A preparation method of 9,9-bisbenzyl-9-hydrogen-fluorene

Abstract

The present invention relates to the field of organic synthesis, discloses a kind of preparation method of 9,9-bis-benzyl-9-hydrogen-fluorene, with fluorene compounds and benzyl quaternary ammonium salt as reaction raw materials, under the effect of alkaline reagents such as sodium tert-butoxide and / or potassium tert-butoxide, 9,9-bis-benzyl substituted fluorenes can be efficiently synthesized. The raw materials used in the present invention are simple to prepare, stable in nature, and there is no need to add organometallic strong base in the reaction, the reaction conditions are safe and mild, experimental operation and post-processing steps are simple, and yield is high, versatility is strong, there is good application value in the field of organic synthesis and organic light-emitting polymer materials, and an effective new approach is provided for the synthesis of substituted fluorene compounds.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and in particular to a method for preparing 9,9-bisbenzyl-9-hydro-fluorene. Background Art

[0002] Conjugated polymers are a class of polymers whose backbones consist of unsaturated π bonds. Due to the highly delocalized structure of the π-conjugated electrons, these polymers often exhibit unique optical properties not found in conventional polymers, such as rapid optical response and good chemical and thermal stability. By modifying monomers with functional groups, material properties can be effectively optimized, resulting in ideal polymeric organic light-emitting materials.

[0003] Polyfluorenes are a class of conjugated polymers that emit blue light. Due to their high fluorescence efficiency, good thermal stability, and chemical properties, they are widely used as luminescent media in LEDs and LECs. Modifying the functional groups on the monomeric fluorene structure (adding different substituents at the 9-position of the monomeric fluorene to adjust the spatial structure of the polymer) can effectively improve their luminescence properties. For example, Qibing Pei reported the synthesis of BDOH-PF (poly[9,9-bis(3,6-dioxaheptyl)-fluorene-2,7-diyl]). This polymer monomer has a 1,4-diphenyl structure that provides holes for electron transport, and a bis(3,6-dioxaheptyl) side chain that improves electron transport efficiency. Therefore, its application in LECs can significantly enhance their luminescence performance (J. Am. Chem. Soc. 1996, 118, 7416). Katsumi Yoshino reported the synthesis of poly(9,9-dihexylfluorene), a compound that can produce blue light in electroluminescent diodes at room temperature, with a peak emission wavelength of 470 nm (Jpn. J. Appl. Phys. 1991, 30, 1941). Wei Huang et al. reported the synthesis of PODPF, a polyfluorene belonging to the 9,9-polydiarylfluorene family. Compared with the two aforementioned 9,9-polydialkylfluorenes, it exhibits stronger antioxidant and polymerization resistance (Macromolecules. 2014, 47, 1001). Hoosung Lee et al. synthesized 9,9-dibenzyl-9-hydro-fluorene and further polymerized it to obtain DBF-DHF. Subsequent property studies revealed that this polyfluorene exhibits a blue shift in fluorescence due to weak orthogonal interactions with the backbone (Synth. Met. 2004, 144, 193).

[0004]

[0005] When modifying the structure of the monomers of the polyfluorene described above, alkyl lithium is usually used as an alkaline reagent (① J. Am. Chem. Soc. 1996, 118, 7416. ② Jpn. J. Appl. Phys. 1991, 30, 1941). Its use and storage conditions are very demanding, requiring a strict anhydrous and oxygen-free environment. If exposed to air, it will spontaneously combust, and careful quenching must be done after the reaction. This leads to harsh reaction conditions, cumbersome experimental operations and post-processing steps. In addition, this type of reaction also requires the use of an excess of bromohydrocarbon as a reactant (Macromolecules. 2011, 44, 7977). The halogenated hydrocarbon and alkyl lithium easily react to form by-products such as lithium halide, long-chain alkanes, and alkenes, thereby affecting the reaction yield.

[0006] To this end, another related technology proposes the reaction of fluorene with benzyl bromide in DMSO using a 50wt% sodium hydroxide solution as an alkaline reagent in the presence of a benzylamine quaternary ammonium salt as a phase transfer catalyst to produce 9,9-bisbenzyl-9-hydro-fluorene. This technology avoids the use of alkyl lithium, resulting in milder reaction conditions. However, the yield is limited to only 85% at most. Summary of the Invention

[0007] In view of this, the present invention aims to provide a method for preparing 9,9-bisbenzyl-9-hydro-fluorene with mild reaction conditions, simple operation and high yield.

