- Synergistic Br?nsted/Lewis acid catalyzed aromatic alkylation with unactivated tertiary alcohols or di-tert-butylperoxide to synthesize quaternary carbon centers
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Dual Br?nsted/Lewis acid catalysis involving environmentally benign, readily accessible protic acid and iron promotes site-selective tert-butylation of electron-rich arenes using di-tert-butylperoxide. This transformation inspired the development of a synergistic Br?nsted/Lewis acid catalyzed aromatic alkylation that fills a gap in the Friedel-Crafts reaction literature by employing unactivated tertiary alcohols as alkylating agents, leading to new quaternary carbon centers. Corroborated by DFT calculations, the Lewis acid serves a role in enhancing the acidity of the Br?nsted acid. The use of non-allylic, non-benzylic, and non-propargylic tertiary alcohols represents an underexplored area in Friedel-Crafts reactivity.
- Chojnacka, Maja,Crowley, Robert,G?ttemann, Lucas,Haines, Brandon E.,Kou, Kevin G. M.,Pan, Aaron
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p. 3539 - 3548
(2022/03/31)
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- MACROCYCLIC BROAD SPECTRUM ANTIBIOTICS
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Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.
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Paragraph 00775
(2018/09/12)
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- Synthesis of 2 - fluoro phenol compounds
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The present invention provides a method for synthetizing a 2-fluoro phenol compound shown in a formula IV. The phenol compound shown in the formula I is prepared into a 2-pyridine oxygroup arene compound shown in a formula II through an Ullmann reaction, the 2-pyridine oxygroup arene compound shown in the formula II is mixed with a palladium catalyst, a fluorinating reagent, an additive and an organic solvent, the mixture is stirred under the temperature of 30-160 DEG C to perform a fluorination reaction to obtain an ortho-position fluoridated 2-pyridine oxygroup arene compound shown in a formula III, and the ortho-position fluoridated 2-pyridine oxygroup arene compound shown in the formula III is prepared into the 2-fluoro phenol compound shown in the formula IV through the action of alkali. The method provided by the present invention has the advantages of mild reaction conditions, simplicity in operations, good substrate adaptability, high fluorination selectivity and the like. The 2-fluoro phenol compound is shown in the figure below.
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Paragraph 0096; 0097; 0100
(2017/04/21)
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- Fluorination of 4-alkyl-substituted phenols and aromatic ethers with fluoroxy and N-F reagents: Cesium fluoroxysulfate and N-fluoro-1,4-diazonia- bicyclo[2.2.2]octane dication salts case Dedicated to Prof. Dr. Boris ?emva in honor to his great contribution to fluorine chemistry.
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4-Alkyl-substituted phenols and aromatic ethers were comparatively fluorinated with electrophilic fluorinating reagents such as cesium fluoroxysulfate (CFS), Selectfluor F-TEDA-BF4, and Accufluor NFTh in MeCN or MeOH. Reactions resulted in the formation of three types of products: 2-fluoro-4-alkyl-substituted corresponding compounds (5) as a result of ortho fluorination process, 4-alkyl-4-fluoro-cyclohexa-2,5- dienone compounds (6), resulting after an addition-elimination process, and 4-fluorosubstituted corresponding compounds (7) derived from ipso attack and release of the 4-alkyl group. The distribution of products depends on the bulkiness of alkyl groups at both positions and reaction media. The reaction in methanol proved more selective toward the formation of 2-fluoro derivatives. Tyramin and l-tyrozine were transformed with NFTh reagent in methanol to their fluorophenyl-substituted derivatives in good yield.
- Pravst, Igor,Stavber, Stojan
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p. 276 - 282
(2014/01/06)
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- Nucleophilic deoxyfluorination of catechols
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Nucleophilic deoxyfluorinaiton of one of the two hydroxyl groups of catechols has been developed via the Umpolung concept. This method was successively applied to naturally occurring catechols, such as catechins and dopamine, to produce novel fluorinated
- Nemoto, Hiroyuki,Nishiyama, Tsuyoshi,Akai, Shuji
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p. 2714 - 2717
(2011/06/28)
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- 4-AMINO-7,8-DIHYDROPYRIDO[4,3-d]PYRIMIDIN-5(6H)-ONE DERIVATIVES
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The invention provides compounds of the general Formula (I) where R1, R2, and A are defined herein, as well as the preparation, compositions and uses thereof.
