- Oxygenation of Organoboronic Acids by a Nonheme Iron(II) Complex: Mimicking Boronic Acid Monooxygenase Activity
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Phenolic compounds are important intermediates in the bacterial biodegradation of aromatic compounds in the soil. An Arthrobacter sp. strain has been shown to exhibit boronic acid monooxygenase activity through the conversion of different substituted phenylboronic acids to the corresponding phenols using dioxygen. While a number of methods have been reported to cleave the C-B bonds of organoboronic acids, there is no report on biomimetic iron complex exhibiting this activity using dioxygen as the oxidant. In that direction, we have investigated the reactivity of a nucleophilic iron-oxygen oxidant, generated upon oxidative decarboxylation of an iron(II)-benzilate complex [(TpPh2)FeII(benzilate)] (TpPh2 = hydrotris(3,5-diphenyl-pyrazol-1-yl)borate), toward organoboronic acids. The oxidant converts different aryl/alkylboronic acids to the corresponding oxygenated products with the incorporation of one oxygen atom from dioxygen. This method represents an efficient protocol for the oxygenation of boronic acids with dioxygen as the terminal oxidant.
- Chatterjee, Sayanti,Paine, Tapan Kanti
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- Iodine-Mediated Synthesis of Methylthio-Substituted Catechols from Cyclohexanones
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A novel and efficient I2-mediated direct synthesis of methylthio-substituted catechols from cyclohexanones was developed. Various cyclohexanones underwent oxygenation, methylthiolation, and dehydrogenative aromatization in one pot to form the desired products in moderate to good yields. DMSO was utilized as the solvent, oxygen source, and methylthiolation agent. A possible reaction mechanism is proposed. (Figure presented.).
- Wu, Yue-Hua,Wang, Nai-Xing,Zhang, Tong,Yan, Zhan,Xu, Bao-Cai,Inoa, Joan,Xing, Yalan
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supporting information
p. 3008 - 3013
(2019/04/30)
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- Identification of MsrA homologues for the preparation of (R)-sulfoxides at high substrate concentrations
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Here we report a methionine sulfoxide reductase A (MsrA) homologue with extremely high substrate tolerance and a wide substrate scope for the biocatalytic preparation of enantiopure sulfoxides. This MsrA homologue which was obtained from Pseudomonas alcaliphila (named paMsrA) showed good activity and enantioselectivity towards a series of aryl methyl/ethyl sulfoxides 1a-1k, with electron-withdrawing or electron-donating substituents at the aromatic ring. Chiral sulfoxides in the R configuration were prepared with approximately 50% of yield and up to 99% enantiomeric excess through the asymmetric reductive resolution of racemic sulfoxide catalyzed by the recombinant paMsrA protein. More importantly, kinetic resolution has been successfully accomplished with high enantioselectivity (E > 200) at initial substrate concentrations up to 320 mM (approximately 45 g L-1), which represents a great improvement in the aspect of the substrate concentration for the biocatalytic preparation of chiral sulfoxides.
- Yang, Jiawei,Wen, Yuanmei,Peng, Liaotian,Chan, Yu,Cheng, Xiaoling,Chen, Yongzheng
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p. 3381 - 3388
(2019/04/01)
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- Biocatalytic Preparation of Chiral Sulfoxides through Asymmetric Reductive Resolution by Methionine Sulfoxide Reductase A
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Here we report an environmentally friendly method for the preparation of chiral sulfoxides under high substrate concentration using recombinant methionine sulfoxide reductase A from Pseudomonas monteilii (pmMsrA) as a biocatalyst. Our results show that this enzyme can effectively accomplish the preparation of (R)-sulfoxides with approximately 50 % yield and 94–99 % enantiomeric excess through asymmetric reductive resolution of racemic sulfoxide. With the establishment of the enzyme regeneration system, the initial substrate concentration could be increased 40–100 times compared to our original report. The (R)-sulfoxides were obtained with high enantioselectivity under the substrate concentration up to 200 mm (approximately 32 g L?1), representing a quite high substrate concentration in biocatalytic preparation of chiral sulfoxides. Moreover, this system showed fairly good activity and enantioselectivity towards a series of ortho- and para-substituted phenyl methyl sulfoxides under high substrate concentration.
