CN103980317B - Dipyridyl tetradentate ligand ruthenium complex as well as preparation method and application thereof - Google Patents

Abstract

The invention relates to a dipyridyl tetradentate ligand ruthenium complex as well as a preparation method of the complex and application of the complex to a reaction for hydrogenating ester compounds into alcohol compounds. A method for catalytically hydrogenating the ester compounds into the alcohol compounds by using the dipyridyl tetradentate ligand ruthenium complex is characterized by comprising the following steps: by taking 0.001mol% to 0.3mol% of the dipyridyl tetradentate ligand ruthenium complex based on the ester compounds, as a catalyst, adding 1mol%-10mol% of alkali based on the ester compounds, and catalytically hydrogenating the ester compounds into the corresponding alcohol compounds under the conditions that the temperature is 25-100 DEG C and the hydrogen pressure is 1-10MPa. The dipyridyl tetradentate ligand ruthenium complex is convenient to prepare, stable in structure and excellent in catalytic activity in hydrogenation reaction of the ester compounds. According to the preparation method, the shortcomings of requirements on high-temperature high-pressure reaction conditions and high catalyst consumption in an existing homogeneous or non-homogeneous catalytic hydrogenation system of the ester compounds are overcome, the catalyst consumption is low, the reaction conditions are mild, the reaction selectivity is good, and the economy and the safety of a production system are improved.

Description

Bipyridine tetradentate ligand ruthenium complex and its preparation method and application

technical field

The invention relates to a novel bipyridine tetradentate ligand ruthenium complex, a preparation method thereof and an application in the hydrogenation reaction of ester compounds into alcohol compounds.

Background technique

The reduction of ester compounds to prepare alcohols is an important reaction in organic synthesis, which is of great significance both in basic scientific research and in industrial production. The reduction of ester compounds to alcohol compounds is commonly used in laboratories such as lithium aluminum hydride and other negative hydrogen reagents, and these negative hydrogen reagents will produce a large amount of inorganic waste during post-treatment, and these active negative hydrogen reagents will It will bring potential safety hazards and limit its application in industrial production. The reduction of esters to alcohols by catalytic hydrogenation is a highly atom-economical method, so the development of catalysts for the hydrogenation of esters has attracted widespread attention.

At present, the heterogeneous catalytic hydrogenation of esters often requires harsh conditions of high temperature and high pressure. For example, catalysts such as Cu-Cr or Cu-Zn-Cr were the first catalysts used in the hydrogenation of esters, but these catalysts Often need very high temperature (200 ~ 300 ℃) and hydrogen pressure (20 ~ 30MPa). Chinese patent CN103566933A discloses a Cu catalyst supported by silica, adding an element of Mg, Zn, Ni, Zr or Mg-Zn, Mg-Zr as an auxiliary agent, and the reaction temperature is 200-270 ° C. The method for preparing ethanol by catalyzing the hydrogenation of acetate under the condition of hydrogen pressure of 3 MPa, the conversion rate of acetate is 98%, and the selectivity of ethanol is 98%. CN102976892A discloses a Cu catalyst supported by mesoporous molecular sieves, adding an oxide of at least one element in La and Ce as an auxiliary agent to prepare ethanol by catalytic hydrogenation of acetate at a reaction temperature of 220 °C and a hydrogen pressure of 3 MPa. method, the conversion rate of acetate is 98.5%, and the selectivity of ethanol is 99.6%. CN102649694A discloses a Cu catalyst supported by a composite carrier of silica and alumina, adding Re, W metal elements and their oxides as additives, at a reaction temperature of 170-270°C and a hydrogen pressure of 1.5-10MPa The method for preparing ethylene glycol by catalytic hydrogenation of oxalate ester, the conversion rate of oxalate ester can reach 100%, and the selectivity of ethylene glycol is greater than 95%. CN101602005B discloses a catalytic hydrogenation of methyl 3,3-dimethylbutyrate to synthesize 3 using a silica-supported Pd-Cu bimetallic catalyst at a reaction temperature of 120-180°C and a hydrogen pressure of 1-5 MPa. The method for 3-dimethylbutanol, the yield of 3,3-dimethylbutanol is 95.6%. CN1097038C discloses a catalyst containing Cu, Mn and Al as basic components to prepare 1 by hydrogenation of adipate and 6-hydroxyhexanoate at a reaction temperature of 150-230°C and a hydrogen pressure of 1-7 MPa. In the method for 6-hexanediol, the conversion rate of raw materials is 100%, and the selectivity of producing 1,6-hexanediol is higher than 95%. CN1974510A discloses a catalytic hydrogenation of various fatty acids using zirconia-supported Ru, Rh or Ru-Zn, Ru-Co, Ru-Sn catalysts at a reaction temperature of 100-150°C and a hydrogen pressure of 3-7 MPa In the method for preparing alcohol from ester, the raw material conversion rate is 75.0-99.5%, and the product selectivity is 68.2-99.5%. These heterogeneous catalytic hydrogenation systems generally have the problem of harsh reaction conditions (for example: high temperature, high pressure), which leads to high production costs and is not conducive to large-scale production.

The development of catalysts for the homogeneous catalytic hydrogenation of esters has attracted attention both in academia and industry. In recent years, ruthenium-based catalysts for the homogeneous catalytic hydrogenation of esters have been studied more, and corresponding reports can be found in recent review articles (ACS Catalysis2012, 2, 1718-1741; Org.ProcessRes.Dev.2014, 18 , 289-302) and literature cited therein. There are also more patent reports on the homogeneous catalytic hydrogenation of ester compounds in the industry. For example, EP1970360A1 discloses a method for preparing alcohol using bisphosphine bisamine ruthenium complex catalytic hydrogenation carboxylate, wherein for aromatic carboxylate such as Methyl benzoate can obtain benzyl alcohol in 97.7% yield at S/C (ratio of the amount of substance of substrate and catalyst)=500, 100 ℃ and 5MPa hydrogen pressure conditions of 500, for fatty acid ester such as caprylic acid methyl Esters can be reacted at S/C=500, 100°C and 5MPa hydrogen pressure for 16h to obtain octanol in a yield of 92.9%. For lactones such as phthalide, react at S/C=500, 100°C and 5MPa hydrogen pressure for 18h. A yield of 98.5% resulted in o-phthalyl dimethanol. EP2141142A1 discloses a method of using triphosphine ligand ruthenium complex to catalyze hydrogenation of carboxylate to prepare alcohol, wherein for aromatic carboxylate such as methyl benzoate at S/C=632, 100°C and 4MPa hydrogen pressure conditions Benzyl alcohol can be obtained at a yield of 54.1% by reacting for 15 hours at the same temperature, and 1,2-propanediol can be obtained at a yield of 88.5% for fatty acid esters such as methyl lactate at S/C=16,377, 120°C and 4MPa hydrogen pressure for 16 hours , for a lactone such as γ-butyrolactone, 1,4-butanediol can be obtained in a yield of 69.0% under the conditions of S/C=679, 100° C. and 4 MPa hydrogen pressure for 13 hours. JP2012224600A discloses a method for preparing 2-(L-menthoxy)ethanol by catalytic hydrogenation of L-menthoxymethyl acetate using PNP tridentate pincer ligand ruthenium complex, at S/C=2000, 85°C The target product can be obtained in 90% yield by reacting with 4.5MPa hydrogen pressure for 6h. US20100125144 discloses a method of using PNNP tetradentate ligand ruthenium complex to catalyze the hydrogenation of carboxylate to prepare alcohol, wherein for aromatic carboxylate such as methyl benzoate at S/C=2000, 100°C and 5MPa hydrogen pressure Conditional reaction 2.5h can obtain 99% conversion rate, can obtain 97% conversion rate for fatty acid ester such as octanoic acid methyl ester at S/C=2000, 100 ℃ and 5MPa hydrogen pressure condition reaction 2.5h, for lactone such as propane Nonalactone reacted for 2.5h at S/C=2000, 100°C and 5MPa hydrogen pressure to obtain a conversion rate of 94%. WO2006106483A1 discloses a method for preparing alcohol by catalytic hydrogenation of carboxylic acid ester using phosphine amine ligand ruthenium complex, wherein for aromatic carboxylic acid ester such as methyl benzoate at S/C=2000, 100°C and 5MPa hydrogen pressure conditions Reaction 2.5h can obtain 98% conversion rate, can obtain 86% conversion rate for fatty acid ester such as methyl octanoate at S/C=2000, 100 ℃ and 5MPa hydrogen pressure condition reaction 2.5h, for lactone such as Nonalactone reacted at S/C=2000, 100°C and 5MPa hydrogen pressure for 2.5h to obtain a conversion rate of 98%. WO2012052996A2 discloses a method of using PNN tridentate pincer ligand ruthenium complex to catalyze the hydrogenation of carboxylic acid esters to prepare alcohols, wherein methyl formate can be reacted under the conditions of S/C=5000, 110°C and 5MPa hydrogen pressure for 14h. The yield of 93.7% is obtained methyl alcohol, for dimethyl carbonate at S/C=5000, 110 ℃ and 5MPa hydrogen pressure conditions can react 14h and can obtain methyl alcohol with the yield of 87.6%, for hexyl hexyl ester at S/C=4000 , 82.1% yield of hexanol can be obtained under the conditions of 110°C and 5MPa hydrogen pressure for 16h.

