Oxidative sulfenylation

Stilbene isomerization. The (Z)- i (E)-Selective Wittig reactions. Tl Ph2S2 under visible light to maximize th Oxidative sulfenylation of fluorim the amines into sulfenylated imines, whi reagents and enolates. 

Oxidative sulfenylation of fluorinated amines. Anodic conditions convert the amines into sulfenylated imines, which can be used to react with organometallic reagents and enolates. 

Oxidation. Disulfides are prepared commercially by two types of reactions. The first is an oxidation reaction uti1i2ing the thiol and a suitable oxidant as in equation 18 for 2,2,5,5-tetramethyl-3,4-dithiahexane. The most common oxidants are chlorine, oxygen (29), elemental sulfur, or hydrogen peroxide. Carbon tetrachloride (30) has also been used. This type of reaction is extremely exothermic. Some thiols, notably tertiary thiols and long-chain thiols, are resistant to oxidation, primarily because of steric hindrance or poor solubiUty of the oxidant in the thiol. This type of process is used in the preparation of symmetric disulfides, RSSR. The second type of reaction is the reaction of a sulfenyl haUde with a thiol (eq. 19). This process is used to prepare unsymmetric disulfides, RSSR such as 4,4-dimethyl-2,3-dithiahexane. Other methods may be found in the Hterature (28). 

Many other reactions of ethylene oxide are only of laboratory significance. These iaclude nucleophilic additions of amides, alkaU metal organic compounds, and pyridinyl alcohols (93), and electrophilic reactions with orthoformates, acetals, titanium tetrachloride, sulfenyl chlorides, halo-silanes, and dinitrogen tetroxide (94). 

The 2-thienylthiourea (245) on oxidation with bromine in acetic acid gave the thieno[3,2-djthiazole (247). It has been suggested that the intermediate electrophilic sulfenyl bromide adds to the 2,3-bond of the thiophene ring to form (246) when then loses HBr to give (247) (71AJC1229, 78JHC81). Pyrazolo(3,4- /]thiazoles are formed in a similar fashion (76GEP2429195). 

Chlorination of thiiranes in hydroxylic solvents gives /3-chloroethylsulfonyl chlorides due to further oxidation of the intermediate sulfenyl chloride by chlorine or hypochlorous acid (Scheme 40). Polymer is usually obtained also unless the reaction is done in concentrated hydrochloric acid, which causes rapid ring cleavage to 2-chloroethylthiols which are subsequently oxidized to the sulfonyl chlorides. An 85% yield of (37) is obtained in concentrated hydrochloric acid-HCl(g) whereas only a 15% yield is obtained in CCI4-H2O. 

Chloroethyldisulfides are obtained by electrophilic attack on the sulfur atom of thiiranes by sulfenyl halides (Scheme 39). Sulfur dichloride and disulfur dichloride react similarly to give more sulfur-rich derivatives di- and tri-sulfenyl halides, and tri- and tetra-sulfides (Scheme 42). A 1 1 ratio of sulfur halide to thiirane gives the di- or tri-sulfenyl halide a 2 1 ratio the tri- or tetra-sulfide. Thiirane 1-oxides are cleaved by sulfenyl halides to thiolsulfinates (Scheme 43) (74JAP7440461). 

Thiirane is more bactericidal than oxirane, and derivatives of 2-mei captomethylthiirane inhibit tuberculosis. The following pharmacological uses have been reported for compounds derived from thiirane derivatives gold complexes of the adducts of diethylphosphine and thiirane (antiarthritic), adducts of thiiranes and malononitrile (antibacterial, blood vessel dilators, muscle relaxants, sedatives), thermolysis products of thiirane 1-oxides and adducts of thiirane 1-oxides with sulfenyl chlorides (antibacterial), adducts of 2,3-diarylthiirene 1,1-dioxides with ynamines (antibacterial, parasiticidal), adducts of 2,3-diarylthiirene 1,1-dioxides with enamines (antifertility), adducts of p-aminophenylacetic esters with thiirane (immunosuppressants), adducts of amines and thiiranes (radioprotective drugs). 

