organosulfur compound

▪ chemical compound

Introduction

also spelled  organosulphur compound , also called  organic sulfur compound 

 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.

      Mustard gas, or bis(β-chloroethyl) sulfide, (ClCH₂CH₂)₂S, is a potent chemical warfare agent, whereas other sulfur compounds such as sulfanilamide (a sulfa drug), penicillin, and cephalosporin are valued antibiotics (antibiotic). Synthetic organosulfur compounds include polysulfones (polysulfone), inert polymers (polymer) used in astronauts' transparent face shields; polythiophenes, materials possessing the metal-like ability to conduct electricity; agricultural chemicals, insecticides (insecticide), and organic solvents, such as dimethyl sulfoxide, CH₃S(=O)CH₃, and carbon disulfide, CS₂; dyes (dye); lubricating oil constituents; food additives; and substances used to make rayon. In chemical research, organosulfur compounds are valued reagents widely used for synthesizing new compounds. A global sulfur cycle exists that interconverts natural organosulfur compounds with either inorganic sulfide or sulfate ions. Sulfide or sulfate ions can also be formed in nature from elemental sulfur.

The sulfur atom

       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

      It is useful to compare features of the compounds of sulfur (electron distribution 1s²2s²2p⁶3s²3p⁴) with those of oxygen, which lies directly above sulfur in the periodic table (electron distribution 1s²2s²2p⁴), and with those of the heavier member of the chalcogen family, selenium (electron distribution 1s²2s²2p⁶3s²3p⁶4s²3d¹⁰4p⁴), which lies directly below sulfur. There are structural similarities, for example, between alcohols (R−OH), thiols (R−SH), and selenols (R−SeH), between hydroperoxides (R−OOH), sulfenic acids (R−SOH), and selenenic acids (R−SeOH), between ethers (ether) (R−O−R), sulfides (R−S−R), and selenides (R−Se−R), between ketones (ketone) (R−C(=O)−R), thioketones (R−C(=S)−R), and selenoketones (R−C(=Se)−R), between peroxides (peroxide) (R−OO−R), disulfides (R−SS−R), and diselenides (R−SeSe−R), and between oxonium (R₃O⁺), sulfonium (R₃S⁺), and selenonium salts (R₃Se⁺), where R represents a general carbon group—e.g., the methyl group, CH₃, or the ethyl group, C₂H₅.

      There are significant differences in the properties of these groups of related compounds. For example, thiols are somewhat stronger acids (acid) than the corresponding alcohols because the S−H bond is weaker than the O−H bond and because the larger sulfur atom better disperses the resulting negative charge as compared with oxygen. For the same reasons, selenols are even stronger acids than thiols. At the same time, SH hydrogen bonding is much weaker than OH hydrogen bonding, with the consequence that thiols are more volatile and have lower boiling points (boiling point) than the corresponding alcohols—for example, 6 °C (43 °F) for methanethiol compared with 66 °C (151 °F) for methanol. Compared with alcohols and ethers, low-molecular-weight thiols and selenols as well as sulfides and selenides have highly unpleasant and obnoxious odours, although the perception of the odour as unpleasant or pleasant can sometimes vary with the concentration of the particular compound. Disulfides and diselenides are far more stable than peroxides, and sulfonium and selenonium salts are much less reactive than oxonium salts; at the same time, simple thiocarbonyl (C=S) and selenocarbonyl (C=Se) compounds are much more reactive than simple carbonyl (C=O) compounds. In the case of the homologues of carbonyl compounds, the difference in reactivity is attributed to the poorer match in the size of the orbitals of the carbon and sulfur double bond (carbon 2p and sulfur 3p) or the carbon and selenium double bond (carbon 2p and selenium 4p) compared with the similar 2p orbitals used for the double bond between carbon and oxygen.

      Both sulfur and selenium also have the ability to form compounds in which atoms of these elements have higher valences; these compounds have no counterpart in oxygen chemistry. In the case of sulfur, some examples are sulfoxides (sulfoxide) (R₂S=O, typically written R₂SO), sulfones (sulfone) (R₂S(=O)₂, typically written R₂SO₂), sulfonic acids (sulfonic acid) (RSO₃H), and oxosulfonium salts (R₃S⁺=O). Analogs of the above sulfur compounds also exist for selenium. These higher-valence compounds of sulfur (or selenium) are stabilized through bonding involving 3d (or 4d) orbitals, not available to oxygen, as well as other factors associated with the larger size of sulfur and selenium as compared with oxygen. The longer, weaker bonds and higher degree of polarizability of selenium compared with sulfur lead to differences in properties and reactions of compounds of these two elements.

Analysis of organosulfur compounds

      In addition to routine methods of analysis that can be used with all classes of organic compounds (see analysis), certain procedures reflect specific characteristics of sulfur. In a mass spectrometer, organosulfur compounds frequently produce strong molecular ions (ion) in which the charge is located predominantly on sulfur. The presence of sulfur is indicated by the occurrence of sulfur-34 (³⁴S) isotope peaks, 4.4 percent of the abundance of ³²S. Organically bound sulfur in the form of the natural isotope ³³S can be directly examined by nuclear magnetic resonance (NMR) spectroscopy, although the low natural abundance (0.76 percent) and small magnetic and nuclear quadrupole moments make analysis more difficult than for protons (proton) (¹H) or carbon-13 (¹³C). Levels of organosulfur compounds in crude petroleum as low as 10 parts per billion or less may have a detrimental effect on metallic catalysis or may cause unpleasant odours. These very low sulfur levels are detected using gas chromatographs (gas chromatography) with sulfur chemiluminescence or atomic-emission detectors with high sensitivity to detect sulfur compounds in the presence of other compounds.

