In
organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J.; ...
, a thiol (; ), or thiol derivative, is any
organosulfur compound of the form , where R represents an
alkyl
In organic chemistry, an alkyl group is an alkane missing one hydrogen.
The term ''alkyl'' is intentionally unspecific to include many possible substitutions.
An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloalk ...
or other organic
substituent
A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as ''side ...
. The
functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...
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
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...
in the
hydroxyl
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
() group of an alcohol), and the word is a blend of "''thio-''" with "alcohol".
Many thiols have strong odors resembling that of
garlic
Garlic (''Allium sativum'') is a species of bulbous flowering plant in the genus ''Allium''. Its close relatives include the onion, shallot, leek, chive, Allium fistulosum, Welsh onion and Allium chinense, Chinese onion. It is native to South A ...
or rotten eggs. Thiols are used as
odorants
An aroma compound, also known as an odorant, aroma, fragrance or flavoring, is a chemical compound that has a smell or odor. For an individual chemical or class of chemical compounds to impart a smell or fragrance, it must be sufficiently vo ...
to assist in the detection of
natural gas
Natural gas (also called fossil gas or simply gas) is a naturally occurring mixture of gaseous hydrocarbons consisting primarily of methane in addition to various smaller amounts of other higher alkanes. Low levels of trace gases like carbo ...
(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 () or mercapto compounds,
a term introduced in 1832 by
William Christopher Zeise
William Christopher Zeise (15 October 1789 – 12 November 1847) was a Danish organic chemist. He is best known for synthesising one of the first organometallic compounds, named Zeise's salt in his honour. He also performed pioneering studi ...
and is derived from the
Latin
Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
('capturing mercury')
[''Oxford American Dictionaries'' (]Mac OS X Leopard
Mac OS X Leopard (version 10.5) is the sixth software versioning, major release of macOS, Apple Inc., Apple's desktop and server operating system for Macintosh computers. Leopard was released on October 26, 2007 as the successor of Mac OS X Tig ...
). because the thiolate group () bonds very strongly with
mercury compounds.
Structure and bonding
Thiols of the structure R−SH are referred to as Alkanethiols or Alkyl thiols, in which an
alkyl
In organic chemistry, an alkyl group is an alkane missing one hydrogen.
The term ''alkyl'' is intentionally unspecific to include many possible substitutions.
An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloalk ...
group (R) is attached to a
sulfhydryl group (SH). Thiols and alcohols have similar connectivity. Because sulfur atoms are larger than oxygen atoms, the C−S
bond lengths – typically around 180
picometres
The picometre (international spelling as used by the International Bureau of Weights and Measures; SI symbol: pm) or picometer (American spelling) is a unit of length in the International System of Units (SI), equal to , or one trillionth of ...
in length – are about 40 picometers longer than a typical C−O bond. The C−S−H angles approach 90° whereas the angle for the C−O−H group is more obtuse. In the solid or liquids, the
hydrogen-bonding
In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a l ...
between individual thiol groups is weak, the main cohesive force being
Van der Waals interaction
In molecular physics, the van der Waals force is a distance-dependent interaction between atoms or molecules. Unlike ionic or covalent bonds, these attractions do not result from a chemical electronic bond; they are comparatively weak and the ...
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
The bond-dissociation energy (BDE, ''D''0, or ''DH°'') is one measure of the strength of a chemical bond . It can be defined as the standard enthalpy change when is cleaved by homolysis to give fragments A and B, which are usually radical ...
(BDE). For CH
3S−H, the BDE is , while for CH
3O−H, the BDE is .
Due to the small difference in the
electronegativity
Electronegativity, symbolized as , is the tendency for an atom of a given chemical element to attract shared electrons (or electron density) when forming a chemical bond. An atom's electronegativity is affected by both its atomic number and the d ...
of sulfur and hydrogen, an S−H bond is moderately
polar
Polar may refer to:
Geography
Polar may refer to:
* Geographical pole, either of two fixed points on the surface of a rotating body or planet, at 90 degrees from the equator, based on the axis around which a body rotates
* Polar climate, the c ...
. In contrast, O−H bonds in hydroxyl groups are more polar. Thiols have a lower
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
naming an alcohol and is used by the
IUPAC
The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...
