EP3489390A1 - Electrochemical method for o-c coupling of unprotected phenols with optically pure arylamines - Google Patents

Abstract

Electrochemical process for the O-C coupling of unprotected phenols with optically pure arylamines.

Description

The following invention relates to an electrochemical process for the O-C coupling of unprotected phenols with optically pure arylamines.

The terms arylamines and phenols are used in this application as a generic term and thus also includes substituted arylamines and substituted phenols.

In the WO 2014/135371 A1 An electrochemical process for the coupling of phenol and aniline is described. The method described here, however, usually leads to the CC coupling product.

The object of the following invention was to provide a process with which unprotected phenols can be O-C coupled with optically pure arylamines.

By "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.

1. a) Einfüllen von 1,1,1,3,3,3 Hexafluorisopropanol in ein Reaktionsgefäß,
2. b) Zugabe eines optisch reinen Arylamins,
3. c) Zugabe eines Phenols, wobei das Phenol gegenüber dem Arylamin im Überschuss zugesetzt wird,
4. d) Einbringen zweier Elektroden in die Reaktionslösung,
5. e) Anlegen einer Spannung an die Elektroden,
6. f) O-C-Kupplung des Phenols und des optisch reinen Arylamins.

Electrochemical process for the OC coupling of phenol with an optically pure arylamine comprising the process steps:

1. a) introduction of 1,1,1,3,3,3-hexafluoroisopropanol into a reaction vessel,
2. b) adding an optically pure arylamine,
3. c) adding a phenol, wherein the phenol is added in excess to the arylamine in excess,
4. d) introducing two electrodes into the reaction solution,
5. e) applying a voltage to the electrodes,
6. f) OC coupling of the phenol and the optically pure arylamine.

In one variant of the process, the phenol is used at least twice the amount of the arylamine.

In a variant of the process, the ratio of phenol to arylamine is in the range of 2: 1 to 4: 1.

In a variant of the method, the reaction solution is free of organic oxidizing agents.

wobei die Substituenten R¹ bis R⁵ unabhängig voneinander ausgewählt sind aus:

         -H, -(C₁-C₁₂)-Alkyl, -(C₄-C₁₄)-Aryl, -(C₃-C₁₄)-Heteroaryl, -(C₃-C₁₂)-Cycloalkyl, -O-(C₁-C₁₂)-Alkyl, -O-(C₄-C₁₄)-Aryl, -O-(C₃-C₁₄)-Heteroaryl, -O-(C₃-C₁₂)-Cycloalkyl.

In a variant of the process, 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.

In a variant of the process, the substituents R ¹ to R ^{5 are} independently selected from:

-H, - (C ₁ -C ₁₂ ) -alkyl, -O- (C ₁ -C ₁₂ ) -alkyl.

In a variant of the process, the substituents R ¹ to R ^{5 are} independently selected from:

-H, -CH ₃ , -O-CH ₃ , - tert -butyl.

wobei die Substituenten R⁶ und R⁷ unabhängig voneinander ausgewählt sind aus:

         -(C₁-C₁₂)-Alkyl, -(C₄-C₁₄)-Aryl, -(C₃-C₁₄)-Heteroaryl, -(C₃-C₁₂)-Cycloalkyl, -O-(C₁-C₁₂)-Alkyl, -O-(C₄-C₁₄)-Aryl, -O-(C₃-C₁₄)-Heteroaryl, -O-(C₃-C₁₂)-Cycloalkyl,

und R⁶ nicht für den gleichen Rest steht wie R⁷.In a variant of the method, 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 .

wobei die Substituenten R⁶ und R⁷ unabhängig voneinander ausgewählt sind aus:

         -(C₁-C₁₂)-Alkyl, -(C₄-C₁₄)-Aryl, -(C₃-C₁₄)-Heteroaryl, -(C₃-C₁₂)-Cycloalkyl, -O-(C₁-C₁₂)-Alkyl, -O-(C₄-C₁₄)-Aryl, -O-(C₃-C₁₄)-Heteroaryl, -O-(C₃-C₁₂)-Cycloalkyl,

und R⁶ nicht für den gleichen Rest steht wie R⁷.In a variant of the method, 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 .

In a variant of the process, 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 .

In a variant of the method, R ^{6 is} -CH ₃ ,
and R ⁶ does not stand for the same radical as R ⁷ .

In a variant of the process, R ^{7 is} phenyl,
and R ⁶ does not stand for the same radical as R ⁷ .

In a variant of the method, 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. As phenyl (C ₆ H ₅ -), naphthyl (C ₁₀ H ₇ -), anthryl (C ₁₄ H ₉ -), preferably phenyl.

Cycloalkyl for saturated cyclic hydrocarbons containing exclusively carbon atoms in the ring.

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.

By 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.

The course of the reaction is shown in the following scheme:

In 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), the selective oxidation of an optically pure arylamine component A , represented by Bucherer reaction, is made possible. This is able to be attacked by the high reactivity of the radical species formed nucleophilic of component B, the phenol.

The workup of the biaryls is very simple and takes place after completion of the reaction according to common separation methods. First, 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.

In the following the invention will be explained in more detail by means of exemplary embodiments.

General work regulations (AAV) chromatography

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.

Thin-layer chromatography (TLC) was carried out on PSC precast plates Kieselgel 60 F254 from Merck KGaA, Darmstadt. Detection of the various substances was carried out initially under UV light and then by staining with Cer-Molybdatophosphorsäure reagent (5.6 g Molybdatophosphorsäure, 2.2 g of cerium (IV) sulfate tetrahydrate and 13.3 g of concentrated sulfuric acid to 200 mL of water) and then by heating a hot air dryer.

