- Azoacetylenes for the Synthesis of Arylazotriazole Photoswitches
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We report a modular approach toward novel arylazotriazole photoswitches and their photophysical characterization. Addition of lithiated TIPS-acetylene to aryldiazonium tetrafluoroborate salts gives a wide range of azoacetylenes, constituting an underexplored class of stable intermediates.In situdesilylation transiently leads to terminal arylazoacetylenes that undergo copper-catalyzed cycloadditions (CuAAC) with a diverse collection of organoazides. These include complex molecules derived from natural products or drugs, such as colchicine, taxol, tamiflu, and arachidonic acid. The arylazotriazoles display near-quantitative photoisomerization and long thermalZ-half-lives. Using the method, we introduce for the first time the design and synthesis of a diacetylene platform. It permits implementation of consecutive and diversity-oriented approaches linking two different conjugants to independently addressable acetylenes within a common photoswitchable azotriazole. This is showcased in the synthesis of several photoswitchable conjugates, with potential applications as photoPROTACs and biotin conjugates.
- Anderl, Felix,Balkenhohl, Moritz,Carreira, Erick M.,Fink, Moritz,Pfaff, Patrick
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p. 14495 - 14501
(2021/09/18)
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- Expanding the Balz–Schiemann Reaction: Organotrifluoroborates Serve as Competent Sources of Fluoride Ion for Fluoro-Dediazoniation
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The Balz–Schiemann reaction endures as a method for the preparation of (hetero)aryl fluorides yet is eschewed due to the need for harsh conditions or high temperatures along with the need to isolate potentially explosive diazonium salts. In a departure from these conditions, we show that various organotrifluoroborates (RBF3?s) may serve as fluoride ion sources for solution-phase fluoro-dediazoniation in organic solvents under mild conditions. This methodology was successfully extended to a one-pot process obviating aryl diazonium salt isolation. Sterically hindered (hetero)anilines are fluorinated under unprecedentedly mild conditions in good-to-excellent yields. Taken together, this work expands the repertoire of RBF3?s to act as fluorine ion sources in an update to the classic Balz–Schiemann reaction.
- Mohy El Dine, Tharwat,Sadek, Omar,Gras, Emmanuel,Perrin, David M.
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supporting information
p. 14933 - 14937
(2018/09/25)
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- Fluorination of aryl boronic acids using acetyl hypofluorite made directly from diluted fluorine
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Aryl boronic acids or pinacol esters containing EDG were converted in good yields and fast reactions to the corresponding aryl fluorides using the readily obtainable solutions of AcOF. In reactions with aryl boronic acids containing EWG at the para position, there are two competing forces: one directing the fluorination to take place ortho to the boronic acid and the other, toward an ipso substitution. With EWG meta to the boronic acid, substitution ipso to the boron moiety takes place in good yields.
- Vints, Inna,Gatenyo, Julia,Rozen, Shlomo
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p. 11794 - 11797
(2014/01/06)
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- Cu-catalyzed fluorination of diaryliodonium salts with KF
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A mild Cu-catalyzed nucleophilic fluorination of unsymmetrical diaryliodonium salts with KF is described. This protocol preferentially fluorinates the smaller aromatic ligand on iodine(III). The reaction exhibits a broad substrate scope and proceeds with high chemoselectivity and functional group tolerance. DFT calculations implicate a CuI/CuIII catalytic cycle.
- Ichiishi, Naoko,Canty, Allan J.,Yates, Brian F.,Sanford, Melanie S.
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supporting information
p. 5134 - 5137
(2013/10/22)
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- Copper-mediated fluorination of aryl iodides
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The synthesis of aryl fluorides has been studied intensively because of the importance of aryl fluorides in pharmaceuticals, agrochemicals, and materials. The stability, reactivity, and biological properties of aryl fluorides can be distinct from those of the corresponding arenes. Methods for the synthesis of aryl fluorides, however, are limited. We report the conversion of a diverse set of aryl iodides to the corresponding aryl fluorides. This reaction occurs with a cationic copper reagent and silver fluoride. Preliminary results suggest this reaction is enabled by a facile reductive elimination from a cationic arylcopper(III) fluoride.
- Fier, Patrick S.,Hartwig, John F.
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supporting information; experimental part
p. 10795 - 10798
(2012/08/07)
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- Synthesis of aryl fluorides on a solid support and in solution by utilizing a fluorinated solvent
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(Figure Presented) F for fast: The perfluorinated solvent C 6F14 is the key to a new variant of the BalzSchiemann reaction for the synthesis of fluorinated arenes. Triazenes are converted into fluoroarenes under mild con-ditions on a support and in solution (see scheme). The method is straightforward and inexpensive, and yields previously difficult-to-prepare fluoroarenes in high purity.
- Doebele, Marion,Vanderheiden, Sylvia,Jung, Nicole,Braese, Stefan
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scheme or table
p. 5986 - 5988
(2010/10/01)
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- Efficient synthesis of aryl fluorides
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Chemical Equation Presented Creating C-F bonds: A novel electrophilic fluorination of aryl and heteroaryl Crignard reagents has been discovered and was used for the efficient synthesis of various aryl fluoride derivatives (see picture; THF = tetrahydrofuran).