, e.g. CH
3SH would be ''
methanethiol
Methanethiol (also known as methyl mercaptan) is an organosulfur compound with the chemical formula . It is a colorless gas with a distinctive putrid smell. It is a natural substance found in the blood, brain and feces of animals (including hum ...
''.
* The word ''mercaptan'' replaces ''alcohol'' in the name of the equivalent alcohol compound. Example: CH
3SH would be methyl mercaptan, just as CH
3OH is called methyl alcohol.
* The term ''sulfhydryl-'' or ''mercapto-'' is used as a prefix, e.g.
mercaptopurine
Mercaptopurine (6-MP), sold under the brand name Purinethol among others, is a medication used for cancer and autoimmune diseases. Specifically it is used to treat acute lymphocytic leukemia (ALL), acute promyelocytic leukemia (APL), Crohn's dis ...
.
Physical properties
Odor
Many thiols have strong
odor
An odor (American English) or odour (English in the Commonwealth of Nations, Commonwealth English; American and British English spelling differences#-our, -or, see spelling differences) is caused by one or more volatilized chemical compounds ...
s resembling that of
garlic
Garlic (''Allium sativum'') is a species of bulbous flowering plant in the genus ''Allium''. Its close relatives include the onion, shallot, leek, chive, Allium fistulosum, Welsh onion and Allium chinense, Chinese onion. It is native to South A ...
. The odors of thiols, particularly those of low molecular weight, are often strong and repulsive. The spray of
skunk
Skunks are mammals in the family Mephitidae. They are known for their ability to spray a liquid with a strong, unpleasant scent from their anal glands. Different species of skunk vary in appearance from black-and-white to brown, cream or ginge ...
s consists mainly of low-molecular-weight thiols and derivatives. These compounds are detectable by the human nose at concentrations of only 10 parts per billion. Human
sweat
Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals.
Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distrib ...
contains (''R'')/(''S'')-3-methyl-3-mercapto-1-ol (MSH), detectable at 2 parts per billion and having a fruity,
onion
An onion (''Allium cepa'' L., from Latin ''cepa'' meaning "onion"), also known as the bulb onion or common onion, is a vegetable that is the most widely cultivated species of the genus ''Allium''. The shallot is a botanical variety of the onion ...
-like odor. (Methylthio)methanethiol (MeSCH
2SH; MTMT) is a strong-smelling volatile thiol, also detectable at parts per billion levels, found in male
mouse
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
urine.
Lawrence C. Katz and co-workers showed that MTMT functioned as a
semiochemical
A semiochemical, from the Greek wiktionary:σημεῖον, σημεῖον (''semeion''), meaning "signal", is a chemical substance or mixture released by an organism that affects the behaviors of other individuals. Semiochemical communication c ...
, activating certain mouse olfactory sensory neurons, attracting female
mice
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
.
Copper
Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
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. A human olfactory receptor,
OR2T11
Olfactory receptor 2T11 is a protein that in humans is encoded by the ''OR2T11'' gene.
Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor ...
, has been identified which, in the presence of copper, is highly responsive to the gas odorants (see below)
ethanethiol
Ethanethiol, commonly known as ethyl mercaptan, is an organosulfur compound with the formula CH3CH2SH. is a colorless liquid with a distinct odor. Abbreviated EtSH, it consists of an ethyl group (Et), CH3CH2, attached to a thiol group, SH. Its st ...
and
''t''-butyl mercaptan as well as other low molecular weight thiols, including
allyl mercaptan
Allyl mercaptan (AM) is a small molecule allyl derivative and an organosulfur compound derived from garlic and a few other genus ''Allium
''Allium'' is a genus of monocotyledonous flowering plants that includes hundreds of species, includi ...
found in human
garlic
Garlic (''Allium sativum'') is a species of bulbous flowering plant in the genus ''Allium''. Its close relatives include the onion, shallot, leek, chive, Allium fistulosum, Welsh onion and Allium chinense, Chinese onion. It is native to South A ...
breath, and the strong-smelling cyclic sulfide
thietane
Thietane is a heterocyclic compound containing a saturated four-membered ring with three carbon atoms and one sulfur atom.
Thietane, and its derivative 2-propylthietane, are strong-smelling mouse alarm pheromones and predator scent analogues. Bo ...
.
