A method for preparing 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compounds

Abstract

The invention discloses a method for preparing a 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compound. The method comprises the following steps: in a protective atmosphere, mixing a 2,9-substituted-phenanthroline compound shown in formula (I), a catalyst, a reducing agent A and a reducing agent B, adding the mixture to an organic solvent, stirring and reacting at 110-150° C. for 6-18 hours, and subjecting the obtained reaction solution to post-treatment to obtain a 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compound shown in formula (II). The catalyst nickel chloride used in the invention has abundant reserves and low price, and does not need to add an additional ligand, thereby reducing the reaction cost, simplifying the operation steps and having an excellent yield.

Description

Technical Field

[0001] The invention relates to a method for synthesizing an organic compound, in particular to a method for synthesizing a 1,2,3,4-tetrahydro-1,10-phenanthroline derivative by hydrogenating and reducing a phenanthroline skeleton using a nickel catalyst. Background Art

[0002] 1,2,3,4-Tetrahydro-1,10-phenanthroline derivatives are a very important class of nitrogen-aromatic compounds. Their skeletons are commonly found in some natural products and drug molecules and show certain biological activities. In addition, hydrogenated 1,10-phenanthroline can also be used as an important class of nitrogen-containing bidentate ligands to complex with transition metals and catalyze different types of chemical reactions.

[0003] So far, relevant literature has reported the selective catalytic hydrogenation of 1,10-phenanthroline, and 1,2,3,4-tetrahydro-1,10-phenanthroline derivatives were obtained with good yields. For example, Francesco Vizza's research group reported a case of hydrogenation reduction of 1,10-phenanthroline catalyzed by silica-supported palladium nanoparticles (Inorganica Chimica Acta. 2008, 361, 3677-3680). However, the reaction uses hydrogen as a reducing agent and needs to be carried out in an autoclave, which is cumbersome and dangerous. In 2013, Fan Qinghua's research group also used high-pressure hydrogen as a negative hydrogen source and achieved the selective hydrogenation of 2,9-substituted 1,10-phenanthroline under the action of ruthenium catalyst. The reaction has a high yield and ee value (Angew. Chem. Int. Ed. 2013, 52, 7172-7176); in 2016, Xu Lijin's research group also reported a reduction method using iridium as a catalyst and formic acid as a negative hydrogen source. 2-substituted and 2,9-disubstituted 1,10-phenanthroline can obtain the corresponding target product in good yield under this catalytic condition (Adv. Synth. Catal. 2016, 358, 567-572).

[0004] Although previous research has made great progress in the hydrogenation reduction reaction of substituted 1,10-phenanthroline, it should be pointed out that the above reactions all use precious metals such as palladium, ruthenium, and iridium as catalysts, which are scarce and expensive, and have high costs for large-scale production. Therefore, the development of an efficient and inexpensive catalytic system to achieve the hydrogenation reduction of substituted 1,10-phenanthroline has important research significance and potential application value. Summary of the invention

[0005] In combination with the reported technical methods, the present invention realizes the hydrogenation reaction of 2,9-disubstituted-1,10-phenanthroline derivatives by catalysis of cheap metal nickel, thereby providing a new method for synthesizing 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compounds.

[0006] To achieve the above object, the technical solution of the present invention is:

[0007] A method for synthesizing 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compounds, wherein the synthesis method is specifically prepared according to the following steps:

[0008] Under a protective atmosphere, a 2,9-substituted phenanthroline compound shown in formula I, a catalyst, a reducing agent A, and a reducing agent B are mixed and added to an organic solvent, and stirred at 110° C.-150° C. for 6-18 hours (preferably at 150° C. for 12 hours), and the resulting reaction solution is post-treated to obtain a 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compound shown in formula II;

[0009] The reaction formula is as follows:

[0010]

[0011] In Formula I or Formula II, R is a C1-C5 alkyl group or a phenyl group;

[0012] The organic solvent is one solvent such as toluene, xylene, tetrahydrofuran, N,N-dimethylformamide, or a mixed solvent of more than one solvent;

[0013] The molar ratio of the 2,9-substituted phenanthroline compound shown in formula I, the catalyst, the reducing agent A, and the reducing agent B is 1:(0.1-1):(0.1-10):(2-10); preferably 1:0.1:10:10.

