Thiol

{{short description|Any organic compound having a sulfanyl group (–SH)}} thumb|upright=0.5|right|Thiol with a {{legend-inline|blue|blue highlighted}} sulfhydryl group.

In organic chemistry, a '''thiol''' ({{IPAc-en|'|θ|aɪ|ɒ|l}};<ref>''Dictionary Reference'': [http://dictionary.reference.com/browse/thiol thiol] {{webarchive|url=https://web.archive.org/web/20130411021707/http://dictionary.reference.com/browse/thiol |date=2013-04-11 }}</ref> {{ety|grc|''θεῖον'' (theion)|sulfur}}<ref>[https://www.perseus.tufts.edu/hopper/text?doc=Perseus%3Atext%3A1999.04.0057%3Aentry%3Dqei%3Don1 θεῖον] {{webarchive|url=https://web.archive.org/web/20170510073237/http://www.perseus.tufts.edu/hopper/text?doc=Perseus%3Atext%3A1999.04.0057%3Aentry%3Dqei%3Don1|date=2017-05-10}}, Henry George Liddell, Robert Scott, ''A Greek–English Lexicon''</ref>), or '''thiol derivative''', is any organosulfur compound of the form {{chem2|R\sSH}}, where R represents an alkyl or other organic substituent. The {{chem2|\sSH}} functional 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 ({{chem2|\sOH}}) group of an alcohol), and the word is a blend of "''thio-''" with "alcohol".

Many thiols have strong odors resembling that of garlic, cabbage or rotten eggs. Thiols are used as odorants to assist in the detection of natural gas (which in pure form is odorless). The smell of natural gas is due to the addition of thiol.

==Nomenclature== Thiols are sometimes referred to as '''mercaptans''' ({{IPAc-en|m|ər|ˈ|k|æ|p|t|æ|n|z}})<ref>''Dictionary Reference'': [http://dictionary.reference.com/browse/mercaptan mercaptan] {{webarchive|url=https://web.archive.org/web/20121113062439/http://dictionary.reference.com/browse/mercaptan|date=2012-11-13 }}</ref> or '''mercapto compounds''',<ref name=Patai>{{Cite book|editor=Patai, Saul|title=The Chemistry of the Thiol Group. Part 1|publisher=Wiley|location=London|date=1974|doi=10.1002/9780470771310|isbn=9780470771310}}</ref><ref>{{Cite book|editor=Patai, Saul|title=The Chemistry of the Thiol Group. Part 2|publisher=Wiley|location=London|date=1974|doi=10.1002/9780470771327|isbn=9780470771327}}</ref><ref name="CremlynAn">{{Cite book|author=R. J. Cremlyn|title = An Introduction to Organosulfur Chemistry|publisher=John Wiley and Sons|location=Chichester|date=1996|isbn=978-0-471-95512-2}}</ref> a term introduced in 1832 by William Christopher Zeise and is derived from the Latin {{lang|la|mercurio captāns}} ('capturing mercury')<ref name="ReferenceA">''Oxford American Dictionaries'' (Mac OS X Leopard).</ref> because the '''thiolate''' group ({{chem2|RS-}}) bonds very strongly with mercury compounds.