Thiophenol, nucleophilic addition

The lO-E-4 chalcogen(IV) species diphenylselenium(IV) dibromide (1, Fig. 1) and diphenyltellurium(IV) dibromide (2, Fig. 1) oxidize thiophenol to diphenyl disulfide in nearly quantitative yield as shown in equations (13) and (14). Tellurium(IV) dihalides 6-11 also oxidize thiophenol to diphenyl disulfide and benzene selenol to diphenyl diselenide. Similarly, the 12-Te-5 molecule dioxatellurapentalene 45 (Fig. 19) is a mild oxidant for ethylmercaptan, thiophenol, and benzene selenol giving diethyl disulfide, diphenyl disulfide, and diphenyl diselenide in essentially quantitative yield. As shown in equation (15), 1,1,5,5,9,9-hexachloro-1,5,9-tritelluracyclododecane oxidizes six molecules of thiophenol to diphenyl disulfide and 1,5,9-tritelluracyclododecane in 90% yield. In contrast, 12-Te-5 pertellurane 44 and 12-Se-5 perselenane 46 do not oxidize thiophenol to diphenyl disulfide. Instead, these molecules undergo a nucleophilic addition of thiophenol followed by cleavage of the tellurium-carbon or selenium-carbon bond. ... 

Nucleophilic additions were studied using the same TSIL with pyrrolidine and thiophenol as models. As with the Diels-Alder reaction above, the reaction gave the required adducts which were then transesterified to give the final products. Heck coupling catalyzed by a transition metal and the Stetter reaction, Scheme 30, to prepare 1,4-dicarbonyl compounds were also studied by the same group using similar TSILs. 

There have been several reports of the use of intramolecular displacements of nitro groups in the synthesis of heterocyclic compounds. Thus, reaction16 of the intermediate (2) with a strong base in DMF results in the substitution of a nitro group by the amide function to yield a dibenzothiazepinone derivative (3). Nucleophilic addition across the double bond of 2,4,6-trinitrostyrene may occur with thiophenol, aniline, and aliphatic amines. The adducts so formed with primary amines may undergo intramolecular substitution of an o-nitro group to give IV-substituted 4,6-dinitroindoles.17... 

Dialkylaminomethyl alkyl (and aryl) sulfides result from the treatment of a-halogeno-amines with mercaptans (thiophenols).325 Dehydrogenation of amino-alcohols with mercuric acetate182,328 is accompanied by the intramolecular nucleophilic addition of the alkoxyl group when formation of a five- or six-membered ring is possible, e.g. ... 

Dihydroazocines. Azocines can be converted into the corresponding iminium salts by treatment with 1 equiv of acid, such as methanesulfonic acid, in CHCI3. Nucleophilic additions to iminium salt 226 afforded substituted azocine derivatives reaction with thiophenol in DCM/H20 at room temperature provided 227, while reaction with sodium azide in CHCI3/DMF provided 228 (Scheme 92 <2005EJ01052>). 

Nucleophilic addition of thiophenol to chiral tiglic acid-derived imides proceeds in excellent yields and diastereoselectivities (eq 59). Complete turnover of both the a- and p-centers results from the use of the (Z) rather than (E) isomer. Poor p-induction was found with the imides derived from cinnamic acid. 

Pyrrolizin-3-one (386) undergoes conjugate nucleophilic addition of piperidine and thiophenol and electrophilic addition of hydrogen chloride to give a range of 1-substituted 1,2-dihydro-pyrrolizin-3-ones (387), (388), and (389) respectively the 1-chloro atom can readily be displaced by nucleophiles, including water (Scheme 129) <93CC1570>. 

The action of sulfur nucleophiles like sodium bisulfite and thiophenols causes even pteridines that are unreactive towards water or alcohols to undergo covalent addition reactions. Thus, pteridin-7-one smoothly adds the named S-nucleophiles in a 1 1 ratio to C-6 (65JCS6930). Similarly, pteridin-4-one (73) yields adducts (74) in a 2 1 ratio at C-6 and C-7 exclusively (equation 14), as do 4-aminopteridine and lumazine with sodium bisulfite. Xanthopterin forms a 7,8-adduct and 7,8-dihydropterin can easily be converted to sodium 5,6,7,8-tetrahydropterin-6-sulfonate (66JCS(C)285), which leads to pterin-6-sulfonic acid on oxidation (59HCA1854). 

