Fluorene-containing alkyl zinc complex as well as preparation method and application thereof
By preparing fluorene-containing alkyl zinc complexes, the preparation process is simplified, and the existing zinc complexes have long preparation routes and poor substrate applicability in imine reduction reactions are solved, thereby achieving efficient and gentle catalytic imine borohydrogenation reaction.
Patent Information
- Application Number
- CN202510438336.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-04-09
- Publication Date
- 2025-07-22
AI Technical Summary
The existing zinc complex catalysts have problems such as long preparation routes or poor substrate applicability in imine reduction reactions, making it difficult to efficiently catalyze the imine borohydrogenation reaction.
The preparation process is simplified by the preparation of fluorene-containing alkyl zinc complexes, including reaction of fluorene, potassium tert-butoxide, sodium methoxide to form 9-fluorene formaldehyde, and then with amino compounds and catalyst to form a formyl fluorene imine ligand, and finally reacting with alkyl zinc to form an alkyl zinc complex, simplifying the preparation process.
It provides a catalyst with short reaction route and easy operation, which can efficiently catalyze the borohydrogenation reaction of various compounds, with mild conditions, high yield and strong applicability.
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Figure CN120349333A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of metal-organic complexes, and particularly relates to a fluorene-alkyl zinc complex, a preparation method thereof, and an application thereof. Background Art
[0002] As an important reaction step in organic synthesis, imine reduction can not only be efficiently converted into amine compounds, but also plays an important role in the fields of medicinal chemistry, natural product synthesis, asymmetric synthesis, etc. With the development of catalytic technology, the selectivity and efficiency of the imine reduction reaction will be further improved, providing more possibilities and solutions for the fields of organic synthesis, drug development, etc. Using pinacol borane to form the corresponding borate ester of imine and then hydrolyzing it can complete the imine reduction. This method has the advantages of high selectivity, mild conditions, and easy control. In order to obtain catalysts with high yields and strong substrate applicability, metal-organic catalysts are also constantly evolving.
[0003] Zinc is one of the most abundant, economical, easily accessible, eco-friendly, and biocompatible metals, and has good application prospects in the field of catalysis. Some zinc complexes have also been mentioned in previous reports. Most of these catalysts are zinc hydride complexes or zinc halide complexes, and some of their limitations are that the preparation route is relatively long or the substrate applicability is poor during the catalytic reaction. Conversely, there are few reports on the use of relatively easily prepared alkyl zinc complexes in the hydroboration of imines. Summary of the Invention
[0004] Therefore, the technical problem to be solved by the present invention is to overcome the defects in the prior art, and thus provide a fluorene-alkyl zinc complex, a preparation method thereof, and an application thereof, which have a short reaction route, are easy to operate, and can efficiently catalyze the hydroboration of imines.
[0005] To this end, the present invention provides a preparation method of a fluorene-alkyl zinc complex, comprising the following steps:
[0006] (1) Adding fluorene, potassium tert-butoxide, and sodium methoxide to a solvent, and reacting to obtain 9-fluorenecarbaldehyde;
[0007] (2) Dissolving 9-fluorenecarbaldehyde in a solvent, adding an amino compound and a catalyst, and reacting to obtain a formylfluorene imine ligand;
[0008] (3) Reacting the formylfluorene imine ligand with alkyl zinc to obtain an alkyl zinc complex.
[0009] Preferably, the solvent in step (1) is toluene, the reaction temperature is 50°C, and the reaction time is 2 - 6 h.
[0010] Preferably, in step (2), the solvent is ethanol, the amino compound is at least one of 2-aminopyridine, o-phenylenediamine, 1,2-cyclohexanediamine, ethylenediamine or N,N-dimethyl-o-phenylenediamine, and the catalyst is acetic acid.
[0011] Preferably, in step (3), the reaction solvent is tetrahydrofuran, and the alkylzinc is at least one of ZnEt2 or ZnMe2.
[0012] The present invention also provides a fluorene alkylzinc complex prepared by the described preparation method.
[0013] In addition, the present invention provides the use of a fluorene alkylzinc complex prepared by a preparation method of a fluorene alkylzinc complex or the described fluorene alkylzinc complex in a catalytic hydroboration reaction.