Generally speaking, the homogeneous catalytic hydrogenation of esters can be carried out under relatively mild conditions, but most of the reported reaction temperatures still require 100 °C and above, and the amount of catalyst used is large, which increases the production cost and is not conducive to Industrial production. Therefore, it is particularly important to develop efficient catalysts for the homogeneous catalytic hydrogenation of esters.

Contents of the invention

The object of the present invention is to propose a novel bipyridyl tetradentate ligand ruthenium complex, a preparation method thereof and an application in the hydrogenation of ester compounds to alcohol compounds. The bipyridine tetradentate ligand ruthenium complex solution generated in situ by the bipyridine tetradentate ligand and the metal ruthenium precursor or the synthetically prepared solid bipyridine tetradentate ligand ruthenium complex as a catalyst are applied to esters In the reaction of hydrogenation of compounds to prepare alcohols. The bipyridine tetradentate ligand ruthenium complex of the invention is convenient to prepare, has a stable structure, and exhibits excellent catalytic activity in the hydrogenation reaction of esters. The present invention overcomes the disadvantages of the existing homogeneous or heterogeneous catalytic hydrogenation system of ester compounds requiring high temperature and high pressure reaction conditions and high catalyst dosage, and has small catalyst dosage, mild reaction conditions, good reaction selectivity, and improves the economy of the production system. sex and safety.

The novel bipyridine tetradentate ligand provided by the present invention has a general structural formula as shown in I:

Among them, the coordination groups L ¹ and L ² can be independently selected from groups containing phosphorus (pR ¹ R ² ), nitrogen (NR ¹ R ² ) or sulfur (SR), and the coordination groups L ₁ and L ₂ Can be the same or different.

R, R ¹ and R ² can be independently selected from C ₁ ~C ₈ alkyl, C ₃ ~C ₈ cycloalkyl, phenyl, substituted phenyl, 1-naphthyl, 2-naphthyl, heteroaryl , benzyl and other groups that have no adverse effect on the reaction. The substituents on the substituted phenyl are C ₁ ~C ₈ alkyl, C ₃ ~C ₈ cycloalkyl, phenyl, alkoxy and halogen groups that have no adverse effect on the reaction, and the number of substituents is 1 to 5; the heteroaryl group is furyl, thienyl or pyridyl; R ¹ and R ² can be the same or different. R ¹ and R ² may be C ₃ -C ₈ aliphatic rings or aromatic rings in combination.

X ¹ and X ² can be independently selected from H, C ₁ -C ₈ alkyl, C ₃ -C ₈ cycloalkyl, phenyl, substituted phenyl, 1-naphthyl, 2-naphthyl, heteroaryl , benzyl, halogen and other groups that have no adverse effect on the reaction; the substituents on the substituted phenyl are C ₁ ~C ₈ alkyl, C ₃ ~C ₈ cycloalkyl, phenyl, alkoxy And halogen and other groups that have no adverse effect on the reaction, the number of substituents is 1 to 5; the heteroaryl is furyl, thienyl or pyridyl, etc.; m=0~3, n=0~3; when When m≥2, two adjacent X ¹ can be a C ₃ ~C ₈ aliphatic ring or an aromatic ring; when n ≥ 2, two adjacent X ² can be a C ₃ ~C ₈ aliphatic ring or Aromatic ring; X ¹ and X ² can be the same or different;

Optionally, the above-mentioned C ₁ -C ₈ alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, etc.; the C ₃ -C ₈ cycloalkyl group Cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.; the alkoxy is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy Base etc.

The definitions of the groups in the present invention are well known to those skilled in the art, and will not be described in detail here and below.

Optionally, the bipyridyl tetradentate ligand includes the following structural formula:

The bipyridine tetradentate ligand ruthenium complex produced in situ or synthesized provided by the present invention has a general structural formula as shown in II:

Among them, the definitions of L ¹ , L ² , X ¹ , X ² , m, and n are the same as those described in general formula I; Y, Z are H or other complex anions such as halogen (Cl, Br, I), ClO ₄ , PF _6. BPh ₄ , B(C ₆ F ₅ ) ₄ , BF ₄ , BH ₄ , OCOR, OCOCF ₃ , OSO ₂ R, OSO ₂ CF ₃ , CN, OR, NR ₂ , SR; R is H, C ₁ ～ C ₈ alkyl, C ₃ ~C ₈ cycloalkyl, phenyl, substituted phenyl, 1-naphthyl, 2-naphthyl, heteroaryl, benzyl and other groups that have no adverse effect on the reaction, said The substituents on the substituted phenyl are C ₁ ~C ₈ alkyl, C ₃ ~C ₈ cycloalkyl, phenyl, alkoxy and halogen groups that have no adverse effect on the reaction, and the number of substituents is 1 ~5; said heteroaryl is furyl, thienyl or pyridyl, etc.; Y and Z can be the same or different.

Optionally, Y, Z are the same halogen: Cl, Br, I.

In the general formula II, Y and Z are the same halogen (Cl, Br, I) when the bipyridine tetradentate ligand ruthenium complex can be generated in situ by the bipyridine tetradentate ligand and the metal ruthenium precursor as follows or Synthetic preparation:

1) In-situ generation: in organic solvents such as dichloromethane, tetrahydrofuran, toluene, N,N-dimethylformamide, dimethyl sulfoxide, etc., the amount of metal ruthenium precursor and ruthenium atomic substance is 1.0 to 1.5 times A quantity of the bipyridine tetradentate ligand of the present invention is reacted at 25-120°C for 4-16 hours to obtain a bipyridine tetradentate ligand ruthenium complex solution. or

2) Synthesis and preparation: In organic solvents such as dichloromethane, tetrahydrofuran, toluene, N,N-dimethylformamide, dimethyl sulfoxide, etc., the amount of metal ruthenium precursor and ruthenium atomic substance is 1.0 to 1.5 times the amount The bipyridine tetradentate ligand of the present invention is reacted at 25-120° C. for 4-16 hours, and the solution is rotary evaporated to 1/10 of the original volume. Add the concentrated solution into a poor solvent such as diethyl ether or n-hexane under stirring, and a deep purple-black solid is precipitated. After vacuum filtration, the filter cake is washed with a poor solvent such as diethyl ether or n-hexane, and the solid bipyridyl tetradentate compound is obtained after the filter cake is vacuum-dried. Bulk ruthenium complexes.

The metal ruthenium precursor can be RuCl ₃ ·nH ₂ O, [RuCl ₂ (CO) ₃ ] ₂ , [Ru(cod)Cl ₂ ] _n , [Ru(nbd)Cl ₂ ] _n , [RuCl ₂ ( Benzene)] ₂ , [RuBr ₂ (Benzene)] ₂ , [RuI ₂ (Benzene)] ₂ , [RuCl ₂ (η ⁶ -p-cymene)] ₂ , [RuBr ₂ (η ⁶ -p-cymene)] ₂ , [RuI ₂ (η ⁶ -p-cymene)] ₂ , [RuCl ₂ (mesitylene)] ₂ , [RuBr ₂ (mesitylene)] ₂ , [RuI ₂ (mesitylene)] ₂ , RuCl ₂ (PPh ₃ ) ₃ , , RuBr ₂ (PPh ₃ ) ₃ , RuI ₂ (PPh ₃ ) ₃ , RuCl ₂ (DMSO) ₄ , wherein: cod=1,5-cyclooctadiene, nbd=2,5-norbornadiene, DMSO= Dimethyl sulfoxide), etc.

Optionally, the bipyridyl tetradentate ligand ruthenium complex generated in situ or synthesized includes the following structural formula:

In general formula II, Y, the bipyridine tetradentate ligand ruthenium complex when Z is H or other coordination anion can be by Y, the bipyridine tetradentate ligand ruthenium when Z is identical halogen (Cl, Br, I) The complex is exchanged with the corresponding amount of sodium hydride, sodium acetate, sodium perchlorate, sodium tetraphenylborate, silver trifluoroacetate and other inorganic salts to exchange anions in situ to obtain the corresponding bipyridine tetradentate ligand ruthenium complex solution Or synthetically prepare the corresponding solid bipyridyl tetradentate ligand ruthenium complex.

In the present invention, the bipyridine tetradentate ligand ruthenium complex solution or the synthetically prepared solid bipyridine tetradentate ligand ruthenium complex formed in situ from the bipyridine tetradentate ligand and the metal ruthenium precursor are used as catalysts in esters In the reaction of catalytic hydrogenation of compounds into alcohol compounds, the applicable ester compounds can be aliphatic carboxylic acid esters, aromatic carboxylic acid esters, formates, carbonates and lactones, etc., and can contain one or more ester groups , can have any substituent that does not affect the hydrogenation reaction.

Described ester compound is shown in general formula III:

Wherein, R ^a and R ^b can be independently selected from C ₁ -C ₃₀ alkyl, C ₃ -C ₃₀ cycloalkyl, C ₂ -C ₃₀ alkenyl, C ₃ -C ₃₀ cycloalkenyl, aryl, etc., These groups can contain any substituents that do not affect the hydrogenation reaction. R ^a and R ^b can be the same or different; R ^a and R ^b can be connected to form a cyclic C ₄ ~ C ₃₀ lactone, lactone The ring can contain any substituents that do not affect the hydrogenation reaction, and the carbon atoms at suitable positions on the lactone ring can be replaced by heteroatoms such as O, N, S, etc. The lactone ring can be monocyclic or polycyclic. The lactone can be a saturated lactone or an unsaturated lactone.

