Classifications

• • C—CHEMISTRY; METALLURGY
  • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
  • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
  • C25B3/00—Electrolytic production of organic compounds
  • C25B3/20—Processes
  • C25B3/29—Coupling reactions

Definitions

• the following invention relates to an electrochemical process for the O-C coupling of unprotected phenols with optically pure arylamines.
• arylamines and phenols are used in this application as a generic term and thus also includes substituted arylamines and substituted phenols.
• the object of the following invention was to provide a process with which unprotected phenols can be O-C coupled with optically pure arylamines.
• O-C coupled or “O-C coupling” is meant in the context of this invention that the oxygen of the phenol is coupled to a carbon atom of the arylamine aromatic.
• the object is achieved by a method according to the invention.
• the phenol is used at least twice the amount of the arylamine.
• the ratio of phenol to arylamine is in the range of 2: 1 to 4: 1.
• the reaction solution is free of organic oxidizing agents.
• the phenol has a structure of the general formula (I): wherein the substituents R 1 to R 5 are independently selected from: -H, - (C 1 -C 12 ) -alkyl, - (C 4 -C 14 ) -aryl, - (C 3 -C 14 ) -heteroaryl, - (C 3 -C 12 ) -cycloalkyl, -O- (C 1 -C 12 ) -alkyl, -O- (C 4 -C 14 ) -aryl, -O- (C 3 -C 14 ) -Heteroaryl, -O- (C 3 -C 12 ) -cycloalkyl.
• the substituents R 1 to R 5 are independently selected from: -H, - (C 1 -C 12 ) -alkyl, -O- (C 1 -C 12 ) -alkyl.
• the substituents R 1 to R 5 are independently selected from: -H, -CH 3 , -O-CH 3 , - tert -butyl.
• the optically pure arylamine has a structure of the general formula ( IIa ) or ( IIb ): wherein the substituents R 6 and R 7 are independently selected from: - (C 1 -C 12 ) -alkyl, - (C 4 -C 14 ) -aryl, - (C 3 -C 14 ) -heteroaryl, - (C 3 -C 12 ) -cycloalkyl, -O- (C 1 -C 12 ) -alkyl, -O- (C 4 -C 14 ) -aryl, -O- (C 3 -C 14 ) -heteroaryl, -O- (C 3 -C 12 ) -cycloalkyl, and R 6 does not stand for the same radical as R 7 .
• the optically pure arylamine has a structure of the general formula ( IIa ): wherein the substituents R 6 and R 7 are independently selected from: - (C 1 -C 12 ) -alkyl, - (C 4 -C 14 ) -aryl, - (C 3 -C 14 ) -heteroaryl, - (C 3 -C 12 ) -cycloalkyl, -O- (C 1 -C 12 ) -alkyl, -O- (C 4 -C 14 ) -aryl, -O- (C 3 -C 14 ) -heteroaryl, -O- (C 3 -C 12 ) -cycloalkyl, and R 6 does not stand for the same radical as R 7 .
• the substituents R 6 and R 7 are independently selected from: - (C 1 -C 12 ) -alkyl, - (C 4 -C 14 ) -aryl, and R 6 does not stand for the same radical as R 7 .
• R 6 is -CH 3 , and R 6 does not stand for the same radical as R 7 .
• R 7 is phenyl, and R 6 does not stand for the same radical as R 7 .
• the oxygen of the phenol couples in ortho position to the nitrogen on the aromatic of the optically pure arylamine.
• Alkyl is a non-branched or branched aliphatic radical.
• Aryl for aromatic (hydrocarbon) radicals preferably having up to 14 carbon atoms, for.
• phenyl C 6 H 5 -
• naphthyl C 10 H 7 -
• anthryl C 14 H 9 -
• phenyl preferably phenyl.
• Cycloalkyl for saturated cyclic hydrocarbons containing exclusively carbon atoms in the ring is
• Heteroaryl is an aryl radical in which one to four, preferably one or two, carbon atoms may be replaced by heteroatoms selected from the group consisting of N, O, S and substituted N, wherein the heteroaryl radical may also be part of a larger condensed ring structure.
• heteroaryl radical which may be part of a fused ring structure is preferably understood systems in which fused five- or six-membered rings are formed, e.g. Benzofuran, isobenzofuran, indole, isoindole, benzothiophene, benzo (c) thiophene, benzimidazole, purine, indazole, benzoxazole, quinoline, isoquinoline, quinoxaline, quinazoline, cinnoline, acridine.
• the process can be performed on different carbon (glassy carbon, boron-doped diamond, graphites, carbon fibers, nanotubes, etc.), metal oxide and metal electrodes. Current densities in the range of 1-50 mA / cm 2 are applied.
• the electrolysis is carried out in the usual, known in the art electrolysis cells.
• HFIP 1,1,1,3,3,3-hexafluoroisopropanol
• the workup of the biaryls is very simple and takes place after completion of the reaction according to common separation methods.
• the electrolyte solution is first distilled and recovered the individual compounds in the form of different fractions separately. Further purification can be carried out, for example, by crystallization, distillation, sublimation or chromatographic.
• Preparative liquid chromatography for the separation of mixtures was carried out using silica gel 60 M (0.040-0.063 mm) from Machery-Nagel GmbH & Co. KG. KG, Düren performed. All technical grade eluents (ethyl acetate, technical grade, cyclohexane, technical grade) were pre-distilled on a rotary evaporator.
