Preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzphenyl)butanone

Abstract

The present invention discloses a preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone, belonging to the field of photoinitiators. Specifically, it includes the following steps: (1) Chlorobenzene and n-butyryl chloride are used to prepare compound I under the catalysis of aluminum trichloride; (2) Compound I and sulfonyl chloride undergo a chlorination reaction to obtain compound II; (3) Compound II and N,N-dimethylarylamine react under the action of a basic catalyst to obtain compound III; (4) Compound III rearranges under basic conditions to obtain compound IV; (5) Compound IV and morpholine react under the action of a metal catalyst to obtain 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone. Implementing the present invention can reduce the raw material cost and the treatment cost of liquid waste.

Description

Technical Field

[0001] The present invention relates to the field of photoinitiators, and particularly to a preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone. Background Art

[0002] The initiator 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone is a highly efficient photoinitiator with a high photosensitive range and good UV absorption. It has the characteristics of small migration and low odor, and is particularly suitable for the rapid curing of dark systems. It can be used alone or in combination with a suitable co-initiator such as UV184 or UV651 in UV-curable inks and varnishes for paper, metal, and plastics. UV369 benefits from its excellent absorption performance, making it suitable for UV-curable inks and colored systems, and even for use in systems containing UV absorbers. UV369 is applied in the fields of pictures and art such as offset printing and screen printing inks, the electronics industry such as photoresists and solder resist inks, and the manufacture of printed boards.

[0003] The existing method usually uses fluorobenzene as the starting material, obtains 4-fluorobenzyl butanone under the catalysis of anhydrous aluminum chloride, then undergoes bromination to obtain a bromide, the bromide undergoes dimethylamine amination to obtain an aminated substituent, the aminated substituent reacts with chlorobenzyl to obtain a quaternary ammonium salt, the quaternary ammonium salt undergoes catalytic rearrangement under alkaline conditions to obtain a rearranged compound, and the rearranged compound reacts with morpholine to obtain 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone. In the synthesis process of this synthetic method route, fluorobenzene is used, and the price of fluorobenzene is relatively high, resulting in a relatively high overall production cost. Moreover, in the last step of the reaction with morpholine, the wastewater generated contains fluoride ions, and the treatment cost of fluoride ion wastewater is relatively high. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone, which has low raw material cost and low liquid waste treatment cost.

[0005] To solve the technical problem of the present invention, the present invention provides a preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone, which includes the following steps:

[0006] S1: Chlorobenzene and n-butyryl chloride are used to prepare compound I under the catalysis of aluminum trichloride;

[0007] S2: Compound I and sulfonyl chloride undergo a chlorination reaction to obtain compound II;

[0008] S3: Compound II reacts with N,N-dimethylarylamine under the action of a basic catalyst to obtain compound III;

[0009] S4: Compound III is rearranged under alkaline conditions to obtain compound IV;

[0010] S5: Compound IV reacts with morpholine in the presence of a metal catalyst to obtain 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone.

[0011]

[0012] Specifically, in one embodiment of the present invention, in step (5), compound IV is dissolved in dimethyl sulfone, and a base, morpholine and a metal catalyst are added in sequence, and the mixture is reacted at 80-150° C. for 10-50 hours. After the reaction is completed, dimethyl sulfoxide is removed, and the mixture is recrystallized in methanol, ethanol or propanol to obtain 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone.

[0013] Wherein, the base is selected from one or more of potassium carbonate, sodium hydroxide, and potassium hydroxide, and the weight ratio of the base to the compound IV is 1:(3-10), exemplarily 1:4, 1:5, 1:6, 1:7 or 1:8, but not limited thereto.

[0014] Preferably, in one embodiment of the present invention, in step (5), the metal catalyst is selected from one or more of a copper catalyst, a nickel catalyst, a nickel-copper alloy catalyst, and a palladium catalyst; illustratively, the metal catalyst may be triphenylphosphine palladium chloride, copper oxide, nickel chloride, or a nickel-copper alloy catalyst. The weight ratio of the metal catalyst to the compound IV is (0.5-5):100, illustratively 0.8:100, 1.3:100, 2.1:100, 3.2:100, or 4.2:100, but not limited thereto.

