Sulfur Dioxide

O=S=O

[7446-09-5]  · O2S  · Sulfur Dioxide  · (MW 64.07)

(reacts with 1,3-dienes in reversible cheletropic addition;2,3 SO2 extrusion from 2,5-dihydrothiophene 1,1-dioxides generates 1,3-dienes,9,10 o-quinodimethanes;4,5 inserts into carbon-metal bonds;14-16 reacts with ylides to give heterocycles;17,18 electrophilic promoter of Mannich reactions;20,21 catalyst for isomerization of alkenes,24 dienes,22,23 and nitrile oxides;25 involved in sulfonic acid26 and sulfonyl chloride synthesis;27 reacts with Wittig reagents or a-silyl carbanions to give sulfines;28,29 reacts with polyenes,30,31 cyclopropanes;32 reduces pyridine N-oxides36 and ozonides;37 solvent for superacid-promoted reactions41)

Physical Data: 1 mp -75.5 °C; bp -10.0 °C; d (liquid) 1.434 g cm-3 at 0 °C; d (vapor, 0 °C) 2.264 g cm-3.

Solubility: sol H2O, alcohol, acetic acid, sulfuric acid, benzene, acetonitrile.

Form Supplied in: colorless liquid or pungent, nonflammable gas; supplied in small cylinders; widely available.

Handling, Storage, and Precautions: corrosive irritant to respiratory system, skin, eyes; mildly toxic by inhalation; teratogenic; reacts violently with numerous substances; use only in well-ventilated fume hood.1

Reversible Cheletropic Addition of SO2 to 1,3-Dienes and Analogs.

Much of the chemistry of SO2 involves its reversible cheletropic addition to 1,3-dienes to give 2,5-dihydrothiophene 1,1-dioxides (sulfolenes) (eq 1).2 Much less commonly observed is the alternative, hetero-Diels-Alder cycloaddition mode, also reversible, leading to the sultine (sulfinic ester) structure.3 At low temperature this latter mode can be kinetically favored with reactive 1,3-dienes, but the cheletropic addition is generally favored thermodynamically.3

Trapping and regeneration of reactive o-quinodimethanes via cheletropic addition and extrusion of SO2 has proven useful in heterocyclic (eqs 2 and 3)4 and carbocyclic systems (eq 4).5 Thermal extrusion of SO2 from the cyclic sulfones yielded the reactive o-quinodimethanes, which were trapped with various dienophiles.

Linear cheletropic addition of SO2 to conjugated diallenes affords 2,5-bis(alkylidene)-2,5-dihydrothiophene 1,1-dioxides via the disrotatory process shown (eq 5).6

Similarly, addition of SO2 to 3-methyl-1,2,4-pentatrienyl-1-phosphonate (eq 6)7 or 5-methyl-1,3,4-hexatrienyl-3-phosphonate esters (eq 7)8 affords the corresponding phosphorylated alkylidene-2,5-dihydrothiophene 1,1-dioxides.

Chemical separation of a mixture of 1,3-diene geometric isomers was accomplished by selective cheletropic addition of SO2 to the trans diastereomer (eq 8).9 Chromatographic purification of the dihydrothiophene and thermolysis cleanly afforded trans-9,11-dodecadien-1-yl acetate, a sex pheromone of the female red bollworm moth.

An elaboration of this tactic is shown in eq 9 for the synthesis of (E)-1-substituted 1,3-dienes and (E,E)-1,4-disubstituted 1,3-dienes.10 The tricyclic sulfone (1) can be metalated and alkylated once or twice, giving (2) or (3), respectively. Thermolysis in the gas phase at 650 °C resulted in sequential loss of cyclopentadiene and SO2 to provide the dienes in 91-98% isomeric purity.

Acyclic Sulfone Synthesis.

Addition of Grignard and organolithium reagents to SO2 is known to produce salts of sulfinic acids.11 An example extending this to the enolate derived from camphor is shown in eq 10.12 The intermediate b-keto sulfinate was alkylated to afford the b-keto sulfone shown in modest yield.

A high yield synthesis of diphenyl sulfone results from the phenylation of SO2 with pentaphenylbismuth (eq 11),13a which proceeds more readily than the corresponding reaction with Triphenylbismuthine.13b

Insertion of SO2 into Carbon-Metal Bonds.

Sulfur dioxide inserts into cyclohex-2-enylstannanes in chloroform via a syn SE process (eqs 12 and 13).14 The g-syn stereospecificity is lost upon changing the solvent to methanol.

The bis(h1,h3-allyl)palladium phosphine complex in eq 14 inserts SO2 to provide the S-sulfinate derivative, which undergoes reductive elimination to a 1:1 mixture of diallyl and allyl 2-propenyl sulfone upon treatment with Carbon Monoxide.15

Triethylaluminum etherate reacts with SO2 to afford the aluminum salt of ethylsulfinic acid (eq 15).16

Heterocycle Synthesis.

Combination of a dihaloketene, a Schiff base and SO2 to give 5,5-dihalo-4-oxo-1,3-thiazolidine 1,1-dioxides is exemplified in eq 16.17 These products can be dehalogenated or heated to extrude SO2, yielding b-lactams.

Generation of a thiocarbonyl ylide in liquid SO2 from a D3-1,3,4-thiadiazoline results in a regioselective 1,3-dipolar cycloaddition, giving 1,2,4-oxadithiolane 2-oxides (eq 17).18

Reaction of the functionalized formamidine in eq 18 with SO2 in the presence of Triethylamine affords the 1,2,4-oxathiazole 2-oxide shown.19

Use of SO2 in Mannich Reactions.