Gas chromatography (GC / GCMS)

The gas chromatographic investigations (GC) of product mixtures and pure substances was carried out with the aid of the gas chromatograph GC-2010 from Shimadzu, Japan. It is attached to a quartz capillary column HP-5 from Agilent Technologies, USA (length: 30 m, internal diameter: 0.25 mm, film thickness of the covalently bonded stationary phase: 0.25 μm, carrier gas: hydrogen, injector temperature: 250 ° C, detector temperature: 310 ° C Program: method "hard": 50 ° C starting temperature for 1 min, heating rate: 15 ° C / min, 290 ° C final temperature for 8 min) or ZB5-MSi from Phenomenex, USA (length: 30 m; 0.25 mm, film thickness of the covalently bonded stationary phase: 0.25 μm, carrier gas: hydrogen, injector temperature: 250 ° C, detector temperature: 310 ° C, program: method "long": 100 ° C start temperature for 1 min, heating rate: 15 ° C / min, 290 ° C final temperature for 30 min).

Gas chromatographic mass spectra (GCMS) of product mixtures and pure substances were recorded using the gas chromatograph GC-2010 combined with the mass detector GCMS-QP2010 from Shimadzu, Japan. It is attached to a quartz capillary column HP-1 from Agilent Technologies, USA (length: 30 m, internal diameter: 0.25 mm, film thickness of the covalently bonded stationary phase: 0.25 μm, carrier gas: hydrogen, injector temperature: 250 ° C, detector temperature: 310 ° C Program: "hard" method: 50 ° C start temperature for 1 min, heating rate: 15 ° C / min, 290 ° C final temperature for 8 min, GCMS: temperature of the ion source: 200 ° C) or on a ZB-5 quartz capillary column Phenomenex, USA (length: 30 m, inner diameter: 0.25 mm, film thickness of the covalently bonded stationary phase: 0.25 μm, carrier gas: hydrogen, injector temperature: 250 ° C, detector temperature: 310 ° C, program: "method1 long" 100 ° C start temperature for 1 min, heating rate: 15 ° C / min, 290 ° C final temperature for 30 min).

Mass spectrometry

All electrospray ionization (ESI +) measurements were carried out on a QTof Ultima 3 from Waters Micromasses, Milford, Massachusetts. EI mass spectra and the high-resolution EI spectra were measured on a MAT 95 XL sector field device from Thermo Finnigan, Bremen.

NMR spectroscopy

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, Karlsruhe. 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 δ values in ppm. The following abbreviations were used for the multiplicities of the NMR signals: s (singlet), bs (broad singlet), d (doublet), t (triplet), q (quartet), m (multiplet), dd (doublet of doublet), dt (doublet of triplet), tq (triplet of quartet). All coupling constants J were given in terms of the number of bound bonds in hertz (Hz). The numbering specified in the signal assignment corresponds to the numbering specified in the formula diagrams.

melting ranges

The melting ranges were determined with a melting point meter B-545 (Büchi, Flawil, Switzerland) and are uncorrected.

rotations

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.

AAV1: Preparation of optically pure arylamine derivatives by Bucherer reaction

10.50 mmol of the naphthol (1.0 equiv.), 52.5 mmol (5 equiv.) Of sodium hydrogensulfite, 52.5 mmol (5 equiv.) Of the optically pure amine and 15-25 ml of water are placed in a 60 ml pressure tube. The reaction mixture is reacted for 21 h at 100 ° C with stirring. The reaction solution is brought to room temperature and water is added (200 mL). The aqueous phase is extracted three times with ethyl acetate (3 × 100 ml). The Combined organic phases are dried over magnesium sulfate. Educts can be recovered under reduced pressure by short path distillation. The residue is either worked up by column chromatography or precipitated as the hydrochloride.

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. 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. Mineralization products and the conductive salt contained are separated by elution with ethyl acetate: cyclohexane over silica gel 60. Unreacted educt is recovered by short path distillation (100 ° C, 10 ^-3 mbar). The resulting reaction products are separated by column chromatography as indicated.

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

Synthesis of optically pure arylamines ( S ) - (-) - 2-α-Methylbenzylaminonaphthalene (A1)

6.0 g (42 mmol, 1.0 equiv) of 2-naphthol are charged with 21.6 g (210 mmol, 5.0 equiv.) Of sodium hydrogen sulfite and 27.0 mL of (S) -1-phenylethylamine (210 mmol, 5.0 equiv.) And 50 mL of water 325 mL pressure tube and reacted for 21 h at 100 ° C for reaction. The reaction solution is mixed with water and the resulting precipitate is filtered off with suction. Crystallization at boiling temperature from ethanol (2mL / g) gives the desired product as a slightly yellowish solid.
Yield: 70% (7.2 g, 29.11 mmol)

Characterization:

• GC (method " hard " , column: HP-5): t _R = 15.9 min
• R _f (chyclohexane: ethyl acetate = 9: 1): 0.58
• Rotation value (acetone, 578 nm, c = 3 × 10 ^-3 g / ml): [α] ²⁴ : -176 °

¹ H-NMR (400 MHz, DMSO-d ₆ ) δ [ppm] = 1.46 (d, ³ J _{12-H, 11-H} = 6.8 Hz, 3H, 10-H), 4.59 (m, 1H, 9- H), 6.49 (d, ³ J _{NH, 11-H} = 7.1 Hz, 1H, NH), 6.51 (d, ⁴ J _{1-H, 3-H} = 2.2 Hz, 1H, 1-H), 7.01-7.06 (m, 2H), 7.15-7.23 (m, 2H), 7.26-7.30 (m, 2H, 13-H, 16-H), 7.36 (m, 1H), 7.41-7.43 (m, 2H, 12-H , 16-H), 7.56 (m, 2H).
¹³ C-NMR (101 MHz, DMSO-d ₆₎ δ [ppm] = 24.58 (10-C), 52.00 (9-C), 103.74 (1-C), 118.46 (3-C), 120.98, 125.30, 125.87 (14-C), 125.94 (12-C, 16-C), 126.31, 126.48, 127.33, 128.18 (4-C), 128.33 (13-C, 15-C), 134.81 (8a-C), 145.73 (2-C), 145.80 (11-C).

