a subclass of organic substances that contain sulfur and that are known for their varied occurrence and unusual properties. They are found in diverse locations, including in interstellar space, inside hot acidic volcanoes, and deep within the oceans. Organosulfur compounds occur in the bodies of all living creatures in the form of certain essential amino acids (amino acid) (such as cysteine, cystine, and methionine, which are components of proteins (protein)), of the tripeptide glutathione, and of enzymes (enzyme), coenzymes, vitamins (vitamin), and hormones (hormone).

Typical organisms contain 2 percent sulfur dry weight. Coenzyme A (CoA), biotin, thiamin chloride (vitamin B₁), α-lipoic acid, insulin, oxytocin, sulfated polysaccharides (polysaccharide), and the nitrogen-fixing nitrogenase enzymes are but a few examples of important natural sulfur-containing compounds. Certain simple organosulfur compounds, such as thiols (thiol), are repugnant to humans and most higher animals even at extraordinarily low concentrations; they are used as defensive secretions by a variety of animal species and figure in unpleasant odours associated with polluted air and water, particularly that resulting from the use of sulfur-rich fossil fuels (fossil fuel). However, related types of organosulfur compounds found in such foods as garlic, onion, chive, leek, broccoli, cabbage, radish, asparagus, mushroom, mustard, truffle, coffee, and pineapple are sources of olfactory and gustatory delight.

Classes of organosulfur compoundsDifferences between the chemistry of sulfur compounds and that of other common heteroatomic organic compounds (i.e., organic compounds (organic compound) containing elements other than carbon 【C】 and hydrogen 【H】, such as those of oxygen 【O】 and nitrogen 【N】), are primarily due to the fact that sulfur is a member of the third period of elements, employing 3s, 3p, and sometimes 3d orbitals, which are significantly larger than the more compact 2s and 2p orbitals of second-period elements such as oxygen and nitrogen. The larger orbital size means that the outer valence electrons (valence electron) are more loosely held, being further removed from the influence of the positive nuclear charge. Such loosely held electrons (electron) are said to be more polarizable, allowing them to engage in bonding interactions with electrophilic partners more easily and earlier during the course of a reaction than in the case of lighter elements, where bonding interactions require close approach of partner atoms. In addition, in protic hydrogen-bonding solvents such as water and alcohols (alcohol), sulfur is more weakly solvated than lighter heteroatoms. In these solvents, heavier heteroatoms such as sulfur show enhanced nucleophilicity compared with lighter heteroatoms because of their higher polarizability combined with decreased solvation (the solvation shell must be disrupted in reaching the transition state), despite the fact that stronger bonds are formed by the lighter heteroatoms. Thus, divalent sulfur compounds, such as thiols (containing an −SH group) and sulfides (containing an −S− group), readily bind to heavy metal ions such as silver (Ag), mercury (Hg), lead (Pb), and cadmium (Cd). Indeed, another name for thiol is mercaptan (from Latin mercurium captans, meaning “seizing mercury”), reflecting the use of thiols in treating mercury poisoning. Interactions between divalent sulfur and the metal ions iron (Fe), molybdenum (Mo), zinc (Zn), and copper (Cu) are crucial in metalloenzymes—for example, cytochrome C, in which the sulfur of methionine is coordinated to the iron in heme; the iron-sulfur proteins, in which cysteine sulfur is bound to iron; and molybdenum-containing enzymes, some of which involve dithiolate (two-sulfur) cofactors. Classes of organosulfur compounds

