Sulfuryl Chloride


[7791-25-5]  · Cl2O2S  · Sulfuryl Chloride  · (MW 134.97)

(widely used chlorinating agent;1 oxidizing agent;32 dehydrating agent;30 esterification catalyst31)

Physical Data: bp 68-70 °C.

Solubility: miscible with most organic solvents.

Form Supplied in: commercially available in 97-98% purity.

Analysis of Reagent Purity: bp.

Purification: fractional distillation.

Handling, Storage, and Precautions: is highly toxic, corrosive, and acts as a lachrymator. It reacts violently with water to liberate hydrogen chloride gas. Sulfuryl chloride is incompatible with DMSO, DMF, and ethers. This reagent should only be handled in a chemical fume hood using proper protective equipment.

Chlorination of Alkanes.

Hydrocarbons can be chlorinated using sulfuryl chloride by either radical or ionic processes. In the radical mediated process developed by Kharasch and Brown,1 a mixture containing an excess of the alkane with sulfuryl chloride and a catalytic amount of Dibenzoyl Peroxide in a suitable solvent such as carbon tetrachloride is heated, initiating chlorination and concomitant evolution of hydrogen chloride and sulfur dioxide. With simple alkanes a mixture of positional isomers is obtained.

Radical chlorination of benzylic positions using sulfuryl chloride proceeds with good selectivity over less activated sites of reaction (eq 1).1 This reaction can be facilitated by transition metal complexes2 or zeolites.3

Certain substituted alkanes can also be selectively chlorinated by this method.4 A good example is Lampman and Aumiller's synthesis of 3-chlorocyclobutanecarboxylic acid (eq 2).5

Ionic chlorination of alkanes can be accomplished by heating a mixture of alkane and excess sulfuryl chloride in sulfolane (eq 3).6 In these chlorinations the reaction mixture is shielded from light to prevent the initiation of radical processes. Since alkanes are more readily chlorinated by this method than sulfolane, competing solvent chlorination is not a problem.

Reactions with Alkenes.

Alkenes react exothermically with sulfuryl chloride to give vicinal dichlorides in generally good yields (eq 4).7

A mixture of sulfuryl chloride and N-methylpyrrolidine can be used to convert styrene into styrylsulfonyl chloride (eq 5).8

b-Chloro methyl sulfides are produced by the action of Dimethyl Sulfide/sulfuryl chloride/Dimethyl Sulfoxide in acetonitrile on alkenes (eq 6).9 It is thought that this reagent combination generates methanesulfenyl chloride, which undergoes exclusive trans addition to the alkenes. The initially formed anti-Markovnikov adducts slowly rearrange to Markovnikov products.

Chlorination of Epoxides.

Sulfuryl chloride reacts with cyclohexene oxide and Pyridine in refluxing chloroform to give 99% cis-1,2-dichlorocyclohexane in 70% yield.10

Chlorination of Alkynes.

Many alkynes react with this reagent via a homolytic pathway to give the corresponding (E)- and (Z)-dichloroalkenes in good to moderate yields.11 The ratio of isomers obtained is kinetically controlled and varies depending on the relative size of the alkyne substituents.

Chlorination of Aromatics.

Sulfuryl chloride reacts with aromatic derivatives under mild conditions to afford ring chlorinated products.12 For example, ethyl 4-hydroxybenzoate reacts at both the 3- and 5-positions when heated with excess sulfuryl chloride. Ester hydrolysis followed by decarboxylation gives 2,6-dichlorophenol (eq 7).13

Regioselective para-monochlorination of various phenols has been accomplished using sulfuryl chloride in combination with either Aluminum Chloride or Iron(III) Chloride as catalyst.14

Thiophenes react with sulfuryl chloride to give 2- or 5-chlorinated products with high selectivity.15 This reagent has been applied with excellent results to the chlorination of 2-thienylamines. For example, the antihistamine methapyrilene can be converted to chlorothen in 84% yield (eq 8).16

Aromatic hydrocarbons can be perchlorinated using a reagent composed of sulfur monochloride (5 g), sulfuryl chloride (850 mL), and aluminum trichloride (2.5 g).17 This reagent combination has been used to prepare highly strained aromatic chlorocarbons, including perchlorotoluene, perchloro-p-xylene, and perchlorophenanthrene.

a-Chlorination of Active Methylene Compounds.

