Preparation method of novel ferrocenyl pyridine hydrazine manganese complex

Abstract

The application provides a preparation method and application of a novel ferrocene pyridine hydrazine manganese complex. The manganese complex has multiple advantages such as low cost, simple synthesis and air stability. Meanwhile, the provided manganese complex can be applied to an asymmetric hydrogenation reaction and has certain industrial application prospect.

Description

Technical Field

[0001] This invention belongs to the field of chemical engineering, specifically relating to a novel type of ferrocene-pyridine-hydrazine manganese complex and its application in asymmetric hydrogenation reactions. Background Technology

[0002] Asymmetric hydrogenation reactions have developed rapidly in organic synthesis, pesticides, pharmaceuticals, and the production of advanced intermediates, becoming a key step in the production of some fine chemicals and drug molecules. In recent decades, noble metal catalysts formed by chiral ligands and noble metals, such as ruthenium, iridium, and rhodium, have greatly promoted the development of asymmetric hydrogenation. Although these noble metal catalysts have high TON values, the scarcity of these precious metals still limits their large-scale application. Therefore, how to utilize inexpensive and readily available metals for asymmetric catalytic reactions is of great significance.

[0003] Manganese complexes have achieved some success in the field of asymmetric hydrogenation. For example, the PNN and PNP manganese complexes developed by Clarke, Professor Zhang Xumu, and Professor Ding Kuiling exhibit good catalytic performance in the asymmetric hydrogenation of simple ketones. However, the efficiency of manganese-catalyzed asymmetric hydrogenation reactions is currently only around 13,000 TON values, which is still significantly lower than that of asymmetric hydrogenation using noble metal complexes. Therefore, developing novel ferrocene-based manganese complexes to improve the reaction efficiency of manganese-catalyzed asymmetric hydrogenation reactions is an urgent problem to be solved. Summary of the Invention

[0004] To overcome the problems existing in the prior art, the technical solution of the present invention is as follows:

[0005] First, this invention provides a novel type of ferrocene-pyridine-hydrazine manganese complex with the following general structural formula:

[0006] ,

[0007] in:

[0008] Ar in the ferrocene pyridine hydrazine manganese complexes shown in Formulas I-II is aryl or substituted aryl;

[0009] R in Equation I-II 1 It is independently selected from one of hydrogen, aryl, alkyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, alkoxy, and substituted aryl;

[0010] R in Equation I-II 2 It is independently selected from one of hydrogen, aryl, alkyl, alkoxy, and substituted aryl groups.

[0011] The Ar is preferably phenyl, and the R is... 1 The preferred compounds are hydrogen, alkyl, and trifluoromethyl, wherein R2 Alkyl groups are preferred.

[0012] Most preferably, the ferrocene pyridine hydrazine-based manganese complex has the following structural formula:

[0013] ,

[0014] ,

[0015] ,

[0016] ,

[0017] ,

[0018] ,

[0019] .

[0020] Secondly, this invention provides a method for preparing ferrocene-pyridine-hydrazine manganese complexes, which are prepared by an addition reaction of ligand I or ligand II with MnBr(CO)5.

[0021] ,

[0022] in,

[0023] Ar is aryl or substituted aryl;

[0024] R 1 It is independently selected from one of hydrogen, aryl, alkyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, alkoxy, and substituted aryl;

[0025] R 2 It is independently selected from one of hydrogen, aryl, alkyl, alkoxy, and substituted aryl groups.

[0026] The reaction solvent for the addition reaction is selected from one of tetrahydrofuran, 2-methyltetrahydrofuran, toluene, benzene, substituted benzene, halogenated hydrocarbons, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, methanol, ethanol, isopropanol, tert-butanol, and acetonitrile, with toluene being a preferred solvent.

[0027] This invention further provides a method for preparing the above-mentioned ligands I and II, which are obtained by substitution reaction of pyridine hydrazine and ligands SI or S-II.

[0028] ,

[0029] in,

[0030] Ar is aryl or substituted aryl;

[0031] R 1 It is independently selected from one of hydrogen, aryl, alkyl, fluorine, chlorine, bromine, iodine, trifluoromethyl, alkoxy, and substituted aryl;

[0032] R 2 It is independently selected from one of hydrogen, aryl, alkyl, alkoxy, and substituted aryl groups.

[0033] The substitution reaction is carried out under acidic conditions, with acetic anhydride being a preferred acid.

[0034] In the substitution reaction, the reaction solvent is an organic solvent, preferably anhydrous methanol.

[0035] In the substitution reaction, the molar ratio of pyridine hydrazine and ligand SI or II is 1:1 to 5, with 1:2 being more preferred.

[0036] The reaction temperature in the substitution reaction is 25~100°C. o C, preferably 50~60 o C.

[0037] The reaction time in the substitution reaction is 12-36 hours, preferably 14-18 hours.

