Thiophenols, from phenols

In the Newman-Kwart Rearrangement (NKR), intramolecular aryl migration of O-thioearbamates at high temperatures leads to S-thiocarbamates. The NKR allows access to thiophenols from phenols, as O-thiocarbamates are readily prepared and hydrolysis of S-thiocarbamates can readily be achieved (Moseley and Lenden, 2007). The yield ranges between 72-91%. 

The procedure described is a good general method3 for obtaining a thiophenol from the respective phenol. It employs three steps conversion of a phenol to the O-aryl dialkylthiocarba-mate by treatment with dialkylthiocarbonyl chloride pyrolysis of the O-aryl dialkylthiocarbamate to the S-aryl dialkylthio-carbamate and hydrolysis of the latter to the aryl mercaptan. 

Reaction of Resin-Bound Iron Complex (54) with Alkyl Mercaptans, Thiophenols, and Phenols (Fig. 9)31. Sodium thiolates are prepared analogously to the alkoxides from thiol and sodium hydride, except that dry DMF is used as a solvent. The substitution on the polymer-bound arene (54) is performed at 70° in DMF within 16 h. The resin is filtered and washed with DMF (2 x 50 ml), MeOH (2 x 50 ml), H20 (2 x 50 ml), MeOH (2 x 50 ml), and CH2CI2 (3 x 50 ml) and then dried in vacuo at 40° to yield a red resin. 

The value of p q for the dissociation of arylnitromethanes can be estimated from the average for the dissociation of groups adjacent to the benzene ring. Thus p = 2.89, 2.24, 2.23 for the dissociation of anilinium ions, thiophenols and phenols respectively. A p value (2.13) may also be calculated from that for the dissociation of substituted benzoic acids assuming an attenuation factor 0.47 for the >C=O group. The average is 2.37 which is taken to be peq for the formation of the carbanion at (0,1). 

Thiophenols can be readily derived from phenolic sources by a number of processes (ref, 120). They are reactive and are susceptible to a variety of reactions either at the sulphur atom or the ring. 

Both benzo[ >]thiophenes and benzo[ >]furans can be obtained from the thiophenol or phenol respectively, by S-/0-alkylation with bromoacetaldehyde acetal and then acid-catalysed ring closure involving intramolecular electrophilic attack on the ring. 

As a related reaction, thiophenols are prepared from phenols. For example, the Pd-catalyzed reaction of 2-naphthyl triflate with sodium triisopropylsilane thiolate (56) gives the silyl ether of 2-thionaphthol 57. Deprotection of 57 affords 2-thionaphthol (58) [17]. 

Ort/io-selectivity is generally observed in the reactions of 2,4-dichloro- and 2,4-difluoro-nitrobenzene with alkoxide and thiophenoxide ions [199]. Also in less activated systems, nucleophiles generated from phenols and thiophenols with potassium fluoride-alumina and 18-crown-6-polyether will react in DMSO with cyano- or nitro-substituted fluoro- or chloro-benzenes [200]. Interestingly, the reaction of difluorobenzenes with two diffoent alcohols can occur sequentially. Introduction of the first etho" function deactivates the ring, and use of more forcing conditions allows substitution of the second fluorine [201]. Consecutive displacements of fluorine and nitro groups have been observed in the reaction of ort/io-fluoronitrobenzene with chiral acyl bicyclic lactones in a highly enantioselective synthesis of spirooxindoles [202]. 

Preparation.— Two procedures for the production of ethers from alky] halides have been mentioned earlier in this Report. From a study of fluoride salts on alumina as reagents for the alkylation of phenols and alcohols, potassium or caesium fluoride on alumina, in acetonitrile or 1,2-dimethoxyethane as the solvent, has been found to be the best combination for general use. A recently reported one-pot synthesis of phenyl ethers from phenol acetates involves their treatment, in solution in acetone, first with potassium carbonate and then with an alkyl halide. Another interesting new procedure for the alkylation of phenols utilizes the gas-liquid phase-transfer catalysis technique that was discussed above. In this case a phenol (or a thiophenol) and an alkyl halide, both gaseous, are passed through a bed of solid K2CO3 (or NaHCOs) at 170°C in the presence of a PEG e,g. Carbowax 6000) as the catalyst. ... 