Organic compounds of bivalent sulfur

Thiols (thiol)

 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.

      When long-chain alkanethiols are exposed to metallic gold, they bind to the gold surfaces, functioning as a type of “molecular alligator clip” and forming self-assembled monolayers (SAMs), of interest in the field of nanotechnology. SAMs can be formed on planar (two-dimensional) as well as particle (three-dimensional) surfaces. The ordering of long-chain alkanethiols is driven by the substantial gold-sulfur binding energy of approximately 160 kilojoules per mole (kJ/mol), as well as by the lateral van der Waals forces between the tethered alkyl chains (10–20 kJ/mol). Dipole interactions between polar end groups on alkyl chains can become important for functionalized thiols. Nanoparticles consisting of alkanethiolate monolayer-protected clusters (MPCs) in the form of ultrafine suspensions (colloids (colloid)) of gold particles are 3-D analogs of the 2-D SAMs. The 2-D and 3-D SAMs can be prepared from ultraclean gold surfaces upon interaction with thiols (unprotected or S-acetyl or S-(N-ethyl)carbamoyl-protected) and disulfides, which are adsorbed about 40 percent more slowly than thiols. These sulfur compounds may have a wide range of alkane (paraffin hydrocarbon) chain lengths (C3–C24) and diverse end-of-chain substituents, such as water-soluble groups (e.g., amino acids and polyethylene glycol), aromatic (aromatic compound) groups, silicon functionalities, fullerenes (fullerene), porphyrins (porphyrin), ferrocene, crown ethers, and tetrathiofulvalenes, among others. There are many potential applications of SAMs and MPCs in fields ranging from materials science (e.g., nanoscale electronics, thin films, and electro-optics) to chemistry (e.g., catalysis, nanoreactors, and chemical sensors) to biology (e.g., membrane mimicry, biosensors, and drug delivery).

      The interconversion of natural thiol pairs and disulfide groups constitutes a key oxidation-reduction reaction (oxidation–reduction reaction) (or redox reaction) used in biochemistry; the redox potential, or tendency to attract electrons and thus become reduced, of the thiol-disulfide system is such that most disulfides are reducible by the biological reducing agent nicotinamide adenine dinucleotide (NADH), which has an optimum redox potential for this system. (See chemical reaction: Oxidation-reduction reactions (chemical reaction) for a discussion of redox reactions.) Proteins (protein) containing the mercapto (thiol) group from the component amino acid cysteine play key roles in many enzymatic processes. The cytoplasmic component glutathione (GSH), which also contains the mercapto group, is important in cellular oxidation and reduction, in nitric oxide (NO) transfer processes, and in protecting cells (cell) against damage from radicals (radical). GSH reacts with NO to form the S-nitrosoglutathione (GSNO), which displays powerful antiplatelet aggregation properties and is therefore useful in coronary angioplasty operations. S-Nitrosothiols such as GSNO are found in vivo and play an important role as NO donors and in the transport and storage of NO, a small molecule that controls a remarkable range of physiological functions. In vivo release of NO from nitrosothiols may be catalyzed by copper ions. The selenium-containing enzyme glutathione peroxidase, which plays a crucial role in prevention of damage due to radicals derived from lipid hydroperoxides, is believed to function via formation of an intermediate with a sulfur-selenium bond that is significantly more reactive toward a thiol nucleophile than a sulfur-sulfur (disulfide) bond. Thus, the enzyme, which contains a selenocysteine (or selenol; RSeH) at its active site, is oxidized to a selenenic acid (RSeOH) in the course of reducing the hydroperoxide R′OOH. The selenenic acid is then converted by GSH to a selenyl sulfide (ESeSG), which reacts further with GSH to regenerate the enzyme RSeH. This reaction also gives glutathione disulfide (GSSG), which is reduced back to GSH, thereby continuing the cycle.

      The sulfur in cysteine—and sulfur in other divalent sulfur compounds found in plants (plant) and animals (animal)—is ultimately derived from sulfate (−SO₄²⁻) in the soil, which is reduced in the cell. In plants and bacteria that utilize sulfate as a source of sulfur, the first step in the reduction process is the formation of adenosine phosphosulfate (APS), since direct reduction of sulfate itself is extremely difficult. The −OSO₂O¹⁻ group of APS is reduced to a sulfite ion (SO₃²⁻) or a protein-bound sulfite, which is then further reduced to hydrogen sulfide (H₂S), a direct precursor of cysteine and other natural organosulfur compounds.

      In animals, sulfur-containing amino acids (amino acid) and other compounds are excreted as inorganic sulfate.

