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Sulfoxide
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<h2 id="structure-and-bonding">Structure and bonding</h2> <p>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°.<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a> Sulfoxides are generally represented with the structural formula R−S(=O)−R', where R and R' are organic groups. The bond between the <a href="/facts/Sulfur/IK0amTfM">sulfur</a> and <a href="/facts/Oxygen/acyn6o8r">oxygen</a> atoms is intermediate of a <a href="/facts/Dative_bond/t7NPflnQ">dative bond</a> and a polarized <a href="/facts/Double_bond/qDemMn0c">double bond</a>.<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> The double-bond resonance form implies 10 electrons around sulfur (10-S-3 in <a href="/facts/N-X-L_notation/goPjlm9W">N-X-L notation</a>). 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.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> The S–O interaction has an <a href="/facts/Electrostatic/bxkuW6s4">electrostatic</a> aspect, resulting in significant <a href="/facts/Bond_dipole_moment/vC3JYlJ4">dipolar</a> character, with negative charge centered on oxygen. </p> <h3>Chirality</h3> <p>A <a href="/facts/Lone_pair/Q6kEAC4g">lone pair</a> of electrons resides on the sulfur atom, giving it tetrahedral electron-pair geometry and <a href="/facts/Trigonal_pyramidal/1hvdUNrp">trigonal pyramidal</a> shape (steric number 4 with one lone pair; see <a href="/facts/VSEPR_theory/WqsRgVRV">VSEPR theory</a>). When the two organic residues are dissimilar, the sulfur atom is a <a href="/facts/Chirality_(chemistry)/p5a9pftB">chiral center</a>, for example, in <a href="/facts/Methyl_phenyl_sulfoxide/UUV94sKo">methyl phenyl sulfoxide</a>. The <a href="/facts/Activation_energy/GqkgPvo0">energy barrier</a> required to invert this <a href="/facts/Stereocenter/t3XGwk1Q">stereocenter</a> is sufficiently high that sulfoxides are optically stable near room temperature. That is, the rate of <a href="/facts/Racemization/t4C1SIXQ">racemization</a> 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.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> </p> <h2 id="preparation">Preparation</h2> <p>Sulfoxides are typically prepared by <a href="/facts/Organic_oxidation/6DdmXG4S">oxidation</a> of <a href="/facts/Organic_sulfide/GdyEz43f">sulfides</a>, sometimes referred to as <a href="/facts/Sulfoxidation/2v5mNVQG">sulfoxidation</a>.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> <a href="/facts/Hydrogen_peroxide/vju6HBIc">hydrogen peroxide</a> is a typical oxidant, but periodate has also been used.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> In these oxidations, care is required to avoid over oxidation to form the <a href="/facts/Sulfone/LJLP1RcT">sulfone</a>. For example, <a href="/facts/Dimethyl_sulfide/mUrg1jol">dimethyl sulfide</a> is oxidized to <a href="/facts/Dimethyl_sulfoxide/T4HSYfuC">dimethyl sulfoxide</a> and then further to <a href="/facts/Methylsulfonylmethane/kaBnyAv8">dimethyl sulfone</a>. Unsymmetrical sulfides are <a href="/facts/Prochiral/31Cpe8tC">prochiral</a>, thus their oxidation gives chiral sulfoxides. This process can be performed enantioselectively.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a><a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> </p><p>Symmetrical sulfoxides can be formed from a <a href="/facts/Organozinc_chemistry/xpcLJCT4">diorganylzinc</a> compound and liquid <a href="/facts/Sulfur_dioxide/jDK1fIDs">sulfur dioxide</a>.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> </p> <h3>Aryl sulfoxides</h3> <p>In addition to the oxidation routes, di<a href="/facts/Aryl/M3z7QRXd">aryl</a> sulfoxides can be prepared by two <a href="/facts/Friedel%E2%80%93Crafts_reaction/N65aEdXA">Friedel–Crafts</a> arylations of <a href="/facts/Sulfur_dioxide/jDK1fIDs">sulfur dioxide</a> using an acid catalyst: </p> 2 ArH + SO2 → Ar2SO + H2O <p>Both aryl sulfinyl chlorides and diaryl sulfoxides can be also prepared from arenes through reaction with <a href="/facts/Thionyl_chloride/nWwvNtvd">thionyl chloride</a> in the presence of Lewis acid catalysts such as BiCl3, Bi(OTf)3, LiClO4, or NaClO4.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a><a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> </p> <h2 id="reactions">Reactions</h2> <h3>Deoxygenation and oxygenation</h3> <p>Sulfoxides undergo deoxygenation to give sulfides. Typically metal complexes are used to catalyze the reaction, using hydrosilanes as the stoichiometric reductant.