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Page/Page column 36
(2010/08/08)
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- Transformations of organic molecules with F-TEDA-BF4 in ionic liquid media
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The transformations of organic molecules with F-TEDA-BF4 (1) were investigated in the hydrophilic ionic liquid (IL) 1-butyl-3-methyl- imidazolium tetrafluoroborate ([bmim][BF4], 2) and the hydrophobic IL 1-butyl-3-methyl-imidazolium hexafluorophosphate ([bmim][PF6], 3). The range of substrates included alkyl substituted phenols 4a-c, 9, 13, 1,1-diphenylethene (15), alkyl aryl ketones 19-22, aldehydes 23-25 and methoxy-substituted benzene derivatives 26-30. The evaluation of the outcome of reactions performed in IL media in comparison to those of the corresponding reactions in conventional organic solvents revealed that the transformations in IL are less efficient and selective. The effect of the presence of a nucleophile (MeOH, H2O, MeCN) on the course of reaction was also studied.
- Pavlinac, Jasminka,Zupan, Marko,Stavber, Stojan
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experimental part
p. 2394 - 2409
(2009/12/03)
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- 2-AMINOBENZAMIDE DERIVATIVE
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To provide a novel and excellent agent for treating or preventing nociceptive pain, neuropathic pain, cancer pain, headache, bladder function disorder and the like, based on the inhibitory action on the capsaicin receptor VR1 activation. The present inven
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Page/Page column 21
(2008/12/07)
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- Solvent-free fluorination of organic compounds using N-F reagents
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Efficient fluorination of 1,3-dicarbonyl compounds, enol acetates of aromatic ketones, and activated aromatic compounds was achieved under solvent-free conditions using Selectfluor F-TEDA-BF4 or Accufluor NFSi.
- Stavber, Gaj,Zupan, Marko,Stavber, Stojan
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p. 2671 - 2673
(2008/02/03)
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- The role of F-N reagent and reaction conditions on fluoro functionalisation of substituted phenols
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The effect of steric interactions on the regioselectivity of fluorination of para alkyl substituted phenols was investigated and the strong effect of size of the alkyl substituent, the structure of the F-N reagent and the solvent on the site of fluorination was established. The course of reaction obeyed a second order rate equation, while the fluorination process required higher ΔH≠ activation than oxidation or oxidative demethylation. Solvent polarity variations had a small effect on the rate of functionalisation, while an excellent Hammett correlation with ρ+=-2.3 was determined.
- Pravst, Igor,Iskra, Maja Pape?,Jereb, Marjan,Zupan, Marko,Stavber, Stojan
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p. 4474 - 4481
(2007/10/03)
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- Chemistry of Organo Halogenic Molecules. 140. Role of the Reagent Structure on the Transformations of Hydroxy Substituted Organic Molecules with the N-Fluoro Class of Fluorinating Reagents
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Hydroxy-substituted organic molecules were used as target molecules in investigations of the role of the reagent structure on the reactivity of three types of N-F class fluorinating reagents: 1-chloromethyl-4-fluoro-1,4-diazoniabicyclooctane bis(tetrafluoroborate) F-TEDA (1a), N-fluorobis(phenylsulfonyl)amine NSF (1b), and N-Fluoropyridinium heptafluorodiborate-pyridine (1/1) NFP (1c).Methanol is stable, but hydroquinone is very quickly transformed in acetonitrile to quinone with F-TEDA at room temperature: on the other hand, NSF is less reactive, while oxidation with NFP is achieved only at an elevated temperature; a structure variation of the hydroquinone derivatives did not influence oxidation.Fluorination was achieved with monohydroxy-substituted aromatic compounds; a similar trend concerning the reactivity of N-F reagent (1) was also observed in reactions with 1- and 2-naphthol, while 9-phenanthrol gave 10,10-difluoro-9-(10H)-phenanthrenone with F-TEDA in acetonitrile and 9,10-phenanthrenequinone with NSF.Dealkylation was observed in a reaction with 4-methoxyphenol; although the thio analogue gave bis(4-methoxyphenyl) disulfide, the reactivity was changed and NSF was more reactive than F-TEDA and NFP.