[0014] The catalyst is a nickel metal catalyst, preferably NiCl2;

[0015] The reducing agent A is manganese powder (Mn powder) or tin powder, or a mixture of the two, preferably Mn powder;

[0016] The reducing agent B is 1,1,3,3-tetramethyldisiloxane, phenylsilane, triethylsilane, preferably 1,1,3,3-tetramethyldisiloxane;

[0017] The "reducing agent A" and "reducing agent B" have no special meanings, and are marked as "A" and "B" only to distinguish different types of reducing agents.

[0018] Furthermore, R is one of methyl, n-butyl, n-pentyl, sec-butyl or phenyl.

[0019] Furthermore, the amount of the organic solvent added is 2.5 ml / mmol based on the amount of the 2,9-substituted phenanthroline compound represented by Formula I; the organic solvent is preferably tetrahydrofuran.

[0020] Furthermore, the protective atmosphere is nitrogen or argon, and the effects are similar.

[0021] The post-treatment of the present invention comprises the following steps: after the reaction is completed, cooling the reaction liquid to room temperature, adding 100-200 mesh silica gel to the reaction liquid, removing the solvent by a rotary evaporator, and then performing column chromatography separation, using a mixed solvent of petroleum ether, ethyl acetate and triethylamine in a volume ratio of 200:1:1 as an eluent for elution, collecting an eluate containing a 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compound shown in formula II as a target product, and removing the eluent by rotary evaporation to obtain the target product; the ratio of the mass of the silica gel to the sum of the mass of the 2,9-substituted phenanthroline compound shown in formula I, the catalyst, the reducing agent A and the reducing agent B is 5-10:1.

[0022] In addition, the 2,9-substituted phenanthroline compounds of formula I described in the present invention are recommended to be prepared according to the following method:

[0023]

[0024] Under nitrogen protection, under magnetic stirring, 1,10-phenanthroline and dry tetrahydrofuran (THF) solvent are added, and then a lithium reagent is slowly added dropwise to obtain a deep red solution. After stirring and reacting at room temperature for 18 hours, the solution is quenched with ice water, extracted with dichloromethane, and the organic phases are combined. An excess of MnO2 is added for oxidation, and the stirring reaction is continued for 1 hour. Anhydrous Na2SO4 is added to the reaction solution, and then the solution is fully stirred at room temperature, usually for 2 hours. After the reaction of 1,10-phenanthroline is completed, 100-200 mesh silica gel is added, and the solvent is removed by rotary evaporation. The solution is eluted with a mixed solvent of n-hexane and dichloromethane in a volume ratio of 1:1 as an eluent, and the eluent containing the target product is collected. After the eluent is removed by rotary evaporation, the 2,9-substituted phenanthroline compound shown in Formula I is obtained, and the purity is detected by HPLC;

[0025] The molar ratio of 1,10-phenanthroline, lithium reagent, MnO2, and anhydrous Na2SO4 is: 1:2-3.5:5-8:5-10;

[0026] The lithium reagent is selected from one of n-butyllithium reagent, n-pentyllithium reagent, phenyllithium reagent and sec-butyllithium reagent;

[0027] The volume of the tetrahydrofuran is 40 ml / g based on the mass of 1,10-phenanthroline.

[0028] Compared with the prior art, the invention has the following beneficial effects: unlike the known literature method, the method uses a noble metal as a catalyst and requires a ligand as an auxiliary. The nickel chloride of the invention has abundant reserves, low price, and does not require the addition of an additional ligand, thus reducing the reaction cost, simplifying the operation steps, and also having an excellent yield. DETAILED DESCRIPTION

[0029] The present invention is further described in detail below in conjunction with specific embodiments, but the protection scope of the present invention is not limited thereto:

[0030] The new cuprous reagent was purchased under the brand name Anage and had a purity of 99.7%.

[0031] Example 1: Preparation of 2,9-di-n-butyl-1,10-phenanthroline compound:

[0032]

[0033] The 2,9-di-n-butyl-1,10-phenanthroline compound represented by formula I-1 of the present invention is prepared specifically according to the following method:

