2,2' -DIAMINOBIARYLS HAVING TWO SECONDARY AMINES

Abstract

Novel 2,2′-diaminobiaryls having two secondary amines and an electrochemical process for preparation thereof.

Claims

1. Compound having one of the general structures (I) to (III): ##STR00022## where R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.1′, R.sup.2′, R.sup.3′, R.sup.4′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —(C.sub.6-C.sub.20)-aryl, halogen, —COO—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.6-C.sub.20)-aryl, —COOH, —OH, —SO.sub.3H, —CN, —N[(C.sub.1-C.sub.12)-alkyl].sub.2; R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.5′, R.sup.6′, R.sup.7′, R.sup.8′, R.sup.9′, R.sup.10′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen, —COO—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.6-C.sub.20)-aryl, —COOH, —OH, —SO.sub.3H, —N[(C.sub.1-C.sub.12)-alkyl].sub.2; where the alkyl and aryl groups mentioned may be substituted; and, in the formula (I), the two radicals of at least one of the four following radical pairs are not the same radical: R.sup.1 and R.sup.1′, R.sup.2 and R.sup.2′, R.sup.3 and R.sup.3′, R.sup.4 and R.sup.4′, and, in the formula (III), the two radicals of at least one of the six following radical pairs are not the same radical: R.sup.5 and R.sup.5′, R.sup.6 and R.sup.6′, R.sup.7 and R.sup.7′, R.sup.8 and R.sup.8′, R.sup.9 and R.sup.9′, R.sup.10 and R.sup.10′, X.sup.1 is selected from: tert-butyloxycarbonyl, methyloxycarbonyl, benzyloxycarbonyl, phenyloxycarbonyl, trifluoroacetyl, benzoyl, sulphonyl, sulphenyl; X.sup.2 is selected from: tert-butyloxycarbonyl, methyloxycarbonyl, benzyloxycarbonyl, phenyloxycarbonyl, acetyl, trifluoroacetyl, benzoyl, sulphonyl, sulphenyl; X.sup.3 is selected from: methyloxycarbonyl, benzyloxycarbonyl, phenyloxycarbonyl, acetyl, trifluoroacetyl, benzoyl, sulphonyl, sulphenyl.

2. Compound according to claim 1, where X.sup.1 is selected from: tert-butyloxycarbonyl, methyloxycarbonyl, benzyloxycarbonyl, phenyloxycarbonyl, trifluoroacetyl, benzoyl.

3. Compound according to claim 1, where X.sup.2 is selected from: tert-butyloxycarbonyl, methyloxycarbonyl, benzyloxycarbonyl, phenyloxycarbonyl, acetyl, trifluoroacetyl, benzoyl.

4. Compound according to claim 1, where X.sup.3 is selected from: methyloxycarbonyl, benzyloxycarbonyl, phenyloxycarbonyl, acetyl, trifluoroacetyl, benzoyl.

5. Compound according to claim 1, where R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.1′, R.sup.2′, R.sup.3′, R.sup.4′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen.

6. Compound according to claim 1, where R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.1′, R.sup.2′, R.sup.3′, R.sup.4′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl.

7. Compound according to claim 1, where R.sup.5′, R.sup.6′, R.sup.7′, R.sup.8′, R.sup.9′, R.sup.10′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen.

8. Compound according to claim 1, where R.sup.5′, R.sup.6′, R.sup.7′, R.sup.8′, R.sup.9′, R.sup.10′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl.