This group, which is more stable than the 2-hitrobenzenesulfenamide, has been developed to protect amino acids. It is readily introduced with the sulfenyl chloride (52-74% yield) and is cleaved with triphenylphosphine or 2-thiopyridine N-oxide. It is stable to CF3COOH but can be cleaved with 0.1 M HCl. ... 

Sulfenamides arc usually oxidized to sulfonamides tns(tnfluorotnetliane-sulfenyl) and bis(tnfluoromethanesulfenyl)arnineare converted to the corresponding sulfonamides by sodium hypochlorite at 20 tor 3 h m 61 and 92% yield, respecbvely [111] Oxidation of pentafluorobenzenesulfendimde by manganese dioxide yields a sulfinamide intermediate that can be trapped [772] (equabon 102)... 

Sulfenyl chlondes react with allyl alcohols to yield allyl sulfenates, whtch are in equihbnum with the allyl sulfoxides [12] (equation 9a) These products can be oxidized to the corresponding sulfones (equation 9b) Pyrolysis of the sulfoxides gives sulfines or evidence for the presence of sulfmes Pyrolysis of sulfones leads to unsamrated compounds by extrusion of sulfur dioxide [12] (equation 9c)... 

A heterocyclic ring may be used in place of one of the benzene rings without loss of biologic activity. The first step in the synthesis of such an agent starts by Friedel-Crafts-like acylation rather than displacement. Thus, reaction of sulfenyl chloride, 222, with 2-aminothiazole (223) in the presence of acetic anhydride affords the sulfide, 224. The amine is then protected as the amide (225). Oxidation with hydrogen peroxide leads to the corresponding sulfone (226) hydrolysis followed by reduction of the nitro group then affords thiazosulfone (227). ... 

Williams and Rastetter also accomplished an elegant synthesis of ( )-hyalodendrin (83) in 1980 [39]. Beginning with the sarcosine anhydride-derived enolic aldehyde 78, silyl protection of the enal enabled alkylation of the glycine center with benzyl bromide and thiolation using LDA and monoclinic sulfur a la Schmidt. After protection of the thiol with methylsulfenyl chloride and deprotection of the silyl ether, the enol was sulfenylated with triphenylmethyl chlorodisulfide to afford bis(disulfide) 82 as a 2 1 mixture of diastereomers favoring the anti isomer. Reduction of the disulfides with sodium borohydride and oxidation with KI3 in pyridine afforded ( )-hyalodendrin (83) in 29 % yield (Scheme 9.4). 

Earlier (Table 6, p. 119) we saw data on the reactivity of various nucleophiles toward an aryl sulfinyl sulfone in (139), a substitution that also involves an arenesulfinate as the leaving group, but one in which the substitution takes place at a sulfinyl ( S=0) rather than a sulfenyl ( S) sulfur. In Section 9 we present data on the rates of reaction of the same nucleophiles in an analogous substitution at a sulfonyl sulfur, Nu- + PhS02S02Ph - PhS02Nu + PhS02. At that point we will discuss how changing the oxidation state of the sulfur atom at which the substitution occurs... 

Just as was true for substitutions at S=0, and as will also be true for substitutions at S02 (Section 9), the experimental results do not clearly resolve the question of whether substitutions at sulfenyl sulfur are best represented as concerted (173a) or stepwise (173b). Proponents of either pathway can find certain results that seem to support their viewpoint and others that are difficult to reconcile with it. In Section 9, in connection with discussion of the same problem vis-a-vis substitutions at sulfonyl sulfur, we shall present a tentative hypothesis that we think may provide a means of reconciling the seemingly contradictory experimental results within a single conceptual framework and that is applicable to substitutions at sulfur in all of the different oxidation states. 

Splitting of the SCN group is not observed and, after the one-electron oxidation, the initial NCSC5H4NO2 anion-radical produces NCSC5H4NO2. The recoveries are close to quantitative disulfides and thiols are not observed. The thiocyanate group (SCN) thus competes less successfully with the nitro group (NO2) for the extra electron than the sulfenyl chloride group (SCI). 

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