Any organic compound having a sulfanyl group (–SH)
Thiol with a blue highlighted sulfhydryl group.
Inorganic chemistry, a thiol (/ˈθaɪɒl/;[1] from Ancient Greekθεῖον (theion) 'sulfur'[2]), or thiol derivative, is any organosulfur compound of the form R−SH, where R represents an alkyl or other organic substituent. The −SHfunctional group itself is referred to as either a thiol group or a sulfhydryl group, or a sulfanyl group. Thiols are the sulfur analogue of alcohols (that is, sulfur takes the place of oxygen in the hydroxyl (−OH) group of an alcohol), and the word is a blend of "thio-" with "alcohol".
Many thiols have strong odors resembling that of garlic or rotten eggs. Thiols are used as odorants to assist in the detection of natural gas (which in pure form is odorless), and the "smell of natural gas" is due to the smell of the thiol used as the odorant. Thiols are sometimes referred to as mercaptans (/mərˈkæptæn/)[3]ormercapto compounds,[4][5][6] a term introduced in 1832 by William Christopher Zeise and is derived from the Latinmercurio captāns ('capturing mercury')[7] because the thiolate group (RS−) bonds very strongly with mercury compounds.[8]
Thiols having the structure R−SH, in which an alkyl group (R) is attached to a sulfhydryl group (SH), are referred to as alkanethiolsoralkyl thiols.[9] Thiols and alcohols have similar connectivity. Because sulfur atoms are larger than oxygen atoms, C−S bond lengths – typically around 180 picometres – are about 40 picometers longer than typical C−O bonds. The C−S−H angles approach 90° whereas the angle for the C−O−H group is more obtuse. In solids and 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.
The S−H bond is much weaker than the O−H bond as reflected in their respective bond dissociation energies (BDE). For CH3S−H, the BDE is 366 kJ/mol (87 kcal/mol), while for CH3O−H, the BDE is 440 kJ/mol (110 kcal/mol).[10]
An S−H bond is moderately polar because of the small difference in the electronegativity of sulfur and hydrogen. In contrast, O−H bonds in hydroxyl groups are more polar. Thiols have a lower dipole moment relative to their corresponding alcohols.
The suffix -thiol is added to the name of the alkane. This method is nearly identical to naming an alcohol and is used by the IUPAC, e.g. CH3SH would be methanethiol.
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.
The term sulfhydryl-ormercapto- is used as a prefix, e.g. mercaptopurine.
Many thiols have strong odors resembling that of garlic. 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.[11][12][13][14][15] These compounds are detectable by the human nose at concentrations of only 10 parts per billion.[16] Human sweat contains (R)/(S)-3-methyl-3-mercapto-1-ol (MSH), detectable at 2 parts per billion and having a fruity, onion-like odor. (Methylthio)methanethiol (MeSCH2SH; MTMT) is a strong-smelling volatile thiol, also detectable at parts per billion levels, found in male mouse urine. Lawrence C. Katz and co-workers showed that MTMT functioned as a semiochemical, activating certain mouse olfactory sensory neurons, and attracting female mice.[17]Copper has been shown to be required by a specific mouse olfactory receptor, MOR244-3, which is highly responsive to MTMT as well as to various other thiols and related compounds.[18] A human olfactory receptor, OR2T11, has been identified which, in the presence of copper, is highly responsive to the gas odorants (see below) ethanethiol and t-butyl mercaptan as well as other low molecular weight thiols, including allyl mercaptan found in human garlic breath, and the strong-smelling cyclic sulfide thietane.[19]
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 that has been exposed to ultraviolet light.
Not all thiols have unpleasant odors. For example, furan-2-ylmethanethiol contributes to the aroma of roasted coffee, whereas grapefruit mercaptan, a monoterpenoid thiol, is responsible for the characteristic scent of grapefruit. The effect of the latter compound is present only at low concentrations. The pure mercaptan has an unpleasant odor.
In the United States, natural gas distributors were required to add thiols, originally ethanethiol, to natural gas (which is naturally odorless) after the deadly New London School explosioninNew London, Texas, in 1937. Many gas distributors were odorizing gas prior to this event. Most currently-used gas odorants contain mixtures of mercaptans and sulfides, with t-butyl mercaptan as the main odor constituent in natural gas and ethanethiolinliquefied petroleum gas (LPG, propane).[20] In situations where thiols are used in commercial industry, such as liquid petroleum gas tankers and bulk handling systems, an oxidizing catalyst is used to destroy the odor. A copper-based oxidation catalyst neutralizes the volatile thiols and transforms them into inert products.