Thiols (thiol), or sulfur analogs of alcohols, are sometimes referred to as mercaptans. In naming these compounds, the suffix -thiol is appended to the name of the appropriate hydrocarbon; e.g., CH₃CH₂CH₂CH₂SH is named butanethiol. The prefix mercapto- is placed before the name of a compound if the −SH group is to be named as a substituent, as in mercaptoacetic acid, HSCH₂COOH. A third naming system uses the prefix thio- in front of the name of the corresponding oxygen compound, as, for example, thiophenol (C₆H₅SH), also called benzenethiol. A number of thiols are found in nature, such as cysteine and glutathione. In addition, 2-butenethiol is found in the defensive spray of the skunk, 2-propanethiol (allyl mercaptan) is found in the breath of people who have eaten garlic, and furfurylthiol contributes to the aroma of fresh coffee. Lower-molecular-weight thiols have strong, generally repugnant, skunky or rotten-egg-like odours, which can be detected by humans in air at very low concentrations—for example, 0.5 part per billion (0.5 × 10⁻⁹) in the case of ethanethiol or benzenethiol. For some thiols such as 4-mercapto-4-methylpentan-2-one (C₆H₁₂OS), which occurs in Sauvignon Blanc wines (wine), the odour varies from pleasant at trace levels to unpleasant at higher levels. Because of their strong odours, thiols, such as 2-methyl-2-propanethiol, are used as odourants and warning agents for natural gas leaks. 2-Mercaptobenzothiazole is a thiol that finds use as an accelerator in the vulcanization of rubber (see below Disulfides and polysulfides and their oxidized products (organosulfur compound)) and as a corrosion inhibitor, whereas 6-mercaptopurine has been employed in cancer therapy.

Sulfides, in which two organic groups are bonded to a sulfur atom (as in RSR′) are the sulfur analogs of ethers (ether) (ROR′). The organic groups, R and R′, may be both alkyl, both aryl, or one of each. If sulfur is simultaneously connected to different positions of the same carbon chain, a cyclic sulfide (a heterocycle (heterocyclic compound)) results. If no other functional group is present in the molecule, sulfides are named as such; e.g., ethyl methyl sulfide is CH₃SC₂H₅. In molecules with other functional groups of higher priority, the sulfide group is designated by thio- (as in thiodiacetic acid, HO₂CCH₂SCH₂CO₂H) or by methylthio- (as in methylthioacetic acid, CH₃SCH₂CO₂H). In saturated cyclic sulfides, the prefix thi- precedes the root associated with ring size; for example, thiirane, thietane, thiolane, and thiane for three-, four-, five-, and six-membered rings, respectively. Unsaturated cyclic sulfides, such as thiophene, which is very stable, are well known. Sulfides have low water solubility and are soluble in organic solvents. Similar to the thiols, lower-molecular-weight sulfides have strong, generally unpleasant odours. For example, allyl methyl sulfide is a major contributor to human “garlic breath.”

A unique property of sulfur is the ability to form chains of sulfur atoms with organic groups at either end—e.g., RS_nR′, where n can range from 2 to 20 or more. They are named by designating, in alphabetical order, the groups attached to sulfur, followed by the word sulfide, which is preceded by the prefix appropriate to the number of sulfur atoms, as in disulfide, trisulfide, tetrasulfide, and so forth or by use of dithio-, as in dithiodiacetic acid. Polysulfides are also named polysulfanes, with individual compounds being named trisulfane, tetrasulfane, and so on. A variety of disulfides occur in nature. The amino acid cystine, a disulfide, is an important component of many proteins; the sulfur-sulfur bond plays a key role in maintaining the molecules in shapes (so-called tertiary structures) essential for their biological activity. Interconversion of cysteine sulfhydryl (−SH) and cystine disulfide groups plays an important role in transport across cell membranes (cell), in the immune process, and in blood clotting. The process of hair waving involves cleavage of the cystine disulfide link of keratine into the cysteine moiety, providing flexibility for the hair to assume the new wave or curl desired, followed by oxidative treatment to fix the hair in its new shape.

The thiocarbonyl functional group (−C(=S)−), analogous to the carbonyl group, is found in thioaldehydes and thioketones, as well as in a variety of compounds with nitrogen or oxygen (or both) attached to the thiocarbonyl carbon (e.g., −XC(=S)Y−, where X and Y = N or O). These compounds are named by analogy with the corresponding oxygen compounds—e.g., thioacetone, CH₃C(=S)CH₃, or 2-propanethione. Many thiocarbonyl compounds tend to be deeply coloured and highly reactive, owing to the fact that the double bond (π bond) between carbon and sulfur uses orbitals of quite different sizes (2p on carbon and 3p on sulfur), which do not overlap well. The parent thiocarbonyl compound, thioformaldehyde (CH₂=S), is extremely reactive and cannot be isolated. However, it is very stable in the gas phase in low concentrations and is formed when various small organosulfur compounds are heated to extremely high temperatures. Thioformaldehyde has been detected in interstellar space by radio astronomers. carbon disulfide, S=C=S, is a common and important organic solvent and raw material containing a thiocarbonyl group; it is used in the manufacture of rayon. Isothiocyanates, R−N=C=S, have cumulated bonding similar to that in carbon disulfide. Allyl isothiocyanate, CH₂=CHCH₂N=C=S, gives horseradish its distinctive flavour; related compounds are found in mustard and radish. The dithiocarbamate thiuram, R₂NC(S)SSC(S)NR₂ (R = CH₃), is used as an antioxidant and accelerator in rubber vulcanization and is also employed as an insect repellent and fungicide. The related compound disulfiram (Antabuse; R = CH₂CH₃) is used in treating alcoholism. A thioamide, ethionamide, is an important drug used in the treatment of tuberculosis, and other thioamides are used as peptide analogs and in peptide synthesis.

