- Mechanism of the aromatic hydroxylation of thiophene by acid-catalyzed peracid oxidation
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The oxidation of thiophene (1) with peracids in a strongly acidic environment yielded thiophen-2-one (4) as the product of an apparent direct hydroxylation of the thiophene aromatic ring together with the anticipated thiophene-S-oxide dimers, 2a,b, as the main products. Formation of the latter dimers can be rationalized in a straightforward manner by initial oxidation at the sulfur atom of thiophene (1) to yield thiophene-S-oxide followed by subsequent dimerization in a Diels-Alder type reaction. Trapping experiments in the presence of a competing dienophile indicated that thiophen-2-one (4) did not originate from the monomeric thiophene-S-oxide but was the product of an independent reaction pathway. The extent of thiophen-2-one (4) formation correlated with the acidity of the reaction medium and was suppressed in the presence of water, the latter presumably acting as a competing base. As evidenced by the use of 2,5-dideuterated thiophene (1-D), its mechanism of formation involved a 1,2-hydride shift, a feature commonly described in the peracid-mediated epoxidation of aromatic hydrocarbons and indicative for the occurrence of cationic intermediates. In agreement with all these observations we propose a mechanism involving initial protonation of thiophene followed by nucleophilic attack of the peracid in position 2 of the thiophene ring. Intramolecular epoxidation may lead to the formation of thiophene 2,3-epoxide as a highly reactive intermediate that then undergoes heterolytic ring opening and a 1,2-hydride shift to yield thiophen-2-one (4) after a final, acid-catalyzed, isomerization of the double bond.
- Treiber, Alexander
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Read Online
- A scalable and green one-minute synthesis of substituted phenols
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A mild, green and highly efficient protocol was developed for the synthesis of substituted phenols via ipso-hydroxylation of arylboronic acids in ethanol. The method utilizes the combination of aqueous hydrogen peroxide as the oxidant and H2O2/HBr as the reagent under unprecedentedly simple and convenient conditions. A wide range of arylboronic acids were smoothly transformed into substituted phenols in very good to excellent yields without chromatographic purification. The reaction is scalable up to at least 5 grams at room temperature with one-minute reaction time and can be combined in a one-pot sequence with bromination and Pd-catalyzed cross-coupling to generate more diverse, highly substituted phenols.
- Elumalai, Vijayaragavan,Hansen, J?rn H.
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p. 40582 - 40587
(2020/11/18)
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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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- Preparation of brominated 2-alkoxythiophenes via oxidation and etherification of 2-thienyltrifluoroborate salts
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The synthesis of ring brominated long-chain 2-alkoxythiophenes is reported, involving mild (Oxone) oxidation of readily prepared 2-thienyltrifluoroborate salts followed by Mitsunobu etherification. Both procedures are operationally straightforward and use inexpensive reagents. Using this approach, several novel mono- and dibrominated octyloxythiophenes with previously elusive substitution patterns were prepared. One such compound was elaborated to a novel 5-alkoxythieno[3,2-b]thiophene-2-carboxylate ester, marking the first synthetic entry into this family of compounds.
- Tietz, Jonathan I.,Seed, Alexander J.,Sampson, Paul
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supporting information
p. 5058 - 5061
(2013/01/15)
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- Addition of 2-tert-butyldimethylsilyloxythiophene to activated quinones: An approach to thia analogues of kalafungin
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The uncatalyzed reaction of 2-tert-butyldimethylsilyloxythiophene 2 with 1,4-quinones bearing either an electron withdrawing acetyl or a carbomethoxy group at C-2, was investigated. No reaction was observed using 1,4-quinones 8 and 9 bearing an ester grou
- Brimble, Margaret A.,Laita, Olivia,Robinson, James E.