[0038] The present invention also provides the application of the above-mentioned ferrocene pyridine hydrazine manganese complex in the asymmetric hydrogenation reaction of prochiral ketone compounds. Under a nitrogen atmosphere, the prochiral ketone compound, the ferrocene pyridine hydrazine manganese complex, the base and the solvent are added, and the reaction is carried out after hydrogen replacement.

[0039] The base is a strong base, preferably potassium tert-butoxide.

[0040] The solvent is an organic solvent, preferably anhydrous methanol.

[0041] The reaction temperature of the asymmetric hydrogenation reaction is 20-100℃, with 50℃ being more preferred.

[0042] The reaction time for the asymmetric hydrogenation reaction is 30-60 hours, with 48 hours being more preferred.

[0043] The preferred method is the application of ferrocene-pyridine-hydrazine manganese complexes in the asymmetric hydrogenation reaction of acetophenone to synthesize 1-phenylethanol:

[0044] .

[0045] The beneficial effects of this invention are:

[0046] The novel ferrocene-pyridine-hydrazine manganese complexes provided by this invention have advantages such as simple synthesis, low cost, and easy scale-up. Furthermore, they can be applied to the asymmetric hydrogenation of prochiral ketone compounds, demonstrating potential for industrial application. Detailed Implementation

[0047] To further understand the present invention, the preparation method of the novel ferrocene-pyridine-hydrazine manganese complex provided by the present invention will be described in detail below with reference to embodiments. It should be understood that these embodiments are described only to further illustrate the features of the present invention, and are not intended to limit the scope of the present invention or the scope of the claims.

[0048] Example 1: Ferrocene pyridine hydrazine manganese complex (S c , R Fc Synthesis method of )-1:

[0049] Synthesis of 2-hydrazinopyridine (SI-II-2):

[0050]

[0051] Add 15.8 g (100 mmol, 1.00 eq) of 2-bromopyridine (SI-II-1) and 80 mL of 80% hydrazine hydrate to the reaction flask. After purging with nitrogen three times, raise the reaction solution to an internal temperature of 80-90°C. o C and maintain the temperature with stirring for 24-30 hours. After the reaction is complete, the temperature inside the reaction solution is lowered to 20-30°C. o C. Subsequently, 100 mL of ethyl acetate was added for extraction three times, and the organic phases were combined. The organic phase was then washed three times with 100 mL of saturated brine, dried over sodium sulfate, filtered, concentrated, and separated by column chromatography (stationary phase: silica gel; eluent: n-hexane:ethyl acetate = 1:2, with the addition of 1% triethylamine). The eluent was concentrated to dryness to give 8.73 g of product SI-II-2 (80% molar yield). 1 H-NMR (400 MHz, CDCl3) δ 8.12 (ddd, J = 5.2, 2.0, 0.8 Hz, 1H), 7.48 (ddd, J =8.4, 7.2, 2.0 Hz, 1H), 6.83 – 6.43 (m, 2H), 5.88 (brs, 1H), 3.32 (brs, 2H).

[0052] Synthesis of 2-hydrazinopyridine (SI-II-3):

[0053]

[0054] Add 9.6 g of sodium hydride (60%, 0.24 mol, 1.20 eq) and 500 mL of anhydrous tetrahydrofuran to the reaction flask. After purging with nitrogen three times, lower the reaction solution to an internal temperature of -10 to 10 °C. o C and keep warm while stirring. Control the internal temperature to -10-10. o C. Add 221.83 g (0.2 mol, 1.00 eq) of SI-II-2 dropwise. After the addition is complete, maintain the internal temperature of the reaction solution at -10 to 10 °C. o Keep stirred at room temperature for 1-2 hours, then slowly return to room temperature until TLC shows complete conversion of the raw materials, then lower to an internal temperature of -10 to 10°C. o C. The reaction was quenched by slowly adding 20 mL of water. After quenching, the mixture was extracted three times with 150 mL of ethyl acetate, and the organic phases were combined. The organic phase was then washed three times with 100 mL of saturated brine, dried over sodium sulfate, filtered, concentrated, and separated by column chromatography (stationary phase: silica gel; eluent: n-hexane:ethyl acetate = 2:1, with the addition of 1% triethylamine). The eluent was concentrated to dryness to give 18.0 g of product SI-II-3 (73% molar yield). 1 H-NMR (400 MHz, CDCl3) δ 8.14 (ddd, J = 5.0, 2.0, 0.8 Hz, 1H), 7.46 (ddd, J = 8.8, 7.2, 2.0 Hz,1H), 6.92 (dt, J = 8.6, 1.0 Hz, 1H), 6.58 (ddd, J = 7.2, 5.0, 1.0 Hz, 1H), 3.97(brs, 2H), 3.25 (s, 3H).