Treatment of 2,5-dimethylphenol with SO2 apparently allows the formation of a half-sulfite ester (eq 19). Addition of an aminol ether affords selective o-aminoalkylation.20 Without SO2, the major pathway of Mannich reaction with 2,5-dimethylphenol leads to the p-amino-alkylation product.

Sulfur dioxide serves as an electrophilic reagent for activating bis(dialkylamino)methanes or alkoxy(dialkylamino)methanes for Mannich reactions with 2-methylfuran (eq 20), N-methylpyrrole (eq 21), and indole (eq 22).21 Dipolar adducts of SO2 and the bis(amino)methane or alkoxyaminomethane reagents are proposed as intermediates, rather than free iminium salts.

Isomerization of Dienes, Alkenes, and Nitrile Oxides by SO2.

Treatment of ergosterol acetate with SO2 in pyridine causes rearrangement of the 5,7-diene to the 6,8(14)-diene isomer (eq 23).22 This result is fundamentally different from related sterol diene rearrangements catalyzed by acid. A consistent rationale for this SO2-induced isomerization is shown.

Addition of SO2 to (5Z)- and (5E)-vitamin D3 (4) yields the sulfolene derivatives (5) (eq 24).23 Thermal extrusion of SO2 from (5) affords isotachysterol3 (6), alone or mixed with isovitamin D3 (7). Treatment of sulfone (5) with methanolic Potassium Hydroxide or Alumina results in the formation of (5E)-vitamin D3.

Regiospecific alkene isomerization has been effected by SO2 with a variety of acyclic and cyclic alkenes, including b-pinene (eq 25) and methylenecyclohexane (eq 26).24a The sequence of steps presented in eq 26 has been advanced to rationalize the process. Interestingly, if the reaction is attempted in the presence of D2O, alkene migration is completely suppressed, and all allylic hydrogens in the substrate alkene are exchanged for deuterium.24b

SO2 catalyzes the conversion of nitrile oxides to isocyanates via a dipolar cycloaddition followed by regioisomeric loss of SO2 and rearrangement (eq 27).25 The intermediate 1,3,2,4-dioxathiazole 2-oxides can be isolated, or converted to hydroxamic acids upon hydrolysis.

Sulfonic Acid and Sulfonyl Chloride Synthesis.

Condensation of benzimidazole with SO2 and an aldehyde or ketone results in the formation of benzimidazoylalkylsulfonic acids (eq 28).26

A wide variety of substituted anilines, especially those with electron-withdrawing substituents, can be converted to substituted arenesulfonyl chlorides via their diazonium salts (eq 29).27

Synthesis of Sulfines.

Reaction of SO2 with fluorenylidene-triphenylphosphorane in benzene gave the corresponding sulfine (eq 30).28 In a related fashion, reaction of SO2 with an a-silyl carbanion leads to the sulfine product (eq 31).29 Thus alkylidenation of SO2 is possible with Wittig or Peterson reagents.

Miscellaneous Addition Reactions of SO2.

A 1,6-addition of SO2 to cis-3-hexatriene gives 2,7-dihydrothiepin 1,1-dioxide in high yield (eq 32).30 Fully unsaturated thiepin dioxides can be elaborated from this and analogous triene-SO2 adducts, or the triene can be regenerated by thermolysis.

A cyclo(copolymerization) between dimethyldiallylammonium chloride and SO2 afforded a 3:1 mixture of the 10- and 20-membered macrocycles containing pyrrolidinium and sulfonyl groups (eq 33).31

Aryl-substituted cyclopropanes undergo g-sultine formation when treated with SO2 in protic acid. The ring opening is regioselective, but the substituted 1,2-oxathiolane 2-oxides are formed as mixtures of diastereomers (eq 34).32

Bicyclo[5.1.0]octa-2,5-diene reacts with dry SO2 at 150 °C in toluene to afford a moderate yield of the bicyclic sulfone shown (eq 35).33

Photoaddition of 4,5-pyrenedione and SO2 proceeds to give the cyclic sulfate (eq 36) in high yield.34

Cheletropic [p2s + p2s + o2s] addition of SO2 to norbornadiene provides a nearly quantitative yield of the tetracyclic sulfone in eq 37.35 Of several homoconjugated dienes examined, only norbornadiene exhibited this mode of reactivity.

Miscellaneous Reactions of SO2.

Two examples of SO2 serving as a reductant are illustrated in eqs 38 and 39. Pyridine N-oxides are deoxygenated under mild conditions in moderate yields.36 The ozonide derived from sulfolene (itself a product of SO2 plus butadiene) is reduced by SO2 to afford the acetal. Treatment of this with ammonium chloride gives 4H-1,4-thiazine 1,1-dioxide (eq 39).37

Vinyldiazomethane reacts with SO2 leading, via the presumed cis-divinyl episulfone intermediate, to the dihydrothiepin 1,1-dioxide through a Cope rearrangement (eq 40).38

Sulfur dioxide also serves as an electrophilic agent for the conversion of orthoesters to esters and dialkyl sulfites. For example, Triethyl Orthoacetate gives only ethyl acetate and diethyl sulfite as products upon treatment with SO2 (eq 41).39

Formation of dithioacetals and O,S-acetals from ketones and aldehydes can be catalyzed by SO2, with yields comparable or superior to protic catalysts.40 Finally, liquid SO2 has served as a solvent for a variety of superacid-mediated cyclization, rearrangement, and sulfinylation reactions.41

Related Reagents.

Copper(I) Chloride-Sulfur Dioxide.


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Steven D. Burke

University of Wisconsin, Madison, WI, USA



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