- Peng, Liaotian,Wen, Yuanmei,Chen, Yu,Yuan, Zhimei,Zhou, Yang,Cheng, Xiaoling,Chen, Yongzheng,Yang, Jiawei
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p. 3284 - 3290
(2018/06/04)
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- A visible-light photocatalytic thiolation of aryl, heteroaryl and vinyl iodides
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The general catalytic synthesis of aryl and vinyl thioethers from readily available halides remains a challenge. Herein we report a unified method for the thiolation of aryl and vinyl iodides with dialkyl disulfides using visible light photoredox catalysis. A range of thioether products bearing diverse functional groups can be accessed in high yield and with excellent chemoselectivity. We demonstrate the versatility of this method through the expedient synthesis of a family of thioether-rich natural products. A detailed investigation of the photocatalytic mechanism is presented from both steady-state and time-resolved luminescent quenching as well as transient absorption spectroscopy experiments.
- Czyz,Weragoda,Monaghan,Connell,Brzozowski,Scully,Burton,Lupton,Polyzos
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supporting information
p. 1543 - 1551
(2018/03/08)
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- Chemoenzymatic synthesis of enantiopure hydroxy sulfoxides derived from substituted arenes
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Enantiopure β-hydroxy sulfoxides and catechol sulfoxides were obtained, by chemoenzymatic synthesis, involving dioxygenase-catalysed benzylic hydroxylation or arene cis-dihydroxylation and cis-diol dehydrogenase-catalysed dehydrogenation. Absolute configurations of chiral hydroxy sulfoxides were determined by X-ray crystallography, ECD spectroscopy and stereochemical correlation. The application of a new range of β-hydroxy sulfoxides as chiral ligands was examined.
- Boyd, Derek R.,Sharma, Narain D.,Malone, John F.,Ljubez, Vera,Murphy, Deirdre,Shepherd, Steven D.,Allen, Christopher C. R.
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p. 2651 - 2664
(2016/03/05)
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- Continuous-flow synthesis of functionalized phenols by aerobic oxidation of grignard reagents
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Phenols are important compounds in chemical industry. An economical and green approach to phenol preparation by the direct oxidation of aryl Grignard reagents using compressed air in continuous gas-liquid segmented flow systems is described. The process tolerates a broad range of functional groups, including oxidation-sensitive functionalities such as alkenes, amines, and thioethers. By integrating a benzyne-mediated in-line generation of arylmagnesium intermediates with the aerobic oxidation, a facile three-step, one-flow process, capable of preparing 2-functionalized phenols in a modular fashion, is established. Putting on airs: Aerobic oxidation of (hetero)aryl Grignard reagents using compressed air proceeds with a gas-liquid continuous-flow system, thus enabling preparation of fucntionalized phenols. By integrating an in-line generation of ArMgBr intermediates with the aerobic oxidation, ortho-functionalized phenols can be assembled. The method demonstrates good functional-group (FG) compatibility, mild reaction conditions, and short reaction times.
- He, Zhi,Jamison, Timothy F.
