active site cysteine residues are the functional unit in cysteine proteases. Cysteine residues may also react with heavy metal ions (Pb²⁺, Hg²⁺, Ag²) because of the high affinity between the soft sulfide and the soft metal (see hard and soft acids and bases). This can deform and inactivate the protein, and is one mechanism of heavy metal poisoning.

Cofactors

Many cofactors (non-protein based helper molecules), feature thiols. The biosynthesis and degradation of fatty acids and related long-chain hydrocarbons is conducted on a scaffold that anchors the growing chain through a thioester derived from the thiol Coenzyme A. The biosynthesis of methane, the principal hydrocarbon on earth, arises from the reaction mediated by coenzyme M, 2-mercaptoethyl sulfonic acid.

Examples of thiols

See also

• Doctor sweetening process
• Thiol-disulfide exchange

References

External links

• Applications, Properties, and Synthesis of w-Functionalized n-Alkanethiols and Disulfides — the Building Blocks of Self-Assembled Monolayers by D. Witt, R. Klajn, P. Barski, B.A. Grzybowski at Northwestern University.
• Mercaptan, by The Columbia Electronic Encyclopedia
• What is Mercaptan?, by Columbia Gas of Pennsylvania and Maryland
• What Is the Worst Smelling Chemical?, by About Chemistry