- Anbarasan, Pazhamalai,Neumann, Helfried,Beller, Matthias
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experimental part
p. 2219 - 2222
(2010/06/17)
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- Conformational flexibility of tetralactam macrocycles and their intermolecular hydrogen-bonding patterns in the solid state
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Despite their rigid scaffold, tetralactam macrocycles (TLMs) display a remarkable degree of conformational flexibility, as revealed by analysis of the corresponding X-ray crystal structures. This flexibility is not limited to the rotatability of the TLM amide groups but also applies to the m-xylene rings, and it thus has a great impact on the overall shape of the macrocycle cavity. The conformational properties of the TLMs give rise to a broad variety of intermolecular hydrogen-bonding patterns, including infinite ladders, an interesting catemer motif, and short C-H... O=C hydrogen bonds. These results are in accord with previous theoretical calculations, support a structural model proposed earlier for an interpretation of scanning tunneling microscopy images, and substantially contribute to the understanding of the adaptability of macrocyclic scaffolds, which is crucial for guest binding or templated syntheses with TLMs.
- Zhu, Sascha S.,Nieger, Martin,Daniels, Joerg,Felder, Thorsten,Kossev, Iordan,Schmidt, Thomas,Sokolowski, Moritz,Voegtle, Fritz,Schalley, Christoph A.
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experimental part
p. 5040 - 5046
(2009/12/26)
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- Fluorination of aromatic compounds with N-fluorobenzenesulfonimide under solvent-free conditions
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Reactions of N-fluorobenzenesulfonimide with methylbenzenes, phenols, and phenol ethers were studied under solvent-free conditions. The rate constant ratio for the reactions with mesitylene and durene indicates polar mechanism of the process. Solvent-free fluorination of aromatic compounds with N-fluorobenzenesulfonimide in some cases is more selective than reactions with other N-F reagents in a solvent.
- Andreev,Borodkin,Shubin
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scheme or table
p. 1468 - 1473
(2010/03/24)
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- Process for the preparation of fluoro compounds from the corresponding amines
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Compounds containing a primary amino group are converted into compounds containing a fluorine atom in place of the amino group by reaction of the amino compound with hydrogen fluoride and a nitrosating reagent under the influence of ultrasound or microwaves.
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- Preparation process of fluorine substituted aromatic compound
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A preparation process of a fluorine substituted aromatic compound comprising reacting an alkali metal or alkali earth metal salt of an aromatic compound having a hydroxy group with an organic fluorinating agent is disclosed. As a representative fluorinating agent, a bis-dialkylamino-difluoromethane compound, for example, 2,2′-difluoro-1,3-dimethylimidazolidine, is exemplified. According to the process, an industrially useful fluorinated aromatic compound, for example, a fluorobenzene, a fluorine substituted benzophenone, a fluorine substituted diarylsulfone can be prepared with ease in economy without specific equipment.
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- Process for preparing o-alkylfluorobenzenes
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o-Alkylfluorobenzenes are advantageously prepared by heating the corresponding chloroformates to from 70° to 200° C. in the liquid phase in the presence of hydrogen fluoride and in the presence of an inert diluent other than a halogenated alkane.
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- Liquid-Phase Decarboxylation of Aromatic Haloformates: A New Access to Chloro- and Fluoroaromatics
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The treatment of phenyl chloroformates 1 with a Lewis acid in the liquid phase resulted in decarboxylation to the corresponding chloroaromatics 2. Fluoroaromatic compounds were synthesized from phenylchloroformates 1 through a sequential fluorination/decarboxylation in the liquid phase by treatment with excess anhydrous hydrogen fluoride under mild conditions. In all cases, yields were increased by performing the reaction in 1,2,4-trichlorobenzene, which is inert to Friedel-Crafts reactions.
- Lui, Norbert,Marhold, Albrecht,Rock, Michael H.
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p. 2493 - 2496
(2007/10/03)
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- A Fluorine-Containing Cryptand for the Complexation of Anions and the Utility of 19F NMR Spectroscopy for the Determination of Host-Guest Association
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The first fluorine-containing cryptand F3-TREN 4 for the complexation of anions was prepared in the 3 + 2-condensation reaction of 2-fluoro-1,3-phthalaldehyde 3 with tris(2-aminoethyl)amine and subsequent reduction with NaBH4.Upon incorporation of anionic guests 4*6HClO4 experiences shifts of its 19F NMR resonances and thus demonstrates the advantages of studying host-guest association by 19F NMR spectroscopy. - Keywords: Macrocycles, 19F NMR Spectra, Fluorine, Anion Complexation
- Plenio, Herbert,Diodone, Ralph
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p. 1075 - 1078
(2007/10/02)
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- Process for the preparation of halogenated aromatics
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Halogenated aromatics are prepared by heating halogenoformic acid esters to 80° to 280° C. in the presence of hydrogen fluoride or a catalytic amount of one or more Lewis acids from the group comprising aluminium halides, iron halides and antimony halides, and in the liquid phase.