[0008] In a first aspect, the present invention provides an application of an alkaline reagent in catalyzing the reaction of a fluorene compound with a benzyl quaternary ammonium salt to prepare 9,9-bisbenzyl-9-hydro-fluorene, wherein the alkaline reagent is at least one of potassium tert-butoxide and sodium tert-butoxide.

[0009] In an optional embodiment, the molar ratio of the fluorene compound to the alkaline reagent is 1:2 to 2.2.

[0010] In an optional embodiment, the molar ratio of the fluorene compound to the benzyl quaternary ammonium salt is 1:2 to 2.5.

[0011] In a second aspect, the present invention provides a method for preparing 9,9-bisbenzyl-9-hydrogen-fluorene, comprising the following steps:

[0012] Under oxygen-free and water-free conditions, in the presence of an alkaline reagent, fluorene compounds react with benzyl quaternary ammonium salt to prepare 9,9-bisbenzyl-9-hydrogen-fluorene;

[0013] The alkaline reagent is at least one of potassium tert-butoxide and sodium tert-butoxide.

[0014] In an optional embodiment, the molar ratio of the fluorene compound to the alkaline reagent is 1:2 to 2.2.

[0015] In an optional embodiment, the molar ratio of the fluorene compound to the benzyl quaternary ammonium salt is 1:2 to 2.5.

[0016] In an optional embodiment, the reaction temperature is 60°C to 80°C, and the reaction time is 8h to 12h.

[0017] In an optional embodiment, the reaction is carried out in an anhydrous solvent, and the anhydrous solvent is at least one of anhydrous 1,4-dioxane and anhydrous dichloromethane.

[0018] In an optional embodiment, the ratio of the amount of the fluorene compound to the volume of the anhydrous solvent is 0.2-0.5:2-5, and the ratio is mol / L.

[0019] In an optional embodiment, after the reaction is completed, the mixture is diluted with ethyl acetate, filtered, and concentrated. The resulting crude product is purified by column chromatography to obtain 9,9-bisbenzyl-9-hydro-fluorene.

[0020] In an optional embodiment, the eluent used is ethyl acetate and petroleum ether in a volume ratio of 1:50-100.

[0021] In an optional embodiment, the volume ratio of the ethyl acetate to the anhydrous solvent is 5-10:2-5.

[0022] In an optional embodiment, the fluorene compound has a structure shown in Formula I:

[0023]

[0024] Wherein, R1 and R2 are each independently selected from hydrogen atom, halogen, and amino group;

[0025] Preferably, the halogen is a bromine atom.

[0026] In an optional embodiment, the benzyl quaternary ammonium salt has a structure shown in Formula II:

[0027]

[0028] Wherein, R3 is any one of a hydrogen atom, an aryl group, and an alkoxy group;

[0029] Preferably, the aryl group is a substituted or unsubstituted phenyl group, and the alkoxy group has 1 to 5 carbon atoms;

[0030] More preferably, R3 is any one of a hydrogen atom, a phenyl group, a methoxy group, a fluorophenyl group, a chlorophenyl group, a trifluoromethylphenyl group, and a methoxyphenyl group.

[0031] In an optional embodiment, the benzyl quaternary ammonium salt is prepared by reacting substituted or unsubstituted benzaldehyde with dimethylamine in the presence of sodium borohydride to obtain N,N-dimethylbenzylamine, which is then reacted with iodomethane to obtain the benzyl quaternary ammonium salt.

[0032] In an optional embodiment, the molar ratio of the substituted or unsubstituted benzaldehyde to the sodium borohydride is 1:1 to 1.1.

[0033] In an optional embodiment, the molar ratio of the substituted or unsubstituted benzaldehyde to the dimethylamine is 1:1 to 1.2.

[0034] In an optional embodiment, the reaction time of the substituted or unsubstituted benzaldehyde and the dimethylamine is 5 hours to 8 hours.

[0035] And / or, the molar ratio of the N,N-dimethylbenzylamine to the methyl iodide is 1:1.1-1.3.

[0036] In an optional embodiment, after the substituted or unsubstituted benzaldehyde and the dimethylamine react completely, an acid solution is added to quench the reaction, and then the pH value is adjusted to 9-10 with an alkaline solution, extracted with dichloromethane, and the organic layers are combined and concentrated to obtain N,N-dimethylbenzylamine.

[0037] In an optional embodiment, after the N,N-dimethylbenzylamine and the iodomethane are completely reacted, diethyl ether is added, and the precipitated solid matter is filtered to obtain the benzyl quaternary ammonium salt.