[0015] It is further preferred that the metal catalyst is a nickel-copper alloy catalyst, which can effectively improve the yield and product purity and reduce the reaction temperature. Specifically, the reaction temperature can be reduced to 100-110°C. Among them, the molar ratio of nickel to copper in the nickel-copper alloy catalyst is (1.5~5): (5~10). It should be noted that although the common palladium catalyst (triphenylphosphine palladium chloride) has a high yield and mild reaction conditions, it will dissolve in the reaction system, resulting in high costs. The yield of a single nickel catalyst is low, and although a single copper catalyst can also have a high yield (up to about 60%), its reaction conditions are harsh and require a reaction at about 150°C for more than 40 hours.

[0016] More preferably, the metal catalyst is a nickel-copper alloy catalyst, and is prepared by the following method:

[0017] Mix a copper nitrate solution with a concentration of 40 - 70 mg / mL and a nickel nitrate solution with a concentration of 10 - 25 mg / L, remove the moisture, and then calcine at 520 - 580 °C for 1.5 - 4 h under a non-oxidizing atmosphere to obtain the product. Among them, the non-oxidizing atmosphere can be a nitrogen atmosphere, an argon atmosphere, but is not limited thereto.

[0018] More specifically, dropwise add the nickel nitrate solution with a concentration of 10 - 25 mg / L into the copper nitrate solution with a concentration of 40 - 70 mg / mL, mix at 20 - 35 °C for 0.2 - 1 h, then raise the temperature to 85 - 95 °C, evaporate the water to dryness, and heat the obtained solid to 520 - 580 °C at a heating rate of 3 - 8 °C / min under a nitrogen atmosphere and calcine for 1.5 - 4 h to obtain the product. Based on the metal catalyst obtained by the above preparation method, the reaction temperature can be further reduced. Specifically, the reaction temperature can be reduced to 80 - 90 °C.

[0019] Specifically, in one embodiment of the present invention, in step (4), dissolve the compound Ⅲ in a sodium hydroxide solution with a concentration of 20 - 40 wt%, and perform a rearrangement reaction at 50 - 60 °C for 4 - 6 h.

[0020] Preferably, after the rearrangement reaction, it further includes a step of purifying the obtained product. More specifically, in one embodiment of the present invention, cool the rearrangement reaction system to 20 - 35 °C, add dichloromethane for extraction, wash the organic phase twice with water, dry with anhydrous sodium sulfate, concentrate, add ethanol, heat to 70 - 80 °C until dissolved clearly, cool down to 0 - 5 °C and keep warm for 2 hours, and perform solid-liquid separation to obtain compound Ⅳ.

[0021] Specifically, in one embodiment of the present invention, in step (3),

[0022] Dissolve the compound Ⅲ in dichloromethane, dropwise add the alkali solution and N,N-dimethylarylamine in sequence at 0 - 10 °C, and react at 10 - 20 °C for 4 - 6 h after the addition is completed; among them, the alkali solution is selected from sodium hydroxide solution and / or potassium hydroxide solution, and its concentration is 20 - 40 wt%.

[0023] Preferably, after the reaction, it further includes a step of extracting the product. Specifically, add dichloromethane and water to the product, separate the aqueous phase for subsequent reaction, and recycle and reuse the organic phase.

[0024] Specifically, in one embodiment of the present invention, in step (2), dissolve the compound Ⅰ in dichloromethane, dropwise add sulfonyl chloride at 0 - 10 °C, and react at 10 - 20 °C for 2 - 3 h after the addition is completed.

[0025] Preferably, after the reaction, it further includes a step of washing the product. Specifically, wash the organic phase with water 1 - 3 times, then dry and concentrate to obtain compound Ⅲ.

[0026] Specifically, in one embodiment of the present invention, in step (1), chlorobenzene is dissolved in dichloroethane, aluminum chloride is added at -5°C to 0°C, n-butyryl chloride is added dropwise, and after the addition is complete, the reaction is carried out at 20 - 30°C for 4 - 6 h.