Described alcohol compound is shown in general formula IV-a, IV-b:

The definitions of R ^a and R ^b are the same as those described in the general formula III. When R ^a and R ^b are not connected, the alcohol compound is shown in IV-a and IV-b; when R ^a and R ^b are connected, the alcohol compound is a binary compound obtained after the reduction of the corresponding lactone Alcohol; when the ester compound used for hydrogenation contains multiple ester groups, the resulting alcohol compound is the corresponding polyhydric alcohol.

Non-limiting examples of ester compounds include methyl benzoate, ethyl acetate, ethylene glycol carbonate, methyl levulinate, dimethyl succinate, γ-butyrolactone, γ-valerolactone, α- Methyl-gamma-butyrolactone, methyl glycolate, methyl lactate, methyl methoxyacetate, methyl laurate, methyl stearate, glyceryl trilaurate, glyceryl tristearate, oxalic acid Dimethyl ester, methyl 1,2-phthalate, methyl 1,3-phthalate, methyl caproate, hexyl caproate, etc.

The method for the catalytic hydrogenation application of the present invention to ester compound comprises the steps:

Under the protection of argon or nitrogen, the catalyst, that is, the bipyridine tetradentate ligand ruthenium complex (the bipyridine tetradentate ligand ruthenium complex solution generated in situ or the synthetically prepared solid bipyridine tetradentate ligand ruthenium complex compound) and alkali into the inner tube of the reaction kettle, add the solution of the substrate dissolved in the corresponding solvent, tighten the reaction kettle and carefully replace it with hydrogen for 3 to 5 times, adjust the hydrogen pressure to the required pressure, and stir the reaction at a suitable temperature to The pressure does not change any more, the reactor is returned to room temperature, and the remaining hydrogen is slowly released. The product is separated and purified by common organic compound purification methods such as column chromatography and distillation.

The present invention uses bipyridine tetradentate ligand ruthenium complex to catalyze the hydrogenation of ester compounds into alcohol compounds, and the method is characterized in that: the amount of catalyst is 0.001-0.3mol% of the amount of substrate substance, and the amount of alkali is the amount of substrate substance 1 to 10 mol%, hydrogen pressure of 1 to 10 MPa, reaction temperature of 25 to 100° C., and reaction time of 2 to 64 hours.

The catalytic hydrogenation of ester compounds in the present invention can be carried out under solvent-free conditions, but a solvent is preferably used. Non-limiting examples of the solvent used are one or a mixed solvent of organic solvents such as tetrahydrofuran, diethyl ether, 2-methyltetrahydrofuran, isopropanol, and toluene.

Non-limiting examples of bases used in the catalytic hydrogenation of ester compounds in the present invention are sodium methoxide, sodium ethoxide, sodium isopropoxide, sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassium isopropoxide, potassium tert-butoxide, and the like. The alkali used can be directly added to the inner tube of the reactor or dissolved in a corresponding solvent and added to the inner tube of the reactor.

In the present invention, the bipyridine tetradentate ligand ruthenium complex solution generated in situ from the bipyridine tetradentate ligand and the metal ruthenium precursor or directly synthesized and prepared solid bipyridine tetradentate ligand ruthenium complex is used as a catalyst in the In the reaction of hydrogenation of ester compounds to prepare alcohol compounds. The bipyridyl tetradentate ligand ruthenium complex of the invention is convenient to prepare, has a stable structure, exhibits excellent catalytic activity in the hydrogenation reaction of esters, has good reaction selectivity and high yield. The present invention overcomes the shortcomings of the existing homogeneous or heterogeneous catalytic hydrogenation systems of ester compounds that require high-temperature and high-pressure reaction conditions and high catalyst dosage, the catalyst dosage is small, the reaction conditions are mild, and the reaction temperature and pressure are far lower than other homogeneous or non-homogeneous hydrogenation systems. The homogeneous catalytic system has good reaction selectivity, improves the economy and safety of the production system, and has broad application prospects.

detailed description

The following non-limiting examples can enable those skilled in the art to understand the present invention more fully, but do not limit the present invention in any way. For the experimental methods that do not indicate specific conditions in the examples, usually follow the conventional conditions and the conditions described in the manual, or according to the conditions suggested by the manufacturer; the materials, reagents, etc. used, if no special instructions, can be purchased from commercial sources. get.

All air-sensitive compounds were weighed in the MBRAUN LABstar argon atmosphere glove box and operated on the vacuum line in strict accordance with standard Schlenk techniques. ¹ H NMR, ¹³ C NMR, and ³¹ p NMR nuclear magnetic resonance spectra were measured by Bruker AV400 nuclear magnetic resonance instrument (operating frequency is 400MHz, 101MHz and 162MHz respectively), the unit of chemical shift is ppm, and ¹ HNMR spectrum uses tetramethylsilane as Internal standard, ¹³ C NMR spectrum uses listed deuterated solvent as internal standard, ³¹ pNMR spectrum uses 85% H ₃ PO ₄ as external standard; Spray ionization) or MALDI (Matrix-Assisted Laser Desorption Ionization) was used as the ion source; elemental analysis was determined by Elementar Vario EL elemental analyzer; single crystal diffraction was determined by Rigaku007Saturn70 single crystal diffractometer; gas chromatography was analyzed by Agilent7890A gas chromatograph.

Example 1

Preparation of Ligand 1

2-methyl-6-(tri-n-butyltin base)pyridine (8): add 2-methyl- 6-bromopyridine (20.0 g, 116 mmol), the system was replaced by an argon atmosphere, and anhydrous tetrahydrofuran (200 mL) was added. The temperature of the system was controlled to -78°C with a liquid nitrogen-acetone cooling bath, and a solution of n-butyllithium in n-hexane (2.4M, 56.0 mL, 134 mmol) was added dropwise for 30 minutes. After dropping, continue to stir at -78°C for 2 hours. Tri-n-butyltin chloride (45.4 g, 140 mmol) was added dropwise into the system with a syringe, and the dropping time was 30 minutes. After dropping, continue to stir at -78°C for 30 minutes, then return to room temperature and react overnight (14 hours). The system was desolvated with a rotary evaporator, the residue was diluted with ether (300 mL), washed with water (200 mL) and saturated brine (200 mL) successively, the organic phase was dried over anhydrous sodium sulfate, and stood still. The desiccant was removed by suction filtration, the filtrate was desolvated by a rotary evaporator, the residue was distilled under reduced pressure, and the 145°C/0.4mmHg fraction was collected to obtain 40.0g of a near-colorless oily liquid product, yield: 90%. ¹ H NMR (400MHz, CDCl ₃ ) δ7.36(t, J=7.5Hz, 1H), 7.18(d, J=7.4Hz, 1H), 6.95(d, J=7.6Hz, 1H), 2.54(s , 3H), 1.69-0.76(m, 27H). ¹³ C NMR (101MHz, CDCl ₃ ) δ173.11(s), 158.70(s), 133.40(s), 129.48(s), 121.62(s), 29.22 (s), 27.47(s), 24.98(s), 13.82(s), 9.95(s). HRMS(ESI) calcd for C ₁₈ H ₃₄ NSn ⁺ ([M+H] ⁺ ): 384.1708; Found: 384.1712.

2-(p-toluenesulfonyloxymethyl)-6-bromopyridine (9): Add 2-hydroxymethyl to a 500mL three-necked round-bottom flask equipped with a constant pressure dropping funnel, an inversion stopper and a magnetic stir bar yl-6-bromopyridine (11.2 g, 59.6 mmol) and tetrahydrofuran (200 mL). The temperature of the system was controlled to 0°C with an ice-salt bath, and a pre-prepared solution of NaOH (7.20 g, 180 mmol) in water (50 ml) cooled in an ice-water bath was added at one time, and p-toluenesulfonyl chloride (12.6 g, 66.1 mmol) was added dropwise ) was dissolved in tetrahydrofuran (50mL) solution, and the dropwise addition time was 30 minutes. After dropping, it was naturally raised to room temperature, and the reaction was stirred overnight (14 hours), and the reaction was complete as monitored by TLC. The system was desolvated with a rotary evaporator, the residue was diluted with dichloromethane (300 mL), washed with water (200 mL) and saturated brine (200 mL) successively, the organic phase was dried over anhydrous sodium sulfate, and stood still. The desiccant was removed by suction filtration, and the filtrate was desolvated by a rotary evaporator to obtain a light yellow solid product, which was directly used in the next reaction. ¹ H NMR (400MHz, CDCl ₃ ) δ7.81(d, J=8.3Hz, 2H), 7.56(d, J=8.0Hz, 1H), 7.40(d, J=7.8Hz, 2H), 7.34(d , J=8.1Hz, 2H), 5.09(s, 2H), 2.44(s, 3H). ¹³ C NMR (101MHz, CDCl ₃ ) δ155.18(s), 145.38(s), 141.47(s), 139.36 (s), 132.48(s), 130.06(s), 128.12(s), 127.82(s), 120.61(s), 70.73(s), 21.73(s).HRMS(ESI) calcd for C ₁₃ H ₁₃ BrNO ₃ S ⁺ ([M+H] ⁺ ): 341.9794; Found: 341.9789.