[0034] Under nitrogen protection, 1,10-phenanthroline (2.5 g, 13.87 mmol) was added to a three-necked flask equipped with a magnetic pole, and then 100 mL of dry tetrahydrofuran (THF) solvent was added. 16.8 mL of n-butyl lithium in n-hexane solution (n-butyl lithium concentration was 2.5 M, and the amount of n-butyl lithium substance was 42 mmol) was slowly added dropwise with a syringe to obtain a deep red solution. After stirring at room temperature for 18 hours, the reaction was quenched with ice water and then extracted with dichloromethane (3×100 mL). The organic phases were combined and an excess of MnO2 (9.56 g, 110 mmol) was added for oxidation. After the reaction was stirred for 1 hour, anhydrous Na2SO4 (14.2 g, 100 mmol) was added to the reaction solution, and stirring was continued at room temperature for 2 hours. After the reaction of 1,10-phenanthroline was completed by TLC monitoring (petroleum ether to ethyl acetate was 5:1), 26g (100-200 mesh) silica gel was added to the reaction solution, and the solvent was removed by rotary evaporator. After column chromatography separation (200-300 mesh), elution was performed with a mixed solvent of n-hexane: dichloromethane in a volume ratio of 1:1 as the eluent, and the eluent containing the target product was collected. After the eluent was removed by rotary evaporation, the target product 2,9-di-n-butyl-1,10-phenanthroline compound shown in Formula I-1 was obtained. The compound was a beige solid with a yield of 2.7g, a HPLC purity of 99.3%, and a yield of 66%.

[0035] Example 2: Preparation of 2,9-di-n-pentyl-1,10-phenanthroline compound:

[0036]

[0037] The 2,9-di-n-pentyl-1,10-phenanthroline compound represented by formula I-2 of the present invention is prepared specifically according to the following method:

[0038] Under nitrogen protection, 1,10-phenanthroline (2.5 g, 13.87 mmol) was added to a three-necked flask equipped with a magnetic rod, and then 100 mL of dry tetrahydrofuran (THF) solvent was added. 32 mL of heptane solution of n-pentyl lithium (n-pentyl lithium concentration was 1.3 M, and the amount of n-pentyl lithium substance was 42 mmol) was slowly added dropwise with a syringe to obtain a deep red solution. After stirring at room temperature for 18 hours, the reaction was quenched with ice water and extracted with dichloromethane (3×100 mL). The organic phases were combined and an excess of MnO2 (9.56 g, 110 mmol) was added for oxidation. After the reaction was stirred for 1 hour, anhydrous Na2SO4 (14.2 g, 100 mmol) was added to the reaction solution, and stirring was continued at room temperature for 2 hours. After the reaction of 1,10-phenanthroline was completed by TLC monitoring (petroleum ether to ethyl acetate was 5:1), 30g (100-200 mesh) silica gel was added to the reaction solution, and the solvent was removed by rotary evaporator. After column chromatography separation (200-300 mesh), elution was performed with a mixed solvent of n-hexane: dichloromethane in a volume ratio of 1:1 as an eluent, and the eluent containing the target product was collected. After the eluent was removed by rotary evaporation, the target product 2,9-di-n-pentyl-1,10-phenanthroline compound shown in Formula I-2 was obtained. The compound was an off-white solid with a yield of 2.6g, a HPLC purity of 99.0%, and a yield of 60%.

[0039] Example 3: Preparation of 2,9-diphenyl-1,10-phenanthroline compound:

[0040]

[0041] The 2,9-diphenyl-1,10-phenanthroline compound represented by formula I-3 of the present invention is prepared specifically according to the following method:

[0042] Under nitrogen protection, 1,10-phenanthroline (2.5 g, 13.87 mmol) was added to a three-necked flask equipped with a magnetic rod, and then 100 mL of dry tetrahydrofuran (THF) solvent was added, and 42 mL of phenyl lithium ether solution (phenyl lithium concentration was 1 M, and the amount of phenyl lithium substance was 42 mmol) was slowly added dropwise with a syringe to obtain a deep red solution. After stirring at room temperature for 18 hours, the reaction was quenched with ice water and extracted with dichloromethane (3×100 mL). The organic phases were combined and an excess of MnO2 (9.56 g, 110 mmol) was added for oxidation. After stirring the reaction for 1 hour, anhydrous Na2SO4 (14.2 g, 100 mmol) was added to the reaction solution, and stirring was continued at room temperature for 2 hours. TLC monitoring (petroleum ether to ethyl acetate was 5:1) After the reaction of 1,10-phenanthroline was completed, 36 g (100-200 mesh) silica gel was added to the reaction solution, and the solvent was removed by rotary evaporator. After column chromatography separation (200-300 mesh), elution was performed with a mixed solvent of n-hexane: dichloromethane in a volume ratio of 1:1 as an eluent, and the eluent containing the target product was collected. After the eluent was removed by rotary evaporation, the target product compound shown in formula I-3 was obtained. The compound was a yellow solid with a yield of 2.1 g, a HPLC purity of 99.5%, and a yield of 46%.

