Thiols

Field of Study: Organic Chemistry

ABSTRACT

The characteristic properties and reactions of thiols are discussed. Thiols are theoretically unlimited in type. Their usefulness in organic synthesis reactions is limited, though they are significantly more reactive as nucleophiles than their oxygen analogs.

The Nature of Thiols

Thiols, also known as mercaptans, are organosulfur compounds characterized by the presence of the sulfhydryl functional group (−SH), the sulfur analog of the hydroxyl functional group (−OH). Accordingly, the series of thiol compounds exactly parallels that of the alcohols, which feature a hydroxyl group bonded to a carbon atom, although the substitution of sulfur for oxygen radically alters the nature of the particular compound. For example, an alcohol compound responsible for the very pleasing scent of roses may become an eye-burning compound with a hideous odor when the hydroxyl group is replaced by the sulfhydryl group. The slightly pungent smell of ethanol is well known to most people; its sulfur analog, ethanethiol (also known as thioethanol or ethyl mercaptan), is equally well known as the odorant added in minute amounts to natural gas and propane to render any leakage obvious. The sulfur analog of the water molecule, hydrogen sulfide, is notorious as the cause of the odor of rotten eggs, while water is essentially odorless.

The difference in odor is attributable to the position of sulfur in period 3 of the periodic table of elements, the chart representing the known elements by atomic number and electron distribution; oxygen is in period 2, though both are in group 16. While both oxygen and sulfur nominally have six electrons in their outermost, or valence, electron shell, oxygen has its electrons in regions known as the 2s and 2p orbitals, while sulfur has its six valence electrons in the 3s and 3p orbitals. Being in period 3, sulfur also has the 3d orbitals available for electronic interactions. Accordingly, sulfur is able to exhibit a much broader range of chemical behaviors than is oxygen. For the same reasons, the sulfur atoms in thiols interact in very different ways with the scent receptors in the nasal passages, replacing the normal alcohol odors with unpleasant counterparts. Thiols occur naturally in biochemical systems in which compounds derived metabolically from the amino acid cysteine are produced.

Nomenclature of Thiols

Thiols have long been commonly known as mercaptans. That name derives from the Latin term mercurium captans, or "seizing mercury," which refers to the ease with which thiols form mercury-based compounds. Thiols are systematically named according to the parent compound from which they are derived. The methanol (CH₃OH) analog is called methanethiol (thiomethanol or methyl mercaptan, CH₃SH). The next in the series is ethanethiol (thioethanol or ethyl mercaptan, CH₃CH₂SH), then propanethiol (CH₃CH₂CH₂SH), and so on. The naming of isomeric structures is analogous to the naming of the normal alcohols.

The prefix "sulfanyl-" (when another group takes priority) or the suffix "-thiol" (when the sulfhydryl group takes priority) is used to indicate the sulfhydryl functional group as a substituent in larger molecules. When naming a thiol compound, some confusion may arise if the prefix "thio-" is used in place of "sulfanyl-." The sulfhydryl group can only be a substituent, but the sulfur atom can be incorporated into the framework of the molecular structure in place of an oxygen atom. Generally, "thio-" is used to indicate the presence of a sulfur atom, and in the International Union of Pure and Applied Chemistry (IUPAC) systematic naming convention, it is used to designate a sulfur atom that forms part of the framework molecular structure. Because of this ambiguity, the compounds 2-butanethiol and 2-thiobutane can be easily confused, though they have very different structures and properties.

Reactions of Thiols

Thiols are reactive compounds that can produce a wide variety of compounds through both redox reactions (reduction-oxidation reactions) and non-redox reactions. Perhaps the most important reaction of thiols is the formation of disulfides, which can generally be formed under mild oxidation conditions. Disulfides play a significant role in the development of the three-dimensional structure of enzymes and proteins. The sulfhydryl substituents on different cysteine residues in the primary structure of the protein molecule can bond together by forming a disulfide linkage between the two sulfur atoms. This effectively locks other substituent groups and reactive functional groups into fixed spatial relationships relative to each other.

