Editing Thiol

{{short description|Any organic compound having a sulfanyl group (–SH)}}
[[File:Mercapto Group General Formulae.png|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.com|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 [[Alcohol (chemistry)|alcohol]]s (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), 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''' ({{IPAc-en|m|ər|ˈ|k|æ|p|t|æ|n}})<ref>''[[Dictionary.com|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 (element)|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 ((C<sub>2</sub>H<sub>5</sub>)HSO<sub>4</sub>) 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>

== Structure and bonding ==
Thiols having the structure R−SH, 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 length]]s—typically around 180 [[Picometre|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 interaction]]s 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 energy|bond dissociation energies]] (BDE). For CH<sub>3</sub>S−H, the BDE is {{cvt|366|kJ/mol|kcal/mol}}, while for CH<sub>3</sub>O−H, the BDE is {{cvt|440|kJ/mol|kcal/mol}}.<ref>{{RubberBible87th}}</ref>

An S−H bond is moderately [[Chemical polarity|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 [[Bond dipole moment|dipole moment]] relative to their corresponding alcohols.

==Nomenclature==
There are several ways to name the alkylthiols:
* The suffix ''-thiol'' is added to the name of the alkane. This method is nearly identical to [[Alcohol (chemistry)|naming an alcohol]] and is used by the [[IUPAC]], e.g. CH<sub>3</sub>SH would be ''[[methanethiol]]''.
* The word ''mercaptan'' replaces ''alcohol'' in the name of the equivalent alcohol compound. Example: CH<sub>3</sub>SH would be methyl mercaptan, just as CH<sub>3</sub>OH is called methyl alcohol.
* The term ''sulfhydryl-'' or ''mercapto-'' is used as a prefix, e.g. [[mercaptopurine]].

==Physical properties==
===Odor===
Many thiols have strong [[odor]]s resembling that of [[garlic]]. The odors of thiols, particularly those of low molecular weight, are often strong and repulsive. The spray of [[skunk]]s 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|s2cid=9451251}}</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 |s2cid=19217201}}</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. |date=July 2004 |title=3-Methyl-3-sulfanylhexan-1-ol as a Major Descriptor for the Human Axilla-Sweat Odour Profile |url=https://onlinelibrary.wiley.com/doi/10.1002/cbdv.200490077 |journal=Chemistry & Biodiversity |language=en |volume=1 |issue=7 |pages=1022–1035 |doi=10.1002/cbdv.200490077 |pmid=17191896 |issn=1612-1872}}</ref> (Methylthio)methanethiol (MeSCH<sub>2</sub>SH; 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 [[Mouse|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|s2cid=162036}}</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 [[Tert-Butylthiol|''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 fault]]s caused by an unintended reaction between sulfur and [[yeast (wine)|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 [[terpene|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 explosion]] in [[New 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 [[Tert-Butylthiol|''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 [[Catalysis|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 bond]]ing, both with water molecules and among themselves. Hence, they have lower [[boiling point]]s and are less [[soluble]] in water and other [[solvent#Polarity, solubility, and miscibility|polar solvents]] than alcohols of similar molecular weight. For this reason also, thiols and their corresponding sulfide functional group [[structural isomer|isomers]] have similar solubility characteristics and boiling points, whereas the same is not true of alcohols and their corresponding isomeric ethers.

===Bonding===
The S−H bond in thiols is weak compared to the O−H bond in alcohols.  For CH<sub>3</sub>X−H, the bond enthalpies are {{val|365.07|2.1|u=kcal/mol}} for X = S and {{val|440.2|3.0|u=kcal/mol}} for X = O.<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<sup>•</sup>, where R = alkyl or aryl.

==Characterization==
Volatile thiols are easily and almost unerringly detected by their distinctive odor. Sulfur-specific analyzers for [[gas chromatograph]]s are useful. Spectroscopic indicators are the [[Heavy water|D<sub>2</sub>O]]-exchangeable S'''H''' signal in the [[Proton NMR|<sup>1</sup>H NMR spectrum]] ([[sulfur-33|<sup>33</sup>S]] 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''<sub>SH</sub> band appears near 2400&nbsp;cm<sup>−1</sup> 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]]:
:CH<sub>3</sub>OH + H<sub>2</sub>S → CH<sub>3</sub>SH + H<sub>2</sub>O
Such reactions are conducted in the presence of acidic catalysts. The other principal route to thiols involves the addition of hydrogen sulfide to [[Alkene|alkenes]]. Such reactions are usually conducted in the presence of an acid catalyst or UV light. [[Halogen|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 [[halogenoalkane|haloalkane]] with sodium hydrosulfide is ''in''efficient 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:<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>