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supporting information
p. 3353 - 3357
(2014/04/03)
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- Highly chemoselective methylation and esterification reactions with dimethyl carbonate in the presence of NaY faujasite. The case of mercaptophenols, mercaptobenzoic acids, and carboxylic acids bearing OH substituents
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In the presence of NaY faujasite, the reactions of dimethyl carbonate (DMC) with several ambident nucleophiles such as o- and p-mercaptophenols (1a,b), o- and p-mercaptobenzoic acids (2a,b), o- and p-hydroxybenzoic acids (3a,b), mandelic and phenyllactic acids (4, 5), have been explored under batch conditions. Highly chemoselective reactions can be performed: at 150 °C, compounds 1 and 2 undergo only a S-methylation reaction, without affecting OH and CO2H groups; at 165 °C, acids 3-5 form the corresponding methyl esters, while both their aromatic and aliphatic OH substituents are fully preserved from methylation and/or transesterification processes. Typical selectivities are of 90-98% and isolated yields of products (S-methyl derivatives and methyl esters, respectively) are in the range of 85-96%. A comparative study with K2CO3 as a catalyst is also reported. Although the base (K2CO3) turns out to be more active than the zeolite, the chemoselectivity is elusive: compounds 2a,b undergo simultaneous S-methylation and esterification reactions, and acids 3-5 yield complex mixtures of products of O-methylation, O-methoxycarbonylation, and esterification of their OH and CO2H groups, respectively. Overall, the combined use of a nontoxic reagent/solvent (DMC) and a safe promoter (NaY) imparts a genuine ecofriendly nature to the investigated synthesis.
- Selva, Maurizio,Tundo, Pietro
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p. 1464 - 1470
(2007/10/03)
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- Synthesis and PET evaluation of (R)-[S-methyl-11C] thionisoxetine, a candidate radioligand for imaging brain norepinephrine transporters
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Introduction: (R)-3-(2-(methylthio)phenoxy)-N-methyl-3-phenylpropan-1-amine [(R)-thionisoxetine; 1] is a potent inhibitor of the norepinephrine transporter (NET). We aimed to label 1 with carbon-11 (t1/2 = 20.4 min) for evaluation as a radioligand for imaging NET in living brain with positron emission tomography (PET). Methods: Methyl 3-(2-((R)-3-(methylamino)-1- phenylpropoxy)phenylthio)-propanoate (MPPP) and 1 were each prepared from o-hydroxythiophenol in three steps. Treatment of MPPP with potassium t-butoxide and [11C]methyl iodide in tetrahydrofuran gave [5-methyl- 11C]thionisoxetine ([11C]1), which was purified with HPLC. The distribution of radioactivity in brain after intravenous injection of [11C]1 into cynomolgus monkey was followed with PET and the appearance of radiometabolites in plasma monitored with radio-HPLC. Results: [11C]1 was obtained in high yield from [11C]methyl iodide. Of the radioactivity injected into monkey, 2.4% entered brain. Ratios of radioactivity in thalamus, mesencephalon, occipital cortex and caudate to that in cerebellum at 93 min were 1.3, 1.2, 1.2 and 1.1, respectively. The radioactivity in plasma corresponding to unchanged radioligand decreased to 53% at 45 min, with the remainder represented by hydrophilic radiometabolites. Conclusions: MPPP is an effective precursor for 11C-methylation to [11C]1, suggesting that the S-γ-propionic acid methyl ester protecting group may have wider value in the 11C-labeling of aryl methyl sulfides. However, the relatively low ratios of radioactivity to the cerebellum together with an unexpected accumulation of radioactivity in the caudate, makes [11C]1 an unpromising NET radioligand. Copyright
- Schou, Magnus,Pike, Victor W.,Varrone, Andrea,Gulyas, Balazs,Farde, Lars,Halldin, Christer
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p. 1007 - 1019
(2008/02/05)
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- Stereoselective reductase-catalysed deoxygenation of sulfoxides in aerobic and anaerobic bacteria.
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Direct and indirect evidence, of unexpected stereoselective reductase-catalysed deoxygenations of sulfoxides, was found. The deoxygenations proceeded simultaneously, with the expected dioxygenase-catalysed asymmetric sulfoxidation of sulfides, during some biotransformations with the aerobic bacterium Pseudomonas putida UV4. Stereoselective reductase-catalysed asymmetric deoxygenation of racemic alkylaryl, dialkyl and phenolic sulfoxides was observed, without evidence of the reverse sulfoxidation reaction, using anaerobic bacterial strains. A purified dimethyl sulfoxide reductase, obtained from the intact cells of the anaerobic bacterium Citrobacter braakii DMSO 11, yielded, from the corresponding racemates, enantiopure alkylaryl sulfoxide and thiosulfinate samples.
