A preparation method and application of 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-acetone

Abstract

The invention relates to a preparation method of 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-acetone and application thereof. In the preparation method, sulfuric acid with a concentration of 30% to 85% is added as an auxiliary agent in a chlorination reaction, which can reduce the occurrence of side reactions on a benzene ring and a methylthio group, improve the selectivity of an α-chlorination reaction, and the purity of an α-chlorinated product is high, which can reach 95% or more. After the reaction in the preparation method is completed, sulfuric acid with a specific concentration can be easily separated by standing and separating liquids, thereby facilitating the recycling of sulfuric acid. In the preparation method of the invention, the yield of the chlorinated product obtained by recycling sulfuric acid can still reach 95% or more. The problem that hydrochloric acid is easily volatile, has a large unpleasant odor in the preparation process, and has a low recycling efficiency is solved.

Description

Technical Field

[0001] The invention belongs to the field of photoinitiator preparation, and relates to a preparation method and application of 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone. Background Art

[0002] Photoinitiator 907, chemical name is 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone. In its structure, methylthio is a color-enhancing group and morpholinyl is a solubilizing group, which makes 907 particularly suitable for dark-colored UV-curable coatings, inks and adhesives containing pigments.

[0003] The reaction process of the preparation process of 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone disclosed in the prior art generally includes halogenation, cyclization and morpholine substitution steps. When the halogenation process adopts a chlorination process, hydrochloric acid is generally added as an auxiliary agent in the traditional process. However, the use of hydrochloric acid as an auxiliary agent has the problems of easy volatility, strong odor in the preparation process, difficulty in recycling, and insufficient purity of the chlorinated product.

[0004] Therefore, it is still of great significance to develop a method for preparing 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone in which an auxiliary agent can be recycled and the yield and purity of the chlorinated product are high. Summary of the invention

[0005] The object of the present invention is to provide a preparation method and application of 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone. In the preparation method, sulfuric acid with a concentration of 30% to 85% is added as an auxiliary agent in the chlorination reaction, which can reduce the occurrence of side reactions on the benzene ring and the methylthio group, improve the selectivity of the α-chlorination reaction, and the purity of the α-chlorinated product is high, which can reach 95% or more; and after the reaction in the above preparation method is completed, sulfuric acid with a specific concentration is easy to separate by standing and separating liquids, so as to facilitate the recycling of sulfuric acid. In the preparation method of the present invention, the yield of the chlorinated product obtained by recycling sulfuric acid can still reach 95% or more; the problem that the traditional process uses hydrochloric acid as an auxiliary agent, which is easy to volatilize, has a strong unpleasant odor in the preparation process, and has low recycling efficiency is solved.

[0006] In order to achieve the purpose of the invention, the present invention adopts the following technical solutions:

[0007] In a first aspect, the present invention provides a method for preparing 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone, the preparation method comprising the following steps:

[0008] (1) mixing p-methylthiophenyl isobutyl ketone with sulfuric acid having a concentration of 30% to 85% (exemplary examples include 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% or 80%) to obtain a mixed solution;

[0009] (2) Chlorine gas is introduced into the mixed solution of step (1) to carry out chlorination reaction to obtain 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone.

[0010] 2-Methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone is an intermediate for preparing photoinitiator 907, which is obtained by chlorination reaction with p-methylthiophenyl isobutyl ketone as a raw material. In the traditional chlorination process, hydrochloric acid is used as an auxiliary agent, and hydrochloric acid is volatile. The purity of the chlorinated product is generally lower than 95%, and the recycling efficiency of hydrochloric acid is low, and the purity of the recycled product drops to less than 90%. Therefore, it is difficult to achieve effective recycling, and the process cost is high. Based on solving the above technical problems, the present invention provides a preparation method of 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone, in which the auxiliary agent can be recycled, the chlorinated product has a high yield and high purity;

[0011] The preparation method of the present invention uses sulfuric acid with a concentration of 30% to 85% as an auxiliary agent, which can effectively inhibit the occurrence of side reactions on the benzene ring and the methylthio group during the chlorination reaction and improve the selectivity of the α-chlorination reaction. The purity and yield of the chlorinated product in the preparation method of the present invention can reach 95% or more; and the sulfuric acid is easy to recover and circulate, and the yield and purity of the chlorinated product obtained by circulation can still reach 95% or more.