Thiols are also responsible for a class of
wine fault
A wine fault or defect is an unpleasant characteristic of a wine often resulting from poor winemaking practices or storage conditions, and leading to wine spoilage. Many of the compounds that cause wine faults are already naturally present in wine ...
s caused by an unintended reaction between sulfur and
yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
and the "skunky" odor of beer that has been exposed to ultraviolet light.
Not all thiols have unpleasant odors. For example,
furan-2-ylmethanethiol
Furan-2-ylmethanethiol (2-Furanmethanethiol) is an organic compound containing a furan substituted with a sulfanylmethyl group. It is a clear colourless liquid when pure, but it becomes yellow coloured upon prolonged standing. It possesses a stro ...
contributes to the aroma of roasted
coffee
Coffee is a drink prepared from roasted coffee beans. Darkly colored, bitter, and slightly acidic, coffee has a stimulant, stimulating effect on humans, primarily due to its caffeine content. It is the most popular hot drink in the world.
S ...
, whereas
grapefruit mercaptan
Grapefruit mercaptan is the common name for a natural organic compound found in grapefruit. It is a monoterpenoid that contains a thiol (also known as a mercaptan) functional group. Structurally a hydroxy group of terpineol is replaced by the th ...
, a
monoterpenoid
Monoterpenes are a class of terpenes that consist of two isoprene units and have the molecular formula C10H16. Monoterpenes may be linear (acyclic) or contain rings (monocyclic and bicyclic). Modified terpenes, such as those containing oxygen funct ...
thiol, is responsible for the characteristic scent of
grapefruit
The grapefruit (''Citrus'' × ''paradisi'') is a subtropical citrus tree known for its relatively large, sour to semi-sweet, somewhat bitter fruit. The interior flesh is segmented and varies in color from pale yellow to dark pink.
Grapefruit is ...
. 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
Natural gas (also called fossil gas or simply gas) is a naturally occurring mixture of gaseous hydrocarbons consisting primarily of methane in addition to various smaller amounts of other higher alkanes. Low levels of trace gases like carbo ...
distributors were required to add thiols, originally
ethanethiol
Ethanethiol, commonly known as ethyl mercaptan, is an organosulfur compound with the formula CH3CH2SH. is a colorless liquid with a distinct odor. Abbreviated EtSH, it consists of an ethyl group (Et), CH3CH2, attached to a thiol group, SH. Its st ...
, to
natural gas
Natural gas (also called fossil gas or simply gas) is a naturally occurring mixture of gaseous hydrocarbons consisting primarily of methane in addition to various smaller amounts of other higher alkanes. Low levels of trace gases like carbo ...
(which is naturally odorless) after the deadly
New London School explosion
The New London School explosion occurred on March 18, 1937, when a natural gas leak caused an explosion and destroyed the London School in New London, Texas, United States. The disaster killed more than 300 students and teachers. , the event i ...
in
New London, Texas
New London is a city in Rusk County, Texas, United States. The population was 958 at the 2020 census.
New London was originally known as just "London". Because Kimble County Texas had already established a US Post Office station named London, ...
, in 1937. Many gas distributors were odorizing gas prior to this event. Most gas odorants utilized currently contain mixtures of mercaptans and sulfides, with
''t''-butyl mercaptan as the main odor constituent in natural gas and
ethanethiol
Ethanethiol, commonly known as ethyl mercaptan, is an organosulfur compound with the formula CH3CH2SH. is a colorless liquid with a distinct odor. Abbreviated EtSH, it consists of an ethyl group (Et), CH3CH2, attached to a thiol group, SH. Its st ...
in
liquefied petroleum gas
Liquefied petroleum gas (LPG or LP gas) is a fuel gas which contains a flammable mixture of hydrocarbon gases, specifically propane, propylene, butylene, isobutane and n-butane.
LPG is used as a fuel gas in heating appliances, cooking e ...
(LPG, propane).
In situations where thiols are used in commercial industry, such as liquid petroleum gas tankers and bulk handling systems, an oxidizing
catalyst
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
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
In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...
ing, both with water molecules and among themselves. Hence, they have lower
boiling point
The boiling point of a substance is the temperature at which the vapor pressure of a liquid equals the pressure surrounding the liquid and the liquid changes into a vapor.
The boiling point of a liquid varies depending upon the surrounding envir ...
s and are less
soluble
In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution.
