Sulfur Trioxide1

SO3

[7446-11-9]  · O3S  · Sulfur Trioxide  · (MW 80.07)

(highly reactive electrophilic agent for replacing (i) a hydrogen atom or other substituent bonded to carbon by an SO3H or derived sulfo group, forming a carbon-sulfur bond (called sulfonation), (ii) a hydrogen atom bonded to oxygen by an SO3H group, forming an oxygen-sulfur bond (called sulfation or O-sulfonation, and (iii) a hydrogen atom bonded to nitrogen by an SO3H group, forming a nitrogen-sulfur bond (called sulfamation or N-sulfonation);1a,1b reagent for cycloaddition to carbon-carbon double bonds;1a,2 moderate oxidizing agent3)

Physical Data: mp 16.8 °C; bp 44.7 °C; d 1.970 g cm-3.

Solubility: miscible in all proportions with liquid SO2; sol dichloromethane, chloroform, carbon tetrachloride, 1,1,1-trichloroethane (some react slowly with SO3, e.g. CCl4 yields phosgene);4 SO3 in dilute solution (<=10 mol %) in SO2, CCl3F, and CCl4 is present as monomer; at higher concentrations the cyclic trimer is also present;5 sol nitromethane (reacts at 0-15 °C slowly, and at 25-40 °C sometimes violently to give nitromethanesulfonic acid and other compounds);6 modestly sol 1,4-dioxane; the resulting complex is unstable;7,8 the solid adduct can decompose violently on standing for some time at rt;9 reacts violently with water.

Form Supplied in: liquid/solid, containing 1% of stabilizer to prevent polymerization, in sealed glass container.

Handling, Storage, and Precautions: in the absence of a suitable stabilizer, SO3 shows a strong tendency to polymerize when exposed even to traces of moisture. Use in a fume hood. Keep the container of SO3 tightly closed and dry. Upon handling open to air, the liquid gives off fumes of a sulfur trioxide-sulfuric acid spray! Reacts violently with water. Causes burns to the skin; is very toxic by inhalation and if swallowed. Contact with combustible material may cause fire. Wear eye and face protection and suitable protective clothing. In case of contact with eyes, rinse immediately with plenty of water, immediately remove all contaminated clothing and seek medical advice.

Organic Sulfur Trioxide Reagents.

Apart from SO3 and its less reactive addition compounds, formed with suitable Lewis bases10 such as Pyridine,11 Trimethylamine,12 Dimethyl Sulfide,13 sulfolane,14 Triphenylphosphine,15,16 triphenylbismuthine,16 triphenylphosphine oxide,17 tricylohexyl-16 and trimethylphosphine oxide,17 triethyl phosphate,18 Dimethyl Sulfoxide,19 N,N-Dimethylformamide,20 Nitromethane,21 1,4-dioxane,1a-d and 1,4-oxathiane,22 there is a class of sulfonating sulfate ester reagents, e.g. dimethyl polysulfate (MeOSO2(OSO2)nOMe)23 and trimethylsilyl chlorosulfate.24,25 There are also the protic sulfonating reagents, concentrated aqueous and fuming Sulfuric Acid, and Fluorosulfuric Acid, Chlorosulfonic Acid, and acetylsulfuric acid.1d The reactivity order of the Lewis base complexes of SO3 varies strongly. On the basis of direct experimental evidence26 and of relative pKB-SO327 and pKBH+28 values, the sulfonation reactivity is suggested to increase in the order trimethylamine-SO3 < Sulfur Trioxide-Pyridine, DMSO-SO3 < N,N-dimethylformamide-SO3, Trimethyl Phosphate-SO3 < Sulfur Trioxide-1,4-Dioxane < sulfolane-SO3, nitromethane-SO3.

Aromatic Sulfonation.

Reaction of an arene (ArH) with SO3 leads to sulfonation with formation of arenesulfonic acids (ArSO3H). Mechanistically two different stages can be recognized, viz. primary and secondary sulfonation.1f,29,30 In the primary stage, arenepyrosulfonic acids (ArS2O6H) are formed. A pyrosulfonic acid is a mixed anhydride, liable to disproportionate to give arenesulfonic anhydride and H2S2O7.30b,31-34 Working up the reaction mixture with water and heating the resulting aqueous mixture to reflux for 15 min leads to complete hydrolysis of the pyrosulfonic acids and sulfonic anhydrides to the corresponding arenesulfonic acids.31 Sulfonylation to give diaryl sulfones is another possible complication in reaction of arenes with SO3, especially when using deactivated arenes at high concentrations.1f

The steric requirements of a sulfonic acid group are very similar to those of a t-butyl group and prevent sulfonation ortho to a t-butyl group. Sulfonation of t-butylbenzene with SO3 gives 98% of the 4-sulfonic acid (4-S), and that of m-di-t-butylbenzene gives 98% of the 5-S.35 Reaction of p-di-t-butylbenzene with SO3 in CCl3F yields 58% of p-t-butylbenzenesulfonic acid by direct sulfo-de-t-butylation.35

Sulfonic acid isomer distribution data for the SO3 sulfonation are available for alkylbenzenes36 and their halogeno derivatives;37 phenol and anisole,31,38 and their methyl,38,39 halogeno,38,40 and hydroxy and methoxy derivatives;32,41 and naphthalene,36 and its methyl,42 and hydroxy and methoxy derivatives.34,43 SO3 sulfonation isomer distribution data are also available for a number of polycyclic aromatic hydrocarbons and 1,6-methano[10]annulenes, including some alkyl derivatives.36

Deviating Sulfonation Behavior of 9-Alkylanthracenes.

