A method for recyclable synthesis of aldehyde compounds

Abstract

The present invention discloses a method for cyclically synthesizing aldehyde compounds. Under a nitrogen atmosphere, using 1,4-dioxane as a solvent, the epoxide can undergo a ring-opening reaction under the catalysis of borate to obtain an aldehyde product. Among them, the borate catalyst can be immobilized in an ionic liquid, and adding the ionic liquid to the reaction system can realize the recycling application of the catalyst. The reaction conditions of the present invention are mild, and the yield of aldehyde is high. The presence of the "ionic liquid-organic" two-phase system can separate the borate catalyst from the reaction system, realize recycling application, and reduce production costs.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and particularly relates to a method for cyclically synthesizing aldehyde compounds. Background Art

[0002] Aldehyde compounds are important intermediates in organic synthesis and are widely used in industries such as medicine, fuel, and chemical engineering. Due to the important application value of aldehyde substances, many synthesis methods have been explored for a long time. Epoxyalkanes are abundant and easily available. At the same time, due to the charge polarization in the epoxy group and the strain of the epoxy three-membered ring, they have high reactivity. Epoxides will undergo ring-opening under the catalysis of an acid. This reaction mainly undergoes the Meinwald rearrangement process. Due to different cleavage positions of the C-O bond and the competition between alkyl migration and hydrogen migration, the reaction often yields a mixture of aldehydes and ketones. The types of rearrangement products are determined by factors such as substrate structure, catalyst type, and solvent. Catalytic regioselective ring-opening of epoxides is an important method for synthesizing aldehydes.

[0003] In the existing technology, Lewis acids have high activity and the catalyzed reactions are easy to control, and they are the most common catalysts for the selective ring-opening of epoxides to aldehydes. A variety of metal catalysts such as [Pd], [Bi], [Sn], [Ni], [Fe], [Co], etc. have been applied to this reaction. For example, the Suda research group used Fe(tpp)OTf as a catalyst, 1,4-dioxane as a solvent, and refluxed under nitrogen to obtain aldehyde products with high selectivity. However, this catalyst has a complex structure, requires a relatively high reaction temperature, and consumes a large amount of energy (Suda K., Baba K., Nakajima S.I., Takanami T., Tetrahedron Lett., 1999, 40(40), 7243-7246). Devendra J. Vyas et al. prepared a Pd(II)-H compound and applied it as a catalyst in the ring-opening process of epoxides. The yield and selectivity of aldehydes are both high, but the use of precious metals inevitably has an adverse impact on production costs (Vyas D.J., Larionov E., Besnard C., Guenee L., Mazet C., J. Am. Chem. Soc., 2013, 135(16), 6177-6183). When using VO(acac) 2 as a catalyst for the ring-opening of epoxides, the yield of aldehydes is not high and the substrate scope is limited, and it is only applicable to the preparation of aryl-substituted aldehyde compounds (Sousa S.C., Fernandes A.C., Tetrahedron Lett., 2016, 57(5), 520-522).

[0004] It can be seen that in the synthesis of aldehyde compounds, there are still problems such as limited substrates, less mild reaction conditions, and relatively high catalytic costs. Therefore, it is necessary to explore new synthesis methods to reduce the influence of adverse factors in the existing technology so as to be better applied to large-scale production. Summary of the Invention

[0005] In view of the deficiencies in the prior art, the present invention provides a new method for the recyclable synthesis of aldehyde compounds. This synthesis method uses N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate to catalyze the ring-opening of epoxides. The reaction conditions are mild and the yield of aldehyde is relatively high. At the same time, the borate catalyst can be immobilized in an ionic liquid. The presence of the "ionic liquid-organic" two-phase can separate the borate catalyst from the reaction system to achieve recycling and further reduce production costs.

