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 sulfoxide, also called a sulphoxide, is an
organosulfur compound containing a sulfinyl ()
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 r ...
attached to two
carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon ma ...
atoms. It is a
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 cli ...
functional group. Sulfoxides are oxidized
derivatives of
sulfides
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 la ...
. Examples of important sulfoxides are
alliin
Alliin is a sulfoxide that is a natural constituent of fresh garlic. It is a derivative of the amino acid cysteine. When fresh garlic is chopped or crushed, the enzyme alliinase converts alliin into allicin, which is responsible for the aroma ...
, a precursor to the compound that gives freshly crushed garlic its aroma, and
dimethyl sulfoxide
Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula ( CH3)2. This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds a ...
(DMSO), a common
solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
.
Structure and bonding
Sulfoxides feature relatively short S–O distances. In DMSO, the S–O distance is 1.531 Å. The sulfur center is pyramidal; the sum of the angles at sulfur is about 306°.
[.]
Sulfoxides are generally represented with the structural formula R−S(=O)−R', where R and R' are organic groups. The bond between the
sulfur
Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formul ...
and
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 ...
atoms is intermediate of a
dative bond
In coordination chemistry, a coordinate covalent bond, also known as a dative bond, dipolar bond, or coordinate bond is a kind of two-center, two-electron covalent bond in which the two electrons derive from the same atom. The bonding of metal ...
and a polarized
double bond.
The double-bond resonance form implies 10 electrons around sulfur (10-S-3 in
N-X-L notation). The double-bond character of the S−O bond may be accounted for by donation of electron density into C−S antibonding orbitals ("no-bond" resonance forms in valence-bond language). Nevertheless, due to its simplicity and lack of ambiguity, the IUPAC recommends use of the expanded octet double-bond structure to depict sulfoxides, rather than the dipolar structure or structures that invoke "no-bond" resonance contributors. The S–O interaction has an
electrostatic
Electrostatics is a branch of physics that studies electric charges at rest ( static electricity).
Since classical times, it has been known that some materials, such as amber, attract lightweight particles after rubbing. The Greek word for ...
aspect, resulting in significant
dipolar
In physics, a dipole () is an electromagnetic phenomenon which occurs in two ways:
*An electric dipole deals with the separation of the positive and negative electric charges found in any electromagnetic system. A simple example of this syste ...
character, with negative charge centered on oxygen.
Chirality
A
lone pair
In chemistry, a lone pair refers to a pair of valence electrons that are not shared with another atom in a covalent bondIUPAC '' Gold Book'' definition''lone (electron) pair''/ref> and is sometimes called an unshared pair or non-bonding pair. L ...
of electrons resides on the sulfur atom, giving it tetrahedral electron-pair geometry and
trigonal pyramidal
In chemistry, a trigonal pyramid is a molecular geometry with one atom at the apex and three atoms at the corners of a trigonal base, resembling a tetrahedron (not to be confused with the tetrahedral geometry). When all three atoms at the corne ...
shape (steric number 4 with one lone pair; see
VSEPR theory). When the two organic residues are dissimilar, the sulfur is a
chiral center, for example, in
methyl phenyl sulfoxide. The
energy barrier
In chemistry and physics, activation energy is the minimum amount of energy that must be provided for compounds to result in a chemical reaction. The activation energy (''E''a) of a reaction is measured in joules per mole (J/mol), kilojoules pe ...
required to invert this
stereocenter is sufficiently high that sulfoxides are optically stable near room temperature. That is, the rate of
racemization is slow at room temperature. The enthalpy of activation for racemization is in the range 35 - 42 kcal/mol and the corresponding entropy of activation is -8 - +4 cal/mol-K. The barriers are lower for allylic and benzylic substituents.
Preparation
Sulfoxides are typically prepared by
oxidation
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 ...
of
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 la ...
s, sometimes referred to as
sulfoxidation.
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 ...
is a typical oxidant, but periodate has also been used. In these oxidations, care is required to avoid over oxidation to form the
sulfone. For example,
dimethyl sulfide is oxidized to
dimethyl sulfoxide
Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula ( CH3)2. This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds a ...
and then further to
dimethyl sulfone. Unsymmetrical sulfides are
prochiral, thus their oxidation gives chiral sulfoxides. This process can be performed enantioselectively.