Reaction of 9-methylanthracene with SO3 in dioxane leads exclusively to methyl sulfonation to give sulfonic acid (1) quantitatively.44 Under comparable conditions, 9-t-butylanthracene gives d-sultone (2).45a Sulfonation of 9-pentylanthracene gives predominantly sulfonic acid (3) with some (4).45b The a-alkenyl-g-sulfonic acid (3) is formed via the corresponding 9-alkenylanthracene as an intermediate.45c

Positional Selectivity.

Judging from the data for toluene,46 o-xylene,47 1-methylnaphthalene,42a,48 phenol,38,49 anisole,38,49 and 2,3-dihydrobenzofuran50 and -pyran,50 the positional selectivity is significantly greater for sulfonation with SO3 than with sulfuric acid containing 90 wt % H2SO4.

For the sulfonation of an (alkyl)arene with SO3 in differing solvents, the variation in the isomer distribution is limited.14,51 With phenol and anisole the ortho:para sulfonation ratio is significantly larger when using CH2Cl2 than the complex-forming solvents nitromethane and dioxane.31 With CH2Cl2 the SO3 forms instead a complex with the C(sp2) oxygen of the substrate which, as result of intramolecular transfer of SO3, leads to enhanced ortho sulfonation. With substituted phenols and anilines, subject to the positions of the other substituents, the positional selectivity changes very significantly on varying the [SO3]:[substrate] from <=1.0 to &egt;4.0 (Table 1).

As for the phenol derivatives, this illustrates the importance of the initial sulfation equilibrium (k1, k-1) (eq 1). Applying <=1.0 equiv SO3 the effective substrate species being sulfonated is the hydroxyarene H-Ar-OH (k2), the OH substituent of which is strongly activating and para directing, whereas on using a large excess of SO3 the entity undergoing sulfonation is the corresponding aryl hydrogen sulfate H-Ar-OSO3H (k3), the OSO3H substituent being deactivating and para (+ ortho) directing. This may accordingly lead to a different substitution pattern. The sulfation equilibrium (k1, k-1) constant is temperature dependent. Phenol with 1.0 equiv SO3 in nitromethane at -35 °C is rapidly sulfated to give phenyl hydrogen sulfate quantitatively, which at &egt;0 °C isomerizes to phenol-4-S as the only eventual product.38 The increase of both the 2- to 3-S ratio in the reaction of p-methoxyphenol with 1.5 equiv SO3,41 and the 2- to 4-S ratio in the reaction of 1-naphthol with 1.0 equiv SO343a with increasing reaction temperature, were ascribed to the increase in the k-1/k1 ratio.

Sulfonation of Unsaturated Aliphatic Compounds.

Sulfur trioxide reacts vigorously with linear52 and branched53 alkenes to give rise to b-sultones as the primary sulfonation products.1a,1b,2 Since neat SO3 is too reactive, complexes of SO3 with dioxane8 or pyridine11 are used to moderate the sulfonation reaction. The formation of b-sultone is stereo- (syn) and regioselective, obeying Markovnikov's rule. However, these b-sultones are thermally unstable at rt and their rearrangement leads to complex mixtures of alkenesulfonic acids and g- and d-sultones. Yields of the isolated alkenesulfonic acids (eq 2)54 and sultones (eq 3)53 vary considerably with the alkene structure and reaction conditions. Halogenated,1h in particular fluorinated,1i ethylenes react with SO3 to give relatively stable halogenated b-sultones. This cycloaddition of SO3 at the double bond proceeds in a regioselective way (eq 4).55

Reaction of an alkene with an excess of SO3 gives a cyclic sulfonate-sulfate anhydride, also referred to as carbyl sulfate or pyrosulfate (eq 5).56 This carbyl sulfate is formed by a slow insertion of SO3 into the intermediate b-sultone.52a The complex of sulfur trioxide with dimethyl sulfide reacts with alkenes and alkynes to afford sulfobetaines in good yields (eq 6).13,57 These sulfobetaines are produced by nucleophilic attack of the dimethyl sulfide on the initially formed b-sultones.

Conjugated dienes are sulfonated by sulfur trioxide reagents to give b-unsaturated d-sultones (eq 7). The yields vary strongly; they increase with the number of alkyl substituents at the 2- and 3-positions of the alkadiene.58

Functionalized alkenes containing a phenyl or carboxylic acid group at appropriate distance from the double bond undergo intramolecular cyclization during the sulfonation.59 On reaction of (E)-4-hexenoic acid59a with SO3 a sulfo-d-lactone is formed (eq 8), and a Friedel-Crafts type cyclization is observed on sulfonation of (E)-5-phenyl-2-pentene59b (eq 9); both cyclizations proceed quantitatively and stereospecifically.

Sulfonation of Saturated Aliphatic Compounds.

Sulfur trioxide reacts with aliphatic acids60 or esters61 to give, initially, insertion of SO3 into the carboxylic acid or ester group, followed by sulfonation at the a-carbon (eq 10). Reactions of aldehydes and ketones with SO3 also afford the a-sulfonated products.62

It should be noted that sulfonation of linear alkylbenzenes, linear long-chain a-alkenes, and fatty esters and the sulfation of fatty alcohols by SO3-air mixtures are widely applied processes in industry for the production of surfactants.63

Related Reagents.

Dimethyl Sulfoxide-Sulfur Trioxide/Pyridine; Sulfur Trioxide-1,4-Dioxane; Sulfur Trioxide-Pyridine.


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Hans Cerfontain & Bert H. Bakker

University of Amsterdam, The Netherlands



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