Ketones are selectively chlorinated at the a-position with sulfuryl chloride to form products consistent with reaction between the reagent and the thermodynamic enol.18 For example, only 2-chloro-2-methylcyclohexanone is obtained from 2-methylcyclohexanone (eq 9).19 Direct chlorination of this ketone with Chlorine gives mixtures of chloro compounds.20

Many other activated methylene compounds can be a-chlorinated with sulfuryl chloride. Examples include the conversion of Ethyl Acetoacetate to ethyl 2-chloroacetoacetate in 93-97% yield;21 the chlorination of pyruvic acid in 96-98% yield;22 the a-chlorination of ε-benzoylaminocaproic acid;23 and the transformation of N-benzoyl-ε-caprolactam to N-benzoyl-a-chloro-ε-caprolactam in 89% yield.24 Aldehydes react with this reagent to give a-chlorinated products that often react further to form cyclic ether trimers and linear polyethers.25,26

4-Ene-3-oxo-steroids react with excess sulfuryl chloride in pyridine solution cleanly to give 4-chloro-4-ene-3-oxo-steroids (eq 10).27 When testosterone acetate is treated with excess sulfuryl chloride in anhydrous ether, 2a,6b-dichlorotestosterone acetate is obtained as the major product.28

Conversion of Alcohols to Chlorides.

Kozikowski and Lee29 report that secondary alcohols can be converted to chlorides with retention of configuration via methyl xanthate formation followed by reaction with sulfuryl chloride (eq 11).

Dehydrating Agent.

A combination of sulfuryl chloride and pyridine is useful as a dehydrating reagent in the synthesis of shikimic acid derivatives (eq 12).30

Esterification Catalyst.

Sulfuryl chloride catalyzes formation of methyl and benzyl esters of N-acylated amino acids and peptides at room temperature in yields ranging from 48-98% without causing racemization.31

Oxidation of Pyrroles.

This reagent is used to oxidize the methyl group at the 5-position of alkyl 3,4-dialkyl-5-methyl-2-pyrrolecarboxylates. Depending on reaction conditions, one can obtain either the ester (eq 13),32 the carboxylic acid,33 the aldehyde,34 or the dichloromethyl derivative.35

Reactions with Sulfides.

Sulfuryl chloride reacts with methyl sulfides to give chloromethyl sulfide derivatives (eq 14).36

With a-methylthioalkyl ethers, the corresponding a-chloroalkyl ethers are obtained in high yields.37 Similarly, a-chloroalkyl esters are obtained from a-phenylthioalkyl esters (eq 15).38 Styrene is added to remove the benzenesulfenyl chloride that is also formed in the reaction.

The facile a-chlorination of sulfides by sulfuryl chloride39 has been used as a means of dehydrogenating 2,5-dihydrothiophenes.40 This reaction is successfully employed in the commercial synthesis of the artificial sweetener thiophenesaccharin (eq 16).41

A reaction sequence involving a-chlorination of dibenzyl sulfides followed by a Ramberg-Bäcklund-like extrusion of sulfur produces diarylethylenes (eq 17).42

3-Phenylthio-2-azetidinones are converted to 3-chloro-3-phenylthio-2-azetidinones in 78-95% yield via a Pummerer-type mechanism. Hydrolysis by moist silica gel in the presence of catalytic Zinc Chloride provides the a-keto-b-lactams in 85-90% yield (eq 18).43

