Many thiols have strong odors resembling that ofgarlic,cabbage or rotten eggs. Thiols are used asodorants to assist in the detection ofnatural 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 asmercaptans (/mərˈkæptæn/)[3] ormercapto compounds,[4][5][6] a term introduced in 1832 byWilliam Christopher Zeise and is derived from theLatinmercurio captāns ('capturing mercury')[7] because thethiolate group (RS−) bonds very strongly withmercury compounds.[8]
Thiols having the structure R−SH, in which analkyl group (R) is attached to asulfhydryl group (SH), are referred to asalkanethiols oralkyl thiols.[9] Thiols and alcohols have similar connectivity. Because sulfur atoms are larger than oxygen atoms, C−Sbond lengths—typically around 180picometres—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, thehydrogen-bonding between individual thiol groups is weak, the main cohesive force beingVan 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 respectivebond 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 moderatelypolar because of the small difference in theelectronegativity of sulfur and hydrogen. In contrast, O−H bonds in hydroxyl groups are more polar. Thiols have a lowerdipole moment relative to their corresponding alcohols.
The suffix-thiol is added to the name of the alkane. This method is nearly identical tonaming an alcohol and is used by theIUPAC, e.g. CH3SH would bemethanethiol.
The wordmercaptan replacesalcohol in the name of the equivalent alcohol compound. Example: CH3SH would be methyl mercaptan, just as CH3OH is called methyl alcohol.
The termsulfhydryl- ormercapto- is used as a prefix, e.g.mercaptopurine.
Many thiols have strongodors resembling that ofgarlic. The odors of thiols, particularly those of low molecular weight, are often strong and repulsive. The spray ofskunks 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] Humansweat 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 malemouse urine.Lawrence C. Katz and co-workers showed that MTMT functioned as asemiochemical, activating certain mouse olfactory sensory neurons, and attracting femalemice.[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 andt-butyl mercaptan as well as other low molecular weight thiols, includingallyl mercaptan found in humangarlic breath, and the strong-smelling cyclic sulfidethietane.[19]
Thiols are also responsible for a class ofwine faults caused by an unintended reaction between sulfur andyeast 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 roastedcoffee, whereasgrapefruit mercaptan, amonoterpenoid thiol, is responsible for the characteristic scent ofgrapefruit. 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, originallyethanethiol, tonatural gas (which is naturally odorless) after the deadlyNew London School explosion inNew 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, witht-butyl mercaptan as the main odor constituent in natural gas andethanethiol inliquefied 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 oxidizingcatalyst 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 byhydrogen bonding, both with water molecules and among themselves. Hence, they have lowerboiling points and are lesssoluble in water and otherpolar solvents than alcohols of similar molecular weight. For this reason also, thiols and their corresponding sulfide functional groupisomers 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 are365.07±2.1 kcal/mol for X = S and440.2±3.0 kcal/mol for X = O.[21] Hydrogen-atom abstraction from a thiol gives athiyl 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 forgas chromatographs are useful. Spectroscopic indicators are theD2O-exchangeable SH signal in the1H NMR spectrum (33S isNMR-active but signals for divalent sulfur are very broad and of little utility[22]). TheνSH band appears near 2400 cm−1 in theIR spectrum.[4] In thenitroprusside reaction, free thiol groups react withsodium nitroprusside andammonium hydroxide to give a red colour.
In industry, methanethiol is prepared by the reaction ofhydrogen sulfide withmethanol. This method is employed for the industrial synthesis ofmethanethiol:
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 toalkenes. 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 ahaloalkane with sodium hydrosulfide isinefficient owing to the competing formation of sulfides. Instead, alkyl halides are converted to thiols via anS-alkylation ofthiourea. This multistep, one-pot process proceeds via the intermediacy of theisothiouronium 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 correspondingdithioketals.[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 ofthioglycolic acid:
Akin to the chemistry of alcohols, thiols formsulfides,thioacetals, andthioesters, which are analogous toethers,acetals, andesters 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 correspondingalkoxides.
Thiols are easily deprotonated.[32] Relative to the alcohols, thiols are more acidic. The conjugate base of a thiol is called athiolate. Butanethiol has apKa of 10.5 vs 15 for butanol. Thiophenol has apKa of 6, versus 10 forphenol. A highly acidic thiol ispentafluorothiophenol (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 formtransition metal thiolate complexes. The termmercaptan is derived from theLatinmercurium captans (capturing mercury)[7] because the thiolate group bonds so strongly withmercury compounds. According tohard/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, calledthiyl radicals, are commonly invoked to explain reactions inorganic chemistry andbiochemistry. They have the formula RS• where R is an organic substituent such asalkyl oraryl.[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 involveshomolysis of organic disulfides.[34] In biology thiyl radicals are responsible for the formation of the deoxyribonucleic acids, building blocks forDNA. This conversion is catalysed byribonucleotide reductase (see figure).[35] Thiyl intermediates also are produced by the oxidation ofglutathione, an antioxidant in biology. Thiyl radicals (sulfur-centred) can transform to carbon-centred radicals viahydrogen atom exchangeequilibria. The formation ofcarbon-centred radicals could lead to protein damage via the formation ofC−C bonds or backbone fragmentation.[36]
As the functional group of theamino 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 ofprotein folding, anoxidation reaction can generate acystine unit with adisulfide bond (−S−S−). Disulfide bonds can contribute to a protein'stertiary structure if the cysteines are part of the samepeptide chain, or contribute to thequaternary structure of multi-unit proteins by forming fairly strong covalent bonds between different peptide chains. A physical manifestation of cysteine-cystine equilibrium is provided byhair straightening technologies.[38]
Manycofactors (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 thiolCoenzyme A. Thebiosynthesis ofmethane, the principalhydrocarbon on Earth, arises from the reaction mediated bycoenzyme 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 ofskunks 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 StoffMercaptum (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 chemistryWilliam 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.; 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.
^M. E. Alonso; H. Aragona (1978). "Sulfide Synthesis in Preparation of Unsymmetrical Dialkyl Disulfides: Sec-butyl Isopropyl Disulfide".Org. Synth.58: 147.doi:10.15227/orgsyn.058.0147.
^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.