<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> The deoxygenation of dimethylsulfoxide is catalyzed by <a href="/facts/DMSO_reductase/dW6uyWb7">DMSO reductase</a>, a molybdoenzyme:<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> </p> OSMe2 + 2 e− + 2 H+ → SMe2 + H2O <h3>Acid-base reactions</h3> <p>The α-CH groups of alkyl sulfoxides are susceptible to deprotonation by strong bases, such as <a href="/facts/Sodium_hydride/Pnsh2T64">sodium hydride</a>:<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> </p> CH3S(O)CH3 + NaH → CH3S(O)CH2Na + H2 <p>In the <a href="/facts/Pummerer_rearrangement/JdMIrNsJ">Pummerer rearrangement</a>, <a href="/facts/Alkyl/vmEk8X4v">alkyl</a> sulfoxides react with <a href="/facts/Acetic_anhydride/hGxHam3M">acetic anhydride</a> to give migration of the oxygen from sulfur to the adjacent carbon as an <a href="/facts/Acetate/U90VVczy">acetate</a> ester. The first step of the reaction sequence involves the sulfoxide oxygen acting as a <a href="/facts/Nucleophile/xYccoaJQ">nucleophile</a>: </p> <h3>Elimination reactions</h3> <p>Sulfoxide undergo thermal elimination via an <a href="/facts/Ei_mechanism/XIGI2B8W">Ei mechanism</a> to yield vinyl <a href="/facts/Alkene/RtYcS6kU">alkenes</a> and <a href="/facts/Sulfenic_acid/kthmLHtJ">sulfenic acids</a>.<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a><a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> </p> CH3S(O)CH2CH2R → CH3SOH + CH2=CHR <p>The acids are powerful <a href="/facts/Antioxidant/4TG4MQ83">antioxidants</a>, but lack long-term stability.<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> Some parent sulfoxides are therefore marketed as antioxidant <a href="/facts/Polymer_stabilisers/vIDYnth0">polymer stabilisers</a>.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> Structures based on thiodipropionate esters are popular.<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a> The reverse reaction is possible. </p> <h3>Coordination chemistry</h3> <p class="note">Main article: <a href="/facts/Transition_metal_sulfoxide_complex/jYrXWa1s">Transition metal sulfoxide complex</a></p> <p>Sulfoxides, especially DMSO, form <a href="/facts/Coordination_complex/1tCyeQUm">coordination complexes</a> with transition metals. Depending on the <a href="/facts/HSAB_theory/yguwscxc">hard-soft properties</a> of the metal, the sulfoxide binds through either the sulfur or the oxygen atom. The latter is particularly common.<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a> </p> <h2 id="applications-and-occurrence">Applications and occurrence</h2> <p>DMSO is a widely used solvent. </p><p>The sulfoxide functional group occurs in several drugs. Notable is <a href="/facts/Esomeprazole/ogcBGRYX">esomeprazole</a>, the optically pure form of the proton-pump inhibitor <a href="/facts/Omeprazole/rJNAvWSR">omeprazole</a>. Another commercially important sulfoxides include <a href="/facts/Armodafinil/6FDlkfXJ">armodafinil</a>. </p><p><a href="/facts/Methionine_sulfoxide/QR979Tk7">Methionine sulfoxide</a> forms from the amino acid <a href="/facts/Methionine/7neydPKo">methionine</a> and its accumulation is associated with aging. The enzyme <a href="/facts/DMSO_reductase/dW6uyWb7">DMSO reductase</a> catalyzes the interconversion of DMSO and dimethylsulfide. </p><p>Naturally-occurring chiral sulfoxides include <a href="/facts/Alliin/yFkD3NNm">alliin</a> and <a href="/facts/Ajoene/1wmeleAc">ajoene</a>. </p> <h2 id="further-reading">Further reading</h2> <ul><li>Gama Á, Flores-López LZ, Aguirre G, Parra-Hake M, Hellberg LH, Somanathan R (2003). <a href="https://doi.org/10.3998%2Fark.5550190.0004.b02">"Oxidation of sulfides to chiral sulfoxides using Schiff base-vanadium (IV) complexes"</a>. <i>Arkivoc</i>. 2003 (11): 4–15. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.3998%2Fark.5550190.0004.b02">10.3998/ark.5550190.0004.b02</a>. <a href="/facts/Hdl_(identifier)/rdebSxmC">hdl</a>:<a href="https://hdl.handle.net/2027%2Fspo.5550190.0004.b02">2027/spo.5550190.0004.b02</a>.</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Patai S, Rappoport Z, eds. (1995). Syntheses of Sulphones, Sulphoxides and Cyclic Sulphides. PATai's Chemistry of Functional Groups. John Wiley & Sons. doi:10.1002/9780470666357. ISBN 9780470666357. <a href="9780470666357" target="_blank">9780470666357</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>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.. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Cunningham TP, Cooper DL, Gerratt J, Karadakov PB, Raimondi M (1997). "Chemical bonding in oxofluorides of hypercoordinate sulfur". 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