Two major groups of organosulfur compounds that have no counterparts among organic oxygen compounds are the sulfoxides (sulfoxide) and sulfones (sulfone). If the bonding in these compounds is represented with doubly bonded structures—e.g., −S(=O)− for sulfoxide and −S(=O)₂− for sulfone—the sulfur atoms “see” 10 and 12 valence electrons (valence electron), respectively. This is more than the octet rule allows, but sulfur is not bound by the octet rule, because it can utilize 3d orbitals in its bonding, as would also be required in compounds such as sulfur hexafluoride (SF₆). While there is some theoretical support for the expansion of the sulfur valence shell to accommodate more than eight electrons, the use of 3d orbitals in bonding schemes has been criticized because 3d orbitals are much higher in energy than the sulfur 3s and 3p orbitals. An alternative bonding model invokes polar bonding such as −S⁺(−O⁻)− for sulfoxide and −S²⁺(−O⁻)₂₋ for sulfone. While it is clear that the polar resonance structures contribute to the overall bonding, it is probable that there is some contribution from sulfur 3d orbitals as well. It should be noted that the sulfoxide group also contains a lone pair of electrons on the sulfur atom, requiring that the sulfoxide group be nonplanar, similar to an amine, but quite different from the planar structure of a carbonyl group, −C(=O)−, to which a sulfoxide group is sometimes compared. An important consequence of the nonplanarity of the sulfoxide group is that sulfoxides of the type R(S=O)R′, where R and R′ are different, are chiral and can in fact be isolated in optically active form, with the sulfone group being tetrahedral. In contrast to amines but similar to phosphines (phosphine), tricoordinate sulfur (trigonal pyramidal sulfur compounds with three ligands (ligand) and a lone pair of electrons on sulfur—as found, for example, in sulfinyl chlorides, sulfite esters, sulfoxides, thiosulfinates, and sulfilimines) has a stable configuration, owing to longer bonds to sulfur (less crowding) and a greater amount of lone pair s-character (the percentage of s orbital in the total number of orbitals used in hybridization). Many optically active tricoordinate compounds occur in nature, and optically active sulfur compounds are widely used in the synthesis of other chiral compounds.

Among compounds isolated from natural sources, S-alkyl cysteine S-oxides (such as S-1- and S-2-propenylcysteine S-oxides)—the precursors to the flavourants of plants of the genus allium—were the first found to have optical activity at carbon as well as at another element (sulfur). A variety of other sulfoxides have since been isolated from natural sources, including sulforaphane (CH₃S(O)(CH₂)₄NCS) from broccoli, reported to inhibit tumour growth, and zwiebelanes from onion extracts. DMSO (dimethyl sulfoxide) is widely found at levels of three parts per million (ppm) or less and is a common component of natural waters, including seawater. Along with dimethyl sulfone, DMSO may be produced through algal metabolism. When found in rainwater, DMSO may result from oxidation of atmospheric dimethyl sulfide, (CH₃)₂S, which occurs as part of the natural transfer of sulfur of biological origin in the global sulfur cycle.

When a garlic clove is cut or crushed, S-2-propenylcysteine S-oxide (alliin) is transformed by the enzyme alliinase into the intermediate compound 2-propenesulfenic acid, CH₂=CHCH₂S−O−H, which immediately condenses to give the antibiotic substance allicin (allyl 2-propenethiosulfinate, formed at a level of roughly 0.4 percent of the weight of fresh cloves), a sulfinyl compound known as a thiosulfinate. Allicin is the principal flavourant of garlic and has antimicrobial, anticandidal (antiyeast), and antifungal properties; it also inhibits lipid synthesis in vitro. Allicin can be transformed into an unsaturated sulfoxide disulfide called ajoene, which has anticlotting (antithrombotic) properties. When an onion bulb is cut or crushed, an odourless substance in the bulb, S-1-propenylcysteine S-oxide, is similarly transformed into 1-propenesulfenic acid, CH₃CH=CH−S−O−H, which rearranges to (Z)-propanethial S-oxide, CH₃CH₂CH=S⁺O⁻, the so-called lacrimatory factor, or tear-inducing substance, of the onion.