Aryl sulfoxides
In addition to the oxidation routes, di
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 ...
sulfoxides can be prepared by two
Friedel–Crafts arylations of
sulfur dioxide
Sulfur dioxide (IUPAC-recommended spelling) or sulphur dioxide (traditional Commonwealth English) is the chemical compound with the formula . It is a toxic gas responsible for the odor of burnt matches. It is released naturally by volcanic a ...
using an acid catalyst:
:2 ArH + SO
2 → Ar
2SO + H
2O
Both aryl sulfinyl chlorides and diaryl sulfoxides can be also prepared from arenes through reaction with
thionyl chloride in the presence of Lewis acid catalysts such as BiCl
3, Bi(OTf)
3, LiClO
4, or NaClO
4.
Reactions
Deoxygenation and oxygenation
Sulfoxides undergo deoxygenation to give sulfides. Typically metal complexes are used to catalyze the reaction, using hydrosilanes as the stoichiometric reductant. The deoxygenation of dimethylsulfoxide is catalyzed by
DMSO reductase, a molybdoenzyme:
:OSMe
2 + 2e- + 2 H
+ → SMe
2 + H
2O
Acid-base reactions
The α-CH groups of alkyl sulfoxides are susceptible to deprotonation by strong bases, such as
sodium hydride
Sodium hydride is the chemical compound with the empirical formula Na H. This alkali metal hydride is primarily used as a strong yet combustible base in organic synthesis. NaH is a saline (salt-like) hydride, composed of Na+ and H− ions, in ...
:
:CH
3S(O)CH
3 + NaH → CH
3S(O)CH
2Na + H
2
In the
Pummerer rearrangement,
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 cycloa ...
sulfoxides react with
acetic anhydride to give migration of the oxygen from sulfur to the adjacent carbon as an
acetate ester. The first step of the reaction sequence involves the sulfoxide oxygen acting as a
nucleophile:
:
Elimination reactions
Sulfoxide undergo thermal elimination via an
Ei mechanism to yield vinyl
alkene
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 ...
s and
sulfenic acids.
:CH
3S(O)CH
2CH
2R → CH
3SOH + CH
2=CHR
The acids are powerful
antioxidant
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubrica ...
s, but lack long-term stability. Some parent sulfoxides are therefore marketed as antioxidant
polymer stabilisers.
Structures based on thiodipropionate esters are popular. The reverse reaction is possible.
Coordination chemistry
Sulfoxides, especially DMSO, form
coordination complex
A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as '' ligands'' or complexing agents. M ...
es with transition metals. Depending on the
hard-soft properties of the metal, the sulfoxide binds through either the sulfur or the oxygen atom. The latter is particularly common.
Applications and occurrence
left, 262 px, ,_a_blockbuster_drug">Esomeprazole,_a_blockbuster_drug,_is_an_enantiopure_drug.html" ;"title="blockbuster_drug.html" ;"title="Esomeprazole, a blockbuster drug">Esomeprazole, a blockbuster drug, is an enantiopure drug">blockbuster_drug.html" ;"title="Esomeprazole, a blockbuster drug">Esomeprazole, a blockbuster drug, is an enantiopure drug containing a sulfoxide functional group. The related drug
omeprazole is the racemic version.
DMSO is a widely used solvent.
The sulfoxide functional group occurs in several drugs. Notable is esomeprazole, the optically pure form of the proton-pump inhibitor
omeprazole. Another commercially important sulfoxides include
armodafinil.
Methionine sulfoxide forms from the amino acid
methionine and its accumulation is associated with aging. The enzyme
DMSO reductase catalyzes the interconversion of DMSO and dimethylsulfide.
Naturally-occurring chiral sulfoxides include
alliin
Alliin is a sulfoxide that is a natural constituent of fresh garlic. It is a derivative of the amino acid cysteine. When fresh garlic is chopped or crushed, the enzyme alliinase converts alliin into allicin, which is responsible for the aroma ...
and
ajoene
Ajoene is an organosulfur compound found in garlic (''Allium sativum'') extracts. It is a colorless liquid that contains sulfoxide and disulfide functional groups. The name (and pronunciation) is derived from "ajo", the Spanish word for garlic. I ...
.
Further reading
*
References
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Functional groups