9. Compound according to claim 1, where R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen.

10. Compound according to claim 1, where R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl.

11. Compound according to claim 1, wherein the compound has the general structure (I).

12. Compound according to claim 1, wherein the compound has the general structure (II).

13. Compound according to claim 1, wherein the compound has the general structure (III).

14. Process for preparing 2,2′-diaminobiaryls, comprising the process steps of: a) reacting a compound of the formula (IVa) or (Va): ##STR00023## with reaction of (IVa) with X.sup.11 or X.sup.12 to give (IVb1) or (IVb2), or of (Va) with X.sup.13 to give (Vb): ##STR00024## b) reacting a compound of the formula (VIa) or (VIIa): ##STR00025## with reaction of (VIa) with X.sup.11 to give (VIb), or of (VIIa) with X.sup.12 or X.sup.13 to give (VIIb1) or (VIIb2): ##STR00026## c) electrochemical coupling of (IVb1) with (VIb) to give (I*), or (IVb2) with (VIIb1) to give (II*), or (Vb) with (VIIb2) to give (III*), in each case with use of the compound having the higher oxidation potential in excess: ##STR00027## where R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.11′, R.sup.12′, R.sup.13′, R.sup.14′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen, —COO—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.6-C.sub.20)-aryl, —COOH, —OH, —SO.sub.3H, —CN, —N[(C.sub.1-C.sub.12)-alkyl].sub.2; R.sup.15, R.sup.16, R.sup.17, R.sup.18, R.sup.19, R.sup.20, R.sup.15′, R.sup.16′, R.sup.17′, R.sup.18′, R.sup.19′, R.sup.20′ are selected from: —H, —(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.1-C.sub.12)-alkyl, —O—(C.sub.6-C.sub.20)-aryl, —(C.sub.6-C.sub.20)-aryl, —S-alkyl, —S-aryl, halogen, —COO—(C.sub.1-C.sub.12)-alkyl, —CONH—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.1-C.sub.12)-alkyl, —CO—(C.sub.6-C.sub.20)-aryl, —COOH, —OH, —SO.sub.3H, —N[(C.sub.1-C.sub.12)-alkyl].sub.2; where the alkyl and aryl groups mentioned may be substituted; X.sup.11, X.sup.12, X.sup.13 are selected from: tert-butyloxycarbonyl, methyloxycarbonyl, benzyloxycarbonyl, phenyloxycarbonyl, acetyl, trifluoroacetyl, benzoyl, sulphonyl, sulphenyl.

Description

[0075] The invention is illustrated in detail hereinafter by working examples and figures.

[0076] FIG. 1 shows the schematic setup of a reaction apparatus in which the coupling reaction to give the corresponding unsymmetric 2,2′-diaminobiaryls can be conducted. The reaction apparatus comprises glassy carbon electrodes (5) held with stainless steel clamps (4). A magnetic stirrer bar (6) ensures mixing in the reaction apparatus. A Teflon stopper (2) rests on top of the reaction apparatus, through which stainless steel holders (1) for the electrodes lead. The reaction apparatus, a beaker cell here, has a fitted outlet (3) for a reflux condenser attachment.

[0077] FIG. 2: E.sub.Ox as a function of the para substituents of acetanilides

##STR00009##

[0078] In general, through addition of methanol, a rise in E.sub.ox of 4-substituted acetanilides is observed. It is noticeable here that E.sub.ox of 4-methoxyacetanilide on addition of about 8% by volume of MeOH is actually raised above E.sub.ox of 4-tert-butylacetanilide. A rise in E by up to 100 mV is possible in a selective manner.

[0079] FIG. 3: E.sub.Ox as a function of the meta substituents of acetanilides

##STR00010##

[0080] The addition of methanol to meta-substituted acetanilides, shown here using the example of 3-methoxyacetanilide, leads to a virtually linear decrease in E.sub.ox. A drop of 80 mV has been measured here.

[0081] FIG. 4: E.sub.Ox as a function of the ortho,para substituents of acetanilide

##STR00011##

[0082] The changes in E.sub.ox in the case of 2,4 disubstitution only have a weak effect on acetanilides. Only a slight rise (R═R′=Me) or drop (R=Me, R′═Cl) in E.sub.ox can be observed. Addition of methanol in the case of this substitution pattern causes a variation in the oxidation potentials by about 30 mV.

[0083] FIG. 5: E.sub.Ox as a function of the meta,para substituents of acetanilides

##STR00012##

[0084] In contrast, a significant lowering in E.sub.ox is possible when using a 3,4 disubstitution. It is found here that the substrate having the higher electron density (a benzodioxole derivative) experiences a distinct drop by almost 300 mV.

[0085] FIG. 6: Comparison of Eo, as a function of the protection of 3,4-dimethoxyaniline

##STR00013##

[0086] The use of trifluoroacetyl rather than acetyl protecting groups, as a result of strong electron withdrawal by the fluorine atoms, causes a rise in E.sub.ox of 3,4-dimethoxyaniline by about 150 mV. At the same time, the influence of MeOH on the trifluoroacetyl derivative is considerably enhanced. The latter derivative, in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), experiences a drop of up to 250 mV in the case of addition of MeOH.