[0014] The technical solution of the present invention has the following advantages:
[0015] The present invention provides a fluorene alkylzinc complex, a preparation method thereof and an application thereof. The fluorene alkylzinc complex of the present invention has a short reaction route, is easy to operate, and can efficiently catalyze the hydroboration reaction of imines. At the same time, the fluorene alkylzinc complex of the present invention, as a catalyst, has a small amount of use, mild reaction conditions, high yield, and can catalyze the hydroboration reaction of various compounds. BRIEF DESCRIPTION OF THE DRAWINGS
[0016] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following will briefly introduce the drawings required for the description of the specific embodiments or the prior art. Obviously, the drawings in the following description are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.
[0017] Figure 1 is the 1H NMR spectrum of compound L of the present invention 1 ;
[0018] Figure 2 is the 13C NMR spectrum of compound L of the present invention 1 ;
[0019] Figure 3 is the 1H NMR spectrum of complex 2 of the present invention
[0020] Figure 4 is the 13C NMR spectrum of complex 2 of the present invention
[0021] Figure 5 is the 1H NMR spectrum of compound a obtained after the reduction of benzyldibenzylamine catalyzed by the alkylzinc complex of the present invention
[0022] Figure 6It is the carbon spectrum of compound a obtained after the reduction of benzyldibenzylamine catalyzed by the alkylzinc complex of the present invention;
[0023] Figure 7 It is the atomic structure diagram of the alkylzinc complex 2 of the present invention. Detailed implementation manners
[0024] The following embodiments are provided to better further understand the present invention. They are not limited to the best implementation manners, and do not constitute limitations on the content and protection scope of the present invention. Any product that is the same as or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with those of other prior arts falls within the protection scope of the present invention.
[0025] For those not specifying specific experimental steps or conditions in the embodiments, the operations or conditions of the conventional experimental steps described in the literature in this field can be followed. For the reagents or instruments not indicating the manufacturers, they are all conventional reagent products that can be obtained through commercial purchase.
[0026] Example 1
[0027] Weigh fluorene (4.15 g, 0.025 mol), potassium tert-butoxide (1.232 g, 0.011 mol), and sodium methoxide (2.288 g, 0.044 mol) and add them to a three-necked flask. Under the condition of the presence of an inert gas, add 30 mL of toluene to the three-necked flask, and finally dropwise add 4 mL of ethyl formate. Reflux with condensation at 50 °C for 2 h. Monitor the reaction progress by TLC during the reaction. After the reaction is completed, add 50 mL of distilled water to quench the reaction. After liquid separation, add acetic acid to the aqueous phase to make the solution neutral, and extract with dichloromethane (30 mL × 2), and then extract with saturated sodium bicarbonate and saturated sodium chloride respectively. Finally, add anhydrous magnesium sulfate, filter, and remove the solvent under reduced pressure to obtain 9-fluorenecarbaldehyde, and calculate the yield (4.27 g, 88%).
[0028] Compound L 1 Synthesis:
[0029]
[0030] Dissolve 9-fluorenecarbaldehyde (25 mmol, 4.85 g) in 40 mL of ethanol. After adding 2-aminopyridine (25 mmol, 2.35 g) and mixing evenly, add a catalytic amount of acetic acid, and track the reaction progress by TLC. After the reaction is completed, remove the solvent under reduced pressure and recrystallize in n-hexane to obtain yellow crystals L 1 (6.075 g, 90%).
[0031] Compound L 1 The hydrogen spectrum and carbon spectrum of are as shown in Figure 1 、 2As shown, it can be seen from the spectrum that compound L was successfully prepared. 1 .
[0032] Synthesis of Complex 1:
[0033]
[0034] ZnEt2 (1.0 mL, 1.0 mmol, 1.0 M in n - hexane) was added dropwise to a 5 mL THF solution of compound L 1 (0.270 g, 1 mmol). After mixing evenly, the reaction was carried out at room temperature for 1 h, then the temperature was raised to 60 °C and stirred for 10 h. After the reaction was completed, the solvent was removed under reduced pressure, and the residue was extracted with a mixed solution of toluene and n - hexane. The extract was allowed to stand at room temperature, and yellow crystals of appropriate size (0.349 g, 80%) were formed after 2 days.
[0035] Synthesis of Complex 2:
[0036]
[0037] ZnMe2 (1.0 mL, 1.0 mmol, 1.0 M in n - hexane) was added dropwise to a 5 mL THF solution of compound L 1 (0.270 g, 1 mmol). After mixing evenly, the reaction was carried out at room temperature for 1 h, then the temperature was raised to 60 °C and stirred for 10 h. After the reaction was completed, the solvent was removed under reduced pressure, and the residue was extracted with a mixed solution of toluene and n - hexane. The extract was allowed to stand at room temperature, and yellow crystals of appropriate size (0.316 g, 75%) were formed after 2 days.