      Thiols and thiol-derived compounds have several important roles in biology. As thiolate, RS⁻, they can function as bases, as ligands (ligand) (e.g., in the binding of metals, as in hemoglobin), and as agents for the transfer of acetyl groups (e.g., in acetyl CoA) in lipid biosynthesis. In acetyl CoA, sulfur exists in the form of a derivative of a thiol, a thioester, CH₃C(O)−SCoA; the (O) represents a (=O). The C(O)−S bond in this coenzyme is weaker than the corresponding C(O)−O bond in an ester. Furthermore, the thiolate anion (in this case, ⁻SCoA) is a better leaving group than the analogous alkoxide anion (⁻OR) because in the larger sulfur atom the negative charge is spread over a larger volume of space. In general, the superior attacking-group (nucleophile) as well as leaving-group qualities of thiolate make it an excellent biocatalyst.

      Low-molecular-weight thiols such as methanethiol (CH₃SH) are found in crude petroleum. As such, they pose serious problems, associated not only with objectionable odours but also with their corrosive effect on equipment and their ability to poison (render nonfunctional) catalysts for air-pollution control or for other chemical processes. If they can be efficiently recovered from crude petroleum, these low-molecular-weight thiols can be used in the manufacture of agricultural chemicals and other chemical commodities.

Preparation

      Thiols were first prepared in the laboratory in 1834. They can be synthesized by several procedures, including reaction of an alkyl halide (RX, where X is a halogen) with the sulfur reagent thiourea, (NH₂)₂C=S, or with thiocyanate salts; reaction of organomagnesium (RMgX) or organolithium (RLiX) compounds with elemental sulfur; or addition of hydrogen sulfide or thioacetic acid (CH₃C(O)SH) to alkenes (olefins (olefin)). 1,2-Dithiols can be prepared by addition of thiocyanogen, (SCN)₂, to olefins, followed by reduction. Aromatic thiols are frequently made from the reduction of arenesulfonyl chlorides (see below Other sulfinyl and sulfonyl compounds (organosulfur compound)).

Reactions

      Similar to alcohols (alcohol), thiols react with alkalies and other bases to form salts. In the presence of heavy metal salts (such as those of mercury, lead, silver, or copper), thiols form mercaptides (metal thiolates), which are insoluble in water but are frequently soluble in organic solvents. The formation of a black precipitate of lead mercaptide (or lead sulfide, PbS) upon the addition of lead salts to liquid petroleum products is the basis for the so-called doctor test for the detection of thiols.

      Thiols form sulfides and thioesters in reactions analogous to those of alcohols. They react readily with aldehydes (aldehyde) and ketones (ketone) to form thioacetals and thioketals, respectively. Thioacetals and thioketals are more stable than the corresponding oxygen compounds and so are especially useful as protecting groups (temporarily suppressing the reactivity of the carbonyl group) as well as reagents in organic synthesis. Thiols are efficient radical scavengers (a radical X^∙ abstracts a thiol hydrogen atom, giving a thiyl radical RS^∙ and XH). The ability of thiols to serve as hydrogen atom donors makes them useful as radioprotective agents, especially since radiation can produce radicals; they are also useful as hydrogen atom donors in various other processes and synthetic reactions. Thiols add across to the multiple bond of unsaturated compounds, either under catalysis by light or acid or, in the case of unsaturated compounds activated by adjacent carbonyl groups, under catalysis by base. In all cases the products are sulfides.

      Oxidation of thiols initially affords disulfides, which can also be formed by the combination of thiyl radicals. Sulfenic acids, R−SO−H, can be isolated as the first-formed oxidation product from sterically hindered thiols; these react further with thiols to form disulfides. There are a number of practical applications associated with the oxidation of thiols. Spills of obnoxious-smelling low-molecular-weight thiols are neutralized by oxidizing the thiols with sodium or calcium hypochlorite ( bleach) solutions. Milder oxidants (e.g., 3 percent hydrogen peroxide, made alkaline with sodium bicarbonate, or 2 percent aqueous potassium iodate) have been used to deodorize pets that have encountered skunks. In petroleum refining, the process of “sweetening” involves oxidation of evil-smelling thiols in crude oil to more innocuous disulfides. Reaction of thiols (or disulfides) with chlorine yields sulfenyl chlorides (RSCl), which are useful reagents in synthesis reactions.

Sulfides

 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 variety of biologically important sulfides occur in nature. Acyclic examples include the essential amino acid methionine, which is involved in biological methyl transfer, and 2-phenylethyl methyl sulfide, C₆H₅CH₂CH₂SCH₃, 5-methylthio-2,3-pentanedione, CH₃C(O)C(O)CH₂CH₂SCH₃, and di(3-methylbutyl)sulfide, ((CH₃)₂CHCH₂CH₂)₂S, which are trail-marking secretions from the red fox, the striped hyena, and the polecat, respectively. Heterocyclic structures include, among others, the four-membered ring 2,2-dimethylthietane, from the mink; the five-membered rings from penicillin, biotin (involved in the biosynthesis of fatty acids and in carbon dioxide fixation), and thiamin (a coenzyme, as is biotin) and the terthienyl pesticide from marigold; and the six-membered ring 5-thio-d-mannose, a novel sugar having a sulfur atom in the ring instead of oxygen, isolated from an orange marine sponge, Clathria pyramida. In nature, sulfides can serve as ligands, as in cytochrome C, in which the sulfur of methionine is coordinated to the heme iron.