<ref>See: * {{cite journal |last1=Zeise |first1=William Christopher |title=Mercaptanet, med bemaerkninger over nogle andre nye producter af svovelvinsyresaltene, som og af den tunge vinolie, ved sulfureter |journal=Kongelige Danske Videnskabers Selskabs Skrifter |date=1834 |volume=6 |pages=1–70 |url=https://babel.hathitrust.org/cgi/pt?id=umn.31951d00004546r&view=1up&seq=131 |series=4th series |trans-title=Mercaptan, with remarks on some other new products of salts of ethyl hydrogen sulfate as well as of heavy oil of wine, by means of hydrogen sulfide |language=da}} On p. 13 the word "mercaptan" is coined. * German translation: {{cite journal |last1=Zeise |first1=W. C. |title=Das Mercaptan, nebst Bermerkungen über einige neue Producte aus der Einwirkung der Sulfurete auf weinschwefelsaure Salze und auf das Weinöl |journal=Annalen der Physik und Chemie |date=1834 |volume=31 |issue=24 |pages=369–431 |url=https://babel.hathitrust.org/cgi/pt?id=wu.89048351654&view=1up&seq=383 |series=2nd series |trans-title=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) |language=de}} 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) … ) * German translation is reprinted in:{{cite journal|first= W. C.|last= Zeise |date=1834 |title=Das Mercaptan, nebst Bemerkungen über einige andere neue Erzeugnisse der Wirkung schwefelweinsaurer Salze, wie auch des schweren Weinöls auf Sulphurete |journal=Journal für Praktische Chemie |volume=1 |issue=1 |pages=257–268, 345–356, 396–413, 457–475 |url=https://babel.hathitrust.org/cgi/pt?id=uiug.30112063582438;view=1up;seq=267 | doi = 10.1002/prac.18340010154 }} * Summarized in: {{cite journal|last=Zeise|first=W. C.|date=1834 |url=https://books.google.com/books?id=dmgTAAAAQAAJ&pg=PA1|title=Ueber das Mercaptan|trans-title=On mercaptan|journal=Annalen der Pharmacie|volume=11|issue=1|pages=1–10|doi=10.1002/jlac.18340110102|url-status=live|archive-url=https://web.archive.org/web/20150320202059/http://books.google.com/books?id=dmgTAAAAQAAJ&pg=PA1|archive-date=2015-03-20}} * {{cite journal|last=Zeise|first=William Christopher|date=1834|url=https://books.google.com/books?id=1Jc5AAAAcAAJ&pg=PA87|title=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 |trans-title=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|journal=Annales de Chimie et de Physique|volume=56|pages=87–97|url-status=live|archive-url=https://web.archive.org/web/20150320194543/http://books.google.com/books?id=1Jc5AAAAcAAJ&pg=PA87|archive-date=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]. * The article in ''Annales de Chimie et de Physique'' (1834) was translated from the German article: {{cite journal|first=W. C.|last=Zeise|date=1834|url=https://books.google.com/books?id=wCUAAAAAMAAJ&pg=PA369|title=Das Mercaptan, nebst Bemerkungen über einige neue Producte aus der Einwirkung der Sulfurete auf weinschwefelsaure Salze und auf das Weinöl |journal=Annalen der Physik und Chemie|volume=107|issue=27|pages=369–431 |bibcode=1834AnP...107..369Z|doi=10.1002/andp.18341072402|url-status=live |archive-url=https://web.archive.org/web/20150320201943/http://books.google.com/books?id=wCUAAAAAMAAJ&pg=PA369 |archive-date=2015-03-20 }}</ref>