[0027] Preferably, in one embodiment of the present invention, after reacting to the preset time, it is quenched with ice water, the obtained organic phase is washed with water 1 - 3 times, and then dried and concentrated to obtain compound I.

[0028] Implementing the present invention has the following beneficial effects:

[0029] In the preparation method of 2-phenylbenzyl-2-dimethylamino-1-(4-morpholinobenzylphenyl)butanone of the present invention, starting from chlorobenzene, sulfonyl chloride is used to replace the highly toxic controlled chemical liquid bromine, which not only reduces the cost of raw materials, but also reduces the cost of subsequent liquid waste. In addition, the yield of the preparation method of the present invention is high, reaching more than 60%, and the purity of the product 2-phenylbenzyl-2-dimethylamino-1-(4-morpholinobenzylphenyl)butanone can reach more than 95%. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 is a flowchart of the preparation method of 2-phenylbenzyl-2-dimethylamino-1-(4-morpholinobenzylphenyl)butanone in one embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0031] To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below in conjunction with specific embodiments.

[0032] Example 1

[0033] This example provides a preparation method of 2-phenylbenzyl-2-dimethylamino-1-(4-morpholinobenzylphenyl)butanone, which specifically includes:

[0034] 224 g of chlorobenzene is dissolved in 1.6 kg of 1,2-dichloroethane, the reaction is placed in a low-temperature bath, the temperature is maintained at -3°C, 293 g of anhydrous aluminum chloride is slowly added, 223 g of n-butyryl chloride is slowly added dropwise, after the addition is complete, the temperature is raised to 25°C and the reaction is carried out for 5 h. The GC in-process control detects that the chlorobenzene is ≤0.5%. The reaction solution is slowly added dropwise to 1.5 kg of ice water at 4°C for quenching. The organic phase is washed twice again, the organic phase is dried with anhydrous sodium sulfate, and concentrated to obtain 370 g of a light brown oily substance (compound I).

[0035] Dissolve the above oily substance in 2.3 kg of dichloroethane. Place the reaction in a low-temperature bath and maintain the temperature at 4°C. Slowly add 297 g of sulfonyl chloride dropwise. After the addition is complete, raise the temperature to 18°C and react for 2.5 h. Monitor the content of compound I by GC, and when it is ≤0.5%, slowly add 500 g of saturated aqueous sodium bisulfite dropwise. Wash the organic phase twice with water, dry it with anhydrous sodium sulfate, and concentrate to obtain 450 g of a brown oily substance (compound II).

[0036] Dissolve the above light brown oily substance in 450 g of dichloromethane. Control the temperature at 4°C and slowly add 1.3 kg of 30 wt% liquid alkali dropwise. After the addition is complete, raise the temperature to 15°C and slowly add 270 g of N,N-dimethylbenzylamine dropwise. After the addition is complete, raise the temperature to 28°C and react for 5.5 h. Monitor the content of compound II by GC, and when it is ≤0.5%, add 2.08 kg of dichloromethane and 2 kg of water, separate the aqueous phase (compound III), and recycle the organic phase after washing with water.

[0037] Dissolve the above aqueous phase in 1.32 kg of 30 wt% liquid alkali solution, raise the temperature to 55°C, and maintain this temperature for 5 h. Monitor the reaction of compound III by TLC. After the reaction is complete, cool to room temperature, add 2 kg of dichloromethane for extraction, wash the organic phase twice with water, dry it with anhydrous sodium sulfate, and concentrate to obtain 504 g of a brownish-yellow solid. Add 2 kg of ethanol, raise the temperature to 73°C until it dissolves clearly, cool down gradually to 2°C and keep warm for 2 h, then filter to obtain 410 g of a yellow solid (compound IV), and the purity detected by HPLC is ≥98%.