[0038] Compared with the prior art, the technical solution of the present invention has the following advantages:

[0039] The preparation method of 9,9-bisbenzyl-9-hydrogen-fluorene provided in an embodiment of the present invention uses a fluorene compound and a benzyl quaternary ammonium salt as reaction raw materials, and under the action of an alkaline reagent such as sodium tert-butoxide and / or potassium tert-butoxide, 9,9-bisbenzyl substituted fluorene can be efficiently synthesized. The raw materials used in the present invention are simple to prepare and have stable properties. No organic metal base is required during the reaction. The reaction conditions are safe and mild. The experimental operation and post-processing steps are simple, and the yield is high. It has strong versatility and has great application value in the fields of organic synthesis and organic light-emitting polymer materials, and provides an effective new approach for the synthesis of substituted fluorene compounds. DETAILED DESCRIPTION

[0040] The following examples are provided for a better understanding of the present invention and are not intended to limit the best mode of implementation. They do not limit the content and scope of protection of the present invention. Any product identical or similar to the present invention obtained by anyone under the guidance of the present invention or by combining the features of the present invention with other prior arts shall fall within the scope of protection of the present invention.

[0041] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in this field can be used. If the manufacturer of the reagents or instruments is not specified, they are all commercially available conventional reagents.

[0042] In order to solve the problems existing in the above-mentioned related technologies, according to the first aspect of the present invention, the present invention provides an application of an alkaline reagent in catalyzing the reaction of a fluorene compound with a benzyl quaternary ammonium salt to prepare 9,9-bisbenzyl-9hydro-fluorene, wherein the alkaline reagent is at least one of potassium tert-butoxide and sodium tert-butoxide.

[0043] In an optional embodiment, the molar ratio of the fluorene compound to the alkaline reagent is 1:2 to 2.2.

[0044] In an optional embodiment, the molar ratio of the fluorene compound to the benzyl quaternary ammonium salt is 1:2 to 2.5.

[0045] In a second aspect, the present invention provides a method for preparing 9,9-bisbenzyl-9-hydrogen-fluorene, comprising the following steps:

[0046] Under oxygen-free and water-free conditions, in the presence of an alkaline reagent, fluorene compounds react with benzyl quaternary ammonium salt to prepare 9,9-bisbenzyl-9-hydrogen-fluorene;

[0047] The alkaline reagent is at least one of potassium tert-butoxide and sodium tert-butoxide.

[0048] In an optional embodiment, the molar ratio of the fluorene compound to the alkaline reagent is 1:2 to 2.2.

[0049] In an optional embodiment, the molar ratio of the fluorene compound to the benzyl quaternary ammonium salt is 1:2 to 2.5.

[0050] In an optional embodiment, the reaction temperature is 60°C to 80°C, and the reaction time is 8h to 12h.

[0051] In an optional embodiment, the reaction is carried out in an anhydrous solvent, and the anhydrous solvent is at least one of anhydrous 1,4-dioxane and anhydrous dichloromethane.

[0052] In an optional embodiment, the ratio of the amount of the fluorene compound to the volume of the anhydrous solvent is 0.2-0.5:2-5, and the ratio is mol / L.

[0053] In an optional embodiment, after the reaction is completed, the mixture is diluted with ethyl acetate, filtered, and concentrated. The resulting crude product is purified by column chromatography to obtain 9,9-bisbenzyl-9-hydro-fluorene.

[0054] In an optional embodiment, the eluent used is ethyl acetate and petroleum ether in a volume ratio of 1:50-100.

[0055] In an optional embodiment, the volume ratio of the ethyl acetate to the anhydrous solvent is 5-10:2-5.

[0056] In an optional embodiment, the fluorene compound has a structure shown in Formula I:

[0057]

[0058] Wherein, R1 and R2 are each independently selected from hydrogen atom, halogen, and amino group;

[0059] Preferably, the halogen is a bromine atom.

[0060] In an optional embodiment, the benzyl quaternary ammonium salt has a structure shown in Formula II:

[0061]

[0062] Wherein, R3 is any one of a hydrogen atom, an aryl group, and an alkoxy group;

[0063] Preferably, the aryl group is a substituted or unsubstituted phenyl group, and the alkoxy group has 1 to 5 carbon atoms;

[0064] More preferably, R3 is any one of a hydrogen atom, a phenyl group, a methoxy group, a fluorophenyl group, a chlorophenyl group, a trifluoromethylphenyl group, and a methoxyphenyl group.

[0065] In an optional embodiment, the benzyl quaternary ammonium salt is prepared by reacting substituted or unsubstituted benzaldehyde with dimethylamine in the presence of sodium borohydride to obtain N,N-dimethylbenzylamine, which is then reacted with iodomethane to obtain the benzyl quaternary ammonium salt.