Thiols show little association by hydrogen bonding, both with 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. For this reason also, thiols and their corresponding sulfide functional group isomers have similar solubility characteristics and boiling points, whereas the same is not true of alcohols and their corresponding isomeric ethers.
The S−H bond in thiols is weak compared to the O−H bond in alcohols. For CH3X−H, the bond enthalpies are 365.07±2.1 kcal/mol for X = S and 440.2±3.0 kcal/mol for X = O.[21] Hydrogen-atom abstraction from a thiol gives a thiyl radical with the formula RS•, where R = alkyl or aryl.
Volatile thiols are easily and almost unerringly detected by their distinctive odor. Sulfur-specific analyzers for gas chromatographs are useful. Spectroscopic indicators are the D2O-exchangeable SH signal in the 1H NMR spectrum (33SisNMR-active but signals for divalent sulfur are very broad and of little utility[22]). The νSH band appears near 2400 cm−1 in the IR spectrum.[4] In the nitroprusside reaction, free thiol groups react with sodium nitroprusside and ammonium hydroxide to give a red colour.
In industry, methanethiol is prepared by the reaction of hydrogen sulfide with methanol. This method is employed for the industrial synthesis of methanethiol:
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 an acid catalyst or UV light. Halide displacement, using the suitable organic halide and sodium hydrogen sulfide has also been used.[23]
In general, on the typical laboratory scale, the direct reaction of a haloalkane with sodium hydrosulfide is inefficient owing to the competing formation of sulfides. Instead, alkyl halides are converted to thiols via an S-alkylation of thiourea. This multistep, one-pot process proceeds via the intermediacy of the isothiouronium salt, which is hydrolyzed in a separate step:[24][25]
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 dithioketals.[26] A related two-step process involves alkylation of thiosulfate to give the thiosulfonate ("Bunte salt"), followed by hydrolysis. The method is illustrated by one synthesis of thioglycolic acid:
Akin to the chemistry of alcohols, thiols form sulfides, thioacetals, and thioesters, which are analogous to ethers, acetals, and esters respectively. Thiols and alcohols are also very different in their reactivity, thiols being more easily oxidized than alcohols. Thiolates are more potent nucleophiles than the corresponding alkoxides.
Thiols are easily deprotonated.[32] Relative to the alcohols, thiols are more acidic. The conjugate base of a thiol is called a thiolate. Butanethiol has a pKa of 10.5 vs 15 for butanol. Thiophenol has a pKa of 6, versus 10 for phenol. A highly acidic thiol is pentafluorothiophenol (C6F5SH) with a pKa of 2.68. Thus, thiolates can be obtained from thiols by treatment with alkali metal hydroxides.
With metal ions, thiolates behave as ligands to form transition metal thiolate complexes. The term mercaptan is derived from the Latinmercurium captans (capturing mercury)[7] because the thiolate group bonds so strongly with mercury compounds. According to hard/soft acid/base (HSAB) theory, sulfur is a relatively soft (polarizable) atom. This explains the tendency of thiols to bind to soft elements and ions such as mercury, lead, or cadmium. The stability of metal thiolates parallels that of the corresponding sulfide minerals.
Free radicals derived from mercaptans, called thiyl radicals, are commonly invoked to explain reactions in organic chemistry and biochemistry. They have the formula RS• where R is an organic substituent such as alkyloraryl.[6] They arise from or can be generated by a number of routes, but the principal method is H-atom abstraction from thiols. Another method involves homolysis of organic disulfides.[34] In biology thiyl radicals are responsible for the formation of the deoxyribonucleic acids, building blocks for DNA. This conversion is catalysed by ribonucleotide reductase (see figure).[35] Thiyl intermediates also are produced by the oxidation of glutathione, an antioxidant in biology. Thiyl radicals (sulfur-centred) can transform to carbon-centred radicals via hydrogen atom exchange equilibria. The formation of carbon-centred radicals could lead to protein damage via the formation of C−C bonds or backbone fragmentation.[36]
As the functional group of the amino acidcysteine, the thiol group plays a very 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.[38]
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 biosynthesisofmethane, the principal hydrocarbon on Earth, arises from the reaction mediated by coenzyme M, 2-mercaptoethyl sulfonic acid. Thiolates, the conjugate bases derived from thiols, form strong complexes with many metal ions, especially those classified as soft. The stability of metal thiolates parallels that of the corresponding sulfide minerals.
