Chiral phosphine nickel (II) complex with one-dimensional supramolecular structure and preparation method and application thereof

Abstract

The present invention relates to the technical field of chemical synthesis, and in particular to a chiral nickel phosphine (II) complex with a one-dimensional supramolecular structure, and a preparation method and application thereof. A chiral nickel phosphine (II) complex with a one-dimensional supramolecular structure, the chemical formula of which is Ni(TFM-Josiphos)Cl2, wherein TFM-Josiphos is (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethylbis(trifluoromethyl)phosphine, the chiral nickel phosphine (II) complex crystal of the present invention belongs to the orthorhombic system, the P222 space group, the unit cell parameters are a=17.3946(7)Å, b=23.1260(7)Å, c=27.7424(6)Å, α=90°, β=90°, γ=90°, V=10736.8(3)Å 3 The preparation method of the chiral phosphine nickel (II) complex of the present invention is simple and convenient to operate, with high purity and good reproducibility. The chiral phosphine nickel (II) complex of the present invention has good thermal stability, exhibits good catalytic performance in the asymmetric catalytic hydrogenation reaction of the side chain of moxifloxacin, a chiral drug intermediate, and has good application prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and in particular to a chiral nickel phosphine (II) complex with a one-dimensional supramolecular structure, and a preparation method and application thereof. Background Art

[0002] Metal complexes are compounds formed by ligands and metal atoms or ions through coordination bonds. The use of transition metal complexes as catalysts can be traced back to the carbon-based cobalt HCo(CO)4 hydroformylation catalyst discovered by Roelen in the 1920s, and the cuprous chloride complex catalyst for chloroprene synthesis discovered by Nieuwland in the 1940s. The development of acetylene and carbon monoxide chemistry in the 1940s further demonstrated that transition metal complexes are catalysts with multiple uses. Transition metal catalysis has become an important organic synthesis method and is widely used in medicine, pesticides, materials science and other fields. Nickel is cheaper and more available than other transition metals, so nickel catalysts are more economical and applicable. Nickel catalysts can catalyze various coupling reactions. When catalyzing coupling reactions, they have many advantages over palladium and have better development prospects. In addition to coupling reactions, nickel catalysts can also catalyze cycloaddition reactions, oxidation reactions, reduction reactions, etc. Recently, research on nickel-catalyzed reactions has been in the ascendant.

[0003] Since ferrocene was discovered in 1951, it has been one of the most important ligand skeletons due to its advantages such as thermal stability, conformational rigidity and face chirality. Chiral ferrocene phosphine ligands have become an indispensable and powerful tool for asymmetric synthesis, have been widely used in drug synthesis, and have received widespread attention from scientific researchers.

[0004] Prior to the present patent application, there were no patent documents or scientific papers reporting on the self-assembly of chiral ferrocenylphosphine ligand (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethylbis(trifluoromethyl)phosphine and nickel chloride in a mixed solvent of ethanol / water to form a complex having a one-dimensional supramolecular structure. Summary of the invention

[0005] The technical problem to be solved by the present invention is to provide a chiral phosphine nickel (II) complex with a one-dimensional supramolecular structure.

[0006] Another object of the present invention is to provide a method for preparing the chiral phosphine nickel (II) complex having a one-dimensional supramolecular structure.

[0007] The present invention also provides application of the chiral phosphine nickel (II) complex with a one-dimensional supramolecular structure in the synthesis of the side chain of moxifloxacin, a chiral drug intermediate.

[0008] The technical problem to be solved by the present invention is achieved through the following technical solutions:

[0009] A chiral nickel phosphine (II) complex with a one-dimensional supramolecular structure, the chemical formula of which is Ni(TFM-Josiphos)Cl2, Wherein TFM-Josiphos is (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethylbis(trifluoromethyl)phosphine, and the structural formula of TFM-Josiphos is:

[0010]

[0011] The chiral phosphine nickel (II) complex crystal belongs to the orthorhombic system, P222 space group, the unit cell parameters are a=17.3946(7)Å, b=23.1260(7)Å, c=27.7424(6)Å, α=90°, β=90°, γ=90°, V =10736.8(3)Å 3 .