There are several ways to name the alkylthiols:{{cn|date=July 2025}} * 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-'' or ''mercapto-'' is used as a prefix, e.g. mercaptopurine.

==Physical properties== ===Odor=== 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.<ref>{{cite journal|journal=Journal of Chemical Ecology|volume=1|issue=4|year=1978|title=Some Chemical Constituents of the Scent of the Striped Skunk (''Mephitis mephitis'')|author1=Andersen K. K.|author2=Bernstein D. T.|doi=10.1007/BF00988589|pages=493–499 }}</ref><ref>{{cite journal|journal=Journal of Chemical Education|volume=55|issue=3|year=1978|title=1-Butanethiol and the Striped Skunk|author= Andersen K. K., Bernstein D. T. |doi=10.1021/ed055p159|pages=159–160|bibcode=1978JChEd..55..159A |last2= Bernstein }}</ref><ref>{{cite journal|journal=Tetrahedron|volume=38|issue=13|year=1982 |title=Chemical Constituents of the Defensive Secretion of the Striped Skunk (''Mephitis mephitis'')|author1=Andersen K. K.|author2=Bernstein D. T.|author3=Caret R. L.|author4=Romanczyk L. J., Jr. |doi=10.1016/0040-4020(82)80046-X|pages=1965–1970}}</ref><ref>{{cite journal|journal=Journal of Chemical Ecology|volume=28|issue=9|year=2002|title=Volatile Components in Defensive Spray of the Hooded Skunk, ''Mephitis macroura''|author1=Wood W. F.|author2=Sollers B. G.|author3=Dragoo G. A.|author4=Dragoo J. W.|doi=10.1023/A:1020573404341|pages=1865–70|pmid=12449512|bibcode=2002JCEco..28.1865W }}</ref><ref>{{cite web|url=http://users.humboldt.edu/wfwood/chemofskunkspray.html|title=Chemistry of Skunk Spray|access-date=January 2, 2008|author=William F. Wood|publisher=Dept. of Chemistry, Humboldt State University|url-status=live|archive-url=https://web.archive.org/web/20101008140758/http://users.humboldt.edu/wfwood/chemofskunkspray.html|archive-date=October 8, 2010}}</ref> These compounds are detectable by the human nose at concentrations of only 10 parts per billion.<ref>{{Cite journal | doi= 10.1084/jem.1.2.323|last=Aldrich|first= T.B.|title=A Chemical Study of the Secretion of the Anal Glands of ''Mephitis mephitiga'' (Common Skunk), with Remarks on the Physiological Properties of This Secretion|journal=J. Exp. Med.|volume=1|issue=2|pages=323–340|year=1896|pmid=19866801|pmc=2117909}}</ref> Human sweat contains (''R'')/(''S'')-3-methyl-3-sulfanylhexan-1-ol (3M3SH), detectable at 2 parts per billion and having an onion-like (S enantiomer) and fruity, grapefruit-like odor (R enantiomer).<ref>{{cite journal |last1=Troccaz |first1=Myriam |last2=Starkenmann |first2=Christian |last3=Niclass |first3=Yvan |last4=van de Waal |first4=Matthijs |last5=Clark |first5=Anthony J. |title=3-Methyl-3-sulfanylhexan-1-ol as a Major Descriptor for the Human Axilla-Sweat Odour Profile |journal=Chemistry & Biodiversity |date=July 2004 |volume=1 |issue=7 |pages=1022–1035 |doi=10.1002/cbdv.200490077 |pmid=17191896 }}</ref> (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.<ref>{{cite journal|last1=Lin|first1=Dayu|last2=Zhang|first2=Shaozhong|last3=Block|first3=Eric|last4=Katz|first4=Lawrence C.|year=2005|title=Encoding social signals in the mouse main olfactory bulb| journal=Nature|volume=434|issue=7032|pages=470–477|doi=10.1038/nature03414|bibcode=2005Natur.434..470L|pmid=15724148 }}</ref> 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.<ref>{{cite journal|last1=Duan|first1=Xufang|last2=Block|first2=Eric|last3=Li|first3=Zhen|last4=Connelly|first4=Timothy|last5=Zhang|first5=Jian|last6=Huang|first6=Zhimin|last7=Su|first7=Xubo|last8=Pan|first8=Yi|last9=Wu|first9=Lifang|last10=Chi|first10=Q.|last11=Thomas|first11=S.|last12=Zhang|first12=S.|last13=Ma|first13=M.|last14=Matsunami|first14 = H.|last15=Chen|first15=G.-Q.|last16=Zhuang|first16=H.|year=2012|title=Crucial role of copper in detection of metal-coordinating odorants|journal=Proc. Natl. Acad. Sci. U.S.A. |volume=109|issue=9|pages=3492–3497|doi=10.1073/pnas.1111297109|bibcode=2012PNAS..109.3492D|pmid=22328155|pmc=3295281|display-authors=8|doi-access=free}}</ref> 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.<ref>{{cite web|url=https://www.chemistryworld.com/news/copper-key-to-our-sensitivity-to-rotten-eggs-foul-smell/1017492.article|title=Copper key to our sensitivity to rotten eggs' foul smell|website=chemistryworld.com|access-date=3 May 2018|url-status=live|archive-url=https://web.archive.org/web/20170510113946/https://www.chemistryworld.com/news/copper-key-to-our-sensitivity-to-rotten-eggs-foul-smell/1017492.article|archive-date=10 May 2017}}</ref>

Thiols are also responsible for a class of wine faults caused by an unintended reaction between sulfur and yeast, as well as 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. Concentrated samples have an unpleasant odor.

In the United States, distributors are required to add thiols, originally ethanethiol, to natural gas (which is naturally odorless) after the deadly New London School explosion in New London, Texas, in 1937, although many 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 ethanethiol in liquefied petroleum gas (LPG, propane).<ref name=Roberts>{{Cite book|editor=Roberts, J. S.|title=Kirk-Othmer Encyclopedia of Chemical Technology|publisher=Wiley-VCH|location=Weinheim|date=1997}}{{page needed|date=May 2019}}</ref> 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.

===Boiling points and solubility=== 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.