[0038] The 1H NMR spectrum and 13C NMR spectrum of Complex 2 are as Figure 3 , 4 shown. It can be seen from the spectrum that Complex 2 was successfully prepared.
[0039] Example 2
[0040] Synthesis of compound L 2 :
[0041]
[0042] 9 - Fluorenecarbaldehyde (25 mmol, 4.85 g) and 0.5 equivalent of o - phenylenediamine (12.5 mmol, 1.35 g) were refluxed in 40 mL of ethanol, and a catalytic amount of acetic acid was added. The reaction progress was monitored by TLC. After the reaction was completed, the solvent was removed under reduced pressure, and the residue was recrystallized with n - hexane to obtain yellow - green crystals L 2 (5.062 g, 88%).
[0043] Synthesis of Complex 3:
[0044]
[0045] Add ZnEt2 (1.0 mL, 1.0 mmol, 1.0 M in n-hexane) dropwise to a 5 mL THF solution of compound L 2 (1 mmol). After mixing evenly, react at room temperature for 1 h, then raise the temperature to 60 °C and stir for 10 h. After the reaction is completed, remove the solvent under reduced pressure, and cultivate the residue with toluene. After standing for 2 days, red crystals of appropriate size grow out (0.508 g, 76%).
[0046] Example 3
[0047] Compound L 3 Synthesis:
[0048]
[0049] 9-Fluorenecarbaldehyde (25 mmol, 4.85 g) and 0.5 equivalent of 1,2-cyclohexanediamine (12.5 mmol, 1.43 g) are refluxed in 40 mL of ethanol, and a catalytic amount of acetic acid is added. The reaction progress is monitored by TLC. After the reaction is completed, remove the solvent under reduced pressure and recrystallize with n-hexane to obtain white crystals of L 3 (5.075 g, 87%).
[0050] Synthesis of complex 4:
[0051]
[0052] Add ZnEt2 (1.0 mL, 1.0 mmol, 1.0 M in n-hexane) dropwise to a 5 mL THF solution of compound L 3 (1 mmol). After mixing evenly, react at room temperature for 1 h, then raise the temperature to 60 °C and stir for 10 h. After the reaction is completed, remove the solvent under reduced pressure, and cultivate the residue with toluene. After standing for 2 days, yellow crystals of appropriate size are obtained (0.505 g, 80%).
[0053] Example 4
[0054] Compound L 4 Synthesis:
[0055]
[0056] 9-Fluorenecarbaldehyde (25 mmol, 4.85 g) and 0.5 equivalent of ethylenediamine (12.5 mmol, 0.75 g) are refluxed in 40 mL of ethanol, and a catalytic amount of acetic acid is added. The reaction progress is monitored by TLC. After the reaction is completed, remove the solvent under reduced pressure and recrystallize with n-hexane to obtain yellowish-green crystals of L 4(4.641 g, 90%)。
[0057] Synthesis of Complex 5:
[0058]
[0059] ZnEt2 (1.0 mL, 1.0 mmol, 1.0 M in n - hexane) was added dropwise to a 5 mL THF solution of Compound L 4 (1 mmol). After mixing evenly, the reaction was carried out at room temperature for 1 h, then the temperature was raised to 60 °C and stirred for 10 h. After the reaction was completed, the solvent was removed under reduced pressure, and the residue was crystallized with a mixed solution of n - hexane and tetrahydrofuran. After standing for 2 days, green crystals of appropriate size (0.404 g, 70%) grew out.
[0060] Example 5
[0061] Compound L 5 Synthesis of:
[0062]
[0063] 9 - Fluorenecarboxaldehyde (25 mmol, 4.85 g) and an equivalent amount of N,N - dimethyl - o - phenylenediamine (25 mmol, 3.40 g) were refluxed in 40 mL of ethanol, and a catalytic amount of acetic acid was added. The reaction progress was monitored by TLC. After the reaction was completed, the solvent was removed under reduced pressure, and the residue was recrystallized with n - hexane to obtain yellow crystals of L 5 (6.640 g, 85%).
[0064] Synthesis of Complex 6:
[0065]
[0066] ZnMe2 (1.0 mL, 1.0 mmol, 1.0 M in n - hexane) was added dropwise to a 5 mL THF solution of Compound L 5 (1 mmol). After mixing evenly, the reaction was carried out at room temperature for 1 h, then the temperature was raised to 60 °C and stirred for 10 h. After the reaction was completed, the solvent was removed under reduced pressure, and the residue was extracted with a mixed solution of toluene and n - hexane. The extract was allowed to stand at room temperature, and yellow crystals of appropriate size (0.334 g, 72%) formed after 2 days.
