Process for preparing unsymmetric OCO pincer ligands from the group of the M-terphenyl compounds

Abstract

The present invention relates to a process for preparing unsymmetric compounds from the group of the m-terphenyls which can be used as unsymmetric OCO pincer ligands, comprising the process steps of a) reacting a first substituted or unsubstituted phenol with a 1,3-disubstituted arene which may likewise be substituted in the 2 and 5 positions to obtain a phenol-arene coupling product and b) optionally protecting the OH group of the phenol-arene coupling product with a protecting group to obtain a protected phenol-arene coupling product, and c) reacting the phenol-arene coupling product from a) or b) with a second substituted or unsubstituted phenol to obtain an unsymmetric m-terphenyl, with the proviso that the first phenol and the second phenol have different substitution, characterized in that at least one of process steps a) and c) is conducted as an electrochemical process step.

Claims

1. A process for preparing unsymmetric compounds from the group of the m-terphenyls, comprising the process steps of a) reacting a first substituted or unsubstituted phenol with a 1,3-disubstituted arene which may be substituted in the 2 and 5 positions to obtain a phenol-arene coupling product and b) optionally protecting the OH group of the phenol-arene coupling product with a protecting group to obtain a protected phenol-arene coupling product, c) reacting the phenol-arene coupling product from a) or b) with a second substituted or unsubstituted phenol to obtain an unsymmetric m-terphenyl, with the proviso that the first phenol and the second phenol have different substitution, wherein at least one of process steps a) and c) is conducted as an electrochemical process step, and the electrochemical process step comprises: mixing at least one solvent and at least one conductive salt to form a mixture; adding compounds to be converted to the mixture to form a reaction mixture: introducing at least two electrodes into the reaction mixture; and applying a voltage to the electrodes.

2. The process according to claim 1, wherein both process steps a) and c) are conducted as electrochemical process steps.

3. The process according to claim 1, wherein the electrochemical process step further comprises: adding the phenol in molar deficiency relative to the other component to be converted, converting the components to the corresponding coupling products, switching off the voltage, and optionally isolating and/or purifying the reaction product.

4. The process according to claim 1, wherein the molar ratio of the 1,3-disubstituted arene which may be substituted in the 2 and 5 positions to the first substituted or unsubstituted phenol is in the range from 1.5:1 to 6:1.

5. The process according to claim 1, wherein the molar ratio of the phenol-arene coupling product to the second phenol is in the range from 1.5:1 to 6:1.

6. The process according to claim 1, wherein the first substituted or unsubstituted phenol corresponds to the formula (A) ##STR00023## the second substituted or unsubstituted phenol to the formula (A) ##STR00024## and the 1,3-disubstituted arene which may be substituted in the 2 and 5 positions to the formula (B) ##STR00025## and R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.10 and R.sup.12 are each independently selected from the group consisting of hydrogen, (C.sub.1-C.sub.12)-alkyl, O(C.sub.1-C.sub.12)-alkyl, (C.sub.6-C.sub.20)-aryl, O(C.sub.6-C.sub.20)-aryl and halogen, in which R.sup.9 and R.sup.11 are each independently selected from the group consisting of (C.sub.1-C.sub.12)-alkyl, O(C.sub.1-C.sub.12)-alkyl, (C.sub.6-C.sub.20)-aryl, O(C.sub.6-C.sub.20)-aryl and halogen, and in which at least one pair among the R.sup.1/R.sup.5, R.sup.2/R.sup.6, R.sup.3/R.sup.7 and R.sup.4/R.sup.8 pairs consists of different radicals.

7. The process according to claim 6, where R.sup.10 and R.sup.12 are identical.

8. The process according to claim 1, wherein the at least one solvent is selected from the group consisting of acetonitrile, propylene carbonate, methyl carbonate, nitromethane, ethylene glycol dimethyl ether, methanesulphonic acid, benzene, toluene, water, methanol, ethanol, propanol, isopropanol, halogenated solvents, halogenated or non-halogenated acids, and mixtures thereof.

9. The process according to claim 8, wherein the solvent is methanol, formic acid, trifluoroacetic acid, hexafluoroisopropanol or mixtures thereof.

10. The process according to claim 1, wherein the reaction is conducted without the use of organic oxidizing agents.

11. The process according to claim 1, wherein the at least one conductive salt is selected from the group consisting of tetra(C.sub.1-C.sub.6-alkyl)ammonium and 1,3-di(C.sub.1-C.sub.6-alkyl)imidazolium salts, with the proviso that the alkyl groups may be halogen-substituted.

12. The process according to claim 11, wherein the counterions of the conductive salts are selected from the group consisting of arsenate, sulphate, hydrogensulphate, alkylsulphate, alkylphosphate, perchlorate, fluoride, arylsulphate, hexafluorophosphate, and tetrafluoroborate.