The extent of the solubil ...
in water and other
polar solvents than alcohols of similar molecular weight. For this reason also, thiols and their corresponding sulfide functional group
isomers
In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of 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
3X−H, the bond enthalpies are for X = S and for X = O. Hydrogen-atom abstraction from a thiol gives a
thiyl radical In chemistry, a thiyl radical has the formula RS, sometimes written RS• to emphasize that they are free radicals. R is typically an alkyl or aryl substituent. Because S–H bonds are about 20% weaker than C–H bonds, thiyl radicals are relativ ...
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 chromatograph
Gas chromatography (GC) is a common type of chromatography used in analytical chemistry for separating and analyzing compounds that can be vaporized without decomposition. Typical uses of GC include testing the purity of a particular substance, ...
s are useful. Spectroscopic indicators are the
D2O-exchangeable SH signal in the
1H NMR spectrum (
33S is
NMR
Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with ...
-active but signals for divalent sulfur are very broad and of little utility). The ''ν''
SH band appears near 2400 cm
−1 in the
IR spectrum.
[ In the nitroprusside reaction, free thiol groups react with ]sodium nitroprusside
Sodium nitroprusside (SNP), sold under the brand name Nitropress among others, is a medication used to lower blood pressure. This may be done if the blood pressure is very high and resulting in symptoms, in certain types of heart failure, and d ...
and ammonium hydroxide
Ammonia solution, also known as ammonia water, ammonium hydroxide, ammoniacal liquor, ammonia liquor, aqua ammonia, aqueous ammonia, or (inaccurately) ammonia, is a solution of ammonia in water. It can be denoted by the symbols NH3(aq). Although ...
to give a red colour.
Preparation
In industry, methanethiol is prepared by the reaction of hydrogen sulfide
Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The unde ...
with methanol
Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is a ...
. This method is employed for the industrial synthesis of methanethiol
Methanethiol (also known as methyl mercaptan) is an organosulfur compound with the chemical formula . It is a colorless gas with a distinctive putrid smell. It is a natural substance found in the blood, brain and feces of animals (including hum ...
:
: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
In organic chemistry, an alkene is a hydrocarbon containing a carbon–carbon double bond.
Alkene is often used as synonym of olefin, that is, any hydrocarbon containing one or more double bonds.H. Stephen Stoker (2015): General, Organic, an ...
. 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 utilized.
Another method entails the alkylation of sodium hydrosulfide
Sodium hydrosulfide is the chemical compound with the formula NaHS. This compound is the product of the half-neutralization of hydrogen sulfide () with sodium hydroxide (NaOH). NaSH and sodium sulfide are used industrially, often for similar purpos ...
.
: RX + NaSH → RSH + NaX(X = Cl, Br, I)
This method is used for the production of thioglycolic acid
Thioglycolic acid (TGA) is the organic compound HSCH2CO2H. TGA is often called mercaptoacetic acid (MAA). It contains both a thiol ( mercaptan) and carboxylic acid functional groups. It is a colorless liquid with a strongly unpleasant odor. TGA i ...
from chloroacetic acid
Chloroacetic acid, industrially known as monochloroacetic acid (MCA), is the organochlorine compound with the formula ClCH2CO2H. This carboxylic acid is a useful building block in organic synthesis. It is a colorless solid. Related compounds a ...
.
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. Instead, alkyl halides are converted to thiols via an ''S''-alkylation of thiourea
Thiourea () is an organosulfur compound with the formula and the structure . It is structurally similar to urea (), except that the oxygen atom is replaced by a sulfur atom (as implied by the ''thio-'' prefix); however, the properties of urea a ...
. This multistep, one-pot process proceeds via the intermediacy of the isothiouronium salt, which is hydrolyzed in a separate step:
: CH3CH2Br + SC(NH2)2 → 3CH2SC(NH2)2">H3CH2SC(NH2)2r
: 3CH2SC(NH2)2">H3CH2SC(NH2)2r + 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. A related two-step process involves alkylation of thiosulfate to give the thiosulfonate ("Bunte salt
In organosulfur chemistry, a Bunte salt is an archaic name for salts with the formula RSSO3–Na+. They are also called S-alkylthiosulfates or S-arylthiosulfates. These compounds are typically derived from alkylation on the pendant sulfur of sodi ...
