Preparation method of 10, 10-diphenylsilaacridine
阅读说明：本技术 一种10,10-二苯基硅杂吖啶的制备方法 (Preparation method of 10, 10-diphenylsilaacridine ) 是由 吴绵园 吕宏飞 徐虹 李猛 梅立鑫 于 2021-08-23 设计创作，主要内容包括：一种10,10-二苯基硅杂吖啶的制备方法,它属于精细化工领域。本发明要解决的技术问题为实现成本低、反应条件温和、收率高、易工业化的工艺方法。本发明是以2-溴苯胺为原料,通过Buchwald-Hartwig偶联、氨基保护、有机锂试剂脱卤素关环和氨基保护基的脱除反应,在一定压力的氢气气氛下,按照一定的料液比向高压反应釜中加入N-苄基-10,10-二苯基硅杂吖啶、催化剂和溶剂,室温反应,反应结束后过滤,减压脱除溶剂,重结晶得到10,10-二苯基硅杂吖啶。与现有技术相比,原料成本低、合成收率高、产品易于纯化,反应总收率达48.1％,适用于工业化生产。(A preparation method of 10, 10-diphenylsilaacridine, which belongs to the field of fine chemical engineering. The technical problem to be solved by the invention is to realize a process method which has low cost, mild reaction condition, high yield and easy industrialization. The method comprises the steps of taking 2-bromoaniline as a raw material, carrying out Buchwald-Hartwig coupling, amino protection, dehalogenation cyclization by an organic lithium reagent and removal reaction of an amino protecting group, adding N-benzyl-10, 10-diphenylsilaacridine, a catalyst and a solvent into a high-pressure reaction kettle according to a certain feed-liquid ratio under a hydrogen atmosphere with a certain pressure, reacting at room temperature, filtering after the reaction is finished, removing the solvent under reduced pressure, and recrystallizing to obtain the 10, 10-diphenylsilaacridine. Compared with the prior art, the method has the advantages of low raw material cost, high synthesis yield, easy purification of products, total reaction yield up to 48.1 percent and suitability for industrial production.)
1. A preparation method of 10, 10-diphenylsilaacridine is characterized by comprising the following steps:
step 1, preparing bis (2-bromophenyl) amine:
under the protection of nitrogen, adding 2-bromoaniline, 1-bromo-2-iodobenzene, sodium tert-butoxide, tris (dibenzylideneacetone) dipalladium, 1' -bis (diphenylphosphino) ferrocene and toluene in a certain material-to-liquid ratio into a reaction vessel for reflux reaction, adding an ammonium chloride aqueous solution after the reflux reaction for washing, carrying out reduced pressure concentration, and recrystallizing to obtain bis (2-bromophenyl) amine;
step 2, preparing N, N-bis (2-bromophenyl) benzylamine:
under the protection of nitrogen, adding bis (2-bromophenyl) amine, alkali, tetrabutylammonium bromide and tetrahydrofuran in a certain material-to-liquid ratio into a reaction vessel, stirring at constant temperature for a certain time, dropwise adding benzyl bromide, carrying out reflux reaction, adding water after the reflux reaction, removing the tetrahydrofuran under reduced pressure, filtering, drying, and then carrying out recrystallization to obtain N, N-bis (2-bromophenyl) benzylamine;
step 3, preparing N-benzyl-10, 10-diphenylsilaacridine:
under the protection of nitrogen, adding N, N-bis (2-bromophenyl) benzylamine and diethyl ether in a certain material-to-liquid ratio into a reaction container, cooling to-70-0 ℃, dropwise adding N-BuLi N-hexane solution, preserving heat for a certain time after dropwise adding, dropwise adding diethyl ether solution of diphenyldichlorosilane again, reacting at room temperature after dropwise adding, washing with water after the reaction is finished, concentrating under reduced pressure, and recrystallizing to obtain N-benzyl-10, 10-diphenylsilaacridine;
step 4, preparing 10, 10-diphenylsilaacridine:
adding N-benzyl-10, 10-diphenylsilaacridine, a catalyst and a solvent into a high-pressure reaction kettle according to a certain material-liquid ratio under a hydrogen atmosphere with a certain pressure, reacting at room temperature, filtering after the reaction is finished, removing the solvent under reduced pressure, and recrystallizing to obtain the 10, 10-diphenylsilaacridine.
2. The method for preparing 10, 10-diphenylsilacridine as claimed in claim 1, wherein: in step 1, 2-bromoaniline, 1-bromo-2-iodobenzene, sodium tert-butoxide and Pd2DBA3And the feed-liquid ratio of the DPPF to the toluene is 86.0-90 g: 155.6-160.0 g: 72.1-75.0 g: 2.7-3.0 g: 6.4-7.0 g: 1000-1200 mL, the reflux reaction temperature is 102-108 ℃, and the reflux reaction time is 10-12 h.
3. The method for preparing 10, 10-diphenylsilacridine as claimed in claim 1 or 2, wherein: in the step 1, the concentration of the ammonium chloride aqueous solution is 10-12 wt%, and the recrystallization solvent is one of cyclohexane, normal hexane, benzene and petroleum ether.
4. The method for preparing 10, 10-diphenylsilacridine as claimed in claim 3, wherein: in the step 2, the feed-liquid ratio of bis (2-bromophenyl) amine, alkali, tetrabutylammonium bromide and tetrahydrofuran is 98.1-100.0 g: 37.0-40.0 g: 9.7-10.0 g: 600-650 mL, keeping the temperature at 25-30 ℃, stirring for 4-5 h, wherein the mass ratio of the added benzyl bromide to the bis (2-bromophenyl) amine is 61.6-65.0 g: 98.1-100.0 g, wherein the alkali is one of sodium hydroxide, potassium hydroxide, sodium tert-butoxide and potassium tert-butoxide.