13. The process according to claim 1, wherein the conductive salt is selected from the group consisting of quaternary ammonium borates, ammonium fluoroalkylphosphates, ammonium fluoroalkylarsenates, ammonium trifluoromethylsulphonates, ammonium bis(fluoromethanesulphon)imides, ammonium tris(fluoromethanesulphonyl)methides, methyltributylammonium methylsulphate, methyltriethylammonium methylsulphate, tetrabutylammonium hexafluorophosphate, tetraethylammonium tetrafluoroborate, lithium hexafluorophosphate, and tetraethylammonium tetrafluoroborate.

14. The process of claim 4, wherein the molar ratio of the 1,3-disubstituted arene which may be substituted in the 2 and 5 positions to the first substituted or unsubstituted phenol is in the range from 2:1 to 3:1.

15. The process of claim 5, wherein molar ratio of the phenol-arene coupling product to the second phenol is in the range from 2:1 to 3:1.

16. The process of claim 6, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.10 and R.sup.12 are each independently selected from the group consisting of hydrogen, (C.sub.1-C.sub.12)-alkyl, O(C.sub.1-C.sub.12)-alkyl and halogen.

17. The process of claim 16, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.10 and R.sup.12 are each independently selected from the group consisting of hydrogen, (C.sub.1-C.sub.12)-alkyl, and O(C.sub.1-C.sub.12)-alkyl.

18. The process of claim 6, wherein R.sup.9 and R.sup.11 are each independently selected from the group consisting of (C.sub.1-C.sub.12)-alkyl, O(C.sub.1-C.sub.12)-alkyl, and halogen.

19. The process of claim 18, wherein R.sup.9 and R.sup.11 are each independently selected from (C.sub.1-C.sub.12)-alkyl or O(C.sub.1-C.sub.12)-alkyl.

20. The process of claim 7, wherein R.sup.10 and R.sup.12 are hydrogen.

21. The process of claim 9, wherein the solvent is methanol, hexafluoroisopropanol, or mixtures thereof.

22. The process of claim 21, wherein the solvent is hexafluoroisopropanol.

23. The process of claim 13, wherein the conductive salt is methyltriethylammonium methylsulphate or methyltributylammonium methylsulphate.

24. The process of claim 23, wherein the conductive salt is methyltributylammonium methylsulphate.

Description

(1) FIG. 1 shows a schematic of a screening cell. Indicated in FIG. 2 are the BDD electrodes (1), a Teflon lid (2), a Teflon beaker (3) and a stirrer magnet (4).

(2) FIG. 2 shows a schematic of a flange cell (glass). Indicated in FIG. 2 are a stainless steel rod with a secured nickel mesh cathode (1), a Teflon stopper (2), a cooling jacket (glass) (3), a screw clamp (4), a BDD electrode (5), an EPDM seal (6) and a stirrer magnet (7).

(3) FIG. 3 shows a schematic of a small beaker cell (glass). Indicated in FIG. 3 are a stainless steel rod for forming contacts (1), a Teflon stopper (2), a cell outlet/connection (3), for example for a Dimroth condenser, electrode holders (stainless steel) (4), glassy carbon electrodes (5) and a stirrer magnet (6).

(4) FIG. 4 shows a schematic of a large beaker cell (glass). Indicated in FIG. 4 are BDD electrodes (1), the connections for forming contacts (2), the glass shell (3), a stirrer magnet (4), a cell outlet/connection (5), for example for a Dimroth condenser, and an electrically conductive contact (stainless steel foil) (6).

(5) The examples adduced below illustrate the present invention by way of example, without any intention that the invention, the scope of application of which is apparent from the entirety of the description and the claims, be restricted to the embodiments specified in the examples.

EXPERIMENTAL

General Methods

(6) Chromatography (GC/GCMS)

(7) Preparative liquid chromatography for separation of substance mixtures was conducted using 60 M silica gel (0.040-0.063 mm) from MACHERY-NAGEL GMBH & CO. KG, Duren at a maximum pressure of 2 bar. All the eluents used (ethyl acetate, technical grade quality; cyclohexane, technical grade quality) were purified beforehand by distillation on a rotary evaporator.

(8) Thin-layer chromatography (TLC) was conducted on ready-made PSC silica gel 60 F.sub.254 plates from Merck KGaA, Darmstadt. The various substances were detected first under UV light and then by staining by means of cerium-molybdophosphoric acid reagent (5.6 g of molybdophosphoric acid, 2.2 g of cerium(IV) sulphate tetrahydrate and 13.3 g of conc. sulphuric acid in 200 ml of water), followed by heating with a hot air gun.

(9) Gas Chromatography (GC/GCMS)

(10) 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 m; carrier gas: hydrogen; injector temperature: 250 C.; detector temperature: 310 C.; programme: hard method: start temperature 50 C. for 1 min, heating rate: 15 C./min, end temperature 290 C. for 8 min). Gas chromatography-mass spectra (GCMS) of product mixtures and pure substances were recorded 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 m; carrier gas: hydrogen; injector temperature: 250 C.; detector temperature: 310 C.; programme: 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.).