[0006] The present invention adopts the following technical solutions:

[0007] A method for the recyclable synthesis of aldehyde compounds, using N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate as a catalyst to catalyze the ring-opening of epoxides, comprising the following steps:

[0008] S1. Add N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate into a Schlenk reaction tube. After evacuating and filling with nitrogen, sequentially add 1,4-dioxane, an ionic liquid, and an epoxide to obtain a mixed solution;

[0009] S2. Stir the mixed solution at 50-70 °C until the reaction is complete, stop heating, and cool to room temperature to obtain a product mixed solution;

[0010] S3. Dilute the product mixed solution with 1,4-dioxane. After standing and separating into layers, separate the organic phase and the ionic liquid phase. Wash the ionic liquid phase 3 times with 1 mL of dichloromethane each time. Collect the organic phase and analyze it using gas chromatography and gas chromatography-mass spectrometry;

[0011] S4. Under a nitrogen atmosphere, directly add the reacted ionic liquid phase into the reaction tube, and then sequentially add 1,4-dioxane and an epoxide for the next reaction.

[0012] The amount of N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate added in step S1 is 1-3 mol%.

[0013] The volume molar ratio of 1,4-dioxane, ionic liquid, and epoxide added in step S1 is 6 mL:(2-2.5) mL:0.5 mmol.

[0014] Preferably, the epoxide is one of 1,2 - epoxyhexane, 1,2 - epoxyoctane, 1,2 - epoxydecane, styrene oxide and 2 - benzyloxirane.

[0015] Preferably, the ionic liquid is selected from 1 - butyl - 3 - methylimidazolium tetrafluoroborate ([Bmim]BF 4 ), 1 - butyl - 3 - methylimidazolium hydrogensulfate ([Bmim]HSO 4 ), 1 - butyl - 3 - methylimidazolium hexafluorophosphate ([Bmim]PF 6 ), 1 - butylpyridinium tetrafluoroborate (BPyBF 4 ).

[0016] The 1,4 - dioxane used is an anhydrous and anaerobic solvent.

[0017] The amount of 1,4 - dioxane added in step S3 is 1 / 6 of the amount added in step S1.

[0018] The amount of 1,4 - dioxane added during the cyclic reaction in step S4 is 2 / 3 of the amount added in step S1, and the amount of epoxide added is the same as that in step S1.

[0019] The reaction time in step S2 is 5 - 7 h.

[0020] Using N,N - dimethylanilinium tetrakis(pentafluorophenyl)borate as a catalyst to catalyze the ring - opening of epoxides, the present invention selects terminal epoxides. During the ring - opening, according to the stability of the carbocation, the cleavage of the C - O bond mainly occurs at position A, followed by hydrogen migration. Therefore, the main product is aldehyde. The reaction mechanism is as follows:

[0021]

[0022] The technical solution of the present invention has the following advantages compared with the prior art:

[0023] A. The present invention uses N,N - dimethylanilinium tetrakis(pentafluorophenyl)borate as a catalyst. Compared with traditional Lewis acids, this catalyst has the advantages of stable chemical properties and convenient use. On the other hand, the catalyst can be immobilized in the ionic liquid, and by constructing an "ionic liquid - organic" two - phase system, the catalyst can be separated from the reaction system, thus realizing the recovery and recycling of the catalyst.

[0024] B. The reaction conditions of the present invention are mild, the yield of the prepared aldehyde is relatively high, and the cyclic reaction effect is good. In addition, this catalytic system is also applicable to the preparation of aldehyde compounds substituted by alkyl and aryl groups. Detailed implementation manners

[0025] The present invention can be implemented in many different forms and should not be construed as limited to the embodiments set forth herein. On the contrary, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the concept of the present invention to those skilled in the art. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the scope of protection of the present invention.

[0026] Example 1

[0027] Add N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate (3 mol%) into a 10 mL Schlenk tube, evacuate and then fill with nitrogen. Then successively add 1,4-dioxane (6 mL) and styrene oxide (0.5 mmol). Stir the mixture at 60 °C for 6 h. After the reaction is completed, cool to room temperature and analyze by gas chromatography. The yield of the product phenylacetaldehyde is 93%.