[0012] The equation of the above-mentioned chlorination reaction of the present invention is as follows:

[0013]

[0014] Preferably, in step (1), the mass ratio of p-methylthiophenyl isobutyl ketone to H2SO4 in sulfuric acid having a concentration of 30% to 85% is 1:0.5 to 1.6; for example, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1.0, 1:1.1, 1:1.2, 1:1.3, 1:1.4 or 1:1.5, etc.

[0015] There are many methods for preparing p-methylthiophenyl isobutyl ketone in the literature: for example, thioanisole and isobutyric anhydride or isobutyryl chloride are prepared under Lewis acid catalysis, or p-chlorophenyl isobutyl ketone is prepared by reacting sodium methyl mercaptan.

[0016] In the present invention, the mass ratio of p-methylthiophenyl isobutyl ketone to H2SO4 in sulfuric acid is controlled within the above range, which is conducive to obtaining a better yield and purity of the chlorinated product; when the amount of sulfuric acid used is too little, the auxiliary agent effect is not obvious, and the sulfuric acid phase cannot be directly separated after the reaction is completed, and a large amount of water needs to be added to separate the liquids. The obtained diluted sulfuric acid cannot be reused, and the generation of waste acid water cannot be effectively reduced. The environmental pressure is large. When the amount of sulfuric acid added is too high, more products will be dissolved, resulting in low yield.

[0017] Preferably, the operating temperature of the mixing in step (1) is -5°C to 5°C, for example -4°C, -3°C, -2°C, -1°C, 0°C, 1°C, 2°C, 3°C or 4°C.

[0018] Preferably, the mixing method in step (1) comprises dropwise adding sulfuric acid having a concentration of 30% to 85% into p-methylthiophenyl isobutyl ketone.

[0019] Preferably, before introducing chlorine gas in step (2), the mixed solution is heated to 20°C to 50°C, for example, 25°C, 30°C, 35°C, 40°C or 45°C.

[0020] Preferably, the temperature of the chlorination reaction in step (2) is 20-50°C, such as 25°C, 30°C, 35°C, 40°C or 45°C.

[0021] Preferably, after the chlorination reaction in step (2) is completed, the step further includes adding an organic solvent and water to the reaction solution, extracting, and separating the liquids to obtain an organic phase and a sulfuric acid phase.

[0022] After the chlorination reaction in the present invention is completed, an organic solvent and water are added to the reaction solution. On the one hand, the organic solvent extracts the chlorinated product, and the added water can adjust the concentration of sulfuric acid to a range that is convenient for static stratification, so that the stratification of the organic phase of the chlorinated product and the sulfuric acid phase is convenient, and the two are separated by liquid separation; it is convenient to realize the recycling of the sulfuric acid phase and the collection and purification of the chlorinated product.

[0023] The present invention has found through research that after the chlorination reaction is completed, when the concentration of the sulfuric acid phase is 30% to 70%, the sulfuric acid phase and the chlorination product organic phase can be well separated and are easy to apply.

[0024] Preferably, the amount of water added to the reaction solution is such that the concentration of the sulfuric acid phase obtained by separation is 30% to 70%, for example, 35%, 40%, 45%, 50%, 55%, 60% or 65%.

[0025] In the present invention, the amount of water added after the chlorination reaction is completed is related to the concentration of the initially added sulfuric acid. When the concentration of the initially added sulfuric acid is within the range of 30-70%, after the chlorination reaction is completed, only an organic solvent needs to be added without adding water, so that the organic phase and the sulfuric acid phase of the chlorinated product can be separated, which is convenient for liquid separation of the two and application of sulfuric acid. The recycling efficiency of the obtained sulfuric acid phase is high, and the purity and yield of the chlorinated product obtained by application are still high. When the concentration of the initially added sulfuric acid is greater than 70%, an organic solvent and water need to be added after the chlorination reaction is completed, and the amount of water added is controlled so that the concentration of the obtained sulfuric acid phase is 30-70%, which is convenient for liquid separation and application of the sulfuric acid phase.

[0026] Preferably, the obtained sulfuric acid phase is used in step (1).

[0027] In the present invention, the sulfuric acid phase with a concentration of 30% to 70% obtained by liquid separation can be recycled and applied to the chlorination reaction, and the purity and yield of the chlorination product are still relatively high.