      Most crude oils contain organosulfur compounds such as thiols, sulfides, and polysulfides, presumably formed from the reaction of hydrocarbons (hydrocarbon) with elemental sulfur, in turn generated from microbial action on sulfate in rocks. As the oil ages, the thiols and sulfides are slowly converted into more stable compounds such as benzothiophene. Molybdenum-containing hydrodesulfurization catalysts are used in the removal of the undesirable sulfur compounds from petroleum, giving hydrocarbons and hydrogen sulfide as the final products. There is considerable interest in the use of monomeric and polymeric compounds made from heterocyclic sulfur compounds—such as thiophene, tetrathiafulvalene (TTF), and the bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) cation—as organic metals and superconductors (e.g., for use as switching elements and light-emitting diodes). Indeed, the 2000 Nobel Prize for Chemistry, awarded to American chemists Alan J. Heeger (Heeger, Alan J.) and Alan G. MacDiarmid (MacDiarmid, Alan G.) and Japanese chemist Shirakawa Hideki, recognized the discovery of plastics that conduct electricity. Poly(phenylene sulfide) (PPS), a polymeric material derived from diphenyl sulfide, which has been known for more than 100 years, is used in electrical, electronic, and mechanical applications. Polythiophene conductors are of great interest for use in molecular electronic devices. Research has led to the preparation of macrocyclic α-conjugated oligothiophenes; for example, α-cyclo[12]thiophene, which has a perfect hexagonal “honeycomb” solid state structure.

      Many fungicides (fungicide) and herbicides (herbicide) incorporate organically bound sulfide sulfur.

Preparation

      A number of examples of syntheses of sulfides were described above as reactions of thiols. A unique synthesis of sulfides is illustrated by the reaction of ethylene with sulfur dichloride to form bis(β-chloroethyl) sulfide, known as sulfur mustard, or mustard gas, a blister-forming (vesicant) chemical warfare agent. This reaction has been applied to the synthesis of cyclic and bicyclic dichlorosulfides as well.

Reactions

      Like thiols, sulfides can form metal complexes, particularly in the case of cyclic polysulfides with crown etherlike structures, such as the hexathia-18-crown-6. Oxidation of sulfides yields sulfoxides (sulfoxide) or, under more vigorous conditions, sulfones (sulfone); reaction with alkyl halides gives sulfonium salts; and reaction with halogen (halogen element) compounds produces halosulfonium salts. Halosulfonium ions and related species formed from sulfoxides are key intermediates in the synthesis of polysaccharides (polysaccharide) from 1-phenylthioglycosides, facilitating replacement of the phenylthio, PhS (or phenylsulfinyl, PhS(O)), group by a nucleophile from a second saccharide molecule, joining the saccharides in a process termed glycosylation. One-electron oxidation of sulfides gives radical cations (cation), of importance in conducting materials; these radical cations can dimerize to give dithia dications, R₂S⁺−S⁺R₂, which can also be formed in reactions involving bis-sulfides, molecules with two spatially separated sulfide groups. With fluorinated reagents, diphenyl sulfide, (C₆H₅)₂S, can be converted into the hexavalent sulfur compound tetrafluorodiphenylsulfur, (C₆H₅)₂SF₄. If one of the carbon groups, R, in a sulfide RSR′ is olefinic, aromatic, or acetylenic and the other group, R′, is a saturated carbon (e.g., methyl or ethyl), the bond to the saturated carbon can be cleaved with sodium or lithium metal in liquid ammonia—for example, RSR′ + Na/NΗ₃→ RSNa + R′−H. Using Raney nickel (Ra-Ni; a type of active nickel), carbon-sulfur bonds in sulfides can be replaced by hydrogen—for example, RSR′ + Ra-Ni → R−H + R′−H. These reduction reactions are useful in synthesis or in determining the structure of an unknown organosulfur compound. Raney nickel desulfurization was a key step in first establishing the structure of penicillin. The high polarizability of sulfur stabilizes a negative charge on the carbon adjacent to divalent sulfur, as in RSCH₂₋(usually as α-lithium sulfides, RSCH₂Li), which proves useful in organic synthesis through nucleophilic reaction with alkylating agents and carbonyl compounds.

      Of particular value in this type of reaction is the 2-lithio derivative of the cyclic bis-sulfide 1,3-dithiane, widely used in the synthesis of ketones and aldehydes (the Corey-Seebach reaction, shown below). 1,3-Dithiane and other thioacetals can also be converted to olefins by the Takeda olefination reaction.

      The cyclic sulfide thiophene undergoes reactions similar to those of benzene, although somewhat more easily.