[0066] In an optional embodiment, the molar ratio of the substituted or unsubstituted benzaldehyde to the sodium borohydride is 1:1 to 1.1.

[0067] In an optional embodiment, the molar ratio of the substituted or unsubstituted benzaldehyde to the dimethylamine is 1:1 to 1.2.

[0068] In an optional embodiment, the reaction time of the substituted or unsubstituted benzaldehyde and the dimethylamine is 5 hours to 8 hours.

[0069] And / or, the molar ratio of the N,N-dimethylbenzylamine to the methyl iodide is 1:1.1-1.3.

[0070] In an optional embodiment, after the substituted or unsubstituted benzaldehyde and the dimethylamine react completely, an acid solution is added to quench the reaction, and then the pH value is adjusted to 9-10 with an alkaline solution, extracted with dichloromethane, and the organic layers are combined and concentrated to obtain N,N-dimethylbenzylamine.

[0071] In an optional embodiment, after the N,N-dimethylbenzylamine and the iodomethane are completely reacted, diethyl ether is added, and the precipitated solid matter is filtered to obtain the benzyl quaternary ammonium salt.

[0072] The present invention is further described in detail below with reference to specific examples. These examples should not be construed as limiting the scope of protection claimed in the present invention.

[0073] Example 1

[0074] A method for preparing 9,9-bisbenzyl-9-hydrogen-fluorene comprises the following steps:

[0075] (1) 5mmol benzaldehyde, 6mmol dimethylamine 40wt% aqueous solution (purchased from Anaiji, W3100925000) and 5mL methanol were added to the reaction flask in sequence, stirred for 15min, and then 5mmol sodium borohydride was added and stirred for 5h. After the reaction was completed, 4M 10mL dilute hydrochloric acid was added to the organic layer and fully shaken, 4M dilute sodium hydroxide solution was added to the aqueous layer to adjust the pH value to 10, 10mL dichloromethane was added to the reaction mixture for extraction, and the organic phase was dried with anhydrous sodium sulfate. After rotary evaporation, 5mmol N,N-dimethylbenzylamine was obtained. The obtained N,N-dimethylbenzylamine was added to a dry flask with a magnetic rod, 10mL anhydrous ethanol was added under nitrogen protection and stirred for 10min, followed by slow dropwise addition of 6mmol iodomethane. After the addition was complete, the mixture was heated and stirred under reflux for 30min. After the reaction is completed, the mixture is cooled to room temperature and 20 mL of anhydrous ether is added. A large amount of solid matter precipitates in the solution. The solid is separated by filtration to obtain a crude product. The crude product is washed three times with 10 mL of anhydrous ether and dried to obtain benzyl quaternary ammonium salt with a yield of 98%.

[0076] The specific reaction formula is:

[0077]

[0078] (2) After the Schlenk flask was evacuated and filled with nitrogen three times, 0.2 mmol of fluorene, 0.4 mmol of benzyl quaternary ammonium salt, 0.4 mmol of potassium tert-butoxide and 2 mL of anhydrous 1,4-dioxane were added in sequence under nitrogen protection. The mixture was reacted in an oil bath at 80°C for 12 h under magnetic stirring. After the reaction was completed, the mixture was cooled to room temperature, diluted with 10 mL of ethyl acetate, filtered and rotary evaporated to remove the solvent. The product was separated by column chromatography (eluent: ethyl acetate and petroleum ether, volume ratio: 1:100) to obtain 9,9-bisbenzyl-9-hydro-fluorene. The yield of this step was 97%; the total yield of the above two-step reaction was 95% calculated based on benzaldehyde.

[0079] The specific reaction formula is:

[0080]

[0081] The 9,9-bisbenzyl-9-hydrogen-fluorene prepared in this example was subjected to H NMR, C NMR, and high-resolution mass spectrometry tests, and the results are shown below:

[0082] 1 H NMR (500MHz, CDCl3) δ7.39 (s, 4H), 7.23 (dd, J = 23.6, 6.3Hz, 4H), 6.93 (dd, J = 16.6, 6.0Hz, 6H), 6.66 (d, J = 5.1Hz, 4H), 3.36 (s, 4H).

[0083] 13 C NMR (126MHz, CDCl3) δ148.29,141.01,137.20,130.36,127.20,127.12,126.36,125.98,124.74,119.79,56.78,45.60.