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p. 3021 - 3027
(2007/10/03)
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- The Pummerer-like reaction of 2,5-bis(trimethylsilyl) thiophene S-oxide with trifluoroacetic anhydride: Intermediary formation of sulfurane [10-S-4(C202)] (λ4-sulfane)
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On treatment of a 2,5-bissilylsubstituted thiophene S-oxide or dibenzothiophene S-oxide with trifluoroacetic anhydride, the equilibria between the corresponding substrates and hypervalent sulfur compounds (sulfurane or λ4-sulfane) have now been first detected by low temperature NMR experiments. By elevating the temperature to room temperature, in the case of the thiophene S-oxide, the sulfurane detected was converted to 3-thiolene-2-one quantitatively via a Pummerer-like reaction.
- Sato, Soichi,Zhang, Shao-Zhong,Furukawa, Naomichi
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p. 444 - 450
(2007/10/03)
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- A new method for the synthesis of normal and medium ring silylated unsaturated thiolactones
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Enolizable ω-carboxy acylsilanes are converted via (Z)ω-carboxy-α- silyl enethiols into unsaturated silylated thiolactones having a ring size in the range from five to ten.
- Bonini, Bianca F.,Comes-Franchini, Mauro,Fochi, Mariafrancesca,Mazzanti, Germana,Ricci, Alfredo
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p. 486 - 488
(2007/10/03)
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- Tautomerism of the Monohydroxy Derivatives of Five-Membered O, N, and S Heterocycles
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The O-deuterated enolic tautomers 3-deuteroxybenzofuran, 3-deuteroxybenzothiophene, 3-deuteroxyindole, 3-deuteroxy-1-methylindole, 3-deuteroxyfuran, 3-deuteroxythiophene, 2-deuteroxybenzothiophene, and 2-deuteroxythiophene have been generated in solution in mixtures of CD3COCD3, CD3CN, or CD3SOCD3 with D2O by hydrolysis of their trimethylsilyl derivatives in the presence of DCl (1E-3 - 1E-4 M) and characterized by 1H NMR spectroscopy.Solutions of 3-hydroxypyrrole and of 3-hydroxy-1-methylpyrrole were obtained by methanolysis of their trimethylsilyl derivatives,evaporation of the methanol, and immediate dissolution in DMSO-d6.The carbocyclic analogues of the bicyclic heterocyclic enols 3-deuteroxyindene and 2-deuteroxyindene were also generated in solution.Attempts to prepare solutions of 2-deuteroxyfuran, 2-deuteroxypyrrole, and 2-deuteroxy-1-methylpyrrole were unsuccessful.The kinetics of ketonization of the OH forms of these enols have been investigated in water or aqueous acetonitrile solution.The equilibrium constants for the keto-enol tautomerism were also determined either by direct measurement when sufficient enol was present at equilibrium or as the ratio of the rate constant for enolization of the keto form to that for ketonization of the enol form, the former being determined by the iodine-trapping technique.The effect of solvent on the equilibrium constants was also studied.Sufficient data were available for the equilibrium between 3-hydroxyindole and 3-ketoindole for them to be analyzed by the four-parameter equation of Mills and Beak to yield an a value of 2.4 and a b value of -3.0.The pKas of the bicyclic enols were measured. 3-Hydroxybenzofuran and3-hydroxybenzothiophene are stronger acids than 3-hydroxyindole and 3-hydroxy-1-methylindole.The ketonization reactions are general acid and general base catalyzed and their mechanisms are discussed.
- Capon, Brian,Kwok, Fu-Chiu
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p. 5346 - 5356
(2007/10/02)
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- THE TAUTOMERISM OF HYDROXY DERIVATIVES OF FIVE-MEMBERED OXYGEN, NIRTOGEN, AND SULFUR HETEROCYCLES
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The unstable enolic tautomers 3-hydroxyfuran, 2- and 3-hydroxy-thiophene, 3-hydroxy-pyrrole, 3-hydroxy-1-methyl-pyrrole and their benzo-derivatives have been generated in solution and the rate and equilibrium constants for their ketoization determined.
- Capon, Brian,Kwok, Fu-Chiu,Road, Pokfulam
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p. 3275 - 3278
(2007/10/02)
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