- Boyd, Derek R,Sharma, Narain D,King, Alistair W T,Shepherd, Steven D,Allen, Christopher C R,Holt, Robert A,Luckarift, Heather R,Dalton, Howard
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p. 554 - 561
(2007/10/03)
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- Enhanced O-dealkylation activity of SiCl4/LiI with catalytic amount of BF3
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Dibenzyloxydihydrobenzoxathiin 1, which resisted debenzylation with SiCl4/LiI, was effectively debenzylated with SiCl4/LiI in the presence of a catalytic amount of BF3. The HCl salt of the bis-debenzylated product 2 was isolated in 90% yield and 99% purity. This enhanced dealkylation activity has also been observed with other substrates.
- Zewge, Daniel,King, Anthony,Weissman, Steven,Tschaen, David
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p. 3729 - 3732
(2007/10/03)
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- Synthetic routes to polyheteroacenes: Characterization of a heterocyclic ladder polymer containing phenoxathiinium-type building blocks
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The synthetic routes to ladder polymers that consist of benzenetetrayl subunits with oxo and methylsulfonio linkages are described. As the key intermediate, poly(phenylene oxide)s having pendant methylsulfenyl groups are prepared by copper-catalyzed oxidative polymerization of the corresponding phenols with O2. The oxidation of the polymer with an equimolar amount of H2O2 in the presence of acetic acid effects the high-yielding conversion of methylsulfenyl to methylsulfinyl groups without the formation of the undesired methylsulfonyl groups. The superacidified condensation of the resulting polymer (Swern reaction of aryl sulfoxides) under dilution conditions induces the polymer-analogous intramolecular electrophilic ring-closing reaction of the hydroxymethylphenylsulfonium cation onto the adjacent benzene ring to yield the required ladder polymer, which has proved to be a semiconductor with an intrinsic electric conductivity of 2 × 10-5 S/cm. A comparison of the spectroscopic properties of the ladder polymer with those of the model compounds such as 5-methylphenoxathiinium triflate and phenoxathiin discloses π-electron delocalization over the methylsulfonio linkages, demonstrating the efficacy of the ladderization for p-π/d-π interactions in arylsulfonium moieties. This synthetic approach permits the thio and alkylsulfonio ladder linkages for a variety of phenyl ethers to form in high yields.
- Oyaizu, Kenichi,Mikami, Takefumi,Mitsuhashi, Fumio,Tsuchida, Eishun
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- Electrochemically generated organothiating reagents and their use
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Electrolysis of organic disulfides in liquid sulfur dioxide is used to obtain organothiating agents, which can then be reacted with appropriate substrates to effect the synthesis of organothioaromatic compounds efficiently and in high yields. With appropriate phenolic compounds, regioselective substitution occurs in which para substitution greatly exceeds ortho substitution.
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- Alkyl- and Arylthiodediazoniations of Dry Arenediazonium o-Benzenedisulfonimides. Efficient and Safe Modifications of the Stadler and Ziegler Reactions to Prepare Alkyl Aryl and Diaryl Sulfides
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The reaction between dry arenediazonium o-benzenedisulfonimides 1 and sodium thiolates in anhydrous methanol represents an efficient and safe procedure, of general validity, for the preparation of unfunctionalized or variously functionalized alkyl aryl and diaryl sulfides. As a rule, the reaction temperature was maintained at 0-5°C for the alkylthiodediazoniations and at room temperature (20-25°C) for the arylthiodediazoniations. The sulfide yields are generally high; of the 63 considered examples, 43 gave yields greater than 80% and 13 were between 70% and 80%. Lower yields were obtained only when sterically hindered diazonium salts or thiols were used. A good amount of the o-benzenedisulfonimide (8) was always recovered from the reactions and could be reused to prepare salts 1. The copious experimental data collected in homogeneous conditions have offered several starting points for the study of the mechanism of these reactions.