[0028] Preferably, the organic solvent is selected from any one or a combination of at least two of toluene, n-hexane, petroleum ether, cyclohexane, dichloroethane, dichloromethane or chlorobenzene.

[0029] Preferably, the ratio of the amount of p-methylthiophenyl isobutyl ketone in step (1) to the volume of the organic solvent added to the reaction solution in step (2) is 2 mol / L to 3 mol / L, for example, 2.1 mol / L, 2.2 mol / L, 2.3 mol / L, 2.4 mol / L, 2.5 mol / L, 2.6 mol / L, 2.7 mol / L, 2.8 mol / L or 2.9 mol / L.

[0030] Preferably, the preparation method further comprises alkali washing and desolventizing the organic phase to obtain an oily substance 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone.

[0031] Preferably, the alkali solution used in the alkali washing is a saturated sodium bicarbonate solution.

[0032] In the present invention, after liquid separation, the organic phase of the chlorinated product is alkaline washed with a saturated sodium bicarbonate solution, which is beneficial to avoid the influence of residual acid on subsequent reactions.

[0033] Preferably, the pH of the organic phase at the end point of the alkaline washing is 7 to 8, for example, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8 or 7.9.

[0034] The purity of the oily 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone obtained after alkali washing and desolventizing of the chlorinated product organic phase of the present invention can reach 95% or more, and can be used to prepare photoinitiator 907 without further purification. After cyclization and morpholine substitution reaction, photoinitiator 907 is obtained, and the purity of the photoinitiator can reach more than 98%.

[0035] In a second aspect, the present invention provides a method for preparing 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone, the preparation method comprising the following steps:

[0036] (a) preparing 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone by the method described in the first aspect;

[0037] (b) mixing the 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone obtained in step (a) with a methanol solution of sodium methoxide, performing a cyclization reaction, and washing with water to obtain an epoxide organic phase;

[0038] (c) mixing the epoxide organic phase obtained in step (b), morpholine and a catalyst, heating, and performing a reflux morpholine substitution reaction, followed by water washing, desolventizing, and recrystallization to obtain 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone.

[0039] In the present invention, 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone obtained by chlorination reaction is subjected to cyclization reaction and morpholine substitution reaction to obtain 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone (photoinitiator 907), and the purity of the obtained product can reach more than 98%. In the present invention, the total yield of chlorination reaction, cyclization reaction and morpholine substitution reaction can reach more than 86%.

[0040] The reaction equation of the above preparation process of the present invention is as follows:

[0041]

[0042] Preferably, the mixing method in step (b) comprises adding 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone dropwise into the sodium methoxide methanol solution.

[0043] Preferably, the concentration of the sodium methoxide methanol solution in step (b) is 10% to 35%, such as 15%, 20%, 25% or 30%.

[0044] Preferably, the temperature of the cyclization reaction in step (b) is 40°C to 60°C, such as 45°C, 50°C or 55°C.

[0045] Preferably, in step (c), the catalyst is selected from saturated sodium bicarbonate solution.

[0046] In the present invention, a saturated sodium bicarbonate solution is added as a catalyst in the morpholine substitution reaction, which can improve the efficiency of the morpholine substitution reaction and improve the yield and purity of the product.

[0047] Preferably, the molar ratio of 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone in step (b) to morpholine in step (c) is 1:2-4, for example 1:2.2, 1:2.5, 1:2.8, 1:3, 1:3.2, 1:3.5 or 1:3.8, etc.

[0048] In the present invention, the amount of morpholine used is within the above range, which is conducive to obtaining a high yield of the morpholine substitution reaction.

[0049] Preferably, the solvent for recrystallization in step (c) is selected from any one of methanol, ethanol, petroleum ether, butanol or propanol, or a combination of at least two thereof.