Disulfides and polysulfides (polysulfide) and their oxidized products

 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 coenzyme lipoic acid, a cyclic disulfide, is a growth factor—ubiquitously distributed in plants, animals, and microorganisms—and is used in photosynthesis and lipid and carbohydrate metabolism in plants and animals. It is involved in biological oxidations, where it oscillates between the oxidized cyclic form and the reduced acyclic dithiol form. Lipoic acid suffers from ring strain caused by repulsion of lone-pair electrons (electron) on adjacent sulfurs in the near planar ring, making it a better oxidizing agent than a six-membered cyclic disulfide, such as 1,2-dithiane, would be. At the same time, in the reduced dithiol form, the thiol groups are in sufficient proximity to facilitate reoxidation. Asparagusic acid (4-carboxy-1,2-dithiolane), found in Asparagus roots, is considered to be a major factor in the natural resistance (i.e., survival in the soil) of this plant; 4-methylthio-1,2-dithiolane is a photosynthesis inhibitor from the stonewort. The characteristic flavour of the shiitake mushroom is due to the presence of the acyclic disulfide-sulfone CH₃SO₂CH₂SCH₂SCH₂SSCH₃ together with several cyclic polysulfides, including lenthionine; thiarubrine is a novel biologically active acetylenic cyclic disulfide found in plants related to marigolds. Dimethyl trisulfide (CH₃SSSCH₃), detectable at levels as low as 0.1 part per billion, is a key contributor to the flavour of beer, wine, whiskey, and various food products. It is also one of a number of organosulfur compounds present in coal.

      When garlic cloves are distilled with water, garlic oil is isolated and is found to contain a mixture of compounds including diallyl disulfide, trisulfide, and polysulfides—e.g., (CH₂=CHCH₂)₂S_n, where n = 2–8. None of these compounds occur naturally in garlic; rather, they are formed from the action of water and heat on allicin, a biologically active thiosulfinate, or disulfide S-oxide, CH₂=CHCH₂S(=O)SCH₂CH=CH₂, in turn formed enzymatically from sulfoxide precursors in the intact garlic bulb (see below Sulfoxides and sulfones: Reactions (organosulfur compound)). Sulfurized olefins (olefin) are used in extreme pressure lubrication, while a highly resistant sulfur cement and concrete can be prepared from cyclopentadiene Diels-Alder oligomers linked by polysulfide chains. Polysulfides with four or more sulfur atoms have a variety of useful properties and have been employed as industrial lubricants, sealants in the glass-insulation industry, and binders in solid propellants for rockets (rocket) (e.g., Thiokol A, (CH₂CH₂S₄)_n). In the vulcanization of rubber, polyolefins (polyolefin) are converted to an elastomeric (elastomer) substance with desirable mechanical properties by cross-linking the chains with two or more sulfur atoms.

Preparation

      Disulfides are generally prepared by oxidation of thiols, whereas polysulfides can be made by reaction of an excess of thiols with sulfur chlorides, S_nCl₂. Some cyclic disulfides and polysulfides can be prepared by reaction of elemental sulfur with unsaturated compounds; for example, the reaction of acetylene with sulfur yields a 1,2-dithiete, a four-membered ring compound with two sulfur atoms that exhibits aromatic stability similar to thiophenes. 1,2-Dithiins, six-membered ring disulfides found in thiarubrines, can be prepared by reaction of titanacyclopentadienes (formed in one step from acetylenes) with sulfur monochloride (S₂Cl₂) or thiocyanogen (SCN)₂ and samarium iodide (SmI₂).

Reactions

      Disulfides can be reduced to thiols both in the laboratory as well as in vivo (biologically). Biological reduction of thiols and the reverse process, oxidation of thiols to disulfides, are essential biochemical processes. Disulfides can be further oxidized to the S-oxides (thiosulfinates, RS(O)SR), the S,S-dioxides (thiosulfonates, RSO₂SR), S,S′-disulfoxides (or α-disulfoxides, RS(O)S(O)R), and, ultimately, with cleavage of the sulfur-sulfur bond, to sulfonic acids, RSO₃H. Polysulfides also undergo certain reactions of this kind. A number of the disulfide S-oxides are flavourants, formed on cutting plants of the allium genus (onion and garlic) as well as cabbage, cauliflower, brussels sprouts, and so forth. With chlorine, disulfides give chlorinated cleavage products such as sulfenyl chlorides, RSCl, or, in the presence of water, RSO₂Cl. The S−S bond can also be cleaved with alkyllithiums and other organometallic compounds to form sulfides.

      Calichimicin (esperamicin) is a highly potent antitumour agent produced by bacteria of the Actinomycetales (actinomycete) order and containing a pendant methyl trisulfide component (CH₃SSS−). Acting much like a molecular “mouse trap,” cleavage of the sulfur-sulfur bond is thought to trigger a chain of events culminating in formation of a phenylene diradical, which removes hydrogen atoms from deoxyribonucleic acid ( DNA). The initial sulfur-sulfur bond cleavage is favoured because this bond is significantly weaker in trisulfides than it is in disulfides.

Thiocarbonyl compounds

 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.