( S ) - N -2- (indanylamino) naphthalene (A2)

Entsprechend AAV1 werden in ein 60 mL Druckrohr 1.5g (10.5 mmol, 1.0 Äquiv.) 2-Naphthol, 5.4 g (52.5 mmol, 5.0 Äquiv.) Natriumhydrogensulfit und 6.9 mL (S)-(+)-1-Aminoindan (52.5 mmol, 5.0 Äquiv.) sowie 25 mL Wasser gegeben. Das Reaktionsgemisch wird für 21 h bei 100 °C zur Reaktion gebracht. Säulenchromatographische Aufreinigung (Cyclohexan:Ethylacetat 100:00 -> 98:2) liefert das gewünschte Produkt als hochviskoses, gelbliches Öl.
Ausbeute: 52% (1.4 g, 5.4 mmol)

According to AAV1, 1.5 g (10.5 mmol, 1.0 equiv.) Of 2-naphthol, 5.4 g (52.5 mmol, 5.0 equiv.) Of sodium hydrogen sulfite and 6.9 mL of ( S ) - (+) - 1-aminoindan (52.5 mmol , 5.0 equiv.) And 25 mL of water. The reaction mixture is reacted at 100 ° C for 21 h. Column chromatographic purification (cyclohexane: ethyl acetate 100: 00 → 98: 2) affords the desired product as a highly viscous, yellowish oil.
Yield: 52% (1.4 g, 5.4 mmol)

Characterization:

• GC (method "hard", column: HP-5): t _R = 16.7 min
• R _f (chyclohexane: ethyl acetate = 9: 1): 0.75
• Rotation value (dichloromethane, 589 nm, c = 3 × 10 ^-3 g / ml): [α] ²⁰ : 8.08 °

¹ H-NMR (400 MHz, DMSO-d ₆ ) δ [ppm] = 1.82-1.92 (m, 1H, 17-H), 2.55-2.63 (m, 1H, 17-H), 2.83-2.91 (m, 1H, 16-H), 2.96-3.03 (m, 1H, 16-H), 5.11 (q, ³ J ₉ -H _{, 16-H, 9-H, NH} = 7.4Hz, 1H, 9-H), 6.27 (d, ³ J _{NH, 9-H} = 8.3 Hz, 1H, NH), 6.98 (d, ³ J _{1-H, 3-H} = 2.2 Hz, 1H, 1-H), 7.08-7.36 (m, 7H), 7.59 (d, J = 8.2 Hz, 1H), 7.62 (d, J = 9.0 Hz, 1H), 7.65 (d, J = 8.1 Hz, 1H).
¹³ C-NMR (101 MHz, DMSO-d ₆₎ δ [ppm] = 29.80 (C-16), 33.28 (C-17), 57.34 (C-9), 102.98 (C-1), 118.57, 121.00, 124.22, 124.60, 125.45, 125.97, 126.26, 126.48, 127.38, 128.33, 135.19, 143.17, 144.86, 146.49.

( S ) - N -2- (3,3-dimethylbutan-2-ylamino) naphthalene (A3)

Entsprechend AAV1 werden in ein 60 mL Druckrohr 1.5 g (10.5 mmol, 1.0 Äquiv.) 2-Naphthol, 5.4 g (52.5 mmol, 5.0 Äquiv.) Natriumhydrogensulfit und 7.0 mL (S)-(+)-3,3-Dimethyl-2-aminobutan (52.5 mmol, 5.0 Äquiv.) sowie 15 mL Wasser gegeben. Das Reaktionsgemisch wird für 21 h bei 100 °C zur Reaktion gebracht. Der Rückstand wird in Diethylether gelöst und durch Zugabe von ca. 6 mL Chlorwasserstoff in Diethylether (ca. 26 gew.%) als das entsprechende Hydrochlorid gefällt. Das entstandene Hydrochlorid wird abgesaugt und in 200 mL 0.1 M Natriumhydroxid-Lösung aufgenommen. Die wässrige Phase wird drei Mal mit Diethylether extrahiert (3 x 150 mL). Die kombinierten organischen Phasen werden über Magnesiumsulfat getrocknet und das Lösungsmittel mittels Rotationsverdampfer entfernt. Das gewünschte Produkt wurde als leicht gelbliches Öl erhalten.
Ausbeute: 48% (1.15 g, 5.1 mmol)

According to AAV1, 1.5 g (10.5 mmol, 1.0 equiv.) Of 2-naphthol, 5.4 g (52.5 mmol, 5.0 equiv.) Of sodium hydrogen sulfite and 7.0 mL of ( S ) - (+) - 3,3-dimethyl- Added 2-aminobutane (52.5 mmol, 5.0 equiv.) And 15 mL of water. The reaction mixture is reacted at 100 ° C for 21 h. The residue is dissolved in diethyl ether and precipitated by adding about 6 ml of hydrogen chloride in diethyl ether (about 26% by weight) as the corresponding hydrochloride. 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)

Characterization:

• R _f (cyclohexane: ethyl acetate = 9: 1): 0.86
• Rotation value (dichloromethane, 589 nm, c = 2.95 × 10 ^-3 g / ml): [α] ²⁰ : 100.7 °
• HRMS (ESI +) [M + H +]: calculated: 228.1747, found: 228.1762

¹ H NMR (400 MHz, DMSO-d6) δ = 0.96 (s, 9H), 1.08 (d, J = 6.5 Hz, 3H), 3.34-3.42 (m, 1H), 5.42 (d, J = 9.4 Hz, 1H), 6.76 (d, J = 2.3 Hz, 1H), 7.05 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.07 (dd, J = 9.0, 2.2 Hz, 1H), 7.25 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.52 (d, J = 7.5 Hz, 1H), 7.55 (d, J = 9.0 Hz, 1H), 7.58 (d, J = 7.9 Hz, 1H).
¹³ C NMR (101 MHz, DMSO-d6) δ = 15.44, 26.50, 34.90, 55.84, 102.13, 118.76, 120.54, 125.23, 125.83, 126.05, 127.26, 128.13, 135.30, 146.98.