(11) Mass Spectrometry

(12) All electrospray ionization analyses (ESI+) were conducted on a QT of 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 Thermo Finnigan, Bremen.

(13) NMR Spectroscopy

(14) 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 .sup.1H and .sup.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 .sup.1H and .sup.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 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 need not necessarily correspond to IUPAC nomenclature.

(15) Single Crystal Structure Analyses

(16) The single crystal structure analyses were conducted in the Institute of Organic Chemistry at the Johannes Gutenberg University of Mainz on an IPDS 2T instrument from STOE & Cie GmbH, Darmstadt.

(17) Melting Points

(18) The relevant melting points were measured with the aid of the SG 2000 melting point determination instrument from HW5, Mainz, and were adopted in uncorrected form.

General Procedures

GP1

Electrochemical Cross-Coupling in L Cells

(19) 5 mmol of the species A or A to be oxidized (deficiency component) were reacted with a 2-3-fold excess (10-15 mmol) of the coupling partner B or AB in 33 ml of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) or 33 ml of (HFIP with 18% by volume of methanol (MeOH) based on the sum total of HFIP and MeOH) in an undivided flange cell with a BDD anode and nickel mesh cathode. The conductive salt used was Bu.sub.3NMe.sup.+MeOSO.sub.3.sup. (MTBS) with a concentration of 0.09 M. The electrolysis was galvanostatic. The outer shell of the electrolysis cell was kept at a controlled temperature of about 10 C. by means of a thermostat, while the reaction mixture was stirred and heated to 50 C. with the aid of an oil bath. After the electrolysis had ended, the cell contents were transferred to a 50 ml round-bottom flask and the solvent was removed under reduced pressure on a rotary evaporator at 50 C., 200-70 mbar. Mineralization products and the conductive salt present were separated by elution by means of ethyl acetate (300 ml) using 50 g of silica gel 60. Unconverted reactant was recovered by means of short-path distillation in a Kugelrohr still (100 C., 10.sup.3 mbar). The reaction products formed were separated by column chromatography as specified in each case.

(20) Electrode Material:

(21) Anode: BDD (15 m diamond layer) on silicon support Cathode: nickel mesh
Electrolysis Conditions: Temperature: 50 C. Current density: 2.8 mA/cm.sup.2 Charge: 2-4 F based on the deficiency component Terminal voltage: 3-6 V

GP2

Electrochemical Cross-Coupling in a Beaker Cell with Stacked Electrode Arrangement

(22) 120 mmol of the species A to be oxidized (deficiency component) were reacted with a 2-3-fold excess (240-360 mmol) of the coupling partner B in 750 ml of 1,1,1,3,3,3-hexafluoroisopropanol or 750 ml of (HFIP with 18% by volume of MeOH, based on the sum total of HFIP and MeOH) in a beaker cell with a stacked arrangement of 10 BDD electrodes (5anode, 5cathode). The conductive salt used was MTBS with a concentration of 0.09 M. The electrolysis was galvanostatic. Evaporating HFIP was redistilled with the aid of a Dimroth condenser and fed to the electrolysis, while the reaction mixture was stirred and heated to 50 C. with the aid of an oil bath. After the electrolysis had ended, the cell contents were transferred to a 1 l round-bottom flask and the solvent was removed under reduced pressure on a rotary evaporator at 50 C., 200-70 mbar. Mineralization products and the conductive salt present were removed by elution by means of ethyl acetate (2 l) using 300 g of silica gel 60. Unconverted reactant was recovered by means of short-path distillation in a Kugelrohr still (100 C., 10.sup.3 mbar).

(23) Electrode material:

(24) Anode: 5BDD on niobium Cathode: 5BDD on niobium
Electrolysis conditions: Temperature: 50 C. Current density: 2.8 mA/cm.sup.2 Charge: 2-4 F based on the deficiency component Terminal voltage: 3-6 V

GP3

Electrochemical Cross-Coupling in a Beaker Cell

(25) 3.8 mmol of the species A to be oxidized (deficiency component) were reacted with a 2-3-fold excess (7.6-11 mmol) of the coupling partner B in 25 ml of 1,1,1,3,3,3-hexafluoroisopropanol or 25 ml of (HFIP with 18% by volume of MeOH, based on the sum total of HFIP and MeOH) in a beaker cell on glassy carbon electrodes. The conductive salt used was MTBS with a concentration of 0.09 M. The electrolysis was galvanostatic. Evaporating HFIP was redistilled with the aid of a Dimroth condenser and fed to the electrolysis, while the reaction mixture was stirred and heated to 50 C. with the aid of an oil bath. After the electrolysis had ended, the cell contents were transferred to a 100 ml round-bottom flask and the solvent was removed under reduced pressure on a rotary evaporator at 50 C., 200-70 mbar. Mineralization products and the conductive salt present were removed by elution by means of ethyl acetate (300 ml) using 50 g of silica gel 60. Unconverted reactant was recovered by means of short-path distillation in a Kugelrohr still (100 C., 10.sup.3 mbar).