[0067] Application Example
[0068] Using the hydroboration reaction of benzylidene benzylamine as a model reaction and pyridyl - alkyl zinc complexes as catalysts, the optimized conditions for the hydroboration reaction catalyzed by the synthesized novel alkyl zinc complexes were systematically studied, namely the effects of factors such as catalyst type, catalyst dosage, reaction time, reaction temperature, reaction solvent, etc. on the hydroboration reaction. The results of the conditional reactions are shown in Table 1.
[0069] Table 1 Influence of the optimized conditions of the alkylzinc complex-catalyzed borohydration reaction on the borohydration reaction
[0070]
[0071] It can be seen from Table 1 that catalyst 2 has the best catalytic effect, and the most suitable conditions are: 4 mL of toluene solution, reaction temperature 80 °C, reaction time 5 h, and the catalyst carrier is 5 mol%.
[0072] On the basis of the above reaction conditions, imine compounds containing different substituents on the aromatic ring were selected to study their borohydration reactions, and the reaction results are shown in Table 2.
[0073] Table 2 Substrate adaptability of the alkylzinc complex-catalyzed borohydration reaction of imine compounds
[0074]
[0075]
[0076] Five formylfluorene imine compounds L 1 ~L 5 were synthesized in this invention. A series of novel alkylzinc complexes 1 - 6 were successfully synthesized by alkyl elimination reaction with ZnEt2 or ZnMe2 using them as ligands.
[0077] The atomic structure of complex 2 was determined. As Figure 7 shown, the research shows that each central metal in such complexes coordinates with N atoms and O atoms, forming a chelate structure centered on zinc metal. These complexes are sensitive to air and water and have good solubility in various polar organic solvents (toluene, tetrahydrofuran). The application of this type of novel alkylzinc complex in the formation of C=N bonds was tested, and the borohydration reactions of imine compounds with various substituents were studied. The results show that: as a catalyst, this type of compound can catalyze the borohydration reaction of imine compounds with high activity, under mild conditions and with less catalyst dosage. The 1H NMR and 13C NMR spectra of the successful preparation of benzyldibenzylamine under the action of the alkylzinc complex in this application are as Figure 5 , Figure 6 shown. Using 5 mol% of the alkylzinc complex as a catalyst to catalyze the borohydration reaction of benzyldibenzylamine, the reaction is carried out at room temperature for 5 hours, and the yield can reach 93%. Under the same conditions, this catalytic system is used for the borohydration reactions of more than 20 different substituted imines, and the yields are all relatively high.
[0078] Obviously, the above embodiments are merely examples for clear illustration and not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or alterations can be made based on the above description. It is not necessary and impossible to list all implementation manners here. And the obvious changes or alterations derived therefrom still fall within the protection scope of the present invention.
Claims
1. A preparation method of a fluorene-alkyl zinc complex, characterized in that, It includes the following steps: (1) Add fluorene, potassium tert-butoxide, and sodium methoxide into a solvent, and react to obtain 9-fluorenecarbaldehyde; (2) Dissolve 9-fluorenecarbaldehyde in a solvent, add an amino compound and a catalyst, and react to obtain a formylfluorenimine ligand; (3) React the formylfluorenimine ligand with alkylzinc to obtain an alkylzinc complex.
2. The preparation method of the fluorene-containing alkyl zinc complex according to claim 1, wherein The solvent described in step (1) is toluene, the reaction temperature is 50 °C, and the reaction time is 2 - 6 h.
3. The preparation method of the fluorene-containing alkyl zinc complex according to claim 1, characterized in that, In step (2), the solvent is ethanol, the amino compound is at least one of 2-aminopyridine, o-phenylenediamine, 1,2-cyclohexanediamine, ethylenediamine, or N,N-dimethyl-o-phenylenediamine, and the catalyst is acetic acid.
4. The preparation method of the fluorenylalkyl zinc complex according to claim 1, characterized in that, In step (3), the reaction solvent is tetrahydrofuran, and the alkylzinc is at least one of ZnEt2 or ZnMe2.
5. A fluorenylalkyl zinc complex, characterized in that, It is prepared by the preparation method described in any one of claims 1 - 4.
6. Use of the fluorenylalkylzinc complex prepared by the preparation method of the fluorenylalkylzinc complex described in any one of claims 1 - 4 or the fluorenylalkylzinc complex described in claim 5 in the catalytic borohydration reaction.