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°.[3]
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.[4] 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.[5] 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.[6]
Preparation
Sulfoxides are typically prepared by
oxidation of
sulfides, sometimes referred to as
sulfoxidation.[7]hydrogen peroxide is a typical oxidant, but periodate has also been used.[8] 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.[9][10]
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.[11][12]
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.[13] The deoxygenation of dimethylsulfoxide is catalyzed by
DMSO reductase, a molybdoenzyme:[14]
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:[15]
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:
The acids are powerful
antioxidants, but lack long-term stability.[18] Some parent sulfoxides are therefore marketed as antioxidant
polymer stabilisers.[19] Structures based on thiodipropionate esters are popular.[20] The reverse reaction is possible.
Sulfoxides, especially DMSO, form
coordination complexes 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.[21]
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.
^Yanagisawa S, Itami K (2011). "Palladium/2,2′-bipyridyl/Ag2CO3 catalyst for C–H bond arylation of heteroarenes with haloarenes". Tetrahedron. 67 (24): 4425–4430.
doi:
10.1016/j.tet.2011.03.093.
^Thomas R, Shoemaker CB, Eriks K (1966). "The Molecular and Crystal Structure of Dimethyl Sulfoxide, (H3C)2SO". Acta Crystallogr. 21: 12–20.
doi:
10.1107/S0365110X66002263..
^Cunningham TP, Cooper DL, Gerratt J, Karadakov PB, Raimondi M (1997). "Chemical bonding in oxofluorides of hypercoordinate sulfur". Journal of the Chemical Society, Faraday Transactions. 93 (13): 2247–2254.
doi:
10.1039/A700708F.
^Fernández I, Khiar N (September 2003). "Recent developments in the synthesis and utilization of chiral sulfoxides". Chemical Reviews. 103 (9): 3651–705.
doi:
10.1021/cr990372u.
PMID12964880.
^Holland, Herbert Leslie (1988). "Chiral Sulfoxidation by Biotransformation of Organic Sulfides". Chemical Reviews. 88 (3): 473–485.
doi:
10.1021/cr00085a002.
^Peyronneau M, Roques N, Mazières S, Le Roux C (2003). "Catalytic Lewis Acid Activation of Thionyl Chloride: Application to the Synthesis of ArylSulfinyl Chlorides Catalyzed by Bismuth(III) Salts". Synlett (5): 0631–0634.
doi:
10.1055/s-2003-38358.
^Michael Carrasco, Robert J. Jones, Scott Kamel, H. Rapoport, Thien Truong (1992). "N-(Benzyloxycarbonyl)-L-Vinylglycine Methyl Ester". Organic Syntheses. 70: 29.
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^Cubbage, Jerry W.; Guo, Yushen; McCulla, Ryan D.; Jenks, William S. (1 December 2001). "Thermolysis of Alkyl Sulfoxides and Derivatives: A Comparison of Experiment and Theory". The Journal of Organic Chemistry. 66 (26): 8722–8736.
doi:
10.1021/jo0160625.
PMID11749600.
^Koelewijn, P.; Berger, H. (2 September 2010). "Mechanism of the antioxidant action of dialkyl sulfoxides". Recueil des Travaux Chimiques des Pays-Bas. 91 (11): 1275–1286.
doi:
10.1002/recl.19720911102.
^Armstrong, C.; Plant, M.A.; Scott, G. (February 1975). "Mechanisms of antioxidant action: the nature of the redox behaviour of thiodipropionate esters in polypropylene". European Polymer Journal. 11 (2): 161–167.
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^Calligaris M (2004). "Structure and Bonding in Metal Sulfoxide Complexes: an Update". Coordination Chemistry Reviews. 248 (3–4): 351–375.
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