In organic chemistry, a sulfoxide, also called a sulphoxide, is an organosulfur compound containing a sulfinyl () functional group attached to two carbon atoms. It is a polar functional group. Sulfoxides are oxidized derivatives of thioether. Examples of important sulfoxides are alliin, a precursor to the compound that gives freshly crushed garlic its aroma, and dimethyl sulfoxide (DMSO), a common solvent.
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°.
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Sulfoxides are generally represented with the structural formula R−S(=O)−R', where R and R' are organic groups. The bond between the
sulfur and
oxygen atoms is intermediate of a
dative bond 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 aspect, resulting in significant dipolar character, with negative charge centered on oxygen.
Chirality
A
lone pair of electrons resides on the sulfur atom, giving it tetrahedral electron-pair geometry and trigonal pyramidal shape (steric number 4 with one lone pair; see
VSEPR theory). When the two organic residues are dissimilar, the sulfur atom is a chiral center, for example, in methyl phenyl sulfoxide. The energy barrier 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 of
Organic sulfide, sometimes referred to as
sulfoxidation.
hydrogen peroxide 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 and then further to dimethyl sulfone. Unsymmetrical sulfides are
prochiral, thus their oxidation gives chiral sulfoxides. This process can be performed enantioselectively.
Symmetrical sulfoxides can be formed from a diorganylzinc compound and liquid sulfur dioxide.
Aryl sulfoxides
In addition to the oxidation routes, di
aryl sulfoxides can be prepared by two Friedel–Crafts arylations of
sulfur dioxide using an acid catalyst:
- 2 ArH + SO2 → Ar2SO + H2O
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 BiCl3, Bi(OTf)3, LiClO4, or NaClO4.
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:
- OSMe2 + 2e− + 2 H+ → SMe2 + H2O
Acid-base reactions
The α-CH groups of alkyl sulfoxides are susceptible to deprotonation by strong bases, such as
sodium hydride:
- CH3S(O)CH3 + NaH → CH3S(O)CH2Na + H2
In the Pummerer rearrangement, alkyl 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
and
.
- CH3S(O)CH2CH2R → CH3SOH + CH2=CHR
The acids are powerful , but lack long-term stability.
Coordination chemistry
Sulfoxides, especially DMSO, form coordination complexes with transition metals. Depending on the
HSAB theory of the metal, the sulfoxide binds through either the sulfur or the oxygen atom. The latter is particularly common.
Applications and occurrence
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 and ajoene.
Further reading