[0012] Furthermore, there is a metal center Ni in the asymmetric structural unit of the chiral phosphine nickel (II) complex with a one-dimensional supramolecular structure. 2+ Cation (Ni1), 2 Cl - anion and a neutral TFM-Josiphos molecule. The metal center Ni (II) is coordinated with two P atoms (P1 and P2) and two chloride ions (Cl1 and Cl2) from a TFM-Josiphos ligand H2L in a four-coordinate manner, forming a distorted tetrahedral coordination configuration. The bond length of the Ni-P bond ranges from 2.168 (2) to 2.197 (2) Å, and the bond length of the Ni-Cl bond ranges from 2.205 (3) to 2.219 (3) Å. In the solid-state structure of the complex, the above complex is further constructed into a zigzag one-dimensional supramolecular structure through the intermolecular hydrogen bond C-H...F.

[0013] A method for preparing a chiral phosphine nickel (II) complex with a one-dimensional supramolecular structure comprises the following steps: adding (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethyldi(trifluoromethyl)phosphine and nickel chloride to a mixed solution of ethanol and water, stirring the mixture fully and filtering the mixture; then placing the filtrate in a high-pressure reactor, heating the mixture under solvent thermal conditions and then slowly cooling the mixture to obtain the chiral phosphine nickel (II) complex with a one-dimensional supramolecular structure.

[0014] Furthermore, the heating temperature is 90-110°C.

[0015] Furthermore, the heating reaction time is 48 to 72 hours.

[0016] Furthermore, the temperature is lowered by 2°C / hour to 10°C / hour to room temperature.

[0017] Furthermore, the volume ratio of ethanol and water in the mixed solution is 1:1.

[0018] Furthermore, the molar ratio of the (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethylbis(trifluoromethyl)phosphine to nickel chloride is 0.9-1.1: 0.9-1.1.

[0019] Furthermore, the molar ratio of the (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethylbis(trifluoromethyl)phosphine to nickel chloride is preferably 1:1.

[0020] Beneficial effects of the present invention:

[0021] The present invention is the first to develop a chiral nickel phosphine (II) complex with a one-dimensional supramolecular structure under solvothermal conditions. Figure 1 , Figure 2 The chiral phosphine nickel (II) complex of the one-dimensional supramolecular structure of the present invention can be stable to about 225°C without decomposition and has good thermal stability ( Figure 3 ), providing a basis for its application; the complex exhibits good catalytic effect in the asymmetric hydrogenation reduction reaction during the synthesis of the chiral drug intermediate (S,S)-2,8-diazabicyclo[4.3.0]nonane (moxifloxacin side chain) ( Figure 4 , Figure 5 ), has good application prospects; the preparation method of the chiral phosphine nickel (II) complex with one-dimensional supramolecular structure of the present invention is simple and convenient to operate, has high purity and good reproducibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 Structural unit diagram of the chiral phosphine nickel (II) complex having a one-dimensional supramolecular structure according to the present invention;

[0023] Figure 2 A one-dimensional supramolecular structure diagram of the chiral phosphine nickel (II) complex having a one-dimensional supramolecular structure according to the present invention;

[0024] Figure 3 Thermogravimetric spectrum of the chiral phosphine nickel (II) complex having a one-dimensional supramolecular structure according to the present invention;

[0025] Figure 4 HNMR spectrum of the asymmetric catalytic hydrogenation reaction product of the chiral phosphine nickel (II) complex prepared by the present invention;

[0026] Figure 5The enantiomeric excess determination HPLC spectrum of the asymmetric catalytic hydrogenation reaction product of the chiral phosphine nickel (II) complex prepared by the present invention. Implementation