2-(Diethylaminomethyl)-6-bromopyridine (10): Add 9, diethylamine (43.9g, 600mmol) and THF (120 mL), the reaction was stirred at room temperature overnight (14 hours), and the reaction was complete as monitored by TLC. The system was desolvated with a rotary evaporator, the residue was diluted with dichloromethane (300 mL), washed successively with saturated aqueous sodium bicarbonate (200 mL), water (200 mL) and saturated brine (200 mL), and the organic phase was washed with anhydrous sulfuric acid Sodium dry and let stand. The desiccant was removed by suction filtration, the filtrate was desolvated with a rotary evaporator, the residue was distilled under reduced pressure, and the 56°C/0.1mmHg fraction was collected to obtain 14.0 g of a light yellow oily liquid product. The two-step reaction yield: 96%. ¹ H NMR (400MHz, CDCl ₃ ) δ7.50(d, J=4.9Hz, 2H), 7.32(t, J=4.8Hz, 1H), 3.70(s, 2H), 2.56(q, J=7.1Hz , 4H), 1.03(t, J=7.1Hz, 6H). ¹³ C NMR (101MHz, CDCl ₃ ) δ163.09(s), 141.04(s), 138.73(s), 125.85(s), 121.37(s ), 59.09(s), 47.51(s), 12.08(s). HRMS(ESI) calcd for C ₁₀ H ₁₆ BrN ₂ ⁺ ([M+H] ⁺ ): 243.0491; Found: 243.0487.

6-Methyl-6'-(diethylaminomethyl)-2,2'-bipyridine (11): Add 8 (14.5 g, 37.9mmol), 10 (7.71g, 31.7mmol), tetrakis(triphenylphosphine) palladium (1.28g, 1.11mmol) and anhydrous lithium chloride (4.10g, 96.7mmol), the system was frozen with liquid nitrogen The melt was degassed three times, and finally replaced with argon atmosphere. The system was heated to 120° C. with an oil bath, and the reaction was stirred for 16 hours until a large amount of palladium black was produced in the system. At this time, GC showed that 10 had been completely converted. Cool the system to room temperature, add ethyl acetate (100 mL) to dilute, filter through celite to remove insoluble matter, add 6N hydrochloric acid to make the system acidic (pH=3), and separate the layers. The aqueous phase was adjusted to alkaline (pH=13) with 6N aqueous sodium hydroxide solution, extracted with diethyl ether (3×100 mL), the organic phase was washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, and allowed to stand. The desiccant was removed by suction filtration, the filtrate was desolvated by a rotary evaporator, the residue was distilled under reduced pressure, and the 130°C/0.1mmHg fraction was collected to obtain 6.40 g of a light yellow oily liquid product, yield: 79%. ¹ H NMR (400MHz, CDCl ₃ ) δ8.24(d, J=7.8Hz, 1H), 8.19(d, J=7.8Hz, 1H), 7.75(t, J=7.7Hz, 1H), 7.68(t , J=7.7Hz, 1H), 7.48(d, J=7.6Hz, 1H), 7.14(d, J=7.6Hz, 1H), 3.83(s, 2H), 2.65-2.58(m, overlap of q and s , 7H), 1.09(t, J=7.1Hz, 6H). ¹³ C NMR (101MHz, CDCl ₃ ) δ160.10(s), 157.87(s), 156.07(s), 155.64(s), 137.12(s ), 137.05(s), 123.09(s), 122.73(s), 119.15(s), 118.27(s), 59.53(s), 47.51(s), 24.77(s), 12.18(s).HRMS(ESI )calcd for C ₁₆ H ₂₂ N ₃ ⁺ ([M+H] ⁺ ): 256.1808; Found: 256.1807.

6-(diethylaminomethyl)-6'-(di-tert-butylphosphinomethyl)-2,2'-bipyridine (1): in a dry and clean Diisopropylamine (2.38 g, 23.5 mmol) and anhydrous tetrahydrofuran (20 mL) were added to a 50 mL Schlenk bottle, and the system was degassed three times by freezing and thawing with liquid nitrogen, and finally replaced with an argon atmosphere. The temperature of the system was controlled to 0° C. with an ice-salt bath, and a solution of n-butyllithium in n-hexane (2.4M, 9.8 mL, 23.5 mmol) was added dropwise to the system with a syringe for 15 minutes. After dropping, continue to stir at 0° C. for 1 hour, and let stand for use.

Add 11 (4.01g, 15.7mmol) and anhydrous tetrahydrofuran (10mL) into a dry and clean 100mL Schlenk bottle equipped with an inversion stopper and a magnetic stir bar, degas the system three times with liquid nitrogen, and finally replace it with argon atmosphere. The temperature of the system was controlled to 0° C. with an ice-salt bath, and the above pre-prepared THF solution of LDA was added dropwise to the system with a syringe for 15 minutes. After dropping, continue to stir at 0°C for 2 hours. The temperature of the system was controlled to -78°C with a liquid nitrogen-acetone cooling bath, and freeze-thawed degassed di-tert-butylphosphine chloride (5.69 g, 31.5 mmol) diluted in anhydrous tetrahydrofuran ( 10mL) solution, the dropwise addition time is 30 minutes. After dropping, continue to stir and react at -78°C for 30 minutes, then return to room temperature and stir overnight (14 hours). Add freeze-thawed degassed ether (30mL) and water (30mL) to the system after vacuum precipitation, separate the liquids, extract the aqueous phase with freeze-thawed degassed ether (2×10mL), combine the organic phases, and use Dry over sodium sulfate water and let stand. The desiccant was removed by filtration, the filtrate was precipitated in vacuum, the residue was distilled under reduced pressure, and the 180°C/0.1mmHg fraction was collected to obtain a light yellow viscous oily liquid, which gradually solidified after standing to obtain 3.30 g of a light yellow solid product, yield: 53% . ¹ H NMR (400MHz, CDCl ₃ ) δ8.26(d, J=7.7Hz, 1H), 8.18(d, J=7.7Hz, 1H), 7.74(t, J=7.7Hz, 1H), 7.68(t , J=7.7Hz, 1H), 7.46(d, J=7.7Hz, 1H), 7.40(d, J=7.7Hz, 1H), 3.82(s, 2H), 3.14(d, J=2.4Hz, 2H ), 2.62(q, J=7.0Hz, 4H), 1.18(d, J=11.0Hz, 18H), 1.09(t, J=7.0Hz, 6H). ¹³ C NMR (101MHz, CDCl ₃ ) δ161.46 (d, J=13.7Hz), 159.88(s), 155.70(s), 155.49(s), 137.16(s), 137.00(s), 123.82(d, J=8.5Hz), 122.75(s), 119.14 (s), 117.99(s), 59.46(s), 47.53(s), 32.09(d, J=21.6Hz), 31.97(d, J=23.9Hz), 29.86(d, J=13.2Hz), 12.18 (s). ³¹ P NMR (162MHz, CDCl ₃ ) δ37.12 (s). HRMS (ESI) calcd for C ₂₄ H ₃₉ N ₃ P ⁺ ([M+H] ⁺ ): 400.2876; Found: 400.2867.

Example 2

Preparation of Ligand 2

2-[(tert-butyldimethylsilyl)methyl]-6-bromopyridine (12): Add 2-hydroxymethyl- 6-bromopyridine (10.6g, 56.4mmol) and imidazole (15.4g, 226mmol), the system was replaced by an argon atmosphere, anhydrous DMF (50mL) was added, and tert-butyldimethyl Chlorosilane (10.2 g, 67.7 mmol). After the addition was complete, the reaction was stirred at room temperature for 1 hour. TLC monitored the reaction to be complete. Water (50 mL) was added to quench the reaction, and the product was extracted with diethyl ether (3×100 mL). The organic phase was washed with water (100 mL) and saturated brine (100 mL) successively. Dry over anhydrous sodium sulfate and let stand. The desiccant was removed by suction filtration, the filtrate was desolvated by a rotary evaporator, the residue was distilled under reduced pressure, and the 92°C/0.1mmHg fraction was collected to obtain 15.3 g of a colorless oily liquid product, yield: 90%. ¹ H NMR (400MHz, CDCl ₃ ) δ7.56(t, J=7.7Hz, 1H), 7.47(dd, J=7.6, 0.8Hz, 1H), 7.33(dd, J=7.8, 0.7Hz, 1H) , 4.80(s, 2H), 0.95(s, 9H), 0.11(s, 6H).

