Sulfides and sulfonates

Metathesis of unsaturated sulfides proceeds to a substantial extent with the tungsten complex [W]=CHCMe3 (1 in Ch. 3). In its presence CH2=CHCH2SMe ([olefin]/ [catalyst] = 25/1) is converted to ethene and a trans/cis (9/1) mixture of MeSCH2CH=CHCH2SMe at 80°C in chlorobenzene (40% conversion in 15h) (Couturier 1993b). 

Alkenyl tosylates of the type RHC=CH(CH2) OTs (n = 7-9) undergo metathesis when catalyzed by WCl6/Me3SnCl (Daly 1982). 

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Sulfoxides are compounds that contain a sulfinyl group covalendy bonded at the sulfur atom to two carbon atoms. They have the general formula RS(0)R, ArS(0)Ar, and ArS(0)R, where Ar and Ar = aryl. Sulfoxides represent an intermediate oxidation level between sulfides and sulfones. The naturally occurring sulfoxides often are accompanied by the corresponding sulfides or sulfones. The only commercially important sulfoxide is the simplest member, dimethyl sulfoxide [67-68-5] (DMSO) or sulfinylbismethane. 

Alcohol, Ether, Ester, Sulfide, and Sulfone Groups / 52... 

Omori, T. Saiki, Y. Kasuga, K., and Kodama, T., Desulfurization of Alkyl and Aromatic Sulfides and Sulfonates by Dibenzothiophene-Desulfurizing Rhodococcus Sp Strain Syl. Bioscience Biotechnology and Biochemistry, 1995. 59(7) pp. 1195-1198. 

Nucleophilic substitution of leaving groups is probably the most important area in pyrimidine reactivity and, in particular, the differential reactivity of C-2 and C-4 is the most investigated topic. The displacement of 2- and 4-sulfide and sulfone groups is referred to in the synthesis section. The selective hydrolysis of 4-amino-2-chloropyrimidines under acidic conditions has been studied in great detail by a process research group <06OPRD921>. 

Buynak et al. [53] synthesized several 6-(mercaptomethyl) penicillanates (9r and 9s, Table 1) that include both C-6 stereoisomers as well as the sulfide and sulfone oxidation states of the penam thiazolidine sulfur. Selected mercaptomethyl penicillanates inactivated both metallo- and serine /5-lactamases, and displayed synergism with piperacillin against various //-lactamase-producing strains, including metallo-/5-lactamase-producing P. aeruginosa strain. Compound 9r would be capable of bidentate chelation of zinc subsequent to enzymatic hydrolysis of the /5-lactam (Scheme 3). 

The acetogenin (+)-solamin and analogs were prepared via a ruthenium-catalyzed Alder-ene reaction/butenolide formation (Scheme 37).96 Of particular note is the ability of the ruthenium to catalyze the reaction in the presence of free hydroxyls, sulfides, and sulfones. Yields ranged from 65% for the sulfide to 88% for the sulfone. Trost has also applied this reaction to the total synthesis of (+)-ancepsenolide, which features a bis-Alder-ene reaction (Scheme 38).97... 

The complexes of sulfur trioxide with various nucleophiles (dioxane, pyridine etc.) are mild sulfonating reagents. Unlike other complexes of sulfur trioxide, dimethyl sulfide-sulfur trioxide readily adds to conjugated multiple bonds. Consequently, not only the sulfo group but also the dimethyl sulfide group add at the multiple bond. The reactions of dimethyl sulfide-sulfur trioxide complex with butadiene, isoprene and 2,3-dimethylbutadiene take place as conjugated l,4- -additions of dimethyl sulfide and sulfonate groups at the double bonds of the diene (equation 103).124... 

Since diorganyl sulfides and sulfoxides can be mutually interconverted electrochemi-cally [222] (for the oxidation of sulfides to sulfoxides and further to sulfones, see Sect. 9.2.3), sulfoxides take an intermediate position between sulfides and sulfones (Eq. 27). 

The chemical purity of the compound is checked by NMR (250 MHz) and thin layer chromatography (silica gel, eluent ethyl acetate) which show the complete absence of the corresponding sulfide and sulfone (Note 8). 

Piazza GA, Rahm AL, Krutzsch M, et al. Antineoplastic drugs sulindac sulfide and sulfone inhibit cell growth by inducing apoptosis. Cancer Res 1995 55 3110-3116. 

Copper-mediated 5n2 displacement of enantiomerically pure allylic mesyloxy vinyl sulfoxides occurs with high yields and stereoselectivities.11 The 5n2 reactions of structurally related mesyloxy sulfides and sulfones with organocuprates have also been examined. 