[0050] As a preferred technical solution of the present invention, the preparation method of 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone comprises the following steps:

[0051] (I) adding sulfuric acid having a concentration of 30% to 85% dropwise to p-methylthiophenyl isobutyl ketone at -5°C to 5°C, with stirring during the adding process, to obtain a mixed solution;

[0052] (II) heating the mixed solution in step (I) to 20°C to 50°C, and introducing chlorine gas into the mixed solution to carry out chlorination reaction. After the reaction is completed, adding an organic solvent and water to the reaction solution, stirring and mixing, and then standing and separating the liquids to obtain an organic phase and a sulfuric acid phase; the concentration of the obtained sulfuric acid phase is 30% to 70%, and the sulfuric acid phase is used in step (I);

[0053] (III) adjusting the pH of the organic phase obtained in step (II) to 7-8, and then removing the solvent to obtain an oily substance 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone;

[0054] (IV) adding the oily substance 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone obtained in step (III) dropwise to a sodium methoxide methanol solution, with stirring during the dropping process, and then heating to 40° C. to 60° C. to carry out a cyclization reaction. After the reaction is completed, water is added to the reaction solution for washing, and the liquid is separated to obtain an aqueous phase and an epoxide organic phase;

[0055] (V) mixing the epoxide organic phase obtained in step (IV) with morpholine, adding a saturated sodium bicarbonate solution, and heating under reflux for morpholine substitution reaction. After the reaction is completed, washing with water, distilling and desolventizing, and recrystallizing to obtain 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone.

[0056] Compared with the prior art, the present invention has the following beneficial effects:

[0057] (1) In the preparation method of the present invention, sulfuric acid with a concentration of 30% to 85% is added as an auxiliary agent in the chlorination reaction, which can inhibit the occurrence of side reactions on the benzene ring and the methylthio group, improve the selectivity of the α-chlorination reaction, and increase the yield and purity of the α-chlorinated product. In the present invention, the yield and purity of the α-chlorinated product can reach 95% or more;

[0058] (2) In the preparation method of the present invention, after the chlorination reaction is completed, sulfuric acid can be easily recovered by separation and reused in the chlorination reaction. The yield and purity of the chlorinated product obtained by the use of sulfuric acid are still relatively high, which solves the problem of high volatility and difficulty in use of hydrochloric acid as an auxiliary agent in the chlorination process of the traditional photoinitiator 907. DETAILED DESCRIPTION

[0059] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0060] Example 1

[0061] This embodiment provides a method for preparing 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone, the preparation method comprising the following steps:

[0062] (I) 50 g (0.255 mol) of p-methylthiophenyl isobutyl ketone was placed in a 250 mL reaction vessel, and 83.3 g of a 60% aqueous sulfuric acid solution was added dropwise with stirring under an ice-water bath to obtain a mixed solution after all the additions were completed;

[0063] (II) At room temperature (25° C.), 18.4 g (0.26 mol) of chlorine gas was introduced into the mixed solution of step (I), and the reaction was detected by LC. After the reaction was complete, 100 mL of toluene was added and stirred for 30 min. The mixture was allowed to stand for separation to obtain an organic phase of the chlorinated product and a sulfuric acid phase, and the sulfuric acid phase was used for standby;

[0064] (III) The pH value of the organic phase of the chlorinated product obtained in step (II) was adjusted to 7.5 with a saturated sodium bicarbonate solution, and the solvent was removed by desolventizing to obtain 58.0 g of 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone as an oil; the purity of 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone by HPLC was 95.8%; the yield of 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone was calculated to be 95.3%.

[0065] Example 2

[0066] This embodiment provides a method for preparing 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone, the preparation method comprising the following steps:

[0067] Steps (I), (II) and (III) are repeated as in Example 1, except that no desolventizing operation is performed in step (III) to obtain a toluene solution of 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone;

[0068] (IV) at room temperature (25°C), 65 g of 30% industrial sodium methoxide methanol solution was placed in a 250 mL reactor and stirred, and the 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone toluene in the above step (III) was added dropwise using a dropping funnel within 1 hour; then the reaction mixture was heated to 50°C for cyclization reaction, 50 mL of water was added after the reaction was completed, and the mixture was allowed to stand for separation to obtain an aqueous phase and an epoxide organic phase, the aqueous phase was separated, and the epoxide organic phase was tested. The epoxide content was 98.2% by HPLC;

[0069] (V) At room temperature, the epoxide organic phase prepared in step (IV) was mixed with 55.6 g of morpholine, and 10 g of saturated sodium bicarbonate solution was added, and the reaction mixture was heated to reflux to carry out morpholine substitution reaction. After the reaction was completed, 55 mL of water was added for washing, and the organic phase was distilled to recover the solvent. The residue was added with methanol for recrystallization to obtain 63.4 g of 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone. The purity was 98.5% according to HPLC, and the calculated yield was 89%.

