A-sulfenylation

Tetrachloropyridine-4-thiol [10357-06-1] (41) reacts with chlorine in carbon tetrachloride to give a sulfenyl chloride (42), which is fairly stable. The sulfenyl chloride may be converted into a number of derivatives (39). 

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). 

Three substituted 5-phenyl unsymmetrical disulfides have been prepared, i, ii, and iii —compounds i and ii by reaction of a thiol with a sulfenyl halide, compound iii from a thiol and an aiyl thiosulfonate (ArS02SAr). The disulfides are cleaved by reduction (NaBH4) or by treatment with excess thiol (HSCH2CH2OH). 

Sulfenamides, R2NSR, prepared from an amine and a sulfenyl halide, " are readily cleaved by acid hydrolysis and have been used in syntheses of peptides, penicillins, and nucleosides. They are also cleaved by nucleophiles, and by Raney nickel desulfurization. ... 

Sulfur-containing groups at an a-position stabilize carbanions. All these species, i.e., the a-sulfonyl 6281-102, a-sulfmyl 6346-80, a-sulfenyl 645,103,104 and a-sulfonio carbanions 65105-1 ancj those derived from sulfonates 66 and sulfonamides 6795 may retain their... 

The a-seleno and a-sulfenyl carbonyl compounds prepared by this reaction can be converted to a,P-unsaturated carbonyl compounds (17-11). The sulfenylation reaction has also been used as a key step in a sequence for moving the position of a carbonyl group to an adjacent carbon. ... 

Selectivity is often conferred by on-board functionality, as in the a-sulfenyl-directed ringopening of l-phenylthio-2,3-epoxyalkanes (e.g., 74) with trimethylaluminum, a reaction which gives exclusively C-2 alkylat products with complete retention of configuration about C-2. 

The first structure determination on a sulfenyl iodide was that of thermally labile Ph3CSI. 

A new stable sulfenylating reagent 3-phenylsulfenyl-2-GV-cyano-imino)thiazolidine 57 has been described. It reacts with amines or thiols to give sulfenamides or disulfides in excellent yields. a-Sulfenylation of carbonyl compounds also proceeds smoothly and if an optically active 4-diphenylmethyl substituent is attached to the thiazolidine ring (58), the cyclic (3-ketoester 59 can be sulfenylated in high yield with an ee of 96% to give the sulfide 60 <00SL32>. 

Insertion of carbon monoxide into Csp2—Zr bonds occurs readily at ambient temperatures or below to produce a,(5-unsaturated, reactive acyl zirconocene derivatives [27—29]. Early work by Schwartz demonstrated the potential of such intermediates in synthesis [5d], as they are highly susceptible to further conversions to a variety of carbonyl compounds depending upon manipulation. More recently, Huang has shown that HC1 converts 16 to an enal, that addition of a diaryl diselenide leads to selenoesters, and that exposure to a sulfenyl chloride gives thioesters (Scheme 4.11) [27,28]. All are obtained with (F)-stereochemistry, indicative of CO insertion with the expected retention of alkene geometry. 

Trichloromethanesulfenyl chloride is a sulfenyl chloride that does not form a thiolsulfinate upon hydrolysis, however. Instead it gives the sulfine C12C=S=0 (Silhanek and Zbirovsky, 1969) because trichloromethanesulfenic acid loses HC1 (13) faster than it undergoes any other reaction. 

We will defer consideration of the particular pattern of nucleophile reactivity observed until Section 9. There we will compare it with what is found for the same group of nucleophiles reacting with (a) an aryl rr-disulfone ArS02S02Ar, a substitution that involves the same leaving group as in (139) but which takes place at a sulfonyl ( S02) rather than a sulfinyl ( S=0) sulfur, and (b) an aryl thiolsulfonate, ArSSOzAr, a substitution where ArSO is displaced from a sulfenyl ( S) sulfur. 

Thiolsulfonates have the structure shown in [58]. That they may be considered the mixed anhydride of a sulfenic and a sulfinic acid is indicated by one of the principal synthetic methods for their preparation, namely reaction (166) of a sulfinic acid with a sulfenyl chloride (Stirling, 1957). Once again, as we have... 

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... 

In earlier days it was fairly common to suggest that sulfenium ions, RS+, were involved as intermediates in a number of these substitutions, particularly those in which sulfenyl halides RSX reacted with very weak nucleophiles, or those where electrophilic catalysis of the substitution was observed (Parker and Kharasch, 1959). However, it has since become evident (Owsley and Helmkamp, 1967 Helmkamp et al., 1968 Capozzi et al., 1975) that sulfenium ions are almost impossible to generate as intermediates. For example, Capozzi et al., (1975) showed that although treatment of a sulfenyl chloride RSC1 with the powerful Lewis acid antimony pentafluoride led to the complete conversion of the sulfenyl chloride to a cation, what was formed was, not the sulfenium ion RS+, but rather the cation [59] in reaction (172). These results, and others... 

Such bimolecular substitutions at a sulfenyl sulfur, just as was true for analogous substitutions at sulfinyl sulfur, can in principle take place either by a mechanism in which bond making and bond breaking are concerted (173a), or alternatively, by one (173b) where bond making precedes bond breaking and an intermediate [60] is present on the reaction co-ordinate. 

Second, in comparing either the behavior of [65] vs. [67], or that of [66] vs. [68], one sees that the rate of intramolecular displacement of CN- from —SCN by —S02 is about 30 times faster than the rate of intramolecular displacement of SO, from —SSOj by —SOj. This is striking because it contradicts the belief sometimes expressed in the literature, but not apparently founded on any real experimental data, that Bunte salts are considerably more reactive as sulfenylating agents than thiocyanates. The data in (178)—(181) clearly indicate that a thiocyanate can be more reactive than a Bunte salt as a sulfenylating agent. 

V. ELECTROPHILIC SULFUR AND SELENIUM A. Sulfenyl Halides and Related Compounds... 

Compounds with excess of tt electrons, as for example, pyrrole and thiophene, form a large number of substitution products in their reactions with perfluorohalogenosulfenyl halides 47, 60). Thus pyrrole reacts with an equimolar quantity of a sulfenyl chloride of the series CFwCl3 n-SCl (w = 1, 2, 3) with the formation of a mixture of isomers of mono-substituted compounds ... 

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