• TLC Thin-layer chromatography
• EI + electrospray ionization
• the NMR spectroscopic investigations were carried out on multicore resonance spectrometers of the type Avance III HD 300 or Avance II 400 from Bruker, Analytical Messtechnik, Düsseldorf.
• the solvent used was CDCl3.
• the 1H and 13C spectra were calibrated according to the residual content of non-deuterated solvent according to the NMR Solvent Data Chart from Cambridge Isotopes Laboratories, USA.
• the assignment of the 1H and 13C signals was carried out in part by means of H, H-COZY, H, H-NOESY, H, C-HSQC and H, C-HMBC spectra.
• the chemical shifts are given as ⁇ values in ppm.
• the melting ranges were determined with a melting point meter B-545 (Büchi, Flawil, Switzerland) and are uncorrected.
• the rotations were determined on a Jasco P-2000 digital polarimeter. For this, the sodium D-line at 589 nm was used. The length of the cell used is 100 mm.
• AAV2 Electrochemical cross-coupling in a beaker cell
• the deficiency component A is reacted with a 3-fold excess of the coupling partner B in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) in a glass beaker cell glassy carbon electrodes.
• the conductive salt used is tributylmethylammonium methylsulfate (MTBS) at a concentration of 0.09M.
• MTBS tributylmethylammonium methylsulfate
• the electrolysis takes place galvanostatically. Evaporating HFIP is redistilled by means of a Dimroth cooler and fed to the electrolysis. After the end of the electrolysis, the cell contents are transferred into a 100 ml round-bottomed flask and the solvent is removed under reduced pressure on a rotary evaporator at 50 ° C., 70-200 mbar.
• Electrode material Anode: Glassy carbon
• Cathode Glassy carbon
• Electrolysis conditions Temperature: 50 ° C Current density: 5.2 mA / cm 2 Amount of charge: 2.0 F referred to the deficit component
• the resulting hydrochloride is filtered off with suction and taken up in 200 ml of 0.1 M sodium hydroxide solution.
• the aqueous phase is extracted three times with diethyl ether (3 ⁇ 150 ml).
• the combined organic phases are dried over magnesium sulfate and the solvent removed by means of rotary evaporator.
• the desired product was obtained as a light yellowish oil. Yield: 48% (1.15 g, 5.1 mmol)
• the resulting hydrochloride is filtered off with suction and taken up in 200 ml of 0.1 M sodium hydroxide solution.
• the aqueous phase is extracted three times with diethyl ether (3 ⁇ 150 ml).
• the combined organic phases are dried over magnesium sulfate and the solvent removed by means of rotary evaporator.
• the desired product is obtained as a slightly yellowish solid. Yield: 18% (0.56 g, 1.9 mmol)
• the resulting hydrochloride is filtered off with suction and taken up in 200 ml of 0.1 M sodium hydroxide solution.
• the aqueous phase is extracted three times with diethyl ether (3 ⁇ 150 ml).
• the combined organic phases are dried over magnesium sulfate and the solvent removed by means of rotary evaporator.
• the desired product is obtained as a slightly yellowish solid. Yield: 34% (0.91 g, 3.5 mmol)
• the resulting hydrochloride is filtered off with suction and taken up in 200 ml of 0.1 M sodium hydroxide solution.
• the aqueous phase is extracted three times with diethyl ether (3 ⁇ 150 ml).
• the combined organic phases are dried over magnesium sulfate and the solvent removed by means of rotary evaporator.
• the desired product is obtained as a slightly yellowish, highly viscous oil. Yield: 53% (1.53 g, 5.1 mmol)
• the electrolysis is carried out at 50 ° C. with 1.57 g (11.36 mmol, 3.0 equiv.) Of 3-methyl-4-methoxyphenol and 936 mg (3.80 mmol, 1.0 equiv.) Of ( S ) - (-) - 2- ⁇ - Methylbenzylaminonaphthalene performed.
• the current density is 5.2 mA / cm 2 and the charge amount is 2.0 F per ( S ) - (-) - 2- ⁇ -methylbenzylaminonaphthalene.
• the product mixture is purified by column chromatography on silica gel 60 with an eluent of 9: 1 (cyclohexane: ethyl acetate).
• Electrode material Anode: Glassy carbon
• Cathode Glassy carbon
• Electrolysis conditions Temperature: 50 ° C Current density: 2.8 mA / cm 2 Amount of charge: 2.0 F referred to the deficit component
• a corresponding OC coupling can be carried out analogously with the other optically pure arylamines ( A2 ) to ( A10 ).
• the products obtained from the coupling reaction can be used, for example, as ligands in the hydroformylation ( A. Börner, R. Franke; Hydroformylation, Wiley-VCH Verlag, 2016, ISBN: 978-3-527-33552-7 ).

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• 2017
  • 2017-11-27 EP EP17203772.3A patent/EP3489390A1/fr not_active Withdrawn

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