- Barbero, Margherita,Degani, Iacopo,Diulgheroff, Nicola,Dughera, Stefano,Fochi, Rita,Migliaccio, Mara
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p. 5600 - 5608
(2007/10/03)
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- Electrochemical electrophilic aromatic methylthiation in liquid SO2
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Controlled potential electrolysis of dimethyldisulfide in liquid sulfur dioxide provides a strongly electrophilic methylthiating agent. This species methylthiates strongly to weakly activated arenes in good to excellent yield.
- Glass, Richard S.,Jouikov, Viatcheslav V.
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p. 6357 - 6358
(2007/10/03)
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- Covalent modification of cyclooxygenase-2 (COX-2) by 2-acetoxyphenyl alkyl sulfides, a new class of selective COX-2 inactivators
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All of the selective COX-2 inhibitors described to date inhibit the isoform by binding tightly but noncovalently at the substrate binding site. Recently, we reported the first account of selective covalent modification of COX-2 by a novel inactivator, 2-acetoxyphenyl hept-2-ynyl sulfide (70) (Science 1998, 280, 1268-1270). Compound 70 selectively inactivates COX-2 by acetylating the same serine residue that aspirin acetylates. This paper describes the extensive structure-activity relationship (SAR) studies on the initial lead compound 2-acetoxyphenyl methyl sulfide (36) that led to the discovery of 70. Extension of the S-alkyl chain in 36 with higher alkyl homologues led to significant increases in inhibitory potency. The heptyl chain in 2-acetoxyphenyl heptyl sulfide (46) was optimum for COX-2 inhibitory potency, and introduction of a triple bond in the heptyl chain (compound 70) led to further increments in potency and selectivity. The alkynyl analogues were more potent and selective COX-2 inhibitors than the corresponding alkyl homologues. Sulfides were more potent and selective COX-2 inhibitors than the corresponding sulfoxides or sulfones or other heteroatom-containing compounds. In addition to inhibiting purified COX-2, 36, 46, and 70 also inhibited COX-2 activity in murine macrophages. Analogue 36 which displayed moderate potency and selectivity against purified human COX-2 was a potent inhibitor of COX-2 activity in the mouse macrophages. Tryptic digestion and peptide mapping of COX-2 reacted with [1-14C-acetyl]-36 indicated that selective COX-2 inhibition by 36 also resulted in the acetylation of Ser516. That COX-2 inhibition by aspirin resulted from the acetylation of Ser516 was confirmed by tryptic digestion and peptide mapping of COX-2 labeled with [1- 14C-acetyl]salicyclic acid. The efficacy of the sulfides in inhibiting COX- 2 activity in inflammatory cells, our recent results on the selectivity of 70 in attenuating growth of COX-2-expressing colon cancer cells, and its selectivity for inhibition of COX-2 over COX-1 in vivo indicate that this novel class of covalent modifiers may serve as potential therapeutic agents in inflammatory and proliferative disorders.
- Kalgutkar, Amit S.,Kozak, Kevin R.,Crews, Brenda C.,Hochgesang Jr., G. Phillip,Marnett, Lawrence J.
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p. 4800 - 4818
(2007/10/03)
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- Electrophilic substitutions with the electrogenerated sulfenium cation R1-S+
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The sulfenium cation R1-S+ electrogenerated by oxidation of organic disulfides, reacts with phenols, aromatic ethers and ketones bearing an hydrogen atom in α position, to give alkyl (aryl) sulfanyl compounds.
- Do, Quang Tho,Elothmani, Driss,Le Guillanton, Georges
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p. 4657 - 4658
(2007/10/03)
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- Acid-catalysed Aromatisation of Benzene cis-1,2-dihydrodiols: a Carbocation Transition State poorly stabilised by Resonance
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Acid-catalysed dehydration of 3-substituted benzene cis-1,2-dihydrodiols exhibits a Hammett plot with ρ=-8.2, consistent with reaction via a benzenonium ion-like intermediate; however, correlation of +M resonance substituents such as Me and MeO by ?p rather than ?+ constants indicates a marked imbalance between resonance and inductive stabilisation of the transition state.
- Boyd, Derek R.,Blacker, John,Byrne, Briege,Dalton, Howard,Hand, Mark V.,et al.