5. The method for preparing 10, 10-diphenylsilacridine as claimed in claim 4, wherein: dissolving benzyl bromide in tetrahydrofuran with the volume of 3-5 times, slowly dropwise adding the benzyl bromide into a reaction system, after the addition is finished, heating to 60-65 ℃ for reflux reaction for 4-5 hours, after the reaction, adding water with the volume of 3-5 times of benzyl bromide, wherein a recrystallization solvent is a mixed solvent of trichloromethane and normal hexane, the recrystallization temperature is-20-15 ℃ for crystallization, and the volume ratio of the trichloromethane to the normal hexane in the recrystallization solvent is 1:3 to 5.
6. The method for preparing 10, 10-diphenylsilacridine as claimed in claim 5, wherein: in the step 3, the feed-liquid ratio of the N, N-bis (2-bromophenyl) benzylamine to the diethyl ether to the N-BuLi N-hexane solution to the diphenyl dichlorosilane diethyl ether solution is 83.4-100.0 g: 1000-1200 mL: 184-200 mL: 300mL, the concentration of the n-BuLi n-hexane solution is 2.5M, and the ether solution of the diphenyldichlorosilane is prepared by dissolving 58.2g of diphenyldichlorosilane in 300mL of ether; and 3, dropwise adding n-BuLi n-hexane solution for 0.5-1.5 h, preserving heat for 1.0-1.5 h after dropwise adding, dropwise adding diphenyl dichlorosilane ether solution for 1.0-1.5 h again, preserving heat for 1.0-1.5 h after dropwise adding, then heating to room temperature, and stirring for reaction for 10-12 h.
7. The method for preparing 10, 10-diphenylsilacridine as claimed in claim 6, wherein: and 3, recrystallizing in a mixed solvent of tetrahydrofuran and ethanol, wherein the volume ratio of tetrahydrofuran to ethanol is 1: 3-5, and the recrystallization temperature is 0-5 ℃.
8. The method for preparing 10, 10-diphenylsilacridine as claimed in claim 7, wherein: in the step 4, the catalyst is one of 5 wt% Pd/C and 10 wt% Pd/C, Pearlman's catalyst, and the solvent is one of a mixed solution of trichloromethane and methanol, a mixed solution of trichloromethane and ethanol, a mixed solution of trichloromethane and isopropanol, a mixed solution of dichloromethane and methanol, a mixed solution of dichloromethane and ethanol, and a mixed solution of dichloromethane and isopropanol.
9. The method for preparing 10, 10-diphenylsilacridine as claimed in claim 8, wherein: in the step 4, the feed-liquid ratio of the N-benzyl-10, 10-diphenylsilaacridine, the catalyst and the solvent is 44.0-50.0 g: 4.4-5.0 g and 600-800 ml, and reacting at room temperature for 10-12 h under the hydrogen atmosphere pressure of one of normal pressure, 0.2MPa, 0.5MPa and 1.0 MPa.
10. The method for preparing 10, 10-diphenylsilacridine as claimed in claim 9, wherein: in the step 4, the recrystallization solvent is one of methanol, ethanol and isopropanol, and the recrystallization temperature is-20 to-15 ℃.
Technical Field
The invention belongs to the field of fine chemical engineering, and particularly relates to a preparation method of 10, 10-diphenylsilacridine.
Background
In recent years, a third generation organic light emitting material, i.e., a Thermally Activated Delayed Fluorescence (TADF), following an organic fluorescent material and an organic phosphorescent material has been rapidly developed. The material generally has smaller singlet state-triplet state energy level difference, and triplet state excitons can be converted into singlet state excitons through reverse intersystem crossing under the conditions of environmental heat and the like, so as to radiate and emit light. Compared with conventional fluorescent and phosphorescent materials, the TADF material can fully utilize singlet excitons and triplet excitons formed under electrical excitation, the internal quantum efficiency of the device can reach 100%, and also has higher luminous efficiency.
Silicon-containing heterocyclic organic donor units have attracted attention during the development of TADF materials. This is because the introduction of silicon atoms into the organic photoelectric material can significantly change the electronic structure and state of the compound, so that the compound has a lower LUMO energy level; on the other hand, the silicon-containing heterocyclic compound has more modification sites, better solubility and film-forming property, does not need harsh reaction conditions in synthesis, and the TADF material combining the silicon-containing heterocyclic compound with an acceptor unit shows excellent characteristics of high efficiency, long service life and the like. The TADF material constructed by using 10, 10-diphenylsilaacridine as a donor unit obtains excellent device performance in application, and is an important intermediate of the TADF material.
At present, the production of 10, 10-diphenylsilacridine is limited to gram-grade products customized in a laboratory, and reports on the preparation method of 10, 10-diphenylsilacridine are less. Sun JW et al (Chemistry of materials: Apublic acid amide Chemistry society,2015, Vol.27, No. 19, pp.6675-6681) and patent application JP2013/063497 all used 4-methoxybenzyl as amino protecting group and finally 10, 10-diphenylsilaacridine was prepared by oxidative removal of the amino protecting group by 2, 3-dichloro-5, 6-dicyano-benzoquinone (DDQ). The preparation route has the defects that strong base NaH is required in the amino protection reaction, DMF is used as a solvent, the reaction condition is harsh, and the post-treatment is difficult; in the reaction for removing the amino protecting group, a plurality of byproducts are generated, and the separation and purification are difficult; the total reaction yields are respectively 11.3% and 32.7%, and the separation and purification are refined by column chromatography, so that the industrial production is difficult.