== Structure and bonding == Thiols having the structure R−S−H, in which an alkyl group (R) is attached to a sulfhydryl group (SH), are referred to as ''alkanethiols'' or ''alkyl thiols''.<ref>{{cite web |title=Alkanethiols |url=https://www.rsc.org/publishing/journals/prospect/ontology.asp?id=CHEBI:47908&MSID=c000442a |publisher=Royal Society of Chemistry |access-date=4 September 2019 }}</ref> 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. 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, and thus thiols are more volatile than the corresponding alcohols. The main cohesive forces for thiols involves 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 {{cvt|366|kJ/mol|kcal/mol}}, while for CH₃O−H, the BDE is {{cvt|440|kJ/mol|kcal/mol}}.<ref>{{cite book|chapter=Bond Dissociation Energies|author1=Luo, Y.-R. |author2=Cheng, J.-P. |title=Handbook of Chemistry and Physics|editor=J. R. Rumble|year=2017|publisher=CRC Press}}</ref> Hydrogen-atom abstraction from a thiol gives a thiyl radical with the formula RS^•, where R = alkyl or aryl.

==Characterization== 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 S'''H''' signal in the ¹H NMR spectrum (³³S is NMR-active but signals for divalent sulfur are very broad and of little utility<ref>{{cite web|url=http://www.pascal-man.com/periodic-table/sulfur.shtml|title=Sulfur-33 NMR references|first=Pascal P.|last=Man|website=www.pascal-man.com|access-date=3 May 2018|url-status=live|archive-url=https://web.archive.org/web/20170823184753/http://www.pascal-man.com/periodic-table/sulfur.shtml|archive-date=23 August 2017}}</ref>). The ''ν''_SH band appears near 2400&nbsp;cm⁻¹ in the IR spectrum.<ref name=Patai/> In the nitroprusside reaction, free thiol groups react with sodium nitroprusside and ammonium hydroxide to give a red colour.

==Preparation== 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.<ref>John S Roberts, "Thiols", in ''Kirk-Othmer Encyclopedia of Chemical Technology'', 1997, Wiley-VCH, Weinheim. {{doi|10.1002/0471238961.2008091518150205.a01}}</ref>

Another method entails the alkylation of sodium hydrosulfide. : RX + NaSH → RSH + NaX{{pad|3em}}(X = Cl, Br, I) This method is used for the production of thioglycolic acid from chloroacetic acid.

===Laboratory methods=== In general, on the typical laboratory scale, the direct reaction of a haloalkane with sodium hydrosulfide is ''in''efficient owing to the competing formation of sulfides (overalkylation). 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:<ref>{{OrgSynth | author = Speziale, A. J. | title = Ethanedithiol | collvol = 4 | collvolpages = 401 | year = 1963 | prep = cv4p0401}}.</ref><ref>{{cite journal|first1=G. G. |last1=Urquhart|first2=J. W. Jr. |last2=Gates|first3=Ralph|last3=Connor|journal=Org. Synth.|year=1941|volume=21|page=36|title=''n''-Dodecyl Mercaptan|doi=10.15227/orgsyn.021.0036}}</ref>

: CH₃CH₂Br + SC(NH₂)₂ → [CH₃CH₂SC(NH₂)₂]Br : [CH₃CH₂SC(NH₂)₂]Br + NaOH → CH₃CH₂SH + OC(NH₂)₂ + NaBr

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.<ref>{{OrgSynth | author = S. R. Wilson, G. M. Georgiadis | title = Mecaptans from Thioketals: Cyclododecyl Mercaptan | collvol = 7 | collvolpages = 124 | year = 1990 | prep = cv7p0124}}.</ref> 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: :ClCH₂CO₂H + Na₂S₂O₃ → Na[O₃S₂CH₂CO₂H] + NaCl

:Na[O₃S₂CH₂CO₂H] + H₂O → HSCH₂CO₂H + NaHSO₄

Organolithium compounds and Grignard reagents react with sulfur to give the thiolates, which are readily hydrolyzed:<ref>{{OrgSynth | author = E. Jones and I. M. Moodie | title = 2-Thiophenethiol | collvol = 6 | collvolpages = 979 | year = 1990 | prep = cv6p0979}}.</ref> :RLi + S → RSLi :RSLi + HCl → RSH + LiCl

Phenols can be converted to the thiophenols via rearrangement of their ''O''-aryl dialkylthiocarbamates.<ref>{{OrgSynth | author = Melvin S. Newman and Frederick W. Hetzel | title = Thiophenols from Phenols: 2-Naphthalenethiol | collvol = 6 | collvolpages = 824 | year = 1990 | prep = cv6p0824}}.</ref>