[0043] Example 4: Preparation of 2,9-di-sec-butyl-1,10-phenanthroline compound:

[0044]

[0045] The 2,9-di-sec-butyl-1,10-phenanthroline compound represented by formula I-4 of the present invention is prepared specifically according to the following method:

[0046] Under nitrogen protection, 1,10-phenanthroline (2.5 g, 13.87 mmol) was added to a three-necked flask equipped with a magnetic pole, and then 100 mL of dry tetrahydrofuran (THF) solvent was added. 42 mL of sec-butyl lithium in n-hexane solution (sec-butyl lithium concentration was 1.0 M, and the amount of sec-butyl substance was 42 mmol) was slowly added dropwise with a syringe to obtain a deep red solution. After stirring at room temperature for 18 hours, the reaction was quenched with ice water and extracted with dichloromethane (3×100 mL). The organic phases were combined and an excess of MnO2 (9.56 g, 110 mmol) was added for oxidation. After the reaction was stirred for 1 hour, anhydrous Na2SO4 (14.2 g, 100 mmol) was added to the reaction solution, and stirring was continued at room temperature for 2 hours. After the reaction of 1,10-phenanthroline was completed by TLC monitoring (petroleum ether to ethyl acetate was 5:1), 30g (100-200 mesh) silica gel was added to the reaction solution, and the solvent was removed by rotary evaporator. After column chromatography separation (200-300 mesh), elution was performed with a mixed solvent of n-hexane: dichloromethane in a volume ratio of 1:1 as the eluent, and the eluent containing the target product was collected. After the eluent was removed by rotary evaporation, the target product compound shown in formula I-4 was obtained. The compound was a yellow solid with a yield of 1.4g, a HPLC purity of 99.1%, and a yield of 35%.

[0047] Example 5

[0048]

[0049] Under nitrogen protection, the new cuprous reagent (0.4mmol, 99mg), NiCl2 (0.1equiv, 0.04mmol, 5.2mg), Mn powder (10equiv, 4mmol, 220mg), and 1,1,3,3-tetramethyldisiloxane (10equiv, 4mmol, 537mg) were added to a Schlenk tube, and 1mL THF was added as a solvent. Then, the reaction was placed in a 150°C oil bath and stirred for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and 5g (100-200 mesh) silica gel was added to the reaction solution, and the solvent was removed by a rotary evaporator. After column chromatography separation (200-300 mesh), elution was performed with a mixed solvent of petroleum ether: ethyl acetate: triethylamine in a volume ratio of 200:1:1 as an eluent, and the eluent containing the target product was collected. After the eluent was removed by rotary evaporation, the target product compound shown in formula II-1 was obtained. The compound was a yellow solid with a yield of 62 mg, a HPLC purity of 98.3%, and a yield of 73%.

[0050] Characterization data: 1H NMR (500MHz, CDCl3) δ7.87(d,J=8.3Hz,1H),7.15(d,J=8.3Hz,1H),7.09(d,J=8.2Hz,1H),6.93(d,J=8.2Hz,1H),5.85(s,1H),3. 61-3.54(m,1H),3.03-2.94(m,1H),2.89-2.82(m,1H),2.67(s,3H),2.07-1.99(m,1H),1.76-1.66(m,1H),1.37(d,J=6.3Hz,3H).

[0051] Example 6

[0052]

[0053] Under nitrogen protection, 2,9-di-n-butyl-1,10-phenanthroline (0.4mmol, 121mg), NiCl2 (0.1equiv, 0.04mmol, 5.2mg), Mn powder (10equiv, 4mmol, 220mg), and 1,1,3,3-tetramethyldisiloxane (10equiv, 4mmol, 537mg) shown in formula I-1 were added to a Schlenk tube, and 1mL THF was added as a solvent. Then, the reaction was placed in a 150°C oil bath and stirred for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and 5g (100-200 mesh) silica gel was added to the reaction solution, and the solvent was removed by a rotary evaporator. After column chromatography separation (200-300 mesh), elution was performed with a mixed solvent of petroleum ether: ethyl acetate: triethylamine in a volume ratio of 200:1:1 as an eluent, and the eluent containing the target product was collected. After the eluent was removed by rotary evaporation, the target product compound represented by formula II-2 was obtained. The compound was a yellow solid with a yield of 107 mg, a HPLC purity of 99.0%, and a yield of 91%.