Sulindac has been chromatographed as the methyl ester (diazomethane) on a 6 x 10.25" 1% SE-30 on Supelcon 80/100 column under isothermal at 262°C with nitrogen as a carrier gas at 100 ml/min. Detection was with electron capture and sample sizes ranges from v50 to 100 ng. The retention time of sulindac was approximately 7 minutes. The sulfide and sulfone analogs have retention times of 1.5 and 5 mi-tion ... 

Several HPLC systems have been used for sulindac including one employing chloroform/ethyl ace-tate/acetic acid (800 200 2) as the mobile phase with a p Porasel, 30 cm, 10 u particle size column UV detection at 280 nm and a flow rate of 2.0 ml/ min (500-3000 psi). Under these conditions sulindac chromatographed with a retention time of approximately 6.3 minutes. The sulfide and sulfone analogs chromatographed with retention times of 1.8 2.5 minutes respectively 1 ). 

Furazan and furoxan sulfides and sulfones have been reported. The sulfides, formed by displacement of nitro from nitrofuroxans by thiophenols, can be oxidized to the corresponding sulfones using hydrogen peroxide. 

The formation and reactions of sulfoxonium ylids demonstrate how sulfoxides occupy a useful and interesting part of the middle ground between sulfides and sulfones—they are weakly nucleophilic, like sulfides (and can be alkylated with methyl iodide to give sulfoxonium salts as we have just seen), but at the same time they stabilize anions almost as well as sulfones. However, sulfoxides are perhaps the most versatile of the three derivatives because of a good deal of chemistry that is unique to them. There are two reasons why this should be so. 

Most examples of pyrolyses of one-sided non-benzylic disulfones come from the synthesis of [3.3]- and [4.4]phanes. The parent compound [3.3]paracyclophane 205 so far only was obtained by ring-enlarging methods in low yields. Haenel et al. succeeded in synthesizing this compound by sulfone pyrolysis in 75% starting from the readily available corresponding sulfide and sulfone, respectively [69]. 

There are few reports of the transition metal complex-catalyzed isomerization of S-allyl sulfides and sulfones. This is clearly a consequence of the very strong coordinating ability of sulfur atoms and the resulting tendency for S-C (allyl) bond cleavage. In the case of a bulky substituent being present at the sulfur atom, the isomerization to 1-propenyl derivatives is successful (Eqs. 12.14 and 12.15) [20]. 

The formation of alkenes from TB or MDC derivatives of (3-hydroxy sulfides and sulfones is also a useful procedure. When the 1,4-bis-MDC derivative (88) was reacted with BusSnH, the tetrahydrothio-phene (89) was produced, presumably by the process shown in Scheme 8. The first intramolecular step is related to the attack on C=S by a carbon radical in the reactions of 1,2-bis-TB derivatives with BusSnH (equation 16). ... 

Allylic alcohols are reduced with lithium or sodium in ammonia, or low molecular weight amines either with or without alcohols. The thermodynamically more stable product is often formed, leading to rearrangement in some cases (equation 71). Methyl and cyclic ethers are similarly reduced (equations 72 and 73), as are allylic acetates, halides and epoxides (equation 74 and 75). 7.i08 Benzylic and allylic sulfides and sulfones are readily reduced to hydrocarbons using lithium or sodium in alcoholic solvents or in amines. " Allylic sulfones are reduced in a similar manner (Scheme 11)," either with or without migration of the double bond, depending on the reaction conditions used. 

Addition of sulfides and sulfones to acid derivatives has been investigated by Agawa. Phenyl and methyl (trimethylsilyl)methyl sulfides and sulfones added to amides (323) to produce the aminovinyl sulfides (324 equation 74) and sulfone (326 equation 7S). The reactions proceeded in good yield with some examples of stereocontrolled synthesis of the ( )-isomer. Other acid derivatives such as esters, carbonates and ureas were investigated, but gave inconsistent results. 

Allyl sulfides and sulfones. Displacement of bisulfite anion from RSSOjNa and... 

Synthesis of these simple type of thiol derivatives will be Just briefly discussed here because comprehensive reviews on thiols and their derivatives are available (2, 21 ). The methyl sulfide compounds are most readily obtained by methylation of the corresponding thiol. Nucleophilic substitutions with methane thlolate on alkyl halides and occasionally with aryl halides lead directly to the methyl sulfide product. The syntheses of methyl sulfide and sulfone metabolites of xenoblotlca are summarized In Table IX. 

Several congeners shown to give methyl sulfides and sulfones. 

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