[0087] FIG. 7: E.sub.Ox as a function of N-(naphthalen-2-yl)acetamide

##STR00014##

[0088] N-(Naphthalen-2-yl)acetamide shows a similar plot to p-methoxyacetanilide. Addition of methanol results in a distinct rise in E.sub.ox to about 15% by volume. A shift of about 140 mV is possible in this way. In the case of greater amounts of MeOH, there is a drop in E.sub.ox here too.

[0089] On the basis of the results shown in FIGS. 2-7, it becomes clear that the oxidation potentials can be influenced by the different protecting groups and hence the electrochemical coupling can be controlled.

Analysis

Chromatography

[0090] The preparative liquid chromatography separations via flash chromatography were conducted with a maximum pressure of 1.6 bar on 60 M silica gel (0.040-0.063 mm) from Macherey-Nagel GmbH & Co. Düren. The unpressurized separations were conducted on Geduran Si 60 silica gel (0.063-0.200 mm) from Merck KGaA, Darmstadt. The solvents used as eluents (ethyl acetate (technical grade), cyclohexane (technical grade)) had been purified by distillation beforehand on a rotary evaporator.

[0091] For thin-film chromatography (TLC), ready-made PSC silica gel 60 F254 plates from Merck KGaA, Darmstadt were used. The Rf values are reported as a function of the eluent mixture used. The TLC plates were stained using a cerium/molybdatophosphoric acid solution as immersion reagent. Cerium/molybdatophosphoric acid reagent: 5.6 g of molybdatophosphoric acid, 2.2 g of cerium(IV) sulphate tetrahydrate and 13.3 g of concentrated sulphuric acid to 200 ml of water.

Gas Chromatography (GC/GCMS)

[0092] The gas chromatography studies (GC) on product mixtures and pure substances were effected with the aid of the GC-2010 gas chromatograph from Shimadzu, Japan. Analysis is effected on an HP-5 quartz capillary column from Agilent Technologies, USA (length: 30 m; internal diameter: 0.25 mm; film thickness of the covalently bound stationary phase: 0.25 μm; carrier gas: hydrogen; injector temperature: 250° C.; detector temperature: 310° C.; program: “hard” method: start temperature 50° C. for 1 min, heating rate: 15° C./min, end temperature 290° C. for 8 min). Gas chromatography-mass spectrometry analyses (GC-MS) of product mixtures and pure substances were conducted with the aid of the GC-2010 gas chromatograph combined with the GCMS-QP2010 mass detector from Shimadzu, Japan. Analysis is effected on an HP-1 quartz capillary column from Agilent Technologies, USA (length: 30 m; internal diameter 0.25 mm; film thickness of the covalently bound stationary phase: 0.25 μm; carrier gas: hydrogen; injector temperature: 250° C.; detector temperature: 310° C.; program: “hard” method: start temperature 50° C. for 1 min, heating rate: 15° C./min, end temperature 290° C. for 8 min; GC-MS: ion source temperature: 200° C.).

Melting Points

[0093] Melting points were measured with the aid of the SG 2000 melting point determination instrument from HW5, Mainz, and are uncorrected.

Elemental Analysis

[0094] The elemental analyses were conducted in the analytical division of the Organic Chemistry department of the Johannes Gutenberg University of Mainz on a Vario EL Cube from Foss-Heraeus, Hanau.

Mass Spectrometry

[0095] All electrospray ionization analyses (ESI+) were conducted on a QTof Ultima 3 from Waters Micromasses, Milford, Mass. EI mass spectra and the high-resolution EI spectra were analysed on an instrument of the MAT 95 XL sector field instrument type from ThermoFinnigan, Bremen.