[0084] HR-MS m / z(ESI):calcd.for C 27 H 22 Na[M+Na] + :369.1614; found:369.1623. Example 2

[0085] A method for preparing 9,9-bis(4-methoxybenzyl)-9-hydrogen-fluorene comprises the following steps:

[0086] (1) 4 mmol of p-methoxybenzaldehyde, 4.4 mmol of a 40 wt% aqueous solution of dimethylamine (purchased from Anaiji, W3100925000) and 4 mL of methanol were added to the reaction flask in sequence. After stirring for 15 min, 4.4 mmol of sodium borohydride was added and the stirring was continued for 7 h. After the reaction was completed, 10 mL of 4M dilute hydrochloric acid was added to the organic layer and the mixture was fully shaken. A 4M dilute sodium hydroxide solution was added to the aqueous layer to adjust the pH value to 10. 10 mL of dichloromethane was added to the reaction mixture for extraction. The organic phase was dried with anhydrous sodium sulfate and rotary evaporated to obtain 4 mmol of 4-methoxy-N, N-dimethylbenzylamine. The obtained N, N-dimethylbenzylamine was added to a dry flask with a magnetic rod. Under nitrogen protection, 10 mL of anhydrous ethanol was added and stirred for 10 min. Then, 4.8 mmol of iodomethane was slowly added dropwise. After the addition was completed, the mixture was heated to reflux for 30 min. After the reaction is completed, the mixture is cooled to room temperature and 20 mL of anhydrous ether is added. A large amount of solid matter precipitates in the solution. The solid is separated by filtration to obtain a crude product. The crude product is washed three times with 10 mL of anhydrous ether and dried to obtain p-methoxybenzyl quaternary ammonium salt with a yield of 97%.

[0087] The specific reaction formula is:

[0088]

[0089] (2) After the Schlenk flask was evacuated and filled with nitrogen three times, 0.2 mmol of fluorene, 0.4 mmol of p-methoxybenzyl quaternary ammonium salt, 0.4 mmol of sodium tert-butoxide and 2 mL of anhydrous 1,4-dioxane were added in sequence under nitrogen protection. The mixture was reacted in an oil bath at 80°C for 10 h under magnetic stirring. After the reaction was completed, the mixture was cooled to room temperature, diluted with 10 mL of ethyl acetate, filtered and rotary evaporated to remove the solvent. The product was separated by column chromatography (eluent: ethyl acetate and petroleum ether, volume ratio: 1:80) to obtain 9,9-bis(4-methoxybenzyl)-9-hydro-fluorene. The yield of this step was 93%, and the total yield of the above two-step reaction was 90% calculated based on p-methoxybenzaldehyde.

[0090] The specific reaction formula is:

[0091]

[0092] The 9,9-bis(4-methoxybenzyl)-9-hydrogen-fluorene prepared in this example was subjected to H NMR, C NMR, and high-resolution mass spectrometry tests. The results are shown below:

[0093] 1H NMR(500MHz, CDCl3) δ7.38(dd,J=12.1,7.4Hz,4H),7.25(t,J=7.4Hz,2H),7.19(t,J =7.4Hz,2H),6.57(d,J=8.7Hz,4H),6.44(d,J=8.7Hz,4H),3.59(s,6H),3.27(s,4H).

[0094] 13 C NMR (101MHz, CDCl3) δ157.75,148.56,141.06,131.23,129.41,127.00,126.30,124.66,119.83,112.62,56.97,55.05,44.63.

[0095] HR-MSm / z(ESI):calcd.for C 29 H 26 O2Na[M+Na] + :429.1825; found:429.1805.

[0096] Example 3

[0097] A method for preparing 9,9-bis(4-phenylbenzyl)-9-hydrogen-fluorene comprises the following steps:

[0098] (1) 5 mmol of p-phenylbenzaldehyde, 6 mmol of a 40 wt% aqueous solution of dimethylamine (purchased from Anaiji, W3100925000) and 5 mL of methanol were added to the reaction flask in sequence. After stirring for 15 min, 5 mmol of sodium borohydride was added and the stirring was continued for 6 h. After the reaction was completed, 10 mL of 4M dilute hydrochloric acid was added to the organic layer and the mixture was fully shaken. 4M dilute sodium hydroxide solution was added to the aqueous layer to adjust the pH value to 10. 10 mL of dichloromethane was added to the reaction mixture for extraction. The organic phase was dried with anhydrous sodium sulfate and rotary evaporated to obtain 5 mmol of 4-phenyl N, N-dimethylbenzylamine. The obtained N, N-dimethylbenzylamine was added to a dry flask with a magnetic rod. Under nitrogen protection, 10 mL of anhydrous ethanol was added and stirred for 10 min. Then, 5.5 mmol of iodomethane was slowly added dropwise. After the addition was completed, the mixture was heated to reflux for 30 min. After the reaction is completed, the mixture is cooled to room temperature and 20 mL of anhydrous ether is added. A large amount of solid matter precipitates in the solution. The solid is separated by filtration to obtain a crude product. The crude product is washed three times with 10 mL of anhydrous ether and dried to obtain p-phenylbenzyl quaternary ammonium salt with a yield of 98%.

