- Tetrafluoropyridyl (TFP): a general phenol protecting group readily cleaved under mild conditions
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Phenols are extremely valuable building blocks in the areas of pharmaceuticals, natural products, materials and catalysts. In order to carry out modifications on phenols, the phenolic oxygen is routinely protected to prevent unwanted side reactions. Presently many of the protecting groups available can require harsh conditions, specialist equipment, expensive or air/moisture-sensitive reagents to install and remove. Here we introduce the use of the tetrafluoropyridyl (TFP) group as a general protecting group for phenols. TFP can be installed in one step with no sensitivity to water or air, and it is stable under a range of commonly employed reaction conditions including acid and base. The TFP protecting group is readily cleaved under mild conditions with quantitative conversion to the parent phenol, observed in many cases in less than 1 hour.
- Brittain, William D. G.,Cobb, Steven L.
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supporting information
p. 2110 - 2115
(2019/02/27)
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- A process for the preparation of key intermediate lei meiti amine, its preparation and use
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The invention discloses critical intermediates (with the structure formula (I) ) used for preparing ramelteon. In the formula (I), A is O or S; R is hydrogen, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, tert-butyl, cyclobutyl, n-pentyl, isopentyl, cyclopentyl, phenyl, benzyl or p-methoxybenzyl; and when chiral carbon exists, the chemical compounds in the formula (I) are racemate or optically active compounds. When the A in the formula (I) is O and the R in the formula (I) is ethyl, the chemical compound is the chemical compound shown as the structure formula (II). In addition, the invention further discloses a preparing method of the chemical compound shown as the formula (II) and applications of the formula (II) in preparation of the ramelteon used for treating insomnia.
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Paragraph 0071-0073
(2020/02/07)
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- Method for continuous flow synthesis of phenol-based compound
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The present invention provides a method for continuous flow synthesis of a phenol-based compound represented by a formula (III), wherein the method is performed in two static mixers, a tubular reactor and an oil-water separator, wherein the two static mixers, the tubular reactor and the oil-water separator are sequentially connected in series. The method comprises that an acid solution and an aniline compound represented by a formula (I) are pumped into the static mixer A; the mixture of the acid solution and the compound represented by the formula (I) flows out from the static mixer A and flows into the static mixer B connected to the static mixer A; a sodium nitrite solution is pumped into the static mixer B, and a reaction is performed to produce a diazonium salt solution represented by a formula (II); and the solution represented by the formula (II) flows out from the static mixer B, is pumped into the tubular reactor connected to the static mixer B, and then into the oil-water separator connected to the tubular reactor, and the water phase is separated to obtain the compound represented by the formula (III). According to the present invention, the method has characteristics of short reaction time, solvent saving and high yield, and can well solve the problems in the synthesis of the phenol-based compound through diazotization hydrolysis in the intermittent kettle type reactor. The formulas (I), (II) and (III) are defined in the specification.
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Paragraph 0053; 0054
(2017/07/21)
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- Thermal Protodeboronation of hydroxyarene Boronic Acids and Its Application to ortho- and meta- Functionalization of hydroxyarene Using Boronic Acids as Blocking and Directing Groups
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The present invention refers to hydroxy arene boron acid compounds that thermal de borohydride of phenolic compounds using functional groups in ortho-or meta-position with hydroxy [...] manufacturing method relates to, more particularly boron position and outputs ortho of phenol then substituted acid, ortho-or meta-position boron arene hydroxy then introduced to a functional groups in making and compounds, thermal de using borohydride said boron acid by removing phenol from ortho-or meta-position functional groups in have been introduced method for preparing the compounds of arene hydroxy relates to. Manufacturing method of arene compound hydroxy the present invention according to such as iridium or a palladium metal catalyst-free, a stronger acid than the acid or base conditions, a low-temperature reaction acid and acetic anhydride the microbeam generating reactions, by causing or permitting a condition without requiring a step of client and, simply phenol from ortho-or meta-position for introducing functional groups to hydroxy arene compound can be produced.