[0028] The reaction equation is

[0029]

[0030] Example 2

[0031] Add N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate (3 mol%) into a 10 mL Schlenk tube, evacuate and then fill with nitrogen. Then successively add 1,4-dioxane (6 mL), 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF 4 , 2 mL), and styrene oxide (0.5 mmol). Stir the mixture at 60 °C for 6 h. After the reaction is completed, cool to room temperature, add 1 mL of 1,4-dioxane for dilution, let it stand until the solution is layered, separate the organic phase and the ionic liquid phase. Wash the ionic liquid phase with dichloromethane (3 × 1 mL), collect the organic phase and analyze by gas chromatography. The yield of the product phenylacetaldehyde is 91%.

[0032] The reaction equation is as shown in Reaction Equation 1.

[0033] Example 3

[0034] Add N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate (3 mol%) into a 10 mL Schlenk tube, evacuate and then fill with nitrogen. Then successively add 1,4-dioxane (6 mL), 1-butylpyridinium tetrafluoroborate (BPyBF 4, 2 mL), styrene oxide (0.5 mmol). The mixture was stirred at 60 °C for 6 h. After the reaction was completed, it was cooled to room temperature, diluted with 1 mL of 1,4-dioxane, allowed to stand for the solution to separate into layers, the organic phase and the ionic liquid phase were separated. The ionic liquid phase was washed with dichloromethane (3 × 1 mL), the organic phase was collected and analyzed by gas chromatography. The yield of the product phenylacetaldehyde was 81%.

[0035] The reaction equation is shown in Reaction Equation 1.

[0036] Example 4

[0037] N,N-Dimethylanilinium tetrakis(pentafluorophenyl)borate (3 mol%) was added to a 10 mL Schlenk tube. After evacuation, nitrogen was filled, and then 1,4-dioxane (6 mL) and 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF 4 , 2 mL), styrene oxide (0.5 mmol) were added in turn. The mixture was stirred at 50 °C for 6 h. After the reaction was completed, it was cooled to room temperature, diluted with 1 mL of 1,4-dioxane, allowed to stand for the solution to separate into layers, the organic phase and the ionic liquid phase were separated. The ionic liquid phase was washed with dichloromethane (3 × 1 mL), the organic phase was collected and analyzed by gas chromatography. The yield of the product phenylacetaldehyde was 82%.

[0038] The reaction equation is shown in Reaction Equation 1.

[0039] Example 5

[0040] N,N-Dimethylanilinium tetrakis(pentafluorophenyl)borate (3 mol%) was added to a 10 mL Schlenk tube. After evacuation, nitrogen was filled, and then 1,4-dioxane (6 mL) and 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF 4 , 2 mL), 1,2-epoxyhexane (0.5 mmol) were added in turn. The mixture was stirred at 60 °C for 6 h. After the reaction was completed, it was cooled to room temperature, diluted with 1 mL of 1,4-dioxane, allowed to stand for the solution to separate into layers, the organic phase and the ionic liquid phase were separated. The ionic liquid phase was washed with dichloromethane (3 × 1 mL), the organic phase was collected and analyzed by gas chromatography. The yield of the product n-hexanal was 75%.

[0041] The reaction equation is

[0042]

[0043] Example 6

[0044] Add N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate (3 mol%) into a 10 mL Schlenk tube. After evacuation, fill it with nitrogen. Then, successively add 1,4-dioxane (6 mL), 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF 4 , 2 mL), and 1,2-epoxyoctane (0.5 mmol). Stir the mixture at 60 °C for 6 h. After the reaction is completed, cool it to room temperature, add 1 mL of 1,4-dioxane for dilution, let it stand for the solution to separate into layers, separate the organic phase and the ionic liquid phase. Wash the ionic liquid phase with dichloromethane (3 × 1 mL), collect the organic phase and analyze it by gas chromatography. The yield of the product n-octanal is 73%.