[0099] The specific reaction formula is:

[0100]

[0101] (2) After the Schlenk flask was evacuated and filled with nitrogen three times, 0.2 mmol of fluorene, 0.45 mmol of p-phenylbenzyl quaternary ammonium salt, 0.42 mmol of potassium tert-butoxide and 2 mL of anhydrous 1,4-dioxane were added in sequence under nitrogen protection. The mixture was reacted in an oil bath at 70°C for 8 h under magnetic stirring. After the reaction was completed, the mixture was cooled to room temperature, diluted with 8 mL of ethyl acetate, filtered and rotary evaporated to remove the solvent. The product was separated by column chromatography (eluent: ethyl acetate and petroleum ether, volume ratio 1:100) to obtain 9,9-bis(4-phenylbenzyl)-9-hydro-fluorene. The yield of this step was 94%; the total yield of the above two-step reaction was 92% calculated based on p-phenylbenzaldehyde.

[0102] The specific reaction formula is:

[0103]

[0104] The 9,9-bis(4-phenylbenzyl)-9-hydrogen-fluorene prepared in this example was subjected to H NMR, C NMR, and high-resolution mass spectrometry tests, and the results are shown below:

[0105] 1 H NMR (500MHz, CDCl3) δ7.45 (d, J = 7.4Hz, 2H), 7.41 (d, J = 8.2Hz, 6H), 7.30 (m, 6H) ,7.25–7.18(m,4H),7.15(d,J=8.2Hz,4H),6.73(d,J=8.2Hz,4H),3.40(s,4H).

[0106] 13 C NMR (126MHz, CDCl3) δ148.28,141.06,140.86,138.54,136.38,130.77,128. 69,127.21,127.02,126.89,126.43,125.86,124.71,119.99,56.78,45.25.

[0107] HR-MSm / z(ESI):calcd.for C 39 H 30 Na[M+Na] + :521.2240; found:521.2222. Example 4

[0108] A method for preparing 9,9-bisbenzyl 2,7-dibromo-9-hydrogen-fluorene comprises the following steps:

[0109] (1) Prepare benzyl quaternary ammonium salt by the same method as in Example 1.

[0110] (2) After the Schlenk flask was evacuated and filled with nitrogen three times, 0.2 mmol 2,7-dibromofluorene, 0.4 mmol benzyl quaternary ammonium salt, 0.4 mmol potassium tert-butoxide and 2 mL anhydrous 1,4-dioxane were added in sequence under nitrogen protection. The mixture was reacted in an oil bath at 80°C for 12 h under magnetic stirring. After the reaction was completed, the mixture was cooled to room temperature, diluted with 10 mL ethyl acetate, filtered and rotary evaporated to remove the solvent. The product was separated by column chromatography (eluent: ethyl acetate and petroleum ether, volume ratio: 1:100) to obtain 9,9-bisbenzyl 2,7-dibromo-9-hydro-fluorene. The yield of this step was 93%. The total yield of the above two-step reaction was 91% calculated based on benzaldehyde.

[0111] The specific reaction formula is:

[0112]

[0113] The 9,9-bisbenzyl 2,7-dibromo-9-hydrogen-fluorene prepared in this example was subjected to H NMR, C NMR, and high-resolution mass spectrometry tests. The results are shown below:

[0114] 1 H NMR (500MHz, CDCl3) δ7.51(d,J=1.7Hz,2H),7.34(dd,J=8.1,1.8Hz,2H),7.20(d,J=8.1Hz,2H),6.98(m,6H),6.66(d,J=8.1Hz,4H),3.32(s,4H).

[0115] 13 C NMR (126MHz, CDCl3) δ150.27,138.95,136.25,130.52,130.28,128.08,127.54,126.42,121.27,120.67,57.28,45.31.

[0116] HR-MSm / z(ESI):calcd.for C 27 H 20 Br2Na[M+Na] + :524.9824; found:524.9818.