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Paragraph 0141; 0142; 0146
(2016/10/27)
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- Continuous-flow hydroxylation of aryl iodides promoted by copper tubing
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A simple and ligand-free synthesis of phenols from the corresponding aryl iodides in a continuous-flow system is described. The reaction is complete in only 4 to 20 minutes when heated between 150 to 165 °C in a reactor consisting of a commercially available copper coil. An example of trapping of the phenoxide in situ is also shown.
- Cyr, Patrick,Charette, André B.
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supporting information
p. 1409 - 1412
(2014/06/23)
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- Synthesis of the melatonin receptor agonist Ramelteon using a tandem C-H activation-alkylation/Heck reaction and subsequent asymmetric Michael addition
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An asymmetric synthesis of the melatonin receptor agonist Ramelteon 1 has been achieved, which involved a tandem C-H activation-alkylation/Heck reaction and subsequent highly diastereoselective asymmetric Michael addition to generate the corresponding chiral intermediate, which was readily converted into Ramelteon 1 in 19% overall yield in 15 linear steps.
- Fu, Xiaodan,Guo, Xingqun,Li, Xingwei,He, Lidong,Yang, Yushe,Chen, Youxi
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p. 827 - 832
(2013/08/23)
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- Protodeboronation of ortho- and para-phenol boronic acids and application to ortho and meta functionalization of phenols using boronic acids as blocking and directing groups
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The first metal-free thermal protodeboronation of ortho- and para-phenol boronic acids in DMSO was developed. The protodeboronation was successfully applied to the synthesis of ortho- and meta-functionalized phenols using the boronic acid moiety as a blocking group and a directing group, respectively. Mechanistic studies suggested that this protodeboronation proceeds through the coordination of water to the boron atom followed by σ-bond metathesis.
- Lee, Chun-Young,Ahn, Su-Jin,Cheon, Cheol-Hong
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p. 12154 - 12160
(2014/01/06)
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- Base-catalyzed dehydration of 3-substituted benzene cis -1,2-dihydrodiols: Stabilization of a cyclohexadienide anion intermediate by negative aromatic hyperconjugation
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Evidence that a 1,2-dihydroxycyclohexadienide anion is stabilized by aromatic "negative hyperconjugation" is described. It complements an earlier inference of "positive" hyperconjugative aromaticity for the cyclohexadienyl cation. The anion is a reactive intermediate in the dehydration of benzene cis-1,2-dihydrodiol to phenol. Rate constants for 3-substituted benzene cis-dihydrodiols are correlated by σ- values with = 3.2. Solvent isotope effects for the reactions are kH2O/kD 2O = 1.2-1.8. These measurements are consistent with reaction via a carbanion intermediate or a concerted reaction with a "carbanion-like" transition state. These and other experimental results confirm that the reaction proceeds by a stepwise mechanism, with a change in rate-determining step from proton transfer to the loss of hydroxide ion from the intermediate. Hydrogen isotope exchange accompanying dehydration of the parent benzene cis-1,2-dihydrodiol was not found, and thus, the proton transfer step is subject to internal return. A rate constant of ～1011 s-1, corresponding to rotational relaxation of the aqueous solvent, is assigned to loss of hydroxide ion from the intermediate. The rate constant for internal return therefore falls in the range 1011-1012 s -1. From these limiting values and the measured rate constant for hydroxide-catalyzed dehydration, a pKa of 30.8 ± 0.5 was determined for formation of the anion. Although loss of hydroxide ion is hugely exothermic, a concerted reaction is not enforced by the instability of the intermediate. Stabilization by negative hyperconjugation is proposed for 1,2-dihydroxycyclohexadienide and similar anions, and this proposal is supported by additional experimental evidence and by computational results, including evidence for a diatropic ("aromatic") ring current in 3,3-difluorocyclohexadienyl anion.
- Kudavalli, Jaya Satyanarayana,Rao, S. Nagaraja,More Oferrall, Rory A.,Bean, David E.,Fowler, Patrick W.,Sharma, Narain D.,Boyd, Derek R.,Kamerlin, Shina Caroline Lynn,Keeffe, James R.,Gronert, Scott
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supporting information
p. 14056 - 14069,14
(2020/08/31)
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- Mild debenzylation of aryl benzyl ether with BCl3 in the presence of pentamethylbenzene as a non-lewis-basic cation scavenger
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Scope and limitations of the debenzylation conditions for aryl benzyl ether, which was developed during our synthetic studies on yatakemycin, were investigated. The chemoselective debenzylation proceeds at low temperature with a combination of BCl3 and pentamethylbenzene as a cation scavenger in the presence of various functional groups.