: CH<sub>3</sub>CH<sub>2</sub>Br + SC(NH<sub>2</sub>)<sub>2</sub> → [CH<sub>3</sub>CH<sub>2</sub>SC(NH<sub>2</sub>)<sub>2</sub>]Br
: [CH<sub>3</sub>CH<sub>2</sub>SC(NH<sub>2</sub>)<sub>2</sub>]Br + NaOH → CH<sub>3</sub>CH<sub>2</sub>SH + OC(NH<sub>2</sub>)<sub>2</sub> + 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 [[Thioketal|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]]:
:ClCH<sub>2</sub>CO<sub>2</sub>H + Na<sub>2</sub>S<sub>2</sub>O<sub>3</sub> → Na[O<sub>3</sub>S<sub>2</sub>CH<sub>2</sub>CO<sub>2</sub>H] + NaCl

:Na[O<sub>3</sub>S<sub>2</sub>CH<sub>2</sub>CO<sub>2</sub>H] + H<sub>2</sub>O → HSCH<sub>2</sub>CO<sub>2</sub>H + NaHSO<sub>4</sub>

[[Organolithium compound]]s and [[Grignard reagent]]s 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<sup>−</sup>):<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|s2cid=196805424 }}</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<sup>−</sup> → ArSH + N<sub>2</sub>

==Reactions==
Akin to the chemistry of alcohols, thiols form [[sulfide]]s, [[thioacetal]]s, and [[thioester]]s, which are analogous to [[ethers]], [[acetal]]s, 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 [[alkoxide]]s.

===''S''-Alkylation===
Thiols, or more specific their conjugate bases, are readily alkylated to give sulfides:
:RSH + R′Br + B → RSR′ + [HB]Br{{pad|3em}} (B = base)

===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 [[pKa|p''K''<sub>a</sub>]] of 10.5 vs 15 for butanol. Thiophenol has a [[pKa|p''K''<sub>a</sub>]] of 6, versus 10 for [[phenol]]. A highly acidic thiol is [[pentafluorothiophenol]] (C<sub>6</sub>F<sub>5</sub>SH) with a p''K''<sub>a</sub> of 2.68. Thus, thiolates can be obtained from thiols by treatment with alkali metal hydroxides. 
[[File:Thiophenolat Synthesis.png|thumb|right|upright=1.8|Synthesis of thiophenolate from thiophenol]]

===Redox===
Thiols, especially in the presence of base, are readily [[Redox|oxidized]] by reagents such as [[bromine]] and [[iodine]] to give an organic [[disulfide]] (R−S−S−R).
: 2&nbsp;R−SH + Br<sub>2</sub> → R−S−S−R + 2&nbsp;HBr
Oxidation by more powerful reagents such as [[sodium hypochlorite]] or [[hydrogen peroxide]] can also yield [[sulfonic acid]]s (RSO<sub>3</sub>H).
: R−SH + 3&nbsp;H<sub>2</sub>O<sub>2</sub> → RSO<sub>3</sub>H + 3&nbsp;H<sub>2</sub>O
Oxidation can also be effected by oxygen in the presence of catalysts:<ref>{{cite journal |url=http://en.ahmadullins.com/index.php/articles/18-heterogeneouscatalyticdemercaptization |title=Heterogeneous catalytic demercaptization of light hydrocarbon feedstock |first1=A. G. |last1=Akhmadullina |first2=B. V. |last2=Kizhaev |first3=G. M. |last3=Nurgalieva |first4=I. K. |last4=Khrushcheva |first5=A. S. |last5=Shabaeva |display-authors=etal |journal=Chemistry and Technology of Fuels and Oils |date=1993 |volume=29 |issue=3 |pages=108–109 |doi=10.1007/bf00728009 |bibcode=1993CTFO...29..108A |s2cid=97292021 |url-status=live |archive-url=https://web.archive.org/web/20110815162747/http://en.ahmadullins.com/index.php/articles/18-heterogeneouscatalyticdemercaptization |archive-date=2011-08-15 }}</ref>
: 2&nbsp;R–SH + {{1/2}}&nbsp;O<sub>2</sub> → RS−SR + H<sub>2</sub>O

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 complex]]es. The term ''mercaptan'' is derived from the [[Latin]] ''mercurium captans'' (capturing mercury)<ref name="ReferenceA"/> because the thiolate group bonds so strongly with [[mercury (element)|mercury]] compounds. According to [[HSAB theory|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.