2-[(tert-butyldimethylsilyl)methyl]-6-(tri-n-butyltinyl)pyridine (13): in a dry and clean 250mL four-neck round bottom bottle equipped with an inversion stopper and a magnetic stir bar Add 12 (15.5g, 51.3mmol) to the system, replace the system with an argon atmosphere, add anhydrous THF (150mL), control the temperature of the system to -78°C with a liquid nitrogen-acetone cooling bath, and inject it dropwise into the system with a syringe A solution of n-butyllithium in n-hexane (2.4M, 25 mL, 60.0 mmol) was added dropwise over 30 minutes. After the dropwise reaction was completed, the stirring reaction was continued at -78°C for 1 hour. A solution of tributyltin chloride (20.0 g, 61.4 mmol) diluted in anhydrous THF (30 mL) was added dropwise to the system with a syringe for 30 minutes. After dropping, continue to stir at -78°C for 30 minutes, then return to room temperature and react overnight (14 hours). The system was desolvated with a rotary evaporator, and the residue was diluted with ether (200 mL), washed with water (200 mL) and saturated brine (200 mL) successively, and the organic phase was dried over anhydrous sodium sulfate and allowed to stand. The desiccant was removed by suction filtration, the filtrate was desolvated with a rotary evaporator, the residue was distilled under reduced pressure, and the 170°C/0.1mmHg fraction was collected to obtain 23.0 g of a colorless oily liquid product, yield: 87%. ¹ H NMR (400MHz, CDCl ₃ ) δ7.49(t, J=7.6Hz, 1H), 7.31(d, J=7.4Hz, 1H), 7.24(d, J=7.8Hz, 1H), 4.83(s , 2H), 1.60-1.49(m, 6H), 1.36-1.28(m, 6H), 1.12-1.05(m, 6H), 0.95(s, 9H), 0.87(t, J=7.3Hz, 9H), 0.12(s, 6H). ¹³ C NMR (101MHz, CDCl ₃ ) δ172.63(s), 161.56(s), 133.78(s), 130.57(s), 118.49(s), 66.77(s), 29.22( s), 27.46(s), 26.10(s), 18.52(s), 13.84(s), 9.98(s), -5.16(s). HRMS(ESI) calcd for C ₂₄ H ₄₈ NOSiSn ⁺ ([M+ H] ⁺ ): 514.2522; Found: 514.2530.

6-Hydroxymethyl-6'-(diethylaminomethyl)-2,2'-bipyridine (14): Add 10 ( 8.51g, 35.0mmol), 13 (21.5g, 42.0mmol), tetrakis (triphenylphosphine) palladium (1.42g, 1.23mmol) and anhydrous lithium chloride (4.49g, 106mmol), the system was frozen with liquid nitrogen The melt was degassed three times, and finally replaced with argon atmosphere. The system was heated to 120°C with an oil bath, and the reaction was stirred for 10 hours until a large amount of palladium black was produced in the system, at which point GC showed that 10 had been completely converted. The system was cooled to room temperature, diluted with ethyl acetate (100 mL), filtered through celite to remove insoluble matter, and 6N hydrochloric acid was added to make the system acidic (pH=3), and the layers were separated. The aqueous phase was adjusted to alkaline (pH=13) with 6N aqueous sodium hydroxide solution, extracted with diethyl ether (3×100 mL), the organic phase was washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, and allowed to stand. The desiccant was removed by suction filtration, the filtrate was desolvated by a rotary evaporator, the residue was distilled under reduced pressure, and the 150°C/0.1mmHg fraction was collected to obtain 8.00 g of a light yellow oily liquid product, yield: 84%. ¹ H NMR (400MHz, CDCl ₃ ) δ8.36(d, J=7.8Hz, 1H), 8.26(d, J=7.8Hz, 1H), 7.81, 7.79(2t, partially overlapped, J=7.8Hz, 2H ), 7.52(d, J=7.8Hz, 1H), 7.22(d, J=7.7Hz, 1H), 4.83(s, 2H), 4.06(s, 1H), 3.84(s, 2H), 2.63(q , J=7.1Hz, 4H), 1.10(t, J=7.1Hz, 6H). ¹³ C NMR (101MHz, CDCl ₃ ) δ160.26(s), 158.22(s), 155.30(s), 154.76(s ), 137.67(s), 137.23(s), 123.19(s), 120.29(s), 119.89(s), 119.06(s), 64.05(s), 59.46(s), 47.53(s), 12.16(s) ). HRMS(ESI) calcd for C ₁₆ H ₂₂ N ₃ O ⁺ ([M+H] ⁺ ): 272.1757; Found: 272.1762.

6-Chloro-6'-(diethylaminomethyl)-2,2'-bipyridine (15): Add 14( 5.81g, 21.4mmol), the system was replaced by an argon atmosphere, anhydrous dichloromethane (80mL) was added, the temperature of the system was controlled at 0°C with an ice-salt bath, and thionyl chloride was added dropwise to the system with a syringe ( 13.0g, 109mmol) diluted in dichloromethane (20mL) solution, the dropwise addition time is 30 minutes. After dropping, remove the cooling bath, heat to 45°C with an oil bath and stir the reaction for 3 hours. TLC monitors that the reaction is complete. After the system is cooled to room temperature, it is poured into a beaker containing ice cubes (100g), and adjusted to alkali with 6N NaOH aqueous solution. (pH=13), extracted with dichloromethane (3×50mL), washed with water (100mL) and saturated brine (100mL) successively, the organic phase was dried over anhydrous sodium sulfate, and left standing. The desiccant was removed by suction filtration, and the filtrate was desolvated with a rotary evaporator to obtain a light brown oily liquid product, which was unstable and was used directly in the next reaction. ¹ H NMR (400MHz, CDCl ₃ ) δ8.36(d, J=7.9Hz, 1H), 8.28(d, J=7.7Hz, 1H), 7.83(t, J=7.7Hz, 1H), 7.77(t , J=7.7Hz, 1H), 7.50, 7.48(2d, partially overlapped, J=8.8Hz and8.4Hz, 2H), 4.75(s, 2H), 3.83(s, 2H), 2.62(q, J=7.0 Hz, 4H), 1.09(t, J=7.1Hz, 6H). ¹³ C NMR (101MHz, CDCl ₃ ) δ160.19(s), 156.25(s), 156.07(s), 154.86(s), 137.93( s), 137.25(s), 123.20(s), 122.56(s), 120.49(s), 119.33(s), 59.47(s), 47.54(s), 47.13(s), 12.18(s).HRMS( ESI) calcd for C ₁₆ H ₂₁ ClN ₃ ⁺ ([M+H] ⁺ ): 290.1419; Found: 290.1427.

6-(Diethylaminomethyl)-6'-(diphenylphosphinomethyl)-2,2'-bipyridine (2): In a dry and clean 250mL container equipped with an inversion plug and a magnetic stir bar Potassium tert-butoxide (3.40 g, 30.3 mmol) was added to the Schlenk bottle, the system was replaced by an argon atmosphere, freeze-thawed degassed anhydrous tetrahydrofuran (50 mL) was added, and the temperature of the system was controlled to 0° C. with an ice-salt bath. A solution of freeze-thawed degassed diphenylphosphine (4.69 g, 25.2 mmol) diluted in anhydrous tetrahydrofuran (15 mL) was added dropwise to the system with a syringe for 15 minutes. After dropping, continue to keep stirring at 0°C for 1 hour to obtain a dark red clear solution. A solution of freeze-thawed and degassed 15 dissolved in anhydrous tetrahydrofuran (15 mL) was added dropwise to the system with a syringe for 30 minutes. After dropping, continue to keep stirring at 0° C. for 30 minutes, then return to room temperature and stir overnight (14 hours). Add freeze-thawed degassed distilled water (30mL) into the system with a syringe, separate the liquids, extract the aqueous phase with freeze-thawed degassed ether (2×10mL), combine the organic phases, and wash with anhydrous sodium sulfate under the protection of argon. Dry and let stand. The desiccant was removed by filtration, the filtrate was precipitated in vacuum, the residue was distilled under reduced pressure, and the 230°C/0.1mmHg fraction was collected to obtain 5.00 g of a light yellow oily liquid product. The two-step reaction yield: 54%. ¹ HNMR (400MHz, CDCl ₃ ) δ8.18(d, J=7.8Hz, 1H), 8.02(d, J=7.7Hz, 1H), 7.69(t, J=7.7Hz, 1H), 7.60(t, J=7.7Hz, 1H), 7.53-7.47(m, 4H), 7.45(d, J=7.7Hz, 1H), 7.37-7.28(m, 6H), 7.02(d, J=7.6Hz, 1H), 3.81(s, 2H), 3.71(s, 2H), 2.62(q, J=7.1Hz, 4H), 1.09(t, J=7.1Hz, 6H). ¹³ C NMR (101MHz, CDCl ₃ ) δ159.93 (s), 157.46(d, J=7.5Hz), 156.02(s), 155.49(s), 138.59(d, J=14.9Hz), 137.06(s, 2C, one carbon missing due to overlap), 133.15( d, J=19.0Hz), 128.74(s), 128.47(d, J=6.8Hz), 123.47(d, J=5.5Hz), 122.81(s), 119.42(s), 118.45(d, J=1.4 Hz), 59.53(s), 47.55(s), 38.72(d, J=16.3Hz), 12.23(s). ³¹ pNMR(162MHz, CDCl ₃ )δ-11.09(s).HRMS(ESI)calcd for C ₂₈ H ₃₁ N ₃ P ⁺ ([M+H] ⁺ ): 440.2250; Found: 440.2258.