Thiols are prepared by reductive dealkylation of sulfides, especially benzyl derivatives and thioacetals.<ref>{{OrgSynth |first1=Ernest L. |last1=Eliel |first2=Joseph E. |last2=Lynch |first3=Fumitaka |last3=Kume |first4=Stephen V. |last4=Frye | title = Chiral 1,3-oxathiane from (+)-Pulegone: Hexahydro-4,4,7-trimethyl-4''H''-1,3-benzoxathiin | collvol = 8 | collvolpages = 302 | year = 1993 | prep = cv8p0302}}</ref>

Thiophenols are produced by ''S''-arylation or the replacement of diazonium leaving group with sulfhydryl anion (SH⁻):<ref>{{cite journal|title=Novel One-Pot Synthesis of Thiophenols from Related Triazenes under Mild Conditions|journal=Synlett|date=2012|volume=23|issue=13|pages=1893–1896|doi=10.1055/s-0032-1316557|last1=Kazem-Rostami|first1=Masoud|last2=Khazaei|first2=Ardeshir|last3=Moosavi-Zare|first3=Ahmad|last4=Bayat|first4=Mohammad|last5=Saednia|first5=Shahnaz }}</ref><ref>{{cite journal|last1=Leuckart |first1=Rudolf |title=Eine neue Methode zur Darstellung aromatischer Mercaptane |trans-title=A new method for the preparation of aromatic mercaptans |journal=Journal für Praktische Chemie |date=1890 |series= 2nd series |volume=41 |pages=179–224 |url=https://books.google.com/books?id=KxlLAAAAYAAJ&pg=PA179 |doi=10.1002/prac.18900410114 |language=de }}</ref> :{{chem|ArN|2|+}} + SH⁻ → ArSH + N₂

==Classes of thiols== ===Alkyl and aryl thiols=== Alkyl thiols are the simplest thiols. Methanethiol (CH₃SH, methyl mercaptan), ethanethiol (C₂H₅SH, ethyl mercaptan), propanethiol (C₃H₇SH), butanethiols (C₄H₉SH, ''n''-butyl mercaptan and ''tert''-Butyl mercaptan, are common reagents. While these thiols have the characteristic unpleasant odors, some thiols are responsible for the flavor and fragrance of foods, e.g. furan-2-ylmethanethiol. 1-Hexadecanethiol is a lipophilic alkylthiol.

Aryl thiols include the parent thiophenol (C₆H₅SH). Pentachlorobenzenethiol has pesticidal properties.

===Dithiols=== 1,3-Propanedithiol and 1,2-ethanedithiol are reagents in organic chemistry. Dimercaptosuccinic acid is a chelating agent. Lipoic acid, a naturally occurring modification of 1,3-propanedithiol, is a cofactor for many enzymes. Dithiothreitol is a reagent in biochemistry.

===Unsaturated thiols=== Vinyl thiols are rare, but other unsaturated thiols are numerous. A textbook unsaturated thiol is grapefruit mercaptan, which exists as two enantiomers, each with distinct odors. The main component of skunk spray is a butenylthiol.<ref>{{cite journal |doi=10.1007/s00897990286a |title=The History of Skunk Defensive Secretion Research |date=1999 |last1=Wood |first1=William F. |journal=The Chemical Educator |volume=4 |issue=2 |pages=44–50 }}</ref>

===Thioalcohols=== 2-Mercaptoethanol is a reagent in biochemistry. 3-Mercaptopropane-1,2-diol is a medicine. These compounds have high solubility in water owing to the presence of OH substituent(s).

===Thiol-carboxylic acids=== Cysteine and penicillamine have the formula {{chem2|HSCR2CH(NH2)CO2H}}, where R = H and CH₃, respectively. Cysteine is common amino acid, and penicillamine has medicinal properties. Coenzyme A and glutathione are more complicated thiol-containing derivatives. Cysteine-rich proteins called metallothionein have high affinity for heavy metals. Thiocarboxylic acids, with the formula {{chem2|HS(O)CR}}, can be considered thiols also. Thioacetic acid is one example.

===Aminothiols=== Cysteine and penicillamine also are classified as an aminothiols. One variation is cysteamine ({{chem2|HSCH2CH2NH2}}.

==Reactions== Thiols form sulfides, thioacetals, and thioesters, which are analogous to ethers, acetals, and esters, respectively.