- Okano, Kentaro,Okuyama, Kei-Ichiro,Fukuyama, Tohru,Tokuyama, Hidetoshi
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scheme or table
p. 1977 - 1980
(2009/04/07)
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- High-yielding cleavage of (aryloxy)acetates
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A reliable and high-yielding one-pot sequence for the removal of O-carboxymethyl moieties from phenols is presented. When diethylphosphoryl azide is employed as the azide transfer reagent in the Curtius rearrangement and glycerol in the subsequent hydrolytic workup, the protocol can be reliably applied to a very broad scope of substrates. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Spurg, Anke,Waldvogel, Siegfried R.
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p. 337 - 342
(2008/09/18)
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- Enantioselective hydrogenation of α-aryloxy α,β- unsaturated acids. Asymmetric synthesis of α-aryloxycarboxylic acids
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(Chemical Equation Presented) A facile preparation of chiral α-aryloxy carboxylic acids via asymmetric hydrogenation of the corresponding unsaturated acids has been discovered. A number of catalysts have been identified that give high product enantioselectivity, and the scope of the reaction has been examined with respect to substitution on the aromatic ring and olefin.
- Maligres, Peter E.,Krska, Shane W.,Humphrey, Guy R.
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p. 3147 - 3150
(2007/10/03)
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- Chemoselective one-pot reductive deamination of aryl amines
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A one-pot deamination of a wide variety of substituted anilines is described. The process involves a diazotization-dediazotization utilizing acetic acid, sodium nitrite, and sodium bisulfite- inexpensive, 'green' reagents. The process occurs quickly under mild conditions, tolerates sensitive functionality, and gives products in modest-to-good yields (16-88%).
- Geoffroy, Otto J.,Morinelli, Thomas A.,Meier, G. Patrick
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p. 5367 - 5369
(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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- Selective desilylation of tert-butyldimethylsilyl ethers of phenols using potassium fluoride-alumina and ultrasound
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The use of potassium fluoride on basic alumina in acetonitrile with ultrasound for the selecting deprotection of tert-butyldimethylsilyl ethers of phenols is described. The method, which features a non-aqueous work-up, readily cleaves tert-butyldimethylsilyl ethers of phenols at room temperature, whereas tert-butyldimethylsilyl ethers of benzyl alcohols or 2-(trimethylsilyl) ethoxymethyl ethers of phenols are stable.
- Schmittling, Elisabeth A.,Sawyer, J. Scott
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p. 7207 - 7210
(2007/10/02)
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- REACTION OF ORGANIC CARBONATES WITH AMINES. II. REACTION OF ALKYL PHENYL CARBONATES WITH SECONDARY AMINES
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The reaction of alkyl phenyl carbonates with secondary amines leads to the formation of N,N-dialkylurethanes and phenols.The reaction has overall second order.The effect of the substituents in the aromatic ring of the alkyl phenyl carbonates and the polarity of the solvent on the reaction rate was investigated.
- Mikheev, V. V.,Svetlakov, N. V.,Garipov, R. M.,Kalmykova, N. D.
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p. 1865 - 1868
(2007/10/02)
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- REACTION OF ORGANIC CARBONATES WITH AMINES I. REACTION OF ALKYL PHENYL CARBONATES WITH PRIMARY ALIPHATIC AMINES
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The reaction of alkyl phenyl carbonates with primary aliphatic amines, leading to the formation of N-alkylurethanes, was investigated.The reaction has overall third order, which is explained by the catalytic action of the amine.The effect of the structure of the alkyl radical and the character of the substituent in the phenyl group of the alkyl phenyl carbonates and also the effect of the polarity of the solvent on the rate of the transformation were investigated.The reaction obeys the Hammett equation.
- Mikheev, V. V.,Svetlakov, N. V.,Garipov, R. M.
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p. 215 - 220
(2007/10/02)
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