Oxidation of thiols under more vigorous conditions produces successive oxidation products by the addition of oxygen atoms to the sulfur atom as it is shifted into higher oxidation states. As part of a thiol, the sulfur atom is in the −2 oxidation state, analogous to an oxygen atom. Mild oxidation to form the disulfide brings the sulfur atom into the −1 oxidation state. Further oxidation first produces the corresponding sulfenic acid, characterized by the presence of an oxygen atom, and then adds a second oxygen atom to the sulfur atom to form the corresponding sulfinic acid derivative, RSO₂H (where R represents a generic alkane). Even further oxidation adds a third oxygen atom to produce the corresponding sulfonic acid compound, RSO₃H.

In the presence of elemental sulfur, thiols can form a variety of polysulfides in which a number of sulfur atoms are connected in a chain. This reaction plays a key role in the production of toughened rubber, which uses a process known as vulcanization. The presence of disulfides and similar cross-links between different rubber molecules in the polymer makes the rubber much stronger.

Production of Thiols

A great many sulfur-containing compounds are produced by the reaction of compounds such as alkyl halides with elemental sulfur. Combustion of sulfur produces sulfur dioxide, for example, while bacterial action and environmental conditions conducive to chemical reduction naturally produce hydrogen sulfide. Vast quantities of elemental sulfur are recovered from the desulfurization of fossil fuels, providing a large supply for the conversion of other compounds. In addition, a number of small thiol compounds such as methanethiol and ethanethiol occur naturally and can be recovered through oil and gas processing. Mineral sources of sulfur are also common, since sulfur readily forms inorganic compounds with metals. Iron pyrite, a common iron ore popularly known as fool’s gold, is composed partially of sulfur, and many other ores are also sulfides. The refining process typically releases the sulfur as sulfur dioxide, which is captured rather than released into the atmosphere.

Specific thiols are prepared by a nucleophilic displacement reaction with a sulfur compound. Sulfur compounds typically have greater reactivity as nucleophiles, or chemicals that tend to react with positively charged or electron-poor species, than their oxygen analogs, and the variety of compounds that sulfur can produce enables the use of a number of non-thiol sulfur compounds in nucleophilic reactions. One common method of producing thiols is to react an alkyl halide (an alkyl group bonded to a halogen) with sodium disulfide (Na₂S₂), followed by hydrolytic reduction of the sulfur-sulfur bond to form two sulfhydryl compounds.

PRINCIPAL TERMS

• functional group: a specific group of atoms with a characteristic structure and corresponding chemical behavior within a molecule.
• mercaptan: an organic compound characterized by the presence of a sulfhydryl functional group (−SH).
• odor: the sensation created when molecules of a volatile chemical compound vaporize and bind to olfactory receptors in the nose.
• organosulfur compound: an organic compound containing one or more carbon-sulfur bonds.
• redox reaction: a reaction in which electrons are transferred from one atom, ion, or molecule (oxidation) to another (reduction).

Bibliography

Berg, Jeremy M., John L. Tymoczko, and Lubert Stryer. Biochemistry. 7th ed. New York: Freeman, 2012. Print.

Hendrickson, James B., Donald J. Cram, and George S. Hammond. Organic Chemistry. 3rd ed. New York: McGraw, 1970. Print.

Mann, J., et al. Natural Products: Their Chemistry and Biological Significance. New York: Wiley, 1994. Print.

Morrison, Robert Thornton, and Robert Neilson Boyd. Organic Chemistry. 6th ed. Englewood Cliffs: Prentice, 1992. Print.

Reece, Jane B., et al. Campbell Biology: Concepts and Connections. 7th ed. San Francisco: Cummings, 2012. Print.

Robinson, Trevor. The Organic Constituents of Higher Plants. 6th ed. North Amherst: Cordus, 1991. Print.

Wuts, Peter G. M., and Theodora W. Greene. Greene’s Protective Groups in Organic Synthesis. 4th ed. Hoboken: Wiley, 2007. Print.