[0045] The reaction equation is

[0046]

[0047] Example 7

[0048] Add N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate (3 mol%) into a 10 mL Schlenk tube. After evacuation, fill it with nitrogen. Then, successively add 1,4-dioxane (6 mL), 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF 4 , 2 mL), and 1,2-epoxydecane (0.5 mmol). Stir the mixture at 60 °C for 6 h. After the reaction is completed, cool it to room temperature, add 1 mL of 1,4-dioxane for dilution, let it stand for the solution to separate into layers, separate the organic phase and the ionic liquid phase. Wash the ionic liquid phase with dichloromethane (3 × 1 mL), collect the organic phase and analyze it by gas chromatography. The yield of the product n-decanal is 73%.

[0049] The reaction equation is

[0050]

[0051] Example 8

[0052] Add N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate (3 mol%) into a 10 mL Schlenk tube. After evacuation, fill it with nitrogen. Then, successively add 1,4-dioxane (6 mL), 1-butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF 4 , 2 mL), and 2-benzylethylene oxide (0.5 mmol). Stir the mixture at 60 °C for 6 h. After the reaction is completed, cool it to room temperature, add 1 mL of 1,4-dioxane for dilution, let it stand for the solution to separate into layers, separate the organic phase and the ionic liquid phase. Wash the ionic liquid phase with dichloromethane (3 × 1 mL), collect the organic phase and analyze it by gas chromatography. The yield of the product phenylpropanal is 77%.

[0053] The reaction equation is

[0054]

[0055] Example 9

[0056] Under an N 2 atmosphere, the ionic liquid phase after the reaction in Example 2, 1,4-dioxane (4 mL), and styrene oxide (0.5 mmol) were successively added to a 10 mL Schlenk tube, and the mixture was stirred at 60 °C for 6 h. After the reaction was completed, it was cooled to room temperature, allowed to stand for the solution to separate into layers, the organic phase and the ionic liquid phase were separated, the ionic liquid phase was washed with dichloromethane (3 × 1 mL), the organic phase was collected and analyzed by gas chromatography, and the yield of the product phenylacetaldehyde was 89%.

[0057] Its reaction equation is as shown in Reaction Equation 1.

[0058] Example 10

[0059] Under an N 2 atmosphere, the ionic liquid phase after the reaction in Example 9, 1,4-dioxane (4 mL), and styrene oxide (0.5 mmol) were successively added to a 10 mL Schlenk tube, and the mixture was stirred at 60 °C for 6 h. After the reaction was completed, it was cooled to room temperature, allowed to stand for the solution to separate into layers, the organic phase and the ionic liquid phase were separated, the ionic liquid phase was washed with dichloromethane (3 × 1 mL), the organic phase was collected and analyzed by gas chromatography, and the yield of the product phenylacetaldehyde was 88%.

[0060] Its reaction equation is as shown in Reaction Equation 1.

[0061] Example 11

[0062] Under an N 2 atmosphere, the ionic liquid phase after the reaction in Example 10, 1,4-dioxane (4 mL), and styrene oxide (0.5 mmol) were successively added to a 10 mL Schlenk tube, and the mixture was stirred at 60 °C for 6 h. After the reaction was completed, it was cooled to room temperature, allowed to stand for the solution to separate into layers, the organic phase and the ionic liquid phase were separated, the ionic liquid phase was washed with dichloromethane (3 × 1 mL), the organic phase was collected and analyzed by gas chromatography, and the yield of the product phenylacetaldehyde was 86%.

[0063] Its reaction equation is as shown in Reaction Equation 1.