In sulfoxides, R−S(=O)−R′, and sulfones, R−S(=O)₂−R′, groups R and R′ both contain a carbon atom bonded to sulfur. A variety of other organosulfur compounds are known of types R−S(=O)−X, Y−S(=O)−X, R−S(=O)₂−X, and Y−S(=O)₂−X, in which X and Y are elements other than carbon—e.g., oxygen, nitrogen, or a halogen (halogen element). Three types of organosulfur oxyacids (oxyacid) are possible: sulfenic acids, RSOH; sulfinic acids, RS(O)OH; and sulfonic acids (sulfonic acid), RSO₂OH. These compounds are named by attaching the name of the alkane, arene, and so on, to the name for the acid, as in trichloromethanesulfenic acid, ethanesulfinic acid, and p-toluenesulfonic acid. The sulfonic acids are very strong—comparable to hydrochloric acid and other mineral acids—and are the most common of the sulfur-containing acids. The colourless and odourless sulfonic acids and their salts are water soluble. Sulfonic acid salts, particularly those of linear alkylbenzenesulfonates, are very useful and widely used as detergents and synthetic surfactants (surface-active agent). Sulfonic acid groups can greatly enhance the water solubility of compounds, as seen with the sulfonic acid derivative of triphenyl phosphine (TPPTS), P(C₆H₄-m-SO₃Na)₃. Metal complexes of this compound are used as homogeneous catalysts for the syntheses of organic compounds in two-phase systems (e.g., in a mixture of water and an organic solvent) in industry and the laboratory. A few sulfonic acids occur naturally—for example, the essential nutrient taurine (2-aminoethanesulfonic acid; NH₂CH₂CH₂SO₃H), the echinosulfonic acids A–C, and the sulfobacins and other sulfonolipids. Sulfinic acids are weaker (having a pK_a of roughly 2.2) and less stable than sulfonic acids. Sulfenic acids and their salts are unstable compounds, are weaker (pK_a ≈ 5) than sulfinic acids, and are rarely isolated. Sulfenic acids containing one or three carbon atoms are key intermediates formed when onion, garlic, and related plants are cut or crushed (see above Sulfoxides and sulfones: Reactions (organosulfur compound)).

Eric Block, Reactions of Organosulfur Compounds (1978); and Shigeru Ōae, Organic Sulfur Chemistry: Structure and Mechanism (1991), are general overviews of the field. Specialized treatments, listed according to sulfur functional groups, include Saul Patai and Zvi Rappoport (eds.), The Chemistry of Sulphonic Acids, Esters, and Their Derivatives (1991), and The Chemistry of Sulphur-Containing Functional Groups (1993); Saul Patai, Zvi Rappoport, and Charles Stirling (eds.), The Chemistry of Sulphones and Sulphoxides (1988); and Saul Patai (ed.), The Chemistry of Sulphenic Acids and Their Derivatives (1990). The biochemistry of sulfur and the chemistry of sulfur compounds in garlic, onion, and related plants are described in the studies Ryan J. Huxtable and W. Mark Lafranconi, Biochemistry of Sulfur (1986); and Eric Block, “The Chemistry of Garlic and Onions,” Scientific American, 252(3):114–119 (March 1985), and “The Organosulfur Chemistry of the Genus Allium and Its Importance to the Organic Chemistry of Sulfur,” Angewandte Chemie (International Edition in English), 31(9):1135–78 (1992). Collections of essays on special topics include Chryssostomos Chatgilialoglu and Klaus-Dieter Asmus (eds.), Sulfur-Centered Reactive Intermediates in Chemistry and Biology (1991); L.I. Belen'kii (ed.), Chemistry of Organosulfur Compounds (1990); and Eric Block (ed.), Advances in Sulfur Chemistry, vol. 1 (1994).Eric Block