Thiophenols bromination

Me3SiCH2CH=CH2i TsOH, CH3CN, 70-80°, 1-2 h, 90-95% yield. This silylating reagent is stable to moisture. Allylsilanes can be used to protect alcohols, phenols, and carboxylic acids there is no reaction with thiophenol except when CF3S03H is used as a catalyst. The method is also applicable to the formation of r-butyldimethylsilyl derivatives the silyl ether of cyclohexanol was prepared in 95% yield from allyl-/-butyldi-methylsilane. Iodine, bromine, trimethylsilyl bromide, and trimethylsilyl iodide have also been used as catalysts. Nafion-H has been shown to be an effective catalyst. 

Benzenesulfonyl chloride, 4-methyl- [p-Tol-uenesulfonyl chloride], 55, 57, 59 Benzenethiol [Phenol, thio-], 55, 122 Benzenethiol, copper(I) salt [Thiophenol, copper(I) salt], 55, 123 Benzenethiol, lithium salt [Thiophenol, lithium salt], 55, 1 22 Benzoic acid, 2-amino- [Anthramlic acid], p bromination of, 55, 23... 

The key structural features of compound 1 are the chiral cis-diaryl benzox-athiin fused ring system, two phenols, and one phenol ether linkage with the pyrrolidinylethanol. Originally, SERM 1 was prepared by medicinal chemists from a key ketone intermediate 5 shown in Scheme 5.1. Compound 5 was prepared in four steps with rather low yield [4a], Among these steps, the high temperature de-methylation step and the use of extremely toxic MOM-C1 were not particularly suitable for scale-up. The ketone 5 was then brominated with PhMe3NBr3 (PTAB) and coupled with thiophenol 7 to produce adduct 8. The key step of the synthesis was the conversion of adduct 8 to cis-diaryl benzoxathiin 9 under the Kursanov-Parne reaction conditions (TFA/Et3SiH). This novel reaction allowed the formation... 

The second cycloaddition substrate took to form of 91 (Scheme 1.9b), incorporating a vinyl sulfone dipolarophile. Beginning with cyano ketone 84, which was readily prepared from 1,5-dicyanopentane via a previously reported three-step sequence [45], condensation with thiophenol produced vinyl sulfide 85 in 84 % yield. Vinyl sulfide 85 underwent bromination in acetonitrile to afford bromo-vinyl sulfide 86 (86 %), which was then treated with isopropylmagnesium chloride [46] to effect metal-halogen exchange affording an intermediate vinyl magnesium bromide species. Subsequent alkylation with Mel in the presence of catalytic CuCN provided the alkylated vinyl sulfide 87 in 93 % yield. The nitrile within vinyl... 

Phenylthioacetylene has been prepared by elimination of thiophenol and dehydrobromination of cis-1,2-bis(phenylthio)ethylene5 and cis-1-bromo-2-phenylthioethylene,2 7 respectively. The latter was obtained by addition of thiophenol to propiolic acid in ethanol and subsequent one-pot bromine addition, decarboxylative dehalogenation, and careful distillation to remove the trans isomer.2.7 on the other hand, cis-1,2-bis(phenylthio)ethylene was prepared by double addition of thiophenol to cis-1,2-dichloroethylene.5a d Although these procedures can provide useful amounts of phenylthioacetylene, they were found to be somewhat less satisfactory in our hands as far as operation and/or overall yields are concerned. Furthermore, we have encountered problems with regard to the reproducibility of one-pot dehydrobrominations of phenylthio-1,2-dibromoethane.6 However, the stepwise execution of the double dehydrobromination, as described in the modified procedure reported here, provides preparatively useful quantities of phenylthioacetylene in a practical manner. 

The much steadier anion-radicals of 4-bromobenzophenone are able to diffuse into the volume without disintegration. In the volume, they lose the bromine anion and form the corresponding radicals, which are intercepted with the thiophenolate anions. The product of so-to-speak nucleophilic substitution is formed. 

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

The nucleophilic substitution of bromine by the thiophenolate ion in 4-bromoben-zophenone requires extremely rigid conditions. When a difference in electric potentials is set up, the reaction proceeds readily and gives products in a high yield (80%). It is sufficient to set up only the potential difference necessary to ensure the formation of the substrate anion radical (with the potential and current strictly controlled). The chemical reaction takes place in the bulk solution and yields 4-bromobenzophenone (Pinson Saveant 1974) (Scheme 5-1). 

Swartz and Stenzel (1984) proposed an approach to widen the applicability of the cathode initiation of nucleophilic substitution, consisting of the use of a catalyst to facilitate one-electron transfer. Thus, in the presence of PhCN, the cathode-initiated reaction between PhBr and BU4NSPI1 leads to diphenydisulfide in such a manner that the yield increases from 10% to 70%. Benzonitrile captures an electron and diffuses into the pool, where it meets bromobenzene. The latter is converted into the anion radical. The next reaction consists of the generation of the phenyl radical, with the elimination of the bromine anion. Since generation of the phenyl radical takes place far from the electrode, this radical is attacked with the anion of thiophenol faster than it is reduced to the phenyl anion. As a result, instead of debromination, substitution develops in its chain variant. In other words, the problem is to choose a catalyst such that it would be reduced more easily than the substrate. Of course, the catalyst anion radical should not decay spontaneously in solution. 

Modification of the butyl linker moiety was then studied on SP, treating 9.26 with Ml (symmetrical anhydrides or diacids, 10 representatives. Fig. 9.19) to give the resin-bound acids 9.34, which were pooled, reduced to alcohols 9.35, and brominated to give the alkyl bromides 9.36. The resin was split into 60 portions and treated with M2 (the same 60 thiophenol and aniline nucleophiles as for L13) to give the 600-member pool library L14 made of 60 pools of 10 individuals (Fig. 9.19). The library quality... 

Zincke disulfide cleavage. Formation of sul-fenyl halides by three essentially similar methods involving the action of chlorine or bromine on aryl disulfides, thiophenols, or arylbenzyl sulfides. 

In a related and more recent study a variety of solid-supported acylating agents were synthesized and used for microwave-mediated transformation of amines, alcohols, phenols, and thiophenols [123]. In a microwave-mediated procedure, Mer-rifield resin was first modified by attaching 1,4-butanediol to introduce a spacer unit. Bromination and subsequent reaction with commercially available 6-methyl-2-thiouracil then treatment with corresponding acyl chloride afforded the desired polymer-bound pyrimidines (Scheme 16.81). The acylating ability of this supported reagent has been proven by reaction with benzylamine. 

Thiophenol reacts with diphenyl-ketene-(p-bromophenyl)imine (50) causing reduction of the aromatic bromine and fracture of the C=N bond ,... 

An ester of l-thiochromanone-2-carboxylic acid, prepared from thiophenol and chlorosuccinic acid, may be brominated and the product dehydrobrominated by heating with pyridine to give an ester of 1-thio-chromone-2-carboxylic acid [63], The overall yield from thiophenol is about 12 per cent. 

Bromine in dry chloroform added dropwise with stirring at room temp, during 5 hrs. to a soln. of benzylidene-p-nitraniline in the same solvent, and kept 6 hrs. at 4° dibromide (Y 71%) treated 6 hrs. at 35° with thiourea in 90%-ethanol benzylidene-p-nitraniline. Y 63%. Also bromine elimination by other nucleophiles such as iodide, thiosulfate, thiophenolate, and thiocyanate ions, or thio-cresol s. Nasir-ud-Din et al., Ghem. Ind. 1967, 1875. 

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