[0070] Example 3

[0071] The only difference between this embodiment and embodiment 1 is that the sulfuric acid jacket obtained in step (II) is used in step (I), and the other parameters and conditions are exactly the same as those in embodiment 1.

[0072] The product obtained in step (III) of this embodiment is 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone, 57.3 g; the purity detected by HPLC is 95.0%.

[0073] Example 4

[0074] The only difference between this embodiment and embodiment 1 is that 83.3 g of 60% aqueous sulfuric acid solution in step (I) is replaced by 66.6 g of 75% aqueous sulfuric acid solution; and the addition of 100 mL of toluene in step (II) is replaced by the addition of 100 mL of toluene and 33.3 mL of water. The other parameters and conditions are exactly the same as those in embodiment 1.

[0075] In step (II) of this embodiment, the liquid is separated to obtain sulfuric acid with a concentration of 50%;

[0076] The product obtained in step (III) of this embodiment is 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone, 57.0 g; the purity detected by HPLC is 95.3%.

[0077] Example 5

[0078] The only difference between this embodiment and embodiment 4 is that the sulfuric acid jacket obtained in step (II) is used in step (I), and the other parameters and conditions are exactly the same as those in embodiment 1.

[0079] The product obtained in step (III) of this embodiment is 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone, 57.5 g; the purity detected by HPLC is 95.0%.

[0080] Comparative Example 1

[0081] The difference between this comparative example and Example 1 is that 83.3 g of 60% sulfuric acid aqueous solution in step (I) is replaced by 250 g of 20% sulfuric acid aqueous solution, and the other parameters and conditions are exactly the same as those in Example 1.

[0082] The product obtained in step (III) of this comparative example is 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone, 58.7 g, with a purity of 90.0% as determined by HPLC; the reason why the mass of the product obtained in this comparative example is greater than that of the product in Example 1 is that multiple chlorination side reactions occur during the chlorination reaction.

[0083] Comparative Example 2

[0084] The difference between this comparative example and Example 1 is that 83.3 g of 60% sulfuric acid aqueous solution in step (Ⅰ) is replaced by 53 g of 95% concentrated sulfuric acid, and the addition of 100 mL of toluene in step (Ⅱ) is replaced by the addition of 100 mL of toluene and 50 mL of water. The other parameters and conditions are exactly the same as those in Example 1.

[0085] The product 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone obtained in step (III) of this comparative example had a purity of 72.0% as determined by HPLC.

[0086] Comparative Example 3

[0087] The difference between this comparative example and Example 1 is that 83.3 g of 60% sulfuric acid aqueous solution in step (I) is replaced by 200 g of 32% hydrochloric acid, and the other parameters and conditions are exactly the same as those in Example 1.

[0088] The product obtained in step (III) of this comparative example is 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone, 58.0 g, with a purity of 92.6% as determined by HPLC.

[0089] The hydrochloric acid solution phase obtained by separation in step (II) of this comparative example is collected for later use.

[0090] Comparative Example 4

[0091] The difference between this comparative example and comparative example 3 is that the hydrochloric acid obtained by separation in step (II) of comparative example 3 is used in step (I), and the other parameters and conditions are exactly the same as those in Example 1.

[0092] The product obtained in step (III) of this comparative example is 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone, 58.4 g, with a purity of 85.0% as determined by HPLC.

[0093] The applicant declares that the above is only a specific implementation mode of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention shall fall within the protection scope and disclosure scope of the present invention.

Claims

1. A method for preparing 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone, characterized in that: The preparation method comprises the following steps: (1) mixing p-methylthiophenyl isobutyl ketone with sulfuric acid having a concentration of 30% to 85% to obtain a mixed solution; (2) introducing chlorine gas into the mixed solution of step (1) to carry out chlorination reaction to obtain 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone; In step (1), the mass ratio of p-methylthiophenyl isobutyl ketone to H2SO4 in sulfuric acid with a concentration of 30% to 85% is 1:0.5 to 1.6; The mixing operation temperature in step (1) is -5°C to 5°C; Before the chlorine gas is introduced in step (2), the mixed solution is heated to 20°C to 50°C; After the chlorination reaction in step (2) is completed, the method further comprises adding an organic solvent and water to the reaction solution, extracting, and separating the liquids to obtain an organic phase and a sulfuric acid phase. The amount of water added to the reaction solution is such that the concentration of the sulfuric acid phase obtained by separation is 30% to 70%. The obtained sulfuric acid phase is used in step (1).