NMR Spectroscopy

[0096] The NMR spectroscopy studies were conducted on multi-nucleus resonance spectrometers of the AC 300 or AV II 400 type from Bruker, Analytische Messtechnik, Karlsruhe. The solvent used was CDCl3. The 1H and 13C spectra were calibrated according to the residual content of undeuterated solvent using the NMR Solvent Data Chart from Cambridge Isotopes Laboratories, USA. Some of the 1H and 13C signals were assigned with the aid of H,H-COSY, H,H-NOESY, H,C-HSQC and H,C-HMBC spectra. The chemical shifts are reported as δ values in ppm. For the multiplicities of the NMR signals, the following abbreviations were used: s (singlet), bs (broad singlet), d (doublet), t (triplet), q (quartet), m (multiplet), dd (doublet of doublets), dt (doublet of triplets), tq (triplet of quartets). All coupling constants J were reported in hertz (Hz) together with the number of bonds covered. The numbering given in the assignment of signals corresponds to the numbering shown in the formula schemes, which do not necessarily have to correspond to IUPAC nomenclature.

[0097] Examples of Possible Protecting Groups:

Carbamates

[0098] ##STR00015##

Amides:

[0099] ##STR00016##

with Bn=benzyl, Ph=phenyl.

[0100] The Y and Z radicals correspond to the definition given above.

[0101] The introduction of the protecting groups can be effected, for example, as described in P. G. M. Wuts, T. W. Greene “Greene's Protective Groups in Organic Synthesis”, fourth edition, 2007, John Wiley and Sons; Hoboken, N.J.

M1: Method for N-acetylation

[0102] The aniline derivative or naphthylamine derivative to be protected (1 equiv.) is initially charged in a round-bottom flask and dissolved in dichloromethane. While cooling with ice, 1.2 equiv. of acetic anhydride are gradually added dropwise to the reaction solution. On completion of addition, the reaction mixture is stirred at room temperature and/or under reflux for 24 hours. After the reaction has ended, the solvent is removed under reduced pressure and the crude product is purified by flash chromatography on silica gel 60 in the eluent CH:EA (4:1 to 1:1).

M2: Method for N-2,2,2-Trifluoroacetamide Protection

[0103] A round-bottom flask is initially charged with the aniline derivative or naphthylamine derivative to be protected (1 equiv.) in dichloromethane solution. While cooling with ice and stirring vigorously, 1.2 equiv. of trifluoroacetic anhydride are added gradually to this solution. After the addition has ended, the reaction flask is heated to 35° C. for 4-5 hours. After the reaction has ended, the solvent is removed under reduced pressure and the crude product is purified by flash chromatography on silica gel 60 in the eluent CH:EA (4:1 to 1:1).

M3: Method for Electrochemical Cross-Coupling

[0104] In an undivided beaker cell having glassy carbon electrodes, 3.8 mmol of component A (cf. Reaction Scheme 2) and 7.6 mmol of component B to be coupled (cf. Reaction Scheme 2) are dissolved in 25 ml of 1,1,1,3,3,3-hexafluoroisopropanol and 0.77 g of MTBS. The electrolysis is galvanostatic. During the electrolysis, the beaker cell is heated to 50° C. with the aid of a water bath and the reaction mixture is stirred. After the electrolysis has ended, the cell contents are transferred to a corresponding round-bottom flask and the solvent is removed on a rotary evaporator at 50° C., 200.fwdarw.90 mbar, under reduced pressure.

[0105] Electrode Material:

[0106] Anode: glassy carbon

[0107] Cathode: glassy carbon

[0108] Electrolysis Conditions:

[0109] Temperature [T]: 50° C.

[0110] Current density [j]: 2.8 mA/cm2

[0111] Charge [Q]: 2 F (per deficiency component)

M4: Method for Electrochemical Cross-Coupling (Screening)

[0112] In an undivided screening cell, 0.76 mmol of component A (cf. Reaction Scheme 2) and 1.51 mmol of component B to be coupled (cf. Reaction Scheme 2) were dissolved in 5 ml of 1,1,1,3,3,3-hexafluoroisopropanol and 154 mg of MTBS. The electrolysis is galvanostatic. During the electrolysis, the screening cell is heated to 50° C. in a screening block and the reaction mixture is stirred. After the electrolysis has ended, the cell contents are transferred to a corresponding round-bottom flask and the solvent is removed on a rotary evaporator at 50° C., 200.fwdarw.90 mbar, under reduced pressure.

[0113] Electrode Material:

[0114] Anode: BDD or glassy carbon

[0115] Cathode; BDD or glassy carbon

[0116] Electrolysis Conditions:

[0117] Temperature [T]: 50° C.