Disclosure of Invention
The invention aims to provide a preparation method of 10, 10-diphenylsilaacridine, which has the advantages of low cost, mild reaction conditions, high yield and easy industrialization.
The invention is realized by the following technical scheme:
a preparation method of 10, 10-diphenylsilaacridine comprises the following steps:
step 1, preparing bis (2-bromophenyl) amine:
under the protection of nitrogen, adding 2-bromoaniline, 1-bromo-2-iodobenzene, sodium tert-butoxide, tris (dibenzylideneacetone) dipalladium, 1' -bis (diphenylphosphino) ferrocene and toluene in a certain material-to-liquid ratio into a reaction vessel for reflux reaction, adding an ammonium chloride aqueous solution after the reflux reaction for washing, carrying out reduced pressure concentration, and recrystallizing to obtain bis (2-bromophenyl) amine;
step 2, preparing N, N-bis (2-bromophenyl) benzylamine:
under the protection of nitrogen, adding bis (2-bromophenyl) amine, alkali, tetrabutylammonium bromide and tetrahydrofuran in a certain material-to-liquid ratio into a reaction vessel, stirring at constant temperature for a certain time, dropwise adding benzyl bromide, carrying out reflux reaction, adding water after the reflux reaction, removing the tetrahydrofuran under reduced pressure, filtering, drying, and then carrying out recrystallization to obtain N, N-bis (2-bromophenyl) benzylamine;
step 3, preparing N-benzyl-10, 10-diphenylsilaacridine:
under the protection of nitrogen, adding N, N-bis (2-bromophenyl) benzylamine and diethyl ether in a certain material-to-liquid ratio into a reaction container, cooling to-70-0 ℃, dropwise adding N-BuLi N-hexane solution, preserving heat for a certain time after dropwise adding, dropwise adding diethyl ether solution of diphenyldichlorosilane again, reacting at room temperature after dropwise adding, washing with water after the reaction is finished, concentrating under reduced pressure, and recrystallizing to obtain N-benzyl-10, 10-diphenylsilaacridine;
step 4, preparing 10, 10-diphenylsilaacridine:
adding N-benzyl-10, 10-diphenylsilaacridine, a catalyst and a solvent into a high-pressure reaction kettle according to a certain material-liquid ratio under a hydrogen atmosphere with a certain pressure, reacting at room temperature, filtering after the reaction is finished, removing the solvent under reduced pressure, and recrystallizing to obtain the 10, 10-diphenylsilaacridine.
The invention relates to a 10, 10-diThe preparation method of phenyl silacridine comprises the steps of 1, 2-bromoaniline, 1-bromo-2-iodobenzene, sodium tert-butoxide and Pd2DBA3And the feed-liquid ratio of the DPPF to the toluene is 86.0-90 g: 155.6-160.0 g: 72.1-75.0 g: 2.7-3.0 g: 6.4-7.0 g: 1000-1200 mL, the reflux reaction temperature is 102-108 ℃, and the reflux reaction time is 10-12 h.
The preparation method of 10, 10-diphenylsilaacridine comprises the step 1, wherein the concentration of an ammonium chloride aqueous solution is 10-12 wt%, and a recrystallization solvent is one of cyclohexane, n-hexane, benzene and petroleum ether.
The invention relates to a preparation method of 10, 10-diphenylsilaacridine, wherein in the step 2, the feed-liquid ratio of bis (2-bromophenyl) amine, alkali, tetrabutylammonium bromide and tetrahydrofuran is 98.1-100.0 g: 37.0-40.0 g: 9.7-10.0 g: 600-650 mL, keeping the temperature at 25-30 ℃, stirring for 4-5 h, wherein the mass ratio of the added benzyl bromide to the bis (2-bromophenyl) amine is 61.6-65.0 g: 98.1-100.0 g, wherein the alkali is one of sodium hydroxide, potassium hydroxide, sodium tert-butoxide and potassium tert-butoxide.
The preparation method of 10, 10-diphenylsilaacridine comprises the following steps of 2, dissolving benzyl bromide in tetrahydrofuran with the volume of 3-5 times, then slowly dropwise adding the mixture into a reaction system, heating to 60-65 ℃ after the addition is finished, carrying out reflux reaction for 4-5 hours, adding water with the volume of 3-5 times that of the benzyl bromide after the reaction is finished, wherein a recrystallization solvent is a mixed solvent of trichloromethane and n-hexane, the recrystallization temperature is-20-15 ℃ for crystallization, and the volume ratio of the trichloromethane to the n-hexane in the recrystallization solvent is 1:3 to 5.
The invention relates to a preparation method of 10, 10-diphenylsilaacridine, in step 3, the feed-to-liquid ratio of N, N-bis (2-bromophenyl) benzylamine, diethyl ether, N-BuLi normal hexane solution and diphenyl dichlorosilane diethyl ether solution is 83.4-100.0 g: 1000-1200 mL: 184-200 mL: 300mL, the concentration of the n-BuLi n-hexane solution is 2.5M, and the ether solution of the diphenyldichlorosilane is prepared by dissolving 58.2g of diphenyldichlorosilane in 300mL of ether; and 3, dropwise adding n-BuLi n-hexane solution for 0.5-1.5 h, preserving heat for 1.0-1.5 h after dropwise adding, dropwise adding diphenyl dichlorosilane ether solution for 1.0-1.5 h again, preserving heat for 1.0-1.5 h after dropwise adding, then heating to room temperature, and stirring for reaction for 10-12 h.