(26) Electrode material:

(27) Anode: glassy carbon Cathode: glassy carbon
Electrolysis conditions: Temperature: 50 C. Current density: 2.8 mA/cm.sup.2 Charge: 2-4 F based on the deficiency component Terminal voltage: 3-6 V

GP4

Electrochemical Cross-Coupling in a Screening Cell

(28) 0.76 mmol of the species A to be oxidized (deficiency component) were reacted with a 2-3-fold excess (1.52-2.28 mmol) of the coupling partner B in 5 ml of 1,1,1,3,3,3-hexafluoroisopropanol or 5 ml of (HFIP with 18% by volume of MeOH, based on the sum total of HFIP and MeOH) in a beaker cell on glassy carbon electrodes. The conductive salt used was MTBS with a concentration of 0.09 M. The electrolysis was galvanostatic. The reaction mixture was placed in a stainless steel block, stirred with the aid of a heated stirrer and kept at 50 C. After the electrolysis had ended, the cell contents were transferred to a 50 ml round-bottom flask and the solvent was removed under reduced pressure on a rotary evaporator at 50 C., 200-70 mbar. Mineralization products and the conductive salt present were removed by elution by means of ethyl acetate (150 ml) using 20 g of silica gel 60. Unconverted reactant was recovered by means of short-path distillation in a Kugelrohr still (100 C., 10.sup.3 mbar).

(29) Electrode material:

(30) Anode: BDD (50 m) on niobium Cathode: BDD (50 m) on niobium
Electrolysis conditions: Temperature: 50 C. Current density: 2.8 mA/cm.sup.2 Charge: 2-4 F based on the deficiency component Terminal voltage: 3-6 V
Two-Stage Pincer Ligand Synthesis

Example 1

3,4-Dimethoxy-2,5-dimethyl-2-hydroxybiphenyl and 2,3-dimethoxy-4,5-dimethyl-2-hydroxybiphenyl

(31) The electrolysis was conducted according to GP1, except that 1.45 g (10.5 mmol, 2.0 equiv.) of 4-methylguaiacol and 639 mg (5.23 mmol, 1.0 equiv.) of 3-methylanisole were used. The current density was 2.8 mA/cm.sup.2, the charge 4 F per 3-methylanisole (Q=2018 C). After removal of the solvent, the product mixture was purified by column chromatography on silica gel 60 with an eluent of volume ratio 9:1 (CH (cyclohexane):EA (ethyl acetate)). The products were obtained as yellowish oily substances.

3,4-Dimethoxy-2,5-dimethyl-2-hydroxybiphenyl

(32) ##STR00014##

(33) Yield: 206 mg (0.8 mmol, 15%)

(34) GC (hard method, HP-5): t.sub.R=13.45 min

(35) R.sub.f (Cy:EA=4:1)=0.44

(36) .sup.1H NMR (400 MHz, CDCl.sub.3) [ppm]=2.20 (s, 3H, H-9), 2.32 (2, 3H, H-8), 3.83 (s, 3H, H-10), 3.92 (s, 3H, H-7), 5.44 (bs, 1H, H-11), 6.57 (m, 1H, H-4, .sup.4J.sub.4,6=1.8 Hz), 6.70 (dd, 1H, H-6, .sup.4J.sub.4,6=1.8 Hz), 6.78-6.82 (dd, 1H, H-5, .sup.4J.sub.3,5=2.7 Hz, .sup.4J.sub.2,3, =8.3 Hz), 6.84 (d, 1H, H-3, .sup.4J.sub.3,5=2.7 Hz), 7.15 (d, 1H, H-6, .sup.4J.sub.2,3=8.3 Hz).

(37) .sup.13C NMR (101 MHz, CDCl.sub.3) [ppm]=21.14 (C-8), 21.57 (C-9), 55.86 (C-10), 55.95 (C-7), 110.73 (C-5), 111.21 (C-4), 112.17 (C-3), 121.85 (C-6), 123.53 (C-1), 125.38 (C-6), 129.09 (C-5), 131.53 (C-1), 139.08 (C-2), 140.93 (C-2), 147.25 (C-3), 155.98 (C-4).

(38) HRMS (ESI, pos. mode): m/z for C.sub.16H.sub.19O.sub.3[M+H.sup.+]: calculated: 259.1334. found: 259.1332.

2,3-Dimethoxy-4,5-dimethyl-2-hydroxybiphenyl

(39) ##STR00015##

(40) Yield: 225 mg (0.88 mmol, 17%)

(41) GC (hard method, HP-5): t.sub.R=13.32 min

(42) R.sub.f (Cy:EA=4:1)=0.57

(43) .sup.1H NMR (400 MHz, CDCl.sub.3) [ppm]=2.33 (s, 3H, H-10), 2.41 (s, 3H, H-8), 3.84 (s, 3H, H-9), 3.91 (s, 3H, H-7), 5.86 (bs, 1H, H-11), 6.68 (m, 1H, H-6), 6.71 (d, 1H, H-4, .sup.4J.sub.4,6=1.7 Hz), 6.84 (m, 1H, H-3), 6.86-6.90 (m, 1H, H-5), 7.19-7.22 (d, 1H, H-6, .sup.3J.sub.5,6=7.6 Hz).