[0118] Current density [j]: 2.8 mA/cm2

[0119] Charge [Q]: 2 F (per deficiency component)

M5: General Method for Removal of N-2,2,2-Trlfluoroacetamide Protecting Groups

[0120] A round-bottom flask is initially charged with 1 equiv. of the substrate to be deprotected, dissolved in a methanol/water mixture in a ratio of 2:1. Then 10 equiv. of potassium carbonate are added to the reaction solution, which is stirred at room temperature for four days. After the reaction has ended, the solvent is removed under reduced pressure. The residue is slurried with water and the deprotected product is extracted with dichloromethane. Unless deprotection is quantitative, the crude product is purified by flash chromatography on silica gel 60.

M6: General Method for Removal of N-Acetyl Protecting Groups

[0121] The substrate to be deprotected (1 equiv.) is initially charged in a round-bottom flask and dissolved in methanol. While stirring vigorously, 12 equiv. of boron trifluoride diethyl etherate are added to the reaction solution, and then the mixture is heated under reflux for 18 hours. The reaction is ended by addition of 20 equiv. of triethylamine, and the product which precipitates out in solid form can be filtered off.

2-(N-Acetyl)amino-1-(2′-(N′-trifluoroacetyl)amino-4′,5′-dimethoxyphenyl)naphthalene

[0122] ##STR00017##

a) Synthesis of 2,2′-Diaminobiaryl on the Screening Scale

[0123] The electrolysis is conducted according to M4 in an undivided screening cell. For this purpose, 140 mg (0.76 mmol. 1.0 equiv.) of N-(naphthalen-2-yl)acetamide and 377 mg (1.51 mmol, 2 equiv.) of N-(3,4-dimethoxyphenyl)-2,2,2-trifluoroacetamide are dissolved in 5 ml of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), 154 mg of MTBS are added and the electrolyte is transferred into the electrolysis cell. After the electrolysis, the solvent and unconverted reactants are removed under reduced pressure. The crude product is then purified by flash chromatography on silica gel 60 in a 2:1 eluent (CH:EA), and the product is obtained as a colourless solid.

[0124] The screening reaction was used to examine different electrode materials. The electrode materials chosen were BDD and glassy carbon, which prepared the C,C cross-coupling product in different yields (Table 1).

TABLE-US-00001 TABLE 1 List of the electrode materials used with the resulting yields Electrode material Yield BDD 24% (78 mg)  glassy carbon 44% (144 mg)

[0125] Electrode material Yield

[0126] BDD 24% (78 mg)

[0127] Glassy carbon 44% (144 mg)

b) Synthesis of 2,2′-Diaminobiaryl in a Beaker Cell

[0128] The electrolysis is conducted according to M3 in an undivided beaker cell with glassy carbon electrodes. 0.70 g (3.79 mmol, 1.0 equiv.) of N-(naphthalen-2-yl)acetamide and 1.89 g (7.57 mmol, 2 equiv.) of N-(3,4-dimethoxyphenyl)-2,2,2-trifluoroacetamide are dissolved in 25 ml of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), 0.77 g of MTBS are added and the electrolyte is transferred into the electrolysis cell. The solvent and unconverted amounts of reactant are removed under reduced pressure after the electrolysis, the crude product is purified by flash chromatography on silica gel 60 in a 2:1 eluent (CH:EA) and the product is obtained as a colourless solid.

[0129] Yield: 1.02 g (62%, 2.36 mmol)

[0130] GC (hard method, HP-5): tR=16.90 min

[0131] Rf (EA:CH=2:1)=0.5

[0132] .sup.1H NMR (300 MHz, CDCl3) δ=2.00 (s, 3H), 3.84 (s, 3H), 4.01 (s, 3H), 6.73 (s, 1H), 7.15 (bs, 1H), 7.27 (d, J=9 Hz, 1H), 7.44 (dt, J=6 Hz, 7.66 (s, 1H), 7.91 (m, 3H) 7.93 (bs, 1H), 8.11 (d, 1H)

[0133] .sup.13C NMR (75 MHz, CDCl3) δ=24.23, 56.33, 56.38, 107.73, 113.15, 113.63, 117.45, 120.79, 122.57, 124.55, 124.88, 125.96, 127.03, 127.54, 128.47, 130.08, 131.51, 132.36, 133.98, 148.10, 149.53, 169.47

[0134] HRMS for C.sub.22H.sub.19F3N.sub.2O.sub.4(ESI+) [M+H+]: calc.: 433.1375, found: 433.1375.