Example 3

Preparation of Ligand 3

6,6'-dimethylol-2,2'-bipyridine (16): add 12 (8.49g, 28.1mmol), 13( 16.9g, 33.0mmol), tetrakis(triphenylphosphine) palladium (1.14g, 0.99mmol) and anhydrous lithium chloride (3.60g, 84.9mmol), the system was degassed three times by freezing and thawing with liquid nitrogen, and finally replaced with Argon atmosphere. The system was heated to 120° C. with an oil bath, and the reaction was stirred for 12 hours until a large amount of palladium black was produced in the system. At this time, GC showed that 12 had been completely converted. The system was cooled to room temperature, diluted with ethyl acetate (100 mL), filtered through celite to remove insoluble matter, and 6N hydrochloric acid was added to make the system acidic (pH=3), and the layers were separated. The aqueous phase was adjusted to alkaline (pH=13) with 6N aqueous sodium hydroxide solution, extracted with diethyl ether (3×100 mL), the organic phase was washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, and allowed to stand. The desiccant was removed by suction filtration, and the filtrate was desolvated by a rotary evaporator to obtain 5.20 g of a white solid product, yield: 85%. ¹ H NMR (400MHz, DMSO) δ8.23(d, J=7.7Hz, 2H), 7.93(t, J=7.8Hz, 2H), 7.52(d, J=7.6Hz, 2H), 5.48(t, J=5.8Hz, 2H), 4.65(d, J=5.7Hz, 4H).

6,6'-Dichloromethyl-2,2'-bipyridine (17): Add 16 (1.71g, 7.91mmol) to a dry and clean 100mL Schlenk bottle equipped with an inversion stopper and a magnetic stir bar, and The system was replaced with an argon atmosphere, anhydrous dichloromethane (40mL) was added, the temperature of the system was controlled at 0°C with an ice-salt bath, and thionyl chloride (4.81g, 40.4mmol) was added dropwise to the system with a syringe to dilute in A solution of dichloromethane (10 mL) was added dropwise over 15 minutes. After dripping, remove the cold bath, heat to 45°C with an oil bath and stir for 3 hours. TLC monitors that the reaction is complete. After cooling the system to room temperature, pour it into a beaker containing ice cubes (100g), and adjust it to alkaline with 6N NaOH aqueous solution. (pH=13), extracted with dichloromethane (3×50 mL), the organic phase was washed with water (100 mL) and saturated brine (100 mL) successively, dried over anhydrous sodium sulfate, and left standing. The desiccant was removed by suction filtration, and the filtrate was desolvated by a rotary evaporator to obtain 1.80 g of a light yellow solid product, yield: 90%. ¹ H NMR (400MHz, CDCl ₃ ) δ8.40(d, J=7.9Hz, 2H), 7.85(t, J=7.8Hz, 2H), 7.51(d, J=7.7Hz, 2H), 4.75(s , 4H).

6,6'-bis(di-tert-butylphosphinomethyl)-2,2'-bipyridine (3): add 17 (1.01 g, 3.99mmol), the system was replaced by an argon atmosphere, a solution of di-tert-butylphosphine (2.34g, 16.0mmol) diluted in anhydrous methanol (30mL) was added, and the system was heated to The reaction was stirred at 60°C for 48 hours to obtain a white suspension. The system was cooled to room temperature, and freeze-thawed degassed triethylamine (2.10 g, 20.8 mmol) was added to the system with a syringe, and the mixture was stirred and reacted at room temperature overnight (14 hours). The system was precipitated in vacuum, the residue was added into freeze-thawed degassed dichloromethane (50 mL), washed with freeze-thawed degassed distilled water (3 × 10 mL), the organic phase was dried over anhydrous sodium sulfate under the protection of argon, and statically place. Filtrate through a short neutral aluminum oxide column, and the filtrate is precipitated in vacuum to obtain 1.30 g of a white solid product, yield: 69%. ¹ H NMR (400MHz, CDCl ₃ ) δ8.17(d, J=7.7Hz, 2H), 7.67(t, J=7.7Hz, 2H), 7.39(d, J=7.7Hz, 2H), 3.13(d , J=3.2Hz, 4H), 1.18(d, J=11.0Hz, 36H). ¹³ CNMR (101MHz, CDCl ₃ ) δ161.33(d, J=13.8Hz), 155.49(s), 136.91(s) , 123.67(d, J=8.4Hz), 117.87(s), 32.03(d, J=21.7Hz), 31.91(d, J=23.9Hz), 29.81(d, J=13.2Hz). ³¹ p NMR( 162MHz, CDCl ₃ )δ37.02(s). HRMS(ESI) calcd for C ₂₈ H ₄₇ N ₂ P ₂ ⁺ ([M+H] ⁺ ): 473.3209; Found: 473.3213.

Example 4

Preparation of Ligand 4

Add 17 (1.50g, 5.93mmol), diethylamine (4.30g, 58.8mmol) and tetrahydrofuran (50mL) into a dry and clean 100mL two-necked round-bottom flask equipped with a reflux condenser, an introversion plug and a magnetic stirrer, The system was heated to 70°C with an oil bath and stirred for 4 hours, and the reaction was complete as monitored by TLC. The system was cooled to room temperature, desolvated with a rotary evaporator, the residue was diluted with dichloromethane (50 mL), washed successively with saturated aqueous sodium bicarbonate (50 mL), water (50 mL) and saturated brine (50 mL), and the organic phase was Dry with anhydrous sodium sulfate and let stand. The desiccant was removed by suction filtration, the filtrate was desolvated by a rotary evaporator, the residue was distilled under reduced pressure, and the 120°C/0.1mmHg fraction was collected to obtain 1.50 g of a light yellow oily liquid product, yield: 78%. ¹ H NMR (400MHz, CDCl ₃ ) δ = 8.25 (d, J = 7.7, 2H), 7.76 (t, J = 7.7, 2H), 7.48 (d, J = 7.6, 2H), 3.83 (s, 4H) , 2.62(q, J=7.1, 8H), 1.09(t, J=7.1, 12H). ¹³ C NMR (101MHz, CDCl ₃ ) δ=160.06(s), 155.69(s), 137.18(s), 122.78 (s), 119.23(s), 59.52(s), 47.53(s), 12.21(s). HRMS(ESI) calcdfor C ₂₀ H ₃₁ N ₄ ⁺ ([M+H] ⁺ ): 327.2543; Found: 327.2550 .

Example 5

Preparation of complex 5

1 (600mg, 1.50mmol) and [RuCl ₂ (η ⁶ -p-cymene)] ₂ (400mg, 0.65mmol) were added to a dry and clean 15mL Schlenk tube equipped with an inversion plug and a magnetic stirrer, and the system was replaced Freeze-thawed degassed anhydrous dichloromethane (5 mL) was added under an argon atmosphere. The reaction was stirred at room temperature for 4 hours to obtain a dark purple-black suspension, which was directly desolvated with a rotary evaporator, and the residue was washed with ether (3×10 mL), filtered with suction, and dried in vacuo to obtain 740 mg of a dark purple-black solid powder. Rate: 99%. ¹ H NMR (400MHz, CDCl ₃ ) δ7.93(d, J=8.0Hz, 1H), 7.80-7.71(m, 2H), 7.48(d, J=7.6Hz, 1H), 7.45-7.33(m, 2H), 4.45(s, 2H), 3.62(d, J=8.5Hz, 2H), 3.57, 3.54(2q, partially overlapped, J=6.8Hz and6.7Hz, 2H), 3.25, 3.22(2q, partially overlapped, J=6.6Hzand6.6Hz, 2H), 1.44(d, J=11.8Hz, 18H), 1.18(t, J=7.0Hz, 6H). ¹³ C NMR (101MHz, CDCl ₃ ) δ169.25(d, J =3.3Hz), 161.58(d, J=2.0Hz), 161.00(s), 158.56(s), 134.17(s), 131.69(s), 121.16(d, J=1.9Hz), 120.56(s), 120.47(s), 120.30(s), 67.79(s), 51.42(s), 38.67(d, J=14.5Hz), 38.31(d, J=7.1Hz), 30.78(d, J=3.9Hz), 10.71(s). ³¹ P NMR (162MHz, CDCl ₃ ) δ63.21(s). Anal. Calcd. for C ₂₄ H ₃₈ Cl ₂ N ₃ PRu: C, 50.44; H, 6.70; N, 7.35. Found: C, 50.34; H, 6.92; N, 7.31.

Example 6

Preparation of complex 6

Add 2 (210mg, 0.48mmol) and [RuCl ₂ (η ⁶ -p-cymene)] ₂ (122mg, 0.20mmol) in a dry and clean 15mL Schlenk tube equipped with an inversion plug and a magnetic stirrer, and replace the system Under an argon atmosphere, freeze-thawed degassed anhydrous toluene (5 mL) was added. The system was heated to 120°C in an oil bath and stirred for 16 hours to obtain a deep purple black suspension, which was precipitated in vacuo, and the residue was washed with diethyl ether (3×5 mL) and ethanol (3×5 mL), filtered with suction, and dried in vacuo. 210 mg of deep purple black solid powder was obtained, yield: 86%. ¹ H NMR (400MHz, CDCl ₃ ) δ8.00(d, J=8.3Hz, 1H), 7.88-7.81(m, 2H), 7.80-7.70(m, 4H), 7.57-7.47(m, 3H), 7.41-7.31(m, 6H), 4.54(s, 2H), 4.27(d, J=10.2Hz, 2H), 3.38, 3.35(2q, partially overlapped, J=6.8Hz and6.7Hz, 2H), 3.20, 3.17(2q, partially overlapped, J=6.4Hz and6.6Hz, 2H), 1.08(t, J=7.0Hz, 6H). ¹³ C NMR(101MHz, CDCl ₃ ) δ165.93(d, J=5.1Hz) , 160.76(d, J=3.1Hz), 160.53(s), 157.62(s), 137.24(d, J=34.5Hz), 134.74(s), 133.61(d, J=10.4Hz), 132.12(s) , 129.27(s), 127.82(d, J=8.9Hz), 121.45(d, J=2.9Hz), 120.82(s), 120.69(s), 120.56(d, J=9.3Hz), 66.63(s) , 51.28(s), 48.59(d, J=25.4Hz), 10.53(s). ³¹ p NMR (162MHz, CDCl ₃ ) δ45.75(s).HRMS(ESI) calcd for C ₂₈ H ₃₀ ClN ₃ PRu ⁺ ([M-Cl] ⁺ ): 576.0904; Found: 576.0897.