(44) .sup.13C NMR (101 MHz, CDCl.sub.3) [ppm]=21.14 (C-8), 21.56 (C-10), 55.87 (C-7), 55.95 (C-9), 111.21 (C-1), 112.17 (C-3), 121.85 (C-4), 123.53 (C-1), 123.99 (C-5), 125.38 (C-6), 129.09 (C-5), 131.53 (C-6), 139.08 (C-4), 140.86 (C-2), 147.26 (C-3), 155.98 (C-2).

(45) HRMS (ESI, pos. mode): m/z for C.sub.16H.sub.18O.sub.3Na [M+Na.sup.+]: calculated: 281.1154. found: 281.1165.

Example 2

2-Hydroxy-5-methyl-2,3,4-trimethoxybiphenyl

(46) The electrolysis was conducted according to GP2 with 16.58 g (120 mmol, 1.0 equiv.) of 4-methylguaiacol and 49.74 mg (360 mmol, 3.0 equiv.) of 1,3-dimethoxybenzene. The current density was 2.8 mA/cm.sup.2, the charge 2 F per 4-methylguaiacol (Q=23156 C). After removal of the solvent and the conductive salt, the product was obtained by short-path distillation in a Kugelrohr still as a yellow oil (140 C., 10.sup.3 mbar).

(47) ##STR00016##

(48) Yield: 9.218 g (33.6 mmol; 28%)

(49) GC (hard method, HP-5): t.sub.R=14.27 min

(50) R.sub.f (Cy:EA=9:1)=0.42

(51) .sup.1H NMR (400 MHz, CDCl.sub.3) [ppm]=2.33 (s, 3H, 9-H), 3.83 (s, 3H, 8-H), 3.85 (s, 3H, 10-H), 3.91 (s, 3H, 11-H), 5.76 (bs, 1H, 7-H), 6.59-6.61 (m, 2H, 5-H, 6-H), 6.67 (s, 1H, 6-H), 6.70 (s, 1H, 4-H), 7.23 (s, 1H, 3-H).

(52) .sup.13C NMR (101 MHz, CDCl.sub.3) [ppm]=21.29 (C-7), 55.56 (C-10), 56.02 (C-9), 56.11 (C-8), 99.12, 105.19 (C-5, C-6), 111.22 (C-4), 119.65 (C-1), 123.83 (C-6), 125.18 (C-1), 129.14 (C-5), 132.30 (C-3), 141.04 (C-2), 147.28 (C-3), 157.40 (C-2), 160.68 (C-4).

(53) HRMS (ESI, pos. mode): m/z for C.sub.16H.sub.18O.sub.4(M+Na.sup.+): calculated: 297.1103. found: 297.1096.

Example 3

2,2-Dihydroxy-5,2-dimethyl-3-(1,1-dimethylethyl)-3,4,5-trimethoxy[1,1;5,1]terphenyl

(54) The electrolysis was conducted according to GP1 with 325 mg (1.81 mmol, 1.0 equiv.) of 2-(1,1-dimethylethyl)-4-methoxyphenol and 1.40 g (5.42 mmol, 3.0 equiv.) of 2,3-dimethoxy-4,5-dimethyl-2-hydroxybiphenyl. The current density was 2.8 mA/cm.sup.2, the charge 2 F per 2-(1,1-dimethylethyl)-4-methoxyphenol (Q=350 C). After removal of the solvent, the reaction product was purified by column chromatography on silica gel 60 with a 9:1 (CH:EA) eluent mixture. The product was obtained as a yellow oil.

(55) ##STR00017##

(56) Yield: 126 mg (0.29 mmol, 8%)

(57) GC (hard method, HP-5): t.sub.R=22.69 min

(58) R.sub.f (Cy:EA=9:1)=0.51

(59) .sup.1H NMR (400 MHz, CDCl.sub.3) [ppm]=1.45 (s, 9H, 7-H), 2.30 (s, 3H, 12-H), 2.31 (s, 3H, 10-H), 3.75 (s, 3H, 13-H), 3.91 (s, 3H, 11-H), 3.92 (s, 3H, 9-H), 5.58, 6.06 (bs, 2H, 8-H/14-H), 6.61 (d, 1H, 6-H, .sup.4J.sub.6,4=1.2 Hz), 6.69 (d, 1H, 6-H, .sup.4J.sub.6,4=4 Hz), 6.71 (d, 1H, 4-H, .sup.4J.sub.4,6=1.2 Hz), 9.91 (d, 1H, 4-H, .sup.4J.sub.4,6=4 Hz), 6.95 (s, 1H, 3-H), 7.22 (s, 1H, 6-H).