( S ) - N -2- α - (Naphthylethylamino) naphthalene (A4)

According to AAV1, 1.5 g (10.5 mmol, 1.0 equiv.) Of 2-naphthol, 5.4 g (52.5 mmol, 5.0 equiv.) Of sodium bisulfite and 9 g (52.5 mmol, 5.0 equiv.) Of S- formaldehyde in a 60 mL pressure tube. S ) - (-) -1- (2-naphthyl) ethylamine and 25 mL of water. The reaction mixture is reacted at 100 ° C for 21 h. The residue is dissolved in diethyl ether and precipitated by adding about 6 ml of hydrogen chloride in diethyl ether (about 26% by weight) as the corresponding hydrochloride. 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)

Characterization:

• R _f (chyclohexane: ethyl acetate = 9: 1): 0.83
• Rotation value (dichloromethane, 589 nm, c = 3.15 × 10 ^-3 g / ml): [α] ²⁰ : -236.11 °
• Melting point = 84-86 ° C
• HRMS (ESI +) [M + H +]: calculated: 298.1590, found: 298.1598

¹ H NMR (400 MHz, DMSO-d6) δ = 1.56 (d, J = 6.7 Hz, 3H), 4.77 (p, J = 6.7 Hz, 1H), 6.57 (d, J = 2.2 Hz, 1H), 6.61 (d, J = 6.9 Hz, 1H,), 7.03 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.09 (dd, J = 9.0, 2.2 Hz, 1H), 7.18 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.35 (dd, J = 8.2, 1.1 Hz, 1H), 7.38-7.50 (m, 2H), 7.56 (d, J = 9.0 Hz, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.61 (dd, J = 8.5, 1.7 Hz, 1H), 7.80 - 7.90 (m, 3H), 7.92 (d, J = 1.6 Hz, 1H,).
¹³ C NMR (101 MHz, DMSO-d6) δ = 24.43, 52.21, 103.80, 118.46, 121.00, 124.09, 124.70, 125.28, 125.41, 125.86, 126.01, 126.32, 127.31, 127.48, 127.51, 128.04, 128.22, 132.17, 133.00 , 134.77, 143.37, 145.73.

( S ) -2- α- ethylbenzylaminonaphthalene (A5)

According to AAV1, 1.5 g (10.5 mmol, 1.0 equiv.) Of 2-naphthol, 5.4 g (52.5 mmol, 5.0 equiv.) Of sodium hydrogen sulfite and 9 g (52.5 mmol, 5.0 equiv.) Of ( S ) - (-) are placed in a 60 mL pressure tube. ) -1-phenylpropylamine and 15 mL of water. The reaction mixture is reacted at 100 ° C for 21 h. The residue is dissolved in diethyl ether and precipitated by adding about 6 ml of hydrogen chloride in diethyl ether (about 26% by weight) as the corresponding hydrochloride. 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. Crystallization from hot methanol (1 mL / g) gives the desired product as colorless crystals.
Yield: 38% (1.00 g, 3.8 mmol)

Characterization:

• R _f (chyclohexane: ethyl acetate = 9: 1): 0.61
• Rotation (dichloromethane, 589 nm, c = 3.24 x 10 ^-3 g / mL): [α] ²⁰ : -173.57 °
• Melting point = 75-76 ° C
• HRMS (ESI +) [M + H +]: calculated: 262.1590, found: 262.1604

¹ H NMR (400 MHz, DMSO-d ₆ ) δ = 0.94 (t, J = 7.3 Hz, 3H), 1.68-1.91 (m, 2H), 4.35 (q, J = 7.2 Hz, 1H), 6.47 (i.e. , J = 7.6 Hz, 1H), 6.55 (d, J = 2.2 Hz), 7.02-7.05 (m, 2H), 7.15-7.24 (m, 2H), 7.27-7.31 (m, 2H), 7.38-7.44 ( m, 3H), 7.54 (d, J = 9.0 Hz, 1H), 7.57 (dd, J = 8.2, 1.2 Hz, 1H).

¹³ C NMR (101 MHz, DMSO-d ₆ ) δ = 11.68, 31.33, 58.74, 103.96, 118.94, 121.35, 125.70, 126.31, 126.70, 126.96, 127.77, 128.59, 128.64. 135.30, 145.05, 146.49.

( R ) - N -2- (hex-2-ylamino) naphthalene ( A6 )

Entsprechend AAV1 werden in ein 60 mL Druckrohr 1.5 g (10.5 mmol, 1.0 Äquiv.) 2-Naphthol, 5.4 g (52.5 mmol, 5.0 Äquiv.) Natriumhydrogensulfit und 7.0 mL (52.5 mmol, 5.0 Äquiv.) (R)-(-)-2-aminohexane sowie 15 mL Wasser gegeben. Das Reaktionsgemisch wird für 21 h bei 100 °C zur Reaktion gebracht. Säulenchromatographische Aufreinigung (Cyclohexan:Ethylacetat 100:00 -> 99:1) liefert das gewünschte Produkt als gelbliches Öl.
Ausbeute: 36% (0.87 g, 3.8 mmol)

According to AAV1, 1.5 g (10.5 mmol, 1.0 equiv) of 2-naphthol, 5.4 g (52.5 mmol, 5.0 equiv.) Of sodium hydrogen sulfite and 7.0 ml (52.5 mmol, 5.0 equiv.) Of ( R ) - (-) are placed in a 60 ml pressure tube. ) 2-aminohexanes and 15 mL of water. The reaction mixture is reacted at 100 ° C for 21 h. Column chromatographic purification (cyclohexane: ethyl acetate 100: 00 → 99: 1) affords the desired product as a yellowish oil.
Yield: 36% (0.87 g, 3.8 mmol)

Characterization:

• R _f (cyclohexane: ethyl acetate = 9: 1): 0.50
• Rotation (dichloromethane, 589 nm, c = 3.45 x 10 ^-3 g / mL): [α] ²⁰ : 4.98 °
• HRMS (ESI +) [M + H ⁺ ]: calculated .: 228.1747, found: 228.1751.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ = 0.88 (t, J = 7.1 Hz, 3H), 1.15 (d, J = 6.3 Hz, 3H), 1.25-1.62 (m, 6H), 3.44-3.54 (m, 1H), 5.67 (d, J = 8.3 Hz), 6.67 (d, J = 2.2 Hz), 6.96 (dd, J = 9.0, 2.2 Hz, 1H), 7.06 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.26 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.56 (d, J = 9.0 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H).
¹³ C NMR (101 MHz, DMSO-d ₆ ) δ = 14.04, 20.21, 22.30, 27.95, 35.84, 47.21, 102.24, 118.56, 120.64, 125.26, 125.86, 126.10, 127.33, 128.28, 135.28, 146.14.