[0038] Add 410 g of compound IV, 1640 g of dimethyl sulfoxide, 180 g of potassium carbonate, 226 g of morpholine, and 4 g of copper catalyst to the reaction flask in sequence. Raise the temperature to 150°C and react for 50 h. Monitor the content of compound IV by HPLC in the middle control, and when it is ≤0.5%, distill off dimethyl sulfoxide and morpholine under reduced pressure for recycling. Add 2 kg of dichloromethane and 2 kg of water, stir and filter to remove the catalyst for recycling. Wash the organic phase twice with water, dry it with anhydrous sodium sulfate, and concentrate to obtain 476 g of a white solid with a purity of 92.3%. Add 2 kg of ethanol to this solid, raise the temperature to 74°C and keep warm for 2 h until it dissolves clearly, cool down gradually to 4°C to precipitate the solid, and filter to obtain 433.2 g of a white solid with a purity of 96.3%. After calculation, the yield is 60.2%.

[0039] Among them, the copper catalyst is copper oxide (CB99335322).

[0040] Example 2

[0041] This example provides a preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzyl)phenyl butanone, which specifically includes:

[0042] Dissolve 224 g of chlorobenzene in 1.6 kg of 1,2-dichloroethane. Place the reaction in a low-temperature bath and maintain the temperature at -3°C. Slowly add 293 g of anhydrous aluminum chloride, and slowly dropwise add 223 g of n-butyryl chloride. After the addition is complete, raise the temperature to 25°C and react for 5 h. Monitor by GC to ensure that the chlorobenzene content is ≤0.5%. Slowly dropwise add the reaction solution to 1.5 kg of ice water at 4°C to quench the reaction. Wash the organic phase twice with water, dry the organic phase with anhydrous sodium sulfate, and concentrate to obtain 370 g of a light brown oil (Compound I).

[0043] Dissolve the above oil in 2.3 kg of dichloroethane. Place the reaction in a low-temperature bath and maintain the temperature at 4°C. Slowly dropwise add 297 g of sulfonyl chloride. After the addition is complete, raise the temperature to 18°C and react for 2.5 h. Monitor by GC to ensure that the content of Compound I is ≤0.5%. Slowly dropwise add 500 g of saturated aqueous sodium bisulfite solution. Wash the organic phase twice with water, dry with anhydrous sodium sulfate, and concentrate to obtain 450 g of a brown oil (Compound II).

[0044] Dissolve the above light brown oil in 450 g of dichloromethane. Control the temperature at 4°C and slowly dropwise add 1.3 kg of 30 wt% liquid alkali. After the addition is complete, raise the temperature to 15°C, and slowly dropwise add 270 g of N,N-dimethylbenzylamine. After the addition is complete, raise the temperature to 28°C and react for 5.5 h. Monitor by GC to ensure that the content of Compound II is ≤0.5%. Add 2.08 kg of dichloromethane and 2 kg of water, separate the aqueous phase (Compound III), and recycle the washed organic phase for reuse.

[0045] Dissolve the above aqueous phase in 1.32 kg of 30 wt% liquid alkali solution, raise the temperature to 55°C, and maintain this temperature for 5 h. Monitor by TLC to ensure that the reaction of Compound III is complete. Cool to room temperature, add 2 kg of dichloromethane for extraction. Wash the organic phase twice with water, dry with anhydrous sodium sulfate, and concentrate to obtain 504 g of a brownish-yellow solid. Add 2 kg of ethanol, raise the temperature to 73°C until it dissolves clearly, gradually cool to 2°C and keep warm for 2 hours, then filter to obtain 410 g of a yellow solid (Compound IV), and the purity detected by HPLC is ≥98%.

[0046] Add 410 g of Compound IV, 1640 g of dimethyl sulfoxide, 180 g of potassium carbonate, 226 g of morpholine, and 4 g of palladium catalyst to the reaction flask in sequence. Raise the temperature to 150°C and react for 45 h. Monitor by HPLC to ensure that the content of Compound IV is ≤0.5%. Distill off dimethyl sulfoxide and morpholine under reduced pressure for recycling. Add 2 kg of dichloromethane and 2 kg of water, stir and filter. Wash the organic phase twice with water, dry with anhydrous sodium sulfate, and concentrate to obtain 476.1 g of a white solid with a purity of 93.6%. Add 2 kg of ethanol to this solid, raise the temperature to 74°C and keep warm for 2 h until it dissolves clearly, gradually cool to 4°C to precipitate the solid, and filter to obtain 436.5 g of a white solid with a purity of 97.5%. The calculated yield is 61.1%.