[0055] (S c , R Fc )- Synthesis of ligand I-L1:

[0056]

[0057] Add ( to the reaction flask) S c , R Fc )- Ligand SI-L1 1.00 g (2.3 mmol, 1.00 eq) and acetic anhydride 5 mL were purged with nitrogen three times, and the reaction solution was then heated to an internal temperature of 90-100°C. oThe mixture was kept at room temperature and stirred for 4–5 hours. Subsequently, the reaction solution was concentrated to dryness and distilled three times with 10 mL of anhydrous toluene. The residue was then treated with 0.57 g (4.6 mmol, 2.00 eq) of SI-II-3 and 10 mL of anhydrous methanol. The reaction solution was then heated to an internal temperature of 50–60°C. o The mixture was kept at temperature and stirred for 14-18 hours. After the reaction was completed, the mixture was concentrated and separated by column chromatography (stationary phase: silica gel; eluent: n-hexane: ethyl acetate = 20:1 to 10:1). The eluent was concentrated to dryness to obtain the product. (S c , R Fc )- Ligand I-L1 0.72 g (60% molar yield). 1 H NMR (400 MHz, CDCl3) δ 8.03 – 7.98 (m,1H), 7.59 – 7.46 (m, 2H), 7.41 – 7.36 (m, 3H), 7.35 – 7.21 (m, 6H), 7.08 (d,J = 8.7 Hz, 1H), 6.47 (ddd, J = 7.0, 5.0, 1.0 Hz, 1H), 4.62 – 4.58 (dd, J =2.8, 1.5 Hz, 1H), 4.47 (dd, J = 6.4, 3.1 Hz, 1H), 4.37 (t, J = 2.5 Hz, 1H), 4.07 (s, 5H), 3.84 – 3.79 (dt, J = 2.4, 1.1 Hz, 1H), 3.05 (brs, 1H), 2.88 (s,3H), 1.38 (d, J = 6.4 Hz, 3H).

[0058] (S c , R Fc )- Synthesis of 1:

[0059]

[0060] Add ( to the reaction flask) S c , R Fc )-Ligand I-L1 571 mg (1.1 mmol, 1.10 eq), manganese pentacarbonyl bromide 275 mg (1.0 mmol, 1.00 eq), and anhydrous toluene 5 mL were added. After purging with nitrogen three times, the reaction solution was heated to an internal temperature of 100-110°C. o The mixture was kept at temperature and stirred for 14-16 hours. Subsequently, the reaction solution was concentrated to dryness, recrystallized using dichloromethane and n-hexane, filtered, and dried to obtain the product. (S c , R Fc )- 1 0.70 g (90% molar yield).

[0061] Example 2: Application of ferrocene-pyridine-hydrazine manganese complexes in the asymmetric hydrogenation of acetophenone. (S c , R Fc )- For example, 1:

[0062]

[0063] Add acetophenone (120 mg, 1 mmol) to an 8 ml hydrogenation vial under a nitrogen atmosphere. (S c , R Fc )- 1 (15.6 mg, 2 mol%), potassium tert-butoxide (4.5 mg, 4 mol%), and anhydrous methanol (3 mL) were then placed in a 250 mL hydrogenation reactor. After purging with hydrogen four times, the reactor was purged with hydrogen at 5.0 MPa and reacted at 50 °C for 48 hours. After the reaction was complete, the chiral purity of the reaction solution was determined by HPLC.

[0064] The liquid phase conditions are:

[0065] Column: OD-H;

[0066] Mobile phase: n-hexane / isopropanol = 95 / 5, flow rate: 1.0 mL / min, isogradient elution;

[0067] Detection wavelength: 210 nm;

[0068] Retention time: 7.46 min ( S ), 9.02 min ( R ).

[0069] The screening results for some of the above ligands are shown in the table below:

[0070]

[0071] Although the invention has been fully described in conjunction with specific embodiments, it should be noted that various changes and modifications will be apparent to those skilled in the art. Such changes and modifications are to be understood to be included within the scope of the invention as defined by the appended claims.

Claims

1. Novel ferrocenyl pyridine hydrazine manganese complexes characterized in that, The structure is: 。 2. A method of preparing the ferrocenyl pyridine hydrazine manganese complex of claim 1, characterized by, The addition reaction is prepared by ligand I or ligand II and MnBr(CO)5, ， wherein Ar, R 1 , R 2 are as defined in claim 1.

3. The method for preparing ferrocene-pyridine-hydrazine manganese complexes according to claim 2, characterized in that, The reaction solvent of the addition reaction is selected from one of tetrahydrofuran, 2-methyltetrahydrofuran, toluene, benzene, halogenated hydrocarbon, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, methanol, ethanol, isopropanol, tert-butyl alcohol, acetonitrile.

4. The application of the ferrocenyl pyridine hydrazine manganese complex in claim 1 in asymmetric hydrogenation reaction of prochiral ketone compounds.

Images