Preparation

      Thioketones are usually prepared through reaction of ketones with phosphorus sulfur reagents, such as Lawesson reagent, Ar₂P₂S₄. Xanthates (xanthate) (from the Greek xanthos, meaning “yellow,” named for the colour of their copper salts), thiocarbonyl derivatives of carbonates (carbonate), ROC(=S)OR, are prepared from alcohols (alcohol) and carbon disulfide. This reaction is used to produce a soluble form of cellulose that can be extruded into an acidic solution, which disrupts the xanthate group, regenerating the cellulose in the form of fibres (rayon) or films ( cellophane). thiourea, the diamide of thiocarbonic acid, is manufactured by heating ammonium thiocyanate, NH₄SCN + heat → H₂NC(=S)NH₂. Thiourea can be used in syntheses of thiols that avoid formation of sulfide by-products. Divalent sulfur-containing derivatives of phosphoric acid, H₃PO₄, with P=S bonds have been used in pesticides (e.g., Malathion and parathion), lubricant additives, and ore-flotation agents. They are generally synthesized from tetraphosphorus decasulfide (P₄S₁₀) or thiophosphoryl chloride (PSCl₃).

Reactions

      Thioketones can be oxidized to give the corresponding thioketone S-oxides, also known as sulfines, such as thioacetone S-oxide, CH₃C(=S=O)CH₃. Thioformaldehyde readily trimerizes to 1,3,5-trithiane or polymerizes to poly(thioformaldehyde). The presence of a π bond in thioketones makes these compounds reactive in Diels-Alder reactions and related cycloaddition reactions. Similar to carbonyl compounds, thioketones can also undergo enolization (thioenolization), giving isomeric enethiols, which in some cases can be isolated. Thioenolization of thioacetone would give 2-propenethiol, CH₃C(SH)=CH₂. Thioketones reversibly add hydrogen sulfide to yield gem-dithiols (i.e., having both −SH groups on the same carbon)—for example, propane-2,2-dithiol, CH₃C(SH)₂CH₃, in the case of thioacetone. It is probably the gem-dithiols rather than the thioketones themselves that are responsible for the extremely offensive smell associated with low-molecular-weight thioketones. Thionocarbonates of type ROC(S)OR′, derived from an alcohol ROH, are widely used in organic synthesis in a procedure that ultimately affords the deoxygenated product R−H (Barton-McCombie deoxygenation).

Organic compounds of polyvalent sulfur: sulfoxides (sulfoxide) and sulfones (sulfone)

 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.

      Sulfoxides are named by simply designating, in alphabetical order, the two organic groups attached to the −S(=O)− group, followed by the word sulfoxide (e.g., ethyl methyl sulfoxide, CH₃S(O)C₂H₅), or by forming a prefix from the name of the simpler of the groups using the particle -sulfinyl- (e.g., 4-(methylsulfinyl)benzoic acid). The nomenclature of sulfones is similar to that of sulfoxides; the particle -sulfonyl- is used in complicated cases. Most sulfoxides are colourless liquids or solids with low melting points (melting point). The low-molecular-weight sulfoxide dimethyl sulfoxide (CH₃S(=O)CH₃, DMSO) is water soluble, exhibits low toxicity, and is an excellent solvent. It possesses the unusual ability to rapidly penetrate skin and can carry compounds through the skin in this way. It has some use in veterinary medicine, particularly in treating lameness in horses. Sulfones are usually colourless crystalline solids. Dimethyl sulfone is water soluble. The diaryl sulfones (p-H₂NC₆H₄SO₂C₆H₄NH₂-p; e.g., dapsone) and related compounds have been used in the treatment of tuberculosis and leprosy. polysulfone resins, which incorporate the −SO₂C₆H₄− unit within a polymer, are used on a large scale for electrical and automotive parts and other applications requiring excellent thermal stability and resistance to oxidation.

Occurrence and preparation

 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.

      Sulfoxides are easily prepared by oxidation of sulfides with such reagents as sodium metaperiodate (NaIO₄) or hydrogen peroxide (H₂O₂). Commercially, DMSO is made from air/nitric oxide-catalyzed oxidation of dimethyl sulfide, which in turn is a major by-product of the Kraft sulfate process (kraft process) for the manufacture of paper. More-vigorous oxidation of sulfides or sulfoxides—as, for example, with potassium permanganate, KMnO₄—produces sulfones. Optically active sulfoxides can be prepared by oxidizing sulfides of type RSR′, where R ≠ R′, with optically active oxidants or microbiological oxidants. Alternatively, optically active sulfoxides can be prepared via reaction of optically active sulfinyl derivatives RS(=O)X, where X = O, N, or S, with reagents such as R′Li or R′MgBr. The solvent sulfolane (thiolane S,S-dioxide) is prepared by first reacting sulfur dioxide with butadiene to give sulfolene (a cyclic, unsaturated, five-membered ring sulfone), followed by hydrogenation to yield sulfolane.

      Aromatic sulfones can also be made by the reaction of sulfonyl chlorides with aromatic hydrocarbons (hydrocarbon). Thiophene S-oxides and S,S-dioxides, formed by oxidation of thiophenes, are far more reactive than the parent thiophenes because of the loss of aromaticity resulting from replacement of one or both pairs of electrons on sulfur by oxygen.