"), followed by hydrolysis. The method is illustrated by one synthesis of thioglycolic acid
Thioglycolic acid (TGA) is the organic compound HSCH2CO2H. TGA is often called mercaptoacetic acid (MAA). It contains both a thiol ( mercaptan) and carboxylic acid functional groups. It is a colorless liquid with a strongly unpleasant odor. TGA i ...
:
:ClCH2CO2H + Na2S2O3 → Na 3S2CH2CO2H">3S2CH2CO2H+ NaCl
:Na 3S2CH2CO2H">3S2CH2CO2H+ H2O → HSCH2CO2H + NaHSO4
Organolithium compounds and Grignard reagents react with sulfur to give the thiolates, which are readily hydrolyzed:
:RLi + S → RSLi
:RSLi + HCl → RSH + LiCl
Phenols can be converted to the thiophenols via rearrangement of their ''O''-aryl dialkylthiocarbamates.
Thiols are prepared by reductive dealkylation of sulfides, especially benzyl derivatives and thioacetals.
Thiophenols are produced by ''S''-arylation or the replacement of diazonium leaving group with sulfhydryl anion (SH−):
: + SH− → ArSH + N2
Reactions
Akin to the chemistry of alcohols, thiols form sulfide
Sulfide (British English also sulphide) is an inorganic anion of sulfur with the chemical formula S2− or a compound containing one or more S2− ions. Solutions of sulfide salts are corrosive. ''Sulfide'' also refers to chemical compounds lar ...
s, thioacetal
In organosulfur chemistry, thioacetals are the sulfur (''thio-'') analogues of acetals (). There are two classes: the less-common monothioacetals, with the formula , and the dithioacetals, with the formula (symmetric dithioacetals) or (asym ...
s, and thioester
In organic chemistry, thioesters are organosulfur compounds with the functional group . They are analogous to carboxylate esters () with the sulfur in the thioester playing the role of the linking oxygen in the carboxylate ester, as implied by t ...
s, which are analogous to ethers
In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be c ...
, acetal
In organic chemistry, an acetal is a functional group with the connectivity . Here, the R groups can be organic fragments (a carbon atom, with arbitrary other atoms attached to that) or hydrogen, while the R' groups must be organic fragments n ...
s, and esters
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides are ...
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.
''S''-Alkylation
Thiols, or more specific their conjugate bases, are readily alkylated to give sulfides:
:RSH + R′Br + B → RSR′ + Br (B = base)
Acidity
Thiols are easily deprotonated. 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
Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it req ...
. A highly acidic thiol is pentafluorothiophenol
Pentafluorothiophenol is an organosulfur compound with the formula C6F5SH. It is a colorless volatile liquid. The compound is prepared by the reaction of sodium hydrosulfide and hexafluorobenzene. With a pKa of 2.68, it is one of the most acid ...
(C6F5SH) with a p''K''a of 2.68. Thus, thiolates can be obtained from thiols by treatment with alkali metal hydroxides.
Redox
Thiols, especially in the presence of base, are readily oxidized
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...
by reagents such as bromine
Bromine is a chemical element with the symbol Br and atomic number 35. It is the third-lightest element in group 17 of the periodic table (halogens) and is a volatile red-brown liquid at room temperature that evaporates readily to form a simila ...
and iodine
Iodine is a chemical element with the symbol I and atomic number 53. The heaviest of the stable halogens, it exists as a semi-lustrous, non-metallic solid at standard conditions that melts to form a deep violet liquid at , and boils to a vi ...
to give an organic disulfide
In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
(R−S−S−R).
: 2 R−SH + Br2 → R−S−S−R + 2 HBr
Oxidation by more powerful reagents such as sodium hypochlorite
Sodium hypochlorite (commonly known in a dilute solution as bleach) is an Inorganic chemistry, inorganic chemical compound with the chemical formula, formula NaOCl (or NaClO), comprising a sodium cation () and a hypochlorite anion (or ). It may ...
or hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3%†...
can also yield sulfonic acids (RSO3H).
: R−SH + 3 H2O2 → RSO3H + 3 H2O
Oxidation can also be effected by oxygen in the presence of catalysts:
: 2 R–SH + 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
Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
''mercurium captans'' (capturing mercury) 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.