The defensive spray of skunks consists mainly of low-molecular-weight thiols and derivatives with a foul odor, which protects the skunk from predators. Owls are able to prey on skunks, as they lack a sense of smell.[40]
German translation: Zeise, W. C. (1834). "Das Mercaptan, nebst Bermerkungen über einige neue Producte aus der Einwirkung der Sulfurete auf weinschwefelsaure Salze und auf das Weinöl" [Mercaptan together with comments on some new products from the effect of hydrogen sulfide on salts of ethyl sulfate ((C2H5)HSO4) and heavy oil of wine (a mixture of diethyl sulfate, diethyl sulfite, and polymerized ethylene)]. Annalen der Physik und Chemie. 2nd series (in German). 31 (24): 369–431. From p. 378: " … nenne ich den vom Quecksilber aufgenommenen Stoff Mercaptum (von: Corpus mercurio captum) … " ( … I name the substance [that is] absorbed by mercury "mercaptum" (from: the body (substance) [that] has been absorbed by mercury) … )
Zeise, William Christopher (1834). "Sur le mercaptan; avec des observations sur d'autres produits resultant de l'action des sulfovinates ainsi que de l'huile de vin, sur des sulfures metalliques" [On mercaptan; with observations on other products resulting from the action of sulfovinates [typically, ethyl hydrogen sulfate] as well as oil of wine [a mixture of diethylsulfate and ethylene polymers] on metal sulfides]. Annales de Chimie et de Physique. 56: 87–97. Archived from the original on 2015-03-20. "Mercaptan" (ethyl thiol) was discovered in 1834 by the Danish professor of chemistry William Christopher Zeise (1789–1847). He called it "mercaptan", a contraction of "corpus mercurio captans" (mercury-capturing substance) [p. 88], because it reacted violently with mercury(II) oxide ("deutoxide de mercure") [p. 92].
^Andersen K. K.; Bernstein D. T. (1978). "Some Chemical Constituents of the Scent of the Striped Skunk (Mephitis mephitis)". Journal of Chemical Ecology. 1 (4): 493–499. doi:10.1007/BF00988589. S2CID9451251.
^Andersen K. K., Bernstein D. T.; Bernstein (1978). "1-Butanethiol and the Striped Skunk". Journal of Chemical Education. 55 (3): 159–160. Bibcode:1978JChEd..55..159A. doi:10.1021/ed055p159.
^Andersen K. K.; Bernstein D. T.; Caret R. L.; Romanczyk L. J., Jr. (1982). "Chemical Constituents of the Defensive Secretion of the Striped Skunk (Mephitis mephitis)". Tetrahedron. 38 (13): 1965–1970. doi:10.1016/0040-4020(82)80046-X.
^Wood W. F.; Sollers B. G.; Dragoo G. A.; Dragoo J. W. (2002). "Volatile Components in Defensive Spray of the Hooded Skunk, Mephitis macroura". Journal of Chemical Ecology. 28 (9): 1865–70. doi:10.1023/A:1020573404341. PMID12449512. S2CID19217201.
^Stubbe, JoAnne; Nocera, Daniel G.; Yee, Cyril S.; Chang, Michelle C. Y. (2003). "Radical Initiation in the Class I Ribonucleotide Reductase: Long-Range Proton-Coupled Electron Transfer?". Chem. Rev. 103 (6): 2167–2202. doi:10.1021/cr020421u. PMID12797828.
^Koch, Cameron J.; Parliament, Matthew B.; Brown, J. Martin; Urtasun, Raul C. (2010). "Chemical Modifiers of Radiation Response". Leibel and Phillips Textbook of Radiation Oncology. Elsevier. pp. 55–68. doi:10.1016/b978-1-4160-5897-7.00004-4. ISBN978-1-4160-5897-7. Sulfhydryls are scavengers of free radicals, protecting chemical damage induced by either ionizing radiation or alkylating agents.
^Reece, Urry; et al. (2011). Campbell Biology (Ninth ed.). New York: Pearson Benjamin Cummings. pp. 65, 83.