( S ) - N -2-α - ((4-methylphenyl) ethylamino) naphthalene (A7)

According to AAV1, 1.5 g (10.5 mmol, 1.0 equiv.) Of 2-naphthol, 5.4 g (52.5 mmol, 5.0 equiv.) Of sodium hydrogen sulfite and 9 g (52.5 mmol, 5.0 equiv.) Of ( S ) - (-) are added to a 60 mL pressure tube. ) -1- (4-methylphenyl) ethylamine and 15 mL of water. The reaction mixture is reacted at 100 ° C for 21 h. The residue is dissolved in diethyl ether and precipitated by adding about 6 ml of hydrogen chloride in diethyl ether (about 26% by weight) as the corresponding hydrochloride. 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)

Characterization:

• R _f (cyclohexane: ethyl acetate = 9: 1): 0.50
• Rotation value (dichloromethane, 589 nm, c = 3.06 × 10 ^-3 g / ml): [α] ²⁰ : -196.03 °
• Melting point = 76-77 ° C
• HRMS (ESI +) [M + H +]: calculated: 262.1590, found: 262.1592

¹ H NMR (400 MHz, DMSO-d ₆ ) δ = 1.44 (d, J = 6.8 Hz, 3H), 2.23 (s, 3H), 4.52-4.59 (m, 1H), 6.44 (d, J = 7.1 Hz , 1H), 6.51 (d, J = 2.2 Hz, 1H), 7.02-7.05 (m, 2H), 7.07-7.10 (m, 2H), 7.19-7.24 (m, 1H), 7.29-7.32 (m, 2H ), 7.37 (dd, J = 8.2, 1.1 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.58 (dd, J = 8.2, 1.1 Hz, 1H).
¹³ C NMR (101 MHz, DMSO-d ₆ ) δ = 21.09, 25.06, 52.19, 104.23, 118.95, 121.41, 125.76, 126.74, 127.79, 128.60, 129.37, 135.27, 135.87, 143.20, 146.24.

( R ) - N -2- (3-methylbutan-2-ylamino) naphthalene (A8)

According to AAV1, 1.5 g (10.5 mmol, 1.0 equiv) of 2-naphthol, 5.4 g (52.5 mmol, 5.0 equiv.) Of sodium hydrogen sulfite and 7.0 ml (52.5 mmol, 5.0 equiv.) Of (R) - (-) are placed in a 60 ml pressure tube. ) -2-amino-3-methylbutane and 15 mL of water. The reaction mixture is reacted at 100 ° C for 21 h. Column chromatographic purification (cyclohexane: ethyl acetate 100: 00 → 99: 1) gives the desired product as a yellowish, highly viscous oil.
Yield: 61% (1.39 g, 6.5 mmol)

Characterization:

• R _f (chyclohexane: ethyl acetate = 9: 1): 0.58
• Rotation value (dichloromethane, 589 nm, c = 3.9 × 10 ^-3 g / ml): [α] ²⁰ : -40.54 °
• HRMS (ESI +) [M + H ⁺ ]: calc .: 214.1590, found: 214.1597.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ = 0.90 (d, J = 6.8 Hz, 3H), 0.97 (d, J = 6.8, 3H), 1.08 (d, J = 6.5 Hz, 3H), 1.80-1.91 (m, 1H), 3.35-2.42 (m, 1H), 5.66 (d, J = 8.5 Hz, 1H), 6.68 (d, J = 2.2 Hz, 1H), 7.00 (dd, J = 9.0, 2.2 Hz, 1H), 7.06 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.26 (ddd, J = 8.2, 6.8, 1.2 Hz, 1H), 7.52 (dd, J = 8.2, 1.2 Hz , 1H), 7.55 (d, J = 9.0 Hz, 1H), 7.59 (dd, J = 8.2, 1.2 Hz, 1H).
¹³ C NMR (101 MHz, DMSO-d ₆ ) δ = 16.04, 17.66, 19.41, 31.50, 52.42, 102.31, 118.62, 120.62, 125.24, 125.86, 126.08, 127.31, 128.26, 135.26, 146.23.

( S ) - N -2- α - ((3-methoxyphenyl) ethylamino) naphthalene (A9)

According to AAV1, 1.5 g (10.5 mmol, 1.0 equiv) of 2-naphthol, 5.4 g (52.5 mmol, 5.0 equiv.) Of sodium hydrogen sulfite and 7.8 ml (52.5 mmol, 5.0 equiv.) Of (S) - (-) are added to a 60 ml pressure tube. ) -1- (3-methoxyphenyl) ethylamine and 15 mL of water. The reaction mixture is reacted at 100 ° C for 21 h. The residue is dissolved in diethyl ether and precipitated by adding about 6 ml of hydrogen chloride in diethyl ether (about 26% by weight) as the corresponding hydrochloride. 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)

Characterization:

• R _f (chyclohexane: ethyl acetate = 9: 1): 0.33
• Rotation value (dichloromethane, 589 nm, c = 3.33 × 10 ^-3 g / ml): [α] ²⁰ : -60.16 °
• HRMS (ESI +) [M + Na +]: calculated: 278.1539, found: 278.1548

¹ H NMR (400 MHz, DMSO-d ₆ ) δ = 1.45 (d, J = 6.7 Hz, 3H), 3.70 (s, 3H), 4.52-4.59 (m, 1H), 6.46 (d, J = 7.2 Hz , 1H), 6.54 (d, J = 2.2 Hz, 1H), 6.72-6.76 (m, 1H), 6.99-7.08 (m, 4H), 7.19-7.24 (m, 2H), 7.39 (dd, J = 8.3 , 1.0 Hz, 1H), 7.56 (d, J = 9.0 Hz, 1H), 7.58 (dd, J = 8.3, 1.2 Hz, 1H). ¹³ C NMR (101 MHz, DMSO-d ₆ ) δ = 24.48, 51.69, 54.88, 103.79, 111.49, 111.84, 118.23, 118.42, 120.99, 125.32, 125.86, 126.32, 127.33, 128.17, 129.37, 134.80, 145.74, 147.65, 159.37.