[0047] Among them, the palladium catalyst is palladium (II) chloride triphenylphosphine (CB71870810).

[0048] Example 3

[0049] This example provides a preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzyl)phenylbutanone, which specifically includes:

[0050] Dissolve 224 g of chlorobenzene in 1.6 kg of 1,2-dichloroethane. Place the reaction in a low-temperature bath, maintain the temperature at -3°C, slowly add 293 g of anhydrous aluminum chloride, and slowly dropwise add 223 g of n-butyryl chloride. After the addition is complete, raise the temperature to 25°C and react for 5 h. Control the content of chlorobenzene by GC to be ≤0.5%. Slowly dropwise add the reaction solution into 1.5 kg of ice water at 4°C to quench. Wash the organic phase twice with water, dry the organic phase with anhydrous sodium sulfate, and concentrate to obtain 370 g of a light brown oily substance (Compound I).

[0051] Dissolve the above oily substance in 2.3 kg of dichloroethane. Place the reaction in a low-temperature bath, maintain the temperature at 4°C, slowly dropwise add 297 g of sulfuryl chloride. After the addition is complete, raise the temperature to 18°C and react for 2.5 h. Control the content of Compound I by GC to be ≤0.5%. Slowly dropwise add 500 g of a saturated aqueous solution of sodium bisulfite. Wash the organic phase twice with water, dry it with anhydrous sodium sulfate, and concentrate to obtain 450 g of a brown oily substance (Compound II).

[0052] Dissolve the above light brown oily substance in 450 g of dichloromethane, control the temperature at 4°C, slowly dropwise add 1.3 kg of 30 wt% liquid alkali. After the addition is complete, raise the temperature to 15°C, slowly dropwise add 270 g of N,N-dimethylbenzylamine. After the addition is complete, raise the temperature to 28°C and react for 5.5 h. Control the content of Compound II by GC to be ≤0.5%. Add 2.08 kg of dichloromethane and 2 kg of water, separate the aqueous phase (Compound III), and recycle the organic phase after washing with water.

[0053] Dissolve the above aqueous phase in 1.32 kg of 30 wt% liquid alkali solution, raise the temperature to 55°C, maintain this temperature and react for 5 h. Control the reaction of Compound III by TLC. Cool down to room temperature, add 2 kg of dichloromethane for extraction. Wash the organic phase twice with water, dry it with anhydrous sodium sulfate, and concentrate to obtain 504 g of a brownish-yellow solid. Add 2 kg of ethanol, raise the temperature to 73°C until it dissolves clearly, cool down gradually to 2°C and keep it warm for 2 hours, and filter to obtain 410 g of a yellow solid (Compound IV), and the purity detected by HPLC is ≥98%.

[0054] Add 410 g of Compound IV to 1640 g of dimethyl sulfoxide, 180 g of potassium carbonate, 226 g of morpholine, and 4 g of nickel-copper alloy catalyst into the reaction flask in sequence. Heat up to 103 °C and react for 14 h. Monitor by HPLC during the reaction to ensure that the content of Compound IV is ≤0.5%. Remove dimethyl sulfoxide and morpholine by vacuum distillation for recycling. Add 2 kg of dichloromethane and 2 kg of water, stir and filter to remove the catalyst for recycling. Wash the organic phase twice with water, dry it with anhydrous sodium sulfate, and concentrate to obtain 492.2 g of white solid with a purity of 94.1%. Add this solid to 2 kg of ethanol, heat up to 74 °C and keep warm for 2 h until it dissolves clearly. Gradually cool down to 4 °C to precipitate solid, and filter to obtain 455.5 g of white solid with a purity of 97.6%. The yield is calculated to be 63.5%.