[0027] The present invention is described in detail below with reference to the accompanying drawings and embodiments. Example 1

[0028] 0.1 mmol (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethylbis(trifluoromethyl)phosphine and 0.1 mmol NiCl2·6H2O were dissolved in 20 mL of ethanol and water ( V : V =1:1) mixed solution, fully stirred for 20 minutes and then filtered, the filtrate was transferred to a stainless steel reactor lined with polytetrafluoroethylene, the stainless steel reactor was sealed and placed in an oven, and solvent thermal reaction was carried out at 100°C for 72 hours, then cooled to room temperature at 2°C / hour, filtered, and washed to obtain orange-yellow block crystals of the chiral phosphine nickel (II) complex with a one-dimensional supramolecular structure, with a yield of 43.7% (based on Ni).

[0029] The chiral phosphine nickel (II) complex crystal with a one-dimensional supramolecular structure prepared in this example is structurally characterized as follows:

[0030] Crystalline X-ray diffraction data were measured using a Bruker Smart Apex CCD single crystal diffractometer. The X-ray diffraction data were obtained at 293 K using graphite monochromatized Cu Kα radiation ( λ = 0.154178nm) as the radiation source, and the diffraction data were collected. The scanning mode was φ-ω scanning, and Lp factor correction and empirical absorption correction were performed. The position coordinates of metal atoms and non-hydrogen atoms were determined by direct method, and all non-hydrogen atom coordinates and their anisotropic thermal parameters were corrected by full matrix least squares method. The crystallographic parameters are shown in Table 1, and the structure is shown in Figure 1 , Figure 2 .

[0031] Table 1 Main crystallographic data of prepared chiral nickel phosphine complex crystals with one-dimensional supramolecular structure

[0032]

[0033] A chiral nickel phosphine (II) complex with a one-dimensional supramolecular structure, the chemical formula of which is Ni(TFM-Josiphos)Cl2, Wherein TFM-Josiphos is (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethylbis(trifluoromethyl)phosphine. The chiral phosphine nickel (II) complex crystal with a one-dimensional supramolecular structure belongs to the orthorhombic system, P222 space group, and the unit cell parameters are a=17.3946(7)Å, b=23.1260(7)Å, c=27.7424(6)Å, α=90°, β=90°, γ=90°, V =10736.8(3)Å 3 The chiral nickel phosphine (II) complex with a one-dimensional supramolecular structure has a metal center Ni in the asymmetric structural unit. 2+ Cation (Ni1), 2 Cl - anion and a neutral TFM-Josiphos molecule. The metal center Ni(II) is coordinated with two P atoms (P1 and P2) and two chloride ions (Cl1 and Cl2) from a TFM-Josiphos ligand H2L in a four-coordinate manner, forming a distorted tetrahedral coordination configuration. In the solid structure, the nickel (II) complex is further constructed into a one-dimensional zigzag supramolecular structure through the strong intermolecular hydrogen bond C-H...F.

[0034] The catalytic performance of the chiral phosphine nickel (II) complex with a one-dimensional supramolecular structure prepared in this example was studied as follows:

[0035] Moxifloxacin side chain

[0036]

[0037] In a 500 mL steel autoclave, 12.0 g (60 mmol) of 6-benzyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridine raw material, 100 mL of methanol, and 2.49 g of Ni(TFM-Josiphos)Cl2 (5 mol%) were added. Hydrogen was slowly passed to 5 MPa, the temperature was slowly raised to 80°C, and then hydrogen was slowly passed to 8 MPa until no hydrogen was absorbed. The reaction was then kept warm and under pressure for 12 hours. After the reaction was completed, the reaction was cooled to room temperature, the pressure was discharged, the mixture was filtered, and the mixture was washed with methanol. The solvent was removed by rotary evaporation, and then the product, moxifloxacin side chain, (S,S)-2,8-diazabicyclo[4.3.0]nonane 9.6 g was obtained by vacuum distillation and purification. The yield was 91.5%, and the ee value was 99.9%.