N - ((1 R, 2 S, 5 R) -5-methyl-2- (1-methylethyl) cyclohexyl) naphthalene-2-amine (A10)

According to AAV1, 1.5 g (10.5 mmol, 1.0 equiv.) Of 2-naphthol, 5.4 g (52.5 mmol, 5.0 equiv.) Of sodium hydrogen sulfite and 8.1 mL (52.5 mmol, 5.0 equiv.) Of (-) - menthylamine are placed in a 60 mL pressure tube 15 mL of water. The reaction mixture is reacted at 100 ° C for 21 h. Column chromatographic purification (cyclohexane: ethyl acetate 100: 00 → 99: 1) affords the desired product as a colorless solid.
Yield: 28% (0.80 g, 2.8 mmol)

Characterization:

• R _f (chyclohexane: ethyl acetate = 9: 1): 0.71
• Rotation (dichloromethane, 589 nm, c = 3.30 x 10 ^-3 g / mL): [α] ²⁰ : -127.36 °
• Melting range: 54-55 ° C
• HRMS (ESI +) [M + H ⁺ ]: calculated: 282.2216, found: 282.2211

¹ H NMR (400 MHz, DMSO-d ₆ ) δ = 0.70 (d, J = 6.9 Hz, 1H), 0.74-0.81 (m, 1H), 0.86-0.91 (m, 7H), 1.05-1.16 (m, 1H), 1.20-1.31 (m, 1H), 1.45-1.56 (m, 1H), 1.64-1.76 (m, 2H), 2.02-2.11 (m, 1H), 2.15-2.24 (m, 1H), 3.24 ( qd, J = 10.5, 3.8 Hz, 1H), 5.58 (d, J = 9.4 Hz, 1H), 6.70 (d, J = 2.3 Hz, 1H), 6.95 (dd, J = 8.8, 2.3 Hz, 1H), 7.04 (ddd, J = 8.0, 6.8, 1.2 Hz, 1H), 7.25 (ddd, J = 8.0, 6.8, 1.2 Hz, 1H), 7.50 (dd, J = 8.2, 1.2 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.58 (dd, J = 8.2 Hz, 1.2 Hz, 1H).
¹³ C NMR (101 MHz, DMSO-d ₆ ) δ = 16.03, 21.13, 22.28, 23.57, 25.70, 31.30, 34.50, 39.52, 41.85, 47.37, 52.17, 101.44, 118.40, 120.43, 125.16, 125.86, 125.97, 127.31, 128.34, 135.41, 146.50.

Electrochemical O-C coupling of phenol with optically pure arylamine

1- (2'-methoxy-4'-methylphenoxy) -2- ( S ) -α-methylbenzylaminonaphthalene (PA1)

Ausbeute: 340 mg (0.88 mmol, 23%)
GC (Methode "hart", HP-5): t_R = 18.5 min
R_f (Cyclohexan:Ethylacetat = 9:1) = 0.38
¹H-NMR (400 MHz, DMSO-d ₆ ) δ[ppm] = 1.40 (d, ³J_10-H,9-H= 7.4 Hz, 3H, 10-H), 2.26 (s, 3H, 8'-H), 3.97 (s, 3H, 7'-H), 4.76(m, 1H, 9-H), 5.35 (d, ³J_NH,9-H= 8.0 Hz, 1H, NH), 6.20 (d, ³J_6'-H,5'-H= 8.1 Hz, 1H, 6'-H), 6.51 (ddd, ^3;4;4J_{5'-H,6'-H,5'-H,3'-H,5'-H,7'-H}= 8.2, 2.0, 0.9 Hz , 1H, 5'-H), 7.01 (d, ⁴J_3'-H,5'-H= 2.1 Hz, 1H, 3'-H), 7.06 (d, ³J_3-H,4-H= 9.0 Hz, 1H, 3-H), 7.13-7.18 (m, 2H), 7.21-7.27 (m, 4H, 12-H,13-H,15-H,16-H), 7.30-7.34 (m, 1H), 7.52-7.55 (m, 2H, 4-H), 7.69 (d, J=8.0 Hz, 1H).
¹³C-NMR (100 MHz, DMSO-d ₆ ) δ[ppm] = 20.70 (8'-C), 24.45 (10-C), 51.88 (9-C), 55.70 (7'-C), 113.39 (3'-C), 114.97, 115.79 (6'-C), 119.31, 120.74, 121.89 (5'-C), 125.46, 125.82 (12-C, 16-C), 126.51, 126.65, 126.69, 127.79, 127.97, 128.34 (13-C, C-15), 131.89(4'-C), 133.67(1-C), 137.38 (2-C), 144.69(1'-C), 145.51 (11-C), 148.64(2-C). HRMS (ESI, pos. mode): m/z für C₂₆H₂₅NO₂ (M+Na⁺): berechnet: 406.1778 gefunden: 406.1779 According to AAV2, 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-α- Methylbenzylaminonaphthalene performed. The current density is 5.2 mA / cm ² and the charge amount is 2.0 F per ( S ) - (-) - 2-α-methylbenzylaminonaphthalene. After removal of the solvent, the product mixture is purified by column chromatography on silica gel 60 with an eluent of 9: 1 (cyclohexane: ethyl acetate). The fractions are tested for product and contained educts by short path distillation removed (100 ° C, 10 ^-3 mbar). Further purification by column chromatography on silica gel 60 with a mobile phase gradient from 100: 00 to 70:30 (cyclohexane: dichloromethane) gives the desired product as a slightly reddish solid.