Thioxanthates
Thiolates react with carbon disulfide
Carbon disulfide (also spelled as carbon disulphide) is a neurotoxic, colorless, volatile liquid with the formula and structure . The compound is used frequently as a building block in organic chemistry as well as an industrial and chemical n ...
to give thioxanthate In chemistry, a thioxanthate is an organosulfur compound with the formula RSCS2X. When X is an alkali metal, the thioxanthate is a salt. When X is a transition metal, the thioxanthate is a ligand, and when X is an organic group, the compounds are ...
().
Thiyl radicals
Free radical
A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing.
Ageing
Ailments of unknown cause
Biogerontology
Biological processes
Causes of death
Cellular processes
Gerontology
Life extension
Metabo ...
s derived from mercaptans, called thiyl radical In chemistry, a thiyl radical has the formula RS, sometimes written RS• to emphasize that they are free radicals. R is typically an alkyl or aryl substituent. Because S–H bonds are about 20% weaker than C–H bonds, thiyl radicals are relativ ...
s, are commonly invoked to explain reactions in organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J.; ...
and biochemistry
Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
. They have the formula RS• where R is an organic substituent such as alkyl
In organic chemistry, an alkyl group is an alkane missing one hydrogen.
The term ''alkyl'' is intentionally unspecific to include many possible substitutions.
An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloalk ...
or aryl
In organic chemistry, an aryl is any functional group or substituent derived from an aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar" is used as ...
. 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. 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). Thiyl intermediates also are produced by the oxidation of glutathione
Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pe ...
, an antioxidant in biology. Thiyl radicals (sulfur-centred) can transform to carbon-centred radicals via hydrogen
Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic, an ...
atom exchange equilibria. The formation of carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent
In chemistry, the valence (US spelling) or valency (British spelling) of an element is the measure of its combining capacity with o ...
-centred radicals could lead to protein damage via the formation of C−C bonds or backbone fragmentation.
Because of the weakness of the S−H bond, thiols can functioning as scavenger
Scavengers are animals that consume dead organisms that have died from causes other than predation or have been killed by other predators. While scavenging generally refers to carnivores feeding on carrion, it is also a herbivorous feeding b ...
s of free radical
A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing.
Ageing
Ailments of unknown cause
Biogerontology
Biological processes
Causes of death
Cellular processes
Gerontology
Life extension
Metabo ...
s.
Biological importance
Cysteine and cystine
As the functional group of the amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
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
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
folding, an oxidation reaction
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
can generate a cystine
Cystine is the oxidized derivative of the amino acid cysteine and has the formula (SCH2CH(NH2)CO2H)2. It is a white solid that is poorly soluble in water. As a residue in proteins, cystine serves two functions: a site of redox reactions and a mec ...
unit with a disulfide bond
In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
(−S−S−). Disulfide bonds can contribute to a protein's tertiary structure
Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may int ...
if the cysteines are part of the same peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
A ...
chain, or contribute to the quaternary structure
Protein quaternary structure is the fourth (and highest) classification level of protein structure. Protein quaternary structure refers to the structure of proteins which are themselves composed of two or more smaller protein chains (also refe ...
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
Hair straightening is a hair styling technique used since the 1890s involving the flattening and straightening of hair in order to give it a smooth, streamlined, and sleek appearance. It became very popular during the 1950s among black males and ...
technologies.
Sulfhydryl groups in the active site
In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...
of an enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
can form noncovalent bond
In chemistry, a non-covalent interaction differs from a covalent bond in that it does not involve the sharing of electrons, but rather involves more dispersed variations of electromagnetic interactions between molecules or within a molecule. The c ...
s with the enzyme's substrate as well, contributing to covalent catalytic activity in catalytic triad
A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes (e.g. proteases, amidases, esterases, acylases, lip ...
s. Active site cysteine residues are the functional unit in cysteine protease
Cysteine proteases, also known as thiol proteases, are hydrolase enzymes that degrade proteins. These proteases share a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic triad or dyad.
Discovered by Gopal Ch ...
catalytic triad
A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes (e.g. proteases, amidases, esterases, acylases, lip ...
s. 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
A toxic heavy metal is any relatively dense metal or metalloid that is noted for its potential toxicity, especially in environmental contexts. The term has particular application to cadmium, mercury and lead, all of which appear in the World H ...
.
Drugs containing thiol group
6-Mercaptopurine
Mercaptopurine (6-MP), sold under the brand name Purinethol among others, is a medication used for cancer and autoimmune diseases. Specifically it is used to treat acute lymphocytic leukemia (ALL), acute promyelocytic leukemia (APL), Crohn's d ...