2. The preparation method according to claim 1, characterized in that: The mixing method in step (1) comprises adding sulfuric acid having a concentration of 30% to 85% dropwise into p-methylthiophenyl isobutyl ketone.

3. The preparation method according to claim 1, characterized in that: The temperature of the chlorination reaction in step (2) is 20-50°C.

4. The preparation method according to claim 1, characterized in that: The organic solvent is selected from any one of toluene, n-hexane, petroleum ether, cyclohexane, dichloroethane, dichloromethane or chlorobenzene, or a combination of at least two thereof.

5. The preparation method according to claim 1, characterized in that: The ratio of the amount of p-methylthiophenyl isobutyl ketone in step (1) to the volume of the organic solvent added to the reaction solution in step (2) is 2 mol / L to 3 mol / L.

6. The preparation method according to claim 1, characterized in that: The preparation method also includes alkali washing and desolventizing the organic phase to obtain an oily substance, 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone.

7. The preparation method according to claim 6, characterized in that: The alkali solution used in the alkali washing is a saturated sodium bicarbonate solution.

8. The preparation method according to claim 6, characterized in that: The pH of the organic phase from the end point of the alkaline washing to the end point is 7-8.

9. A method for preparing 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone, characterized in that: The preparation method comprises the following steps: (a) preparing 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone by the method according to any one of claims 1 to 8; (b) mixing the 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone obtained in step (a) with a methanol solution of sodium methoxide, performing a cyclization reaction, and washing with water to obtain an epoxide organic phase; (c) The epoxide organic phase obtained in step (b), morpholine and the catalyst are mixed, heated, and subjected to a reflux morpholine substitution reaction, followed by water washing, desolventization, and recrystallization to obtain 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone.

10. The preparation method according to claim 9, characterized in that: The mixing method in step (b) comprises adding 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone dropwise to the sodium methoxide methanol solution.

11. The preparation method according to claim 9, characterized in that: The concentration of the sodium methoxide methanol solution in step (b) is 10% to 35%.

12. The preparation method according to claim 9, characterized in that: The temperature of the cyclization reaction in step (b) is 40°C to 60°C.

13. The preparation method according to claim 9, characterized in that: In step (c), the catalyst is selected from saturated sodium bicarbonate solution.

14. The preparation method according to claim 9, characterized in that: The molar ratio of 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone in step (b) to morpholine in step (c) is 1:2-4.

15. The preparation method according to claim 9, characterized in that: The solvent for recrystallization in step (c) is selected from any one of methanol, ethanol, petroleum ether, butanol or propanol, or a combination of at least two thereof.

16. The preparation method according to claim 9, characterized in that: The preparation method comprises the following steps: (I) adding sulfuric acid having a concentration of 30% to 85% dropwise to p-methylthiophenyl isobutyl ketone at -5°C to 5°C, with stirring, to obtain a mixed solution; (II) heating the mixed solution in step (I) to 20°C to 50°C, and introducing chlorine gas into the mixed solution to carry out chlorination reaction. After the reaction is completed, adding an organic solvent and water to the reaction solution, stirring and mixing, and then standing and separating the liquids to obtain an organic phase and a sulfuric acid phase; the concentration of the obtained sulfuric acid phase is 30% to 70%, and the sulfuric acid phase is used in step (I); (III) adjusting the pH of the organic phase obtained in step (II) to 7-8, and then removing the solvent to obtain an oily substance 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone; (IV) adding the oily substance 2-methyl-2-chloro-1-[4-(methylthio)phenyl]-1-propanone obtained in step (III) dropwise to a sodium methoxide methanol solution, with stirring during the dropping process, and then heating to 40° C. to 60° C. to carry out a cyclization reaction. After the reaction is completed, water is added to the reaction solution for washing, and the liquid is separated to obtain an aqueous phase and an epoxide organic phase; (V) The epoxide organic phase obtained in step (IV) is mixed with morpholine, and a saturated sodium bicarbonate solution is added to carry out a morpholine substitution reaction by heating under reflux. After the reaction is completed, the mixture is washed with water, desolventized by distillation, and recrystallized to obtain 2-methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone.

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