[0054] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.83(d,J=8.4Hz,1H),7.10(d,J=8.3Hz,1H),7.05(d,J=8.2Hz,1H),6.90(d,J=8.2Hz,1H),6.01(s,1H),3.43-3.33(m,1H),2.9 7-2.86(m,3H),2.86-2.77(m,1H),2.09-1.96(m,1H),1.83-1.75(m,2H),1 .75-1.62(m,2H),1.62-1.53(m,1H),1.52-1.34(m,6H),0.99-0.91(m,6H).

[0055] Example 7

[0056]

[0057] Under nitrogen protection, 2,9-di-n-pentyl-1,10-phenanthroline (0.4mmol, 131mg), NiCl2 (0.1equiv, 0.04mmol, 5.2mg), Mn powder (10equiv, 4mmol, 220mg), and 1,1,3,3-tetramethyldisiloxane (10equiv, 4mmol, 537mg) shown in formula I-2 were added to a Schlenk tube, and 1mL THF was added as a solvent. Then, the reaction was placed in a 150°C oil bath and stirred for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and 5g (100-200 mesh) silica gel was added to the reaction solution, and the solvent was removed by a rotary evaporator. After column chromatography (200-300 mesh), elution was performed with a mixed solvent of petroleum ether: ethyl acetate: triethylamine in a volume ratio of 200:1:1 as an eluent, and the eluent containing the target product was collected. After the eluent was removed by rotary evaporation, the target product compound represented by formula II-3 was obtained. The compound was a yellow solid with a yield of 58 mg, a HPLC purity of 97.7%, and a yield of 45%.

[0058] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.88(d,J=8.4Hz,1H),7.15(d,J=8.3Hz,1H),7.08(d,J=8.2Hz,1H),6.92(d,J=8.2Hz,1H),6.01(s,1H),3.46-3.36(m,1H),3 .00-2.81(m,4H),2.11-2.04(m,1H),1.82(m,2H),1.78-1.65(m,2H),1.6 5-1.57(m,1H),1.57-1.45(m,2H),1.43-1.32(m,8H),0.96-0.88(m,6H).

[0059] Example 8

[0060]

[0061] Under nitrogen protection, 2,9-phenyl-1,10-phenanthroline (0.4mmol, 136mg), NiCl2 (0.1equiv, 0.04mmol, 5.2mg), Mn powder (10equiv, 4mmol, 220mg), and 1,1,3,3-tetramethyldisiloxane (10equiv, 4mmol, 537mg) shown in formula I-3 were added to a Schlenk tube, and 1mL THF was added as a solvent. Then, the reaction was placed in a 150°C oil bath and stirred for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and 5g (100-200 mesh) silica gel was added to the reaction solution, and the solvent was removed by a rotary evaporator. After column chromatography separation (200-300 mesh), elution was performed with a mixed solvent of petroleum ether: ethyl acetate: triethylamine in a volume ratio of 200:1:1 as an eluent, and the eluent containing the target product was collected. After the eluent was removed by rotary evaporation, the target product compound represented by formula II-4 was obtained. The compound was a yellow solid with a yield of 71 mg, a HPLC purity of 98.4%, and a yield of 53%.

[0062] Characterization data: 1 H NMR (500MHz, CDCl3) δ8.16-8.11(m,3H),7.83(d,J=8.5Hz,1H),7.51-7.47(m,4H),7.44-7.38(m,3H),7.35-7.30(m,1H),7.20(d,J=8.2Hz,1H),7. 06(d,J=8.2Hz,1H),6.49(s,1H),4.75(dd,J1=8.0Hz,J2=3.5Hz,1H),3.0 9-3.01(m,1H),2.91-2.83(m,1H),2.33-2.26(m,1H),2.19-2.08(m,1H).