[0117] Example 5

[0118] A method for preparing 9,9-bisbenzyl-2-bromo-9-hydrogen-fluorene comprises the following steps:

[0119] (1) Prepare benzyl quaternary ammonium salt by the same method as in Example 1.

[0120] (2) After the Schlenk flask was evacuated and filled with nitrogen three times, 0.2 mmol 2-bromofluorene, 0.4 mmol benzyl quaternary ammonium salt, 0.44 mmol potassium tert-butoxide and 2 mL anhydrous 1,4-dioxane were added in sequence under nitrogen protection, and the mixture was reacted in an oil bath at 80°C for 12 h under magnetic stirring. After the reaction was completed, the mixture was cooled to room temperature, diluted with 7 mL ethyl acetate, filtered, and rotary evaporated to remove the solvent. The product was separated by column chromatography (eluent: ethyl acetate and petroleum ether, volume ratio: 1:100) to obtain 9,9-bisbenzyl-2-bromo-9-hydro-fluorene. The reaction yield of this step was 94%; the total yield of the above two steps was 92% calculated based on benzaldehyde.

[0121] The specific reaction formula is:

[0122]

[0123] The 9,9-bisbenzyl-2-bromo-9-hydrogen-fluorene prepared in this example was subjected to H NMR, C NMR, and high-resolution mass spectrometry tests, and the results are shown below:

[0124] 1 H NMR (500MHz, CDCl3) δ7.51(d,J=1.6Hz,1H),7.40(d,J=7.5Hz,1H),7.31(m,3H),7.21(t,J= 8.1Hz, 2H), 6.96 (dt, J=22.0, 7.1Hz, 6H), 6.66 (d, J=7.0Hz, 4H), 3.39–3.28 (q, J=15Hz, 4H).

[0125] 13 C NMR (126MHz, CDCl3) δ150.54,148.04,140.01,139.94,136.71,130.31,130.23, 128.01,127.36,126.86,126.19,124.78,121.15,120.13,119.92,57.06,45.45.

[0126] HR-MSm / z(ESI):calcd.for C 27 H 21 BrNa[M+Na] + :447.0719; found:447.0757.

[0127] Example 6

[0128] A method for preparing 9,9-bisbenzyl-9-hydrogen-fluoren-2-amine comprises the following steps:

[0129] (1) Prepare benzyl quaternary ammonium salt by the same method as in Example 1.

[0130] (2) After the Schlenk flask was evacuated and filled with nitrogen three times, 0.2 mmol of 2-aminofluorene, 0.5 mmol of benzyl quaternary ammonium salt, 0.4 mmol of potassium tert-butoxide and 2 mL of anhydrous 1,4-dioxane were added in sequence under nitrogen protection. The mixture was reacted in an oil bath at 80°C for 12 h under magnetic stirring. After the reaction was completed, the mixture was cooled to room temperature, diluted with 10 mL of ethyl acetate, filtered and rotary evaporated to remove the solvent. The product was separated by column chromatography (eluent: ethyl acetate and petroleum ether, volume ratio: 1:50) to obtain 9,9-bisbenzyl-9-hydrogen-fluorene-2-amine. The yield of this step was 96%; the total yield of the above two-step reaction was 94% calculated based on benzaldehyde.

[0131] The specific reaction formula is:

[0132]

[0133] The 9,9-bisbenzyl-9-hydrogen-fluoren-2-amine prepared in this example was subjected to H NMR, C NMR, and high-resolution mass spectrometry tests, and the results are shown below:

[0134] 1 H NMR(500MHz, CDCl3)δ7.32–7.27(m,2H),7.22(d,J=8.0Hz,1H),7.20–7.14(m,2H),7.06–6.94(m,6H),6.75 (d,J=6.7Hz,4H),6.72(d,J=2.0Hz,1H),6.57(dd,J=8.0,2.1Hz,1H),3.83(br,2H),3.33(q,J=10.0Hz,4H).

[0135] 13 C NMR (126MHz, CDCl3) δ150.29,147.38,145.32,141.35,137.37,132.37,130.44,127.31, 126.97,125.96,124.68,124.56,120.61,118.50,114.39,111.58,56.32,45.67,36.92.

[0136] HR-MSm / z(ESI):calcd.for C 27 H 24 N[M+H] + :362.1903; found:362.1928.

[0137] Comparative Example 1

[0138] The preparation method of 9,9-bisbenzyl-9-hydro-fluorene provided in this comparative example has substantially the same reaction conditions as those in Example 1, with the only difference being that an equimolar amount of NaOH is used to replace the potassium tert-butoxide in Example 1.