[0055] Among them, the preparation method of the nickel-copper alloy catalyst is as follows: Mix nickel acetylacetonate, copper acetylacetonate and γ-cyclodextrin in a molar ratio of 1:1:4, disperse them in DMF, stir and mix for 12 h, then react at 180 °C for 24 h, wash with water and ethanol, and then dry to obtain the product.

[0056] Example 4

[0057] This example provides a preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzyl)phenylbutanone, which specifically includes:

[0058] Dissolve 224 g of chlorobenzene in 1.6 kg of 1,2-dichloroethane. Place the reaction in a low-temperature bath, keep the temperature at -3 °C, slowly add 293 g of anhydrous aluminum chloride, and slowly dropwise add 223 g of n-butyryl chloride. After the addition is completed, heat up to 25 °C and react for 5 h. Monitor by GC during the reaction to ensure that the content of chlorobenzene is ≤0.5%. Slowly dropwise add the reaction solution to 1.5 kg of ice water at 4 °C to quench. Wash the organic phase twice with water, dry the organic phase with anhydrous sodium sulfate, and concentrate to obtain 370 g of light brown oily substance (Compound I).

[0059] Dissolve the above oily substance in 2.3 kg of dichloroethane. Place the reaction in a low-temperature bath, keep the temperature at 4 °C, slowly dropwise add 297 g of sulfuryl chloride. After the addition is completed, heat up to 18 °C and react for 2.5 h. Monitor by GC during the reaction to ensure that the content of Compound I is ≤0.5%. Slowly dropwise add 500 g of saturated aqueous sodium bisulfite solution. Wash the organic phase twice with water, dry it with anhydrous sodium sulfate, and concentrate to obtain 450 g of brown oily substance (Compound II).

[0060] Dissolve the above light brown oil in 450 g of dichloromethane, control the temperature at 4 °C, slowly add dropwise 1.3 kg of 30 wt% liquid caustic soda, after the addition is completed, raise the temperature to 15 °C, slowly add dropwise 270 g of N,N-dimethylbenzylamine, after the addition is completed, raise the temperature to 28 °C and react for 5.5 h, control the content of compound Ⅱ by GC to be ≤0.5%, add 2.08 kg of dichloromethane and 2 kg of water, separate out the aqueous phase (compound Ⅲ), and recycle the organic phase after washing with water.

[0061] Dissolve the above aqueous phase in 1.32 kg of 30 wt% caustic soda solution, raise the temperature to 55 °C, keep reacting at this temperature for 5 h, control the reaction of compound Ⅲ by TLC, cool down to room temperature, add 2 kg of dichloromethane for extraction, wash the organic phase twice with water, dry with anhydrous sodium sulfate, concentrate to obtain 504 g of yellowish-brown solid, add 2 kg of ethanol, raise the temperature to 73 °C until dissolved clearly, cool down gradually to 2 °C and keep warm for 2 h, filter to obtain 410 g of yellow solid (compound Ⅳ), and detect the purity by HPLC to be ≥98%.

[0062] Add 410 g of compound Ⅳ to 1640 g of dimethyl sulfoxide, add 180 g of potassium carbonate, 226 g of morpholine, and 4 g of nickel-copper alloy catalyst to the reaction flask in sequence, raise the temperature to 88 °C and react for 14 h, control the content of compound Ⅳ by HPLC to be ≤0.5%, remove dimethyl sulfoxide and morpholine by vacuum distillation for recycling, add 2 kg of dichloromethane and 2 kg of water, stir and filter to remove the catalyst for recycling, wash the organic phase twice with water, dry with anhydrous sodium sulfate, concentrate to obtain 495.6 g of white solid with a purity of 96.4%, add 2 kg of ethanol to this solid, raise the temperature to 74 °C and keep warm for 2 h until dissolved clearly, cool down gradually to 4 °C to precipitate solid, filter to obtain 459.4 g of white solid with a purity of 99.3%, and calculate the yield to be 65.5% through calculation.

