After completing this section, you should be able to
- Nomenclature and Reactivity
- write the IUPAC name of a thiol, given its Kekulé, condensed or shorthand structure.
- draw the structure of a thiol, given its IUPAC name.
- write an equation to represent the formation of a thiol by the reaction of hydrosulfide anion with an alkyl halide.
- write an equation to illustrate the preparation of a thiol by the reaction of thiourea with an alkyl halide.
- write an equation to show the interconversion between thiols and disulfides.
- mercapto group
The chemistry of sulfur-containing organic compounds is often omitted from introductory organic chemistry courses. However, we have included a short section on these compounds, not for the sake of increasing the amount of material to be digested, but because much of the chemistry of these substances can be predicted from a knowledge of their oxygen-containing analogues. A thiol is a compound which contains an SH functional group. The -SH group itself is called a mercapto group. A disulfide is a compound containing an -S-S- linkage. Table 18.1, below, provides a quick comparison of oxygen-containing and sulfur-containing organic compounds.
Thiols, which are also called mercaptans, are analogous to alcohols. They are named in a similar fashion as alcohols except the suffix -thiol is used in place of -ol. By itself the -SH group is called a mercapto group. The main physical characteristic of thiols is their pungent, disagreeable odor. According to IUPAC, thiols are named in a similar fashion as alcohols except the suffix -thiol is used instead of -ol. The root of the alkane name retains the final letter “e”.
Physical properties of thiols
Since they are incapable of hydrogen bonding, thiols have lower boiling points and are less soluble in water and other polar solvents than alcohols of similar molecular weight.
|Table 6.8.1. Physical properties of thiols and other compounds
Solubility in water
0.7 g/ 100mL (20ºC)
7.3g/100 mL (25ºC)
0.06 g/100 mL (20ºC)
The most recognizable property of thiols is their odors. The odors of thiols, particularly those of low molecular weight, are often strong and repulsive. The spray of skunks consists mainly of low-molecular-weight thiols and derivatives. These compounds are detectable by the human nose at concentrations of only 10 parts per billion. The negative. Since natural gas is odorless, natural gas distributors are required to add thiols, originally ethanethiol, to natural gas to detect leaking gas before a spark or match sets off an explosion.
Chemical structure of some of the compounds in skunk musk. Image by Karlhahn, Public domain, via Wikimedia Commons
Chemical properties of thiols
Disulfides bond formation
Oxidation of thiols and other sulfur compounds changes the oxidation state of sulfur rather than carbon. We see some representative sulfur oxidations in the following examples. In the first case, mild oxidation converts thiols to disufides. An equivalent oxidation of alcohols to peroxides is not normally observed. The reasons for this different behavior are not hard to identify. The S–S single bond is nearly twice as strong as the O–O bond in peroxides, and the O–H bond is more than 25 kcal/mole stronger than an S–H bond. Thus, thermodynamics favors disulfide formation over peroxide.
Disulfide (sulfur-sulfur) linkages between two cysteine residues are an integral component of the three-dimensional structure of many proteins. The interconversion between thiols and disulfide groups is a redox reaction: the thiol is the reduced state, and the disulfide is the oxidized state.
Notice that in the oxidized (disulfide) state, each sulfur atom has lost a bond to hydrogen and gained a bond to a sulfur - this is why the disulfide state is considered to be oxidized relative to the thiol state.
The redox agent that mediates the formation and degradation of disulfide bridges in most proteins is glutathione, a versatile coenzyme in biological systems:
In its oxidized form, glutathione exists as a dimer of two molecules linked by a disulfide group, and is abbreviated 'GSSG'.
A new disulfide in a protein forms via a 'disulfide exchange' reaction with GSSH, a process that can be described as a combination of two SN2-like attacks. The end result is that a new cysteine-cysteine disulfide forms at the expense of the disulfide in GSSG.
In its reduced (thiol) state, glutathione can reduce disulfides bridges in proteins through the reverse of the above reaction.
In the biochemistry lab, proteins are often maintained in their reduced (free thiol) state by incubation in buffer containing an excess concentration of b-mercaptoethanol (BME) or dithiothreitol (DTT). These reducing agents function in a manner similar to that of GSH, except that DTT, because it has two thiol groups, forms an intramolecular disulfide in its oxidized form.
Reaction with heavy metals
Thiols can also react with heavy metals (Pb2+, Hg2+, etc) forming insoluble compounds. This reaction is responsible for the biological toxicity of heavy metal salts, due to the inactivation of proteins containing -SH group as cysteine residues. Example:
2 R-SH + Pb(NO3)2 ---> R-S-Pb-S-R + 2 HNO3
Prof. Steven Farmer (Sonoma State University)
- Wikipedia contributors. (2021, May 14). Thiol. In Wikipedia, The Free Encyclopedia. Retrieved 23:23, May 20, 2021, from https://en.wikipedia.org/w/index.php?title=Thiol&oldid=1023095689