Yield: 340 mg (0.88 mmol, 23%)
GC ( "hard" method , HP-5): t _R = 18.5 min
R _f (cyclohexane: ethyl acetate = 9: 1) = 0.38
¹ H-NMR (400 MHz, DMSO-d ₆ ) δ [ppm] = 1.40 (d, ³ J _{10-H, 9-H} = 7.4 Hz, 3H, 10-H), 2.26 (s, 3H, 8 ' -H), (3.97 s, 3H, 7'-H), 4.76 (m, 1H, 9-H), 5:35 (d, ³ J _{NH, 9-H} = 8.0 Hz, 1H, NH), 6.20 (d , ³ J _{6'-H, 5'-H} = 8.1 Hz, 1H, 6'-H), 6:51 (ddd, ^{3, 4, 4} J _{H 5 ', 6'-H, 5'-H, 3 '-H, 5'-H, 7'-H} = 8.2, 2.0, 0.9 Hz, 1H, 5'-H), 7:01 (d, ⁴ J _{3'-H, 5'-H} = 2.1 Hz, 1H, 3'-H), 7:06 (d, ³ J _{3-H, 4H} = 9.0 Hz, 3-H 1H,), 7:13 to 7:18 (m, 2H), 7:21 to 7:27 (m, 4H, 12-H , 13-H, 15-H, 16-H), 7.30-7.34 (m, 1H), 7.52-7.55 (m, 2H, 4-H), 7.69 (d, J = 8.0 Hz, 1H).
¹³ C-NMR (100 MHz, DMSO-d ₆ ) δ [ppm] = 20.70 (8'-C), 24.45 (10-C), 51.88 (9-C), 55.70 (7'-C), 113.39 ( 3'-C), 114.97, 115.79 (6'-C), 119.31, 120.74, 121.89 (5'-C), 125.46, 125.82 (12-C, 16-C), 126.51, 126.65, 126.69, 127.79, 127.97 , 128.34 (13-C, C-15), 131.89 (4'-C), 133.67 (1-C), 137.38 (2-C), 144.69 (1'-C), 145.51 (11-C), 148.64 (2-C). HRMS (ESI, pos mode): m / z for C ₂₆ H ₂₅ NO ₂ (M + Na ⁺ ): calculated: 406.1778 found: 406.1779

1- (4 '- (1,1-dimethylethyl) -2'-methylphenoxy) -2- ( S ) -α-methylbenzylaminonaphthalene (PA2)

• Ausbeute: 320 mg (0.78 mmol, 21%)
• GC (Methode "hart", HP-5): t_R = 21.8 min
• R_f (Cyclohexan:Ethylacetat = 9:1) = 0.80
• ¹H-NMR (400 MHz, DMSO-d ₆ ) δ[ppm] = 1.24 (s, 9H, 7a'-H), 1.42 (d, ³J_10-H,9-H= 6.7 Hz, 3H, 10-H), 2.57 (s, 3H, 8'-H), 4.81 (m, 1H, 9-H), 5.36 (d, ³J_NH,9-H= 8.0 Hz, 1H, NH), 6.04 (d, ³J_6'-H,5'-H= 8.5 Hz, 1H, 6'-H), 6.94 (dd, ^3;4J_{5'-H,6'-H; 5'-H;3'-H}= 8.6, 2.3 Hz, 1H, 5'-H), 7.10-7.18 (m, 3H), 7.23-7.37 (m, 7H), 7.55 (d, ³J_4-H,3-H= 9.0 Hz, 1H, 4-H), 7.70 (d, J = 8.3 Hz, 1H).
• ¹³C-NMR (101 MHz, DMSO-d ₆ ) δ[ppm] = 16.62 (8'-C), 24.43 (10-C), 31.37 (7a'-C), 33.78 (7'-C), 52.12 (9-C), 111.98 (6'-C), 115.94, 119.29, 121.87, 123.34 (5'-C), 124.86, 125.55, 125.87, 126.48, 126.63, 126.88, 127.62, 127.85, 128.06, 128.32, 123.29, 137.64 (2-C), 143.60 (4'-C), 145.67 (11-C), 153.68 (1'-C).

HRMS (ESI, pos. mode): m/z für C₂₉H₃₁NO (M+H⁺): berechnet: 410.2478 gefunden: 410.2475 According to AAV2, 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-α- Methylbenzylaminonaphthalene performed. The current density is 5.2 mA / cm ² , the charge amount 2.0 F per ( S ) - (-) - 2-α-methylbenzylaminonaphthalene. After removal of the solvent, the product mixture is purified by column chromatography on silica gel 60 with an eluent of 9: 1 (cyclohexane: ethyl acetate). The fractions are tested for product and contained educts by short path distillation removed (100 ° C, 10 ^-3 mbar). Further purification by column chromatography on silica gel 60 with a mobile phase gradient from 100: 00 to 70:30 (cyclohexane: dichloromethane) gives the desired product as a slightly reddish solid.

• Yield: 320 mg (0.78 mmol, 21%)
• GC ( "hard" method , HP-5): t _R = 21.8 min
• R _f (cyclohexane: ethyl acetate = 9: 1) = 0.80
• ¹ H-NMR (400 MHz, DMSO-d ₆ ) δ [ppm] = 1.24 (s, 9H, 7a'-H), 1.42 (d, ³ J _{10-H, 9-H} = 6.7 Hz, 3H, 10 -H), (2:57 s, 3H, 8'-H), 4.81 (m, 1H, 9-H), 5:36 (d, ³ J _{NH, 9-H} = 8.0 Hz, 1H, NH), 6:04 (d , ³ J _{6'-H, 5'-H} = 8.5 Hz, 1H, 6'-H), 6.94 (dd, ^{3, 4} J _{5'-H, 6'-H, 5'-H, 3'- H} = 8.6, 2.3 Hz, 1H, 5'-H), 7.10-7.18 (m, 3H), 7.23-7.37 (m, 7H), 7.55 (d, ³ J _{4-H, 3-H} = 9.0 Hz, 1H, 4-H), 7.70 (d, J = 8.3 Hz, 1H).
• ¹³ C-NMR (101 MHz, DMSO-d ₆₎ δ [ppm] = 16.62 (8'-C), 24.43 (10-C), 31.37 (7a'-C), 33.78 (7'-C), 52.12 (9-C), 111.98 (6'-C), 115.94, 119.29, 121.87, 123.34 (5'-C), 124.86, 125.55, 125.87, 126.48, 126.63, 126.88, 127.62, 127.85, 128.06, 128.32, 123.29, 137.64 (2-C), 143.60 (4'-C), 145.67 (11-C), 153.68 (1'-C).

