Direct oxidative sulfonylation

Keywords Thiols, hydrogen peroxide, thionyl chloride, amines, acetonitrile, room temperature, direct oxidative sulfonylation, sulfonamides... 

Direct oxidation of bis-sulfides by trifluoromethanesulfonic anhydride was suggested only recently.57 For example, treatment of 10 with triflic anhydride affords the corresponding dication salt 34 in high yield via intermediate formation of a sulfonyl sulfonium salt 33.58 A number of other cyclic and acyclic bis-sulfides 35 undergo facile oxidation to dications under these conditions (Scheme ll).57... 

Arylsulfonyl chlorides, which are known to oxidize a variety of thioamides,127 also cyclize A-(sulfonamidino)thioureas directly to sulfonyl derivatives of amino-1,2,4-thiadiazloes.110... 

While other more costly catalysts such as a variety of palladium salts also enabled direct 2-sulfonylation of the quinoline A/-oxides, the copper salts are more flexible and inexpensive. While a number of aryl sulfonyl chlorides coupled with quinoline N-oxides and isoquiniohne-AT-oxide, related compounds (N-oxides of pyridine and pyrazines) failed to react under these conditions. 

Synthetic strategy Direct oxidative conversion of thiols to sulfonyl chlorides, followed by sulfonamide formation... 

General Reaction Chemistry of Sulfonic Acids. Sulfonic acids may be used to produce sulfonic acid esters, which are derived from epoxides, olefins, alkynes, aHenes, and ketenes, as shown in Figure 1 (10). Sulfonic acids may be converted to sulfonamides via reaction with an amine in the presence of phosphoms oxychloride [10025-87-3] POCl (H)- Because sulfonic acids are generally not converted directiy to sulfonamides, the reaction most likely involves a sulfonyl chloride intermediate. Phosphoms pentachlotide [10026-13-8] and phosphoms pentabromide [7789-69-7] can be used to convert sulfonic acids to the corresponding sulfonyl haUdes (12,13). The conversion may also be accompHshed by continuous electrolysis of thiols or disulfides in the presence of aqueous HCl [7647-01-0] (14) or by direct sulfonation with chlorosulfuric acid. Sulfonyl fluorides are typically prepared by direct sulfonation with fluorosulfutic acid [7789-21-17, or by reaction of the sulfonic acid or sulfonate with fluorosulfutic acid. Halogenation of sulfonic acids, which avoids production of a sulfonyl haUde, can be achieved under oxidative halogenation conditions (15). 

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