Example 7

Preparation of complex 7

Add 3 (113mg, 0.24mmol) and [RuCl ₂ (η ⁶ -p-cymene)] ₂ (61mg, 0.10mmol) to a dry and clean 15mL Schlenk tube equipped with an inversion plug and a magnetic stirrer, and replace the system Freeze-thawed degassed anhydrous dichloromethane (5 mL) was added under an argon atmosphere. The reaction was stirred at room temperature for 4 hours to obtain a dark purple-black suspension, which was directly desolvated with a rotary evaporator, and the residue was washed with ether (3×5 mL), filtered with suction, and dried in vacuo to obtain 117 mg of a dark purple-black solid powder. Rate: 91%. ¹ H NMR (400MHz, CDCl ₃ ) δ7.87(d, J=7.8Hz, 2H), 7.63(t, J=7.8Hz, 2H), 7.57(d, J=7.7Hz, 2H), 3.87(d , J=8.3Hz, 4H), 1.45(d, J=11.3Hz, 36H). ¹³ C NMR (101MHz, CDCl ₃ ) δ166.50(s), 159.51(s), 134.04(s), 122.30(vt , J=4.8Hz), 120.45(s), 39.25(dd, J=11.8, 6.7Hz), 37.46(vt, J=3.8Hz), 30.70(s). ³¹ P NMR (162MHz, CDCl ₃ ) δ66. 25(s). Anal. Calcd. for C ₂₈ H ₄₆ Cl ₂ N ₂ P ₂ Ru: C, 52.17; H, 7.19; N, 4.35. Found: C, 52.29; H, 6.91; N, 4.56.

Example 8

Taking γ-valerolactone as an example to illustrate the operation of catalytic hydrogenation reaction of ester compounds:

a) Using in situ generated bipyridine tetradentate ligand ruthenium complex solution

Weigh ligand 1 (1.4mg, 3.6μmol) and [RuCl ₂ (η ⁶ -p-cymene)] ₂ (0.9mg, 1.5μmol) in a 10mL Schlenk equipped with an introvert stopper and a magnetic stir bar in a glove box Add freeze-thawed degassed tetrahydrofuran (2.0 mL) into the tube, and stir the reaction at 25°C for 30 minutes under the protection of an argon balloon to obtain a tetrahydrofuran solution of bipyridyl tetradentate ligand ruthenium complex 5. Weigh sodium methoxide (17 mg, 0.3 mmol) into a glass reaction tube equipped with a magnetic stirrer, quickly place it in an autoclave, and replace it with an argon atmosphere. Add the tetrahydrofuran solution of the above-mentioned bipyridyl tetradentate ligand ruthenium complex 5 and the freeze-thawed degassed pre-prepared γ-valerolactone (300mg, 3.0mmol) solution in tetrahydrofuran (3.0mL) into the high-pressure hydrogenation autoclave by syringe In the process, replace the gas in the autoclave with hydrogen for five times, finally adjust the hydrogen pressure to 5MPa, stir and react at 25°C for 6 hours until the pressure gauge does not change, slowly release the hydrogen in the autoclave, and add 1,5-pentanediol As an internal standard, a small amount of sample was filtered through a short silica gel column, and the yield of 1,4-pentanediol was determined to be 96% by gas chromatography.

After using ligand 2 and [RuCl ₂ (η ⁶ -p-cymene)] ₂ in situ generated bipyridyl tetradentate ligand ruthenium complex solution for catalytic hydrogenation of γ-valerolactone for 14 hours, 1,4-pentane The yield of diol was 67%; using ligand 3 and [RuCl ₂ (η ⁶ -p-cymene)] ₂ in situ generated bipyridyl tetradentate ligand ruthenium complex solution to catalyze the hydrogenation of γ-valerolactone 14 After 1 hour, the yield of 1,4-pentanediol was 25%; using ligand 4 and [RuCl ₂ (η ⁶ -p-cymene)] ₂ in situ generated bipyridyl tetradentate ligand ruthenium complex solution catalysis After hydrogenation of γ-valerolactone for 14 hours, the yield of 1,4-pentanediol was 15%.

The gas chromatography analysis conditions are: Agilent DB-35 chromatographic column (30m×0.32mm×0.25μm), FID detector, the temperature of the inlet is 230°C, the temperature of the detector is 250°C, the carrier gas is nitrogen, and the flow rate is constant at 1.0 mL/min. Programmed temperature rise: the initial temperature is 50°C, raised to 250°C at a rate of 10°C/min, and kept at this temperature for 10 minutes. The retention times of 1,4-pentanediol, γ-valerolactone, and 1,5-pentanediol were 7.92min, 8.30min, and 9.04min, respectively.

b) Using synthetically prepared solid bipyridyl tetradentate ligand ruthenium complexes

Weigh bipyridyl tetradentate ligand ruthenium complex 5 (1.7mg, 3.0μmol) and sodium methoxide (17mg, 0.3mmol) in a glove box in a glass reaction tube equipped with a magnetic stirrer, inject it with a syringe Add freeze-thawed and degassed pre-prepared γ-valerolactone (300mg, 3.0mmol) solution in tetrahydrofuran (5.0mL), stir evenly, quickly place in an autoclave, and replace with argon atmosphere. Replace the gas in the autoclave with hydrogen for five times, finally adjust the hydrogen pressure to 5MPa, stir and react at 25°C for 4 hours until the pressure gauge does not change, slowly release the hydrogen in the autoclave, and add 1,5-pentanediol as an internal The yield of 1,4-pentanediol was 98% as determined by gas chromatography after a small amount of sample was filtered through a short silica gel column.

Using the synthetically prepared solid bipyridine tetradentate ligand ruthenium complex 6 as a catalyst to catalyze the hydrogenation of γ-valerolactone for 7 hours, the yield of 1,4-pentanediol was 96%; using the synthetically prepared solid bipyridine The tetradentate ligand ruthenium complex 7 was used as a catalyst to catalyze the hydrogenation of γ-valerolactone for 14 hours, and the yield of 1,4-pentanediol was 30%.

Example 9

Using γ-valerolactone as the substrate, the synthetically prepared bipyridine tetradentate ligand ruthenium complex 5 was used to optimize and compare the experimental conditions of the catalytic hydrogenation reaction. The reaction results of different catalysts, solvents, alkalis and hydrogen pressures and other experimental conditions are shown in the table 1.

Table 1 Comparison of experimental conditions for hydrogenation of γ-valerolactone ^a

^a Reaction conditions: S/C=1000, 3.0 mmol γ-valerolactone, 3.0 μmol5, 5.0 mL ¹ PrOH, 25°C. ^b Determined by gas spectrometry, the separation yields are in parentheses, and only 1,4-pentanediol and unreacted γ-valerolactone were observed in all reactions. ^c S/C = 10,000, 12 mmol γ-valerolactone, 1.2 μmol 5, 1.0 mL ¹ PrOH, 1.2 mmol NaOMe. ^d S/C = 100,000, 36 mmol γ-valerolactone, 0.36 μmol 5, 4.0 mL ^l PrOH, 3.6 mmol NaOMe. ^e 40°C.

Example 10

The hydrogenation reaction results of using the synthetically prepared bipyridyl tetradentate ligand ruthenium complex 5 to catalyze the hydrogenation of other ester compounds are shown in Table 2:

Hydrogenation reaction ^a of other ester compounds of table 2

^a Reaction conditions: S/C=1000, 3.0 mmol substrate, 3.0 μmol 5, 3.0 mL ¹ PrOH, 0.3 mmol NaOMe, 5 MPaH ₂ , 25°C. ^b Gas spectrum yield, the separation yield in parentheses, only the target product and unreacted raw materials were observed in all reactions. ^c The remaining substance is γ-valerolactone. ^d 100°C. ^e S/C = 333, 100°C, 1.0 mmol substrate. ^f Tetrahydrofuran is the solvent. ^g S/C=10,000, 12 mmol substrate, 1.2 μmol5, 1.2 mmol NaOMe. ^h S/C = 100,000, 100 mmol methyl benzoate, 1.0 μmol 5, 20 mL ^l PrOH, 10.0 mmol NaOMe. ^l 40°C. ^J 10MPa H ₂ . ^k S/C=100,000, 200 mmol ethyl acetate, 2.0 μmol5, 20.0 mmol NaOEt.