When alkyl sulfides are treated with sulfuryl chloride at -78 °C, the intermediate chlorosulfonium salts thought to be involved in formation of a-chloro sulfides can be hydrolyzed by treatment with ethanol at -70 °C and then at 25 °C to provide sulfoxides in high yield (eq 19).44 Alternatively, the oxidation can be performed by dropwise addition of sulfuryl chloride to a stirred mixture of the sulfide and wet silica gel in dichloromethane.45 The latter method has also been recommended as a convenient means of thioacetal oxidative cleavage, giving the carbonyl compounds in nearly quantitative yields.46

Reaction of benzyl thioethers with sulfuryl chloride can result in cleavage to form sulfenyl chlorides and benzyl chlorides. An example is Kharasch and Langford's preparation of 2,4-dinitrobenzenesulfenyl chloride (eq 20).47

Reaction with Thiols, Disulfides, and Thioesters.

Sulfinyl chlorides can be conveniently prepared in high yield by the action of sulfuryl chloride in acetic acid on disulfides (eq 21)48 or thiols49 at low temperature. Similarly, thioesters are rapidly converted to sulfinyl chlorides in high yields by sulfuryl chloride in acetic anhydride at -10 °C.50

Similarly, sulfenyl chlorides can be prepared from disulfides in carbon tetrachloride51 and from thiols in pentane by treatment with sulfuryl chloride52 in the presence of Triethylamine. The reaction of thioesters with sulfuryl chloride in carbon tetrachloride has been used in the synthesis of optically active sulfenyl chlorides (eq 22).53

Chlorination of Sulfoxides.

Sulfoxides are rapidly a-monochlorinated by sulfuryl chloride at -78 to 0 °C in dichloromethane containing CaO.54 Longer reaction times lead to a,a-dichlorination. Sulfoxides with two available sites of reaction undergo selective chlorination to form the more highly substituted chlorides. a-Chlorination of sulfoxides can also be effected using SO2Cl2/pyridine/CH2Cl2.55

a,b-Unsaturated Ester Synthesis.

b-Hydroxy sulfoxides react with sulfuryl chloride to form alkenes. This reaction has been used to synthesize a,b-unsaturated esters (eq 23).56 The products obtained from aldehydes in this synthesis have the (E) configuration, whereas ethyl methyl ketone gives a 1:1 mixture of geometric isomers.

Chlorination of Sulfones.

Unlike the reaction with sulfides and sulfoxides, chlorination of sulfones using sulfuryl chloride is slow and occurs mostly at b-, g-, and d-positions. Sulfolane is quantitatively converted to b-chlorosulfolane (eq 24).57

Synthesis of Sulfonyl Chlorides and Sulfamides.

Alkyllithiums react with sulfuryl chloride in pentane at -65 to -20 °C to give sulfonyl chlorides in moderate yields.58 Aromatic sulfonyl chlorides can be prepared from aryllithiums by reaction with sulfur dioxide to form the sulfinate salts followed by oxidation with sulfuryl chloride (eq 25).59

Sulfuryl chloride oxidizes thiols to sulfonyl chlorides in the presence of potassium nitrate or Silver(I) Nitrate in Acetonitrile at 0 °C (eq 26).60 This transformation probably occurs via initial formation of the sulfenyl chloride followed by conversion to a sulfenyl nitrate and further oxidation.

N-Monoalkyl amidosulfonyl chlorides are produced by the reaction of this reagent with primary amine hydrochlorides in refluxing acetonitrile with an appropriate Lewis acid (eq 27).61

Treatment of alkylamines62 or anilines63 in pyridine with sulfonyl chloride results in formation of the corresponding sulfamides (eq 28).

Synthesis of 2-Aminobenzothiazoles.

Phenylthioureas react with sulfuryl chloride to give 2-aminobenzothiazoles (eq 29).64

Other Transformations.

Sulfuryl chloride can be used to prepare n-butyl sulfate by heating the reagent with 2 equiv of n-butyl sulfite and removing the n-butyl chloride formed by distillation.65

Sulfuryl chloride oxidizes benzoin to benzil via a cyclic dienol ester that decomposes to extrude sulfur dioxide.66

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George D. Maynard

Marion Merrell Dow, Cincinnati, OH, USA

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