No addition products with S-nucleophiles have yet been reported except for the reaction of 2-methylthio-4,6-diphenylthiopyrylium iodide with sodium thiophenolate involving a 2//-thiopyran intermediate (86S916). 

The Marshall Unker [23] has been widely used to synthesize compounds that can be cleaved by primary and secondary amines to afford the corresponding amides. Marshall linker was used in the synthesis of three or more diversity-site hbraries because it allowed the addition of one more diversity element at the cleavage step. While the original reported linker [23] involved the oxidation of the Unker before cleavage, the efficient release of the resin-bound compounds using nucleophiles from the unoxidized linker has been reported [16, 24]. Similarly to the acid-labile linkers, the kinetics of the cleavage reaction and time required for this reaction directly affect the synthesis efficiency, purity and yield of the final products. A cleavage study was carried out on seven resin-bound thiophenol esters (34—40) on Marshall Unker with 3 amines (41-43) (Scheme 12.11 and Tab. 12.4). 

It is not surprising that chloro esters 1, 2 readily add thiols, catalyzed by sodium thiolates or triethylamine, to give the corresponding 2-(r-organylthiocy-clopropyl)-2-chloroacetates 85,86 (Scheme 22) [15 b, 22b, 27]. This reaction with thiophenol has been used to quantify the Michael reactivity of 1-Me, 2-Me, 3-X in comparison to simple acrylates (see above). With an excess of PhSH, the nucleophilic substitution of the chlorine in 85 a (but not in 85h) proceeded to give the corresponding bis(phenylthio) derivative in 63% yield [15bj. Alkali thiolates (e.g. NaSMe, NaSBn) add smoothly onto 1-Me, 2c-Me and 2p-Me at - 78 °C, because at this temperature subsequent nucleophilic substitution of the chlorine is much slower [7l, 9]. The Michael additions of sodium phenylselenide and sodium arylsulfenates onto 1-Me and their synthetic utility have been discussed above (see Table 1). 

Attention may now be directed to the reactions of aromatic thiols with epoxides. Mu tz,IH for example, haa investigated the course of addition of thiophenol to propylene oxide, both in alkaline and in acidic solutions. Significantly lower yields obtained in acid tended to confirm the premise that thiophenoxide ion rather than undissociated thiophenol is the attacking nucleophile. Likewise predictable was the isolation of two isomeric phenylthioprcpanois under add conditions, hut of only one in base (Eq. 663). 

Some strategies used for the preparation of support-bound thiols are listed in Table 8.1. Oxidative thiolation of lithiated polystyrene has been used to prepare polymeric thiophenol (Entry 1, Table 8.1). Polystyrene functionalized with 2-mercaptoethyl groups has been prepared by radical addition of thioacetic acid to cross-linked vinyl-polystyrene followed by hydrolysis of the intermediate thiol ester (Entry 2, Table 8.1). A more controllable introduction of thiol groups, suitable also for the selective transformation of support-bound substrates, is based on nucleophilic substitution with thiourea or potassium thioacetate. The resulting isothiouronium salts and thiol acetates can be saponified, preferably under reductive conditions, to yield thiols (Table 8.1). Thiol acetates have been saponified on insoluble supports with mercaptoethanol [1], propylamine [2], lithium aluminum hydride [3], sodium or lithium borohydride, alcoholates, or hydrochloric acid (Table 8.1). 

The 2,3-double bond in benzo[6]thiophene-1,1-dioxides undergoes addition reactions with nucleophiles in a manner comparable to that of other a,/9-unsaturated sulfones no aromatic properties are detectable in this way for the thiophene ring.718-723 For example, thiophenol and p-thiocresol give the adducts (340 R = H or Me) in the presence of base.723 However, if the aryl mercaptan and the sulfone are heated together, a radical reaction occurs to give the corresponding 2-substituted compound.723 In contrast to the behavior of aryl mercap-... 

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