[0063] Example 9

[0064]

[0065] Under nitrogen protection, 2,9-sec-butyl-1,10-phenanthroline (0.4mmol, 120mg), NiCl2 (0.1equiv, 0.04mmol, 5.2mg), Mn powder (10equiv, 4mmol, 220mg), and 1,1,3,3-tetramethyldisiloxane (10equiv, 4mmol, 537mg) shown in formula I-4 were added to a Schlenk tube, and 1mL THF was added as a solvent. Then, the reaction was placed in a 150°C oil bath and stirred for 12 hours. After the reaction was completed, the reaction solution was cooled to room temperature, and 5g (100-200 mesh) silica gel was added to the reaction solution, and the solvent was removed by a rotary evaporator. After column chromatography (200-300 mesh), elution was performed with a mixed solvent of petroleum ether: ethyl acetate: triethylamine in a volume ratio of 200:1:1 as an eluent, and the eluent containing the target product was collected. After the eluent was removed by rotary evaporation, the target product compound represented by formula II-5 was obtained. The compound was a yellow solid with a yield of 79 mg, a HPLC purity of 98.0%, and a yield of 67%.

[0066] Characterization data: 1 H NMR (500MHz, CDCl3) δ7.89 (d, J = 8.4Hz, 1H), 7.15 (d, J = 8.5Hz, 1H), 7.08 (d, J = 8. 2Hz,1H),6.92(d,J=8.2Hz,1H),6.08(s,1H),3.39-3.27(m,1H),3.02-2.82(m,3 H),2.06-1.97(m,1H),1.93-1.76(m,2H),1.75-1.60(m,3H),1.34(dd,J1=6.9Hz ,J2=1.4Hz,4H),1.07(d,J=6.7Hz,2H),1.04-0.97(m,4H),0.88(t,J=7.4Hz,3H).

[0067] Example 10

[0068]

[0069] The method described in Example 5 was followed, except that the amount of catalyst NiCl2 used was (1 eq, 0.4 mmol, 52 mg). The target product, compound represented by formula II-1, was obtained as a yellow solid with a yield of 55 mg, a HPLC purity of 98.1%, and a yield of 65%.

[0070] Embodiment 11

[0071]

[0072] The method described in Example 5 was followed, except that the amount of reducing agent A Mn powder used was (1 equiv, 0.4 mmol, 22 mg). The target product, compound represented by formula II-1, was obtained as a yellow solid with a yield of 30 mg, a HPLC purity of 98.8%, and a yield of 35%.

[0073] Example 12

[0074]

[0075] The method described in Example 5 was followed, except that the amount of reducing agent B1,1,3,3-tetramethyldisiloxane used was (5 equiv, 2 mmol, 269 mg). The target product, compound represented by formula II-1, was obtained as a yellow solid with a yield of 48 mg, a HPLC purity of 99.0%, and a yield of 57%.

[0076] Example 13

[0077]

[0078] The method described in Example 5 was followed, except that the catalyst was NiBr2 (0.1 eq, 0.04 mmol, 8.7 mg). The target product, compound represented by formula II-1, was obtained as a yellow solid with a yield of 59 mg, a HPLC purity of 98.7%, and a yield of 70%.

[0079] Embodiment 14

[0080]

[0081] The method described in Example 5 was followed, except that the reducing agent A was tin powder (10 equiv, 4 mmol, 474 mg). The target product, compound represented by formula II-1, was obtained as a yellow solid with a HPLC purity of 49 mg, 98.7%, and a yield of 58%.

[0082] Embodiment 15

[0083]

[0084] The method described in Example 5 was followed, except that the reducing agent B was phenylsilane (10 equiv, 4 mmol, 432 mg), to obtain the target product, the compound of formula II-1, which was a yellow solid, with a yield of 36 mg, HPLC purity of 98.0%, and a yield of 42%.

[0085] Example 16

[0086]

[0087] The method described in Example 5 was followed, except that the reducing agent B was triethylsilane (10 equiv, 4 mmol, 465 mg), to obtain the target product, the compound of formula II-1, which was a yellow solid, with a yield of 52 mg, a HPLC purity of 98.5%, and a yield of 61%.

[0088] Embodiment 17

[0089]

[0090] The method described in Example 5 was followed, except that the organic solvent was 1 mL of toluene, to obtain the target product, a compound represented by formula II-1, which was a yellow solid with a yield of 50 mg, a HPLC purity of 98.9%, and a yield of 59%.

[0091] Embodiment 18

[0092]

[0093] The method described in Example 5 was followed, except that the reaction temperature was 110° C. The target product, compound represented by formula II-1, was obtained as a yellow solid with a yield of 43 mg, a HPLC purity of 98.0%, and a yield of 50%.