(60) .sup.13C NMR (101 MHz, CDCl.sub.3) [ppm]=20.38 (C-12), 21.24 (C-10), 29.84 (C-7), 35.30 (C-15), 55.82 (C-13), 56.15 (C-9), 56.35 (C-11), 110.75 (C-4), 112.80 (C-6), 113.14 (C-3), 113.98 (C-4), 123.70 (C-6), 124.90 (C-1), 126.98 (C-1), 127.36 (C-1), 129.07 (C-5), 131.60 (C-5), 134.27 (C-6), 138.41 (C-2), 139.03 (C-3), 140.64 (C-2), 146.35 (C-5), 146.64 (C-3), 152.88 (C-2), 154.85 (C-4).

(61) HRMS (ESI, pos. mode): m/z for C.sub.27H.sub.32O.sub.5 (M+Na.sup.+): calculated: 459.2147. found: 459.2147.

Example 4

2,2-Dihydroxy-4,5-dimethyl-2,3,4,5-tetramethoxy[1,1;5,1]terphenyl

(62) The electrolysis was conducted according to GP1 with 250 mg (1.8 mmol, 1.0 equiv.) of 4-methoxy-3-methylphenol and 1.49 g (5.4 mmol, 3.0 equiv.) of 2-hydroxy-5-methyl-2,3,4-trimethoxybiphenyl. The current density was 2.8 mA/cm.sup.2, the charge 2 F per 4-methoxy-3-methylphenol (Q=350 C). First purification was effected by removing the reactants on a Kugelrohr still (120 C., 10.sup.3 mbar). The product was purified by column chromatography using silica gel 60 with a gradient of 4:1, then 7:3, then 2:1 (CH:EA). The terphenyl compound was obtained as a yellowish solid.

(63) ##STR00018##

(64) Yield: 126 mg (0.3 mmol, 17%)

(65) GC (hard method, HP-5): t.sub.R=23.54 min

(66) R.sub.f (Cy:EA=2:1)=0.14

(67) .sup.1H NMR (400 MHz, CDCl.sub.3) [ppm]=2.25 (s, 3H), 2.34 (s, 3H), 3.79 (s, 3H), 3.93 (s, 3H), 3.93 (s, 3H), 3.97 (s, 3H), 5.57 (bs, 2H), 6.76-6.70 (m, 4H), 6.87 (s, 1H), 7.35 (s, 1H).

(68) .sup.13C NMR (101 MHz, CDCl.sub.3) [ppm]=16.06, 21.22, 56.06, 56.09, 56.37, 56.66, 77.36, 96.56, 111.26, 112.87, 119.82, 119.93, 120.96, 123.04, 123.75, 124.46, 127.65, 129.24, 135.01, 141.03, 147.08, 152.09, 156.00, 157.29.

(69) MS (ESI, pos. mode): m/z for C.sub.24H.sub.26O.sub.6 (M+Na.sup.+): calculated: 433.16. found: 433.16.

(70) The inventive examples showed that the unsymmetric OCO pincer ligands can be prepared in satisfactory yields by the process according to the invention.

Example 5

Derivatization of the Phenol-Arene Component from Example 2 with Protecting Groups Protection with (1,1-dimethylethyl)dimethylsilyl chloride (TBDMS chloride)

(71) ##STR00019##

(72) A round-bottom flask with a drying tube was initially charged with 2.26 g of imidazole (33.2 mmol, 1.1 equ.). 8.29 g (30.2 mmol, 1.0 equ.) of the AB compound from Example 2 (2-hydroxy-5-methyl-2,3,4-trimethoxybiphenyl) were dissolved in about 50 ml of dry dichloromethane and transferred into the flask. Subsequently, 5.92 g (39.3 mmol, 1.3 equ.) of TBDMS chloride were likewise dissolved in about 50 ml of dry dichloromethane and transferred into the flask. A further 100 ml of dichloromethane were added. The mixture was then stirred at room temperature for 24 h. During the reaction time, a colourless flaky precipitate formed. The product was isolated by means of extraction three times with 100 ml each time of water in order to remove the salt formed. After drying by means of sodium sulphate and removal of the dichloromethane on a rotary evaporator, the excess silyl chloride was removed by distillation (50 C., 10.sup.3 mbar), in the course of which the product precipitated out as a colourless solid.

(73) Yield: 98% (11.5 g, 29.6 mmol)

(74) GC (hard method, HP-5): t.sub.R=14.5 min

(75) R.sub.f (CH:EA=5:1): 0.68

(76) HRMS (ESI, pos. mode): m/z for CHO [M+Na.sup.+]:

(77) Calculated: 411.1968.

(78) Found: 411.1960.

(79) Melting point: 67.8 C.