HRMS (ESI, pos mode): m / z for C ₂₉ H ₃₁ NO (M + H ⁺ ): calculated: 410.2478 found: 410.2475

Comparative test

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

N -acetyl-2-amino-3'-methyl-4 '- (methylethyl) -4,5-dimethoxydiphenyl ether

• GC (Methode hart, HP-5): t_R= 16.38 min
• R_f (Cyclohexan:Ethylacetat)= 0.26
• m_p= 112°C (aus CH umkristallisiert)
• ¹H-NMR (400 MHz, CDCl₃) δ= 1.20 (s, 3H), 1.22 (s, 3H), 2.10 (s, 3H), 2.29 (s, 3H), 3.09 (hept, J= 6.9, 6.9, 6.8, 6.8, 6.8, 6.8 Hz, 1H), 3.74 (s, 3H), 3.90 (s, 3H), 6.52 (s, 1H), 6.65-6.79 (m, 2H), 7.16 (d, J= 8.4 Hz, 1H), 7.53 (s, 1H), 8.10 (s, 1H);
• ¹³C-NMR (101 MHz, CDCl₃) δ= 19.52, 23.43, 24.85, 28.84, 56.32, 56.35, 77.16, 104.23, 104.98, 114.49, 118.50, 123.77, 126.13, 137.07, 137.81, 141.81, 145.33, 145.44, 155.17, 168.31. HRMS für C₂₀H₂₅NO₄ (ESI+) [M+Na⁺]: ber: 366.1681, gef.: 366.1676;
• MS (EI, GCMS): m/z(%): 343 (100) [M]⁺˙, 301 (20) [M-C₂H₂O˙]⁺, 286 (80) [M-C₂H₅NO˙]⁺.

The electrolysis is carried out at 50 ° C with 0.75 g (5.00 mmol, 1.0 equiv.) 3-Methyl-4- (methylethyl) phenol and 2.93 g (15.00 mmol, 3.0 equiv.) Of N - (3,4-dimethoxyphenyl) acetamide performed , The current density is 2.8 mA / cm ² . After removal of the solvent, the product mixture is purified by column chromatography on silica gel 60 with an eluent of 3: 2 (cyclohexane: ethyl acetate). The product is obtained as a colorless solid. Yield: 313 mg (18%, 0.91 mmol)

• GC ( hard method , HP-5): t _R = 16.38 min
• R _f (cyclohexane: ethyl acetate) = 0.26
• m _p = 112 ° C (recrystallized from CH)
• ¹ H-NMR (400 MHz, CDCl ₃₎ δ = 1.20 (s, 3H), 1.22 (s, 3H), 2.10 (s, 3H), 2.29 (s, 3H), 3:09 (hept, J = 6.9, 6.9 , 6.8, 6.8, 6.8, 6.8 Hz, 1H), 3.74 (s, 3H), 3.90 (s, 3H), 6.52 (s, 1H), 6.65-6.79 (m, 2H), 7.16 (d, J = 8.4 Hz, 1H), 7.53 (s, 1H), 8.10 (s, 1H);
• ¹³ C-NMR (101 MHz, CDCl ₃₎ δ = 19:52, 23:43, 24.85, 28.84, 56.32, 56.35, 77.16, 104.23, 104.98, 114.49, 118.50, 123.77, 126.13, 137.07, 137.81, 141.81, 145.33, 145.44, 155.17 , 168.31. HRMS for C ₂₀ H ₂₅ NO ₄ (ESI +) [M + Na ⁺ ]: via: 366.1681, found: 366.1676;
• MS (EI, GCMS): m / z (%): 343 (100) [M] ⁺ ˙, 301 (20) [MC ₂ H ₂ O˙] ⁺ , 286 (80) [MC ₂ H ₅ NO˙] ⁺ .

3:1 23

3:1 21

1:3 18 The test results are summarized in the following table: Phenol (P) Arylamine (A) Ratio P: A yield

3: 1 23

3: 1 21

1: 3 18

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 ).

As the test results show, the object is achieved by a method according to the invention.

Claims (13)

Electrochemical process for the OC coupling of phenol with an optically pure arylamine comprising the process steps: a) introduction of 1,1,1,3,3,3-hexafluoroisopropanol into a reaction vessel, b) adding an optically pure arylamine, c) adding a phenol, wherein the phenol is added in excess to the arylamine in excess, d) introducing two electrodes into the reaction solution, e) applying a voltage to the electrodes, f) OC coupling of the phenol and the optically pure arylamine. Method according to claim 1,
wherein the phenol is used relative to the arylamine in at least twice the amount. Method according to one of claims 1 or 2,
wherein the ratio of phenol to arylamine is in the range of 2: 1 to 4: 1. Method according to one of claims 1 to 3,
wherein the reaction solution is free of organic oxidizing agents. Method according to one of claims 1 to 4,
wherein 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.

Method according to claim 5,
wherein the substituents R ¹ to R ^{5 are} independently selected from:

-H, - (C ₁ -C ₁₂ ) -alkyl, -O- (C ₁ -C ₁₂ ) -alkyl.

Method according to one of claims 5 or 6,
wherein the substituents R ¹ to R ^{5 are} independently selected from:

-H, -CH ₃ , -O-CH ₃ , - tert -butyl.

Method according to one of claims 1 to 7,
wherein 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 . Method according to one of claims 1 to 8,
wherein 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 . Method according to one of claims 8 or 9,
wherein 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 . Method according to one of claims 8 to 10,
where R ^{6 is} -CH ₃ ,
and R ⁶ does not stand for the same radical as R ⁷ . Method according to one of claims 8 to 11,
where R ^{7 is} -phenyl,
and R ⁶ does not stand for the same radical as R ⁷ . Method according to one of claims 1 to 12,
wherein the oxygen of the phenol in ortho-position to the nitrogen couples to the aromatic of the optically pure arylamine.