[0038] like Figure 4 The figure shows the HNMR spectrum of the asymmetric catalytic hydrogenation reaction product of the chiral nickel phosphine (II) complex having a one-dimensional supramolecular structure prepared by the present invention. 1 H NMR (500 MHz, Chloroform- d) δ 3.11 (td, J = 4.5,1.5 Hz, 1H), 2.99 – 2.80 (m, 4H), 2.72 (dd, J = 11.4, 1.6 Hz, 1H), 2.55 (td, J = 11.5, 2.8 Hz, 1H), 2.02 (dp, J = 13.5, 4.4 Hz, 1H), 1.75 (d, J = 9.1 Hz,2H), 1.65 (dt, J = 11.0, 4.5 Hz, 2H), 1.49 (ddddt, J = 19.7, 13.6, 9.4, 7.0,3.3 Hz, 1H), 1.43 – 1.31 (m, 1H); the two hydrogens at 1.75 ppm are on nitrogen atoms, and the remaining hydrogens are on carbon atoms.

[0039] like Figure 5 The figure shows the enantiomeric excess HPLC spectrum of the asymmetric catalytic hydrogenation reaction product of the chiral nickel phosphine (II) complex with a one-dimensional supramolecular structure. Chiral chromatographic column: CHIRALCEL® OD-H (4.6 mm*250 mm, 5μm), mobile phase: methanol / ethanol / triethylamine = 500:500:1, flow rate: 1mL / min, detection wavelength 261nm injection volume: 20μL; the retention time is 16.4min for the compound of formula e, and the retention time is 14.6min for its isomer. The ee value calculated by peak area integration is 99.9%.

[0040] In summary, the chiral phosphine nickel (II) complex with a one-dimensional supramolecular structure prepared in the present invention exhibits good catalytic selectivity in asymmetric catalytic hydrogenation reactions, especially in the synthesis of moxifloxacin side chains. Example 2

[0041] 0.09 mmol (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethylbis(trifluoromethyl)phosphine and 0.1 mmol NiCl2·6H2O were dissolved in 20 mL of ethanol and water ( V : V=1:1) mixed solution, fully stirred for 20 minutes and then filtered, the filtrate was transferred to a stainless steel reactor lined with polytetrafluoroethylene, the stainless steel reactor was sealed and placed in an oven, and solvent thermal reaction was carried out at 90°C for 72 hours, then cooled to room temperature at 2°C / hour, filtered, and washed to obtain orange-yellow block crystals of the chiral phosphine nickel (II) complex with a one-dimensional supramolecular structure, with a yield of 40.3% (based on Ni). Example 3

[0042] 0.11mmol (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethylbis(trifluoromethyl)phosphine and 0.1mmol NiCl2·6H2O were dissolved in 20mL ethanol and water ( V : V =1:1) mixed solution, fully stirred for 20 minutes and then filtered, the filtrate was transferred to a stainless steel reactor lined with polytetrafluoroethylene, the stainless steel reactor was sealed and placed in an oven, and solvent thermal reaction was carried out at 110°C for 72 hours, then cooled to room temperature at 10°C / hour, filtered, and washed to obtain orange-yellow block crystals of the chiral phosphine nickel (II) complex with a one-dimensional supramolecular structure, with a yield of 42.5% (based on Ni). Example 4

[0043] 0.1 mmol (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethylbis(trifluoromethyl)phosphine and 0.11 mmol NiCl2·6H2O were dissolved in 20 mL of ethanol and water ( V : V =1:1) mixed solution, fully stirred for 20 minutes and then filtered, the filtrate was transferred to a stainless steel reactor lined with polytetrafluoroethylene, the stainless steel reactor was sealed and placed in an oven, and solvent thermal reaction was carried out at 90°C for 54 hours, then cooled to room temperature at 5°C / hour, filtered, and washed to obtain orange-yellow block crystals of the chiral phosphine nickel (II) complex with a one-dimensional supramolecular structure, with a yield of 39.2% (based on Ni). Example 5