Reactions

      Sulfoxides are easily reduced to sulfides with a variety of reducing agents such as lithium aluminum hydride. In contrast, removal of the sulfone oxygens is extremely difficult. The sulfinyl and sulfonyl groups resemble carbonyl groups in the acidifying effect on α-hydrogens (i.e., those hydrogens bonded to the carbon adjacent to the carbonyl or sulfonyl group). Thus, both DMSO and dimethyl sulfone (and related alkyl sulfoxides and sulfones) undergo loss of a proton to bases (base) such as sodium hydride (NaH₂), giving the corresponding salts—e.g., CH₃S(O)CH₂Na and CH₃SO₂CH₂Na. These salts are useful as strong bases as well as reagents for organic synthesis. Sulfoxides undergo a variety of reactions, including both thermal- and enzyme-induced elimination of sulfenic acids; Pummerer rearrangement results in oxidation of the carbon atom adjacent to the sulfoxide group at the same time the sulfoxide is reduced to sulfide.

      Ligand coupling reactions of sulfoxides, involving concerted intramolecular coupling of two groups bonded to sulfur, occur via a tetrasubstituted sulfurane intermediate with a trigonal pyramidal structure. Ortho-metallation of a chiral sulfoxide involves lithiation of the aromatic ring ortho to the sulfoxide group, with coordination of lithium by sulfoxide oxygen. Subsequent reaction with aldehyde occurs in a manner minimizing steric hindrance.

      DMSO finds considerable use in organic synthesis as a mild oxidant in a process termed Swern oxidation. Notable rearrangements of the sulfone group include the Ramberg-Bäcklund reaction and the Truce-Smiles rearrangement.

 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.

Other sulfinyl and sulfonyl compounds

 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)).

      Aromatic sulfonic acids and sulfonyl chlorides can be prepared by sulfonation of benzene derivatives with fuming sulfuric acid and chlorosulfonic acid, ClSO₃H, respectively, while aliphatic sulfonic acids are prepared by vigorous oxidation of thiols (thiol) or by reaction of amine sulfur trioxide complexes (e.g., Me₃NSO₃) with organolithium compounds. Trifluoromethanesulfonic acid (triflic acid; CF₃SO₃H), one of the strongest known organic acids, is manufactured by electrochemical fluorination of methanesulfonyl chloride or fluoride and is used as a polymerization catalyst, in fuel cells (fuel cell), in gasoline production, and in synthesis of organic and organometallic compounds (organometallic compound). Reaction of sulfonyl chlorides with amino compounds, R′NH₂, gives sulfonamides (sulfonamide) and related compounds, RSO₂NHR′, whereas reaction of alcohols in the presence of tertiary amines yields sulfonates, RSO₂OR′.

      Carbanions (carbanion) attack sulfonyl chlorides at chlorine rather than sulfur, forming carbon-chlorine rather than carbon-sulfur bonds. Attack at sulfur can be realized by substituting sulfonyl fluorides, RSO₂F, for sulfonyl chlorides. Aromatic sulfonyl chlorides can be reduced to aromatic thiols such as thiophenol with zinc metal-hydrochloric acid (Zn/HCl). Sulfinyl chlorides can be made by treating disulfides with chlorine in the presence of acetic anhydride. Sulfinyl chlorides react with amines and alcohols to yield sulfinamides (RS(O)NR′₂) and sulfinates (RS(O)OR′), respectively. As previously noted (see above Disulfides and polysulfides and their oxidized products: Reactions (organosulfur compound)), sulfenyl chlorides can be prepared by reaction of disulfides with equimolar quantities of chlorine. Sulfenyl chlorides readily add to olefins (olefin) to produce chlorine-containing sulfides and react with amines to form sulfenamides, RSNR′₂.

      Sulfonylureas, RSO₂NHC(O)NRR′, which are widely used herbicides (herbicide), inhibit acetolactic synthase, a key plant enzyme. Anticlotting medical plastics have been prepared containing sulfonated polymers that bind heparin, a natural polysulfate. Sulfonamides, RSO₂NH₂, played an important role in the development of certain medicines. Sulfanilamide, p-aminobenzenesulfonamide, a compound used in the manufacture of azo dyes (azo dye), was found to inhibit the growth of bacteria. This discovery led to the development of sulfa drugs (sulfa drug), which still find some use today in the treatment of infections, although they have been largely replaced by newer antibiotics, to which bacteria are less resistant. Other sulfonamides include sildenafil ( Viagra), a popular drug for the treatment of erectile dysfunction; piroxicam (Feldene), a cyclic sulfonamide used to treat arthritis; and acetazolamide (Diamox), a diuretic used in the treatment of glaucoma.

      Esters (ester) of sulfuric acid—such as dimethyl sulfate, MeOSO₂OMe, and diethyl sulfate, EtOSO₂OEt, made from the alcohols methanol and ethanol (ethyl alcohol), respectively, as well as sulfur trioxide/sulfuric acid—are important industrial chemicals used to introduce methyl (Me) and ethyl (Et) groups into organic molecules. Both dimethyl and diethyl sulfate are highly toxic. Esters of sulfurous acid known as dialkyl sulfites—dimethyl sulfite, MeOS(O)OMe, for example—can be made from alcohols and thionyl chloride: 2MeOH + Cl₂S=O → MeOS(=O)OMe. Cyclic sulfite esters, made in a similar manner from 1,2-diols (1,2-dialcohols), and their oxidation products, cyclic sulfate esters, find considerable use in organic synthesis.