[0064] Example 12

[0065] Under an N 2Under this atmosphere, the ionic liquid phase after the reaction in Example 11, 1,4-dioxane (4 mL), and styrene oxide (0.5 mmol) were successively added to a 10 mL Schlenk tube. The mixture was stirred at 60 °C for 6 h. After the reaction was completed, it was cooled to room temperature and allowed to stand until the solution was layered. The organic phase and the ionic liquid phase were separated. The ionic liquid phase was washed with dichloromethane (3 × 1 mL). The organic phase was collected and analyzed by gas chromatography. The yield of the product phenylacetaldehyde was 78%.

[0066] The reaction equation is shown in Reaction Equation 1.

[0067] In summary, the present invention uses N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate as a catalyst. Compared with traditional Lewis acids, this catalyst has the advantages of stable chemical properties and convenient use. On the other hand, the catalyst can be immobilized in an ionic liquid, and the catalyst can be separated from the reaction system by constructing an "ionic liquid - organic" two-phase system, thereby realizing the recovery and recycling of the catalyst. In addition, the reaction conditions of the present invention are mild, the yield of the prepared aldehyde is high, and the recycling reaction effect is good.

[0068] What is not described in the present invention is applicable to the prior art.

[0069] Obviously, the above examples are only for clear illustration and not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the implementation manners here. And the obvious changes or modifications derived therefrom are still within the protection scope of the present invention.

Claims

1. A method for recyclable synthesis of aldehyde compounds, characterized in that, using N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate as a catalyst to catalyze the ring-opening of epoxides, comprising the following steps: S1. Add N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate into a Schlenk reaction tube, evacuate and then fill with nitrogen, and sequentially add 1,4-dioxane, ionic liquid and epoxide to obtain a mixed solution; S2. Stir the mixed solution at 50-70 °C until the reaction is complete, stop heating, and cool to room temperature to obtain a product mixed solution; S3. Dilute the product mixed solution with 1,4-dioxane, let it stand and separate into layers, separate the organic phase and the ionic liquid phase, wash the ionic liquid phase 3 times with 1 mL of dichloromethane each time, collect the organic phase and analyze it using gas chromatography and gas chromatography-mass spectrometry; S4. Under a nitrogen atmosphere, directly add the reacted ionic liquid phase into the reaction tube, and then sequentially add 1,4-dioxane and epoxide for the next reaction; Among them, the epoxide is one of 1,2 - epoxyhexane, 1,2 - epoxyoctane, 1,2 - epoxydecane, styrene oxide and 2 - benzyloxirane; the ionic liquid is selected from 1 - butyl - 3 - methylimidazolium tetrafluoroborate ([Bmim]BF 4 ), 1 - butyl - 3 - methylimidazolium hydrogensulfate ([Bmim]HSO 4 ), 1 - butyl - 3 - methylimidazolium hexafluorophosphate ([Bmim]PF 6 ), 1 - butylpyridinium tetrafluoroborate (BPyBF 4 ) and is one of them.

2. The method for recyclable synthesis of aldehyde compounds according to claim 1, characterized in that, the amount of N,N-dimethylanilinium tetrakis(pentafluorophenyl)borate added in step S1 is 1-3 mol%.

3. The method for recyclable synthesis of aldehyde compounds according to claim 1, characterized in that, the volume molar ratio of 1,4-dioxane, ionic liquid and epoxide added in step S1 is 6 mL:(2-2.5) mL:0.5 mmol.

4. The method for recyclable synthesis of aldehyde compounds according to claim 1, characterized in that, the 1,4-dioxane is selected as an anhydrous and oxygen-free solvent.

5. The method for recyclable synthesis of aldehyde compounds according to claim 1, characterized in that, the amount of 1,4-dioxane added in step S3 is 1 / 6 of the amount added in step S1.

6. The method for recyclable synthesis of aldehyde compounds according to claim 1, characterized in that, the amount of 1,4-dioxane added during the cyclic reaction in step S4 is 2 / 3 of the amount added in step S1, and the amount of epoxide added is the same as that in step S1.

7. The method for recyclable synthesis of aldehyde compounds according to claim 1, characterized in that, the reaction time in step S2 is 5-7 h.

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