According to the preparation method of 10, 10-diphenylsilaacridine, a recrystallization solvent in the step 3 is a mixed solvent of tetrahydrofuran and ethanol, wherein the volume ratio of tetrahydrofuran to ethanol is 1: 3-5, and the recrystallization temperature is 0-5 ℃.
In the preparation method of 10, 10-diphenylsilaacridine, the catalyst in the step 4 is one of 5 wt% Pd/C and 10 wt% Pd/C, Pearlman's catalyst, and the solvent is one of a mixed solution of trichloromethane and methanol, a mixed solution of trichloromethane and ethanol, a mixed solution of trichloromethane and isopropanol, a mixed solution of dichloromethane and methanol, a mixed solution of dichloromethane and ethanol, and a mixed solution of dichloromethane and isopropanol.
The invention relates to a preparation method of 10, 10-diphenylsilacridine, wherein in the step 4, the feed-liquid ratio of N-benzyl-10, 10-diphenylsilacridine, catalyst and solvent is 44.0-50.0 g: 4.4-5.0 g and 600-800 ml, and reacting at room temperature for 10-12 h under the hydrogen atmosphere pressure of one of normal pressure, 0.2MPa, 0.5MPa and 1.0 MPa.
According to the preparation method of 10, 10-diphenylsilaacridine, a recrystallization solvent in the step 4 is one of methanol, ethanol and isopropanol, and the recrystallization temperature is-20 to-15 ℃.
According to the preparation method of 10, 10-diphenylsilacridine, the amino protecting group is benzyl, and the protecting group reagent, namely benzyl bromide, is low in cost and easy to store.
According to the preparation method of 10, 10-diphenylsilaacridine, the protection and removal reaction conditions of benzyl protecting groups are milder, the reaction selectivity is good, and the purification treatment is easy.
According to the preparation method of 10, 10-diphenylsilaacridine, the intermediate and the target product are purified by a recrystallization method, and the operation is simple and convenient.
The preparation method of 10, 10-diphenylsilaacridine has the advantages of low cost, easy operation, high yield and easy industrial production, and the total reaction yield reaches 48.1%.
Drawings
FIG. 1 is a synthetic route of a preparation method of 10, 10-diphenylsilaacridine according to the invention;
FIG. 2 is a high performance liquid chromatogram of bis (2-bromophenyl) amine prepared by the method for preparing 10, 10-diphenylsilaacridine according to the first embodiment;
FIG. 3 is a nuclear magnetic resonance spectrum of bis (2-bromophenyl) amine prepared by the method for preparing 10, 10-diphenylsilaacridine according to the first embodiment;
FIG. 4 is a high performance liquid chromatogram of N, N-bis (2-bromophenyl) benzylamine prepared by the method for preparing 10, 10-diphenylsilacridine according to the first embodiment;
FIG. 5 is a nuclear magnetic resonance spectrum of N, N-bis (2-bromophenyl) benzylamine prepared by the method for preparing 10, 10-diphenylsilacridine according to the first embodiment;
FIG. 6 is a high performance liquid chromatogram of N-benzyl-10, 10-diphenylsilacridine prepared by the method for preparing 10, 10-diphenylsilacridine according to the first embodiment;
FIG. 7 is a nuclear magnetic hydrogen spectrum of N-benzyl-10, 10-diphenylsilacridine prepared by the method for preparing 10, 10-diphenylsilacridine according to the first embodiment;
FIG. 8 is a high performance liquid chromatogram of 10, 10-diphenylsilacridine prepared by the method for preparing 10, 10-diphenylsilacridine according to the first embodiment;
FIG. 9 is a nuclear magnetic hydrogen spectrum of 10, 10-diphenylsilacridine prepared by the method for preparing 10, 10-diphenylsilacridine according to the first embodiment;
FIG. 10 is a nuclear magnetic carbon spectrum of 10, 10-diphenylsilacridine prepared by the method for preparing 10, 10-diphenylsilacridine according to the first embodiment.
Detailed Description
The following is a detailed description of the embodiments and specific procedures of the present invention, but the scope of the present invention is not limited to the following examples.