===Thioxanthates===
Thiolates react with [[carbon disulfide]] to give [[thioxanthate]] ({{chem|RSCS|2|-}}).

== Thiyl radicals ==
{{main|Thiyl radical}}[[Free radical]]s derived from mercaptans, called [[thiyl radical]]s, are commonly invoked to explain reactions in [[organic chemistry]] and [[biochemistry]]. They have the formula RS<sup>•</sup> 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 (chemistry)|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 }}</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 [[chemical equilibrium|equilibria]]. The formation of [[carbon]]-centred radicals could lead to protein damage via the formation of [[Carbon|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 [[scavenger (chemistry)|scavenger]]s of [[free radical]]s.<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|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 bond]]s with the enzyme's [[substrate (biochemistry)|substrate]] as well, contributing to covalent [[catalysis|catalytic activity]] in [[catalytic triad]]s. Active site cysteine residues are the functional unit in [[cysteine protease]] [[catalytic triad]]s. Cysteine residues may also react with heavy metal ions (Zn<sup>2+</sup>, Cd<sup>2+</sup>, Pb<sup>2+</sup>, Hg<sup>2+</sup>, Ag<sup>+</sup>) 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 [[cofactor (biochemistry)|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.
The [[methane biosynthesis|biosynthesis of methane]], 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)
*[[Sodium aurothiolate]] (antiarthritic)<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>

===In skunks===
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.<ref>{{cite web|url=https://theowlstrust.org/owl-hub/owl-education-programmes/understanding-owls/|title=Understanding Owls – The Owls Trust|website=theowlstrust.org|access-date=3 May 2018|url-status=live|archive-url=https://web.archive.org/web/20180205131745/https://theowlstrust.org/owl-hub/owl-education-programmes/understanding-owls/|archive-date=5 February 2018}}</ref>

==Examples of thiols==
{{colbegin|colwidth=20em}}
* [[Methanethiol]] – CH<sub>3</sub>SH [methyl mercaptan]
* [[Ethanethiol]] – C<sub>2</sub>H<sub>5</sub>SH [ethyl mercaptan]
* [[Propanethiol|1-Propanethiol]] – C<sub>3</sub>H<sub>7</sub>SH [''n''-propyl mercaptan]
* [[2-Propanethiol]] – CH<sub>3</sub>CH(SH)CH<sub>3</sub> [2C3 mercaptan]
* [[Allyl mercaptan]]{{snd}} CH<sub>2</sub>=CHCH<sub>2</sub>SH [2-propenethiol]
* [[Butanethiol]] – C<sub>4</sub>H<sub>9</sub>SH [''n''-butyl mercaptan]
* [[tert-Butyl mercaptan|''tert''-Butyl mercaptan]] – (CH<sub>3</sub>)<sub>3</sub>CSH [''t''-butyl mercaptan]
* [[Pentanethiols]] – C<sub>5</sub>H<sub>11</sub>SH [pentyl mercaptan]
* [[Thiophenol]] – C<sub>6</sub>H<sub>5</sub>SH
* [[Dimercaptosuccinic acid]]
* [[Thioacetic acid]]
* [[Coenzyme A]]
* [[Glutathione]]
* [[Metallothionein]]
* [[Cysteine]]
* [[2-Mercaptoethanol]]
* [[Dithiothreitol]]/[[dithioerythritol]] (an [[epimer]]ic pair)
* [[2-Mercaptoindole]]
* [[Grapefruit mercaptan]]
* [[Furan-2-ylmethanethiol]]
* [[3-Mercaptopropane-1,2-diol]]
* [[3-Mercapto-1-propanesulfonic acid]]
* [[1-Hexadecanethiol]]
* [[Pentachlorobenzenethiol]] 
{{colend}}

==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?], 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.

{{Functional Groups}}
{{Authority control}}

[[Category:Thiols| ]]
[[Category:Functional groups]]
[[Category:Organosulfur compounds]]