(80) .sup.1H NMR (400 MHz, CDCl.sub.3): [ppm]=0.12 (s, 6H, 9, 10-H), 0.69 (s, 9H, 11-H, 12-H, 13-H), 2.30 (s, 3H, 8-H), 3.73 (s, 3H, 8-H), 3.80 (s, 3H, 7-H), 3.83 (s, 3H, 7-H), 6.50-6.53 (m, 2H, 3-H, 5-H), 6.65-6.68 (m, 1H, 4-H), 7.11-7.14 (m, 2H, 6-H, 6-H)

(81) .sup.13C NMR (101 MHz, CDCl.sub.3): [ppm]=4.51 (C-9,C-10), 18.47 (C-14), 21.35 (C-8), 25.68 (C-11, C-12, C-13), 55.12 (C-8), 55.55 (C-7), 55.62 (C-7), 98.70 (C-3), 103.95 (C-5), 111.59 (C-4), 121.38 (C-1), 124.12 (C-6), 129.91 (C-6), 130.51 (C-1), 132.39 (C-5), 140.53 (C-2), 150.41 (C-3), 158.18 (C-4), 160.31 (C-2)

Example 6

Derivatization of the Phenol-Arene Components from Example 2 with Protecting Groups Protection with tri(methylethyl)silyl chloride (TIPS chloride)

(82) ##STR00020##

(83) A round-bottom flask with a drying tube was initially charged with 5.27 g of imidazole (27.3 mmol, 2.5 equ.). 8.50 g (31.0 mmol, 1.0 equ.) of the AB compound from Example 2 (2-hydroxy-5-methyl-2,3,4-trimethoxybiphenyl) were dissolved in about 60 ml of dry dichloromethane and transferred into the flask. Subsequently, 11.57 g (62.0 mmol, 2.0 equ.) of TIPS chloride were likewise added to the mixture, forming an orange/yellowish solution. The mixture was stirred at RT for 24 h. Subsequently, a further 0.5 equ. of TIPS chloride was added and the mixture was stirred at room temperature for a further 48 h. During the reaction time, a colourless flaky precipitate formed. The product was isolated by means of extraction three times with 100 ml each time of water in order to remove the salt formed. After drying by means of sodium sulphate and removal of the dichloromethane on a rotary evaporator, the excess silyl chloride was removed by distillation (50 C., 10.sup.3 mbar), in the course of which the product precipitated out as a colourless solid.

(84) Yield: 92% (13.3 g, 30.9 mmol)

(85) GC (hard method, HP-5): t.sub.R=15.8 min

(86) R.sub.f (CH:EA=5:1): 0.73

(87) HRMS (ESI, pos. mode): m/z for CHO [M+Na.sup.+]:

(88) Calculated: 453.2437.

(89) Found: 453.2423.

(90) Melting point: 78.4 C.

(91) .sup.1H NMR (400 MHz, CDCl.sub.3): [ppm]=0.87 (d, 18H, 9-H, 11-H, 12-H, 14-H, 15-H, 17-H), 1.56 (q, 3H, 10-H, 13-H, 16-H), 2.29 (s, 3H, 8-H), 3.70 (s, 3H, 8-H), 3.78 (s, 3H, 7-H), 3.83 (s, 3H, 7-H), 6.59-6.61 (m, 2H, 3-H, 5-H), 6.62-6.65 (m, 1H, 4-H), 7.09-7.12 (m, 2H, 6-H, 6-H)

(92) .sup.13C NMR (101 MHz, CDCl.sub.3): [ppm]=13.69 (C-8), 17.73 (C-9, C-11, C-12, C-14, C-15, C-17), 21.00 (C-10, C-13, C-16), 54.47 (C-8), 55.08 (C-7), 55.32 (C-7), 98.23 (C-3), 103.48 (C-5), 110.87 (C-4), 121.39 (C-1), 123.61 (C-6), 128.81 (C-6), 129.70 (C-1), 131.53 (C-5), 141.02 (C-2), 149.23 (C-3), 157.86 (C-4), 159.93 (C-2)

Example 7

Preparation of 2,2-dihydroxy-3-(1,1-Dimethylethyl)-5-methyl-2,3,4,5-tetramethoxy-[1,1,5,1]-terphenyl

(93) ##STR00021##

(94) The electrolysis was conducted according to the general procedure GP1 in a flange cell. For this purpose, an electrolyte volume of 33 ml of HFIP with 1.03 g of MTBS as conductive salt was used (0.09 M). For electrochemical cross-coupling, 0.90 g (5.0 mmol, 1.0 equ.) of 2-(1,1-dimethylethyl)-4-methoxyphenol and 6.45 g (15 mmol, 3.0 equ.) of the protected phenol-arene coupling product from Example 6 were used. The electrolysis was conducted in a galvanostatic manner, forming a deeply coloured solution. After the electrolysis had ended, the solvent was removed under reduced pressure on a rotary evaporator and the brown residue was filtered through silica gel 60 together with about 300 ml of ethyl acetate. The subsequent column chromatography separation (column measurements: 503 cm) of the product mixture through silica gel 60 as a flash chromatography was conducted twice with the following gradient in the eluent mixture: 95:5 to 9:1 to 5:1 to 2:1 (CH:EA, about 3 l of CH and 2 l of EA used per column). This afforded the corresponding product with the protecting group removed as a deep red solid.