2-(N-Acetyl)amino-1-(2′-amino-4′,5′-dimethoxyphenyl)naphthalene

[0135] ##STR00018##

[0136] In a round-bottom flask, according to M5, 0.65 g (1.50 mmol, 1 equiv.) of 2-(N-acetyl)amino-1-(2′-(N′-trifluoroacetyl)-amino-4′,5′-dimethoxyphenyl)naphthalene is dissolved in 120 ml of a methanol/water mixture in a ratio of 2:1, 2.07 g (15.01 mmol, 10 equiv.) of potassium carbonate are added to this solution and the reaction mixture is stirred at room temperature for four days. After the reaction has ended, the solvent is removed under reduced pressure, the residue is slurried with water and the deprotected product is extracted with dichloromethane.

[0137] Yield: 500 mg (99%, 1.49 mmol)

[0138] GC (hard method, HP-5): tR=18.68 min

[0139] Rf (EA:CH=2:1)=0.46

[0140] .sup.1H NMR (300 MHz, CDCl3) δ=2.03 (s, 3H), 3.12 (bs, 2H), 3.77 (s, 3H), 3.94 (s, 3H), 6.59 (d, J=15 Hz, 2H), 7.35-7.46 (m, 4H), 7.87 (dd, J=9 Hz, 2H), 8.40 (d, J=9 Hz, 1H)

[0141] .sup.13C NMR (75 MHz, CDCl3) δ=24.87, 56.02, 56.58, 101.21, 111.55, 114.60, 121.36, 123.50, 125.18, 125.61, 126.81, 128.25, 129.01, 131.28, 132.77, 134.48, 137.70, 143.04, 150.28, 168.96

[0142] HRMS for C.sub.20H.sub.20N.sub.2O.sub.3 (ESI+) [M+H+]: calc.: 337.1552, found: 337.1552.

2-(N-Acetyl)amino-1-(2′-(N′-4-methylphenylsulphonyl))amino-4′,5′-dimethoxyphenyl)naphthalene

[0143] ##STR00019##

[0144] 278 mg (0.83 mmol, 1 equiv.) of N-acetyl-2-amino-1-(2′-amino-4′,5′-dimethoxyphenyl)naphthalene in 110 ml of dichloromethane are initially charged in a round-bottom flask. Added to this reaction solution are 173 mg (0.91 mmol, 1.1 equiv.) of p-methylsulphonyl chloride and 0.13 ml (0.91 mmol, 1.1 equiv.) of triethylamine, and the mixture is stirred at room temperature for 111 hours. After the reaction has ended, the solvent is removed under reduced pressure and the crude product is purified by flash chromatography on silica gel 60 in a 2:1 eluent (CH:EA).

[0145] Yield: 342 mg (84%, 0.70 mmol)

[0146] GC (hard method, HP-5): tR=16.87 min

[0147] Rf(EA:CH=2:1)=0.21

[0148] .sup.1H NMR (300 MHz, CDCl3) δ=1.87 (s, 3H), 2.38 (s, 3H), 3.75 (s, 3H), 3.94 (s, 3H), 6.09 (s, 1H), 6.56 (s, 1H), 6.68 (s, 1H), 6.94 (d, J=9 Hz, 1H), 7.10 (d, J=6 Hz, 2H), 7.24 (t, J=6 Hz, 1H), 7.29 (bs, 1H), 7.36 (d, J=9 Hz, 2H), 7.42 (t, J=6 Hz, 1H), 7.88 (dd, J=15 Hz, J=9 Hz, 2H), 8.32 (d, J=9 Hz, 1H)

[0149] .sup.13C NMR (75 MHz, CDCl3) δ=21.70, 24.58, 56.19, 56.27, 106.87, 113.17, 119.35, 121.46, 124.49, 124.89, 125.40, 125.92, 127.40, 127.40, 127.44, 128.50, 129.74, 129.74, 129.81, 130.98, 132.28, 134.61, 136.40, 144.15, 147.38, 149.75, 168.58

[0150] HRMS for C.sub.20H.sub.20N.sub.2O.sub.3(ESI+) [M+H+]: calc.: 491.1641, found: 491.1651.