The first embodiment is as follows:
a preparation method of 10, 10-diphenylsilaacridine comprises the following steps:
step 1, preparing bis (2-bromophenyl) amine:
86.0g of 2-bromoaniline, 155.6g of 1-bromo-2-iodobenzene, 72.1g of sodium tert-butoxide and Pd are added into a three-necked bottle under the nitrogen atmosphere2DBA32.7g, 6.4g of DPPF and 1000mL of toluene, heating to 108 ℃ for reflux reaction, monitoring the reaction process by HPLC (high performance liquid chromatography), when the reaction lasts for 10 hours, completely reacting 2-bromoaniline, cooling the reaction solution to room temperature, adding 500mL of 10 wt% ammonium chloride aqueous solution, removing an aqueous layer, extracting the aqueous layer with toluene, combining organic layers, drying with anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and recrystallizing with n-hexane to obtain bis (2-bromophenyl) amine;
step 2, preparing N, N-bis (2-bromophenyl) benzylamine:
under the atmosphere of nitrogen, 98.1g of bis (2-bromophenyl) amine, 37.0g of potassium hydroxide, 9.7g of tetrabutylammonium bromide and 600mL of tetrahydrofuran are added into a three-necked bottle, the mixture is kept at 30 ℃ and stirred for 4 hours, reaction liquid is light yellow paste, 61.6g of benzyl bromide is dissolved in 300mL of tetrahydrofuran and slowly dripped into a reaction system, after the addition is finished, the temperature is raised to 65 ℃ for reflux reaction, the reaction process is monitored by HPLC (high performance liquid chromatography), the raw materials are completely reacted when the reaction is carried out for 4 hours, 300mL of water is added after the reaction is finished, the tetrahydrofuran is removed under reduced pressure, white-like solid is obtained by filtering and drying, and mixed solvent (V is mixed solventTrichloromethane:VN-hexaneDissolving the compound (1: 3), cooling to-20 ℃ and crystallizing to obtain N, N-bis (2-bromophenyl) benzylamine;
step 3, preparing N-benzyl-10, 10-diphenylsilaacridine:
adding 83.4g of N, N-bis (2-bromophenyl) benzylamine and 1000mL of diethyl ether into a three-necked bottle under the atmosphere of nitrogen, cooling to-10 ℃, keeping the system to be white suspension, dripping 184mL of 2.5M N-BuLi N-hexane solution for 0.5h, keeping the temperature for 1.0h after finishing dripping, finally changing the system state from the white suspension to yellow viscous liquid through orange clear liquid, dissolving 58.2g of diphenyldichlorosilane into 300mL of diethyl ether, keeping the temperature to-10 ℃, dripping into the reaction system for 1.0h, keeping the temperature for 1.0h after finishing adding, and then slowly adding the diphenyldichlorosilane into the reaction systemHeating to room temperature, stirring overnight, monitoring by HPLC for complete reaction of raw materials, changing yellow viscous liquid into white suspension, washing with water after reaction, removing solvent under reduced pressure, and mixing with solvent (V)Tetrahydrofuran (THF):VEthanolDissolving the compound 1:3), cooling to 0 ℃, and crystallizing to obtain N-benzyl-10, 10-diphenylsilaacridine;
step 4, preparing 10, 10-diphenylsilaacridine:
adding 44.0g of N-benzyl-10, 10-diphenylsilaacridine, 4.4g of Pearlman's catalyst, 300mL of dichloromethane and 300mL of absolute ethanol into a high-pressure reaction kettle under the atmosphere of normal-pressure hydrogen, reacting at room temperature, monitoring the reaction process by HPLC, completely reacting the raw materials when reacting for 10 hours, filtering the Pearlman's catalyst, removing the solvent under reduced pressure, and recrystallizing the ethanol to obtain the 10, 10-diphenylsilaacridine.
In the preparation method of 10, 10-diphenylsilacridine according to the embodiment, bis (2-bromophenyl) amine prepared in step 1 is a white solid, the yield is 151.3g, the purity is 99.05%, and the yield is 92.5%. Fig. 2 is a high performance liquid chromatogram of bis (2-bromophenyl) amine prepared by the preparation method of 10, 10-diphenylsilaacridine according to the embodiment, and the detection conditions are high performance liquid detection chromatographic conditions: waters Symmetry C18 column, UV detection wavelength: 254nm, mobile phase: methanol-water (90: 10 by volume), flow rate: 1.0mL/min, column temperature: 35 ℃, sample introduction: 10 mu L of the solution; FIG. 3 is a nuclear magnetic spectrum of bis (2-bromophenyl) amine prepared by the method for preparing 10, 10-diphenylsilaacridine according to the embodiment, and the obtained detection result is1H NMR(300MHz，CDCl3):δ(ppm)7.44(dd，J＝8.0,1.4Hz，2H)，7.16(dd，J＝8.2，1.6Hz，2H)，7.11-7.00(m，2H)，6.74-6.61(m，2H)，6.42(s，1H)。
In the preparation method of 10, 10-diphenylsilaacridine according to the embodiment, N-bis (2-bromophenyl) benzylamine prepared in step 2 is a white solid, the yield is 108.9g, the purity is 99.29%, and the yield is 87.0%. Fig. 4 is a high performance liquid chromatogram of N, N-bis (2-bromophenyl) benzylamine prepared by the method for preparing 10, 10-diphenylsilaacridine according to the embodiment, and high performance liquid detection chromatographic conditions: waters Symmetry C18 column, UV testMeasuring the wavelength: 254nm, mobile phase: methanol-water (90: 10 by volume), flow rate: 1.0mL/min, column temperature: 35 ℃, sample introduction: 10 μ L. FIG. 5 shows the NMR spectrum of N, N-bis (2-bromophenyl) benzylamine prepared by the method for preparing 10, 10-diphenylsilaacridine according to the embodiment, and the obtained detection result is1H NMR(300MHz,DMSO-d6):δ(ppm)7.61(dd,J＝7.9,1.4Hz,2H),7.53(d,J＝7.2Hz,2H),7.26(t,J＝7.1Hz,4H),7.15(dd,J＝8.3,6.3Hz,1H),7.09-6.93(m,4H),4.79(s,2H)。