[0094] Embodiment 19

[0095]

[0096] The method described in Example 5 was followed, except that the reaction temperature was 130° C. The target product, compound represented by formula II-1, was obtained as a yellow solid with a yield of 52 mg, a HPLC purity of 98.6%, and a yield of 61%.

[0097] Embodiment 20

[0098]

[0099] The method described in Example 5 was followed, except that the reaction time was 6 h to obtain the target product, a compound represented by formula II-1, which was a yellow solid with a yield of 41 mg, a HPLC purity of 99.0%, and a yield of 48%.

[0100] Embodiment 21

[0101]

[0102] The method described in Example 5 was followed, except that the protective atmosphere was argon, to obtain the target product, compound represented by formula II-1, which was a yellow solid with a yield of 62 mg, a HPLC purity of 99.3%, and a yield of 73%.

Claims

1. A method for preparing a 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compound, characterized in that: The following steps are involved: Under a protective atmosphere, a 2,9-substituted phenanthroline compound represented by formula (I), a catalyst, a reducing agent A, and a reducing agent B are mixed and added to an organic solvent, and stirred at 150° C. for 12 hours. The resulting reaction solution is post-treated to obtain a 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compound represented by formula (II); In formula (I) or formula (II), R is a C1-C5 alkyl group or a phenyl group; The molar ratio of the 2,9-substituted phenanthroline compound represented by formula (I), the catalyst, the reducing agent A, and the reducing agent B is 1:0.1:10:10; The catalyst is NiCl2 or NiBr2; The reducing agent A is Mn powder; The reducing agent B is 1,1,3,3-tetramethyldisiloxane; The organic solvent is tetrahydrofuran.

2. The method for preparing 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compounds according to claim 1, characterized in that: The R is methyl, n-butyl, n-pentyl, sec-butyl or phenyl.

3. The method for preparing 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compounds according to claim 1, characterized in that: The amount of the organic solvent added is 2.5 ml / mmol based on the amount of the 2,9-substituted phenanthroline compound represented by formula (I).

4. The method for preparing 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compounds according to claim 1, characterized in that: The protective atmosphere is one of nitrogen and argon.

5. The method for preparing 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compounds according to claim 1, characterized in that: The post-treatment comprises: after the reaction is completed, cooling the reaction solution to room temperature, adding 100-200 mesh silica gel, removing the solvent by a rotary evaporator, and then performing column chromatography separation, eluting with a mixed solvent of petroleum ether, ethyl acetate and triethylamine in a volume ratio of 200:1:1 as an eluent, collecting the eluate containing the target product, and removing the eluent by rotary evaporation to obtain the target product 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compound shown in formula (II); the ratio of the mass of the silica gel to the sum of the mass of the 2,9-substituted phenanthroline compound shown in formula (I), the catalyst, the reducing agent A and the reducing agent B is 5-10:

1.

6. The method for preparing 2,9-disubstituted-1,2,3,4-tetrahydro-1,10-phenanthroline compounds according to claim 1, characterized in that: The 2,9-substituted phenanthroline compound represented by formula (I) is prepared according to the following method: Under the protection of nitrogen and magnetic stirring, 1,10-phenanthroline and dry tetrahydrofuran solvent are added, and then a lithium reagent is added dropwise to obtain a deep red solution. After stirring and reacting at room temperature for 18 hours, the solution is quenched with ice water, extracted with dichloromethane, and the organic phases are combined. MnO2 is added for oxidation, and the stirring reaction is continued for 1 hour. Anhydrous Na2SO4 is added to the reaction solution, and the solution is fully stirred at room temperature. After the reaction of 1,10-phenanthroline is completed, 100-200 mesh silica gel is added, and the solvent is removed by rotary evaporation. Column chromatography is performed using a mixed solvent of n-hexane and dichloromethane in a volume ratio of 1:1 as an eluent, and the eluent containing the target product is collected. After the eluent is removed by rotary evaporation, a 2,9-substituted phenanthroline compound shown in formula (I) is obtained; The molar ratio of 1,10-phenanthroline, lithium reagent, MnO2, and anhydrous Na2SO4 is: 1:2-3.5:5-8:5-10; The lithium reagent is selected from one of n-butyllithium reagent, n-pentyllithium reagent, phenyllithium reagent and sec-butyllithium reagent; The volume of the tetrahydrofuran is 40 ml / g based on the mass of 1,10-phenanthroline.

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