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- Facile conversion of arenediazonium salts to the corresponding fluoroarenes using boron trifluoride diethyl ether complex
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The conversion of various arenediazonium salts 1 to the corresponding fluoroarenes 2 has been achieved in good yields under mild conditions in boron trifluoride diethyl ether complex.
- Shinhama,Aki,Furuta,Minamikawa
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p. 1577 - 1582
(2007/10/02)
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- Mechanism of aromatic hydroxylation in a copper monooxygenase model system. 1,2-methyl migrations and the NIH shift in copper chemistry
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The NIH shift mechanism appears to be operative in a copper monooxygenase model system involving dicopper ion complex mediated O2 hydroxylation of an arene substrate. Previous studies have shown that when a dicopper(I) complex containing two tridentate PY2 units (PY2 = bis[2-(2-pyridyl)ethyl]amine) which are linked by a m-xylyl group, i.e., [Cu2(XYL-H)]2+ (1), is reacted with dioxygen, a Cu2O2 intermediate forms and hydroxylation in the intervening 2-xylyl position occurs. Here, corresponding reactions of 2-methyl substituted analogues [Cu2(Me2XYL-CH3)]2+ (4) and [Cu2(XYL-CH3)]2+ (5) are described in detail. Oxygenation of these causes xylyl hydroxylation reactions producing new phenol products, with concomitant 1,2-migration of the methyl group, loss of one PY2 ligand arm, and formaldehyde formation. Manometric O2 uptake experiments and an 18O2 labeling study confirm that the stoichiometry of these reactions are consistent with that observed for monooxygenases. A reaction carried out using a dinucleating ligand which has been deuterated in benzylic positions confirms that the CH2O product is derived from this carbon atom, a result also consistent with migration of the 2-methyl group. A small yield of methylbis[2-(2-pyridyl)ethyl]amine (MePY2) is consistently obtained, and experiments suggest this may be derived from the reduction of an intermediate iminium salt [CH2=N[CH2CH2PY]2]+ (PY = 2-pyridyl). The hydroxylation induced 1,2-methyl migrations observed here are reminiscent of the NIH shift reactions previously observed only in iron hydroxylases and suggest that the copper ion mediated reactions proceed by the electrophilic attack of a Cu2O2 intermediate upon the proximate aromatic substrate. A detailed mechanism is proposed and discussed in terms of the known O2 reactivity and structure of these dinuclear copper complexes. The biological relevance and significance of this monooxygenase model system is also discussed.
- Nasir, M. Sarwar,Cohen, Brett I.,Karlin, Kenneth D.
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p. 2482 - 2494
(2007/10/02)
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- Metacyclophanes and Related Compounds. Part 16. Preparation of 8-Fluoro-t-butylmetacyclophanes and their Treatment with Aluminium Chloride-Nitromethane in Benzene
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The preparation of 8-fluoro-t-butylmetacyclophanes (5) are described.Dithiametacyclophane (3) and metacyclophane bis(sulphones) (4) were obtained as a mixture of transoid and cisoid conformers, but metacyclophanes (5) were exclusively obtained as the transoid conformer after pyrolysis of the sulphones (4).AlCl3-MeNO2-Catalyzed trans-t-butylation of 8-fluoro-16-methyl-5,13-di-t-butylmetacyclophane (5a) in benzene under a variety of conditions faild to give 8-fluoro-16-methylmetacyclophane (32) but, instead, the tetrahydropyrenes (33) and/or (34) were obtained depending upon the conditions used.Internally substituted metacyclophanes were isomerized to the strainless metacyclophanes and these were then oxidized to the tetrahydropyrene (33).
- Yamato, Takehiko,Arimura, Takashi,Tashiro, Masashi
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- Synthesis and antiinflammatory evaluation of substituted isophthalonitriles, trimesonitriles, benzonitriles, and terephthalonitriles
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In an effort to develop nonacidic, nonsteroidal, antiinflammatory agents without gastrointestinal complications, a series of cyanobenzenes was synthesized for antiinflammatory evaluation. Twenty-seven substituted isophthalonitriles, 19 trimesonitriles, 30 benzonitriles, and 16 terephthalonitriles were tested in the rat utilizing the carrageenan-induced pedal edema assay. Based on the performance of phenylbutazone in this assay (43.8% reduction at 100 mg/kg), six compounds, dosed at 50 mg/kg, produced reductions in inflammation comparable to this standard. However, the LD50 value of each compound dosed at this level was in the range of 40-56 mg/kg in the mouse; therefore, further study was not warranted. Fifteen compounds possessed activity in excess of 20% reduction at 200 mg/kg and also possessed LD50 values greater than 300 mg/kg. Of these cyanobenzenes, trimesonitrile, 4-chlorobenzonitrile, 2-chloroterephthalonitrile, and 2-fluoroterephthalonitrile with reductions in edema of 32, 30, 46, and 49%, respectively, represent the best candidates for subsequent study.
- Heilman,Battershell,Pyne,Goble,Magee
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p. 906 - 913
(2007/10/06)
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