(95) Yield: 0.91 g of unprotected pincer ligands, (40%, 2.01 mmol)

(96) GC (hard method, HP-5): t.sub.R=22.34 min

(97) R.sub.f (CH:EA=5:1): 0.10

(98) HRMS (ESI, pos. mode): m/z for CHO [M+Na.sup.+]:

(99) Calculated: 475.2097.

(100) Found: 475.2103.

(101) .sup.1H NMR (400 MHz, CDCl.sub.3): [ppm]=1.44 (s, 9H, 8-H, 9-H, 10-H), 2.31 (s, 3H, 8-H), 3.75 (s, 3H, 11-H), 3.91 (s, 3H, 8-H), 3.91 (s, 3H, 7-H) 3.93 (s, 3H, 7-H), 5.79 (s, 1H, 2-H), 5.89 (s, 1H, 2-H), 6.65 (d, 1H, 3-H), 6.67-6.72 (m, 3H, 4-H, 6-H, 6-H), 6.91 (d, 1H, 4-H), 7.30 (s, 1H, 6-H)

(102) .sup.13C NMR (101 MHz, CDCl.sub.3): [ppm]=20.90 (C-8), 29.51 (C-8, C-9, C-10), 34.98 (C-7), 55.50 (C-11), 55.86 (C-8), 56.16 (C-7), 56.32 (C-7), 96.27 (C-3), 111.04 (C-6), 112.42 (C-4), 113.59 (C-4), 119.79 (C-5), 120.65 (C-1), 123.49 (C-6), 124.20 (C-1), 126.59 (C-1), 129.02 (C-6), 135.15 (C-5), 138.61 (C-3), 140.72 (C-2), 146.22 (C-3), 146.84 (C-2), 152.55 (C-5), 156.03 (C-2), 157.13 (C-4)

Example 8

Preparation of 2,2-dihydroxy-4,5-dimethyl-2,3,4,5-tetramethoxy-[1,1,5,1]-terphenyl

(103) ##STR00022##

(104) The electrolysis was conducted according to the general procedure GP1 in a flange cell. For this purpose, an electrolyte volume of 33 ml of HFIP with 1.03 g of MTBS as conductive salt was used (0.09 M). For electrochemical cross-coupling, 0.69 g (5.0 mmol, 1.0 equ.) of 4-methoxy-3-methylphenol and 6.45 g (15 mmol, 3.0 equ.) of the protected phenol-arene coupling product from Example 6 were used. The electrolysis was galvanostatic, forming a black solution. After the electrolysis had ended, the solvent was removed under reduced pressure on a rotary evaporator and the brown solution that remained was filtered through silica gel 60 together with about 300 ml of ethyl acetate. The subsequent column chromatography separation (column measurements: 503 cm) of the product mixture through silica gel 60 as a flash chromatography was conducted twice with the following gradient in the eluent mixture: 95:5 to 9:1 to 5:1 to 2:1 (CH:EA, about 3 l of CH and 2 l of EA used per column). This afforded the corresponding product with the protecting group removed as a deep red solid.

(105) Yield: 0.88 g of unprotected pincer ligands, (43%, 2.15 mmol)

(106) GC (hard method, HP-5): t.sub.R=20.3 min

(107) R.sub.f (CH:EA=5:1): 0.1

(108) HRMS (ESI, pos. mode): m/z for CHO [M+H.sup.+]:

(109) Calculated: 411.1802.

(110) Found: 411.1797.

(111) .sup.1H NMR (400 MHz, CDCl.sub.3): [ppm]=2.22 (s, 3H, 7-H), 2.31 (s, 3H, 8-H), 3.76 (s, 3H, 8-H), 3.91 (s, 3H, 8-H), 3.91 (s, 3H, 7-H), 3.96 (s, 3H, 7-H), 5.79 (s, 1H, 2-H), 5.93 (bs, 1H, 2-H), 6.67-6.74 (m, 3-H, 4-H, 6-H, 6-H), 6.83 (s, 1H, 3-H), 7.31 (s, 1H, 6-H)

(112) .sup.13C NMR (101 MHz, CDCl3): [ppm]=15.79 (C-7), 20.99 (C-8), 55.83 (C-8), 55.85 (C-8), 56.15 (C-2), 56.44 (C-7), 96.26 (C-3), 110.99 (C-4), 112.62 (C-6), 119.62 (C-3), 120.69 (C-4), 122.17 (C-5), 123.37 (C-1), 124.15 (C-6), 127.43 (C-1), 129.03 (C-1), 134.79 (C-6), 140.77 (C-5), 146.84 (C-2), 151.88 (C-5), 155.75 (C-3), 157.05 (C-2), 158.29 (C-4), 158.43 (C-2)

(113) As Examples 7 and 8 show, it was possible to further increase the yield of m-terphenyl compound by the introduction of a protecting group (silyl group) into the phenol-arene coupling product in the subsequent coupling in process step c) conducted by electrochemical means (two- to threefold increase in yield). In this way, it is thus possible to distinctly increase the efficiency of the overall process.