- Zupan, Marko,Iskra, Jernej,Stavber, Stojan
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p. 1655 - 1660
(2007/10/02)
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- The effect of heteroatoms on the reactions of organic molecules with caesium fluoroxysulphate
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CsSO4F reacted at room temperature, or at 35°C in acetonitrile with various heteroatom-containing organic molecules, and three types of transformations have been observed. Fluoro substitution process took place with triphenylmethane, triphenylsilane, triphenylchlorosilane, 4-tert-butylphenol, benzaldehyde, and octanol, thus forming fluorotriphenylmethane, fluorotriphenylsilane, 2-fluoro-4-tert-butylphenol, benzoyl fluoride, or octanoyl fluoride in high yields. Substitution reaction was accompanied by fluoroaddition process in the case of 2-fluoro-4-tert-butylphenol, where 2,2-difluoro-4-tert-butylcyclohexadienon-4,6- was isolated. CsSO4F easily oxidised secondary alcohols to ketones, and 1,2-dihydro-4-tert-butylbenzene to quinone derivate. Oxygenation process was observed in the case of triphenylphosphine, and dibenzothiophene, while ethyl iodide was transformed to ethyliodo(III) difluoride. Solvent plays an important role in these reactions, being successfully performed in CH3CN, and completely inhibited in CH2Cl2, while different shapes of the effect on fluorination of various organic molecules were observed by altering solvent nature by successive mixing of CH3CN with CH2Cl2.
- Stavber,Zupan
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p. 5875 - 5882
(2007/10/02)
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- Selective Preparation. 31. Oxidative Coupling of 2-Halo-4,6-di-tert-butylphenols with Potassium Hexacyanoferrate (III) in Benzene
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When 2-bromo-4,6-di-tert-butylphenol (1b) was treated with K3Fe(CN)6 in benzene, 1,4-dihydro-4-bromo-2,4,6,8-tetra-tert-butyl-1-oxodibenzofuran (3) was obtained in 81percent yield together with a small amount of 2,4,6,8-tetra-tert-butyldibenzofuran (4).Heating of 3 in primary alcohols such as methanol and ethanol afforded the corresponding 1,4-dihydro-4-alkoxy-2,4,6,8-tetra-tert-butyl-1-oxodibenzofuran (9) in good yields.However, treatment of 3 with boiling isopropyl alcohol gave in 85percent yield 1-hydroxy-2,4,6,8-tetra-tert-butyldibenzofuran (5), which afforded 1-hydroxydibenzofuran (6) by its AlCl3-catalyzed trans tert-butylation in toluene.Compound 6 was obtained also by the AlCl3-catalyzed trans alkylation of 3.Similar trans alkylation of 4 afforded dibenzofuran (19). 1-Hydroxy-4-methoxy- (11) and 1,4-dihydro-1,4-dioxo-2,6,8-tri-tert-butyldibenzofuran (12) were also prepared from compound 3.Similar oxidation of 2-chloro-4,6-di-tert-butylphenol (1c) afforded 6,6'-bis (22) and 2,4-di-tert-butyl-4-chloro-6-(2,4-di-tert-butyl-6-chlorophenoxy)-cyclohexa-2,5-dien-1-one (23) in 23percent and 53percent yields, respectively.However, oxidation of 2-fluoro-4,6-di-tert-butylphenol (1d) gave only one product, 2,4-di-tert-butyl-4-fluoro-6-(2,4-di-tert-butyl-6-fluorophenoxy)-cyclohexa-2,5-dien-1-one (36), in 63percent yield.The mechanisms of oxidation of 2-halo-4,6-di-tert-butylphenols with K3Fe(CN)6 in benzene were also discussed in this paper.
- Tashiro, Masashi,Yoshiya, Haruo,Fukata, Gouki
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p. 3784 - 3789
(2007/10/02)
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- 2-(Aminomethyl)phenols, a new class of saluretic agents. I. Effect of nuclear substitution
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A series of 2-(aminomethyl)phenols was synthesized and tested in rats and dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration. The most active compounds belong to a subseries of 4-alkyl-6-halo derivatives of which 2,2(aminomethyl)-4-(1,1-dimethylethyl)-6-iodophenyl, is the most active. Compound 2 also possesses significant antihypertensive activity, an adjunctive pharmacological parameter which distinguishes 2 from the other compounds prepared in this series. In addition, 2 displays both topical saluretic and antiinflammatory activities.
- Stokker,Deana,deSolms,Schultz,Smith,Cragoe Jr.,Baer,Ludden,Russo,Scriabine,Sweet,Watson
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p. 1414 - 1427
(2007/10/02)
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