(anticancer)
Captopril
Captopril, sold under the brand name Capoten among others, is an ACE inhibitor, angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first oral ACE inh ...
(antihypertensive)
D-penicillamine
Penicillamine, sold under the brand name of Cuprimine among others, is a medication primarily used for the treatment of Wilson's disease. It is also used for people with kidney stones who have cystinuria, high urine cystine levels, rheumatoid ar ...
(antiarthritic)
Sodium aurothiolate
Sodium is a chemical element with the Symbol (chemistry), symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the ...
(antiarthritic)
Cofactors
Many cofactors
Cofactor may also refer to:
* Cofactor (biochemistry), a substance that needs to be present in addition to an enzyme for a certain reaction to be catalysed
* A domain parameter in elliptic curve cryptography, defined as the ratio between the order ...
(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
Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a subs ...
. The biosynthesis
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecules. ...
of methane
Methane ( , ) is a chemical compound with the chemical formula (one carbon atom bonded to four hydrogen atoms). It is a group-14 hydride, the simplest alkane, and the main constituent of natural gas. The relative abundance of methane on Eart ...
, the principal hydrocarbon
In organic chemistry, a hydrocarbon is an organic compound consisting entirely of hydrogen and carbon. Hydrocarbons are examples of group 14 hydrides. Hydrocarbons are generally colourless and hydrophobic, and their odors are usually weak or ex ...
on Earth, arises from the reaction mediated by coenzyme M
Coenzyme M is a coenzyme required for methyl-transfer reactions in the metabolism of archaeal methanogens, and in the metabolism of other substrates in bacteria. It is also a necessary cofactor in the metabolic pathway of alkene-oxidizing bacteria. ...
, 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.
In skunks
The defensive spray of skunks
Skunks are mammals in the family Mephitidae. They are known for their ability to spray a liquid with a strong, unpleasant scent from their anal glands. Different species of skunk vary in appearance from black-and-white to brown, cream or ging ...
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.
Examples of thiols
* Methanethiol
Methanethiol (also known as methyl mercaptan) is an organosulfur compound with the chemical formula . It is a colorless gas with a distinctive putrid smell. It is a natural substance found in the blood, brain and feces of animals (including hum ...
– CH3SH ethyl mercaptan
Ethanethiol, commonly known as ethyl mercaptan, is an organosulfur compound with the formula CH3CH2SH. is a colorless liquid with a distinct odor. Abbreviated EtSH, it consists of an ethyl group (Et), CH3CH2, attached to a thiol group, SH. Its s ...
* Ethanethiol
Ethanethiol, commonly known as ethyl mercaptan, is an organosulfur compound with the formula CH3CH2SH. is a colorless liquid with a distinct odor. Abbreviated EtSH, it consists of an ethyl group (Et), CH3CH2, attached to a thiol group, SH. Its st ...
– C2H5SH thyl mercaptan* 1-Propanethiol – C3H7SH 'n''-propyl mercaptan* 2-Propanethiol – CH3CH(SH)CH3 C3 mercaptan C3, C-3, C.3, C03, C.III or C-III may refer to:
Life and biology
* C3 carbon fixation in plants
* C3-convertase, an enzyme
* Complement component 3, a protein of the innate immune system
* Apolipoprotein C3, a human very low density lipoprotein ...
* Allyl mercaptan
Allyl mercaptan (AM) is a small molecule allyl derivative and an organosulfur compound derived from garlic and a few other genus ''Allium
''Allium'' is a genus of monocotyledonous flowering plants that includes hundreds of species, includi ...
CH2=CHCH2SH -propenethiol* Butanethiol
1-Butanethiol, also known as butyl mercaptan, is a volatile, clear to yellowish liquid with a fetid (extremely foul-smelling) odor, commonly described as " skunk" odor. In fact, 1-butanethiol is structurally similar to several major constituents ...
– C4H9SH 'n''-butyl mercaptan* ''tert''-Butyl mercaptan – (CH3)3CSH 't''-butyl mercaptan* Pentanethiols – C5H11SH entyl mercaptan* Thiophenol
Thiophenol is an organosulfur compound with the formula C6H5SH, sometimes abbreviated as PhSH. This foul-smelling colorless liquid is the simplest aromatic thiol. The chemical structures of thiophenol and its derivatives are analogous to phen ...