      Optically active unsymmetrically substituted cyclic sulfites are especially useful in the synthesis of other optically active compounds.

Sulfonium and oxosulfonium salts; sulfur ylides

      Sulfides (sulfide) react with alkyl halides to give trivalent sulfonium salts, as in the case of trimethyl sulfonium bromide, (CH₃)₃S⁺Br⁻, formed from dimethyl sulfide and methyl bromide. The sulfonium salts are named by putting the names of the several alkyl groups before “sulfonium halide.” Similarly, sulfoxides can be converted into the corresponding oxosulfonium salts, as in the case of trimethyl oxosulfonium chloride, [(CH₃)₃S=O]⁺Cl⁻, converted from dimethyl sulfoxide and methyl chloride. Like sulfoxides, sulfonium and oxosulfonium salts are chiral and can be isolated in optically active form if the attached carbon groups are all different, as in RR′R″S⁺ and RR′R″S(=O)⁺. The first known optically active sulfur compounds were sulfonium salts, prepared in 1900. A number of sulfonium salts occur in nature; some examples include S-adenosyl methionine, a key biological source of the methyl group; thetin or 3-dimethylsulfonium propanoate, (CH₃)₂S⁺CH₂CH₂CO₂⁻; and certain (2-hydroxyethyl)dimethylsulfoxonium salts, (CH₃)₂S⁺(O)CH₂CH₂OH. The latter two compounds occur in marine organisms. Thetin is an example of a zwitterion, a compound that is an internal ion pair; in the name of this compound, “dimethylsulfonium” precedes the name of the root compound. In the above examples of sulfonium salts, sulfur is bonded to three carbon groups, but sulfonium salts are known in which one or more of the carbon groups are replaced by other elements such as oxygen, nitrogen, sulfur, or a halogen.

      Nucleophilic attack at the carbon bonded to sulfonium sulfur forms the basis of biological methylations, as illustrated by the reaction of S-adenosylmethionine.

      Sulfonium and oxosulfonium salts react with bases, each losing a proton to give zwitterions of a special type, with the negative charge on the carbon adjacent to the positively charged sulfonium sulfur. These compounds are called sulfonium and oxosulfonium ylides, respectively—or, more broadly, sulfur ylides, by analogy with phosphorus ylides employed in the Wittig reaction. The structures of sulfonium ylides and oxosulfonium ylides are analogous to those of sulfoxides and sulfones, respectively. Stabilization of the negative charge on carbon is primarily due to the high polarizability of sulfur. While phosphorus ylides react with aldehydes (aldehyde) and ketones (ketone) to give olefins, sulfur ylides instead give epoxides (epoxide) (oxiranes). This is an important reaction in organic synthesis. If sulfur ylides derived from optically active sulfonium and oxosulfonium salt precursors are used, then optically active ylides can be prepared and these can be used in asymmetric syntheses of chiral epoxides and other products. Sulfonium and aminosulfoxonium ylides have also been used to synthesize “designer” polymers (polymer) (e.g., polymers containing various groups not obtainable through conventional polymerization). Exposure of triaryl sulfonium salts to ultraviolet light releases protons. This process of photogeneration of acid has important applications.

Sulfuranes: hypervalent organosulfur compounds

      In organosulfur compounds of type SR₄ and SR₆, analogous to the well-known fluorosulfur compounds SF₄ and SF₆, the valence of sulfur has been expanded beyond the normal octet to a dectet or dodecet, respectively. Pentacoordinate compounds SR₄, called σ-sulfuranes, typically have four ligands (ligand) and one lone pair of electrons (electron) and are classified as (10-S-4), in which, according to the Martin nomenclature scheme, the number preceding the central atom S refers to the total number of electrons shared by S, and the number following S, the number of ligands. These compounds adopt a trigonal bipyramidal structure in which the lone pair always occupies an equatorial position. (For a discussion of molecular shapes, see chemical bonding: Bonds between atoms (chemical bonding).)

      Among the four ligands, the two that are most electronegative (electronegativity) take the apical positions (a), whereas the less-electronegative groups occupy the remaining two equatorial positions (e). The central sulfur in σ-sulfuranes is described as being part of a three-centre, four-electron bond. A related type of compound is the sulfurane S-oxide, classified as (10-S-5), formed by oxidation of a sulfurane. Hexacoordinate compounds SR₆, with six ligands, called persulfuranes, have a square bipyramidal structure and are classified as (12-S-6). The σ-sulfuranes, sulfurane S-oxides, and persulfuranes are termed hypervalent compounds because their valences are expanded beyond eight. Because of this fact, these types of compounds are relatively unstable, with the central atom seeking to return to the octet state by extruding one or more ligands. For example, the σ-sulfurane (C₆F₅)₄S, named tetrakis-(pentafluorophenyl)sulfurane, prepared at temperatures below 0 °C (32 °F), decomposes to C₆F₅C₆F₅ and C₆F₅SC₆F₅ upon warming. On the other hand, if protected from moisture, acyclic and cyclic dialkyloxysulfuranes of type R₂(R′O)₂S are stable at room temperature and find utility as reagents in organic synthesis.

Eric Block

Additional Reading

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

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