[0044] 0.1 mmol (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethylbis(trifluoromethyl)phosphine and 0.1 mmol NiCl2·6H2O were dissolved in 20 mL of ethanol and water ( V : V=1:1) mixed solution, fully stirred for 20 minutes and then filtered, the filtrate was transferred to a stainless steel reactor lined with polytetrafluoroethylene, the stainless steel reactor was sealed and placed in an oven, and solvent thermal reaction was carried out at 100°C for 48 hours, then cooled to room temperature at 10°C / hour, filtered, and washed to obtain orange-yellow block crystals of the chiral phosphine nickel (II) complex with a one-dimensional supramolecular structure, with a yield of 42.9% (based on Ni).

[0045] The above-mentioned embodiments merely express the implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the patent scope of the present invention. Any technical solution obtained in the form of equivalent replacement or equivalent transformation shall fall within the protection scope of the present invention.

Claims

1. A chiral nickel phosphine (II) complex with a one-dimensional supramolecular structure, the chemical formula of which is Ni(TFM-Josiphos)Cl2, wherein TFM-Josiphos is (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethylbis(trifluoromethyl)phosphine, the chiral nickel phosphine (II) complex crystal belongs to the orthorhombic system, P222 space group, the unit cell parameters are a=17.3946(7)Å, b=23.1260(7)Å, c=27.7424(6)Å, α=90°, β=90°, γ=90°, V =10736.8(3)Å 3 ; It is characterized by The asymmetric structural unit of the chiral phosphine nickel (II) complex crystal with a one-dimensional supramolecular structure contains one Ni (II) metal center Ni1, two Cl - anion and a TFM-Josiphos neutral molecule, the metal center Ni(II) is coordinated with two P atoms P1 and P2 and two chloride ions Cl1 and Cl2 from a TFM-Josiphos ligand H2L in a four-coordinate manner to form a distorted tetrahedral coordination configuration. The nickel complex is further constructed into a one-dimensional zigzag supramolecular structure through intermolecular hydrogen bonds C-H...F.

2. The method for preparing the chiral phosphine nickel (II) complex having a one-dimensional supramolecular structure according to claim 1, comprising the following steps: (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethyldi(trifluoromethyl)phosphine and nickel chloride are added to a mixed solution of ethanol and water, and the mixture is fully stirred and filtered. The filtrate is then placed in a high-pressure reactor, heated under solvent thermal conditions for reaction, and then slowly cooled to obtain the chiral phosphine nickel (II) complex having a one-dimensional supramolecular structure.

3. The method for preparing a chiral phosphine nickel (II) complex having a one-dimensional supramolecular structure according to claim 2, characterized in that The molar ratio of (R)-1-{(S)-2-[bis(3,5-di-trifluoromethylphenyl)phosphino]ferrocenyl}ethylbis(trifluoromethyl)phosphine to nickel chloride is 0.9~1.1: 0.9~1.

1.

4. The method for preparing a chiral phosphine nickel (II) complex having a one-dimensional supramolecular structure according to claim 2, characterized in that: The volume ratio of ethanol to water in the mixed solution of ethanol and water is 1:

1.

5. The method for preparing a chiral phosphine nickel (II) complex having a one-dimensional supramolecular structure according to claim 2, characterized in that: The temperature of the solvent thermal reaction is 90-110° C., and the reaction time is 48-72 hours.

6. Use of the chiral phosphine nickel (II) complex having a one-dimensional supramolecular structure as claimed in claim 1 as a catalyst in the asymmetric catalytic hydrogenation reduction reaction of the side chain of moxifloxacin, a synthetic drug intermediate.

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