Heating 2-amidofuran 253 at 165 °C was reported to give the phenolic indoline 252 in 87% yield, and this occurs by elimination of thiophenol from the initially formed cycloadduct. The cycloaddition behavior of the thermally more robust iV-ethyl carbamate derivative 255 proceeded quite smoothly to furnish phenol 254 in 80% yield when heated at 160 °C for 7h. It should be noted that the phenolic functionality present in the aromatic ring of indolines 252 and 254 has the potential to be transformed into an aryl triflate and used for palladium-catalyzed cross-coupling chemistry to afford more highly functionalized products (Scheme 13.58) [102]. 

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. 

Although phenols have not participated in the Conrad-Limpach reaction under certain conditions thiophenols were not as innocent. Lee and coworkers reported mixtures of thiochromenones and quinolones from reactions of amino-thiophenols with ethyl benzoyl acetate. Amino-thiophenol 67 reacted with ethyl benzoylacetate 68 in PPA to give a mixture of thiochromenone 70 and quinolone 69 in which the quinolone predominated. 

With OH and SH, the nucleophilic substitution of Cl has been reported. Thus, with NaOH, there is a report of successful nucleophilic substitution in 50% aq. acetone at room temperature to give the phenol complex in 36% yield. The latter is then spontaneously deprotonated to give the cyclohexadienyl complex (Eq. (24)). An identical reaction was carried out using NaSH in MeCN (50% yield) to give the thiophenol complex which was deprotonated [72] Eq. (25). These reactions would be especially valuable because direct synthesis of the phenol or thiophenol complexes from ferrocene is not possible due to the strong interaction between the heteroatom and A1C13 [11, 19]. Recent improvement and use of this reaction were achieved [88],... 

SOMe the enhancement in the meta-position is almost as large as in the para-position. The authors go on to show the applicability of op (g) values to certain solution processes, particularly those in non-aqueous solvents, but including the dissociation of thiophenols in 48% ethanol, the results of Bordwell and Andersen80 to which reference has been made earlier (Section III.A.1). A separation of field/inductive and resonance effects is also essayed for the gas-phase acidities of the phenols, and SOMe and S02Me feature in the discussion. There is reference to a oR° value of + 0.07 for SOMe as an unpublished result of Adcock, Bromilow and Taft (cf. 0.00 from Ehrenson and coworkers65 and — 0.07 from Katritzky, Topsom and colleagues128.)... 

From the point of view of the synthetic organic chemist, the importance of aromatic thallation, and the remarkable degree of orientation control which can be exercised over this process, lies in the ease with which the resulting ArTlXj compounds can be converted into substituted aromatic derivatives in which the new substituent group has entered the ring at the position to which thallium was originally attached. Syntheses of phenols, nitroso compounds, biaryls, aromatic nitriles, thiophenols, and deuterated aromatic compounds have all been achieved these results are summarized briefly below. 

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 asymmetric reduction of the benzoxathiin is very appealing because of its simplicity (Scheme 5.3). It was envisioned that intermediate 16 could be prepared from thiol-phenol 7 and bro moke tone 17. Scheme 5.8 summarized the synthesis for 16. The l,3-benzoxathiol-2-one 35 was prepared from 1,4-benzoquinone and thiourea following a literature procedure with minor modifications. Benzylation of 35 with benzyl bromide in the presence of KI gave benzyl ether 36 as a crystalline solid. It was observed that the benzylation gave better results when the reaction was run under anaerobic conditions. Hydrolysis of thiocarbonate 36 gave free thiophenol 7 which was used directly in the next reaction. 

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