The above examples prove that the bipyridyl tetradentate ligand ruthenium complex is easy to prepare, has good stability, and exhibits excellent catalytic activity in the hydrogenation reaction of esters, with a small amount of catalyst, mild reaction conditions, and high selectivity of the reaction. Well, it shows high industrial application value.

Claims (10)

1. a kind of bipyridyl tetradentate ligandses are it is characterised in that it has a structural formula as shown in i:

Wherein, coordinating group l¹And l²Independently selected from: pr¹r²、nr¹r², but it is not simultaneously selected from pr¹r²、nr¹r²；

r¹And r²Independently selected from: c₁～c₈Alkyl, c₃～c₈Cycloalkyl, phenyl, the phenyl replacing, 1- naphthyl, 2- naphthyl, heteroaryl Base, benzyl；Substituent group on described substituted phenyl is c₁～c₈Alkyl, c₃～c₈Cycloalkyl, phenyl, alkoxyl and halogen Element, substituent group quantity is 1～5；Described heteroaryl is furyl, thienyl or pyridine radicals；r¹、r²Identical or different；Or r¹、 r²And be c₃～c₈Cycloaliphatic ring or aromatic rings；

x¹、x²Independently selected from: h, c₁～c₈Alkyl, c₃～c₈Cycloalkyl, phenyl, the phenyl replacing, 1- naphthyl, 2- naphthyl, miscellaneous Aryl, benzyl, halogen；Substituent group on described substituted phenyl is c₁～c₈Alkyl, c₃～c₈Cycloalkyl, phenyl, alkoxyl And halogen, substituent group quantity is 1～5；Described heteroaryl is furyl, thienyl or pyridine radicals；M=0～3, n=0～ 3；When m >=2, two adjacent x¹Can and be c₃～c₈Cycloaliphatic ring or aromatic rings；When n >=2, two adjacent x²Can and be c₃ ～c₈Cycloaliphatic ring or aromatic rings；x¹、x²Identical or different.

2. according to the bipyridyl tetradentate ligandses described in claim 1 it is characterised in that described c₁～c₈Alkyl be methyl, ethyl, N-pro-pyl, isopropyl, normal-butyl, the tert-butyl group；Described c₃～c₈Cycloalkyl is cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl；Institute The alkoxyl stated is methoxyl group, ethyoxyl, positive propoxy, isopropoxy, n-butoxy, tert-butoxy.

3. according to the bipyridyl tetradentate ligandses described in claim 1 it is characterised in that described bipyridyl tetradentate ligandses are structure Shown in formula 1,2:

4. a kind of bipyridyl tetradentate ligandses ruthenium complex by the bipyridyl tetradentate ligandses preparation described in claim 1, its feature It is that it has a structural formula as shown in ii:

Wherein, l¹、l²、x¹、x², m, n definition identical with described in formula i；Y, z are h, cl, br, i, clo₄、pf₆、bph₄、b (c₆f₅)₄、bf₄、bh₄、ocor、ococf₃、oso₂r、oso₂cf₃、cn、or、nr₂、sr；R is h, c₁～c₈Alkyl, c₃～c₈Cycloalkanes Base, phenyl, the phenyl replacing, 1- naphthyl, 2- naphthyl, heteroaryl, benzyl；Substituent group on described substituted phenyl is c₁~ c₈Alkyl, c₃～c₈Cycloalkyl, phenyl, alkoxyl and halogen, substituent group quantity is 1～5；Described heteroaryl be furyl, Thienyl or pyridine radicals；Y, z are identical or different.

5. it is characterised in that described y, z is identical halogen to bipyridyl tetradentate ligandses ruthenium complex according to claim 4 Element: cl, br, i.

6. bipyridyl tetradentate ligandses ruthenium complex according to claim 4 is it is characterised in that described bipyridyl four tooth is joined Body ruthenium complex is shown in structural formula 5,6:

7. the preparation method of the bipyridyl tetradentate ligandses ruthenium complex described in claim 4 is it is characterised in that include following method:

1) in-situ preparation: in dichloromethane, oxolane, toluene, n, in n- dimethylformamide or dimethyl sulfoxide organic solvent, Metal ruthenium precursor and the described bipyridyl tetradentate ligandses of amount 1.0～1.5 times amount with respect to ruthenium atom material, at 25～120 DEG C Reaction 4～16 hours, you can obtain bipyridyl tetradentate ligandses ruthenium complex solution；

Or

2) synthetically prepared: in dichloromethane, oxolane, toluene, n, n- dimethylformamide, dimethyl sulfoxide organic solvent, Metal ruthenium precursor and the described bipyridyl tetradentate ligandses of amount 1.0～1.5 times amount with respect to ruthenium atom material, at 25～120 DEG C Reaction 4～16 hours, solution rotating is evaporated to original volume 1/10；The solution of concentration is added ether or normal hexane under agitation, Separate out dark purple black solid, vacuum filtration, wash filter cake with ether or normal hexane, after filter cake vacuum drying, obtain solid bipyridyl Tetradentate ligandses ruthenium complex；

Described metal ruthenium precursor is rucl₃·nh₂o、[rucl₂(co)₃]₂、[ru(cod)cl₂]_n、[ru(nbd)cl₂]_n、 [rucl₂ph]₂、[rubr₂ph]₂、[rui₂ph]₂、[rucl₂(p -Methylisopropylbenzene)]₂、[rubr₂(to isopropyl methyl Benzene)]₂、[rui₂(p -Methylisopropylbenzene)]₂、[rucl₂(1，3，5-trimethyl-benzene)]₂、[rubr₂(1，3，5-trimethyl-benzene) ]₂、[rui₂(1，3，5-trimethyl-benzene)]₂、rucl₂(pph₃)₃、rubr₂(pph₃)₃、rui₂(pph₃)₃、rucl₂(dmso)₄, its In, cod=1,5- cyclo-octadiene, nbd=2,5- norbornadiene, dmso=dimethyl sulfoxide.

8. the application of the bipyridyl tetradentate ligandses ruthenium complex described in claim 4 is it is characterised in that it is used for as catalyst Ester type compound catalytic hydrogenation synthesizes in the reaction of alcohol compound, and described ester type compound is as shown in formula iii:

Wherein, r^a、r^bSelected from c₁～c₃₀Alkyl, c₃～c₃₀Cycloalkyl, c₂～c₃₀Thiazolinyl, c₃～c₃₀Cycloalkenyl group, aryl, these bases The substituent group arbitrarily not affecting hydrogenation, r is contained in group^a、r^bIdentical or different；Or r^a、r^bIt is connected and form the c of ring-type₄~ c₃₀Lactone, lactonic ring contains arbitrarily does not affect the substituent group of hydrogenation, and on lactonic ring, the carbon atom of correct position can quilt O, n, s hetero atom replaces, and lactonic ring is monocyclic or multi-ring；Described lactone is saturation lactone or unsaturated lactone；

Described alcohol compound is as shown in formula iv-a, iv-b:

r^a、r^bDefinition identical with described in formula iii；Work as r^a、r^bAlcohol compound such as iv-a, iv-b institute described in when not being connected Show；Work as r^a、r^bAlcohol compound described in when connected is the dihydroxylic alcohols of gained after corresponding lactone reduction；When hydrogenation esters used When containing multiple ester group in compound, the alcohol compound of gained is corresponding polyhydric alcohol.

9. the application of bipyridyl tetradentate ligandses ruthenium complex according to claim 8 is it is characterised in that described esters Compound is: essence of Niobe, ethyl acetate, ethylene carbonate, methyl ester levulinate, dimethyl succinate, gamma-butyrolacton, Gamma-valerolactone, Alpha-Methyl-gamma-butyrolacton, methyl glycollate, methyl lactate, methoxy menthyl acetate, methyl laurate, Hard Fat Sour methyl ester, trilaurin, glyceryl tristearate, dimethyl oxalate., 1,2- phthalic acid methyl ester, 1,3- phthalic acid Methyl ester, methyl caproate, hexyl hexanoate.

10. the application of bipyridyl tetradentate ligandses ruthenium complex according to claim 8 is it is characterised in that to ester type compound Catalytic hydrogenation application method comprise the steps:

Under argon or nitrogen are protected, by catalyst be bipyridyl tetradentate ligandses ruthenium complex and alkali adds in reactor inner tube, Add substrate to be dissolved in the solution of coordinative solvent, tighten reactor and with the careful displacement of hydrogen 3～5 times, adjust Hydrogen Vapor Pressure to institute After needing pressure, stirring reaction no longer changes to pressure at appropriate temperatures, and reactor is recovered room temperature, slowly discharges residual hydrogen Gas；Product carries out separating-purifying by column chromatography, the conventional organic compound purification process of distillation；

Catalyst amount be substrate materials amount 0.001～0.3mol%, alkali consumption be substrate materials amount 1～ 10mol%, Hydrogen Vapor Pressure 1～10mpa, reaction temperature is 25～100 DEG C, and the response time is 2～64 hours；

Solvent for use is one of oxolane, ether, 2- methyltetrahydrofuran, isopropanol, toluene organic solvent or wherein Several mixed solvents；Alkali used is Feldalat NM, Sodium ethylate, sodium isopropylate, sodium tert-butoxide, Feldalat KM, potassium ethoxide, isopropanol Potassium, potassium tert-butoxide；The consumption of alkali is 1～10mol% of the amount of ester type compound material.