In the method for preparing 10, 10-diphenylsilacridine according to the embodiment, the N-benzyl-10, 10-diphenylsilacridine prepared in the step 3 is a white solid, the yield is 68.6g, the purity is 99.08%, and the yield is 78.0%. Fig. 6 is a high performance liquid chromatogram of N-benzyl-10, 10-diphenylsilacridine prepared by the method for preparing 10, 10-diphenylsilacridine according to the embodiment, and the high performance liquid detection chromatographic conditions are as follows: waters Symmetry C18 column, UV detection wavelength: 254nm, mobile phase: methanol-acetonitrile (30: 70 by volume), flow rate: 1.0mL/min, column temperature: 35 ℃, sample introduction: 10 μ L. FIG. 7 shows the NMR spectrum of N-benzyl-10, 10-diphenylsilacridine prepared by the method for preparing 10, 10-diphenylsilacridine according to the present embodiment, and the obtained detection result is1H NMR(300MHz,CDCl3):δ(ppm)7.58-7.55(m,4H),7.53-7.50(m,2H),7.41-7.35(m,5H),7.33-7.25(m,6H),7.23-7.20(m,2H),7.00-6.95(m,4H),5.21(s,2H)。
In the method for preparing 10, 10-diphenylsilacridine according to the embodiment, the 10, 10-diphenylsilacridine prepared in the step 4 is a white solid, the yield is 26.8g, the purity is 99.30%, and the yield is 76.6%. Fig. 8 is a high performance liquid chromatogram of 10, 10-diphenylsilacridine prepared by the preparation method of 10, 10-diphenylsilacridine, and the high performance liquid detection chromatographic conditions are as follows: waters Symmetry C18 column, UV detection wavelength: 254nm, mobile phase: methanol-water (90: 10 by volume), flow rate: 1.0mL/min, column temperature: 35 ℃, sample introduction: 10 μ L. FIG. 9 shows the nuclear magnetic hydrogen spectrum of 10, 10-diphenylsilacridine prepared by the method for preparing 10, 10-diphenylsilacridine according to the embodiment, and the detection result is1H NMR(300MHz,DMSO-d6) δ (ppm)9.44(s,1H),7.50-7.43(m,6H),7.42-7.32(m,8H),7.10(d, J ═ 8.0Hz,2H),6.88(td, J ═ 7.3,0.9Hz, 2H). FIG. 10 shows NMR spectra of 10, 10-diphenylsilacridine prepared by the method for preparing 10, 10-diphenylsilacridine according to the present embodiment, and the result of the detection is13C NMR(75MHz,DMSO-d6):δ(ppm)146.96,135.70,135.30,130.78,129.42,128.01,119.10,115.76,111.58。
The preparation method of 10, 10-diphenylsilacridine according to the embodiment has the total yield of 48.1% in four steps of 10, 10-diphenylsilacridine preparation.
In the method for preparing 10, 10-diphenylsilaacridine according to the embodiment, when the recrystallization solvent in the step 1 is one of n-hexane, benzene and petroleum ether, the purity and yield of the prepared bis (2-bromophenyl) amine product are shown in table 1:
TABLE 1 purity and yield of bis (2-bromophenyl) amine
Recrystallization solvent
Purity of
Yield of
N-hexane
99.05％
92.5％
Cyclohexane
96.62％
94.2％
Benzene and its derivatives
99.35％
43.7％
Petroleum ether
98.62％
87.6％
As can be seen from Table 1, n-hexane is preferred.
In the method for preparing 10, 10-diphenylsilaacridine according to the embodiment, when the base in the step 2 is one of sodium hydroxide, potassium hydroxide, sodium tert-butoxide and potassium tert-butoxide, the purity and yield of the prepared N, N-bis (2-bromophenyl) benzylamine are shown in table 2:
TABLE 2N, N-bis (2-bromophenyl) benzylamine purity and yield
Alkali
Purity of
Yield of
Potassium hydroxide
99.29％
87.0％
Sodium hydroxide
98.40％
82.4％
Sodium tert-butoxide
99.24％
84.6％
Tert butylPotassium alcoholate
99.33％
87.2％
As can be seen from table 2, potassium hydroxide is preferred.
In the method for preparing 10, 10-diphenylsilacridine according to this embodiment, when the temperature of step 3 is decreased to-70 ℃, -50 ℃, -30 ℃, -10 ℃, and 0 ℃, the purity and yield ratio of the prepared N-benzyl-10, 10-diphenylsilacridine are as shown in table 3:
TABLE 3 purity and yield of N-benzyl-10, 10-diphenylsilaacridine
Temperature of
Purity of
Yield of
-10℃
99.08％
78.0％
0℃
97.86％
69.5％
-30℃
99.12％
77.8％
-50℃
99.02％
78.4％
-70℃
99.10％
78.2％
As can be seen from Table 3, it is preferable that the temperature is-10 ℃.
The second embodiment is as follows:
the first difference between the present embodiment and the specific embodiment is: and 4, selecting hydrogen pressure of 0.2MPa in the process of preparing the 10, 10-diphenylsilaacridine.
The third concrete implementation mode:
the first difference between the present embodiment and the specific embodiment is: and 4, selecting hydrogen pressure of 0.5MPa in the process of preparing the 10, 10-diphenylsilaacridine.
The fourth concrete implementation mode:
the first difference between the present embodiment and the specific embodiment is: and 4, selecting hydrogen pressure of 1.0MPa in the process of preparing the 10, 10-diphenylsilaacridine.