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p. 313 - 314
(2007/10/02)
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- PREPARATION OF ORTHO-(ALKYLTHIO)PHENOLS OVER ZEOLITE CATALYSTS
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Amorphous and crystalline (zeolite) aluminosilicates are good catalysts for the alkylthiolation of phenols with disulfides.Zeolites offer product selectivity via catalyst shape selectivity.Product distribution equilibrations are operative, and distributions depend upon reaction time, temperature, catalyst, and stoichiometry.Aluminosilicate and Bronsted acid catalysts give para-(alkylthio)phenols as the major kinetic product while metal phenoxides give ortho as the major.All catalysts give ortho as the major thermodynamic product.
- Wojtkowski, Paul W.,Shannon, Robert D.
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p. 275 - 278
(2007/10/02)
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- Preparation of ortho-(alkyl-or arylthio) phenols
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Strong acids, e.g., aluminosilicates and sulfonic acids are employed as catalysts for the (alkyl or aryl)thiolation of phenols using dialkyl or diaryl disulfides and/or (alkyl- or arylthio)phenols as thiolating agents, and for the isomerization of (alkyl- or arylthio)phenols, to prepare ortho--(alkyl- or arylthio)phenols as the predominant products.
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- Preparation of ortho-(alkyl- or arylthio)phenols
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Strong acids, e.g., aluminosilicates and sulfonic acids are employed as catalysts for the (alkyl or aryl)thiolation of phenols using dialkyl or diaryl disulfides and/or (alkyl- or arylthio)phenols as thiolating agents, and for the isomerization of (alkyl- or arylthio)phenols, to prepare ortho(alkyl- or arylthio)phenols as the predominant products.
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- Process for preparing ortho-(alkylthio)phenols
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The process of the invention involves reacting a phenol with a dialkyl disulfide in the presence of a zirconium phenoxide catalyst to prepare the corresponding ortho-(alkylthio)phenol.
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- Reductive Cleavage of Ether and Thioether Bonds on 1,3-Benzodioxole and 1,3-Benzoxathiole Derivatives
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The reaction of lithium and sodium diethylamide with 1,3-benzodioxoles and 1,3-benzoxathioles is here reported. 1,3-Benzodioxoles exhibit selective cleavage of the ether bond with formation of alkoxyphenols; 1,3-benzoxathioles when reacting with sodium diethylamide lead to 2-alkoxybenzenethiols while with lithium diethylamide give 2-alkoxybenzenethiols together with 2-(alkylthio)phenols.
- Melis, Stefana,Piras, Pier Paolo,Plumitallo, Antonio,Sotgiu, Francesca
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p. 1413 - 1414
(2007/10/02)
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- Process for the preparation of ortho-(hydrocarbylthio)-phenols
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Disclosed is a process for the preparation of otho-(hydrocarbylthio)-phenols, having at least one hydrogen on a carbon atom ortho to a hydroxy group, with hydrocarbyl disulfides in the presence of catalytic amounts of aluminum phenoxide.
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- SELECTIVE CLEAVAGE OF THE CARBON-SULPHUR AND CARBON-OXYGEN BONDS IN METHOXYTHIOANISOLES
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Selective cleavage of thioether or ether functions in methoxythioanisoles in hexamehtylphosphoramide (HMPA) with sodium gives methoxythiophenols by cleavage of the carbon-sulphur bond.Reactions with sodium isopropanethiolate give instead the thiomethoxyphenols by dealkylation of the methoxy function.When the methoxythioanisoles were treated first with sodium isopropanethiolate and then with sodium complete dealkylation was achieved with formation of mercaptophenols.The present methods have considerable advantages over existing procedures for the synthesis of methoxythiophenols, thiomethoxyphenols and mercaptophenols.The mechanistic implications of the reactions investigated are also discussed.
- Testaferri, L.,Tiecco, M.,Tingoli, M.,Chianelli, D.,Maiolo, F.
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p. 2721 - 2724
(2007/10/02)
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