2-Amino-1-(2′-N-(4-methylphenylsulphonyl)-amino-4,5′-dimethoxyphenyl)naphthalene

[0151] ##STR00020##

[0152] According to M6, 342 mg (0.70 mmol, 1 equiv.) of N-acetyl-2-amino-1-(2′-N-(4-methylphenylsulphonyl)-amino-4′,5′-dimethoxyphenyl)naphthalene are initially charged in 40 ml of methanol. 1.06 ml (8.37 mmol, 12 equiv.) of boron trifluoride diethyl etherate are added to this solution while stirring vigorously, and the mixture is heated under reflux for 18 hours. The reaction is ended by the addition of 2 ml of triethylamine, and the product which precipitates out in solid form can be filtered off.

[0153] Yield: 219 mg (70%, 0.49 mmol)

[0154] GC (hard method, HP-5): tR=15.64 min

[0155] Rf (EA:CH=2:1)=0.78

[0156] .sup.1H NMR (300 MHz, CDCl3) δ=2.21 (s, 3H), 3.00 (bs, 2H), 3.76 (s, 3H), 3.98 (s, 3H), 6.64 (s, 1H), 6.73-6.83 (m, 4H), 7.00-7.08 (m, 2H), 7.15-7.24 (m, 3H), 7.40 (s, 1H), 7.70 (dd, J=6 Hz, J=9 Hz, 2H)

[0157] .sup.13C NMR (75 MHz, CDCl3) δ=21.61, 56.18, 56.27, 108.18, 114.19, 114.95, 118.02, 120.61, 122.65, 123.75, 126.88, 126.98, 126.98, 128.08, 128.34, 128.49, 129.25, 129.25, 130.04, 133.51, 135.97, 140.54, 143.28, 147.20, 149.30

[0158] HRMS for C.sub.20H.sub.20N.sub.2O.sub.3(ESI+) [M+H+]: calc.: 449.1535, found: 449.1542.

2-Amino-1-(2′-N-(4-methylphenylsulphonyl)-amino-4′5′-dimethoxyphenyl)naphthalene

[0159] ##STR00021##

[0160] In a round-bottom flask, 300 mg (0.69 mmol, 1 equiv.) of 2-(N-acetyl)amino-1-(2′-(N′-trifluoroacetyl)-amino-4′,5′-dimethoxyphenyl)naphthalene are dissolved in 80 ml of hydrazine hydrate solution (80% aqueous solution). The reaction solution is stirred under reflux at 120° C. for 4 days. After the reaction has ended, the mixture is extracted 3 times with 20 ml of dichloromethane each time, and the solvent is removed under reduced pressure. The product is obtained as a brownish foam.

[0161] Yield: 200 mg (98%, 0.68 mmol)

[0162] GC (hard method, HP-5): tR=17.21 min

[0163] Rf (EA:CH=2:1)=0.44

[0164] .sup.1H NMR (300 MHz, CDCl3) δ=3.61 (s, 3H), 3.77 (s, 3H), 4.01 (bs, 2H), 4.77 (bs, 2H), 6.50 (s, 1H), 6.58 (s, 1H), 7.09-7.25 (m, 4H), 7.66 (d, J=9 Hz, 1H), 7.69 (d, J=6 Hz, 1H)

[0165] .sup.13C NMR (75 MHz, CDCl3) δ=55.25, 56.37, 100.60, 111.34, 113.66, 116.07, 118.46, 120.99, 123.45, 125.97, 127.07, 127.88, 128.19, 133.70, 140.43, 140.84, 143.58, 149.32

[0166] HRMS for C.sub.18H.sub.18N.sub.2O.sub.2 (ESI+) [M+H+]: calc.: 295.1447, found: 295.1458.

[0167] The compounds shown in the examples solve the stated problem. It has been possible for the first time to prepare novel 2,2′-diaminobiaryls in good to very good yields. At the same time, an entirely novel synthesis strategy is employed: Both aminoaryls are first protected independently, then electrochemically coupled, and can then be selectively deprotected if required. Through this procedure, it is possible to prepare compounds having two identical protecting groups which were unobtainable because of the existing procedure specified in the prior art.