The purity and yield of 10, 10-diphenylsilaacridine prepared in embodiment one and embodiments two to four are shown in table 4:
TABLE 410 purity and yield of 10-Diphenylsilacridine
Detailed Description
Pressure of hydrogen gas
Purity of
Yield of
A
Atmospheric pressure
99.30％
76.6％
II
0.2MPa
99.21％
76.8％
III
0.5MPa
99.34％
75.9％
Fourthly
1.0MPa
99.19％
76.3％
As can be seen from table 4, atmospheric pressure is preferred.
The fifth concrete implementation mode:
the first difference between the present embodiment and the specific embodiment is: the debenzylation catalyst selected in the process of preparing 10, 10-diphenylsilaacridine in the step 4 is 5 percent Pd/C.
The sixth specific implementation mode:
the first difference between the present embodiment and the specific embodiment is: the debenzylation catalyst selected in the process of preparing 10, 10-diphenylsilaacridine in the step 4 is 10% Pd/C.
The purity and yield of 10, 10-diphenylsilaacridine prepared in the first embodiment and the fifth and sixth embodiments are shown in Table 5:
TABLE 510 purity and yield of 10-Diphenylsilacridine
As can be seen from Table 5, the Pearlman's catalyst is preferred.
The seventh embodiment:
the first difference between the present embodiment and the specific embodiment is: and 4, selecting a reaction solvent from the process of preparing the 10, 10-diphenylsilaacridine in the step 4 as trichloromethane/methanol.
The specific implementation mode is eight:
the first difference between the present embodiment and the specific embodiment is: and 4, selecting a reaction solvent from the process of preparing the 10, 10-diphenylsilaacridine in the step 4 as trichloromethane/ethanol.
The specific implementation method nine:
the first difference between the present embodiment and the specific embodiment is: and 4, selecting a reaction solvent from the process of preparing the 10, 10-diphenylsilaacridine in the step 4 as trichloromethane/isopropanol.
The detailed implementation mode is ten:
the first difference between the present embodiment and the specific embodiment is: the reaction solvent selected in the process of preparing 10, 10-diphenylsilaacridine in the step 4 is dichloromethane/methanol.
The concrete implementation mode eleven:
the first difference between the present embodiment and the specific embodiment is: the reaction solvent selected in the process of preparing 10, 10-diphenylsilaacridine in the step 4 is dichloromethane/isopropanol.
The purity and yield of 10, 10-diphenylsilaacridine prepared in embodiment one and embodiments seven to eleven were plotted in table 6:
TABLE 610 purity and yield of 10-Diphenylsilacridine
Detailed Description
Reaction solvent
Purity of
Yield of
A
Methylene dichloride/ethanol
99.30％
76.6％
Seven-piece
Chloroform/methanol
96.41％
78.2％
Eight-part
Chloroform/ethanol
99.28％
76.3％
Nine-piece
Trichloromethane/isopropyl alcohol
99.25％
75.3％
Ten pieces of cloth
Methylene chloride/methanol
93.34％
80.5％
Eleven points of the design
Methylene dichloride/isopropanol
99.24％
75.8％
As can be seen from table 6, a dichloromethane/ethanol mixture is preferred.
The specific implementation mode twelve:
the first difference between the present embodiment and the specific embodiment is: and 4, methanol is used as a recrystallization solvent selected in the process of preparing the 10, 10-diphenylsilaacridine.
The specific implementation mode is thirteen:
the first difference between the present embodiment and the specific embodiment is: and 4, the recrystallization solvent selected in the process of preparing the 10, 10-diphenylsilaacridine in the step 4 is isopropanol.
The purity and yield of 10, 10-diphenylsilacridine prepared in the first embodiment and the twelfth and thirteenth embodiments are shown in Table 7:
TABLE 710 purity and yield of 10-Diphenylsilacridine
Detailed Description
Recrystallization solvent
Purity of
Yield of
A
Ethanol
99.30％
76.6％
Twelve aspects
Methanol
97.54％
78.9％
Thirteen-layer rubber
Isopropanol (I-propanol)
99.35％
65.2％
As can be seen from table 7, ethanol is preferred.
The specific implementation mode is fourteen:
a preparation method of 10, 10-diphenylsilaacridine comprises the following steps:
step 1, preparing bis (2-bromophenyl) amine:
under the protection of nitrogen, adding 2-bromoaniline, 1-bromo-2-iodobenzene, sodium tert-butoxide, tris (dibenzylideneacetone) dipalladium, 1' -bis (diphenylphosphino) ferrocene and toluene in a certain material-to-liquid ratio into a reaction vessel for reflux reaction, adding an ammonium chloride aqueous solution after the reflux reaction for washing, carrying out reduced pressure concentration, and recrystallizing to obtain bis (2-bromophenyl) amine;
step 2, preparing N, N-bis (2-bromophenyl) benzylamine:
under the protection of nitrogen, adding bis (2-bromophenyl) amine, alkali, tetrabutylammonium bromide and tetrahydrofuran in a certain material-to-liquid ratio into a reaction vessel, stirring at constant temperature for a certain time, dropwise adding benzyl bromide, carrying out reflux reaction, adding water after the reflux reaction, removing the tetrahydrofuran under reduced pressure, filtering, drying, and then carrying out recrystallization to obtain N, N-bis (2-bromophenyl) benzylamine;
step 3, preparing N-benzyl-10, 10-diphenylsilaacridine:
under the protection of nitrogen, adding N, N-bis (2-bromophenyl) benzylamine and diethyl ether in a certain material-to-liquid ratio into a reaction container, cooling to-70-0 ℃, dropwise adding N-BuLi N-hexane solution, preserving heat for a certain time after dropwise adding, dropwise adding diethyl ether solution of diphenyldichlorosilane again, reacting at room temperature after dropwise adding, washing with water after the reaction is finished, concentrating under reduced pressure, and recrystallizing to obtain N-benzyl-10, 10-diphenylsilaacridine;
step 4, preparing 10, 10-diphenylsilaacridine:
adding N-benzyl-10, 10-diphenylsilaacridine, a catalyst and a solvent into a high-pressure reaction kettle according to a certain material-liquid ratio under a hydrogen atmosphere with a certain pressure, reacting at room temperature, filtering after the reaction is finished, removing the solvent under reduced pressure, and recrystallizing to obtain the 10, 10-diphenylsilaacridine.