[0063] Among them, the preparation method of the nickel-copper alloy catalyst is as follows: Add 1.9 g of copper nitrate to a 100 mL round-bottom flask, and then add 40 mL of distilled water, stir and dissolve it fully at room temperature. Take another 50 mL round-bottom flask, add 270 mg of nickel nitrate, and dissolve it with 20 mL of distilled water. Dropwise add the nickel nitrate solution to the copper nitrate solution under stirring, stir at room temperature for 30 min to make it mix evenly, then raise the temperature to 90 °C and evaporate the water until it is completely dry. Scrape the obtained solid, collect it in a porcelain boat, under a nitrogen atmosphere, heat it in a tube furnace at a heating rate of 5 °C / min to 550 °C and calcine for 3 h, wash the obtained solid with distilled water for 3 - 5 times, and store it in an inert environment for standby.

[0064] The above are the preferred embodiments of the invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements are also regarded as the protection scope of the present invention.

Claims

1. A preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone, characterized in that, It includes the following steps: (1) Chlorobenzene and n-butyryl chloride are used to prepare compound I under the catalysis of aluminum trichloride; (2) Compound I and sulfonyl chloride are subjected to a chlorination reaction to obtain compound II; (3) Compound II and N,N-dimethylarylamine react under the action of a basic catalyst to obtain compound III, wherein the basic catalyst is selected from sodium hydroxide or potassium hydroxide; (4) Compound III is rearranged under basic conditions to obtain compound IV; (5) Compound IV and morpholine react under the action of a metal catalyst to obtain 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone, wherein the metal catalyst is selected from a nickel-copper alloy catalyst.

2. The preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone according to claim 1, characterized in that, In step (5), the weight ratio of the metal catalyst to compound IV is (0.5-5):

100.

3. The preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone according to claim 1, characterized in that, The preparation method of the nickel-copper alloy catalyst is as follows: A copper nitrate solution with a concentration of 40-70 mg / mL and a nickel nitrate solution with a concentration of 10-25 mg / L are mixed, and after removing moisture, they are calcined at 520-580 °C for 1.5-4 h under a non-oxidizing atmosphere to obtain the product.

4. The preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone according to claim 1, characterized in that, In step (5), compound IV is dissolved in dimethyl sulfoxide, and an alkali, morpholine, and a metal catalyst are added in sequence, and the reaction is carried out at 80-150 °C for 10-50 h; Among them, the alkali is selected from one or more of potassium carbonate, sodium hydroxide, and potassium hydroxide, and the weight ratio of the alkali to compound IV is 1:(3-10).

5. The preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone according to claim 4, characterized in that, In step (5), after the reaction is completed, dimethyl sulfoxide is removed, and recrystallization is carried out in methanol, ethanol, or propanol to obtain 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone.

6. The preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone according to claim 1, characterized in that, In step (4), compound III is dissolved in a sodium hydroxide solution with a concentration of 20-40 wt%, and rearrangement reaction is carried out at 50-60 °C for 4-6 h.

7. The preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone according to claim 1, characterized in that, In step (3), compound II is dissolved in dichloromethane, and an alkali solution and N,N-dimethylarylamine are added dropwise in sequence at 0-10 °C, and the reaction is carried out at 10-20 °C for 4-6 h after the addition is completed; Among them, the alkali solution is selected from a sodium hydroxide solution and / or a potassium hydroxide solution, and its concentration is 20-40 wt%.

8. The preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone according to claim 1, characterized in that, In step (2), compound I is dissolved in dichloromethane, and sulfonyl chloride is added dropwise at 0-10 °C, and the reaction is carried out at 10-20 °C for 2-3 h after the addition is completed.

9. The preparation method of 2-phenylbenzyl-2-dimethylamine-1-(4-morpholinobenzylphenyl)butanone according to claim 1, characterized in that, In step (1), chlorobenzene is dissolved in dichloroethane, aluminum chloride is added at -5 °C - 0 °C, n-butyryl chloride is added dropwise, and the reaction is carried out at 20-30 °C for 4-6 h after the addition is completed.

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