– C6H5SH
* Dimercaptosuccinic acid
Succimer, sold under the brand name Chemet among others, is a medication used to treat lead, mercury, and arsenic poisoning. When radiolabeled with technetium-99m, it is used in a number of types of diagnostic testing. A full course is 19 days ...
* Thioacetic acid
Thioacetic acid is an organosulfur compound with the molecular formula . It is the sulfur analogue of acetic acid (), as implied by the ''thio-'' prefix. It is a yellow liquid with a strong thiol-like odor. It is used in organic synthesis for the ...
* Coenzyme A
Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a subs ...
* Glutathione
Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pe ...
* Metallothionein
Metallothionein (MT) is a family of cysteine-rich, low molecular weight (MW ranging from 500 to 14000 Da) proteins. They are localized to the membrane of the Golgi apparatus. MTs have the capacity to bind both physiological (such as zinc, copp ...
* Cysteine
* 2-Mercaptoethanol
* Dithiothreitol
Dithiothreitol (DTT) is the common name for a small-molecule redox reagent also known as Cleland's reagent, after W. Wallace Cleland. DTT's formula is C4H10O2S2 and the chemical structure of one of its enantiomers in its reduced form is shown o ...
/dithioerythritol
Dithioerythritol (DTE) is a sulfur containing sugar derived from the corresponding 4-carbon monosaccharide erythrose. It is an epimer of dithiothreitol (DTT). The molecular formula for DTE is C4H10O2S2.
Like DTT, DTE makes an excellent reduci ...
(an epimer
In stereochemistry, an epimer is one of a pair of diastereomers. The two epimers have opposite configuration at only one stereogenic center out of at least two. All other stereogenic centers in the molecules are the same in each. Epimerization i ...
ic pair)
* 2-Mercaptoindole
* Grapefruit mercaptan
Grapefruit mercaptan is the common name for a natural organic compound found in grapefruit. It is a monoterpenoid that contains a thiol (also known as a mercaptan) functional group. Structurally a hydroxy group of terpineol is replaced by the th ...
* Furan-2-ylmethanethiol
Furan-2-ylmethanethiol (2-Furanmethanethiol) is an organic compound containing a furan substituted with a sulfanylmethyl group. It is a clear colourless liquid when pure, but it becomes yellow coloured upon prolonged standing. It possesses a stro ...
* 3-Mercaptopropane-1,2-diol
* 3-Mercapto-1-propanesulfonic acid
* 1-Hexadecanethiol
* Pentachlorobenzenethiol
Pentachlorobenzenethiol is a chemical compound from the group of thiols and organochlorine compounds. The chemical formula is .
Synthesis
Pentachlorobenzenethiol can be obtained from hexachlorobenzene.
Properties
Pentachlorobenzenethiol is a com ...
See also
* Doctor sweetening process
* Odorizer
An odorizer is a device that adds an odorant to a gas. The most common type is one that adds a mercaptan liquid into natural gas distribution systems so that leaks can be readily detected. Other types have been used for carbon dioxide fire ex ...
* Persulfide
In chemistry, persulfide refers to the functional group R-S-S-H. Persulfides are intermediates in the biosynthesis of iron-sulfur proteins and are invoked as precursors to hydrogen sulfide, a signaling molecule.
Nomenclature
The nomenclature use ...
* Saville reaction
The Saville reaction is a chemical reaction in which mercury replaces a nitrosyl from a thiol group.
It is used as a method of replacing the nitrosyl from the modified cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic ...
* Thiol-disulfide exchange
In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
References
External links
Mercaptans (or Thiols)
at ''The Periodic Table of Videos
''Periodic Videos'' (also known as ''The Periodic Table of Videos'') is a video project and YouTube channel on chemistry. It consists of a series of videos about chemical elements and the periodic table, with additional videos on other topics i ...
'' (University of Nottingham)
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.
by ''The Columbia Electronic Encyclopedia
The ''Columbia Encyclopedia'' is a one-volume encyclopedia produced by Columbia University Press and, in the last edition, sold by the Gale Group. First published in 1935, and continuing its relationship with Columbia University, the encyclopedi ...
''
What is Mercaptan?
by Columbia Gas of Pennsylvania and Maryland.
by About Chemistry.
{{Authority control
Functional groups
Organosulfur compounds