===Acidity=== Thiols are easily deprotonated.<ref>{{cite journal|title=Sulfide Synthesis in Preparation of Unsymmetrical Dialkyl Disulfides: Sec-butyl Isopropyl Disulfide|journal=Org. Synth.|year=1978|volume=58|page=147|doi=10.15227/orgsyn.058.0147|author1=M. E. Alonso |author2=H. Aragona }}</ref> Relative to the alcohols, thiols are more acidic. The conjugate base of a thiol is called a '''thiolate'''. Butanethiol has a p''K''_a of 10.5 vs 15 for butanol. Thiophenol has a p''K''_a of 6, versus 10 for phenol. A highly acidic thiol is pentafluorothiophenol (C₆F₅SH) with a p''K''_a of 2.68. Thus, thiolates can be obtained from thiols by treatment with alkali metal hydroxides. thumb|right|upright=1.8|Synthesis of thiophenolate from thiophenol

===''S''-Based nucleophilicity=== The conjugate base of thiols are potent nucleophiles. They alkylate to give sulfides: :RSH + R′Br + B → RSR′ + [HB]Br{{pad|3em}} (B = base) Many electrophiles participate in this reaction. α,β-Unsaturated carbonyl compounds add thiols, especially in the presence of base catalysts. Thiolates react with carbon disulfide to give thioxanthate ({{chem|RSCS|2|-}}).

===Redox=== Thiols, especially in the presence of base, are readily oxidized by reagents such as bromine and iodine to give an organic disulfide (R−S−S−R). : 2&nbsp;R−SH + Br₂ → R−S−S−R + 2&nbsp;HBr Oxidation by more powerful reagents such as sodium hypochlorite or hydrogen peroxide can also yield sulfonic acids (RSO₃H). : R−SH + 3&nbsp;H₂O₂ → RSO₃H + 3&nbsp;H₂O Oxidation can also be effected by oxygen in the presence of catalysts:<ref>{{cite journal |last1=Akhmadullina |first1=A. G. |last2=Kizhaev |first2=B. V. |last3=Nurgalieva |first3=G. M. |last4=Khrushcheva |first4=I. K. |last5=Shabaeva |first5=A. S. |last6=Tugushi |first6=S. O. |last7=Bednov |first7=B. V. |title=Heterogeneous catalytic demercaptization of light hydrocarbon feedstock |journal=Chemistry and Technology of Fuels and Oils |date=March 1993 |volume=29 |issue=3 |pages=108–109 |doi=10.1007/bf00728009 |bibcode=1993CTFO...29..108A }}</ref> : 2&nbsp;R–SH + {{1/2}}&nbsp;O₂ → RS−SR + H₂O

Thiols participate in thiol-disulfide exchange: :RS−SR + 2 R′SH → 2 RSH + R′S−SR′ This reaction is important in nature.

===Metal ion complexation=== With metal ions, thiolates behave as ligands to form transition metal thiolate complexes. The term ''mercaptan'' is derived from the Latin ''mercurium captans'' (capturing mercury)<ref name="ReferenceA"/> 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. Sodium aurothiolate is an antiarthritic drug.<ref>{{cite journal | doi = 10.1038/sj.bjp.0707358 | volume=152 | title=Myeloperoxidase: a target for new drug development? | year=2007 | journal=British Journal of Pharmacology | pages=838–854 | last1 = Malle | first1 = E| issue=6 | pmid=17592500 | pmc=2078229 }}</ref>

== Thiyl radicals == {{main|Thiyl radical}}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 alkyl or aryl.<ref name="CremlynAn" /> 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.<ref name=Ullmann>{{Ullmann|first=Kathrin-Maria |last=Roy |title=Thiols and Organic Sulphides |year=2005|doi=10.1002/14356007.a26_767}}</ref> 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).<ref>{{cite journal|first1=JoAnne |last1=Stubbe |first2=Daniel G. |last2=Nocera |first3=Cyril S. |last3=Yee |first4=Michelle C. Y. |last4=Chang |title=Radical Initiation in the Class I Ribonucleotide Reductase: Long-Range Proton-Coupled Electron Transfer? |journal=Chem. Rev. |date=2003 |volume=103 |issue=6 |pages=2167–2202 |doi=10.1021/cr020421u|pmid=12797828 |bibcode=2003ChRv..103.2167S }}</ref> 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.<ref name=Hofstetter>{{cite journal | last1 = Hofstetter | first1 = Dustin | last2 = Nauser | first2 = Thomas | last3 = Koppenol | first3 = Willem H. | year = 2010 | title = Hydrogen Exchange Equilibria in Glutathione Radicals: Rate Constants | journal = Chem. Res. Toxicol. | volume = 23 | issue = 10| pages = 1596–1600 | doi = 10.1021/tx100185k | pmc = 2956374 | pmid = 20882988 }}</ref>