[0139] The results showed that the yield of this step was 42%; the total yield of the above two-step reaction was 41% calculated based on benzaldehyde.

[0140] Comparative Example 2

[0141] The preparation method of 9,9-bisbenzyl-9-hydro-fluorene provided in this comparative example has substantially the same reaction conditions as those in Example 1, with the only difference being that an equal molar amount of benzyl iodide is used to replace the benzyl quaternary ammonium salt in Example 1.

[0142] It was found that the yield of this step was 9%.

[0143] Comparative Example 3

[0144] The preparation method of 9,9-bisbenzyl-9-hydro-fluorene provided in this comparative example has substantially the same reaction conditions as those in Example 1, with the only difference being that anhydrous 1,4-dioxane in Example 1 is replaced by an equal amount of anhydrous DMSO.

[0145] The results showed that the yield of this step was 27%; the total yield of the above two-step reaction was 26% calculated based on benzaldehyde.

[0146] Obviously, the above embodiments are merely examples for clarity of explanation and are not intended to limit the implementation methods. Those skilled in the art will readily appreciate that other variations or modifications based on the above descriptions are possible. It is not necessary and impossible to enumerate all implementation methods here. Obvious variations or modifications arising therefrom remain within the scope of protection of the present invention.

Claims

1. A method for preparing 9,9-bisbenzyl-9-hydrogen-fluorene, characterized in that: The following steps are involved: Under oxygen-free and water-free conditions, in the presence of an alkaline reagent, fluorene compounds react with benzyl quaternary ammonium salt to prepare 9,9-bisbenzyl-9-hydrogen-fluorene; The alkaline reagent is at least one of potassium tert-butoxide and sodium tert-butoxide; The molar ratio of the fluorene compound to the alkaline reagent is 1:2 to 2.2; The molar ratio of the fluorene compound to the benzyl quaternary ammonium salt is 1:2 to 2.5; The reaction temperature is 60°C to 80°C, and the reaction time is 8h to 12h; The reaction is carried out in an anhydrous solvent, and the anhydrous solvent is anhydrous 1,4-dioxane; The ratio of the amount of the fluorene compound to the volume of the anhydrous solvent is 0.2-0.5:2-5, and the ratio is mol / L; The fluorene compound has a structure shown in Formula I: Wherein, R1 and R2 are each independently selected from hydrogen atom, halogen, and amino group; The halogen is a bromine atom; The benzyl quaternary ammonium salt has a structure shown in Formula II: R3 is any one of a hydrogen atom, a phenyl group, and a methoxy group.

2. The preparation method according to claim 1, characterized in that After the reaction is completed, the mixture is diluted with ethyl acetate, filtered, and concentrated. The resulting crude product is purified by column chromatography to obtain 9,9-bisbenzyl-9-hydrogen-fluorene.

3. The preparation method according to claim 2, characterized in that The eluent used was ethyl acetate and petroleum ether in a volume ratio of 1:50-100; And / or, the volume ratio of the ethyl acetate to the anhydrous solvent is 5-10:2-5.

4. The preparation method according to claim 1, characterized in that The benzyl quaternary ammonium salt is prepared by reacting substituted or unsubstituted benzaldehyde with dimethylamine in the presence of sodium borohydride to obtain N,N-dimethylbenzylamine, which is then reacted with iodomethane to obtain the benzyl quaternary ammonium salt.

5. The preparation method according to claim 4, characterized in that The molar ratio of the substituted or unsubstituted benzaldehyde to the sodium borohydride is 1:1 to 1.

1.

6. The preparation method according to claim 5, characterized in that The molar ratio of the substituted or unsubstituted benzaldehyde to the dimethylamine is 1:1 to 1.

2.

7. The preparation method according to claim 4, characterized in that The reaction time of the substituted or unsubstituted benzaldehyde and the dimethylamine is 5 hours to 8 hours.

8. The preparation method according to claim 4, characterized in that The molar ratio of the N,N-dimethylbenzylamine to the methyl iodide is 1:1.1-1.

3.

9. The preparation method according to claim 4, characterized in that After the substituted or unsubstituted benzaldehyde and the dimethylamine react completely, an acid solution is added to quench the reaction, and then the pH value is adjusted to 9-10 with an alkaline solution. The mixture is extracted with dichloromethane, and the organic layers are combined and concentrated to obtain N,N-dimethylbenzylamine.

10. The preparation method according to claim 4, characterized in that After the N,N-dimethylbenzylamine and the iodomethane react completely, ether is added and the precipitated solid matter is filtered to obtain the benzyl quaternary ammonium salt.

Images