The concrete implementation mode is fifteen:
according to the fourteenth specific embodiment, the preparation method of 10, 10-diphenylsilaacridine comprises the steps of 1, 2-bromoaniline, 1-bromo-2-iodobenzene, sodium tert-butoxide and Pd2DBA3And the feed-liquid ratio of the DPPF to the toluene is 86.0-90 g: 155.6-160.0 g: 72.1-75.0 g: 2.7-3.0 g: 6.4-7.0 g: 1000-1200 mL, the reflux reaction temperature is 102-108 ℃, and the reflux reaction time is 10-12 h.
The specific implementation mode is sixteen:
according to a fourteenth specific embodiment, in the step 1, the concentration of the ammonium chloride aqueous solution is 10-12 wt%, and the recrystallization solvent is one of cyclohexane, n-hexane, benzene, and petroleum ether.
Seventeenth embodiment:
according to a fourteenth specific embodiment, in the step 2, the ratio of bis (2-bromophenyl) amine, alkali, tetrabutylammonium bromide and tetrahydrofuran is 98.1-100.0 g: 37.0-40.0 g: 9.7-10.0 g: 600-650 mL, keeping the temperature at 25-30 ℃, stirring for 4-5 h, wherein the mass ratio of the added benzyl bromide to the bis (2-bromophenyl) amine is 61.6-65.0 g: 98.1-100.0 g, wherein the alkali is one of sodium hydroxide, potassium hydroxide, sodium tert-butoxide and potassium tert-butoxide.
The specific implementation mode is eighteen:
according to a fourteenth specific embodiment, in the step 2, benzyl bromide is dissolved in tetrahydrofuran with a volume of 3-5 times, then the mixture is slowly added dropwise to a reaction system, after the addition is finished, the temperature is raised to 60-65 ℃ for reflux reaction for 4-5 hours, water with a volume of 3-5 times that of the benzyl bromide is added after the reaction, a recrystallization solvent is a mixed solvent of trichloromethane and n-hexane, the recrystallization temperature is-20 to-15 ℃ for crystallization, and the volume ratio of the trichloromethane to the n-hexane in the recrystallization solvent is 1:3 to 5.
The detailed embodiment is nineteen:
according to a fourteenth specific embodiment, in the step 3, the material-to-liquid ratio of the N, N-bis (2-bromophenyl) benzylamine, diethyl ether, N-BuLi N-hexane solution, and diethyl ether solution of diphenyldichlorosilane is 83.4-100.0 g: 1000-1200 mL: 184-200 mL: 300mL, the concentration of the n-BuLi n-hexane solution is 2.5M, and the ether solution of the diphenyldichlorosilane is prepared by dissolving 58.2g of diphenyldichlorosilane in 300mL of ether; and 3, dropwise adding n-BuLi n-hexane solution for 0.5-1.5 h, preserving heat for 1.0-1.5 h after dropwise adding, dropwise adding diphenyl dichlorosilane ether solution for 1.0-1.5 h again, preserving heat for 1.0-1.5 h after dropwise adding, then heating to room temperature, and stirring for reaction for 10-12 h.
The specific implementation mode twenty:
according to the fourteenth embodiment, in the preparation method of 10, 10-diphenylsilacridine, the recrystallization solvent in the step 3 is a mixed solvent of tetrahydrofuran and ethanol, wherein the volume ratio of tetrahydrofuran to ethanol is 1: 3-5, and the recrystallization temperature is 0-5 ℃.
The specific implementation mode is twenty one:
according to the fourteenth embodiment, in the step 4, the catalyst is one of 5 wt% Pd/C and 10 wt% Pd/C, Pearlman's, and the solvent is one of a mixed solution of chloroform and methanol, a mixed solution of chloroform and ethanol, a mixed solution of chloroform and isopropanol, a mixed solution of dichloromethane and methanol, a mixed solution of dichloromethane and ethanol, and a mixed solution of dichloromethane and isopropanol.
Specific embodiment twenty-two:
according to a fourteenth specific embodiment, in the step 4, the material-to-liquid ratio of the N-benzyl-10, 10-diphenylsilacridine, the catalyst and the solvent is 44.0-50.0 g: 4.4-5.0 g and 600-800 ml, and reacting at room temperature for 10-12 h under the hydrogen atmosphere pressure of one of normal pressure, 0.2MPa, 0.5MPa and 1.0 MPa.
Specific embodiment twenty-three:
according to the fourteenth embodiment, in the preparation method of 10, 10-diphenylsilaacridine, the recrystallization solvent in the step 4 is one of methanol, ethanol and isopropanol, and the recrystallization temperature is-20 to-15 ℃.
While the invention has been described in conjunction with specific embodiments thereof, it will be understood that they have been presented for purposes of illustration and description, and are not intended to limit the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.