Because of the weakness of the S−H bond, thiols can function as scavengers of free radicals.<ref name="Koch Parliament Brown Urtasun 2010 pp. 55–68">{{cite book | last1=Koch | first1=Cameron J. | last2=Parliament | first2=Matthew B. | last3=Brown | first3=J. Martin | last4=Urtasun | first4=Raul C. | title=Leibel and Phillips Textbook of Radiation Oncology | chapter=Chemical Modifiers of Radiation Response | publisher=Elsevier | year=2010 | isbn=978-1-4160-5897-7 | doi=10.1016/b978-1-4160-5897-7.00004-4 | pages=55–68 | quote=Sulfhydryls are scavengers of free radicals, protecting chemical damage induced by either ionizing radiation or alkylating agents.}}</ref>

==Biological importance== [[File:RNR reaction.png|thumb|upright=1.8|The catalytic cycle for ribonucleotide reductase, demonstrating the role of thiyl radicals in producing the genetic machinery of life.]]

=== Cysteine and cystine === As the functional group of the proteinogenic amino acid cysteine, 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.<ref>{{cite book|last=Reece |first=Urry |display-authors=etal |title=Campbell Biology |url=https://archive.org/details/campbellbiology00reec |url-access=limited |edition=Ninth |publisher=Pearson Benjamin Cummings |location=New York |date=2011 |pages=[https://archive.org/details/campbellbiology00reec/page/n112 65], 83}}</ref>

Sulfhydryl groups in the active site of an enzyme can form noncovalent bonds with the enzyme's substrate as well, contributing to covalent catalytic activity in catalytic triads. Active site cysteine residues are the functional unit in cysteine protease catalytic triads. Cysteine residues may also react with heavy metal ions (Zn²⁺, Cd²⁺, Pb²⁺, Hg²⁺, Ag⁺) because of the high affinity between the soft sulfide and the soft metal (see hard and soft acids and bases). This can deform and inactivate the protein, and is one mechanism of heavy metal poisoning.

===Cofactors=== 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. Dihydrolipoic acid, a dithiol, is the reduced form of lipoic acid, a cofactor in several metabolic processes in mammals. Methane biosynthesis, the principal hydrocarbon on Earth, arises from the reaction mediated by coenzyme M (2-mercaptoethyl sulfonic acid) and coenzyme B (7-mercaptoheptanoylthreoninephosphate). 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.

===Drugs=== Drugs containing thiol group: * 6-Mercaptopurine (anticancer) * Captopril (antihypertensive) * D-penicillamine (antiarthritic)

==See also== * Doctor sweetening process * Odorizer * Persulfide * Saville reaction * Thiol-disulfide exchange

==References== {{Reflist|30em}}

==External links== * [http://www.periodicvideos.com/videos/mv_smelly.htm Mercaptans (or Thiols)] at ''The Periodic Table of Videos'' (University of Nottingham) * [https://web.archive.org/web/20061010191459/http://dysa.northwestern.edu/CurrOrgChem.pdf Applications, Properties, and Synthesis of ω-Functionalized n-Alkanethiols and Disulfides – the Building Blocks of Self-Assembled Monolayers] by D. Witt, R. Klajn, P. Barski, B.A. Grzybowski at Northwestern University. * [http://www.factmonster.com/ce6/sci/A0832739.html Mercaptan], by ''The Columbia Electronic Encyclopedia'' * [http://www.columbiagaspamd.com/community_outreach/mercaptan.htm What is Mercaptan?] {{Webarchive|url=https://web.archive.org/web/20081220153149/http://www.columbiagaspamd.com/community_outreach/mercaptan.htm |date=2008-12-20 }}, by Columbia Gas of Pennsylvania and Maryland. * [http://chemistry.about.com/od/chemistryfaqs/f/blsmell.htm What Is the Worst Smelling Chemical?] {{Webarchive|url=https://web.archive.org/web/20110606080415/http://chemistry.about.com/od/chemistryfaqs/f/blsmell.htm |date=2011-06-06 }}, by About Chemistry.

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Category:Thiols Category:Functional groups Category:Organosulfur compounds